Name: 79200-56-9|(1R,4S)-2-Azabicyclo[2.2.1]hept-5-en-3-one|98%
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1
[ 24424-99-5 ]
[ 79200-56-9 ]
[ 151792-53-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With dmap; triethylamine In tetrahydrofuran	10.A.1 Intermediate 10; (3S, lR)- (-)-3-N-BOC-Aminocyclopentane-l-carboxylic acid; Method A; Step 1: (4S, 1R)- (-)-2-N-BOC-Azabicyclo [2,2, 1] hept-5-ene-3-one; This intermediate was prepared from (1R, 4S)-(-)-2-azabicyclo [2,2, 1] hept-5-ene-3-one (10 g, 91.74 mmol) and di-tert-butyl dicarbonate (23.9 g, 109.6 mmol) in the presence of triethylamine (13.90 g, 137.3 mmol) and DMAP (1. 1 g, 9.00 mmol) in THF (50 ml) as described in Intermediate 2, Step 1 (Method B) to give 19.1 g (100 %) of the product as a white solid; IR and'H NMR spectra were identical with that of the racemic intermediate.
99%	With dmap In tetrahydrofuran at 20℃; for 3h;
98%	With dmap In dichloromethane for 16h; Inert atmosphere;

95%	With dmap; triethylamine In chloroform at 20℃; for 18h;	4.1.1. tert-Butyl (1S,4R)-3-oxo-2-azabicyclo[2.2.1]hept-5-en-2-carboxylate (2) (1S)-(+)-2-Azabicyclo[2.2.1]hept-5-en-3-one 1 (0.65 g, 5.96 mmol), Boc2O (2.08 g, 9.54 mmol, 1.6 equiv) and DMAP (0.73 g, 5.96 mmol, 1 equiv) were dissolved in dry EFC (12 mL) and TEA (0.83 mL, 5.96 mmol) was added. The mixture was stirred at rt for 18 h. After this time, the solvent was evaporated in vacuo. The residue was purified by chromatography on silica gel (petroleum ether/Et2O 1:3) to yield 2 (1.18 g, 5.64 mmol, 95%) as a white solid. Mp: 85-87 °C; 1H NMR (400 MHz, CDCl3): δ=1.44 (s, 9H, Boc), 2.09 (d, 2J=8.4 Hz, 1H, H7a), 2.29 (d, 2J=8.4 Hz, 1H, H7b), 3.32 (m, 1H, H4), 4.90 (m, 1H, H1), 6.60 (m, 1H, H5), 6.84 (m, 1H, H6). MS (ESI): m/z=232 [M+Na]+.
93%	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With dmap; triethylamine In tetrahydrofuran at 0℃; for 0.0833333h; Stage #2: di-<i>tert</i>-butyl dicarbonate In tetrahydrofuran at 20℃; for 24h;	14.A To a solution of (1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (1.50 g, 13.7 mmol) in THF (100 mL) was added TEA (1.90 mL, 13.7 mmol) and DMAP (0.27 g, 2.2 mmol). The mixture was stirred for about 5 min at about 0° C. followed by the addition of di-tert-butyl dicarbonate (3.40 mL, 14.4 mmol) in THF (15 mL). The reaction was stirred at ambient temperature for about 24 h. The solvent was removed under reduced pressure and the crude residue was taken up in DCM (50 mL) and washed with water (25 mL) and brine (25 mL). The organic layer was dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-30% EtOAc/heptane to afford (1R,4S)-tert-butyl 3-oxo-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate (2.7 g, 93%) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ 7.26-6.86 (dd, 1H), 6.86-6.64 (m, 1H), 5.08-4.78 (d, 1H), 3.52-3.21 (dd, 1H), 2.32-2.24 (d, 1H), 2.09-2.02 (d, 1H), 1.05-1.36 (s, 9H).
92%	With dmap; triethylamine In tetrahydrofuran at 0 - 20℃; for 12h; Inert atmosphere;	A round bottom flask was charged with (1S)-(+)-2-azabicyclo[2.2.1]hept-5-en-3-one(1.00 g, 9.80 mmol) and dissolved in anhydrous THF (7 mL) at 0 oC.Triethylamine (1.37 mL, 9.80 mmol), DMAP (12 mg, 0.98 mmol) and Boc2O(2.35 g, 10.8 mmol) were added sequentially and the reaction was stirred atroom temperature for 12 h. The reaction mixture was washed with water (10 mL)and extracted into ethyl acetate (20 mL x 2). The combined organics were washedwith brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo to afford the title compound asa bright red powder (1.83 g, 9.0 mmol, 92%). Mp 84-85 oC (lit. 85-86oC); νmax/cm-1 3393, 2976, 1749, 1702, 1506and 1457; 1H NMR (400 MHz, CDCl3) δ = 6.99-6.81 (m, 1H), 6.68-6.64 (m,1H), 4.97-4.94 (m, 1H), 3.41-3.37 (m, 1H), 2.37-2.33 (m, 1H), 2.17-2.13 (m,1H), 1.51 (s, 9H); 13C NMR (100 MHz, CDCl3) δ = 176.3,150.4, 140.0, 138.2, 82.6, 62.4, 54.9, 54.4, 28.0; Hi-Res LC-MS (ESI) m/z calcd for C11H15NNaO3 (M+Na) 232.0950, found 232.0944
91%	With dmap; triethylamine In dichloromethane
90%	With dmap; triethylamine In dichloromethane at 20℃; for 24h;
88%	With dmap In acetonitrile at 20℃;
86%	With dmap; triethylamine In dichloromethane at 0 - 25℃; for 12h;	7 COMPOUND 11 Tert-butoxy carbonyl tert-butyl carbonate (30.00 g, 137.46 mmol, 31.58 mL, 1.5 eq.) was added dropwise to a mixture of (lS,4R)-3-azabicyclo[2.2.1]hept-5-en-2-one (1H) (10 g, 91.64 mmol, 1 eq.), DMAP (1.12 g, 9.16 mmol, 0.1 eq.) and TEA (18.55 g, 183.27 mmol, 25.51 mL, 2 eq.) in DCM (150 mL) at 0 °C. The mixture was stirred at 25 °C for 12 h. The reaction progress was monitored by TLC (PE:EA=3: 1). Upon completion, the reaction was quenched by NaHCCh (sat. aq., 20 mL) and extracted with DCM (2 x 20 mL). The combined organic layers were washed with brine (2 x 20 mL), dried over MgSCri and concentrated to give a residue. The residue was purified by column chromatography (S1O2, PE:EA=15: 1 to 5: 1) to afford tert-butyl (IS, 4R)-2-oxo-3-azabicyclo [2.2.1] hept-5-ene-3- carboxylate (2H) (16.5 g, 78.86 mmol, 86% yield) as a white solid. LCMS: (ESI): m/z calcd. for CiiHisNNaOs 232.09 [M+Na]+, found 232.0.
86%	With dmap; triethylamine In dichloromethane at 0 - 25℃; for 12h;	7 COMPOUND 11 Tert-butoxy carbonyl tert-butyl carbonate (30.00 g, 137.46 mmol, 31.58 mL, 1.5 eq.) was added dropwise to a mixture of (lS,4R)-3-azabicyclo[2.2.1]hept-5-en-2-one (1H) (10 g, 91.64 mmol, 1 eq.), DMAP (1.12 g, 9.16 mmol, 0.1 eq.) and TEA (18.55 g, 183.27 mmol, 25.51 mL, 2 eq.) in DCM (150 mL) at 0 °C. The mixture was stirred at 25 °C for 12 h. The reaction progress was monitored by TLC (PE:EA=3:1). Upon completion, the reaction was quenched by NaHCOs (sat. aq., 20 mL) and extracted with DCM (2 x 20 ml,). The combined organic layers were washed with brine (2 x 20 mL), dried over MgSCri and concentrated to give a residue. The residue was purified by column chromatography (S1O2, PE:EA=T5:1 to 5:1) to afford tert-butyl (IS, 4R)-2-oxo-3-azabicyclo [2.2.1] hept-5-ene-3- carboxylate (2H) (16.5 g, 78.86 mmol, 86% yield) as a white solid. LCMS: (ESI): m/z calcd. for CiiHisNNaCb 232.09 [M+Na]+, found 232.0.
71%	With dmap; triethylamine In dichloromethane at 20℃; for 24h;	tert-Butyl (1R,4S)-3-oxo-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate (33) Compound 33 was synthesized using a modification of the procedures reported by Taylor and co-workers [9] and Katagari et al. [10].(1R, 4S)-2-Azabicyclo[2.2.1]hept-5-en-3-one (32) (0.546 g, 5 mmol) (commercial from Sigma-Aldrich Company; purity ≥ 98%, optical purity ee: 99% (HPLC); [α]20/D -565∘, c =1 in CHCl3; available synthetically as reported by [9, 10])was dissolved in CH2Cl2 (10 ml). Triethylamine (0.7 ml, 5 mmol), di-tert-butyl dicarbonate (2.183 g, 10 mmol), and 4-dimethylaminopyridine (0.611 g, 5 mmol) were then added to the reaction. The mixture was stirred for 24 h at room temperature. The solvent was removed in vacuo. To the resulting residue was added water (5 ml) and ether (5 ml). The organic layer was collected, dried (anhydrous MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (hexane: EtOAc = 5:1) to give the product (0.740 g, 71%) as colorless prisms. mp 85-86 °C (lit. 84-86 °C) [9]1H NMR (300 MHz, CDCl3) δ 1.48 (9H, s, Boc, C(CH3) 3), 2.14 and 2.34 (each 1H, AB type, C7-H2), 3.36 (1H, br s, C4-H), 4.93 (1H, m, C1-H), 6.65 (1H, dm, C5-H), 6.88 (1H, dd, J = 5.3 Hz, 2.2 Hz, C6-H). The 1H NMR spectrum recorded was in complete agreement with the data reported previously [10]
	With pyridine; dmap for 22h; Yield given;
	With dmap In tetrahydrofuran at 25 - 30℃; for 2h;
	With dmap In dichloromethane
	With dmap In tetrahydrofuran at 20℃;
	With dmap; triethylamine In dichloromethane at 25℃; for 2h;	1 Step 1: To a mixture of (li?, S)-2-azabicyclo[2.2.l]hept-5-en-3-one (50 g, 458 mmol), di-tert- butyl dicarbonate (120 g, 550 mmol) and V,Ar-dimethylpyridin-4-amine (5.6 g, 45.8 mmol) in DCM (500 mL) was added triethylamine (69.5 g, 687 mmol) at 25 °C. The reaction mixture was stirred for 2 hours at 25 °C. The reaction was quenched by saturated aqueous NaHCO? (1500 mL) and extracted with EtOAc (2000 mL x 3). The combined organic layers were dried over anhydrous Na2S04 and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography and eluted with 0-20% of ethyl acetate in petroleum ether to afford (li?,4,S)-to7-butyl-3-oxo-2-azabicydo[2.2.1]hept-5-ene-2- carboxylate. MS: 154 (M-55).

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2005/75426, 2005, A1 Location in patent: Page/Page column 29-30
[2]Ober, Matthias; Mueller, Heiko; Pieck, Carsten; Gierlich, Johannes; Carell, Thomas [Journal of the American Chemical Society, 2005, vol. 127, # 51, p. 18143 - 18149]
[3]Wehn, Paul M.; Bois, J. Du [Angewandte Chemie - International Edition, 2009, vol. 48, p. 3802 - 3805][Angew. Chem., Int. Ed., 2009, vol. 121, p. 3860 - 3863]
[4]Location in patent: experimental part Giorgi, Gianluca; Guideri, Luca; Ponticelli, Fabio [Tetrahedron, 2011, vol. 67, # 7, p. 1463 - 1467]
[5]Current Patent Assignee: ABBVIE INC - US2009/312338, 2009, A1 Location in patent: Page/Page column 66
[6]Hensbergen, Albertus Wijnand; Mills, Vanessa R.; Collins, Ian; Jones, Alan M. [Tetrahedron Letters, 2015, vol. 56, # 46, p. 6478 - 6483]
[7]Taylor, Stephen J C; McCague, Raymond; Wisdom, Richard; Lee, Carol; Dickson, Karen; et al. [Tetrahedron Asymmetry, 1993, vol. 4, # 6, p. 1117 - 1128]
[8]Arjona, Odon; Cabas, Ma Jose; Nieto-Rubio, Jose; Querejeta, Ana [Heterocycles, 2006, vol. 68, # 10, p. 2079 - 2086]
[9]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]
[10]Current Patent Assignee: ALIGOS THERAPEUTICS - WO2020/205867, 2020, A1 Location in patent: Paragraph 0216
[11]Current Patent Assignee: ALIGOS THERAPEUTICS - WO2021/202480, 2021, A1 Location in patent: Paragraph 0217
[12]Lu, Meijun; Lu, Qing-Bin; Honek, John F. [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 2, p. 282 - 287]
[13]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[14]Daluge, Susan M.; Martin, Michael T.; Sickles, Barry R.; Livingston, Douglas A. [Nucleosides, nucleotides and nucleic acids, 2000, vol. 19, # 1-2, p. 297 - 327]
[15]Smith, Mark E.B.; Derrien, Nadine; Lloyd, Michael C.; Taylor, Stephen J.C.; Chaplin, David A.; McCague, Raymond [Tetrahedron Letters, 2001, vol. 42, # 7, p. 1347 - 1350]
[16]McGuigan, Christopher; Hassan-Abdallah, Alshaimaa; Srinivasan, Sheila; Wang, Yikang; Siddiqui, Adam; Daluge, Susan M.; Gudmundsson, Kristjan S.; Zhou, Huiqiang; McLean, Ed W.; Peckham, Jennifer P.; Burnette, Thimysta C.; Marr, Harry; Hazen, Richard; Condreay, Lynn D.; Johnson, Lance; Balzarini, Jan [Journal of Medicinal Chemistry, 2006, vol. 49, # 24, p. 7215 - 7226]
[17]Current Patent Assignee: MERCK & CO INC - WO2020/33288, 2020, A1 Location in patent: Page/Page column 66-67

2
[ 79200-56-9 ]
[ 130931-84-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	With hydrogenchloride;	EXAMPLE 102 (1S,4R)-(-)-4-Aminocyclopent-2-en-1-carboxylic Acid Hydrochloride (112, Scheme 13) A mixture of (-)-(1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (109, 15 g, 137 mmol) and 1N HCl (375 mL) was heated at reflux for 1 h. The mixture was concentrated and the residue dried in vacuo to yield 112 in 95% yield. It was used as such for the next step.
	With hydrogenchloride; water; at 80℃; for 2.0h;	To a solution of(1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (5.0 g, 46 mmol) in water (30.5 mL) was added aqueous HCl (2 M, 23.0 mL, 46.0 mmol). After heating at about 80 C. for about 2 h, the reaction mixture was cooled to ambient temperature and the solvent was removed under reduced pressure. The solid was dried in a vacuum oven at about 70 C. and used without further purification. To a solution of (1S,4R)-4-aminocyclopent-2-enecarboxylic acid hydrochloride (9.20 g, 45.8 mmol) in 1,4-dioxane (15 mL) and water (18.3 mL) at about 0 C. was added DIEA (32.0 mL, 183 mmol). After stirring for about 5 min, a solution of di-tert-butyl dicarbonate (11.7 mL, 50.4 mmol) in 1,4-dioxane (5 mL) was added. The reaction mixture was warmed to ambient temperature and stirred for about 18 h. Solvent was removed under reduced pressure and the crude oil was dried in a vacuum oven at about 65 C. for about 3 h. The crude product was purified by silica gel chromatography eluting with a gradient of 80-100% EtOAc/heptane to afford (1S,4R)-4-(tert-butoxycarbonylamino)cyclopent-2-enecarboxylic acid (5.2 g, 50% over 2 steps): LC/MS (Table 2, Method a) Rt=1.81 min; MS m/z: 226 (M-H)-.

Reference： [1]Patent: US6562861,2003,B1
[2]Journal of the Chemical Society. Perkin transactions I,1992,p. 589 - 592
[3]Patent: US2009/312338,2009,A1 .Location in patent: Page/Page column 68

3
[ 79200-56-9 ]
[ 824-94-2 ]
[ 168960-17-6 ]

Yield	Reaction Conditions	Operation in experiment
83%	With tetra-(n-butyl)ammonium iodide; sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 2h;
75%	With sodium hydride In N,N-dimethyl-formamide; mineral oil at 50℃; for 3h; Inert atmosphere;
65%	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide for 0.5h; Cooling with ice; Stage #2: p-methoxybenzyl chloride With tetra-(n-butyl)ammonium iodide In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 20℃; for 3h;

	With potassium hydroxide Yield given;
	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With tetra-(n-butyl)ammonium iodide; sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: p-methoxybenzyl chloride In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 25℃; for 1h;	1 Method C NaH (40.3 g, 1.01 mol, 60% purity, 1.1 equiv) and Bu4NI (16.9 g, 45.8 mmol, 0.05 equiv) were added to THF (300 mL), then a solution of (1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (100.0 g, 916.3 mmol, 1 equiv) in DMF (900 mL) was added dropwise to the mixture at 0° C. The mixture was stirred for 0.5 h, and para-methoxybenzyl chloride (215.2 g, 1.37 mol, 186.5 mL, 1.50 equiv) was added dropwise to the above mixture at 0° C. The mixture was stirred at 25° C. for 1 h. TLC (petroleum ether:ethyl acetate=1:1, Rf=0.20) showed the reactants were consumed completely. The mixture was diluted with MTBE (2 L) and water (3.5 L) was added. Any solids were filtered, and the layers were separated. The aqueous layer was extracted with MTBE (800 mL×2) and the organic layers were combined and washed with brine (1 L×2). The combined organic layers were dried over anhydrous Na2SO4 and concentrated to give a residue as a yellow oil. The residue was purified by column chromatography on silica gel with petroleum ether: ethyl acetate (10:1-1:1) to give a yellow oil. The crude (1R,4S)-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]hept-5-en-3-one (3) (89.5 g, 390.3 mmol, 42.6% yield) was obtained as a yellow oil, which was used in the next step without further purification

Reference： [1]Lu, Hejun; Silverman, Richard B. [Journal of Medicinal Chemistry, 2006, vol. 49, # 25, p. 7404 - 7412]
[2]Kamlet, Adam S.; Preville, Cathy; Farley, Kathleen A.; Piotrowski, David W. [Angewandte Chemie - International Edition, 2013, vol. 52, # 40, p. 10607 - 10610][Angew. Chem., 2013, vol. 125, # 40, p. 10801 - 10804]
[3]Shen, Sida; Doubleday, Peter F.; Weerawarna, Pathum M.; Zhu, Wei; Kelleher, Neil L.; Silverman, Richard B. [ACS Medicinal Chemistry Letters, 2020, vol. 11, # 10, p. 1949 - 1955] Beaupre, Brett A.; Butrin, Arseniy; Doubleday, Peter F.; Ferreira, Glaucio M.; Kelleher, Neil L.; Liu, Dali; Melani, Rafael D.; Moran, Graham R.; Shen, Sida; Silverman, Richard B.; Tavares, Mauricio T. [Journal of the American Chemical Society, 2021, vol. 143, # 23, p. 8689 - 8703]
[4]Palmer, Christopher F.; McCague, Raymond [Journal of the Chemical Society. Perkin transactions I, 1995, # 10, p. 1201 - 1204]
[5]Current Patent Assignee: NORTHWESTERN UNIVERSITY (ILLINOIS) - US2019/359555, 2019, A1 Location in patent: Paragraph 0044; 0121-0122

4
[ 79200-56-9 ]
[ 79200-55-8 ]

Yield	Reaction Conditions	Operation in experiment
98%	With osmium(VIII) oxide; 4-methylmorpholine N-oxide In 1,4-dioxane at 0 - 20℃; for 3h;	1 Example 1. (1R,4S,5R,6S)-5,6-dihydroxy-2-azabicyclo[2.2.1]heptan-3-one (1) [0368] To an ice-cold solution of (1R)-(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (21.8 g, 0.2 mol) in dioxane (400 mL) was added 4-methylmorpholine N-oxide monohydrate (40.5 g, 0.3 mol) followed by slow addition of OsO4 (0.15 M soln in water, 2 mL). Slow dissolution of NMMO indicated reaction progress, reaction mixture was stirred for 1 h at 0°C and 2 h at room temperature. Reaction was quenched by addition of sodium bisulfite (30% soln. in water, 5 mL), volatiles were evaporated, crude product was adsorbed on silica, applied on a plug of silica and pure compound was eluted with a gradient of MeOH in CHCl3 (0-20%) to yield the title compound (28.16 g, 98%) as white solid. NMR spectra matched the data in the literature reference J. Org. Chem.1981, 46(16), 3268.
98%	With osmium(VIII) oxide; 4-methylmorpholine N-oxide; 4-methylmorpholine 4-oxide monohydrate In 1,4-dioxane; water at 0 - 20℃; for 3h;	3 (1R,4S,5R,6S)-5,6-dihydroxy-2-azabicyclo[2.2.1]heptan-3-one (21) To an ice-cold solution of 58 (1R)-(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (21.8 g, 0.2 mol) in 59 dioxane (400 mL) was added 60 4-methylmorpholine N-oxide monohydrate (40.5 g, 0.3 mol) followed by slow addition of 61 OsO4 (0.15 M soln in 26 water, 2 mL). Slow dissolution of NMMO indicated reaction progress, reaction mixture was stirred for 1 h at 0° C. and 2 h at room temperature. Reaction was quenched by addition of 62 sodium bisulfite (30% soln. in water, 5 mL), volatiles were evaporated, crude product was adsorbed on silica, applied on a plug of silica and pure compound was eluted with a gradient of 9 MeOH in 63 CHCl3 (0-20%) to yield the 64 title compound (28.16 g, 98%) as white solid. NMR spectra matched the data in the literature reference J. Org. Chem. 1981, 46(16), 3268.
94%	With osmium(VIII) oxide; 4-methylmorpholine N-oxide In water; <i>tert</i>-butyl alcohol at 70℃; for 0.5h;

91%	With osmium(VIII) oxide; N-methyl-2-indolinone In acetone for 3h; Ambient temperature;
91%	With osmium(VIII) oxide; N-methyl-2-indolinone In acetone
75%	With osmium(VIII) oxide; 4-methylmorpholine N-oxide In i-Amyl alcohol; water; <i>tert</i>-butyl alcohol at 70℃; Sealed tube;
75%	With osmium(VIII) oxide; i-Amyl alcohol; 4-methylmorpholine N-oxide In water; <i>tert</i>-butyl alcohol at 70℃;	(1R,4S,5R,6S)-5,6-dihydroxy-2-azabicyclo[2.2.1]heptan-3-one (e-2) It contains 4.33g (39.7mmol) (1R, 4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (e-1)And 5.14g (43.9mmol) of N-methylmorpholine N-oxide in a resealable tube of a solution of 20mL of isoamyl alcohol and 20mL of water,Add 3 mL (0.24 mmol) 2.5% (w/w) osmium tetroxide solution in tert-butanol.The tube was sealed with a PTFE cap, and the reaction was heated at 70°C for 1-4 hours.TLC (20% i-PrOH/80% EtOAc, silica gel plate, potassium permanganate or p-anisaldehyde staining) showed complete consumption of raw materials after this time. (If any raw materials remain, additional osmium tetroxide solution can be added.) Remove the heat, add 500 mg (4.81 mmol) sodium bisulfite, and stir the mixture for 45 minutes while cooling to ambient temperature. The solvent was removed in vacuo at 40°C. The thick dark brown oily residue was suspended in 30 mL methanol, and 30 mL 2-propanol was added. The mixture was concentrated in vacuo to remove as much water and N-methylmorpholine as possible to obtain a brown solid. The solid was suspended in 50 mL methanol, slurried with 50 mL silica gel, and concentrated to dryness in vacuo at 40°C. A 120 g silica gel column was equilibrated with 10% 2-propanol/90% ethyl acetate, and the silica gel product mixture was assembled on the top of the column. The column was eluted with 10% i-PrOH/EtOAc at a rate of 85 mL/min for 5 minutes, 10% to 30% i-PrOH/EtOAc gradient for 20 minutes, and then 30% i-PrOH/EtOAc. 5 minutes. The product eluted at about 20% i-PrOH/EtOAc and produced a very weak UV absorbance at 254 nm. TLC (20% i-PrOH/EtOAc, stained with freshly prepared p-anisaldehyde stain) shows that the undesired all-cis isomer elutes first and produces pink spots, while the desired isomer appears yellow next to it Spots, which turn brown and heat further. The product-containing fractions were concentrated in vacuo at 30-40°C to obtain a white solid. This material was dissolved in 20 mL of hot methanol and concentrated in vacuo to remove residual chromatography solvent. White crystalline solid e-2, yield 4.27g, 75%.
69%	With osmium(VIII) oxide; 4-methylmorpholine N-oxide In i-Amyl alcohol; <i>tert</i>-butyl alcohol at 15 - 70℃;	1.1; 2.1 step 1:(1R,4S,5R,6S)-5,6-Dihydroxy-2-azabicyclo[2.2.1]heptan-3-oneSynthesis of (A-2) At room temperature (15°C) in isoamyl alcohol (500 mL) and water (500 mL)(1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-oneA-1 (Chemical Reviews, 2012, 112 (8), pp. 4642 to 4686) (100 g, 916 mmol) and NMO (118 g, 1.01 mol)The light yellow biphasic mixture was added to 2.5% OsO4 in t-BuOH (1.5 g, 5.9 mmol, 76 mL). The mixture was heated at 70 °C for 2 hours.The mixture was cooled to room temperature (15°C).NaHSO 3 (12 g) was added and stirred at room temperature (15° C.) for 45 minutes.The mixture was concentrated in vacuo to provide the crude product as a dark solid (150 g).It is made by tannin chromatography with MeOH in DCM = 10%It was purified by stripping to provide A-2 (90 g, 69%) as a pale pink solid.
	With osmium(VIII) oxide; 4-methylmorpholine N-oxide In 1,4-dioxane; water at 0 - 20℃; for 3h;	1 (1R4S.5R6S)-5.6-dihydroxy-2-azabicyclo[2.2.1]heptan-3-one (1): To an ice-cold solution of (1R) -(-)-2- Azabicyclo [2.2.1]hept-5 -en-3 -one (21.8 g, 0,2 mol) in dioxane (400 mL) was added 4-methylmorpholine N-oxide monohydrate (40.5 g, 0.3 mol) followed by slow addition of OsO4 (0.15 M in water, 2 mL) (Scheme 1). Slow dissolution of NMMO indicated reaction progress, reaction mixture was stirred for 1 h at 0 °C and 2 h at room temperature. Reaction was quenched by addition of sodium bisulfite (30% in water, 5 mL), volatiles were evaporated, erode product was adsorbed on silica, applied on a plug of silica and pure compound was eluted with a gradient ofMeOH in CHCl3 (0-20%) to yield the title compound. NMR spectra match literature data (J. Org. Chem. 1981, 46(16), 3268).

Reference： [1]Current Patent Assignee: INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY V; CZECH ACADEMY OF SCIENCES - WO2019/211799, 2019, A1 Location in patent: Paragraph 0368
[2]Current Patent Assignee: CZECH ACADEMY OF SCIENCES - US2019/185510, 2019, A1 Location in patent: Paragraph 0936; 0937
[3]Nair, Vasu; Zhang, Fan [Molecules, 2013, vol. 18, # 9, p. 11576 - 11585]
[4]Hutchinson, Edward J.; Taylor, Brian F.; Blackburn, G. Michael [Chemical Communications, 1996, # 24, p. 2765 - 2766]
[5]Hutchinson, Edward J.; Blackburn, G. Michael [Collection of Czechoslovak Chemical Communications, 1996, vol. 61, p. S96 - S98]
[6]Szczepankiewicz, Bruce G.; Dai, Han; Koppetsch, Karsten J.; Qian, Dongming; Jiang, Fan; Mao, Cheney; Perni, Robert B. [Journal of Organic Chemistry, 2012, vol. 77, # 17, p. 7319 - 7329]
[7]Current Patent Assignee: Zhou Yutian; Liu Jianbo - CN111410661, 2020, A Location in patent: Paragraph 0205-0208
[8]Current Patent Assignee: PFIZER INC - TW2018/2074, 2018, A Location in patent: Page/Page column 86
[9]Current Patent Assignee: CZECH ACADEMY OF SCIENCES - WO2020/178768, 2020, A1 Location in patent: Paragraph 0364

5
[ 79200-56-9 ]
2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether for 7h; Heating;
	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 60℃; for 15h; Inert atmosphere; Stage #2: With water In tetrahydrofuran at 0℃;	B.B2 (1R,4S)-tert-Butyl 2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate (B2) (1R)-(-)-2-Azabicyclo[2.2.1]hept-5-en-3-one (5.00 g, 45.8 mmol, ee=99%) dissolved in anhydrous THF (15.0 mL) was slowly added to a solution of lithium aluminum hydride (57.3 mL, 57.3 mmol, 1M solution in THF) in anhydrous THF (35.0 mL) under nitrogen atmosphere at 0° C. After the addition was successfully completed, the mixture was stirred for 3 h at 23° C. and then heated at 60° C. for 12 h. The resulting heterogeneous mixture was cooled to 0° C. and H2O (5.00 mL) was carefully added to the mixture via syringe. The white colored suspension was filtered through a Celite filter aid and the pad was washed with anhydrous diethyl ether (50.0 mL). The filtrate was then treated with (Boc)2O (15.0 g, 68.7 mmol) and stirred for 24 h at 23° C. The mixture was concentrated in vacuo and the crude material was purified by column chromatography (SiO2, EtOAc:n-Hex 1:7 (v/v)) to provide the title compound B2 as a colorless crystal. (After the solvent was evaporated by rotavap, the resulting colorless oil quickly crystallized at 23° C.)
	With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 60℃; for 15h; Inert atmosphere;	6.B.6a; 6.B.6c Example 6 SECTION B: Synthesis of unique R⁴ pieces Example 6a Asymmetric Synthesis of (lR,4R,5R)tert-butyl5-amino-2-azabicyclo[2.2.1]heptane-2- carboxylate Example 6 SECTION B: Synthesis of unique R4 pieces Example 6a Asymmetric Synthesis of (lR,4R,5R)tert-butyl5-amino-2-azabicyclo[2.2.1]heptane-2- carboxylate General Scheme: Bl B2 B3 B4 B5 B6 B7 THF Sol. (lR,4S)-tert-Buty 2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate (B2) [0462] (li?)-(-)-2-Azabicyclo[2.2.1]hept-5-en-3-one (5.00 g, 45.8 mmol, ee = 99%) dissolved in anhydrous THF (15.0 mL) was slowly added to a solution of lithium aluminum hydride (57.3 mL, 57.3 mmol, 1M solution in THF) in anhydrous THF (35.0 mL) under nitrogen atmosphere at 0 °C. After the addition was successfully completed, the mixture was stirred for 3 h at 23 °C and then heated at 60 °C for 12 h. The resulting heterogeneous mixture was cooled to 0 °C and H20 (5.00 mL) was carefully added to the mixture via syringe. The white colored suspension was filtered through a Celite filter aid and the pad was washed with anhydrous diethyl ether (50.0 mL). The filtrate was then treated with (Boc)20 (15.0 g, 68.7 mmol) and stirred for 24 h at 23 °C. The mixture was concentrated in vacuo and the crude material was purified by column chromatography (Si02, EtOAc:-Hex 1 :7 (v/v)) to provide the title compound B2 as a colorless crystal. (After the solvent was evaporated by rotavap, the resulting colorless oil quickly crystallized at 23 °C) OH (lR,4R,5S)-fert-Butyl 5-hydroxy-2-azabicyclo[2.2.1]heptanes-2-carboxylate (B3) [0463] The mixture of {R, S)-tert- vXy 2-azabicyclo[2.2.1]hept-5-ene-2- carboxylate (1.50 g, 7.68 mmol) and sodium borohydride (0.24g, 6.30 mmol) in THF (9.5 mL) was stirred for 0.5 h under nitrogen atmosphere at 23 °C. After being stirred for 0.5 h, the mixture was warmed to 35 °C and then dimethylsulfate (0.57 mL, 6.30 mmol) dissolved in THF (2.0 mL) was added dropwise via syringe. The resulting mixture was stirred for 4 h at 35 °C, then cooled to 0 °C and quenched by dropwise addition of H20 (5.0 mL). A solution of sodium hydroxide (15.0 mL, 15.0 mmol, 1 M solution of NaOH) was added at 0 °C followed by addition of hydrogen peroxide (0.96 mL, 30 wt.% in H20). The mixture was warmed to 23 °C and stirred for additional 1 h. The resulting colorless solution was diluted with diethyl ether (75.0 mL) and the organic layer was separated, washed with brine (50.0 mL) and dried over magnesium sulfate. The mixture was concentrated by rotavap and the resulting colorless oil as crude product was purified by column chromatography (Si02, EtOAc:-Hex 1 : 1 (v/v)) to provide the title compound B3 (1.00 g, 4.69 mmol, 61 %) as a colorless oil. (lR,4R)-tert-Buty 5-oxo-2-azabicyclo[2.2.1] heptanes-2-carboxylate (B4) [0464] 2-Iodoxybenzoic acid (3.43 g, 5.52 mmol, 45 wt.% (SIBX)) was added to a solution of {R, R,5S)-tert- vXy 5-hydroxy-2-azabicyclo[2.2.1]heptanes-2-carboxylate (0.87 g, 4.09 mmol) dissolved in dimethylsulfoxide (5.0 mL) and toluene (10.0 mL) under nitrogen atmosphere at 23 °C. The mixture was stirred for 3 h at 60 °C and cooled to 23 °C. The resulting mixture was treated with saturated sodium carbonate (aq.) (50.0 mL) and filtered under reduced pressure to remove a white solid. The filtrate was extracted with ethyl acetate (75.0 mL x 3) and the organic extracts were washed with brine, dried over magnesium sulfate and concentrated in vacuo. The crude material as colorless oil was purified by column chromatography (Si02, EtOAc:-Hex 1 :2 (v/v)) to provide the title compound B4 (0.62 g, 2.91 mmol, 71 %) as a white solid. (lR,4R,5R)-tert-Buty 5-(benzylamino)-2-azabicyclo[2.2.1]heptanes-2-carboxylate (B5) [0465] Sodium triacetoxyboro hydride (23.4 g, 105 mmol) and glacial acetic acid (4.66 g, 77.6 mmol) were added to a solution of (lR,4R)-tert-bu yl 5-oxo-2- azabicyclo[2.2.1]heptane-2-carboxylate (16.4 g, 77.6 mmol) and benzylamine (8.32 g, 77.6 mmol) in 1,2-dichloroethane (250 mL) under nitrogen atmosphere at 23 °C. The resulting mixture was stirred for 5 h at 23 °C and then quenched with saturated sodium bicarbonate (aq.) (300 mL). The mixture was extracted with ethyl acetate (350 mL x 3) and the organic extracts were washed with brine, dried over magnesium sulfate and concentrated in vacuo. The crude material was purified by column chromatography (Si02, EtOAc:-Hex. 9: 1 (v/v)) to provide the title compound B5 (20.0 g, 66.1 mmol, 85 %) as colorless oil. [0466] 1H NMR (300 MHz, CDC13): δ 7.35-7.27 (m, 5H), 4.21 (s, 0.5H), 4.08 (s, 0.5H), 3.80-3.68 (m, 2H), 3.58 (d, J = 10.0 Hz, 1H), 3.28-3.22 (m, 1H), 3.20-3.1 1 (m, 1H), 2.62 (m, 1H), 2.05-1.97 (m, 1H), 1.76-1.69 (m, 1H), 1.55-1.51 (m, 1H), 1.48 (s, 9H), 1.30- (lR,4R,5R)-tert-Buty 5-amino-2-azabicyclo[2.2.1]heptanes-2-carboxylate (B6) [0467] The mixture of palladium hydroxide (4.30 g, 6.12 mmol, 10.0 mol%, 20 wt.% on carbon, 50 % wet) and (lR,4R,5R)-tert-butyl 5-(benzylamino)-2-azabicyclo[2.2.1] heptane-2-carboxylate (18.5 g, 61.2 mmol) in ethanol (100 mL) was stirred for 36 h under hydrogen atmosphere at 23 °C. The resulting mixture was filter through Celite and the pad was washed with ethyl acetate (500 mL). The filtrate was concentrated under reduced pressure to provide the title compound B6 (12.8 g, 60.3 mmol, 99 %) as a colorless crystal. [0468] 1H NMR (300 MHz, MeOD): δ 4.1 1 (s, 1H), 3.56-3.51 (m, 1H), 3.43-3.39 (m, 1H), 3.18-3.15 (m, 1H), 2.49 (bs, 1H), 2.14-2.05 (m, 1H), 1.74-1.68 (m, 1H), 1.61 (d, J = - 1.10 (m, 1H). [0469] Preparation of (lR,4R,5R)-2-azabicyclo[2.2.1]heptan-5-amine (B7): The Boc protected amine (200 mg, 0.94 mmol) in CH2CI2 (10 mL) was added dropwise of TFA (5 mL) and the mixture was stirred at RT for 10 minutes. The solvent was removed at vacuum and the amine (100 mg, 99%) was used for the reactions without further purification

With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 60℃; for 7h;

2-2.1 1.Preparation of (1R, 4S)-2-azabicyclo[2.2.1]hept-5-ene 1. Preparation of (1R, 4S)-2-azabicyclo[2.2.1]hept-5-ene (1R, 4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (5.0 g, 45.8 mmol) was added to anhydrous THF (100 mL), and lithium aluminum hydride (2.26 g, 59.5 mol) was added in batches at 0 °C. The mixture solution reacted at 25 °C for 3 hrs. Then the solution was heated to 60 °C and reacted for 4 hrs. The reaction solution was quenched with water at 0 °C. EA (100 mL) and sodium chloride aqueous solution (80 mL) were added for extraction, and the organic phase was dried over anhydrous sodium sulfate to obtain a crude product which would be directly used in the next step without being purified.

Reference： [1]Arakawa, Yasushi; Yasuda, Mika; Ohnishi, Masafumi; Yoshifuji, Shigeyuki [Chemical and Pharmaceutical Bulletin, 1997, vol. 45, # 2, p. 255 - 259]
[2]Current Patent Assignee: LAWRENCE LIVERMORE NATIONAL SECURITY, LLC - US2012/238751, 2012, A1 Location in patent: Page/Page column 35
[3]Current Patent Assignee: MERCK & CO INC; LAWRENCE LIVERMORE NATIONAL SECURITY, LLC - WO2014/43272, 2014, A1 Location in patent: Paragraph 0461; 0462; 0472; 0473
[4]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - EP3650449, 2020, A1 Location in patent: Paragraph 0196-0198

6
[ 59473-45-9 ]
[ 79200-56-9 ]
[ 195830-50-3 ]

Yield	Reaction Conditions	Operation in experiment
53%	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With sodium hydride In tetrahydrofuran at 20℃; for 1h; Stage #2: 2-(chloromethyl)iodobenzene In tetrahydrofuran for 12h; Heating;
53%	With sodium hydride In tetrahydrofuran at 65℃; for 16h;

Reference： [1]Grigg, Ronald; Sansano, Jose M.; Santhakumar, Vijayaratnam; Sridharan, Visuvanathar; Thangavelanthum, Ravishanker; Thornton-Pett, Mark; Wilson, David [Tetrahedron, 1997, vol. 53, # 34, p. 11803 - 11826]
[2]Fretwell, Paul; Grigg, Ronald; Sansano, Jose M; Sridharan, Visuvanathar; Sukirthalingam, Sukanthini; Wilson, David; Redpath, James [Tetrahedron, 2000, vol. 56, # 38, p. 7525 - 7539]

7
[ 67-56-1 ]
[ 79200-56-9 ]
[ 138923-03-2 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride for 10h; Heating;
	With hydrogenchloride
	With hydrogenchloride In water for 2.5h; Inert atmosphere; Reflux;	4.5.8. Methyl 4-(2,2,2-trifluoroacetamido)cyclopent-2-ene-1-carboxylate (3e) General procedure: Under an atmosphere of argon, a mixture of lactam (±)-2 (1.09 g,10.0 mmol) and hydrochloride in methanol (1.25 M, 20 mL) was heated under reflux for 12 h. The mixture was then concentrated under reduced pressure. To the residue were added CH2Cl2 (10 mL) and triethylamine (4.66 mL, 33.5 mmol). Trifluoroacetic anhydride (3.34 mL, 24.0 mmol) was then added dropwise at 0 C. The mixture was stirred at room temperature for 18 h to complete the acylation reaction. The mixture was extracted with CH2Cl2 and brine. The organic phase was dried over MgSO4, filtered, and concentratedunder reduced pressure. The residue was purified by silica gel chromatography (hexane/EtOAc 10:1) to afford (±)-3e,1.76 g, 75%yield). By a similar procedure, optically active lactam (-)-2 underwent solvolysis in 4M HCl methanolic solution for 2.5 h, followed by acylation with trifluoroacetic anhydride, to give (-)-3e.

3.85 g	Stage #1: methanol; (-)-2-azabicyclo[2.2.1]hept-5-en-3-one at 20℃; for 0.25h; Stage #2: With thionyl chloride In methanol; water at 25 - 30℃; for 1.5h; Further stages;	1 Preparation of (1S,4R)-4-aminocyclopent-2-enecarboxylic acid methyl ester (2) To a 150 mL three-necked flask, 10 g (0.092 mol) (1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (1) was dissolved in 9.43 g methanol. Add a drying tube and stir at room temperature for 15 min. After that, 5.72 g (0.048 mol) of sulfoxide chloride was slowly added dropwise to control the ground acceleration. During the dropwise addition, the temperature rose to 25-30°C. After the drop, continue to stir the reaction for 1.5h. Then, a solution of 6.88 g (0.046 mol) of L-tartaric acid dissolved in 20 mL of water was added, and the reaction was continuously stirred for 8 h. Suction filtration removes insoluble sludge-like solids. Afterwards, 5.17 g of triethylamine was added dropwise, and when it was added halfway, the stirring was slowed down to control the acceleration of the drop, and the reaction temperature was below 50°C. After the completion of the drop, the reaction was stirred for 2h. Then, at room temperature, a small amount of seed crystals were added to naturally crystallize. Suction filtration gave 3.85 g of off-white square crystals.
	With thionyl chloride at 20℃; Cooling with ice;

Reference： [1]Chand; Montgomery; Kotian; Dehghani; El-Kattan; Lin; Hutchison; Babu; Bantia; Elliott [Journal of Medicinal Chemistry, 2001, vol. 44, # 25, p. 4379 - 4392]
[2]Babu; Chand; Bantia; Kotian; Dehghani; El-Kattan; Lin; Hutchison; Elliott; Parker; Ananth; Horn; Laver; Montgomery [Journal of Medicinal Chemistry, 2000, vol. 43, # 19, p. 3482 - 3486]
[3]Chen, Chien-Liang; Chiu, Tzu-Wei; Chen, Yung-Wen; Fang, Jim-Min [Tetrahedron, 2019, vol. 75, # 33, p. 4458 - 4470]
[4]Current Patent Assignee: HANGZHOU CANGHAIFAN PHARMACEUTICAL TECH - CN111116592, 2020, A Location in patent: Paragraph 0043; 0045-0047
[5]Rydzik, Anna M.; Balk, Regina; Koegler, Martin; Steinle, Tobias; Riether, Doris; Gottschling, Dirk [Organic Letters, 2021, vol. 23, # 17, p. 6735 - 6739]

8
[ 67-56-1 ]
[ 79200-56-9 ]
[ 229613-83-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With thionyl chloride at 0℃; for 2h;
100%	With thionyl chloride at 0 - 20℃; for 14h;
100%	With thionyl chloride at 0℃;

96%	With hydrogenchloride at 20℃; for 5h; Reflux;
92%	With thionyl chloride at 0 - 8℃; for 18.5h; Inert atmosphere; Industry scale;	1 EXAMPLE 1 : Preparation of (1 S,4R)-methyl 4-aminocyclopent-2-enecarboxylate, hydrochloride salt, 10.7 10Methanol (11 L) is combined with 7 (2.50 kg, 22.91 mol) under nitrogen.The solution is cooled to 00C and thionyl chloride (1.88 L, 25.78 mol) is added over 2.5 hours. The mixture is allowed to warm to 8°C, stirred for 16 hours, then concentrated to a volume of 7.5 L. MTBE (20 L) is added and the resulting precipitate is collected and dried to give 10 as an off-white solid (3.74 kg, 92% yield).1H NMR (400MHz, MeOH): δ 6.24-6.23 (1 H, m), 6.06-6.0.3 (1 H, m), 4.40(1 H, brs), 3.81 -3.74 (4H, m), 2.77-2.69 (1 H, m), 2.22-2.15 (1 H, m).
	With thionyl chloride at 5℃; for 2h;	1 Methyl-(1S,4R)-4-aminocyclopent-2-ene-1-carboxylate hydrochloride (-)-2-Azabicyclo[2,2,1]hept-5-en-3-one (20.00 g, 0.1833 mmol) was dissolved in MeOH (140 mL) and this mixture was cooled to 0° C. Thionyl chloride (29.4 mL, 0.403 mol) was then added dropwise, keeping the temperature less than 15° C. Upon completion of addition, the mixture was left to stir at 5° C. for 2 hours. The solvent was removed under reduced pressure to yield an oil, which was dried further under high vacuum overnight at 35° C. to afford the title compound as a white solid (33 g) which was used without further purification. 1H NMR (300 MHz, DMSO, δ): 8.45 (s, 3H), 6.03 (m, 1H), 5.87 (m, 1H), 4.13 (m, 1H), 3.60 (m, 4H), 2.53 (m, 1H) and 1.89 (m, 1H).
	With hydrogenchloride for 18h; Inert atmosphere; Reflux;	(1R,4S)-(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (70 mg, 0.64 mmol) was heated to reflux for 18 h in methanolic hydrochloride (10 mL). The solvent was removed in vacuo to yield methyl (1S,4R)-4-aminocyclopent-2-enecarboxylate hydrochloride as a white solid. To a mixture of the crude hydrochloride salt and sodium carbonate (207 mg, 1.95 mmol) in 10 mL distilled water at 0 °C was added benzyl chloroformate dropwise via syringe (100 μL, 0.70 mmol). The solution was stirred for 30 min at 0 °C and 30 min at room temperature. The aqueous layer was extracted with 3 x 20 mL dichloromethane and the organic layers were combined and dried over anhydrous sodium sulfate. The solvent was removed in vacuo to yield a colorless oil. Flash-column chromatography (silica, hexanes-ether 2:1, Rf 0.22)afforded O-methyl, N-carboxybenzoyl (1S,4R)-4-aminocyclopent-2-enecarboxylate as a white solid (105 mg, 0.382 mmol, 60%). MP 155 °C; IR (cm-1, film) 3428, 1731, 1716, 1506; 1H NMR (500 MHz, CDCl3) δ 7.27-7.36 (m, 5H), 5.84-5.90 (m, 2H), 5.16 (d, J = 9.7 Hz, 1H), 5.08 (s, 2H), 4.80-4.87 (m, 1H), 3.68 (s, 3H), 3.43-3.49 (m, 1H), 2.48 (dt, J = 14.2, 8.4 Hz, 1H), 1.88 (dt, J = 14.2, 3.8 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 175.4, 155.8, 136.8, 134.7, 131.8, 128.7, 128.3, 128.3, 66.8, 56.5, 52.4, 49.4, 34.7.
	With hydrogenchloride for 12h; Reflux;

Reference： [1]Smith, Mark E.B.; Derrien, Nadine; Lloyd, Michael C.; Taylor, Stephen J.C.; Chaplin, David A.; McCague, Raymond [Tetrahedron Letters, 2001, vol. 42, # 7, p. 1347 - 1350]
[2]Smith, Mark E.B.; Lloyd, Michael C.; Derrien, Nadine; Lloyd, Richard C.; Taylor, Stephen J.C.; Chaplin, David A.; Casy, Guy; McCague, Raymond [Tetrahedron Asymmetry, 2001, vol. 12, # 5, p. 703 - 705]
[3]Armitage, Ian; Elliott, Eric L.; Hicks, Frederick; Langston, Marianne; McCarron, Ashley; McCubbin, Quentin J.; Obrien, Erin; Stirling, Matt; Zhu, Lei [Organic Process Research and Development, 2015, vol. 19, # 9, p. 1299 - 1307]
[4]Jia, Fei; Hong, Juan; Sun, Ping-Hua; Chen, Jian-Xin; Chen, Wei-Min [Synthetic Communications, 2013, vol. 43, # 19, p. 2641 - 2647]
[5]Current Patent Assignee: DR REDDY'S LABORATORIES LIMITED - WO2011/3061, 2011, A2 Location in patent: Page/Page column 9
[6]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US2009/36678, 2009, A1 Location in patent: Page/Page column 24
[7]Bromba, Caleb M.; Mason, Jeremy W.; Brant, Michael G.; Chan, Tracy; Lunke, Martine D.; Petric, Martin; Boulanger, Martin J.; Wulff, Jeremy E. [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 23, p. 7137 - 7141]
[8]Wang, Peng-Cheng; Fang, Jim-Min; Tsai, Keng-Chang; Wang, Shi-Yun; Huang, Wen-I; Tseng, Yin-Chen; Cheng, Yih-Shyun E.; Cheng, Ting-Jen Rachel; Wong, Chi-Huey [Journal of Medicinal Chemistry, 2016, vol. 59, # 11, p. 5297 - 5310]

9
[ 49805-30-3 ]
[ 79200-56-9 ]
[ 49805-30-3 ]

Reference： [1]Heterocycles,2001,vol. 54,p. 405 - 410
[2]Process Biochemistry,2013,vol. 48,p. 1674 - 1678
[3]ChemCatChem,2014,vol. 6,p. 2517 - 2521
[4]RSC Advances,2016,vol. 6,p. 21293 - 21301

10
[ 79200-56-9 ]
[ 134003-03-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogen In methanol at 20℃; for 5h; atmospheric pressure;
98%	With hydrogen; acetic acid In ethyl acetate at 20℃; for 1.5h;
98%	With palladium 10% on activated carbon; hydrogen In methanol for 3h;	43 Preparation 43: (1S,4R)-2-azabicyclo[2.2.1]heptan-3-one A mixture of (1R)-(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (1.0 g, 9.2 mmol) and 10% palladium on carbon (0.4 g) in methanol (50 mL) was stirred under an atmosphere of hydrogen for 3 hrs. The mixture was filtered through Celite and the filter cake washed with methanol. The combined organics were concentrated in vacuo to afford the require product (1 g, 98%). 1H NMR (300 MHz, CDCl3): δ 5.91 (br s, 1H), 3.89 (s, 1H), 2.74 (s, 1H), 1.96-1.59 (m, 5H), 1.42-1.37 (m, 1H).

98%	With hydrogen In ethyl acetate for 1.5h; Ambient temperature;
	With palladium 10% on activated carbon; hydrogen In ethyl acetate at 20℃; for 24h;
	With hydrogen In ethyl acetate for 5h;	1.1 (1S,4R)-2-Azabicyclo[2.2.1]heptan-3-one A suspension of (1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (20.0 g), palladium (5% on activated carbon; 2.0 g) and ethyl acetate (250 ml) was stirred vigorously under an atmosphere of hydrogen for 5 hours. The catalyst was filtered off with suction and the filtrate was concentrated. This afforded the product with the molecular weight of 111.14 (C6H9NO); MS (ESI): 112 (M+H+).
	With palladium 10% on activated carbon; hydrogen In ethyl acetate at 20℃; for 12h;	To a stirred solution of (1R,4S)-2- azabicyclo[2.2.i]hept-5-en-3-one (15, 100 mg, 0.91 mmol) in ethyl acetate (5 mE) was added 10% Pd/C (15 mg) and hydrogenated for 12 h by using hydrogen balloons at room temperature. Reaction mixture was filtered through celite bed, filter cake washed with ethyl acetate (3 mE). The combined organic layers was concentrated under reduced pressure afforded (1 S,4R)-2-azabicyclo[2.2. i]heptan-3-one as a white solid, which was directly used in the next reaction. To an ice-cool stirred solution of (1S,4R)-2-azabicyclo[2.2. i]heptan-3-one in methanol (3 mE) was added thionylchloride (0.2 mE, 1.64 mmol). After 24 h at room temperature, reaction mixture was concentrated under diminished pressure afforded 16 as a white solid: yield 109mg (66%), which was directly used in the next reaction; ‘H NMR (400 MHz, D20) ö 1.80-1.89 (m, 1H), 1.90-1.97 (m, 1H), 1.99-2.06 (m, 1H), 2.09-2.13 (m, 1H), 2.14-2.21 (m, 1H), 2.42-2.50 (m, 1H), 3.03-3.11 (m, 1H) and 3.76-3.82 (m, 4H (3+1)), ‘3C NMR (100 MHz, D20) ö 27.4, 29.8, 33.6, 42.2, 51.4, 52.6 and 178.3.
	With palladium 10% on activated carbon; hydrogen In methanol at 25℃; for 5h; Inert atmosphere;	tert-Butyl (1S,4R)-3-oxo-2-azabicyclo[2.2.1]heptane-2-carboxylate (3) [Reduction] To a solution of the commercially available (1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (2) (10g, 91.70mmol) in anhydrous MeOH (180mL) was added 10% palladium on activated carbon (3g). After stirring at 25°C for 5h under H2 atmosphere, the reaction mixture was filtered through a pad of Celite, and the filtrate was concentrated in vacuo to give the corresponding lactam [30] (9.17g). The crude lactam was used in the following step without further purification: 1H NMR (400MHz, CDCl3) δ 5.75 (br s, 1H), 3.89 (s, 1H), 2.74 (s, 1H), 1.94-1.91 (m, 1H), 1.88-1.80 (m, 2H), 1.65-1.57 (m, 2H), 1.42-1.36 (m, 1H); [Boc Protection] A mixture of the lactam (9.17g, 82.51mmol), Boc2O (28.60g, 131.04mmol), and DMAP (5.04g, 41.25mmol) in anhydrous MeCN (300mL) was stirred at 25°C for 1h. The solvents were removed in vacuo and the residue was purified by column chromatography (silica gel, hexanes/EtOAc, 5/2) to afford the known Boc-protected lactam 3 [30] (15.68g, 81% for two steps) as a white solid: 1H NMR (400MHz, CDCl3) δ 4.53 (s, 1H), 2.85 (s, 1H), 1.95-1.90 (m, 2H), 1.80-1.73 (m, 2H), 1.51 (s, 9H), 1.43-1.39 (m, 2H).

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]
[2]Cardoso do Vale, Maria Luísa; Rodríguez-Borges, José Enrique; Caamaño, Olga; Fernández, Franco; García-Mera, Xerardo [Tetrahedron, 2006, vol. 62, # 40, p. 9475 - 9482]
[3]Current Patent Assignee: SYNCHRONICITY PHARMA - US2015/284362, 2015, A1 Location in patent: Paragraph 0356
[4]Blanco, Jose M.; Caamano, Olga; Fernandez, Franco; Garcia-Mera, Xerardo; Lopez, Carmen; Rodriguez, Gonzalo; Rodriguez-Borges, Jose E.; Rodriguez-Hergueta, Antonio [Tetrahedron Letters, 1998, vol. 39, # 31, p. 5663 - 5666]
[5]Location in patent: experimental part Kothandaraman, Shankaran; Donnely, Karla L.; Butora, Gabor; Jiao, Richard; Pasternak, Alexander; Morriello, Gregori J.; Goble, Stephen D.; Zhou, Changyou; Mills, Sander G.; MacCoss, Malcolm; Vicario, Pasquale P.; Ayala, Julia M.; DeMartino, Julie A.; Struthers, Mary; Cascieri, Margaret A.; Yang, Lihu [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 6, p. 1830 - 1834]
[6]Current Patent Assignee: SANOFI - US2012/22039, 2012, A1 Location in patent: Page/Page column 64
[7]Current Patent Assignee: ARIZONA BOARD OF REGENTS - US2016/375131, 2016, A1 Location in patent: Paragraph 0094
[8]Kwak, Seung-Hwa; Lim, Won Young; Hao, Aili; Mashalidis, Ellene H.; Kwon, Do-Yeon; Jeong, Pyeonghwa; Kim, Mi Jung; Lee, Seok-Yong; Hong, Jiyong [European Journal of Medicinal Chemistry, 2021, vol. 215]

11
[ 24424-99-5 ]
[ 79200-56-9 ]
[ 702666-73-7 ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether for 7h; Heating; Stage #2: di-<i>tert</i>-butyl dicarbonate at 25℃; for 14h; Further stages.;
52%	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether for 7h; Heating; Stage #2: di-<i>tert</i>-butyl dicarbonate at 20℃; for 14h; Further stages.;

Reference： [1]Hodgson, David M.; Maxwell, Christopher R.; Miles, Timothy J.; Paruch, Edyta; Matthews, Ian R.; Witherington, Jason [Tetrahedron, 2004, vol. 60, # 16, p. 3611 - 3624]
[2]Arjona, Odon; Cabas, Ma Jose; Nieto-Rubio, Jose; Querejeta, Ana [Heterocycles, 2006, vol. 68, # 10, p. 2079 - 2086]

12
[ 74-85-1 ]
[ 79200-56-9 ]
(3S,5R)-(-)-3,5-divinylpyrrolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	In dichloromethane at 20℃; for 2.5h;

Reference： [1]Arjona, Odon; Cabas, Ma Jose; Nieto-Rubio, Jose; Querejeta, Ana [Heterocycles, 2006, vol. 68, # 10, p. 2079 - 2086]

13
[ 79200-56-9 ]
(1S,4R,6SR)-6-hydroxy-6-trifluoromethyl-2-(4-methoxybenzyl)-azabicyclo[2.2.1]heptan-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 83 percent / sodium hydride; Bu₄NI / dimethylformamide / 2 h / 0 - 20 °C 2: 97 percent / 1,3-dibromo-5,5-dimethylhydantoin / 20 h / 20 °C 3: 95 percent / Bu₃SnH; AIBN / benzene / 12 h / Heating 4: 87 percent / aq. K₂CO₃ / methanol / 2 h / 20 °C 5: 70 percent / NMO; tetra-n-propylammonium perruthenate / CH₂Cl₂ / 24 h / 20 °C 6: 94 percent / tetrabutylammonium fluoride / tetrahydrofuran / 2 h / 20 °C

Reference： [1]Lu, Hejun; Silverman, Richard B. [Journal of Medicinal Chemistry, 2006, vol. 49, # 25, p. 7404 - 7412]

14
[ 79200-56-9 ]
(1S,4R,6SR)-6-hydroxy-6-pentafluoroethyl-2-(4-methoxybenzyl)-azabicyclo[2.2.1]heptan-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 83 percent / sodium hydride; Bu₄NI / dimethylformamide / 2 h / 0 - 20 °C 2: 97 percent / 1,3-dibromo-5,5-dimethylhydantoin / 20 h / 20 °C 3: 95 percent / Bu₃SnH; AIBN / benzene / 12 h / Heating 4: 87 percent / aq. K₂CO₃ / methanol / 2 h / 20 °C 5: 70 percent / NMO; tetra-n-propylammonium perruthenate / CH₂Cl₂ / 24 h / 20 °C 6: tetrabutylammonium fluoride / tetrahydrofuran / 2 h / 20 °C

Reference： [1]Lu, Hejun; Silverman, Richard B. [Journal of Medicinal Chemistry, 2006, vol. 49, # 25, p. 7404 - 7412]

15
[ 79200-56-9 ]
(1S,4R,6S)-toluene-4-sulfonic acid 2-(4-methoxybenzyl)-3-oxo-6-trifluoromethyl-2-azabicyclo[2.2.1]hept-6-yl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: 83 percent / sodium hydride; Bu₄NI / dimethylformamide / 2 h / 0 - 20 °C 2.1: 97 percent / 1,3-dibromo-5,5-dimethylhydantoin / 20 h / 20 °C 3.1: 95 percent / Bu₃SnH; AIBN / benzene / 12 h / Heating 4.1: 87 percent / aq. K₂CO₃ / methanol / 2 h / 20 °C 5.1: 70 percent / NMO; tetra-n-propylammonium perruthenate / CH₂Cl₂ / 24 h / 20 °C 6.1: 94 percent / tetrabutylammonium fluoride / tetrahydrofuran / 2 h / 20 °C 7.1: NaH / diethyl ether / 0.25 h / 0 °C 7.2: 79 percent / diethyl ether / 16 h / 20 °C

Reference： [1]Lu, Hejun; Silverman, Richard B. [Journal of Medicinal Chemistry, 2006, vol. 49, # 25, p. 7404 - 7412]

16
[ 79200-56-9 ]
(1S,4R,6S)-toluene-4-sulfonic acid 2-(4-methoxybenzyl)-3-oxo-6-pentafluoroethyl-2-azabicyclo[2.2.1]hept-6-yl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: 83 percent / sodium hydride; Bu₄NI / dimethylformamide / 2 h / 0 - 20 °C 2.1: 97 percent / 1,3-dibromo-5,5-dimethylhydantoin / 20 h / 20 °C 3.1: 95 percent / Bu₃SnH; AIBN / benzene / 12 h / Heating 4.1: 87 percent / aq. K₂CO₃ / methanol / 2 h / 20 °C 5.1: 70 percent / NMO; tetra-n-propylammonium perruthenate / CH₂Cl₂ / 24 h / 20 °C 6.1: tetrabutylammonium fluoride / tetrahydrofuran / 2 h / 20 °C 7.1: NaH / diethyl ether / 0 °C 7.2: diethyl ether / 20 °C

Reference： [1]Lu, Hejun; Silverman, Richard B. [Journal of Medicinal Chemistry, 2006, vol. 49, # 25, p. 7404 - 7412]

17
[ 79200-56-9 ]
2-[3-(6-amino-purin-9-yl)-cyclopentylmethoxy]-phenoxy-phosphorylamino}-propionic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: 4-dimethylaminopyridine / tetrahydrofuran / 20 °C 2.1: aq. sodium borohydride / tetrahydrofuran / 35 °C 3.1: aq. HCl / ethanol / 3 h / Heating 4.1: 30.3 g / triethylamine / butan-1-ol / 16 h / Heating 5.1: 13.3 g / methanesulfonic acid / 4 h 6.1: 2.8 g / NH₃ / 18 h / 25 °C 7.1: 350 mg / H₂ / Pd/C / ethanol / 12 h / 2068.59 Torr 8.1: t-BuMgCl; pyridine / tetrahydrofuran / 0.17 h / 20 °C 8.2: 0.25 g / tetrahydrofuran / 20 °C

Reference： [1]McGuigan, Christopher; Hassan-Abdallah, Alshaimaa; Srinivasan, Sheila; Wang, Yikang; Siddiqui, Adam; Daluge, Susan M.; Gudmundsson, Kristjan S.; Zhou, Huiqiang; McLean, Ed W.; Peckham, Jennifer P.; Burnette, Thimysta C.; Marr, Harry; Hazen, Richard; Condreay, Lynn D.; Johnson, Lance; Balzarini, Jan [Journal of Medicinal Chemistry, 2006, vol. 49, # 24, p. 7215 - 7226]

18
[ 79200-56-9 ]
[ 168960-18-7 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 7215 - 7226
[2]Journal of the American Chemical Society,2005,vol. 127,p. 8846 - 8855
[3]Nucleosides, nucleotides and nucleic acids,2000,vol. 19,p. 297 - 327
[4]Nucleosides, nucleotides and nucleic acids,2000,vol. 19,p. 297 - 327
[5]Journal of Organic Chemistry,1995,vol. 60,p. 4602 - 4616
[6]Tetrahedron Asymmetry,1993,vol. 4,p. 1117 - 1128

19
[ 79200-56-9 ]
[ 112966-73-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: 4-dimethylaminopyridine / tetrahydrofuran / 20 °C 2: aq. sodium borohydride / tetrahydrofuran / 35 °C 3: aq. HCl / ethanol / 3 h / Heating 4: 30.3 g / triethylamine / butan-1-ol / 16 h / Heating 5: 13.3 g / methanesulfonic acid / 4 h 6: 2.8 g / NH₃ / 18 h / 25 °C 7: 350 mg / H₂ / Pd/C / ethanol / 12 h / 2068.59 Torr

Reference： [1]McGuigan, Christopher; Hassan-Abdallah, Alshaimaa; Srinivasan, Sheila; Wang, Yikang; Siddiqui, Adam; Daluge, Susan M.; Gudmundsson, Kristjan S.; Zhou, Huiqiang; McLean, Ed W.; Peckham, Jennifer P.; Burnette, Thimysta C.; Marr, Harry; Hazen, Richard; Condreay, Lynn D.; Johnson, Lance; Balzarini, Jan [Journal of Medicinal Chemistry, 2006, vol. 49, # 24, p. 7215 - 7226]

20
[ 79200-56-9 ]
[ 874486-35-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 11 steps 1: 99 percent / DMAP / tetrahydrofuran / 3 h / 20 °C 2: 71 percent / mCPBA / CH₂Cl₂ / 20 h / 20 °C 3: sodium borohydride / methanol / 0.5 h / 0 °C 4: 537 mg / imidazole / dimethylformamide / 3 h / 20 °C 5: 93 percent / Red-Al(R) / toluene / 1 h / 20 °C 6: 100 percent / H₂O / Heating 7: 86 percent / diisopropylethylamine / dimethylformamide / 3 h / 0 - 75 °C 8: 79 percent / imidazole / dimethylformamide / 3 h / 20 °C 9: H₂ / Pd/C / ethanol / 900.07 Torr 10: 75.3 mg / 20 - 100 °C 11: 85 percent / pyridine*HF / ethyl acetate / 20 °C

Reference： [1]Ober, Matthias; Mueller, Heiko; Pieck, Carsten; Gierlich, Johannes; Carell, Thomas [Journal of the American Chemical Society, 2005, vol. 127, # 51, p. 18143 - 18149]

21
[ 79200-56-9 ]
[ 874486-34-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1: 99 percent / DMAP / tetrahydrofuran / 3 h / 20 °C 2: 71 percent / mCPBA / CH₂Cl₂ / 20 h / 20 °C 3: sodium borohydride / methanol / 0.5 h / 0 °C 4: 537 mg / imidazole / dimethylformamide / 3 h / 20 °C 5: 93 percent / Red-Al(R) / toluene / 1 h / 20 °C 6: 100 percent / H₂O / Heating 7: 86 percent / diisopropylethylamine / dimethylformamide / 3 h / 0 - 75 °C 8: 79 percent / imidazole / dimethylformamide / 3 h / 20 °C 9: H₂ / Pd/C / ethanol / 900.07 Torr 10: 75.3 mg / 20 - 100 °C

Reference： [1]Ober, Matthias; Mueller, Heiko; Pieck, Carsten; Gierlich, Johannes; Carell, Thomas [Journal of the American Chemical Society, 2005, vol. 127, # 51, p. 18143 - 18149]

22
[ 79200-56-9 ]
[ 874486-36-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 12 steps 1: 99 percent / DMAP / tetrahydrofuran / 3 h / 20 °C 2: 71 percent / mCPBA / CH₂Cl₂ / 20 h / 20 °C 3: sodium borohydride / methanol / 0.5 h / 0 °C 4: 537 mg / imidazole / dimethylformamide / 3 h / 20 °C 5: 93 percent / Red-Al(R) / toluene / 1 h / 20 °C 6: 100 percent / H₂O / Heating 7: 86 percent / diisopropylethylamine / dimethylformamide / 3 h / 0 - 75 °C 8: 79 percent / imidazole / dimethylformamide / 3 h / 20 °C 9: H₂ / Pd/C / ethanol / 900.07 Torr 10: 75.3 mg / 20 - 100 °C 11: 85 percent / pyridine*HF / ethyl acetate / 20 °C 12: 60 percent / pyridine / 2.5 h

Reference： [1]Ober, Matthias; Mueller, Heiko; Pieck, Carsten; Gierlich, Johannes; Carell, Thomas [Journal of the American Chemical Society, 2005, vol. 127, # 51, p. 18143 - 18149]

23
[ 79200-56-9 ]
(1S,2R,4R)-4-(2-acetylamino-6-oxo-1,6-dihydro-purin-9-yl)-2-[(dimethoxytrityl)oxy]methyl}cyclopentyl-O-(N,N-diisopropyl)-(2-cyanoethyl)phosphoramidite [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 13 steps 1: 99 percent / DMAP / tetrahydrofuran / 3 h / 20 °C 2: 71 percent / mCPBA / CH₂Cl₂ / 20 h / 20 °C 3: sodium borohydride / methanol / 0.5 h / 0 °C 4: 537 mg / imidazole / dimethylformamide / 3 h / 20 °C 5: 93 percent / Red-Al(R) / toluene / 1 h / 20 °C 6: 100 percent / H₂O / Heating 7: 86 percent / diisopropylethylamine / dimethylformamide / 3 h / 0 - 75 °C 8: 79 percent / imidazole / dimethylformamide / 3 h / 20 °C 9: H₂ / Pd/C / ethanol / 900.07 Torr 10: 75.3 mg / 20 - 100 °C 11: 85 percent / pyridine*HF / ethyl acetate / 20 °C 12: 60 percent / pyridine / 2.5 h 13: diisopropylethylamine / tetrahydrofuran / 2 h / 20 °C

Reference： [1]Ober, Matthias; Mueller, Heiko; Pieck, Carsten; Gierlich, Johannes; Carell, Thomas [Journal of the American Chemical Society, 2005, vol. 127, # 51, p. 18143 - 18149]

24
[ 79200-56-9 ]
[ 244057-70-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 99 percent / DMAP / tetrahydrofuran / 3 h / 20 °C 2: 71 percent / mCPBA / CH₂Cl₂ / 20 h / 20 °C
	Multi-step reaction with 2 steps 1: Oxone / H₂O / 7 h / pH 6 2: 67 percent / DMAP / CH₂Cl₂ / 5 h / 0 - 20 °C
	Multi-step reaction with 2 steps 1: sodium dihydrogenphosphate; disodium hydrogenphosphate / water / 7 h / 0 °C / pH 6 2: triethylamine; dmap / dichloromethane / 16 h / 25 °C

Multi-step reaction with 2 steps 1: triethylamine; dmap / dichloromethane / 12 h / 0 - 25 °C 2: 3-chloro-benzenecarboperoxoic acid / 1,2-dichloro-ethane / 108 h / 25 °C

Reference： [1]Ober, Matthias; Mueller, Heiko; Pieck, Carsten; Gierlich, Johannes; Carell, Thomas [Journal of the American Chemical Society, 2005, vol. 127, # 51, p. 18143 - 18149]
[2]Smith, Mark E.B.; Derrien, Nadine; Lloyd, Michael C.; Taylor, Stephen J.C.; Chaplin, David A.; McCague, Raymond [Tetrahedron Letters, 2001, vol. 42, # 7, p. 1347 - 1350]
[3]Current Patent Assignee: BLUEPRINT MEDICINES CORP - WO2017/35354, 2017, A1
[4]Current Patent Assignee: ALIGOS THERAPEUTICS - WO2020/205867, 2020, A1

25
[ 79200-56-9 ]
[ 244057-71-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 99 percent / DMAP / tetrahydrofuran / 3 h / 20 °C 2: 71 percent / mCPBA / CH₂Cl₂ / 20 h / 20 °C 3: sodium borohydride / methanol / 0.5 h / 0 °C
	Multi-step reaction with 3 steps 1.1: dmap / acetonitrile / 16 h / 20 °C 1.2: 0.33 h / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 88 h / 20 °C 3.1: sodium tetrahydroborate / 0 °C
	Multi-step reaction with 3 steps 1: triethylamine; dmap / dichloromethane / 12 h / 0 - 25 °C 2: 3-chloro-benzenecarboperoxoic acid / 1,2-dichloro-ethane / 108 h / 25 °C 3: sodium tetrahydroborate; methanol / 1 h / 0 °C

Multi-step reaction with 3 steps 1: triethylamine; dmap / dichloromethane / 12 h / 0 - 25 °C 2: 3-chloro-benzenecarboperoxoic acid / 1,2-dichloro-ethane / 108 h / 25 °C 3: sodium tetrahydroborate / methanol / 1 h / 0 °C

Reference： [1]Ober, Matthias; Mueller, Heiko; Pieck, Carsten; Gierlich, Johannes; Carell, Thomas [Journal of the American Chemical Society, 2005, vol. 127, # 51, p. 18143 - 18149]
[2]Haffner, Curt D.; Charnley, Adam K.; Aquino, Christopher J.; Casillas, Linda; Convery, Máire A.; Cox, Julie A.; Elban, Mark A.; Goodwin, Nicole C.; Gough, Peter J.; Haile, Pamela A.; Hughes, Terry V.; Knapp-Reed, Beth; Kreatsoulas, Constantine; Lakdawala, Ami S.; Li, Huijie; Lian, Yiqian; Lipshutz, David; Mehlmann, John F.; Ouellette, Michael; Romano, Joseph; Shewchuk, Lisa; Shu, Arthur; Votta, Bartholomew J.; Zhou, Huiqiang; Bertin, John; Marquis, Robert W. [ACS Medicinal Chemistry Letters, 2019, vol. 10, # 11, p. 1518 - 1523]
[3]Current Patent Assignee: ALIGOS THERAPEUTICS - WO2020/205867, 2020, A1
[4]Current Patent Assignee: ALIGOS THERAPEUTICS - WO2021/202480, 2021, A1

26
[ 79200-56-9 ]
[ 153045-91-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 99 percent / DMAP / tetrahydrofuran / 3 h / 20 °C 2: 71 percent / mCPBA / CH₂Cl₂ / 20 h / 20 °C 3: sodium borohydride / methanol / 0.5 h / 0 °C 4: 537 mg / imidazole / dimethylformamide / 3 h / 20 °C 5: 93 percent / Red-Al(R) / toluene / 1 h / 20 °C
	Multi-step reaction with 4 steps 1.1: dmap / acetonitrile / 16 h / 20 °C 1.2: 0.33 h / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 88 h / 20 °C 3.1: sodium tetrahydroborate / 0 °C 4.1: aluminum / toluene; dichloromethane / 7.5 h / -2 - 20 °C / Inert atmosphere

Reference： [1]Ober, Matthias; Mueller, Heiko; Pieck, Carsten; Gierlich, Johannes; Carell, Thomas [Journal of the American Chemical Society, 2005, vol. 127, # 51, p. 18143 - 18149]
[2]Haffner, Curt D.; Charnley, Adam K.; Aquino, Christopher J.; Casillas, Linda; Convery, Máire A.; Cox, Julie A.; Elban, Mark A.; Goodwin, Nicole C.; Gough, Peter J.; Haile, Pamela A.; Hughes, Terry V.; Knapp-Reed, Beth; Kreatsoulas, Constantine; Lakdawala, Ami S.; Li, Huijie; Lian, Yiqian; Lipshutz, David; Mehlmann, John F.; Ouellette, Michael; Romano, Joseph; Shewchuk, Lisa; Shu, Arthur; Votta, Bartholomew J.; Zhou, Huiqiang; Bertin, John; Marquis, Robert W. [ACS Medicinal Chemistry Letters, 2019, vol. 10, # 11, p. 1518 - 1523]

27
[ 79200-56-9 ]
N-{2-amino-4-[(1R,3S,4R)-3-hydroxy-4-hydroxymethyl-cyclopentylamino]-6-oxo-1,6-dihydro-pyrimidin-6-yl}formamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 12 steps 1: 99 percent / DMAP / tetrahydrofuran / 3 h / 20 °C 2: 71 percent / mCPBA / CH₂Cl₂ / 20 h / 20 °C 3: sodium borohydride / methanol / 0.5 h / 0 °C 4: 537 mg / imidazole / dimethylformamide / 3 h / 20 °C 5: 93 percent / Red-Al(R) / toluene / 1 h / 20 °C 6: 100 percent / H₂O / Heating 7: 86 percent / diisopropylethylamine / dimethylformamide / 3 h / 0 - 75 °C 8: 79 percent / imidazole / dimethylformamide / 3 h / 20 °C 9: H₂ / Pd/C / ethanol / 900.07 Torr 10: 1.17 g / N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride; diisopropylethylamine / dimethylformamide / 48 h / 20 °C 11: 94 percent / pyridine*HF / ethyl acetate / 20 °C 12: 99 percent / aq. NH₃ / ethanol / 15 °C

Reference： [1]Ober, Matthias; Mueller, Heiko; Pieck, Carsten; Gierlich, Johannes; Carell, Thomas [Journal of the American Chemical Society, 2005, vol. 127, # 51, p. 18143 - 18149]

28
[ 79200-56-9 ]
[ 636569-58-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 11 steps 1: 99 percent / DMAP / tetrahydrofuran / 3 h / 20 °C 2: 71 percent / mCPBA / CH₂Cl₂ / 20 h / 20 °C 3: sodium borohydride / methanol / 0.5 h / 0 °C 4: 537 mg / imidazole / dimethylformamide / 3 h / 20 °C 5: 93 percent / Red-Al(R) / toluene / 1 h / 20 °C 6: 100 percent / H₂O / Heating 7: 86 percent / diisopropylethylamine / dimethylformamide / 3 h / 0 - 75 °C 8: 79 percent / imidazole / dimethylformamide / 3 h / 20 °C 9: H₂ / Pd/C / ethanol / 900.07 Torr 10: 1.17 g / N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride; diisopropylethylamine / dimethylformamide / 48 h / 20 °C 11: 94 percent / pyridine*HF / ethyl acetate / 20 °C

Reference： [1]Ober, Matthias; Mueller, Heiko; Pieck, Carsten; Gierlich, Johannes; Carell, Thomas [Journal of the American Chemical Society, 2005, vol. 127, # 51, p. 18143 - 18149]

29
[ 79200-56-9 ]
[ 636569-54-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1: 99 percent / DMAP / tetrahydrofuran / 3 h / 20 °C 2: 71 percent / mCPBA / CH₂Cl₂ / 20 h / 20 °C 3: sodium borohydride / methanol / 0.5 h / 0 °C 4: 537 mg / imidazole / dimethylformamide / 3 h / 20 °C 5: 93 percent / Red-Al(R) / toluene / 1 h / 20 °C 6: 100 percent / H₂O / Heating 7: 86 percent / diisopropylethylamine / dimethylformamide / 3 h / 0 - 75 °C 8: 79 percent / imidazole / dimethylformamide / 3 h / 20 °C 9: H₂ / Pd/C / ethanol / 900.07 Torr

Reference： [1]Ober, Matthias; Mueller, Heiko; Pieck, Carsten; Gierlich, Johannes; Carell, Thomas [Journal of the American Chemical Society, 2005, vol. 127, # 51, p. 18143 - 18149]

30
[ 79200-56-9 ]
[ 636569-56-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1: 99 percent / DMAP / tetrahydrofuran / 3 h / 20 °C 2: 71 percent / mCPBA / CH₂Cl₂ / 20 h / 20 °C 3: sodium borohydride / methanol / 0.5 h / 0 °C 4: 537 mg / imidazole / dimethylformamide / 3 h / 20 °C 5: 93 percent / Red-Al(R) / toluene / 1 h / 20 °C 6: 100 percent / H₂O / Heating 7: 86 percent / diisopropylethylamine / dimethylformamide / 3 h / 0 - 75 °C 8: 79 percent / imidazole / dimethylformamide / 3 h / 20 °C 9: H₂ / Pd/C / ethanol / 900.07 Torr 10: 1.17 g / N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride; diisopropylethylamine / dimethylformamide / 48 h / 20 °C

Reference： [1]Ober, Matthias; Mueller, Heiko; Pieck, Carsten; Gierlich, Johannes; Carell, Thomas [Journal of the American Chemical Society, 2005, vol. 127, # 51, p. 18143 - 18149]

31
[ 79200-56-9 ]
[ 636569-60-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 12 steps 1: 99 percent / DMAP / tetrahydrofuran / 3 h / 20 °C 2: 71 percent / mCPBA / CH₂Cl₂ / 20 h / 20 °C 3: sodium borohydride / methanol / 0.5 h / 0 °C 4: 537 mg / imidazole / dimethylformamide / 3 h / 20 °C 5: 93 percent / Red-Al(R) / toluene / 1 h / 20 °C 6: 100 percent / H₂O / Heating 7: 86 percent / diisopropylethylamine / dimethylformamide / 3 h / 0 - 75 °C 8: 79 percent / imidazole / dimethylformamide / 3 h / 20 °C 9: H₂ / Pd/C / ethanol / 900.07 Torr 10: 1.17 g / N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride; diisopropylethylamine / dimethylformamide / 48 h / 20 °C 11: 94 percent / pyridine*HF / ethyl acetate / 20 °C 12: 56 percent / molecular sieves 4 Angstroem; pyridine / 4 h / 0 °C

Reference： [1]Ober, Matthias; Mueller, Heiko; Pieck, Carsten; Gierlich, Johannes; Carell, Thomas [Journal of the American Chemical Society, 2005, vol. 127, # 51, p. 18143 - 18149]

32
[ 79200-56-9 ]
(1S,2R,4R)-4-[2-(acetylamino)-5-(formylamino)-6-oxo-1,6-dihydro-4-pyrimidinyl]amino}-2-[(dimethoxytrityl)oxy]methyl}cyclopentyl-O-(N,N-diisopropyl)-(2-cyanoethyl)phosphoramidite [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 13 steps 1: 99 percent / DMAP / tetrahydrofuran / 3 h / 20 °C 2: 71 percent / mCPBA / CH₂Cl₂ / 20 h / 20 °C 3: sodium borohydride / methanol / 0.5 h / 0 °C 4: 537 mg / imidazole / dimethylformamide / 3 h / 20 °C 5: 93 percent / Red-Al(R) / toluene / 1 h / 20 °C 6: 100 percent / H₂O / Heating 7: 86 percent / diisopropylethylamine / dimethylformamide / 3 h / 0 - 75 °C 8: 79 percent / imidazole / dimethylformamide / 3 h / 20 °C 9: H₂ / Pd/C / ethanol / 900.07 Torr 10: 1.17 g / N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride; diisopropylethylamine / dimethylformamide / 48 h / 20 °C 11: 94 percent / pyridine*HF / ethyl acetate / 20 °C 12: 56 percent / molecular sieves 4 Angstroem; pyridine / 4 h / 0 °C 13: diisopropylaminotetrazolate / CH₂Cl₂ / 20 °C

Reference： [1]Ober, Matthias; Mueller, Heiko; Pieck, Carsten; Gierlich, Johannes; Carell, Thomas [Journal of the American Chemical Society, 2005, vol. 127, # 51, p. 18143 - 18149]

33
[ 79200-56-9 ]
[ 859147-51-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 100 percent / H₂ / Pd-C / methanol / 5 h / 20 °C / atmospheric pressure 2: 100 percent / DMAP / acetonitrile / 1 h / 20 °C 3: 95 percent / NaBH₄ / methanol / 0.5 h / 0 °C 4: 100 percent / water / 18 h / Heating 5: 85 percent / K₂CO₃ / methanol / 14 h / 20 °C

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]

34
[ 79200-56-9 ]
[ 859147-59-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1.1: 100 percent / H₂ / Pd-C / methanol / 5 h / 20 °C / atmospheric pressure 2.1: 100 percent / DMAP / acetonitrile / 1 h / 20 °C 3.1: 95 percent / NaBH₄ / methanol / 0.5 h / 0 °C 4.1: 100 percent / water / 18 h / Heating 5.1: 85 percent / K₂CO₃ / methanol / 14 h / 20 °C 6.1: 97 percent / pyridine / 4 h / 20 °C 7.1: 100 percent / TBAF; AcOH / tetrahydrofuran / 1 h / 20 °C 8.1: 2,4,6-triisopropylbenzenesulfonyl chloride; pyridine / 1 h / 20 °C 8.2: 69 percent / pyridine / 1 h / 20 °C 9.1: 85 percent / aq. AcOH / 7 h / 20 °C

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]

35
[ 79200-56-9 ]
[ 859147-55-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: 100 percent / H₂ / Pd-C / methanol / 5 h / 20 °C / atmospheric pressure 2: 100 percent / DMAP / acetonitrile / 1 h / 20 °C 3: 95 percent / NaBH₄ / methanol / 0.5 h / 0 °C 4: 100 percent / water / 18 h / Heating 5: 85 percent / K₂CO₃ / methanol / 14 h / 20 °C 6: 97 percent / pyridine / 4 h / 20 °C 7: 100 percent / TBAF; AcOH / tetrahydrofuran / 1 h / 20 °C

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]

36
[ 79200-56-9 ]
[ 859147-53-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 100 percent / H₂ / Pd-C / methanol / 5 h / 20 °C / atmospheric pressure 2: 100 percent / DMAP / acetonitrile / 1 h / 20 °C 3: 95 percent / NaBH₄ / methanol / 0.5 h / 0 °C 4: 100 percent / water / 18 h / Heating 5: 85 percent / K₂CO₃ / methanol / 14 h / 20 °C 6: 97 percent / pyridine / 4 h / 20 °C

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]

37
[ 79200-56-9 ]
2'',3''-dideoxy-2'',3''-didehydro-cyclic ADP-carbocyclic ribose triethylammonium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 11 steps 1.1: 88 percent / DMAP / acetonitrile / 20 °C 2.1: 97 percent / NaBH₄ / methanol / 0.5 h / 0 °C 3.1: 100 percent / water / 18 h / Heating 4.1: 82 percent / K₂CO₃ / methanol / 14 h / 20 °C 5.1: 84 percent / pyridine / 4 h / 20 °C 6.1: 97 percent / TBAF; AcOH / tetrahydrofuran / 1 h / 20 °C 7.1: 2,4,6-triisopropylbenzenesulfonyl chloride; pyridine / 1 h / 20 °C 7.2: 54 percent / pyridine / 1 h / 20 °C 8.1: 77 percent / aq. AcOH / 7 h / 20 °C 9.1: POCl₃ / various solvent(s) / 1 h / 0 °C 9.2: aq. NaHCO₃ / various solvent(s) / 0.17 h / 0 °C 9.3: 64 percent / N-methylmorpholine; H₃PO₂ / 4 h / 0 °C 10.1: 84 percent / AgNO₃; Et₃N; molecular sieves 3 Angstroem / pyridine / 15 h / 20 °C 11.1: 100 percent / aq. HCO₂H / 9.5 h / 20 °C

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]

38
[ 79200-56-9 ]
2'',3''-dideoxy-2'',3''-didehydro-cyclic ADP-carboxylic-ribose acetonide triethylammonium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1.1: 88 percent / DMAP / acetonitrile / 20 °C 2.1: 97 percent / NaBH₄ / methanol / 0.5 h / 0 °C 3.1: 100 percent / water / 18 h / Heating 4.1: 82 percent / K₂CO₃ / methanol / 14 h / 20 °C 5.1: 84 percent / pyridine / 4 h / 20 °C 6.1: 97 percent / TBAF; AcOH / tetrahydrofuran / 1 h / 20 °C 7.1: 2,4,6-triisopropylbenzenesulfonyl chloride; pyridine / 1 h / 20 °C 7.2: 54 percent / pyridine / 1 h / 20 °C 8.1: 77 percent / aq. AcOH / 7 h / 20 °C 9.1: POCl₃ / various solvent(s) / 1 h / 0 °C 9.2: aq. NaHCO₃ / various solvent(s) / 0.17 h / 0 °C 9.3: 64 percent / N-methylmorpholine; H₃PO₂ / 4 h / 0 °C 10.1: 84 percent / AgNO₃; Et₃N; molecular sieves 3 Angstroem / pyridine / 15 h / 20 °C

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]

39
[ 79200-56-9 ]
2'',3''-dideoxy-cyclic ADP-carbocyclic ribose triethylammonium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 12 steps 1.1: 100 percent / H₂ / Pd-C / methanol / 5 h / 20 °C / atmospheric pressure 2.1: 100 percent / DMAP / acetonitrile / 1 h / 20 °C 3.1: 95 percent / NaBH₄ / methanol / 0.5 h / 0 °C 4.1: 100 percent / water / 18 h / Heating 5.1: 85 percent / K₂CO₃ / methanol / 14 h / 20 °C 6.1: 97 percent / pyridine / 4 h / 20 °C 7.1: 100 percent / TBAF; AcOH / tetrahydrofuran / 1 h / 20 °C 8.1: 2,4,6-triisopropylbenzenesulfonyl chloride; pyridine / 1 h / 20 °C 8.2: 69 percent / pyridine / 1 h / 20 °C 9.1: 85 percent / aq. AcOH / 7 h / 20 °C 10.1: POCl₃ / various solvent(s) / 1 h / 0 °C 10.2: aq. NaHCO₃ / various solvent(s) / 0.17 h / 0 °C 10.3: 75 percent / N-methylmorpholine; H₃PO₂ / 4 h / 0 °C 11.1: 81 percent / AgNO₃; Et₃N; molecular sieves 3 Angstroem / pyridine / 15 h / 20 °C 12.1: 100 percent / aq. HCO₂H / 9.5 h / 20 °C

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]

40
[ 79200-56-9 ]
2'',3''-dideoxy-cyclic ADP-carbocyclic-ribose acetonide triethylammonium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 11 steps 1.1: 100 percent / H₂ / Pd-C / methanol / 5 h / 20 °C / atmospheric pressure 2.1: 100 percent / DMAP / acetonitrile / 1 h / 20 °C 3.1: 95 percent / NaBH₄ / methanol / 0.5 h / 0 °C 4.1: 100 percent / water / 18 h / Heating 5.1: 85 percent / K₂CO₃ / methanol / 14 h / 20 °C 6.1: 97 percent / pyridine / 4 h / 20 °C 7.1: 100 percent / TBAF; AcOH / tetrahydrofuran / 1 h / 20 °C 8.1: 2,4,6-triisopropylbenzenesulfonyl chloride; pyridine / 1 h / 20 °C 8.2: 69 percent / pyridine / 1 h / 20 °C 9.1: 85 percent / aq. AcOH / 7 h / 20 °C 10.1: POCl₃ / various solvent(s) / 1 h / 0 °C 10.2: aq. NaHCO₃ / various solvent(s) / 0.17 h / 0 °C 10.3: 75 percent / N-methylmorpholine; H₃PO₂ / 4 h / 0 °C 11.1: 81 percent / AgNO₃; Et₃N; molecular sieves 3 Angstroem / pyridine / 15 h / 20 °C

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]

41
[ 79200-56-9 ]
[ 859147-57-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: 100 percent / H₂ / Pd-C / methanol / 5 h / 20 °C / atmospheric pressure 2.1: 100 percent / DMAP / acetonitrile / 1 h / 20 °C 3.1: 95 percent / NaBH₄ / methanol / 0.5 h / 0 °C 4.1: 100 percent / water / 18 h / Heating 5.1: 85 percent / K₂CO₃ / methanol / 14 h / 20 °C 6.1: 97 percent / pyridine / 4 h / 20 °C 7.1: 100 percent / TBAF; AcOH / tetrahydrofuran / 1 h / 20 °C 8.1: 2,4,6-triisopropylbenzenesulfonyl chloride; pyridine / 1 h / 20 °C 8.2: 69 percent / pyridine / 1 h / 20 °C

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]

42
[ 79200-56-9 ]
N-1-{(1S,4R)-4-(phosphonoxymethyl)cyclopentyl}-5'-O-{(phenylthio)phosphoryl}-2',3'-O-isopropylideneadenosine triethylammonium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1.1: 100 percent / H₂ / Pd-C / methanol / 5 h / 20 °C / atmospheric pressure 2.1: 100 percent / DMAP / acetonitrile / 1 h / 20 °C 3.1: 95 percent / NaBH₄ / methanol / 0.5 h / 0 °C 4.1: 100 percent / water / 18 h / Heating 5.1: 85 percent / K₂CO₃ / methanol / 14 h / 20 °C 6.1: 97 percent / pyridine / 4 h / 20 °C 7.1: 100 percent / TBAF; AcOH / tetrahydrofuran / 1 h / 20 °C 8.1: 2,4,6-triisopropylbenzenesulfonyl chloride; pyridine / 1 h / 20 °C 8.2: 69 percent / pyridine / 1 h / 20 °C 9.1: 85 percent / aq. AcOH / 7 h / 20 °C 10.1: POCl₃ / various solvent(s) / 1 h / 0 °C 10.2: aq. NaHCO₃ / various solvent(s) / 0.17 h / 0 °C 10.3: 75 percent / N-methylmorpholine; H₃PO₂ / 4 h / 0 °C

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]

43
[ 79200-56-9 ]
[ 117957-62-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 100 percent / H₂ / Pd-C / methanol / 5 h / 20 °C / atmospheric pressure 2: 100 percent / DMAP / acetonitrile / 1 h / 20 °C 3: 95 percent / NaBH₄ / methanol / 0.5 h / 0 °C 4: 100 percent / water / 18 h / Heating
	Multi-step reaction with 4 steps 1: palladium 10% on activated carbon; hydrogen / methanol / 5 h / 25 °C / Inert atmosphere 2: dmap / acetonitrile / 1 h / 25 °C 3: sodium tetrahydroborate / methanol / 3 h / 25 °C / Inert atmosphere 4: water / 20 h / 100 °C / Inert atmosphere

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]
[2]Kwak, Seung-Hwa; Lim, Won Young; Hao, Aili; Mashalidis, Ellene H.; Kwon, Do-Yeon; Jeong, Pyeonghwa; Kim, Mi Jung; Lee, Seok-Yong; Hong, Jiyong [European Journal of Medicinal Chemistry, 2021, vol. 215]

44
[ 79200-56-9 ]
[ 136522-35-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 88 percent / DMAP / acetonitrile / 20 °C 2: 97 percent / NaBH₄ / methanol / 0.5 h / 0 °C 3: 100 percent / water / 18 h / Heating
	Multi-step reaction with 2 steps 1: 1.264 g / tetrahydrofuran; H₂O / 18 h / 20 - 60 °C 2: 90.5 percent / LiAlH₄ / tetrahydrofuran / 19.5 h / 0 °C / Heating
	Multi-step reaction with 3 steps 1: 91 percent / triethylamine, N,N-4-dimethylaminopyridine / CH₂Cl₂ 2: NaBH₄ 3: CF₃CO₂H

Multi-step reaction with 5 steps 1: 1M aq. hydrochloric acid / 1 h / Heating 2: conc. HCl / methanol / 20 h / Ambient temperature 3: pyridine / CH₂Cl₂ / 24 h / Ambient temperature 4: 73 percent / calcium chloride, sodium borohydride / tetrahydrofuran / 3 h / 40 °C / sonication 5: 2 M hydrochloric acid / ethanol / 48 h / Heating

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]
[2]Daluge, Susan M.; Martin, Michael T.; Sickles, Barry R.; Livingston, Douglas A. [Nucleosides, nucleotides and nucleic acids, 2000, vol. 19, # 1-2, p. 297 - 327]
[3]Taylor, Stephen J C; McCague, Raymond; Wisdom, Richard; Lee, Carol; Dickson, Karen; et al. [Tetrahedron Asymmetry, 1993, vol. 4, # 6, p. 1117 - 1128]
[4]Evans, Chris T.; Roberts, Stanley M.; Shoberu, Karoline A.; Sutherland, Alan G. [Journal of the Chemical Society. Perkin transactions I, 1992, # 5, p. 589 - 592]

45
[ 79200-56-9 ]
[ 204913-00-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 100 percent / H₂ / Pd-C / methanol / 5 h / 20 °C / atmospheric pressure 2: 100 percent / DMAP / acetonitrile / 1 h / 20 °C
	Multi-step reaction with 2 steps 1: DMAP / CH₂Cl₂ 2: H₂ / Pd/C / methanol

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]
[2]Smith, Mark E.B.; Derrien, Nadine; Lloyd, Michael C.; Taylor, Stephen J.C.; Chaplin, David A.; McCague, Raymond [Tetrahedron Letters, 2001, vol. 42, # 7, p. 1347 - 1350]

46
[ 79200-56-9 ]
[ 664341-72-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 100 percent / H₂ / Pd-C / methanol / 5 h / 20 °C / atmospheric pressure 2: 100 percent / DMAP / acetonitrile / 1 h / 20 °C 3: 95 percent / NaBH₄ / methanol / 0.5 h / 0 °C
	Multi-step reaction with 3 steps 1: palladium 10% on activated carbon; hydrogen / methanol / 5 h / 25 °C / Inert atmosphere 2: dmap / acetonitrile / 1 h / 25 °C 3: sodium tetrahydroborate / methanol / 3 h / 25 °C / Inert atmosphere

Reference： [1]Kudoh, Takashi; Fukuoka, Masayoshi; Ichikawa, Satoshi; Murayama, Takashi; Ogawa, Yasuo; Hashii, Minako; Higashida, Haruhiro; Kunerth, Svenja; Weber, Karin; Guse, Andreas H.; Potter, Barry V. L.; Matsuda, Akira; Shuto, Satoshi [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8846 - 8855]
[2]Kwak, Seung-Hwa; Lim, Won Young; Hao, Aili; Mashalidis, Ellene H.; Kwon, Do-Yeon; Jeong, Pyeonghwa; Kim, Mi Jung; Lee, Seok-Yong; Hong, Jiyong [European Journal of Medicinal Chemistry, 2021, vol. 215]

47
[ 79200-56-9 ]
[ 168683-02-1 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 4379 - 4392
[2]Journal of Medicinal Chemistry,2000,vol. 43,p. 3482 - 3486
[3]Journal of Medicinal Chemistry,1999,vol. 42,p. 4725 - 4728
[4]Patent: WO2011/3061,2011,A2
[5]Synthetic Communications,2013,vol. 43,p. 2641 - 2647
[6]Journal of Medicinal Chemistry,2016,vol. 59,p. 5297 - 5310

48
[ 79200-56-9 ]
[ 229613-93-8 ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3482 - 3486
[2]Synthetic Communications,2013,vol. 43,p. 2641 - 2647
[3]Journal of Medicinal Chemistry,2016,vol. 59,p. 5297 - 5310
[4]Tetrahedron,2019,vol. 75,p. 4458 - 4470

49
[ 79200-56-9 ]
[ 151907-79-8 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4725 - 4728

50
[ 79200-56-9 ]
[ 172015-79-1 ]

Reference： [1]Nucleosides, nucleotides and nucleic acids,2000,vol. 19,p. 297 - 327

51
[ 168773-48-6 ]
[ 79200-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 2: 97 percent / TBAF / tetrahydrofuran / 0.33 h 3: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 4: 98 percent / DBU / xylene / 16.5 h / Heating 5: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 6 steps 1: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 2: 97 percent / TBAF / tetrahydrofuran / 0.33 h 3: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 4: 20 percent 5: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 6: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 6 steps 1: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 2: 97 percent / TBAF / tetrahydrofuran / 0.33 h 3: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 4: 40 percent / LiHMDS 5: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 6: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

Reference： [1]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[2]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[3]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]

52
[ 168773-55-5 ]
[ 79200-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 2: 98 percent / DBU / xylene / 16.5 h / Heating 3: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 4 steps 1: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 2: 20 percent 3: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 4: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 4 steps 1: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 2: 40 percent / LiHMDS 3: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 4: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

Reference： [1]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[2]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[3]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]

53
[ 168773-42-0 ]
[ 79200-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 2: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 3: 97 percent / TBAF / tetrahydrofuran / 0.33 h 4: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 5: 98 percent / DBU / xylene / 16.5 h / Heating 6: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 7 steps 1: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 2: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 3: 97 percent / TBAF / tetrahydrofuran / 0.33 h 4: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 5: 20 percent 6: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 7: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 7 steps 1: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 2: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 3: 97 percent / TBAF / tetrahydrofuran / 0.33 h 4: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 5: 40 percent / LiHMDS 6: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 7: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

Reference： [1]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[2]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[3]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]

54
[ 168773-45-3 ]
[ 79200-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 2: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 3: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 4: 97 percent / TBAF / tetrahydrofuran / 0.33 h 5: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 6: 98 percent / DBU / xylene / 16.5 h / Heating 7: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 8 steps 1: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 2: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 3: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 4: 97 percent / TBAF / tetrahydrofuran / 0.33 h 5: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 6: 20 percent 7: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 8: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 8 steps 1: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 2: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 3: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 4: 97 percent / TBAF / tetrahydrofuran / 0.33 h 5: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 6: 40 percent / LiHMDS 7: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 8: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

Reference： [1]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[2]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[3]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]

55
[ 168773-41-9 ]
[ 79200-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 2: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 3: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 4: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 5: 97 percent / TBAF / tetrahydrofuran / 0.33 h 6: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 7: 98 percent / DBU / xylene / 16.5 h / Heating 8: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 9 steps 1: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 2: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 3: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 4: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 5: 97 percent / TBAF / tetrahydrofuran / 0.33 h 6: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 7: 20 percent 8: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 9: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 9 steps 1: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 2: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 3: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 4: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 5: 97 percent / TBAF / tetrahydrofuran / 0.33 h 6: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 7: 40 percent / LiHMDS 8: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 9: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

Reference： [1]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[2]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[3]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]

56
[ 168773-47-5 ]
[ 79200-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 97 percent / TBAF / tetrahydrofuran / 0.33 h 2: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 3: 98 percent / DBU / xylene / 16.5 h / Heating 4: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 5 steps 1: 97 percent / TBAF / tetrahydrofuran / 0.33 h 2: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 3: 20 percent 4: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 5: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 5 steps 1: 97 percent / TBAF / tetrahydrofuran / 0.33 h 2: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 3: 40 percent / LiHMDS 4: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 5: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

Reference： [1]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[2]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[3]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]

57
[ 168773-44-2 ]
[ 79200-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 2: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 3: 97 percent / TBAF / tetrahydrofuran / 0.33 h 4: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 5: 98 percent / DBU / xylene / 16.5 h / Heating 6: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 7 steps 1: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 2: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 3: 97 percent / TBAF / tetrahydrofuran / 0.33 h 4: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 5: 20 percent 6: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 7: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 7 steps 1: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 2: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 3: 97 percent / TBAF / tetrahydrofuran / 0.33 h 4: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 5: 40 percent / LiHMDS 6: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 7: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

Reference： [1]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[2]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[3]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]

58
[ 168773-46-4 ]
[ 79200-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 2: 97 percent / TBAF / tetrahydrofuran / 0.33 h 3: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 4: 98 percent / DBU / xylene / 16.5 h / Heating 5: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 6 steps 1: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 2: 97 percent / TBAF / tetrahydrofuran / 0.33 h 3: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 4: 20 percent 5: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 6: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 6 steps 1: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 2: 97 percent / TBAF / tetrahydrofuran / 0.33 h 3: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 4: 40 percent / LiHMDS 5: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 6: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

Reference： [1]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[2]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[3]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]

59
[ 168773-40-8 ]
[ 79200-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 2: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 3: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 4: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 5: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 6: 97 percent / TBAF / tetrahydrofuran / 0.33 h 7: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 8: 98 percent / DBU / xylene / 16.5 h / Heating 9: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 10 steps 1: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 2: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 3: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 4: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 5: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 6: 97 percent / TBAF / tetrahydrofuran / 0.33 h 7: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 8: 20 percent 9: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 10: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 10 steps 1: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 2: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 3: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 4: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 5: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 6: 97 percent / TBAF / tetrahydrofuran / 0.33 h 7: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 8: 40 percent / LiHMDS 9: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 10: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

Reference： [1]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[2]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[3]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]

60
[ 168773-43-1 ]
[ 79200-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 2: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 3: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 4: 97 percent / TBAF / tetrahydrofuran / 0.33 h 5: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 6: 98 percent / DBU / xylene / 16.5 h / Heating 7: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 8 steps 1: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 2: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 3: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 4: 97 percent / TBAF / tetrahydrofuran / 0.33 h 5: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 6: 20 percent 7: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 8: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 8 steps 1: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 2: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 3: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 4: 97 percent / TBAF / tetrahydrofuran / 0.33 h 5: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 6: 40 percent / LiHMDS 7: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 8: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

Reference： [1]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[2]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[3]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]

61
(6R)-5-Hydroxy-6-<(benzyloxy)methyl>-2-piperidinone [ No CAS ]
[ 79200-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 11 steps 1: imidazole / dimethylformamide / 15 h 2: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 3: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 4: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 5: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 7: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 8: 97 percent / TBAF / tetrahydrofuran / 0.33 h 9: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 10: 98 percent / DBU / xylene / 16.5 h / Heating 11: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 12 steps 1: imidazole / dimethylformamide / 15 h 2: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 3: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 4: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 5: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 7: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 8: 97 percent / TBAF / tetrahydrofuran / 0.33 h 9: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 10: 20 percent 11: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 12: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 12 steps 1: imidazole / dimethylformamide / 15 h 2: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 3: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 4: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 5: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 7: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 8: 97 percent / TBAF / tetrahydrofuran / 0.33 h 9: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 10: 40 percent / LiHMDS 11: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 12: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

	Multi-step reaction with 9 steps 1: imidazole / dimethylformamide / 15 h 2: 97 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 3: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 4: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 5: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 97 percent / TBAF / tetrahydrofuran / 0.33 h 7: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 8: 98 percent / DBU / xylene / 16.5 h / Heating 9: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 10 steps 1: imidazole / dimethylformamide / 15 h 2: 97 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 3: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 4: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 5: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 97 percent / TBAF / tetrahydrofuran / 0.33 h 7: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 8: 20 percent 9: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 10: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 10 steps 1: imidazole / dimethylformamide / 15 h 2: 97 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 3: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 4: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 5: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 97 percent / TBAF / tetrahydrofuran / 0.33 h 7: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 8: 40 percent / LiHMDS 9: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 10: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

Reference： [1]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[2]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[3]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[4]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[5]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[6]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]

62
[ 168773-36-2 ]
[ 79200-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 11 steps 1: 92 percent / imidazole / dimethylformamide / 15 h 2: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 3: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 4: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 5: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 7: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 8: 97 percent / TBAF / tetrahydrofuran / 0.33 h 9: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 10: 98 percent / DBU / xylene / 16.5 h / Heating 11: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 12 steps 1: 92 percent / imidazole / dimethylformamide / 15 h 2: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 3: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 4: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 5: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 7: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 8: 97 percent / TBAF / tetrahydrofuran / 0.33 h 9: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 10: 20 percent 11: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 12: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 12 steps 1: 92 percent / imidazole / dimethylformamide / 15 h 2: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 3: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 4: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 5: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 7: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 8: 97 percent / TBAF / tetrahydrofuran / 0.33 h 9: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 10: 40 percent / LiHMDS 11: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 12: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

	Multi-step reaction with 9 steps 1: 92 percent / imidazole / dimethylformamide / 15 h 2: 97 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 3: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 4: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 5: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 97 percent / TBAF / tetrahydrofuran / 0.33 h 7: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 8: 98 percent / DBU / xylene / 16.5 h / Heating 9: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 10 steps 1: 92 percent / imidazole / dimethylformamide / 15 h 2: 97 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 3: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 4: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 5: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 97 percent / TBAF / tetrahydrofuran / 0.33 h 7: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 8: 20 percent 9: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 10: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 10 steps 1: 92 percent / imidazole / dimethylformamide / 15 h 2: 97 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 3: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 4: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 5: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 97 percent / TBAF / tetrahydrofuran / 0.33 h 7: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 8: 40 percent / LiHMDS 9: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 10: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

Reference： [1]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[2]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[3]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[4]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[5]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[6]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]

63
[ 168773-38-4 ]
[ 79200-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 2: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 3: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 4: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 5: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 6: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 7: 97 percent / TBAF / tetrahydrofuran / 0.33 h 8: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 9: 98 percent / DBU / xylene / 16.5 h / Heating 10: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 11 steps 1: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 2: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 3: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 4: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 5: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 6: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 7: 97 percent / TBAF / tetrahydrofuran / 0.33 h 8: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 9: 20 percent 10: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 11: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 11 steps 1: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 2: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 3: 93 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 4: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 5: 99 percent / NH₃, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 6: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 7: 97 percent / TBAF / tetrahydrofuran / 0.33 h 8: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 9: 40 percent / LiHMDS 10: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 11: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

	Multi-step reaction with 8 steps 1: 97 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 2: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 3: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 4: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 5: 97 percent / TBAF / tetrahydrofuran / 0.33 h 6: 97 percent / PPh₃, imidazole, I₂ / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 7: 98 percent / DBU / xylene / 16.5 h / Heating 8: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 9 steps 1: 97 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 2: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 3: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 4: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 5: 97 percent / TBAF / tetrahydrofuran / 0.33 h 6: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 7: 20 percent 8: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 9: CAN / acetonitrile; H₂O / 0.28 h / 0 °C
	Multi-step reaction with 9 steps 1: 97 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 2: 100 percent / H₂ / 10percent Pd/C / ethanol / 23 h 3: 89 percent / CBr₄, PPh₃ / CH₂Cl₂ / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 4: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 5: 97 percent / TBAF / tetrahydrofuran / 0.33 h 6: 1.) (COCl)2, DMSO, 2.) Et₃N / 1.) CH₂Cl₂, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 7: 40 percent / LiHMDS 8: 39 percent / HCO₂H, Bu₃N / PPh₃, Pd(OAc)2 / dimethylformamide / 6 h 9: CAN / acetonitrile; H₂O / 0.28 h / 0 °C

Reference： [1]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[2]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[3]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[4]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[5]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]
[6]Campbell, Jeffrey A.; Lee, Won Koo; Rapoport, Henry [Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4602 - 4616]

64
[ 79200-56-9 ]
[ 625108-11-4 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen In ethyl acetate at 20℃; for 24h;	2.A.A INTERMEDIATE 2 INTERMEDIATE 2 Procedure A: Step A: A mixture of (1S)- (+)-2-azabicyclo [2.2. 1] hept-5-en-3-one (10.3g, 94. 4MMOL) in ethyl acetate (200ML) and 10% Pd/C (0. 5G), was hydrogenated at rt. After 24h the reaction mixture was filtered and evaporated leaving behind 10.4g (100%) of the product that was taken in 250ML methanol and HCl (12M, 6ML). The resultant mixture was stirred at rt, until the reaction was complete (72h). Evaporation of methanol followed by drying under high vacuum, yielded title compound as an off white SOLID. H NMR (500 MHz, D20) : 8 3.70 (s, 3H), 3.01 (M, 1H), 2.38 (M, 1H), 2.16-1. 73 (M, 6H).

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2004/92124, 2004, A2 Location in patent: Page 48

65
[ 79200-56-9 ]
[ 71830-07-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogen In ethyl acetate at 20℃; for 24h;	A Intermediate 6; Step A; A mixture of (1S)-(+)-2-azabicyclo[2.2.1]hept-5-en-3-one (10.3 g, 94.4 mmol) in ethyl acetate (200 mL) and 10% Pd/C (0.5 g), was hydrogenated at room temperature. After 24 h the reaction mixture was filtered and evaporated leaving behind 10.4 g (100%) of the crude product. This was taken in 250 mL methanol and HCl (12 M, 6 mL) was added. The resultant mixture was stirred at room temperature, until the reaction was complete (72 h). The solvent was evaporated and the crude product was dried under high vacuum to yield the title compound as an off white solid (16.0 g, 96%). 1H NMR (500 MHz, D2O): δ 3.70 (s, 3H), 3.01 (m, 1H), 2.38 (m, 1H), 2.16-1.73 (m, 6H).
100%	With hydrogen In ethyl acetate at 20℃; for 24h;	INTERMEDIATE 3 A mixture of (1(at)-(+)-2-azabicyclo[2.2.1]hept-5-en-3-one (10.3 g, 94.4 mmol) in EtOAc (200 mL) and 10% Pd/C (0.5 gm), was hydrogenated at room temperature under a hydrogen balloon. After 24 h the reaction mixture was filtered and evaporated leaving behind 10.4 g (100%) of a product that was taken in 250 mL methanol and HCI (12M, 6 mL). The resultant mixture was stirred at RT, until the reaction was complete (72 h). Evaporation of methanol followed by drying under high vacuum, yielded the title compound as an off white solid (16.0 g, 96%).

Reference： [1]Current Patent Assignee: MERCK & CO INC - US2007/155731, 2007, A1 Location in patent: Page/Page column 30
[2]Current Patent Assignee: MERCK & CO INC - WO2005/105092, 2005, A2 Location in patent: Page/Page column 29

66
[ 79200-56-9 ]
[ 98-09-9 ]
(1R)-2-aza-2-(benzenesulfonyl)bicyclo[2.2.1]hept-5-ene-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; Inert atmosphere; Stage #2: benzenesulfonyl chloride In tetrahydrofuran; mineral oil at 20℃; for 1.5h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Neres, João; Labello, Nicholas P.; Somu, Ravindranadh V.; Boshoff, Helena I.; Wilson, Daniel J.; Vannada, Jagadeshwar; Chen, Liqiang; Barry III, Clifton E.; Bennett, Eric M.; Aldrich, Courtney C. [Journal of Medicinal Chemistry, 2008, vol. 51, # 17, p. 5349 - 5370]

67
[ 201230-82-2 ]
[ 79200-56-9 ]
[ 1259382-47-2 ]
[ 1259382-46-1 ]

Yield	Reaction Conditions	Operation in experiment
	With acetylacetonatodicarbonylrhodium(l); hydrogen; Kelliphite In toluene at 50℃; for 1.5h; Autoclave; regioselective reaction;
	With hydrogen In toluene at 20℃; for 5h; autoclave;	1 Example 1 (1 ?,4 ?,6fl)-3-oxo-2-azabicyclo[2.2.1]heptane-6- carbaldehyde (2). To a 50 ml_ autoclave (pre-purged with nitrogen) was added a catalyst solution containing (H.^-Kelliphite (4.8 mg, 0.5 mol%) andRh(acac)(CO)2 (1 mg, 0.4 mol%) in toluene (1 ml_). Three pump-purge cycles were carried out using CO:H2, the mixture placed under 5 bar of CO:H2 (1 :1 ), heated to 50 °C in an oil bath and stirred at 1000 rpm with a magnetic cross stirrer bar for 1 hour. The autoclave was subsequently removed from the heating bath, depressurized and a solution containing the unsaturated 1 (109 mg, 1 mmol) and tetraethyl silane (30 μΙ_, 33 mol %) as internal standard in toluene (2 ml_) was injected into the autoclave. The autoclave was then pressurized to 4.5 bar CO:H2 (1 :1 ) heated to 50 °C and stirred at 1000 rpm with a magnetic cross stirrer bar for 90 minutes. The autoclave was then removed from heating, allowed to cool to room temperature and depressurized. Solvent was removed from the crude reaction mixture and the product isolated by column chromatography with ethyl acetate as eluent, the product was isolated as (97% conversion to aldehydes by 1H NMR spectroscopy based on internal standard, regio-isomeric ratio of 6.3:1 , the major product isomer being 2). Yield: 76 mg (colorless oil), 0.55 mmol (55%). aD25= -278.4° (c= 2.85, CDCI3); vmax/cm"1= 3279, 2960, 2886, 1683, 1466, 1450, 1401 , 1329, 1290, 1229, 1209, 1 151 , 1 1 16, 1064; 1H NMR (300 MHz, CDCI3) δΗ= 9.73 (d, 1 H, J= 1 .0 Hz, C8H), 6.33 (bs, 1 H, N2H), 4.1 1 (s, 1 H, C1 H), 2.86-2.94 (m, 1 H, C6H), 2.73-2.79 (m, 1 H, C4H), 2.13-2.22 (dt, 1 H, J= 12.9, 4.5 Hz, C5H), 1 .87- 1 .94 (m, 1 H, C7H), 1.74-1 .84 (ddd, 1 H, J= 2.9, 9.0, 2.4 Hz, C5H) .37- .44 (ddd, 1 H, J= 9.9, 3.5, 1 .5 Hz, C7H); 13C NMR (CDCI3) 6C= 200.6 (C8), 181 .7 (C3), 56.5 (C1 ), 56.3 (C6), 44.6 (C4), 39.6 (C7), 25.3 (C5); m/z (CI+) 140.0715 (M+Na)+ C7H10NO2 requires 140.0712. 2D-NMR spectroscopy used to determine identity of regioisomer (COSY, HMBC, and HSQC).
	With hydrogen In toluene at 20℃; for 5h; autoclave;	9 Example 9 (1 S,4S,5S)-3-Oxo-2-azabicyclo[2.2.1]heptane-5-carb aldehyde (3). When the asymmetric hydroformylation was carried out, according to the procedure for compound 2, using (S,S)-Kelliphite as modifying ligand the other regio-isomer, 3 was formed in excess (up to 7.15:1 ). 1H NMR (300 MHz, CDCI3) δΗ= 9.74 (s, 1 H, C8H), 7.08 (bs, 1 H, N2H), 3.92 (s, 1 H, C1 H), 2.96 (s, 1 H, C4H), 2.78-2.86 (m, 1 H, C5H), 2.1 1 -2.23 (m, 1 H, C6H), 1 .80-1.91 (m, 1 H, C7H), 1.73-1.81 (m, 1 H, C6H), 1 .32-1.40 (m, 1 H, C7H); 13C NMR (75.5 Hz, CDCI3) δ0=199.9 (C8), 179.7 (C3), 55.1 (C1 ), 49.1 (C5), 46.3 (C4), 39.5 (C7), 31.9 (C6). NOESY confirms exo-epimer formed exclusively. 2D-NMR spectroscopy used to determine identity of regioisomer (COSY, HMBC, and HSQC).

Reference： [1]Noonan, Gary M.; Cobley, Christopher J.; Lebl, Tomas; Clarke, Matthew L. [Chemistry - A European Journal, 2010, vol. 16, # 43, p. 12788 - 12791]
[2]Current Patent Assignee: DR REDDY'S LABORATORIES LIMITED - WO2011/150205, 2011, A2 Location in patent: Page/Page column 14; 15-16
[3]Current Patent Assignee: DR REDDY'S LABORATORIES LIMITED - WO2011/150205, 2011, A2 Location in patent: Page/Page column 14; 21

68
[ 79200-56-9 ]
[ 1312161-65-1 ]
[ 151907-79-8 ]
[ 298716-03-7 ]

Reference： [1]Patent: WO2011/3061,2011,A2

69
[ 79200-56-9 ]
[ 298716-03-7 ]

Reference： [1]Patent: WO2011/3061,2011,A2

70
[ 79200-56-9 ]
[ 148490-97-5 ]
[ 1311258-54-4 ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium phosphate In toluene at 110℃; for 18h; Inert atmosphere;	65 Preparation No.65: Preparation of Methyl 2-methoxy-4-((lR,4S)-3-oxo-2- azabicyclo[2.2.1]hept-5-en-2-yl)benzoate; A 50 mL round bottom flask equipped with reflux condenser outfitted with a nitrogen inlet adapter was charged with (lR,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (1.480 g, 13.56 mmol), copper(I) iodide (0.129 g, 0.678 mmol), potassium phosphate tribasic (5.76 g, 27.1 mmol), evacuated and filled with nitrogen (three cycles), and then toluene (27.1 mL) was added to give a white suspension. Methyl 4-iodo-2-methoxybenzoate (4.95 g, 16.95 mmol) and N.,N2- dimethylethane- 1,2 -diamine (0.146 mL, 1.356 mmol) were each added sequentially in one portion. The reaction mixture was heated at about 110 °C for about 18 h. The reaction mixture was filtered and deposited onto silica gel. The crude material was purified via automated silica gel chromatography (10%-50% EtOAc : Heptane; EA -80g column, 18 x 150 mm test tubes). The fractions containing product were combined and concentrated to afford methyl 2-methoxy-4-((lR,4S)-3-oxo-2-azabicyclo[2.2.1]hept-5-en-2-yl)benzoate (2.69 g, 74%) as a solid. LC/MS (Table 1 , Method g) Rt = 1.95 min, m/z 21 (M+H)+.

Reference： [1]Current Patent Assignee: ABBOTT LABORATORIES INC - WO2011/71570, 2011, A1 Location in patent: Page/Page column 202-203

71
[ 67-56-1 ]
[ 79200-56-9 ]
(+)-methyl (1R,4S)-4-aminocyclopent-2-ene-1-carboxylate hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride In methanol at 0 - 15℃; for 3h;	1.A (1R,4S)-methyl 4-aminocyclopent-2-enecarboxylate Example 1A (1R,4S)-methyl 4-aminocyclopent-2-enecarboxylate To a cooled mixture of (1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (13 g, 119 mmol) in methanol (150 mL) at 0° C. was added thionyl chloride (20 mL, mmol) dropwise, keeping the reaction temperature under 15° C. Upon completion of the addition, the reaction mixture was stirred at 5° C. for 3 hours. The solvent was removed under reduced pressure, and the product was dried in vacuo to give Example 1A as a hydrochloride salt.
	With thionyl chloride at 0 - 15℃; for 3h;	g.1.1A Example 1A ( 1 R,4S)-methyl 4-aminocyclopent-2-enecarboxylate Example 1A ( 1 R,4S)-methyl 4-aminocyclopent-2-enecarboxylate To a cooled mixture of (lR,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (13 g, 119 mmol) in methanol (150 mL) at 0 °C was added thionyl chloride (20 mL, mmol) dropwise, keeping the reaction temperature under 15 °C. Upon completion of the addition, the reaction mixture was stirred at 5 °C for 3 hours. The solvent was removed under reduced pressure, and the product was dried in vacuo to give Example 1 A as a hydrochloride salt.

Reference： [1]Current Patent Assignee: ABBVIE INC - US2013/261129, 2013, A1 Location in patent: Paragraph 0265
[2]Current Patent Assignee: ABBVIE INC - WO2013/149376, 2013, A1 Location in patent: Page/Page column 62

72
[ 126147-86-2 ]
[ 79200-56-9 ]
2-azabicyclo[2.2.1]hept-2-yl([2,1,3]-benzoxadiazol-5-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.28 g	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With palladium 10% on activated carbon; hydrogen; triethylamine In tetrahydrofuran; dichloromethane at 20℃; for 18h; Stage #2: With lithium aluminium tetrahydride In tetrahydrofuran for 1h; Reflux; Stage #3: benzofurazan-5-carbonyl chloride With triethylamine In dichloromethane	7 EXAMPLE 72-Azabicyclo[2.2.1]hept-2-yl([2,1,3]-benzoxadiazol-5-yl)methanone EXAMPLE 72-Azabicyclo[2.2.1]hept-2-yl([2,1,3]-benzoxadiazol-5-yl)methanone [0104] 10% Pd/C (0.25g) was added to a solution of 2-azabicyclo[2.2.1]hept-5-en-3-one in THF (30 ml) and dichloromethane(30 ml) and the mixture hydrogenated at room temperature for 18h. The solids were filtered off, the solventevaporated under vacuum, the residue dissolved in THF (60 ml) and lithium aluminum hydride (2g) added slowly. Themixture was refluxed for 1h and cooled to +5°C before adding hexane (60 ml) and concentrated sodium hydroxidesolution (4 ml). Celite (2g) was added and the mixture stirred for 1h before filtering off the solids and washing with THF(10 ml). To the mixture was added triethylamine (3 ml) and a solution of [2,1,3]-benzoxadiazole-5-carbonylchloride (2g,11.0 mmol) in dichloromethane (10 ml) and the mixture stirred overnight. Water (100 ml) was added, acidified to pH 2with sulfuric acid and extracted with ethyl acetate (2x100 ml). The combined organics were washed with saturatedsodium bicarbonate solution (100 ml), dried (NaSO4) and evaporated onto silica gel (5g) and the residue was chromatographedon silica gel eluting with ethyl acetate/hexane (1:1) → (3:1) → (1:0) to give the desired product as whitecrystals (0.28g) after crystallization from MTBE/hexane: mp = 92-93 °C, LC-MS, MH+ = 244; 1H NMR (300 MHz, CDCl3,rotamers) δ 7.93-7.87 (m, 2H), 7.59-7.54 (m, 1H), 4.79 and 4.17 (s, total 1H), 3.61 and 3.48 (m, total 1H), 3.28 and 3.08(dd, J = 9.3 and 1.5Hz, total 1H), 2.74 and 2.64 (s, total 1H), 1.90-1.47ppm (m, 6H).

Reference： [1]Current Patent Assignee: RESPIRERX PHARMACEUTICALS - EP2187888, 2015, B1 Location in patent: Paragraph 0103; 0104

73
[ 49805-30-3 ]
[ 79200-56-9 ]
[ 130931-83-8 ]
(-)-(1S, 4R)-4-amino-2-cyclopentene-1-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 99 % ee 2: 50 % ee	With water; lipase B from Candida antarctica In isopropyl alcohol at 60℃; for 0.5h; Enzymatic reaction;	General procedure: In a typical small-scale experiment, to the racemic substrate (0.05M solution) in i-Pr2O (1mL) CAL-B (30mg), H2O (0.5equiv) and then benzylamine (1equiv) were added. The mixture was shaken (167rpm) at 60°C. The progress of the reaction was followed by taking samples from the reaction mixtures and analyzing them by a GC method on a Chrompack Chirasil-Dex CB column [140°C for 25min→190°C (temperature rise 20°Cmin-1; 140kPa; retention times (min), (1S,4R)-1: 5.84 (antipode: 5.66)], (1R,4S)-2: 7.47 (antipode: 7.11)]. The ee values for the product γ-amino acids [after pre-column derivatization16 with CH2N2 (Caution derivatization with CH2N2 should be performed under a well-ventillating hood)] were determined by a GC method [120°C for 25min→160°C (temperature rise 10°Cmin-1; 140kPa; retention times (min), (1S,4R)-6: 27.38 (antipode: 27.84)], (1R,3S)-8: 28.74 (antipode: 28.98)].

Reference： [1]Galla, Zsolt; Forró, Enikő; Fülöp, Ferenc [Tetrahedron Asymmetry, 2016, vol. 27, # 16, p. 729 - 731]

74
[ 79200-56-9 ]
[ 329910-40-9 ]

Yield	Reaction Conditions	Operation in experiment
26.16%	With disodium hydrogenphosphate; sodium dihydrogenphosphate In water at 0℃; for 7h;	17.1 To a solution of (lR,4S)-2-azabicyclo[2.2. l]hept-5-en-3-one (30.00 g, 274,90 mmol, 1.00 eq) in NaH2P04 (395.00 mL, 0.2M) and Na2HP04 (55.00 ml,, 0.2 M) was added H20 (450.00 mL) and oxone (669.31 g, 4.40 mol, 16.00 eq) at 0°C portion-wise over 5 hrs, and maintaining the pH = 6 by addition of aq. NaOH ( 12 M) and keeping the temperature at 0°C. After addition, the mixture was stirred at 0°C for further 2 hrs, TLC (PE:EtOAc = 1 : 1) showed the starting material was consumed completely, the mixture was filtered and aqueous phase was extracted with DCM (400 mL*5) , the combined organic layers were dried over Na2S04, concentrated in vacuum to get (0555) (lS,2R,4S,5R)-3-oxa-6-azatricyclo[3.2.1.02,4]octan-7-one (9.00 g, 71.93 mmol, yield: 26.16%) as a yellow solid. 1H-NMR (400 MHz, CDC13) δ ppm 5.96 (br.s, 1 H), 3.86 (s, 1 H), 3.62 (1H, d, 7 = 3.2 Hz), 3.53 (1H, d, 7 = 2.8 Hz), 2.86 (s, IH), 1.82 (d, 1H, 7 = 9.6 Hz), 1.64 (d, 1H, 7 = 10.0 Hz).

Reference： [1]Current Patent Assignee: BLUEPRINT MEDICINES CORP - WO2017/35354, 2017, A1 Location in patent: Page/Page column 77

75
[ 67-56-1 ]
[ 79200-56-9 ]
(1R,3S)-methyl 3-aminocyclopentanecarboxylate hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With palladium 10% on activated carbon; hydrogen In ethyl acetate at 20℃; for 12h; Stage #2: methanol With thionyl chloride at 0 - 20℃; for 24h;

Reference： [1]Arutla, Viswanath; Leal, Joseph; Liu, Xiaowei; Sokalingam, Sriram; Raleigh, Michael; Adaralegbe, Adejimi; Liu, Li; Pentel, Paul R.; Hecht, Sidney M.; Chang, Yung [ACS Combinatorial Science, 2017, vol. 19, # 5, p. 286 - 298]

76
[ 79200-56-9 ]
2-ethyl-N-hydroxybutanimidoyl chloride [ No CAS ]
C₁₂H₁₈N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In toluene at 20℃;	1 Example 1 Add (-)-vencos lactone (1 mmol) to a 250 ml three-necked flask.Add triethylamine (3mmmol), stir well,Adding a toluene solution (2 mmol) of the newly prepared proguanil intermediate,The reaction solution was stirred at room temperature,After the reaction is completed, water is added, the layers are separated, and the toluene phase is taken.The toluene phase was washed twice with water and allowed to stand overnight.

Reference： [1]Current Patent Assignee: NANJING ACESYS PHARMATECH - CN108997171, 2018, A Location in patent: Paragraph 0021; 0022; 0023

77
[ 79200-56-9 ]
[ 501-53-1 ]
(1R,45)-benzyl 2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 60℃; for 27h; Inert atmosphere; Stage #2: benzyl chloroformate With trimethylamine In tetrahydrofuran; water at 0 - 20℃; for 48h;	3.1 Step 1. Benzyl (1R,4S)-2-azabicyclo 12.2.11 hept-5-ene-2-carboxylate (C-2) A solution of (1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one C-4a (5.0 g, 45.8 mmol) in anhydrousTHF (5OmL) was added slowly to a solution of LAH ( 28.7mL, 57.3 mmol, 2M solution inTHF) in anhydrous THF (50 mL) under a nitrogen atmosphere at 0 °C. The resulting mixture was then stirred at room temperature for 3 h and then heated at 60 °C for 24 h. The mixture was cooled to 0 °C and H20 (5.0 mL) was added carefully to the mixture. The resulting white suspension was filtered through a Celite pad and the pad was washed with anhydrous THF(250.0 mL). The clear filtrate was cooled to 0 °C and then treated with trimethylamine (12.8 mL, 91.6 mmol) and CbzCl (10.3mL, 68.7 mmol). The reaction mixture was slowly warmed to room temperature and stirred for 48 hours. The white precipitate was filtered and the resulting clear filtrate solution was concentrated to dryness. The crude material was purified by column chromatography (hexane: EtOAc 4:1) to give benzyl (1R,4S)-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate C-4b (7.06 g, 63%) as a clear oil. MS (ES, m/z): [M+1] = 230.

Reference： [1]Current Patent Assignee: ARDELYX, INC. - WO2019/55808, 2019, A1 Location in patent: Page/Page column 100

78
[ 75-21-8 ]
[ 79200-56-9 ]
(1R,4S)-2-(2-hydroxyethyl)-2-azabicyclo[2.2.1]hept-5-en-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With lithium diisopropyl amide In tetrahydrofuran for 1h; Stage #2: oxirane In tetrahydrofuran	C2.1 Step 1 : (l/?,4A)-2-(2-hydroxyethyl)-2-azabicyclo[2.2.1]hept-5-en-3-one (1-554) To a solution of (lf?,4ri)-2-azabicyclo[2.2. l]hept-5-en-3-one (3 g, CAS: 79200-56-9, 27.5 mmol) in THF (50 mL) was added LDA (2M in THF, 13.8 mL ,1.0 equiv.) at 25 °C. The reaction mixture was stirred for 1 h at 25 °C and then oxirane (cas: 75-21-8, 20 mL, 17.6 g, 0.4 mol, 14.5 equiv.) was added. The reaction mixture was stirred at 25 °C for 48 hours. When the reaction was deemed complete by LC-MS analysis, the pH of the reaction mixture was adjusted to 6-7 with HC1 (1M). The reaction mixture was concentrated to a residue, which was purified by reversed phase column chromatography (0.1% Formic acid in MeCN/H20) to afford (lf?,4ri)-2-(2- hydroxyethyl)-2-azabicyclo [2.2. l]hept-5-en-3-one, 1-554(2.8 g, 67% yield) as a yellow oil. MS (ESI, pos. ion) found m/z: 154.1 (MH+).

Reference： [1]Current Patent Assignee: CARMOT THERAPEUTICS - WO2019/183577, 2019, A1 Location in patent: Page/Page column 373

79
[ 79200-56-9 ]
[ 105-13-5 ]
[ 168960-17-6 ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: 4-Methoxybenzyl alcohol With hydrogenchloride In water for 1h; Stage #2: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 6.5h; Inert atmosphere;	1 Method A 4-Methoxybenzyl alcohol (35.80 mL, 0.29 mol, 1.5 equiv) was added dropwise to concentrated HCl (300 mL) and stirred for 1 h. Water was added, and the liquid was extracted (2×100 mL) with diethyl ether. The diethyl ether was dried over Na2SO4 and concentrated to a volume of about 50 mL. To a 2 L flask, equipped with an addition funnel, was added (1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (21.00 g, 0.19 mol), DMF (600 mL), and THF (600 mL), and the flask was cooled to 0° C. NaH (8.45 g, 0.21 mol, 1.1 equiv, 60% dispersion in mineral oil) was added portionwise. The flask was placed under N2 and stirred for 30 min. The Et2O/PMBCl solution was transferred to the addition funnel and was added dropwise at 0° C. The reaction was stirred for 6 h at room temperature. Upon completion, THF was removed in vacuo, and diethyl ether and water were added. Any solids were filtered, and the layers were separated. The aqueous layer was extracted (3×100 mL) with diethyl ether, and the organic layers were combined and washed with brine (2×200 mL). After drying over Na2SO4 and concentration, a yellow oil was obtained. The crude oil was purified by flash chromatography to yield 32.2 g (0.14 mol, 73% yield) of protected (1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (3). Spectra matched those in the literature. See, Qiu, J.; Silverman, R. B. J. Med. Chem. 2000, 43, 706-720.

Reference： [1]Current Patent Assignee: NORTHWESTERN UNIVERSITY (ILLINOIS) - US2019/359555, 2019, A1 Location in patent: Paragraph 0044; 0120; 0121

80
[ 134003-04-6 ]
[ 79200-56-9 ]

Yield	Reaction Conditions	Operation in experiment
98 % ee	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate In N,N-dimethyl-formamide at 45℃; for 15h;	1.6; 2.6; 3.6 (6) (1R, 4S) 2-azabicyclo[2.2.1]hept-5-en-3-one Dissolve 2.5 g of (1R, 4S) 4-aminocyclopent-2-ene-1-carboxylic acid in 10 mL of N, N-dimethylformamide, and add three7.4g of pyrrolidinylphosphonium bromide hexafluorophosphate, heated at 45°C to react for 15H. After the reaction, add water to dilute and extract with ethyl acetate. Take, wash the organic phase once with saturated ammonium chloride, wash once with saturated sodium bicarbonate, then dry the organic phase and spin dry to obtain the crude product. Ethyl acetate/n-hexane system is crystallized to obtain refined products with an ee value of 98%.

Reference： [1]Current Patent Assignee: NANJING ZENJI MEDICINE RES INSTITUTE - CN111072547, 2020, A Location in patent: Paragraph 0023; 0038-0040; 0041; 0056-0058; 0059; 0074-0076

81
[ 79200-56-9 ]
[ 229613-86-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogenchloride In ethanol for 2h; Heating / reflux;	1 A mixture of (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (10 g, 91.7 mmol), ethanol (200 ML) and conc. HCl (10 ML) was heated at reflux for 2 h.. The mixture was concentrated and the residue dried under vacuum.. A white solid was obtained which was suspended in ether to give 17.5 g (100%) of (-)-ethyl cis-4-amino-2-cyclopentene-1-carboxylate hydrochloride.
	With thionyl chloride In ethanol at 10 - 30℃; for 1h;	1.S1; 2.S1; 3.S1; 4.S1; 5.S1; 6; 7; 1-4 A preparation method of (1S,4R)-4-amino-2-cyclopentene-1-methanol hydrochloride, including : S1. Add 50g of (1R,4S)-2-azabicyclo[2,2,1]hept-5-en-3-one and 100g of absolute ethanol into the flask, and cool to 0 while stirring. Then 60g of thionyl chloride was added dropwise to the system, and the temperature of the system was controlled to be less than 10°C during the dropping process.After the addition of thionyl chloride was completed, the system was heated to 30 and the reaction was stirred for 1h. After the reaction, the obtained (1S,4R)-(-)ethyl-4-aminocyclopent-2-ene-1-carboxyl The hydrochloride salt is concentrated and dried for later use.

Reference： [1]Current Patent Assignee: BIOCRYST PHARMACEUTICALS INC - US6762316, 2004, B1 Location in patent: Page column 11
[2]Current Patent Assignee: ANHUI REDWOOD BIOMEDICAL TECH - CN111484418, 2020, A Location in patent: Paragraph 0019; 0037-0039; 0042-0044; 0047-0049; 0052-0054

82
[ 1470-91-3 ]
[ 79200-56-9 ]
C₁₀H₁₁NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: but-3-enoyl chloride In tetrahydrofuran at 20℃; Inert atmosphere;

Reference： [1]Location in patent: experimental part Aljarilla, Ana; Plumet, Joaquin [European Journal of Organic Chemistry, 2008, # 23, p. 3984 - 3990]

83
[ 39716-58-0 ]
[ 79200-56-9 ]
C₁₁H₁₃NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: pent-4-enoyl chloride In tetrahydrofuran at 20℃; Inert atmosphere;

Reference： [1]Location in patent: experimental part Aljarilla, Ana; Plumet, Joaquin [European Journal of Organic Chemistry, 2008, # 23, p. 3984 - 3990]

84
[ 79200-56-9 ]
[ 814-68-6 ]
C₉H₉NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With dmap; triethylamine In dichloromethane at 20℃; Inert atmosphere;

Reference： [1]Location in patent: experimental part Aljarilla, Ana; Plumet, Joaquin [European Journal of Organic Chemistry, 2008, # 23, p. 3984 - 3990]

85
[ 908094-01-9 ]
[ 79200-56-9 ]
(-)-exo-7-azatricyclo[3.2.1.0^2.4]octan-6-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	In diethyl ether at 20℃; for 24h;

Reference： [1]Bhushan, Rashmi Gupta; Vince, Robert [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 7, p. 2325 - 2333]

86
[ 79200-56-9 ]
1R-(-)-exo-cis-5,6-dihydroxy-2-azabicyclo[2.2.1]heptan-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With osmium(VIII) oxide; 4-methylmorpholine N-oxide In water; acetone; <i>tert</i>-butyl alcohol at 20℃; Cooling with ice;	A.I I. 1R-(-)-exo-cis-5,6-dihydroxy-2-azabicyclo[2.2. 1] heptan-3-one (1) A solution of 16.4 g (147 mmol) 1R-(-)-2-azabicyclo[2.2.1]hept-5-en-3-one in 400 ml acetone is added to a solution of 22.5 g (167 mmol) N-methyl-morpholine-N-oxide in 80 ml deionised water in a 1 L round-bottomed flask. 15 ml (1.2 mmol) of a 2.5% solution of osium tetraoxide in tert-butanol is added within 15 min while cooling on ice. The mixture is subsequently stirred overnight at room temperature. The solvent is removed by distillation in a rotary evaporator. It is stirred with 100 ml and again distilled off in a rotary evaporator. Afterwards it is dissolved in 600 ml deionised water and 35 g activated carbon is added. The mixture is stirred vigorously for 1 h and then filtered over a Seitz K 250 deep-bed filter. Water is removed from the filtrate by distillation in a rotary evaporator. The product is used without further purification. TLC (Merck silica gel 60 F-254): ethyl acetate/methanol/glacial acetic acid 7:2:1 Rf 0.75 (starting material), 0.53 (1). Staining with TDM/development in a chlorine chamber. *TDM reagent: Solution 1: 10 g N,N,N',N'-tetramethyl-4,4'-diamino-diphenyl methane in 40 ml glacial acetic acid and 200 ml deionised water. Solution 2: 20 g potassium chloride in 400 ml deionised water. Solution 3: Dissolve 0.3 g ninhydrin in 10 ml glacial acetic acid and add 90 ml deionised water. Finished reagent: A mixture of solution 1 and 2 and addition of 6 ml of solution 3

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US9399790, 2016, B2 Location in patent: Page/Page column 12

87
[ 79200-56-9 ]
(1R,4S)-2-methyl-2-azabicyclo[2.2.1]hept-5-en-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: With methyl iodide In tetrahydrofuran at 0℃;	5 Example 5: (0564) Synthesis of methyl (1S,4R)-4-(methylamino)cyclopent-2-ene-1-carboxylate (Inter C) To a solution of (1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (CAS 79200-56-9) (20.0 g, 183 mmol) in tetrahydrofuran (50 ml_) sodium hydride (8.8 g, 0.22 mol) was added at 0 °C. After stirring for 30 minutes iodomethane (52 g, 0.37 mmol) was added at 0 °C and the mixture stirred overnight. After quenching with sat. ammonium chloride solution (50 ml_), the aqueous phase was separated and extracted with ethyl acetate (3 x 50 ml_). The combined extracts were washed with brine, dried over sodium sulfate and concentrated to give (1R,4S)-2-methyl-2- azabicyclo[2.2.1]hept-5-en-3-one (5.6 g, 25%) as a colorless oil.

Reference： [1]Current Patent Assignee: BASF SE - WO2021/170464, 2021, A1 Location in patent: Page/Page column 87-88

88
[ 24424-99-5 ]
[ 79200-56-9 ]
[ 1007125-06-5 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: di-<i>tert</i>-butyl dicarbonate; (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With dmap In tetrahydrofuran at 0 - 20℃; Stage #2: With osmium(VIII) oxide; water; 4-methylmorpholine N-oxide In acetone at 0 - 20℃; for 2h;

Reference： [1]Akabane-Nakata, Masaaki; Chickering, Tyler; Harp, Joel M.; Schlegel, Mark K.; Matsuda, Shigeo; Egli, Martin; Manoharan, Muthiah [Organic Letters, 2022, vol. 24, # 2, p. 525 - 530]

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	79200-56-9	MDL No. :	MFCD00211274
Formula :	C₆H₇NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	DDUFYKNOXPZZIW-UHNVWZDZSA-N
M.W :	109.13	Pubchem ID :	2725037
Synonyms :

Num. heavy atoms :	8
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.5
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	33.17
TPSA :	29.1 Å²

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.92 cm/s

[ CAS No. 79200-56-9 ] {[proInfo.proName]}

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[ 79200-56-9 ] Synthesis Path-Upstream 1~6

[ 79200-56-9 ] Synthesis Path-Downstream 1~88

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[ 79200-56-9 ]

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[ 79200-56-9 ]

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[ 79200-56-9 ]

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Log Po/w (iLOGP) :	1.21
Log Po/w (XLOGP3) :	0.07
Log Po/w (WLOGP) :	-0.32
Log Po/w (MLOGP) :	0.37
Log Po/w (SILICOS-IT) :	0.73
Consensus Log Po/w :	0.41

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-0.56
Solubility :	30.0 mg/ml ; 0.275 mol/l
Class :	Very soluble
Log S (Ali) :	-0.23
Solubility :	63.5 mg/ml ; 0.582 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.49
Solubility :	35.6 mg/ml ; 0.326 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	4.09

Signal Word:	Danger	Class:	N/A
Precautionary Statements:	P261-P264-P270-P272-P280-P301+P312-P302+P352-P305+P351+P338-P310-P321-P330-P333+P313-P363-P501	UN#:	N/A
Hazard Statements:	H302-H317-H318	Packing Group:	N/A
GHS Pictogram:

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P378
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P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
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P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
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P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
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P337 + P313	IF eye irritation persists: Get medical advice/attention.
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P370 + P376	In case of fire: Stop leak if safe to Do so.
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P401
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P411 + P235	Keep cool.
Disposal
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P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 79200-56-9 ] {[proInfo.proName]}

Quality Control of [ 79200-56-9 ]

Related Doc. of [ 79200-56-9 ]

Product Details of [ 79200-56-9 ]

Calculated chemistry of [ 79200-56-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 79200-56-9 ]

Application In Synthesis of [ 79200-56-9 ]

[ 79200-56-9 ] Synthesis Path-Upstream 1~6

[ 79200-56-9 ] Synthesis Path-Downstream 1~88

Pharmaceutical Intermediates of [ 79200-56-9 ]

Peramivir Related Intermediates

Related Functional Groups of [ 79200-56-9 ]

Alkenes

Amides

Related Parent Nucleus of [ 79200-56-9 ]

Aliphatic Heterocycles

Other Aliphatic Heterocycles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Pharmaceutical Intermediates of
[ 79200-56-9 ]

Related Functional Groups of
[ 79200-56-9 ]

Related Parent Nucleus of
[ 79200-56-9 ]