Name: 39110-74-2|Naphthalen-1-ylmethanamine hydrochloride|97%
Brand: Ambeed
SKU: A211410
Rating: 94 (26 reviews)

1
[ 50-00-0 ]
[ 151-50-8 ]
[ 39110-74-2 ]
[ 63086-36-2 ]

Yield	Reaction Conditions	Operation in experiment
	With diethyl ether; water

Reference： [1]Baker; Ollis; Poole [Journal of the Chemical Society, 1949, p. 307,314]

2
[ 39110-74-2 ]
[ 1934-75-4 ]
[ 93070-49-6 ]

Yield	Reaction Conditions	Operation in experiment
75%	In butan-1-ol at 150℃; for 5h;	3 EXAMPLE 3; Synthesis of Compound Number 3: 14.3 g (0.1 M) of benzylamine hydrochloride was reacted with 8.9 g (0.1 M) of sodium dicyanamide in 100 ml of n-butanol at 150° C. for 5 hrs. and treated with 50 ml of water. The collected organic layer was washed with 0.1N HCl (2×50 ml) and water (1×50 ml) consequently and concentrated in vacuo to leave a viscous material which was taken up by ethyl acetate. This was dried over MgSO4 and crystallized from ethylacetate-hexane to afford 13 g (75% yield). m.p. 95-100° C. Without further purification, this was used for the next reaction. By following the same procedure as described in the synthesis of Compound 1, with 0.987 g (3 mM) of N,N-dodecylmethyl-1,3-propanediamine dihydrochlorides and 0.678 g (3.9 mmol) of the above cyanoguanidine, the desired compound was obtained. Elemental Analysis: Calcd. for C25H49N6Cl3: C, 55.60; H, 9.14; N, 15.56; Cl 19.69 Found: C, 55.32; H, 925; N, 15.53; C, 19.36. Nmr. (DMSO-d6) δ 7.35 (app. s, C6H5, 5H), 4.4 (s, 2H, CH2C6H5), 3.2 (t, 2H), 3.0 (broad, 4H), 2.7 (s, 3H, N-CH3), 1.9 (m, 2H), 1.6 (t, 3H), 1.3 (app. s, 18H), and 0.9 (t, 3H, CH3-CH2).
	With butan-1-ol

Reference： [1]Current Patent Assignee: ALCON, INC. - US6664294, 2003, B1 Location in patent: Page column 4; 5
[2]Shapiro et al. [Journal of the American Chemical Society, 1959, vol. 81, p. 4635,4636]

3
[ 86-86-2 ]
[ 39110-74-2 ]

Reference： [1]Journal of Organic Chemistry,1984,vol. 49,p. 4272 - 4276

4
phenylmagnesium bromide [ No CAS ]
[ 26964-90-9 ]
[ 39110-74-2 ]

Yield	Reaction Conditions	Operation in experiment
82%	With hydrogenchloride; triphenylphosphine 1.) THF/ether, 30 min; 2.) diethyl ether, 1h;

Reference： [1]Katritzky, Alan R.; Jiang, Jinlong; Urogdi, Laszlo [Tetrahedron Letters, 1989, vol. 30, # 25, p. 3303 - 3306]

5
[ 50-00-0 ]
[ 39110-74-2 ]
[ 542-92-7 ]
[ 112375-05-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	In water
73%	In water at 20℃; for 3h;
	In water for 3h; Ambient temperature; Yield given;

6.69 g	In water for 16h; Ambient temperature;
	In water at 20℃; for 3h;	4.1.1. Synthesis of azanorbornenes Azanorbornenes were produced as described in our previous work[11].To obtainN-benzyl-2-azanorbornene-5 benzylamine hydrochloride (0.20mol, 28.8g) was dissolved in water (75ml) and 37% aqueous formaldehyde (0.34mol, 26ml) was added to the solution. After that freshly prepared cyclopentadiene (0.51mol, 33.67g) was added drop wise under vigorously stirring and the reactive mixture was stirred for 3h at room temperature. The reaction was washed twice with ether:hexane mixture (1:1). The aqueous phase was made basic with solid potassium hydroxide. The product was isolated by extraction with ether.To obtainN-allyl-2-azanorbornene-5 the reaction flask was cooled in an ice bath and was loaded consecutively with water (75ml), concentrated HCl (0.20mol), allylamine (0.2mol, 11.4g), 37% aqueous formaldehyde (0.34mol, 26ml) and freshly prepared cyclopentadiene (0.51mol, 33.67g). The reactive mixture was stirred for 3h at room temperature. The reaction was washed twice with ether:hexane mixture (1:1). The aqueous phase was made basic with solid potassium hydroxide. The product was isolated by extraction with ether.To obtainN-(2-azanorbornene-5-en)methylacetate glycine methyl ester hydrochloride (0.10mol, 12.6g) was dissolved in water (50ml) and 37% aqueous formaldehyde (0.20mol, 15ml) was added to the solution. After that cyclopentadiene (0.30mol, 19.8g) was added drop wise under vigorously stirring and the reactive mixture was stirred for 3h at room temperature. The reaction was washed twice with ether:hexane mixture (1:1). The aqueous phase was made basic with solid potassium hydroxide. The product was isolated by extraction with ether.The yields of BANB, AANB and ANBM were 82, 74 and 70% from the theory, respectively. The fractions ofN-benzyl-2-azanorbornene-5 withTb=99-102°C (66.6Pa),nD20=1.5489;N-allyl-2-azanorbornene-5 withTb=51-53°C (133.3Pa),nD20=1.4880;N-(2-azanorbornene-5-en)methylacetate withTb=80-82°C (160.0Pa),nD20=1.4830 were used for copolymerization. The structures of the compounds were confirmed by13C NMR spectra (Table1).

Reference： [1]Bowser, Amy M.; Madalengoitia, Jose S. [Organic Letters, 2004, vol. 6, # 19, p. 3409 - 3412]
[2]Sosonyuk; Bulanov; Leshcheva; Zyk [Russian Chemical Bulletin, 2002, vol. 51, # 7, p. 1254 - 1261]
[3]Grieco, Paul A.; Bahsas, Ali [Tetrahedron Letters, 1988, vol. 29, # 46, p. 5855 - 5858]
[4]Fray; Augeri; Kleinman [Journal of Organic Chemistry, 1988, vol. 53, # 4, p. 896 - 899]
[5]Gorbunova, Marina; Anikina, Lada [European Journal of Medicinal Chemistry, 2013, vol. 63, p. 655 - 661]

6
[ 39110-74-2 ]
[ 68-94-0 ]
[ 14013-11-7 ]

Yield	Reaction Conditions	Operation in experiment
40%	With N,N-dimethyl-cyclohexanamine; phosphorus pentoxide at 150℃; for 24h;

Reference： [1]Girgis; Pedersen [Synthesis, 1982, vol. No. 6, # 6, p. 480 - 482]

7
[ 50-00-0 ]
[ 39110-74-2 ]
[ 78-79-5 ]
[ 32018-56-7 ]

Yield	Reaction Conditions	Operation in experiment
59 % Spectr.	In water at 35℃; for 70h;

Reference： [1]Larsen, Scott D.; Grieco, Paul A. [Journal of the American Chemical Society, 1985, vol. 107, # 6, p. 1768 - 1769]

8
[ 542-05-2 ]
[ 3287-99-8 ]
[ 111-30-8 ]
9-benzyl-3-oxo-9-azoniabicyclo[3.3.1]nonane bromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%		Glutaraldehyde (25% solution in water) (910 ml_, 2.4 mol) and <strong>[3287-99-8]benzylamine hydrochloride</strong> (344.1 g, 2.4 mol) in water (1050 ml.) was cooled to 0 0C. 3-Oxopentanedioic acid (350.Og, 2.4 mol) was added followed by addition of sodium acetate (aq.) (79.7 g in 797 ml. water) resulting in formation of a thick orange precipitate. The reaction mixture was heated to 50 0C and stirred at this temperature for 4 h. It was then cooled to ambient temperature and allowed to stand for 24 h. The reaction mixture was acidified to pH2 with 5N aqueous hydrochloric acid (-150 ml.) and the resulting aqueous mixture was washed with diethyl ether (2 x 500 ml_). The aqueous extracts were basified to pH12 with 4N aqueous sodium hydroxide (-650 ml.) and extracted with dichloromethane (6 x 500 ml_). The organic phase was dried (MgSO4) and concentrated under reduced pressure to afford the crude product as a red oil. Purification by chromatography on silica gel with dichloromethane:methanol (49:1 , v/v) as eluent afforded 9-benzyl-9- azabicyclo[3.3.1]nonan-3-one (300.0 g, 1.3 mol, 54%) as a pale orange solid.
54%		Glutaraldehyde (25% solution in water) (910 mL, 2.4 mol) and <strong>[3287-99-8]benzylamine hydrochloride</strong> (344.1 g, 2.4 mol) in water (1050 mL) was cooled to 0 C. 3-Oxopentanedioic acid (350.0 g, 2.4 mol) was added followed by addition of sodium acetate (aq.) (79.7 g in 797 mL water) resulting in formation of a thick orange precipitate. The reaction mixture was heated to 50 C. and stirred at this temperature for 4 h. It was then cooled to ambient temperature and allowed to stand for 24 h. The reaction mixture was acidified to pH2 with 5N aqueous hydrochloric acid (150 mL) and the resulting aqueous mixture was washed with diethyl ether (2 500 mL). The aqueous extracts were basified to pH12 with 4N aqueous sodium hydroxide (650 mL) and extracted with dichloromethane (6 500 mL). The organic phase was dried (MgSO4) and concentrated under reduced pressure to afford the crude product as a red oil. Purification by chromatography on silica gel with dichloromethane:methanol (49:1, v/v) as eluent afforded 9-benzyl-9-azabicyclo[3.3.1]nonan-3-one (300.0 g, 1.3 mol, 54%) as a pale orange solid.

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1997,p. 1307 - 1313
[2]Tetrahedron Letters,2019,vol. 60
[3]Angewandte Chemie - International Edition,2018,vol. 57,p. 6686 - 6690
Angew. Chem.,2018,vol. 130,p. 6796 - 6800,5
[4]Patent: WO2007/39563,2007,A1 .Location in patent: Page/Page column 13
[5]Patent: US2007/112019,2007,A1 .Location in patent: Page/Page column 7/1-7/2

9
[ 706-14-9 ]
[ 39110-74-2 ]
[ 259675-58-6 ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium 2-ethylhexanoic acid In tetrahydrofuran at 20℃; for 24h;

Reference： [1]Liu, Wenming; Xu, David D.; Repič, Oljan; Blacklock, Thomas J. [Tetrahedron Letters, 2001, vol. 42, # 13, p. 2439 - 2441]

10
[ 39110-74-2 ]
[ 7693-46-1 ]
[ 124068-97-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium carbonate In dichloromethane for 168h;

Reference： [1]Peterson, Matt A.; Shi, Houguang; Ke, Pucheng [Tetrahedron Letters, 2006, vol. 47, # 20, p. 3405 - 3407]

11
[ 39110-74-2 ]
[ 14152-97-7 ]
[ 58314-12-8 ]

Yield	Reaction Conditions	Operation in experiment
77%	With triethylamine In dichloromethane at 20℃; for 5h;

Reference： [1]Rodriguez-Lucena, David; Benito, Juan M.; Mellet, Carmen Ortiz; Garcia Fernandez, Jose M. [Chemical Communications, 2007, # 8, p. 831 - 833]

12
[ 542-05-2 ]
[ 39110-74-2 ]
[ 123-38-6 ]
[ 940925-98-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium acetate In water at 5 - 20℃; for 71h;	16 Synthesis of 1-benzyl-2,6-dethylpiperidin-4-one (123). A 1L, 3-necked round-bottom flask, equipped with a mechanical stirrer, reflux condenser, thermometer and addition funnel was charged with a solution of propionaldehyde (25.3 g, 0.4 mol) in water (150 mL) and stirred. The solution was cooled in an ice-bath to 5 °C. The solution was treated with benzylamine hydrochloride (37.2 g, 0.26 mol) and stirred at 5 0C for 30 min. Solid acetone dicarboxylic acid 89 (31.6 g, 0.2 mol) was added at 5 0C, followed within 5 min with a solution of sodium acetate (7.65 g, 0.093mol) in water (60 mL). The reaction mixture was stirred at 5 "C for 1. hour and then allowed to warm up to rt and stirred for 70 hours. CH2CI2 (350 mL) was added and the pH of the mixture was adjusted to 9 by cautious addition of solid sodium carbonate. The organic layer was separated and the aqueous layer was extracted with CH2CI2 (300 mL). The combined extracts were washed with sat. aq. sodium bicarbonate (200 mL), water (200 mL), brine (200 mL) and dried over anhydrous Na2SO4. The solution was filtered and evaporated to give a brown liquid, ca. 57g. This was diluted with CH2CI2 (100 mL) and filtered through a plug of basic alumina (ca. 3 x 2 in), washing with CH2CI2 (1L). The combined filtrates were evaporated to give the product 123 as a light orange liquid, 50.1 g, which was used without further purification.

Reference： [1]Current Patent Assignee: PERRIGO COMPANY PUBLIC LIMITED COMPANY - WO2007/64914, 2007, A2 Location in patent: Page/Page column 127

13
[ 3287-99-8 ]
[ 100-52-7 ]
[ 1485-70-7 ]

Yield	Reaction Conditions	Operation in experiment
78%	With tert.-butylhydroperoxide; calcium carbonate; In water; at 60℃; for 16h;Inert atmosphere; Green chemistry;	General procedure: Amixture of Fe(NO3)3.9H2O (20 mg, 0.05 mmol,5.0 mol %), TEMPO (15.6 mg, 0.10 mmol, 10 mol %) and benzyl alcohol (1.0 mmol,1 equiv) in acetonitrile (1.0 mL) was stirred under open air at roomtemperature (ca 23 oC) for 2 h. Amine hydrochloride salt (1.2 mmol,1.2 equiv), powdered CaCO3 (110 mg, 1.1 mmol, 1.1 equiv) and TBHP(70 wt% in H2O, 0.16 mL, 1.1 mmol, 1.1 equiv) were added sequentiallyto the mixture. The reaction vessel was capped and allowed to stir at 60 oCfor 16 h. After cooled to room temperature, the volatiles were removed under reducedpressure and the crude product was purified by flash chromatography on silicagel by gradient elution of ethyl acetate in petroleum ether to obtain the amideproduct. All amides were identified by full spectroscopic characterization andcomparison with literature or analogous literature data.
78%	With tert.-butylhydroperoxide; copper nanoparticles on black carbon; sodium carbonate; In acetonitrile; at 60℃; for 6h;Inert atmosphere;	General procedure: To a mixture of catalyst (20 mg, 3.68 mol %), amine hydrochloride salt (2 mmol) and Na2CO3 (212 mg, 2 mmol) in acetonitrile (1 mL) was added aldehyde (1 mmol) and TBHP (1.5 equiv) under an argon atmosphere at room temperature. The reaction vessel was capped and stirred at 60 C for 6 h. The progress of the reaction was monitored by thin-layer chromatography. After completion, the reaction mixture was allowed to cool to room temperature, then diluted with ethyl acetate and the catalyst separated from the reaction mixture by filtration. The combined organic layers were concentrated under vacuum and the resulting residue was purified by column chromatography.

Reference： [1]Applied Organometallic Chemistry,2017,vol. 31
[2]Journal of Coordination Chemistry,2017,vol. 70,p. 3217 - 3232
[3]Journal of Organic Chemistry,2012,vol. 77,p. 8007 - 8015,9
[4]Applied Organometallic Chemistry,2014,vol. 28,p. 101 - 108
[5]Tetrahedron Letters,2013,vol. 54,p. 4922 - 4925
[6]Tetrahedron Letters,2016,vol. 57,p. 95 - 99
[7]Advanced Synthesis and Catalysis,2012,vol. 354,p. 1407 - 1412
[8]Journal of the American Chemical Society,2006,vol. 128,p. 13064 - 13065
[9]European Journal of Organic Chemistry,2015,vol. 2015,p. 1824 - 1828

14
[ 39110-74-2 ]
[ 338414-89-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: 89 percent / acetic acid; butan-1-ol / 70 h 2.1: aq. NaOH / methanol / 20 °C 2.2: 83 percent / methanol / 20 °C
	Multi-step reaction with 2 steps 1: acetic acid / butan-1-ol / 72 h 2: sodium hydroxide / methanol

Reference： [1]Hadizadeh; Shafiee; Kazemi; Mohammadi [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2002, vol. 41, # 12, p. 2679 - 2682]
[2]Shafiee; Ebrahimzadeh; Zarghi; Dehpour [Pharmacy and Pharmacology Communications, 1998, vol. 4, # 2, p. 99 - 101]
[3]Shakour, Neda; Sahebkar, Amirhossein; Karimi, Gholamreza; Paseban, Maryam; Tasbandi, Aida; Mosaffa, Fatemeh; Tayarani-Najaran, Zahra; Ghodsi, Razieh; Hadizadeh, Farzin [Bioorganic Chemistry, 2021, vol. 115]

15
[ 39110-74-2 ]
[ 30345-85-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: conc. HCl / H₂O / 3 h / Heating 2: tetrahydrofuran / 3 h / Ambient temperature

Reference： [1]Ishii; Kotani; Nagaki; Shibayama; Toyomaki; Okukado; Ienaga; Okamoto [Journal of Medicinal Chemistry, 1996, vol. 39, # 9, p. 1924 - 1927]

16
[ 39110-74-2 ]
[ 775-11-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: H₂O / 18 h / Ambient temperature 2: aq. AcOH, NaNO₂ / Ambient temperature

Reference： [1]Moschel, Robert C.; Hudgins, W. Robert; Dipple, Anthony [Journal of Organic Chemistry, 1986, vol. 51, # 22, p. 4180 - 4185]

17
[ 39110-74-2 ]
[ 542-92-7 ]
[ 112375-05-0 ]

Yield	Reaction Conditions	Operation in experiment
	With formaldehyd In water	1 Preparation of Endo-2-aza-2-benzyl-bicyclo[2.2.1]heptan-7-ol PREPARATION 1 Preparation of Endo-2-aza-2-benzyl-bicyclo[2.2.1]heptan-7-ol According to the procedure of J. Am. Chem. Soc., 107, 1768-1769 (1985), cyclopentadiene (61.7 g, 935 mmol) was added to a solution of benzylamine hydrochloride (67.1 g, 467 mmol), 37% aqueous formaldehyde (65.4 mL/654 mmol), and water (190 mL). The solution was stirred at room temperature for three hours. Water (190 mL) was added to the reaction mixture then washed with diethyl ether (2250 mL). The aqueous layer was basified with solid KOH then extracted with diethyl ether (3250 mL). The combined extracts were dried over magnesium sulfate then evaporated to yield 2-aza-2-benzylbicyclo[2.2.1]hept-5-ene (79.6 g, 430 mmol).
	With formaldehyd In water	28 Synthesis of 2-Aza-2-benzylbicyclo[2.2.1]hept-5-ene STR40 EXAMPLE 28 Synthesis of 2-Aza-2-benzylbicyclo[2.2.1]hept-5-ene STR40 Cyclopentadiene (61.7 g/935 mmol) was added to a solution of benzylamine hydrochloride (67.1 g/467 mmol), 37% aqueous formaldehyde (65.4 mL/807 mmol), and water (190 mL). The solution was stirred at room temperature for three hours. Water (190 mL) was added to the reaction then washed with diethyl ether (2250 mL). The aqueous layer was basified with solid KOH then extracted with diethyl ether (3250 mL). The combined extracts were dried over magnesium sulfate then evaporated to yield 2-aza-2-benzylbicyclo[2.2.1]hept-5-ene (79.6 g/430 mmol)
	With potassium hydroxide; formaldehyd In water	17 2-Benzyl-2-azabicyclo[2.2.1]hept-5-ene Example 17 2-Benzyl-2-azabicyclo[2.2.1]hept-5-ene Following the procedure of Grieco, (S. D. Larson et al., J. Am. Chem. Soc. , 107 , 1768 (1985)), a mixture of 5.0 g (0.0348 mol) of benzylamine hydrochloride, 3.95 g (0.0487 mol) of aqueous 37% formaldehyde solution, 4.6 g (0.0696 mol) of cyclopentadiene, and 10 ml of water was stirred vigorously for 16 hours at room temperature. The mixture was diluted with 20 ml of water and the separated oil was extracted with ether (2 x 20 ml). The aqueous layer was basified by the addition of 4 g of KOH pellets, and the turbid mixture was extracted with ether (3 x 25 ml). Drying (K2CO3) of the combined extracts and evaporation of the solvent afforded 7.5 g (greater than theory) of the title compound as an oil: 1H-NMR(90 MHz, CDCl3) δ 1.3-1.8 (3H, m), 2.95 (1H, S), 3.3-3.1 (1H, m), 3.49 (2H, centroid of AB pattern, J=14), 3.85 (1H, S), 6.05-6.2 (1H, m), 6.35-6.5 (1H, m), 7.25-7.5 (5H, m).

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US6559171, 2003, B1
[2]Current Patent Assignee: ELI LILLY & CO - US6124312, 2000, A
[3]Current Patent Assignee: PFIZER INC - EP297858, 1990, A3

18
[ 542-05-2 ]
[ 3287-99-8 ]
[ 111-30-8 ]
[ 2291-58-9 ]

Yield	Reaction Conditions	Operation in experiment
78%	With sodium acetate; In water;	EXAMPLE 6 Synthesis of the compound 9-benzyl-9-azabicyclo[3.3.1]nonan-3-one To a solution in water (400 ml) of pentandial (84.5 g) and benzylamine hydrochloride (36.3 g), cooled at 0C, 30.8 g of 1,3-acetonedicarboxylic acid are added. 70 ml of an aqueous solution of sodium acetate at 10% are then added. The obtained mixture is kept under stirring at room temperature for one hour and then heated for 4 hours to 50C. The mixture is then acidified at pH 2 with a 10% w. HCl aqueous solution and then washed with diethyl ether. The pH is then brought to 6 with sodium bicarbonate and the aqueous phase extracted with dichloromethane. The organic extracts are anhydrified on sodium sulphate and the solvent evaporated to obtain 38.5 g of the compound 9-benzyl-9-azabicyclo[3.3.1]nonan-3-one (6a) as a light coloured solid. Yield: 78%; B.p.: 165-169C/0.2 mmHg; 1H-NMR (CDCl3): delta (ppm) 1.49-1.59 (m, 6H), 2.26 (d,2H,J=19Hz), 2.76 (dd,2H,J=8 and 19Hz), 3.28-3.49 (bs,2H), 3.91 (s,2H), 7.22-7.46 (m,5H).
78%		To a solution in water (400 ml) of pentandial (84.5 g) and benzylamine hydrochloride (36.3 g), cooled at 0 C., 30.8 g of 1,3-acetonedicarboxylic acid are added. 70 ml of an aqueous solution of sodium acetate at 10% are then added. The obtained mixture is kept under stirring at room temperature for one hour and then heated for 4 hours to 50 C. The mixture is then acidified at pH 2 with a 10% w. HCl aqueous solution and then washed with diethyl ether. The pH is then brought to 6 with sodium bicarbonate and the aqueous phase extracted with dichloromethane. The organic extracts are anhydrified on sodium sulphate and the solvent evaporated to obtain 38.5 g of the compound 9-benzyl-9-azabicyclo[3.3.1]nonan-3-one (6a) as a light coloured solid. Yield: 78%; B.p.: 165-169 C./0.2 mmHg; 1H-NMR (CDCl3): delta (ppm) 1.49-1.59 (m, 6H), 2.26 (d,2H,J=19 HZ), 2.76 (dd,2H,J=8 and 19 Hz), 3.28-3.49 (bs,2H), 3.91 (s,2H), 7.22-7.46 (m 5H).
78%		To a solution in water (400 ml) of pentandial (84.5 g) and benzylamine hydrochloride (36.3 g), cooled at 0C, 30.8 g of 1,3-acetonedicarboxylic acid are added. 70 ml of an aqueous solution of sodium acetate at 10% are then added. The obtained mixture is kept under stirring at room temperature for one hour and then heated for 4 hours to 50C. The mixture is then acidified at pH 2 with a 10% w. HCl aqueous solution and then washed with diethyl ether. The pH is then brought to 6 with sodium bicarbonate and the aqueous phase extracted with dichloromethane. The organic extracts are anhydrified on sodium sulphate and the solvent evaporated to obtain 38.5 g of the compound 9-benzyl-9-azabicyclo[3.3.1]nonan-3-one (6a) as a light coloured solid. [Show Image] Yield: 78%; B.p.: 165-169C/0.2 mmHg; 1H-NMR (CDCl3): delta (ppm) 1.49-1.59 (m, 6H), 2.26 (d,2H,J=19Hz), 2.76 (dd,2H,J=8 and 19Hz), 3.28-3.49 (bs,2H), 3.91 (s,2H), 7.22-7.46 (m,5H).

47%	With sodium acetate; In water;	A two-liter, 2-neck flask, an overhead stirrer and an addition funnel were used. Glutaraldehyde (100 ml_, 50% aq. solution) was placed in the flask. Water (63 mL) was added. 36.5 grams of 1 ,3-acetonedicarboxylic acid were added. Some bubbling was observed. NaOAc (14.25 g) was added and the mixture was stirred vigorously. A solution of benzylamine hydrochloride (35.6 g) in 112 mL of water was placed in the addition funnel. Alternatively it may be advantageous to dissolve the benzylamine hydrochloride in 80 mL of water and 30 mL of 0.12 N aqueous HCI, instead of 112 mL of H2O. The amine solution was added to the reaction mixture portionwise. Foaming and bubbling was observed. A dark yellow, sticky solid formed. The reaction mixture was allowed to stir overnight. Methylene chloride (500 mL) was added, followed by K2CO3 which was added until the pH ~ 8. The layers were separated and the aqueous layer was extracted with CH2CI2 (500 mL). The combined organic layers were passed through 300 mL of basic alumina and dried over EPO <DP n="92"/>MgSO4. The solution was then passed through 1.2 L of silica gel. The silica gel was washed with 300 mL of CH2CI2 after which the silica gel was eluted with 2000 mL of 5% MeOH in CH2CI2. The combined organic layers were concentrated by rotary evaporation to afford 26.9 g (47% yield) of 9-benzyl-9-azabicyclo[3.3.1]nonan-3-one as a pale yellow solid. The pale yellow solid was dissolved in THF and 4 N HCI in dioxane was added to obtain the hydrochloride salt as a white precipitate. NB. This is a modification of a procedure found in: G. Gonzalez Trigo, Anales de Quimica, 1979, 782-783
	With sodium acetate; In water;	Example 6 Synthesis of 9-benzyl-9-azabicyclo[3.3.1]nonan-3-one To a solution in water (400 ml) of pentandial (84.5 g) and benzylamine hydrochloride (36.3 g), cooled at 0 C. 30.8 g of 1,3-acetonedicarboxylic acid are added. 70 ml of an aqueous solution of sodium acetate at 10% are then added. The obtained mixture is kept under stirring at room temperature for one hour and then heated for 4 hours to 50 C. The mixture is then acidified at pH 2 with a 10% w. HCl aqueous solution and then washed with diethyl ether. The pH is then brought to 6 with sodium bicarbonate and the aqueous phase extracted with dichloromethane. The organic extracts are anhydrified on sodium sulphate and the solvent evaporated to obtain 38.5 g of the compound 9-benzyl-9-azabicyclo[3.3.1]nonan-3-one (6a) as a light coloured solid.

Reference： [1]Patent: EP2149370,2010,A1
[2]Patent: US2010/29622,2010,A1 .Location in patent: Page/Page column 17
[3]Patent: EP2149575,2010,A1 .Location in patent: Page/Page column 28-29
[4]Patent: WO2007/22502,2007,A2 .Location in patent: Page/Page column 90-91
[5]Patent: US2010/28257,2010,A1

19
[ 65292-99-1 ]
[ 3287-99-8 ]
[ 54761-04-5 ]
[ 1006606-04-7 ]

Reference： [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 205 - 208

20
[ 542-05-2 ]
[ 3287-99-8 ]
[ 34160-24-2 ]
[ 28957-72-4 ]

Yield	Reaction Conditions	Operation in experiment
70%		Step 7 8-Benzyl-8-aza-bicyclo[3.2.1]octan-3-one: Aqueous hydrochloric acid (0.025 M, 16 mL) was slowly added to a cold (0-5 C.) solution of 2,5-dimethoxyfuran (5.0 g, 37.8 mmol) and the mixture was stirred at ambient temperature for 15 hours. Benzylamine hydrochloride (6.5 g, 45.3 mmol), acetone 1,3-dicarboxylic acid, and an aqueous solution of sodium acetate (0.68 M, 30 mL) were added, and the mixture was stirred at ambient temperature for 1 hour and then at 50 C. for additional 1.5 hours. The pH was adjusted to 12 with 2N sodium hydroxide, and the mixture was extracted with ethyl acetate. The combined organic layers were dried and concentrated under reduced pressure. Purification by flash chromatography gave the title compound as a light yellow oil. Yield: 5.67 g, (70%). 1H-NMR (CDCl3.) delta: 1.62 (m, 2H), 2.12 (m, 2H), 2.20 (m, 1H), 2.36 (m, 1H), 2.70 (m, 2H), 3.50 (m, 2H), 3.75 (s, 2H), 7.20-7.50 (m, 5H).

Reference： [1]Patent: US2008/146605,2008,A1 .Location in patent: Page/Page column 40

21
[ 696-59-3 ]
[ 542-05-2 ]
[ 3287-99-8 ]
[ 28957-72-4 ]

Yield	Reaction Conditions	Operation in experiment
67%		To a solution of 0.025 M aqueous hydrochloric acid (100 ml) at [0C] was added 2, [5-DIMETHOXY-TETRAHYDROFURAN] (30 ml 231 [MMOL).] The reaction was stirred at [0C] overnight. The reaction was then diluted with water (200 ml) and benzyl amine hydrochloride (40 grams, 278 [MMOL),] 3-oxo-pentanedioic acid (33.7 grams, 231 [MMOL),] and sodium acetate (10.7 grams, 130 [MMOL)] were added. The reaction was stirred for 5 minutes at [0C,] warmed to ambient temperature and stirred for 90 minutes, then heated to [50C] for two hours, cooled to [0C] and basified to pH = 10 with 50 [%] aqueous sodium hydroxide (14 [ML).] The reaction mixture was extracted with ethyl acetate (3 times) and the organic layers were combined and washed with a saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo to give a brown oil. Silica gel chromatography gave the title compound (33.46 grams, 67 % yield

Reference： [1]Patent: WO2004/9588,2004,A1 .Location in patent: Page 63

22
[ 542-05-2 ]
[ 56999-16-7 ]
[ 39110-74-2 ]
9-benzyl-9-aza-bicyclo[3.3.1]nonane-3,7-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	Stage #1: 2-(2,2-diethoxyethoxy)-1,1-diethoxyethane With acetic acid In water for 1h; Heating / reflux; Stage #2: acetonedicarboxylic acid; benzylamine hydrochloride With sodium acetate In water at 50℃; for 3h; Stage #3: With sodium hydroxide In water at 20℃;	96 [9-BENZYL-9-AZA-BICVCLOR3.] 3. [11NONANE-317-DIONE] A solution of [2- (2, 2-DIETHOXY-ETHOXY)-1, 1-DIETHOXY-ETHANE] (12.0 grams, 47.9 [MMOL)] in acetic acid (2. [8MI)] and water (12 ml) was heated at reflux for one hour, cooled to an ambient temperature and stirred overnight. To the reaction mixture was then added benzyl amine hydrochloride (6.9 grams, 47.9 [MMOL),] 3-oxo- pentanedioic acid (5.48 g, 39.9 [MMOL),] sodium acetate (2.7 grams, 20 [MMOL)] and water (24 [ML).] The reaction was stirred for one hour, heated at [50°C] for three hours, cooled to ambient temperature and then basified with 50% aqueous sodium hydroxide. The reaction mixture was extracted with ethyl acetate (3). The organic layers were combined, dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel chromatography gave the title compound (4.23 grams, 38 [%] yield)

Reference： [1]Current Patent Assignee: PFIZER INC - WO2004/9588, 2004, A1 Location in patent: Page 65

23
[ 50-00-0 ]
[ 39110-74-2 ]
[ 67-64-1 ]
[ 84689-68-9 ]

Yield	Reaction Conditions	Operation in experiment
68%	at 75℃; for 18h; Heating / reflux;	79.1 A mixture of benzylamine hydrochloride (34.5 mmol, 5.01 g), acetone (173 mmol, 12.79 ml, 10.13 g) and formaldehyde (34.5 mmol, 2.59 ml, 2.80 g) was refluxed at 75 0C for 18h. The mixture was concentrated under reduced pressure then recrystallized from acetone to afford 4-(benzylamino)butan-2-one hydrochloride (68%).

Reference： [1]Current Patent Assignee: MERCK & CO INC; ORGANON & CO - WO2009/37220, 2009, A1 Location in patent: Page/Page column 102

24
[ 588-46-5 ]
[ 39110-74-2 ]

Yield	Reaction Conditions	Operation in experiment
49%	Stage #1: N-(phenylmethyl)acetamide With pyridine; oxalyl dichloride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: With propylene glycol In tetrahydrofuran at 0 - 20℃; Inert atmosphere;

Reference： [1]Koenig, Stefan G.; Vandenbossche, Charles P.; Zhao, Hang; Mousaw, Patrick; Singh, Surendra P.; Bakale, Roger P. [Organic Letters, 2009, vol. 11, # 2, p. 433 - 436]

25
[ 542-05-2 ]
[ 39110-74-2 ]
[ 115973-49-4 ]
[ 1215183-25-7 ]

Yield	Reaction Conditions	Operation in experiment
40%	Stage #1: acetonedicarboxylic acid; benzylamine hydrochloride; 3-ethoxycarbonylglutaric dialdehyde With hydrogenchloride; sodium acetate In water at 20℃; for 72h; Stage #2: With potassium carbonate In water	1 Example 1 Synthesis of 9-benzyl-7-oxo-9-aza-bicyclo[3.3.1]nonane-3-carboxylic acid ethyl ester (3) Acetone-1,3-dicarboxylic acid (2) (8.81 g, 60.36 mmol) and sodium acetate (5.04 g, 61.5 mmol) were added to a solution of 4-oxo-2-(2-oxo-ethyl)-butyric acid ethyl ester (1) (European Patent EP 0330788A1) (10.3 g, 60.36 mmol) in H2O (75 mL). Benzylamine (6.59 mL, 60.36 mmol) was dissolved in aqueous HCl (3 N, 41 mL) and was subsequently added to the stirring solution of the dialdehyde and the dicarboxylic acid over a 15 minute period. The reaction mixture was stirred for 3 days at room temperature after which the pH was adjusted to 8 by the addition of potassium carbonate. The resulting solution was extracted with CH2Cl2 (4*50 mL), the organic extracts dried (Na2SO4), filtered and concentrated under vacuum. The resulting residue was purified by silica gel chromatography, (eluant hexane/EtOAc 9/1 to 1/1, v/v) to give 7.43 g (40%) of 9-benzyl-7-oxo-9-aza-bicyclo[3.3.1]nonane-3-carboxylic acid ethyl ester (3) as a brown oil. Retention time (min)=0.963, method [1], MS (ESI) 302.2 (M+H); 1H NMR (300 MHz, CDCl3) δ 7.43-7.10 (m, 5H), 4.10 (q, J=7.1 Hz, 2H), 3.91 (s, 2H), 3.41-3.38 (m, 2H), 2.74 (dd, J=16.5, 6.6 Hz, 2H), 2.61-2.48 (m, 1H), 2.30 (d, J=16.5 Hz, 2H), 2.08 (dt, J=3.8 Hz, J=13.2 Hz, 2H), 1.81-1.72 (m, 2H), 1.22 (t, J=7.1 Hz, 3H).

Reference： [1]Current Patent Assignee: PERRIGO COMPANY PUBLIC LIMITED COMPANY - US2010/81680, 2010, A1 Location in patent: Page/Page column 47-48

26
[ 696-59-3 ]
[ 542-05-2 ]
[ 39110-74-2 ]
[ 28957-72-4 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: cis,trans-2,5-dimethoxytetrahydrofuran With hydrogenchloride In water for 0.333333h; Stage #2: acetonedicarboxylic acid; benzylamine hydrochloride With sodium hydroxide; disodium hydrogenphosphate In water at 0 - 20℃; Stage #3: With hydrogenchloride; sodium hydroxide more than 3 stages;	1.a Preparation 1: (1S,3R,5R)-3-amino-8-azabicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester a. Preparation of 8-benzyl-8-azabicyclo[3.2.1]octan-3-one Concentrated hydrochloric acid (30 mL) was added to a heterogeneous solution of 2,5-dimethoxy tetrahydrofuran (82.2 g, 0.622 mol) in water (170 mL) while stirring. In a separate flask cooled to 0° C. (ice bath), concentrated hydrochloric acid (92 mL) was added slowly to a solution of benzyl amine (100 g, 0.933 mol) in water (350 mL). The 2,5-dimethoxytetrahydrofuran solution was stirred for approximately 20 min, diluted with water (250 mL), and then the benzyl amine solution was added, followed by the addition of a solution of 1,3-acetonedicarboxylic acid (100 g, 0.684 mol) in water (400 mL) and then the addition of sodium hydrogen phosphate (44 g, 0.31 mol) in water (200 mL). The pH was adjusted from pH 1 to pH 4.5 using 40% NaOH. The resulting cloudy and pale yellow solution was stirred overnight. The solution was then acidified to pH 3 from pH 7.5 using 50% hydrochloric acid, heated to 85° C. and stirred for 2 hours. The solution was cooled to room temperature, basified to pH 12 using 40% NaOH, and extracted with dichloromethane (3×500 mL). The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure to produce the crude title intermediate as a viscous brown oil. To a solution of the crude intermediate in methanol (1000 mL) was added di-tert-butyl dicarbonate (74.6 g, 0.342 mol) at 0° C. The solution was allowed to warm to room temperature and stirred overnight. The methanol was removed under reduced pressure and the resulting oil was dissolved in dichloromethane (1000 mL). The intermediate was extracted into 1 M H3PO4 (1000 mL) and washed with dichloromethane (3×250 mL) The aqueous layer was basified to pH 12 using aqueous NaOH, and extracted with dichloromethane (3×500 mL). The combined organic layers were dried (MgSO4), filtered and concentrated under reduced pressure to produce the title intermediate as a viscous, light brown oil. 1H-NMR (CDCl3) δ (ppm) 7.5-7.2 (m, 5H, C6H5), 3.7 (s, 2H, CH2Ph), 3.45 (broad s, 2H, CH-NBn), 2.7-2.6 (dd, 2H, CH2CO), 2.2-2.1 (dd, 2H, CH2CO), 2.1-2.0 (m, 2H, CH2CH2), 1.6 (m, 2H, CH2CH2). (m/z): [M+H]+ calcd for C14H17NO 216.14; found, 216.0.

Reference： [1]Current Patent Assignee: THERAVANCE BIOPHARMA, INC. - US2006/229332, 2006, A1 Location in patent: Page/Page column 8-9

27
[ 39110-74-2 ]
[ 2004-06-0 ]
[ 4294-16-0 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In propan-1-ol at 70℃; for 8h;	1 First step, benzaldehyde (1.08 g), hydroxyamine hydrochloride (1.29 g), and NaOAc (1.67 g) were dissolved in EtOH (40 ml). The reaction mixture was stirred at room temperature for 6 h. EtOH was removed under reduced pressure. H2O (20 ml) was added to the residue, and extracted with EtOAc (3 × 20 ml). The EtOAc of the combined organic layer was removed by a rotary evaporation under reduced pressure to yield benzaldehyde oxime (1.13 g) as a pale yellowish solid. Second step, a solution of benzaldehyde oxime (1.13 g) and concentrated HCl (1 ml) in EtOH (40 ml) was subjected to hydrogenation at atmospheric pressure in the presence of 10% Pd/C (85 mg). The reaction mixture was filtered and the filtrate was concentrated to yield benzylamine hydrochloride (1.29 g) as a white solid. Third step, a mixture of benzylamine (355 mg, the hydrochloride), 6-chloropurine riboside (143 mg), and N,N-diisopropylethylamine (2 ml) in PrOH (40 ml) was heated to 70°C and reacted for 8h. After evaporation of the reaction mixture, the residue was separated by column chromatography oversilica gel eluting with CHCl3-CH3OH (30 : 1) to yield N6-(benzyl)-adenosine(151 mg) as a colorless solid: positive ESIMS at m/z 358 [M + H]+; negative ESIMS at 356 [M - H]- and 392 [M + Cl]-; 1H NMR (300 MHz, CD3OD): the adenosine moiety δ 8.20 (1H, s, H-2), 8.18 (1H, brs, H-8), 5.90 (1H, d, J = 6.6 Hz, H-1, H-1'), 4.69 (1H, dd, J= 6.6, 5.4 Hz, H-2'), 4.26 (1H, dd, J= 5.4 and 2.4 Hz, H-3'), 4.11 (1H, q, J = 2.4 Hz, H-4'), 3.83 (1H, dd, J = 12.6 and 2.4 Hz, H-5'a), 3.68 (1H, dd, J = 12.6 and 2.4 Hz, H-5'b); the benzyl moiety δ 7.14-7.34 (5H, m, H-2" ∼ H-6"), 4.77 (2H, brs, H-7"); 13C NMR (75 MHz, DMSO-d6): the adenosine moiety δ 154.6 (C-6), 152.4 (C-2), 148.5 (C-4), 140.0 (C-8), 119.8 (C-5), 88.0 (C-1'), 85.9 (C-4'), 73.5 (C-2'), 70.7 (C-3'), 61.7 (C-5'); the benzyl moiety δ 128.2 (C-3", C-5"), 127.1 (C-2", C-6"), 126.6 (C-4"), 42.9 (C-7").
151 mg	With N-ethyl-N,N-diisopropylamine In propan-1-ol at 70℃; for 8h;	1 Preparation of N6-(benzyl)-adenosine Third step, a mixture of benzylamine (355 mg, the hydrochloride), 6-chloropurine riboside (143 mg), and N,N-diisopropylethylamine (2 ml) in PrOH (40 ml) was heated to 70° C. and reacted for 8 h. After evaporation of the reaction mixture, the residue was separated by column chromatography oversilica gel eluting with CHCl3-CH3OH (30:1) to yield N6-(benzyl)-adenosine (151 mg) as a colorless solid: positive ESIMS at m/z 358 [M+H]+: negative ESIMS at 356 [M-H]- and 392 [M+Cl]-; 1H NMR (300 MHz, CD3OD): the adenosine moiety δ 8.20 (1H, s, H-2), 8.18 (1H, brs, H-8), 5.90 (1H, d, J=6.6 Hz, H-1, H-1'), 4.69 (1H, dd, J=6.6, 5.4 Hz, H-2'), 4.26 (1H, dd, J=5.4 and 2.4 Hz, H-3'), 4.11 (1H, q, J=2.4 Hz, H-4'), 3.83 (1H, dd, J=12.6 and 2.4 Hz, H-5'a), 3.68 (1H, dd, J=12.6 and 2.4 Hz, H-5'b); the benzyl moiety δ 7.14-7.34 (5H, m, H-2"˜H-6"), 4.77 (2H, brs, H-7"); 13C NMR (75 MHz, DMSO-d6): the adenosine moiety δ 154.6 (C-6), 152.4 (C-2), 148.5 (C-4), 140.0 (C-8), 119.8 (C-5), 88.0 (C-1'), 85.9 (C-4'), 73.5 (C-2'), 70.7 (C-3'), 61.7 (C-5'); the benzyl moiety δ 128.2 (C-3", C-5"), 127.1 (C-2", C-6"), 126.6 (C-4"), 42.9 (C-7").
151 mg	With N-ethyl-N,N-diisopropylamine In propan-1-ol at 70℃; for 8h;	1.3 Third step 335 mg of benzylamine hydrochloride was taken, dissolved in propanol (40 mL), and 6-chloropurine nucleoside (143 mg) and N, N-diisopropylethylamine base (2 mL) were added and heated to 70 ° C, reacted for 8 hours, recovered the solvent in the reaction solution, Separation by silica gel column chromatography, washed off with chloroform-methanol (30: 1), to obtain 151 mg of colorless solid N6-(benzyl)-adenosine,

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF MEDICAL SCIENCES - EP2511283, 2012, A1 Location in patent: Page/Page column 37-38
[2]Current Patent Assignee: CHINESE ACADEMY OF MEDICAL SCIENCES - US2013/45942, 2013, A1 Location in patent: Paragraph 0080; 0083
[3]Current Patent Assignee: CHINESE ACADEMY OF MEDICAL SCIENCES - JP2015/172077, 2015, A Location in patent: Paragraph 0093

28
[ 542-05-2 ]
[ 1085458-56-5 ]
[ 3287-99-8 ]
[ 81514-40-1 ]

Yield	Reaction Conditions	Operation in experiment
		9-benzyl-3-oxa-9-azabicvclor3.3.1"\|nonan-7-one (C-2) A solution of C-I (18 g, 81 mmol) in 40 mL of water and 14 mL acetic acid was heated to 120C for 2 h, cooled to room temperature and diluted with 400 mL of pH 4 buffer (160 mL 0.1 M citric acid and 240 mL 0.1 M K2HPO4). After cooling to 0C, a preformed solution of 9.54 g (66.4 mmol) benzylamine hydrochloride, 100 mL water, and 31 mL concentrated HCl was added dropwise over 10 minutes, keeping the internal temperature below 50C. Acetonedicarboxylic acid (23.3 g, 160 mmol) was then added in four equal portions, five minutes apart. The pH of the solution was increased to 4 by adding K2HPO4, and the reaction was allowed to warm to room temperature and stir overnight. Solid citric acid was added to return the pH to 4, and the reaction was stirred at room temperature 48 h more, at which time it was cooled to 0C and acidified to pH 2 with HCl, and extracted twice with Et2theta. The aqueous layer was again cooled to 0C and basified to pH 11 with NaOH, and extracted three times with CH2CI2. The combined organic extracts were washed with 0.1 M citric acid, then with saturated NaHCtheta3, brine, dried over Na2SO4, and concentrated. The residue was purified by column chromatography on silica gel (0 to 100% EtOAc in hexanes) to provide C-2 as a yellowish solid. Data for C^/. IH NMR (CDCI3, 500 MHz) delta 7.45 - 7.2 (m, 5H), 3.9 (s, 2H), 3.8 (m, 2H), 3.7 ? (m, 2H), 3.2 (m, 2H), 2.7 (m, 2H), 2.3 (m, 2H) ppm.

Reference： [1]Patent: WO2008/143856,2008,A1 .Location in patent: Page/Page column 32

29
[ 3287-99-8 ]
[ 100-51-6 ]
[ 1485-70-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With tert.-butylhydroperoxide; calcium carbonate; In water; acetonitrile; at 80℃; for 4h;	General procedure: Benzyl alcohol (0.75 mmol, 1.5 equiv.), and 4 equiv. TBHP(70 wt% in H2O) was added to the mixture of hydrochloric saltsof amines (0.5 mmol, 1 equiv.), and CaCO3(1.1 equiv.) in MeCN(1 mL). The mixture was stirred at 80C for 4 h. After the comple-tion of reaction, the catalyst was removed by an external magnet.Then 1 N HCl (5 mL) and EtOAc (5 mL) were added. The mixturewas extracted with EtOAc and the combined organic phase waswashed with a saturated aqueous solution of NaHCO3(10 mL), brine(10 mL), dried over anhydrous Na2SO4. After removal of the sol-vent under vacuum, the crude product was purified by columnchromatography to afford the desired product.
87%	With tert.-butylhydroperoxide; calcium carbonate; sodium iodide; In water; acetonitrile; at 80℃; for 4h;Inert atmosphere; Green chemistry;Catalytic behavior;	General procedure: To a mixture of NaI (10 mol %), amine hydrochloride salt(1.5 mmol), and CaCO3 (2.2 mmol) in CH3CN (4 mL) were added benzyl alcohol(1 mmol) and TBHP (70 wt % in H2O, 8 equiv) under an argon atmosphere at room temperature. The reaction vessel was capped and the mixture allowed to stir at 80 C for 4 h. The progress of the reaction was monitored by TLC. After completion, the mixture was allowed to cool to room temperature. The product was extracted with EtOAc (3 10 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuum. The crude product was purified by column chromatography. All compounds were identified from their melting points (in some cases), and IR, mass, 1H NMR, and 13C NMR spectra.The spectral data of known compounds were compared with those reported in the literature.
63%	With tert.-butylhydroperoxide; iron(II) chloride tetrahydrate; calcium carbonate; In water; acetonitrile; at 80℃; for 4h;Sealed tube;	General procedure: In a sealed tube were added FeCl2·4H2O (9.9 mg, 0.05 mmol, 10 mol %), cyclohexylamine·HCl (67.8 mg, 0.5 mmol, 1 equiv) and CaCO3 (50.1 mg, 0.5 mmol, 1 equiv). 1 mL of CH3CN, benzyl alcohol (67 muL, 0.65 mmol, 1.3 equiv) and tert-butylhydroperoxide (70% in H2O, 140 muL, 2 equiv) were then added. After 2 h of stirring at 80 C, another 2 equiv of tert-butylhydroperoxide (70% in H2O) were added, and the mixture was further stirred for 2 h. After cooling to rt, HCl 1 N (5 mL) and AcOEt (5 mL) were added. The mixture was extracted with AcOEt (2×5 mL), and the combined organic phases were washed with saturated aqueous NaHCO3 solution (10 mL), brine (10 mL), dried over magnesium sulfate and concentrated under reduced pressure. The crude mixture was purified by chromatography on silica gel using mixtures of cyclohexane and ethyl acetate as eluant.

63%

With tert.-butylhydroperoxide; iron(II) chloride tetrahydrate; calcium carbonate; In water; acetonitrile; at 80℃; for 4h;Sealed tube;

General procedure: In a sealed tube were added FeCl2*4H2O (9.9 mg, 0.05 mmol, 10 mol %), cyclohexylamine*HCl (67.8 mg, 0.5 mmol, 1 equiv) and CaCO3 (50.1 mg, 0.5 mmol, 1 equiv). 1 mL of CH3CN, benzyl alcohol (67 mL, 0.65 mmol, 1.3 equiv) and tert-butyl hydroperoxide (70% in H2O, 140 mL, 2 equiv) were then added. After 2 h of stirring at 80C, another 2 equiv of tert-butyl hydroperoxide (70% in H2O) were added, and the mixture was further stirred for 2 h. After cooling to rt, HCl 1 N (5 mL) and AcOEt (5 mL) were added. The mixture was extracted with AcOEt (25 mL), and the combined organic phases were washed with saturated aqueous NaHCO3 solution (10 mL), brine (10 mL), dried over magnesium sulfate and concentrated under reduced pressure. The crude mixture was purified by chromatographyon silica gel using mixtures of cyclohexane and ethylacetate as eluant.

Reference： [1]Applied Catalysis A: General,2014,vol. 482,p. 336 - 343
[2]Tetrahedron Letters,2014,vol. 55,p. 5351 - 5353
[3]ACS Combinatorial Science,2015,vol. 17,p. 341 - 347
[4]Tetrahedron,2014,vol. 70,p. 5093 - 5099
[5]Tetrahedron,2014,vol. 70,p. 5093 - 5099
[6]European Journal of Organic Chemistry,2015,vol. 2015,p. 417 - 422

30
[ 39110-74-2 ]
[ 100-51-6 ]
[ 1485-70-7 ]
[ 65-85-0 ]

Yield	Reaction Conditions	Operation in experiment
74%	With tert.-butylhydroperoxide In water; acetonitrile at 100℃; for 8h; Inert atmosphere; chemoselective reaction; Further stages;
	With tert.-butylhydroperoxide; calcium carbonate In water; acetonitrile at 80℃; for 4h;	1 Catalytic performance in the direct amidation of benzylalcohols General procedure: Benzyl alcohol (0.75 mmol, 1.5 equiv.), and 4 equiv. TBHP(70 wt% in H2O) was added to the mixture of hydrochloric saltsof amines (0.5 mmol, 1 equiv.), and CaCO3(1.1 equiv.) in MeCN(1 mL). The mixture was stirred at 80C for 4 h. After the comple-tion of reaction, the catalyst was removed by an external magnet.Then 1 N HCl (5 mL) and EtOAc (5 mL) were added. The mixturewas extracted with EtOAc and the combined organic phase waswashed with a saturated aqueous solution of NaHCO3(10 mL), brine(10 mL), dried over anhydrous Na2SO4. After removal of the sol-vent under vacuum, the crude product was purified by columnchromatography to afford the desired product.
	With dihydrogen peroxide; calcium carbonate In water; acetonitrile at 80℃; for 4h;	1 Catalytic performance in the direct amidation of benzylalcohols General procedure: Benzyl alcohol (0.75 mmol, 1.5 equiv.), and 4 equiv. TBHP(70 wt% in H2O) was added to the mixture of hydrochloric saltsof amines (0.5 mmol, 1 equiv.), and CaCO3(1.1 equiv.) in MeCN(1 mL). The mixture was stirred at 80C for 4 h. After the comple-tion of reaction, the catalyst was removed by an external magnet.Then 1 N HCl (5 mL) and EtOAc (5 mL) were added. The mixturewas extracted with EtOAc and the combined organic phase waswashed with a saturated aqueous solution of NaHCO3(10 mL), brine(10 mL), dried over anhydrous Na2SO4. After removal of the sol-vent under vacuum, the crude product was purified by columnchromatography to afford the desired product.

Reference： [1]Arefi, Marzban; Darvishi, Atefeh; Heydari, Akbar; Kazemi Miraki, Maryam [New Journal of Chemistry, 2020, vol. 44, # 27, p. 11777 - 11785]
[2]Azizi, Kobra; Karimi, Meghdad; Nikbakht, Fatemeh; Heydari, Akbar [Applied Catalysis A: General, 2014, vol. 482, p. 336 - 343]
[3]Azizi, Kobra; Karimi, Meghdad; Nikbakht, Fatemeh; Heydari, Akbar [Applied Catalysis A: General, 2014, vol. 482, p. 336 - 343]

31
[ 6343-54-0 ]
[ 39110-74-2 ]

Yield	Reaction Conditions	Operation in experiment
85%	With ammonium iodide; hydrazine at 20℃; for 6h;	4.2 Following separation with separatory funnel with NaOH aqueous solution and ether, 7 mL of 1 M HCl in diethyl ether was added for stirring overnight at room temperature. Filtration was then conducted to obtain a white solid product. Yield 122 mg (85% as hydrochloride salt).

Reference： [1]Current Patent Assignee: KYUSHU UNIVERSITY - EP2821389, 2015, A1 Location in patent: Paragraph 0074

32
[ 39896-97-4 ]
[ 39110-74-2 ]
[ 100-51-6 ]

Yield	Reaction Conditions	Operation in experiment
1: 73% 2: 84%	With ammonium bromide; 3-azapentane-1,5-diamine at 100℃; for 5h; Microwave irradiation;	6.5 After termination of the reaction, the reaction mixture was subjected to separation with separatory funnel with HCl aqueous solution and dichloromethane to obtain a colorless and transparent liquid product (BnOH, 91 mg, 84%). BnNH2 was back-extracted from the aqueous layer. The target amine was obtained as a hydrochloride salt (104 mg, 73%).

Reference： [1]Current Patent Assignee: KYUSHU UNIVERSITY - EP2821389, 2015, A1 Location in patent: Paragraph 0103

33
[ 1485-70-7 ]
[ 925-90-6 ]
[ 3287-99-8 ]
[ 93-55-0 ]

Yield	Reaction Conditions	Operation in experiment
63%		General procedure: Tf2O (185muL, 1.1mmol) was added dropwise to a cooled (0C) solution of amide (1.0mmol) and 2-fluoropyridine (103muL, 1.2mmol) in dichloromethane (4mL). After stirring at 0C for 30min, the mixture was cannulated to a freshly prepared organocerium reagent/complex (3.0mmol) in THF (15mL) at -78C and stirred for 2h. Aqueous HCl solution (3mol/L, 5mL) was added to quench the reaction and the mixture was allowed to warm to r.t. and stirred for 2h. Ammonium hydroxide solution (25%, 5mL) was then added to the mixture. The organic layer was separated and the aqueous phase was extracted with diethyl ether (3× 10mL). The combined organic layers were washed with brine (3× 3mL) and concentrated under reduced pressure to about 1/3 volume. The residual organic phase was then extracted with aqueous HCl solution (3mol/L, 3× 5mL). The separated organic phase was washed with brine (5mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure, and the residue was purified by flash column chromatography on silica gel to afford ketone. The aqueous phases were combined, washed with diethyl ether (5mL), basified with an ammonium hydroxide solution (25%, 5mL) and back-extracted with diethyl ether (5× 20mL). The ether layers were combined, washed with brine (5mL), dried over anhydrous MgSO4, filtered, acidified with a solution of HCl in ethyl acetate (3mol/L, 5mL) and concentrated under reduced pressure to afford the desired amine hydrochloride salt.

Reference： [1]Chinese Chemical Letters,2015,vol. 26,p. 1055 - 1058

34
[ 542-05-2 ]
[ 39110-74-2 ]
[ 675-20-7 ]

Yield	Reaction Conditions	Operation in experiment
26.4%	With sodium acetate In water	1.s Synthesis of Compound (No. 37) First step In a 300-mL Erlenmeyer flask, isobutyraldehyde (T-1) (24.50 g, 0.34 mol) and 130 g of water were put, and the resulting mixture was cooled to 4° C. Benzylamine hydrochloride (31.60 g, 0.22 mol) was added thereto, and the resulting mixture was stirred for 30 minutes, and then acetonedicarboxylic acid (24.80 g, 0.17 mol) and a sodium acetate aqueous solution (sodium acetate (6.4 g, 0.078 mol), water 50 g) were added thereto. The resulting reaction mixture was slowly heated to room temperature, and stirred at room temperature for 30 hours. Deposited crystals were obtained by filtration to obtain piperidinone form (T-2) (12.25 g, yield 26.4%).

Reference： [1]Current Patent Assignee: CHISSO CORPORATION - US2016/90534, 2016, A1

35
[ 542-05-2 ]
[ 39110-74-2 ]
[ 78-84-2 ]
C₁₈H₂₇NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26.4%	Stage #1: benzylamine hydrochloride; isobutyraldehyde In water at 4℃; Stage #2: acetonedicarboxylic acid With sodium acetate In water at 20℃; for 30h;	1.1 First process: The triangular flask in 300 ml aminoaldehyde halogenoimides (T-1) (24.50g, 0.34mol), water containing 130g, cooled to 4 °C. Phenylbenzylamine hydrocloride (31.60g, 0.22mol) is added, with stirring, after 30 minutes, hydroxyacetone dicarboxylic acid (24.80g, 0.17mol), sodium acetate solution (sodium acetate (6.4g, 0.078mol), water 50g) is added. Slowly to room temperature to raise the temperature of the reaction mixture, 30 hours at room temperature. The precipitated crystals filtering, piperidinone body (T-2) (12.25g, yield 26.4%) is obtained.

Reference： [1]Current Patent Assignee: CHISSO CORPORATION - JP2016/64995, 2016, A Location in patent: Paragraph 0134; 0135

36
[ 542-05-2 ]
[ 56999-16-7 ]
[ 3287-99-8 ]
[ 81514-40-1 ]

Yield	Reaction Conditions	Operation in experiment
		2-(2,2-Diethoxyethoxy)-1 ,1 -diethoxyethane A1 (5 g, 20.0 mmol) in a mixture of acetic acid (1 .2 mL) and water (5 mL) was heated at reflux for 1 hour then cooled to room temperature. Benzylamine hydrochloride (2.1 g, 20.0 mmoL) and 3-oxopentanedioic acid (2.5 g, 16.6 mmoL), NaOAc (0.69 g, 83.8 mmoL) and water (10 mL) were added and the reaction heated at 50 C for 5 hours. The reaction was cooled to room temperature and aqueous NaOH solution (42 mL, 50% w/v) was added into the mixture. The aqueous phase was extracted with EtOAc (3x30 mL) and the combined organic fractions concentrated and purified by column chromatography (100% petroleum ether to 10% EtOAc in petroleum ether) to give the title compound as a yellow solid. LCMS: RT 0.50 min, m/z 232.1 [M+H]+

Reference： [1]Patent: WO2017/153519,2017,A1 .Location in patent: Page/Page column 65; 66

37
[ 39110-74-2 ]
[ 1122-91-4 ]
[ 80311-89-3 ]

Yield	Reaction Conditions	Operation in experiment
67%	With tert.-butylhydroperoxide; 4Yb⁽³⁺⁾4C₂₄H₁₂N₃O₆^(3-)CHO₂^(1-)5H₂OC₂H₇N*H⁽¹⁺⁾; calcium carbonate In acetonitrile at 25℃; for 16h;

Reference： [1]Hashemzadeh, Alireza; Amini, Mostafa M.; Khavasi, Hamid Reza; Ng, Seik Weng [Journal of Coordination Chemistry, 2017, vol. 70, # 18, p. 3217 - 3232]

38
[ 1445-45-0 ]
[ 39110-74-2 ]
[ 588-46-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	In methanol at 135℃; for 0.25h; Microwave irradiation;	General procedure for the preparation of acetamides 3a-3u (via microwave irradiation) General procedure: To a solution of 1.5 eq trimethyl orthoacetate in 2 mL MeOH was added amine hydrochloride (0.0015 mol). After heating via microwave irradiation to 135°C for 15 minutes, the product was isolated by concentration in vacuo to give essentially pure acetamides. In general, these reactions were accompanied by an expected but slight increase in pressure - none exceeded the pressure limits of the instrument.

Reference： [1]Di Grandi, Martin J.; Bennett, Caitlin; Cagino, Kristen; Muccini, Arnold; Suraci, Corey; Saba, Shahrokh [Synthetic Communications, 2015, vol. 45, # 22, p. 2601 - 2607]

39
[ 696-59-3 ]
[ 542-05-2 ]
[ 39110-74-2 ]
[ 83393-23-1 ]

Yield	Reaction Conditions	Operation in experiment
80%	With hydrogenchloride; disodium hydrogenphosphate; at 25 - 30℃;	To a solution 2,5-dimethoxy tetrahydrofuran (25 gm,0.18 mol) in water (200 ml), concentrated hydrochloric acid(2 mL) was added. After five minutes, 1,3-acetone dicarboxylicacid (29 gm, 0.19 mol), benzyl amine hydrochloride (27 gm,0.18 mol), sodium hydrogen phosphate (6 gm, 0.04mol) wasadded and the mixture was allowed to stir overnight. Workupwas done after adding NaOH solution (pH=8-9) and extracting with methylene chloride in 150 ml. Evaporation of thesolvent gave crude product that was crystallized from isopropylalcohol hydrochloric acid (25% w/v, 50 ml) as acreamy solid (38 gm) in 80% yield

Reference： [1]Letters in drug design and discovery,2018,vol. 15,p. 895 - 904

40
[ 39110-74-2 ]
[ 4546-55-8 ]
N-(9-((2R,6S)-4-benzyl-6-(hydroxymethyl)morpholin-2-yl)-9H-purin-6-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: benzylamine hydrochloride; N-benzoyladenosine With sodium periodate; sodium tetraborate decahydrate In methanol for 2.5h; Stage #2: With sodium cyanoborohydride; triethylamine In methanol for 1h; Stage #3: With trifluoroacetic acid In methanol for 3h;	General procedure a for N-benzyl morpholino nucleoside synthesis General procedure: A ribonucleoside, 5-methyluridine, N2-isobutirylguanosine, N4-benzoylcytidine,or N6-benzoyladenosine (2 mmol), was mixed with sodium periodate(0.44 g, 2.04 mmol), sodium tetraborate decahydrate (0.80 g, 4 mmol), benzylaminehydrochloride (0.66 g, 4.6 mmol), and 40mL of methanol withintense stirring via a stirrer bar. The mixture was stirred for 2.5 h, afterwhich the reaction mixture was filtered. The reaction flask was then placedin a water bath, and a stirrer bar, sodium cyanoborohydride (0.30 g,4.8 mol), and triethylamine (0.66 mL) were added to the reaction mixture,and the mixture was left to stir for 1 h. Next, 0.8mL of trifluoroacetic acidwas mixed with 5mL of methanol and added slowly over 10 min dropwise,and the mixture was left to stir for 3 h. The reaction was quenched withpotassium carbonate (0.72 g, 5.24 mmol), after which the solution was concentratedto 10-mL volume and mixed with 20mL of water and 90mL ofdichloromethane. Then, the aqueous layer was extracted twice with dichloromethane-methanol (9:1). The organic layers were combined, dried oversodium sulphate, filtered, and concentrated under reduced pressure. Thecrude product was purified on a silica gel column poisoned with ammoniain a methanol/dichloromethane system.

Reference： [1]Nekrasov, Mikhail D.; Lukyanenko, Evgeny R.; Kurkin, Alexander V. [Nucleosides, Nucleotides and Nucleic Acids, 2020, vol. 39, # 9, p. 1223 - 1244]

41
[ 332-77-4 ]
[ 542-05-2 ]
[ 39110-74-2 ]
(±) 6-hydroxy-8-benzyl 8-azabicyclo[3.2.1]octan-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; disodium hydrogenphosphate; sodium hydroxide In 1,4-dioxane; methanol; dichloromethane; water at 99℃; for 0.333333h; Inert atmosphere;	B2b.1 Step 1: Synthesis of (±) 6-hydroxy-8-benzyl 8-azabicyclo[3.2.1]octan-3-one. 2,5-Dimethoxy-2,5- dihydrofuran (97.5 g, 750 mmol) was dissolved in water (650 mL) and treated with aqueous hydrochloric acid (3.75 ml, 2M) under an atmosphere of nitrogen. The mixture was heated to 99 °C with stirring and aqueous methanol (about 100 mL) was distilled from the reaction mixture. The reaction was cooled to ambient temperature, acetone dicarboxylic acid (146 g, 1.33 mol) wase added in one portion followed by a solution of sodium hydrogen phosphate (53.25 g, 375 mmol) and sodium hydroxide (15.0 g, 375 mmol) in water (500 mL).1,4-Dioxane (100 mL) was added and a solution of benzylamine hydrochloride (71.75 g, 502 mmol) in water (330 mL) was added dropwise over 10 minutes. The mixture was rapidly stirred for a further 4 h, acidified with aqueous hydrochloric acid (2M). Dichloromethane (500 mL) was added and the reaction mixture stirred for 10 minutes. The aqueous phase was separated and filtered through a pad of Celite brand filter agent. The filtrate was extracted with dichloromethane (500 mL x 3). The aqueous phase was collected, basified with potassium carbonate and extracted with ethyl acetate (1000 mL x 3). The organic fractions were combined, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (36 g, 21% yield) as a brown oil, containing a mixture of exo- and endo-6-hydroxy-8-benzyl 8- azabicyclo[3.2.1]octan-3-one, which was used directly to next step. LCMS: m/z 232.1 [M+H]+; tR = 1.52 min.

Reference： [1]Current Patent Assignee: SKYHAWK THERAPEUTICS INC; SKYHOKE THERAPY - WO2020/163541, 2020, A1 Location in patent: Paragraph 0791

42
[ 332-77-4 ]
[ 542-05-2 ]
[ 39110-74-2 ]
rac-6-hydroxy-8-benzyl 8-azabicyclo[3.2.1]octan-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%	Stage #1: 2,5-dihydro-2,5-dimethoxyfuran With hydrogenchloride; water at 99℃; Inert atmosphere; Stage #2: acetonedicarboxylic acid; benzylamine hydrochloride With disodium hydrogenphosphate; sodium hydroxide In 1,4-dioxane; water at 20℃; for 4.16667h;	B1.1 Step 1. Synthesis of rac-6-hydroxy-8-benzyl 8-azabicyclo[3.2.1]octan-3-one. 2,5-Dimethoxy-2,5- dihydrofuran (97.5 g, 750 mmol) was dissolved in water (650 mL) and treated with aqueous hydrochloric acid (3.75 ml, 2M) under an atmosphere of nitrogen. The mixture was heated to 99 °C with stirring and aqueous methanol (about 100 mL) was distilled from the reaction mixture. The reaction was cooled to ambient temperature, acetone dicarboxylic acid (146 g, 1.33 mol) wase added in one portion followed by a solution of sodium hydrogen phosphate (53.25 g, 375 mmol) and sodium hydroxide (15.0 g, 375 mmol) in water (500 mL). 1,4-Dioxane (100 mL) was added and a solution of benzylamine hydrochloride (71.75 g, 502 mmol) in water (330 mL) was added dropwise over 10 minutes. The mixture was rapidly stirred for a further 4 h, acidified with aqueous hydrochloric acid (2M). Dichloromethane (500 mL) was added and the reaction mixture stirred for 10 minutes. The aqueous phase was separated and filtered through a pad of Celite brand filter agent. The filtrate was extracted with dichloromethane (500 mL x 3). The aqueous phase was collected, basified with potassium carbonate and extracted with ethyl acetate (1000 mL x 3). The organic fractions were combined, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (36 g, 21% yield) as a brown oil, containing a mixture of exo- and endo-6-hydroxy-8-benzyl 8-azabicyclo[3.2.1]octan-3-one, which was used directly to next step. LCMS: m/z 232.1 [M+H]+; tR = 1.52 min.

Reference： [1]Current Patent Assignee: SKYHAWK THERAPEUTICS INC - WO2020/163544, 2020, A1 Location in patent: Paragraph 0789

43
[ 39110-74-2 ]
[ 302963-94-6 ]
2-(tert-butoxycarbonylamino)-4-methylthiazole-5-carboxylic acid benzylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With 1-[(1-(cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino)]-uronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 16h;

Reference： [1]Rajan, Remya; Schepmann, Dirk; Schreiber, Julian A.; Seebohm, Guiscard; Wünsch, Bernhard [European Journal of Medicinal Chemistry, 2021, vol. 209]

44
[ 39110-74-2 ]
[ 127-09-3 ]
[ 588-46-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In water; acetonitrile at 20℃; for 0.5h; Green chemistry;

Reference： [1]Nielsen, John; Tung, Truong Thanh [Organic and Biomolecular Chemistry, 2021, vol. 19, # 46, p. 10073 - 10080]

45
[ 588676-02-2 ]
[ 39110-74-2 ]
C₂₁H₂₀BrNO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium cyanotrihydridoborate; glacial acetic acid In methanol at 20℃; for 12h;	General procedure for reductive amination (e.g., synthesis of compound 19(SGT525). General procedure: Compound 1 (0.043 g, 0.203 mmol), AcOH (0.012 mL, 0.210 mmol),and NaBH3CN (0.013 g, 0.207 mmol) were added to stirred mixture of benzylamine (0.020 mL,0.183 mmol) in MeOH (2.5 mL). The mixture was stirred at room temperature for 12 h. Thesolution was then made alkaline with NaOH (1 N) and extracted with EtOAc (10 mL). The organiclayers were collected, dried over MgSO4, and evaporated to dryness under reduced pressure toafford compound 19 (0.012 g, 21%) as a colorless oil: 1H NMR (400 MHz, CDCl3, Fig. S29) d7.42-7.32 (m, 5H), 7.29-7.20 (m, 7H), 6.97-6.92 (m, 2H), 5.08 (s, 2H), 3.87 (s, 2H), 3.76 (s, 2H),2.30 (br s, 1H); 13C NMR (100 MHz, CDCl3, Fig. S30) d 157.1, 140.2, 137.2, 130.4, 128.8, 128.7,128.60, 128.58, 128.5, 128.2, 127.5, 127.4, 127.1, 121.0, 111.9, 70.2, 53.2, 49.1; LRMS m/z calcdfor C21H22NO [M+H]+: 304.2; found 304.1.
86%	With sodium cyanotrihydridoborate; glacial acetic acid In methanol at 20℃; for 12h;	General procedure for reductive amination (e.g., synthesis of compound 19(SGT525). General procedure: Compound 1 (0.043 g, 0.203 mmol), AcOH (0.012 mL, 0.210 mmol),and NaBH3CN (0.013 g, 0.207 mmol) were added to stirred mixture of benzylamine (0.020 mL,0.183 mmol) in MeOH (2.5 mL). The mixture was stirred at room temperature for 12 h. Thesolution was then made alkaline with NaOH (1 N) and extracted with EtOAc (10 mL). The organiclayers were collected, dried over MgSO4, and evaporated to dryness under reduced pressure toafford compound 19 (0.012 g, 21%) as a colorless oil: 1H NMR (400 MHz, CDCl3, Fig. S29) d7.42-7.32 (m, 5H), 7.29-7.20 (m, 7H), 6.97-6.92 (m, 2H), 5.08 (s, 2H), 3.87 (s, 2H), 3.76 (s, 2H),2.30 (br s, 1H); 13C NMR (100 MHz, CDCl3, Fig. S30) d 157.1, 140.2, 137.2, 130.4, 128.8, 128.7,128.60, 128.58, 128.5, 128.2, 127.5, 127.4, 127.1, 121.0, 111.9, 70.2, 53.2, 49.1; LRMS m/z calcdfor C21H22NO [M+H]+: 304.2; found 304.1.

Reference： [1]Pang, Allan H.; Green, Keith D.; Chandrika, Nishad Thamban; Garzan, Atefeh; Punetha, Ankita; Holbrook, Selina Y.L.; Willby, Melisa J.; Posey, James E.; Tsodikov, Oleg V.; Garneau-Tsodikova, Sylvie [European Journal of Medicinal Chemistry, 2022, vol. 242]
[2]Pang, Allan H.; Green, Keith D.; Chandrika, Nishad Thamban; Garzan, Atefeh; Punetha, Ankita; Holbrook, Selina Y.L.; Willby, Melisa J.; Posey, James E.; Tsodikov, Oleg V.; Garneau-Tsodikova, Sylvie [European Journal of Medicinal Chemistry, 2022, vol. 242]

46
[ 52803-59-5 ]
[ 39110-74-2 ]
C₂₁H₂₀ClNO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With sodium cyanotrihydridoborate; glacial acetic acid In methanol at 20℃; for 12h;	General procedure for reductive amination (e.g., synthesis of compound 19(SGT525). General procedure: Compound 1 (0.043 g, 0.203 mmol), AcOH (0.012 mL, 0.210 mmol),and NaBH3CN (0.013 g, 0.207 mmol) were added to stirred mixture of benzylamine (0.020 mL,0.183 mmol) in MeOH (2.5 mL). The mixture was stirred at room temperature for 12 h. Thesolution was then made alkaline with NaOH (1 N) and extracted with EtOAc (10 mL). The organiclayers were collected, dried over MgSO4, and evaporated to dryness under reduced pressure toafford compound 19 (0.012 g, 21%) as a colorless oil: 1H NMR (400 MHz, CDCl3, Fig. S29) d7.42-7.32 (m, 5H), 7.29-7.20 (m, 7H), 6.97-6.92 (m, 2H), 5.08 (s, 2H), 3.87 (s, 2H), 3.76 (s, 2H),2.30 (br s, 1H); 13C NMR (100 MHz, CDCl3, Fig. S30) d 157.1, 140.2, 137.2, 130.4, 128.8, 128.7,128.60, 128.58, 128.5, 128.2, 127.5, 127.4, 127.1, 121.0, 111.9, 70.2, 53.2, 49.1; LRMS m/z calcdfor C21H22NO [M+H]+: 304.2; found 304.1.
77%	With sodium cyanotrihydridoborate; glacial acetic acid In methanol at 20℃; for 12h;	General procedure for reductive amination (e.g., synthesis of compound 19(SGT525). General procedure: Compound 1 (0.043 g, 0.203 mmol), AcOH (0.012 mL, 0.210 mmol),and NaBH3CN (0.013 g, 0.207 mmol) were added to stirred mixture of benzylamine (0.020 mL,0.183 mmol) in MeOH (2.5 mL). The mixture was stirred at room temperature for 12 h. Thesolution was then made alkaline with NaOH (1 N) and extracted with EtOAc (10 mL). The organiclayers were collected, dried over MgSO4, and evaporated to dryness under reduced pressure toafford compound 19 (0.012 g, 21%) as a colorless oil: 1H NMR (400 MHz, CDCl3, Fig. S29) d7.42-7.32 (m, 5H), 7.29-7.20 (m, 7H), 6.97-6.92 (m, 2H), 5.08 (s, 2H), 3.87 (s, 2H), 3.76 (s, 2H),2.30 (br s, 1H); 13C NMR (100 MHz, CDCl3, Fig. S30) d 157.1, 140.2, 137.2, 130.4, 128.8, 128.7,128.60, 128.58, 128.5, 128.2, 127.5, 127.4, 127.1, 121.0, 111.9, 70.2, 53.2, 49.1; LRMS m/z calcdfor C21H22NO [M+H]+: 304.2; found 304.1.

Reference： [1]Pang, Allan H.; Green, Keith D.; Chandrika, Nishad Thamban; Garzan, Atefeh; Punetha, Ankita; Holbrook, Selina Y.L.; Willby, Melisa J.; Posey, James E.; Tsodikov, Oleg V.; Garneau-Tsodikova, Sylvie [European Journal of Medicinal Chemistry, 2022, vol. 242]
[2]Pang, Allan H.; Green, Keith D.; Chandrika, Nishad Thamban; Garzan, Atefeh; Punetha, Ankita; Holbrook, Selina Y.L.; Willby, Melisa J.; Posey, James E.; Tsodikov, Oleg V.; Garneau-Tsodikova, Sylvie [European Journal of Medicinal Chemistry, 2022, vol. 242]

47
[ 101046-14-4 ]
[ 39110-74-2 ]
C₂₁H₂₀BrNO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With sodium cyanotrihydridoborate; glacial acetic acid In methanol at 20℃; for 12h;	General procedure for reductive amination (e.g., synthesis of compound 19(SGT525). General procedure: Compound 1 (0.043 g, 0.203 mmol), AcOH (0.012 mL, 0.210 mmol),and NaBH3CN (0.013 g, 0.207 mmol) were added to stirred mixture of benzylamine (0.020 mL,0.183 mmol) in MeOH (2.5 mL). The mixture was stirred at room temperature for 12 h. Thesolution was then made alkaline with NaOH (1 N) and extracted with EtOAc (10 mL). The organiclayers were collected, dried over MgSO4, and evaporated to dryness under reduced pressure toafford compound 19 (0.012 g, 21%) as a colorless oil: 1H NMR (400 MHz, CDCl3, Fig. S29) d7.42-7.32 (m, 5H), 7.29-7.20 (m, 7H), 6.97-6.92 (m, 2H), 5.08 (s, 2H), 3.87 (s, 2H), 3.76 (s, 2H),2.30 (br s, 1H); 13C NMR (100 MHz, CDCl3, Fig. S30) d 157.1, 140.2, 137.2, 130.4, 128.8, 128.7,128.60, 128.58, 128.5, 128.2, 127.5, 127.4, 127.1, 121.0, 111.9, 70.2, 53.2, 49.1; LRMS m/z calcdfor C21H22NO [M+H]+: 304.2; found 304.1.
91%	With sodium cyanotrihydridoborate; glacial acetic acid In methanol at 20℃; for 12h;	General procedure for reductive amination (e.g., synthesis of compound 19(SGT525). General procedure: Compound 1 (0.043 g, 0.203 mmol), AcOH (0.012 mL, 0.210 mmol),and NaBH3CN (0.013 g, 0.207 mmol) were added to stirred mixture of benzylamine (0.020 mL,0.183 mmol) in MeOH (2.5 mL). The mixture was stirred at room temperature for 12 h. Thesolution was then made alkaline with NaOH (1 N) and extracted with EtOAc (10 mL). The organiclayers were collected, dried over MgSO4, and evaporated to dryness under reduced pressure toafford compound 19 (0.012 g, 21%) as a colorless oil: 1H NMR (400 MHz, CDCl3, Fig. S29) d7.42-7.32 (m, 5H), 7.29-7.20 (m, 7H), 6.97-6.92 (m, 2H), 5.08 (s, 2H), 3.87 (s, 2H), 3.76 (s, 2H),2.30 (br s, 1H); 13C NMR (100 MHz, CDCl3, Fig. S30) d 157.1, 140.2, 137.2, 130.4, 128.8, 128.7,128.60, 128.58, 128.5, 128.2, 127.5, 127.4, 127.1, 121.0, 111.9, 70.2, 53.2, 49.1; LRMS m/z calcdfor C21H22NO [M+H]+: 304.2; found 304.1.

Reference： [1]Pang, Allan H.; Green, Keith D.; Chandrika, Nishad Thamban; Garzan, Atefeh; Punetha, Ankita; Holbrook, Selina Y.L.; Willby, Melisa J.; Posey, James E.; Tsodikov, Oleg V.; Garneau-Tsodikova, Sylvie [European Journal of Medicinal Chemistry, 2022, vol. 242]
[2]Pang, Allan H.; Green, Keith D.; Chandrika, Nishad Thamban; Garzan, Atefeh; Punetha, Ankita; Holbrook, Selina Y.L.; Willby, Melisa J.; Posey, James E.; Tsodikov, Oleg V.; Garneau-Tsodikova, Sylvie [European Journal of Medicinal Chemistry, 2022, vol. 242]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	39110-74-2	MDL No. :	MFCD15147375
Formula :	C₁₁H₁₂ClN	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NEXZCFUBZJBRCP-UHFFFAOYSA-N
M.W :	193.67	Pubchem ID :	458436
Synonyms :

Num. heavy atoms :	13
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.09
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	58.59
TPSA :	26.02 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.42 cm/s

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	2.91
Log Po/w (WLOGP) :	2.95
Log Po/w (MLOGP) :	2.85
Log Po/w (SILICOS-IT) :	2.61
Consensus Log Po/w :	2.26

[ CAS No. 39110-74-2 ] {[proInfo.proName]}

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[ 39110-74-2 ] Synthesis Path-Downstream 1~47

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[ 39110-74-2 ]

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Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Log S (ESOL) :	-3.38
Solubility :	0.0812 mg/ml ; 0.000419 mol/l
Class :	Soluble
Log S (Ali) :	-3.12
Solubility :	0.148 mg/ml ; 0.000763 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.11
Solubility :	0.0152 mg/ml ; 0.0000785 mol/l
Class :	Moderately soluble

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

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
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.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling