Name: 34619-03-9|Di-tert-butyl carbonate|98%
Brand: Ambeed
SKU: A989340
Price: 20.0 USD
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1
[ 487-89-8 ]
[ 34619-03-9 ]
[ 57476-50-3 ]

Reference： [1]Advanced Synthesis and Catalysis,2016,vol. 358,p. 1157 - 1163
[2]Liebigs Annalen der Chemie,1985,p. 413 - 417

2
[ 53855-47-3 ]
[ 34619-03-9 ]
[ 122946-64-9 ]

Reference： [1]Journal of Organic Chemistry,1989,vol. 54,p. 4785 - 4795

3
[ 34619-03-9 ]
[ 6335-76-8 ]
benzenepropanoic acid β-[[(1,1-dimethylethoxy)carbonyl]amino]ethyl ester [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1990,vol. 55,p. 4175 - 4180

4
[ 34619-03-9 ]
[ 29968-78-3 ]
[ 144226-16-4 ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 4264 - 4269

5
[ 34619-03-9 ]
[ 117106-22-6 ]
[ 117106-21-5 ]

Reference： [1]Tetrahedron,1988,vol. 44,p. 1773 - 1782

6
[ 7037-49-2 ]
[ 34619-03-9 ]
[ 156185-63-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; potassium hydrogensulfate; In 1,4-dioxane;	b 3-[N-(tert-butoxycarbonyl)piperidin-4-yl]propanol A solution of 6 g of di(tert-butyl)carbonate in 20 ml of dioxan was introduced into a solution of 3.2 g of 3-(4-piperidinyl)propanol in 50 ml of dioxan containing 25 ml of a 2N aqueous solution of sodium hydroxide, cooled at 0° C. The mixture was allowed to react for 16 hours at room temperature. The solution was then evaporated and the residue was extracted with ethylether. The organic layer was washed with a 10percent solution of KHSO4 and then dried over MgSO4. The solvent was evaporated and the residue was chromatographied on silica gel (eluent: CH3 COOEt/cyclohexane:2/8-1/1:v:v). 3 g of the desired compound in the form of an oil were obtained. RMN (CDCl3, 200 MHz) 4.05 ppm (m, 2H); 3.6 (t, 2H); 2.64 (m,2H); 1.7 a 1.1 (m, 18H).

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 2537 - 2551
[2]Patent: US5714497,1998,A

7
[ 34619-03-9 ]
[ 1119-34-2 ]
[ 13726-76-6 ]

Reference： [1]Journal of Medicinal Chemistry,1982,vol. 25,p. 1209 - 1213

8
[ 34619-03-9 ]
[ 119433-80-6 ]
[ 119434-75-2 ]

Reference： [1]Heterocycles,2004,vol. 63,p. 2385 - 2392

9
[ 120277-39-6 ]
[ 34619-03-9 ]
tert-butyl (E)-3-(pyridine-3'-yl)prop-2-en-1-yl carbonate [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3266 - 3268

10
[ 34619-03-9 ]
[ 19777-66-3 ]
[ 121103-15-9 ]

Yield	Reaction Conditions	Operation in experiment
		(5)-(-)-l,2-Diaminopropane dihydrochloride (6.94 g, 47.2 mmol) was suspended in 300 mL of dry CH2Cl2, treated with l,8-diaxabicyclo[5,4,0]undec-7-ene (15.5 mL, 103.8 <n="104"/>mmol), and cooled to 0 0C under an atmosphere of N2. Di-tert-butyl dicarbonate (10.29 g, 47.2 mmol) was dissolved in 100 mL of dry CH2Cl2 and was slowly added into the reaction via cannula. The reaction was kept cool for another hour before allowing it to warm to ambient temperature overnight. The reaction was then treated with 200 mL of acetic acid (10%), and the layers were separated. The organic layer was dried overNa2SO4, filtered, and concentrated under reduced pressure to give a white solid (5.51 g). This material was suspended in 50 mL of HCl/ethanol (3.0 M) and heated to 60 0C for 30 minutes. The solution was allowed to cool to ambient temperature, and the white precipitate was filtered off to cleanly give back (5)-(-)-l,2-diaminopropane dihydrochloride (2.0Og, 13.6 mmol). This material was resubmitted to the reaction conditions, and the aqueous phases from both reactions were combined and made basic with concentrated ammonium hydroxide, until the pH ~11. The aqueous layer was extracted with CH2Cl2 (6 x 150 mL). The combined organic layers were washed with brine and dried over Na2SO4, filtered, and concentrated under reduced pressure to give a light yellow oil (2.40 g). Chromatography (SiO2, 40-60% CMA/CHC13) afforded tert- butyl (25)-2-aminopropylcarbamate (2.14 g) as a light yellow oil.

Reference： [1]Patent: WO2007/106852,2007,A2 .Location in patent: Page/Page column 102

11
[ 34619-03-9 ]
[ 57591-61-4 ]
[ 143323-49-3 ]

Yield	Reaction Conditions	Operation in experiment
77%	With sodium hydrogencarbonate; In tetrahydrofuran; water; at 20℃; for 18h;	To a solution of D-p-phenylglycine hydrochloride (3.0 g, 13.8 mmol) and NaHCO3 (3.0 g, 27.6 mmol) in THF/H2O (2:8, 30 mL) was added di-t-butyl carbonate (3.6 g, 16.5 mmol) and stirred at room temperature for 18 h. After the THF was removed, the residue was partitioned with EtOAc/H2O, dried over Na2SO4 and concentrated to yield the title compound (3.1 g, 77percent). 1H-NMR (CDCl3) delta 1.44 (s, 9H), 3.71 (s, 3H), 5.22 (d, J=6.8 Hz, 1H), 5.53 (br, 1H), 6.91 (m, 4H), 6.75 (d, J=8 Hz, 2H), 7.21 (br, 2H).

Reference： [1]Patent: US2008/33024,2008,A1 .Location in patent: Page/Page column 9; 18

12
[ 34619-03-9 ]
[ 123986-64-1 ]

Reference： [1]Tetrahedron Letters,2003,vol. 44,p. 3043 - 3046

13
[ 34619-03-9 ]
[ 135050-44-1 ]
[ 209995-92-6 ]

Reference： [1]Patent: US6335350,2002,B1 .Location in patent: Example 8

14
[ 34619-03-9 ]
[ 124-68-5 ]
[ 102520-97-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In 1,4-dioxane; water; at 0 - 20℃; for 2h;	Reference O Synthesis of [2-AMINO-2-METHYL-1-OXAZOLO] [4,5-b] [PYRIDIN-2-YL-PROPAN-1-OL] Step 1 [2-AMINO-2-METHYL-1-PROPANOL] (17. [8] g, 200 mmol) was dissolved in a mixture of water and dioxane (100 mL) and cooled to [0 C. NAOH] (8g, [200MMOL)] and di-t-butyl- dicarbonate (52.4 g, 240 mmol) were added and the reaction was allowed to warm to room temperature with stirring for 2 h. After removing the dioxane, the residue was extracted with EtOAc, washed with brine, dried with anhydrous [MGS04,] filtered and concentrated to yield 35g of [2-BOC-AMINO-2-METHYL-1-PROPANOL.] Step 2 A solution of oxalyl chloride (15.24 g, 120 mmol) in 200 mL of MeCl2 was stirred and cooled to-60 C followed by the drop wise addition [OF DIMETHYLSULFOXIDE] (19.7 g, 252 mmol) in 60mL of MeCl2. After 10 min, a solution of [2-BOC-AMINO-2-METHYL-1-PROPANOL] (18.9 g, 100 mmol) in MeCl2 (60 mL) was added drop wise [AT-70 C.] The reaction mixture was allowed to warm [TO-40 C] for 10 min followed by cooling to-70 C before the addition of a solution of triethylamine (28.28 g, 280 mmol) in [MECL2] (60 mL). The reaction mixture was allowed to warm to room temperature over a two-hour period and 40 mL of saturated sodium dihydrogen phosphate was added. The organic layer was washed with brine and dried over [MGS04.] The solvent was removed to yield 17.3 g of 2-Boc-amino-2- methylpropionaldehyde. Step 3 A mixture of 2-amino-3-hydroxypyridine (11 g, 100 mmol), triethylorthoformate (80 mL) and p-toluenesulfonic acid (61 mg) was heated at [140 C] for 8 h. Excess [TRIETHYLORTHOFORMATE] was removed under vacuum. The product was crystallized from ethyl acetate to yield 9g of 1-oxazolo [4,5-b] pyridine. Step 4 To a stirred solution [OF THE 1-OXAZOLO] [4,5-b] pyridine (2.4 g, [20MMOL)] in THF (100 mL) was added n-BuLi (1.6 M solution in 12.5 mL of hexane) drop wise under N2 [AT-78 C.] After 1 h, MgBr. [ET20] (5.16 g, 20 mmol) was added and the reaction mixture was allowed to warm to-45 [C] for 1 h before being treated with 2-Boc-amino-2-methylpropionaldehyde (2.24 g, 12 mmol) in THF (20 mL). The reaction mixture was stirred for 1 h, quenched with saturated [NH4C1,] and extracted with ethyl acetate. The organic layer was washed with brine, dried with MgS04 and concentrated. The residue was purified by silica gel column chromatography to yield 2-Boc-amino-2-methyl-1-oxazolo [4,5-b] [PYRIDIN-2-YL-1-PROPANOL] [(1. 18G).] Step 5 [2-BOC-AMINO-2-METHYL-1-OXAZOLO] [4,5-b] pyridin-2-yl-1-propanol (156 mg, 0.508 mmol) and [MECL2] (5 mL) were mixed and TFA (0.5 [ML)] was added at room temperature. After stirring for 1 h, the solvent and excess TFA were removed under vacuum to produce 2- amino-2-methyl-1-oxazolo [4,5-b] [PYRIDIN-2-YL-PROPAN-1-OL.] TFA salt (165 mg).

Reference： [1]Patent: WO2004/838,2003,A1 .Location in patent: Page 71-72

15
[ 5856-62-2 ]
[ 34619-03-9 ]
[ 150736-72-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In 1,4-dioxane; water; at 0 - 20℃; for 2h;	Reference P Synthesis of [()-2-AMINO-1- (5-METHOXYMETHYL- [1,] 3,4] [OXADIAZOL-2-YL)-BUTAN-1-OL] Step 1 [(S)- (+)-2-AMINO-L-BUTANOL] (50 g, 561 mmol) in a mixture of water and dioxane (200 mL of water and: 200 mL) dioxane was cooled to [0 C] and mixed with [NAOH] (26.9 g, 673 mmol) and di-tert-butyl-dicarbonate (146.96 g, 673 mmol). After the addition, the reaction was allowed to warm to room temperature. The reaction mixture was stirred for 2 h. After removing the dioxane, the residue was extracted with EtOAc, then washed with brine and dried with anhydrous [MGS04,] filtered and concentrated. Without further purification, the crude [(S)-2-BOC-AMINO-L-BUTANOL] (120 g) was used for next step reaction. Step 2 A solution of oxalyl chloride (40.39 g, 265 mmol) in [MECLZ] (700 mL) was stirred and cooled to-60 [C.] Dimethylsulfoxide (51.7 g, 663 mmol) in [MECL2] (100 [ML)] was added dropwise. After 10 min. , a solution of [(S)-2-BOC-AMINO-L-BUTANOL] (50 g, 265 mmol) in [MECL2] (100 mL) was added dropwise [AT-70 C.] The reaction mixture was allowed to warm to-40 C for 10 min. and then cooled to-70 C again. A solution of triethylamine (74.9 g, 742 mmol) in MeCl2 (100 mL) was added. The reaction mixture was allowed to warm to room temperature over 2 h. Saturated sodium dihydrogen phosphate (100 [ML)] was added, and then the organic layer was washed with brine and dried over [MGS04. THE] solvent was removed to yield 45g of [(S)-2-BOC-AMINO-BUTYRALDEHYDE (L-FORMYL-PROPYL)-CARBAMIC] acid [TERT-BUTYL] ester. Step 3 A mixture of methyl methoxyacetate (52 g, 500 mmol), hydrazine hydrate (30 mL) was heated to reflux for 8 h. Excess hydrazine and water were removed under vacuum. The residue was extracted with n-butanol, dried with [NA2SO4.] Excess n-butanol was removed to yield 45g of hydrazide. Step 4 A mixture of above hydrazide (45 g), [TRIETHYLORTHOFORMATE] (146 mL) and p- toluenesulfonic acid (61mg) was heated at [140 C] for 8 h. Excess [TRIETHYLORTHOFORMATE] was removed under vacuum. The product was purified by silica gel column chromatography to yield 4.6g of 2-methoxymethyl-1, 3,4-oxadiazole. Step 5 To a stirred solution of 2-methoxymethyl-1, 3,4-oxadiazole (4.6 g, 40 mmol) in THF (100 mL) was added n-BuLi (1.6 M solution in 25.2 mL of hexane) dropwise under N2 at-78 [C.] After 1 h, MgBr. Et2O (10.4 g, 40.3 mmol) was added and the reaction mixture was allowed to warm to-45 [C] for 1 h before being treated with (S)-2-Boc-amino- propanylaldehyde butyraldehyde (5.28 g, 28.25 mmol) in THF (20 mL). The reaction mixture was stirred for 1 h, quenched with saturated [NH4C1,] and extracted with ethyl acetate. The organic layer was washed with brine, dried with MgS04 and concentrated. The residue was purified by silica gel column chromatography to yield [(S)-2-BOC-AMINO-1- (5-] methoxymethyl-[1, 3, [4]-OXADIAZOLE-2-YL)-1-PROPANOL] butanol (500 mg). Step 6 [2-BOC-AMINO-1- (5-METHOXYMETHYL- [1,] 3, [4]-OXADIAZOLE-2-YL)-1-PROPANOL] butanol (500 mg, 1.66 mmol), and MeCl2 (5 mL) were mixed and TFA (0.5 mL) was added at room temperature. After stirring for 1 h, the solvent and excess TFA were removed under vacuum to produce [(S)-2-AMINO-L- (5-METHOXYMETHYL- [1,] 3,4] oxadiazol-2-yl)-butan-1-ol. TFA salt (340 mg).

Reference： [1]Patent: WO2004/838,2003,A1 .Location in patent: Page 73

16
[ 34619-03-9 ]
[ 16636-51-4 ]
[ 334932-13-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium hydroxide; In 1,4-dioxane; water;	A solution of <strong>[16636-51-4]3-aminocyclohexanecarboxylic acid</strong> (1.005 g, 7.02 mmol) in a mixture of a 2N-aqueous sodium hydroxide solution (14 ml, 28 mmol) and 1,4-dioxane (15 ml) was cooled on a water bath, and di-tert-butyl dicarbonate (3.25 ml, 14.1 mmol) was added thereto and stirred overnight. The resulting solution was diluted with water and washed with diethyl ether, and the aqueous layer was adjusted to pH 6 to 7 with 1N-hydrochloric acid and then to pH 2 to 3 with a 5%-aqueous potassium hydrogensulfate solution. The aqueous layer was extracted three times with ethyl acetate, and the extract solution was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 3-[(tert-butoxycarbonyl)amino]cyclohexanecarboxylic acid (1.587 g, 93%).

Reference： [1]Patent: EP1403255,2004,A1 .Location in patent: Page 76

17
[ 34619-03-9 ]
[ 27489-62-9 ]
[ 224309-64-2 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium hydroxide; In water; tert-butyl alcohol; at 20℃;	An aqueous solution (52.5 ml) of sodium hydroxide (2.91 g, 72.8 mmol) was added to a t-butanol suspension (122.5 ml) of trans-4-aminocyclohexanol (8.06 g, 70.0 mmol) at room temperature, followed by adding thereto di-t-butyl dicarbonate (15.9 g, 72.9 mmol), and the resulting mixture was stirred overnight at room temperature. Water was added to the reaction mixture, followed by extraction with n-hexane. The suspended organic layer was filtered and the precipitate was dried to obtain tert-butyl 4-hydroxycyclohexylcarbamate (2.70 g) as a white solid. The aqueous layer was neutralized with 1N-hydrochloric acid and then extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: chloroform/ethyl acetate) to obtain tert-butyl 4-hydroxycyclohexylcarbamate (11.3 g) (14.0 g in total, 93%).1H-NMR (DMSO-d6): 1.06-1.20 (4H, m), 1.35 (9H, s), 1.69-1.76 (4H, m), 3.12-3.31 (2H, m), 4.48 (1H, s), 6.64 (1H, d, J=7.5Hz).

Reference： [1]Patent: EP1403255,2004,A1 .Location in patent: Page 71

18
[ 34619-03-9 ]
[ 6850-65-3 ]
[ 224309-64-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; at 20℃; for 2h;	Example 15A: CIS-7- (4-AMINO-CYCLOHEXYL)-5- (3-BENZYLOXY-PHENYL)-7H-PYRROLOF2. 3-DLPYRIMIDIN- 4-ylamine ; and Example 15B : TRANS-7-(4-AMINO-CVCLOHEXVL)-5-(3-BENZVIOXV-PHENVL)-7H-PVRROLOR2, 3- DLPYRIMIDIN-4-YLAMINE Step 15.1 : (4-Hydroxy-cyclohexyl)-carbamic acid tert-butyl ester 10 ml of cis/trans-4-amino-cyclohexanol (50% solution in water; Fluka, Buchs, Switzerland) and 11 ML of di-tert-butyl-dicarbonate (Fluka, Buchs, Switzerland) are added to 20 ml of 0.1 N NaOH. After stirring for 2 h at RT, the solution is extracted with petroleum ether and the organic phase is discarded. The aqueous phase is treated with 0.1 N HCI to pH= 4 and ex- tracted with ethyl acetate. The organic phase is dried over sodium sulfate and concentrated in vacuo to yield the title compound. Rf= 0.47 (DICHLOROMETHANE/METHANOL/WATER/ACETIC acid, 850: 130: 15: 5, V/V/V/V).

Reference： [1]Patent: WO2004/43962,2004,A1 .Location in patent: Page 37

19
[ 28954-12-3 ]
[ 34619-03-9 ]
[ 2592-18-9 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 14h;	To a mixture of H-allo-THr-OH (5.0 g, 41.98 mmol) and DIEA (10.9 g, 83.96 mmol) in DCM (150 mL) was added di-tert-butyl dicarbonate (13.7 g, 62.97 mmol). After stirring at rt for 14h, the reaction mixture was washedwith3x100 mL DCM. The combined organic layer was dried over MgS04 and conentrated. LC/MS indicated most product stayed in theH20 layer. Thus the water layer was concentrated. The product was purified by a flash column chromatography(Si02, 90: 10 DCM: MeOH) to give Boc-allo-THr-OH ; LC-MS (retention time: 0.727 min. ),MS m/z 242 (MNa+).

Reference： [1]Patent: WO2003/99274,2003,A1 .Location in patent: Page 210

20
[ 34619-03-9 ]
[ 3054-01-1 ]
[ 5068-28-0 ]

Yield	Reaction Conditions	Operation in experiment
		Example 4 Synthesis [OFN [1 ()- (BENZOXAZOL-2-YLCARBONYL)-PROPYL]-3-PHENYLMETHANESULFONYL-2 (R)-] { [N- (2,2, 2-trifluoroethyl)-morpholin-4-ylcarboximidoyl] amino} propionamide Step 1 To a solution [OF N-TERT-BUTOXYVARBONYL-S-BENZYLCYSTEINE] (7.75 g, 28 mmol, 1.0 equiv. ) (prepared by reacting S-benzylcysteine with boc anhydride via a standard protocol) in methanol (250 mL) was added, with stirring, Oxone (19 g, 31 mmol, 1.1 equiv. ) in H20 (100 mL). The resulting suspension was stirred for 2 h at ambient temperature after which methanol was removed in vacuo. The aqueous layer was extracted with ethyl acetate to give [2-N-TERT-BUTOXYCARBONYL-3-PHENYLMETHANESULFONYLPROPIONIC] acid (7.85 g, 25.5 mmol) which was converted to [{1-] [[1-(BENZOXAZOL-2-YL-HYDROXYMETHYL)-PROPYLCARBAMOYL]-2-] phenylmethanesulfonylethyl)-carbamic acid [TERT-BUTYL] ester as described in Example 1, Step 2 above. Step 2 [L,] [L'-THIOCARBONYLDIIMIDAZOLE] (0.980 g, 5.50 mmol, 1.2 equiv. ) was dissolved in [CH2C12] (200 mL), followed by addition of diisopropylethylamine (3.2 mL), and trifluoroethylamine hydrochloride (0.620 g, 4.58 mmol, 1.0 equiv. ). The solution was stirred for 1 h at ambient temp, then 2-amino-N-[l-(benzoxazol-2-ylhydroxymethyl)-propyl]-3- phenylmethanesulfonylpropionamide was added in one portion. After stirring overnight, the reaction mixture was diluted with EtOAc (150 mL), washed with saturated bicarb, brine, dried over [MGS04.] Purification with flash chromatography (50% ETOAc/hexanes as eluent) afforded [N [L- (BENZOXAZOL-2-YLHYDROXYMETHYL)-PROPYL]-3-PHENYLMETHANESULFONYL-2- [3-] (2, 2, 2-trifluoroethyl) thioureido] propionamide (0.720 g) as a mixture of diasteomers. Step 3 Copper [SULFATE-5H20] (0.75 g) was added to flash silica gel (2.25 g) and the mixture placed in an oven and heated at [240 C] for 2 h, then cooled in a dessicator. In a dry microwave tube was placed THF (4 mL), [N [L- (BENZOXAZOL-2-YLHYDROXYMETHYL)-PROPYL]-3-] [PHENYLMETHANESULFONYL-2- [3- (2,] 2,2-trifluoroethyl) thioureido] propionamide (0.20 g, 0.350 mmol, 1.0 equiv), morpholine (0.122 g, 1.40 mmol, 4.0 equiv), [CUSO4/SIO2] (0.525 g, 1.5 equiv. ), and Et3N (0.035 g, 1.0 equiv. ). The mixture was heated via microwave to [80 C] for 30 min. The suspension was filtered and the solid washed with 10% [MEOH/CH2CL2.] The filtrate was concentrated and the resulting residue was purified by reverse phase chromatography to afford [N [L- (BENZOXAZOL-2-YL-HYDROXYMETHYL)-PROPYL]-3-] phenylmethanesulfonyl-2- { [[N-(2,] 2, [2-TRIFLUOROETHYL)-MORPHOLIN-4-YLCARBOXIMIDOYL]-] amino} propionamide (0.090 g) as a mixture of diastereomers. Step 4 [ TO N- [L- (BENZOXAZOL-2-YL-HYDROXYMETHYL)-PROPYL]-3-PHENYLMETHANESULFONYL-2- { [N-] (2,2, [2-TRIFLUOROETHYL)-MORPHOLIN-4-YLCARBOXIMIDOYL]-AMINO}] propionamide (40 mg, 0.064 mmol) in [CH2C12] (0.5 mL) was added Dess-Martin Periodinane (110 mg, 0.256 mmol) and the solution stirred for 2 h at ambient temperature. The reaction mixture was quenched with 0.26 M Na2S204 in sat'd [NAHCO3] and diluted with EtOAc. The organic layer was washed with water, brine, and dried over MgS04 and concentrated to give the title compound as a white solid. MS = 624.5 (M+1).

Reference： [1]Patent: WO2004/838,2003,A1 .Location in patent: Page 85

21
[ 18881-17-9 ]
[ 34619-03-9 ]
[ 183958-71-6 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; for 2h;	To 50 mL dichloromethane solution containing (S)-3-hydroxymethy-1,2,3,4-tetrahydroisoquinoline (4.53 g, 27.75 mmol) was added di-tert-butyl dicarbonate (5.45 g, 25.0 mmol, 0.9 eq) and the reaction mixture was stirred for 2 hours until no gas bubbling was observed. The reaction mixture was washed with 0.5 N HCl (50 mL) followed by brine (50 mL) to remove the residual starting material. After drying wth MgSO4 and filtration , dichloromethane mixture was evaporated to yield crude (S)-N-tert-Butyloxycarbonyl-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline. The crude N-tert-Butyloxycarbonyl-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline was redissolved in 100 mL tetrahydrofuran. NaH (60%, 1.22 g) was added portion by portion to the solution at 0C and after 30 min stirring at room temperature, MeNCS (2.23 g) was added and the mixture was stirred for 2 h at rt. Brine (50 mL) was added to the mixture to quench the reaction and after evaporation of volatile in vacuo, it was extracted with dichloromethane (50mLx 2) and combined layer was dried (MgSO4), filtered, evaporated. The resulting material was chromatographed with hexane-EtOAc (4:1) mixture over SiO2 to provide 7.07 g-(81.8 %) of (S)-N-tert-butyloxycarbonyl-3-(N-Methyl-thiocarbamoyloxymethyl)-1,2,3,4-tetrahydroisoquinoline. This material was dissolved in THF(30 mL) and 10 mL conc. HCl was added to the solution. One hour later, 5 mL of conc, HCl was added and stirred another 1 h until the reaction is finished. The reaction mixture was diluted with 30 mL of water and volatile were evaporated. During the evaporation, desired product was precipitated as white solid. The solid was filtered and dried to yield the product as the hydrochloride salt (4.8 g). 1H-NMR (200 MHz, DMSO-d6) delta: 10.5-9.7 (m, 2H), 9.30 (s, 1H), 7.23 (s, 4H), 4.90 (m, 2H), 4.38 (s, 2H), 3.15-3.00 (m, 2H), 2.95 (d, 2H), 2.80 (1H)

Reference： [1]Patent: EP1149079,2004,B1 .Location in patent: Page 18

22
[ 1122-58-3 ]
[ 34619-03-9 ]
[ 113305-94-5 ]
[ 710322-07-9 ]

Yield	Reaction Conditions	Operation in experiment
	With N,N,N,N,-tetramethylethylenediamine; In 1,4-dioxane; at 25℃; for 20h;	A solution of <strong>[113305-94-5]2-amino-5-cyanopyrazine</strong> (500.0 mg, 4.162 mmol) in 1,4- dioxane (8.3 ML) was treated with 4- (dimethylamino) pyridine (305.1 mg, 2.497 mmol), N, N, N', N'-TETRAMETHYLETHYLENEDIAMINE (241.8 mg, 2.081 mmol), and di-tert-butyl dicarbonate (2.9 mL, 12.49 mmol). The reaction stirred at 25C for 20 h and then was concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 10% ethyl acetate/hexanes) afforded 5- [ [BIS [ (L, 1-dimethylethoxy) carbonyl] ] amino]-2- pyrazinecarbonitrile as a white solid: mp 67-68C ; (ES) +-HRMS m/e calcd for CISH2ON404 (M+Na) + 343. 1377, found 343.1379.

Reference： [1]Patent: WO2004/52869,2004,A1 .Location in patent: Page 76

23
[ 22190-33-6 ]
[ 34619-03-9 ]
[ 261732-38-1 ]

Yield	Reaction Conditions	Operation in experiment
		A solution of the title A compound, 5-bromo-2, 3-DIHYDRO-1 H-INDOLE (15. 75 g, 79.54 mmol) in 200 mL acetonitrile and 200 mL dichloromethane is treated with DMAP (0.971 g, 7.95 mmol) and di-t-butyl dicarbonate (19.14 g, 87.49 MMOL). The solution is stirred at RT for 16 h. The mixture is diluted with 300 mL dichloromethane and washed twice with 1 N aqueous HCI and once with brine, dried over anhydrous MGS04, and concentrated to afford 5-bromo-2,3- dihydro-indole-1-carboxylic acid tert-butyl ester.

Reference： [1]Patent: WO2004/65351,2004,A1 .Location in patent: Page 82

24
[ 34619-03-9 ]
[ 2549-14-6 ]
[ 86013-50-5 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In methanol; at 20℃; for 4h;	(R)-a- (Aminomethyl) benzenemethanol (1.70 g) and bis (1, 1-dimethylethyl) carbonate (2.98 g) were dissolved in methanol (20 ml) and triethylamine (4.3 ml) added. The mixture was stirred at room temperature for 4 days and then concentrated to leave the sub-title compound as an oil (2.60 g). [LH] NMR [300MHZ] [(CDCH)] 7.27-7. 38 [(SH,] [M),] 4.92 [(1H,] [M),] 4.83 [(1H,] [M),] 3.50 [(1H,] [M),] 3.25 [(1H, M),] 1.45 (9H, s)

Reference： [1]Patent: WO2004/9579,2004,A1 .Location in patent: Page 17

25
[ 34619-03-9 ]
piperidine-4-acetic acid ethyl ester hydrochloride [ No CAS ]
[ 135716-09-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In tetrahydrofuran; at 0 - 20℃; for 20h;	(1) Ethyl.(piperidin-4-yl) acetate hydrochloride obtained in Reference Example 124 (10.00 g) is suspended in tetrahydrofuran (95 ml), and thereto are added sodium hydrogen carbonate (12.14 g) and water (150 ml), and then thereto is added a solution of di-t-butyl dicarbonate (11.60 g) in tetrahydrofuran (55 ml) dropwise under ice-cooling. The reaction solution is stirred at room temperature for 20 hours, aqueous potassium carbonate solution is poured to the solution and the mixture is extracted with ethyl acetate. The organic layer is washed with saturated brine, dried over magnesium sulfate and evaporated to remove the solvent under reduced pressure. The resulting residue is purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate = 5/1) to give ethyl (1-t-butoxycarbonylpiperidin-4-yl)acetate (13.06 g). APCI-MS M/Z:272[M+H]+.(2) Ethyl (1-t-butoxycarbonylpiperidin-4-yl)acetate (13.00 g) obtained in Reference Example 135(1) is dissolved in tetrahydrofuran-ethanol (2:1, 180 ml) and thereto is added a solution of sodium hydroxide (4.80 g) in water (60 ml). The reaction solution is stirred at room temperature overnight, concentrated under reduced pressure and the resulting aqueous layer is washed with diethyl ether. The aqueous layer is acidified with 1 N hydrochloric acid under ice-cooling, and then extracted with ethyl acetate. The organic layer is washed with water and saturated brine, and then dried with magnesium sulfate. The solvent is evaporated under reduced pressure to give the title compound (11.10 g).ESI-MS M/Z: 242[M-H]-.

Reference： [1]Patent: EP1489078,2004,A1 .Location in patent: Page 188

26
[ 34619-03-9 ]
[ 109-07-9 ]
[ 120737-59-9 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; at -10℃; for 0.166667h;	To a stirred solution of 2-METHYLPIPERAZINE (2 equivalents) in DICHLOROMETHANE AT-10 C, was added di-tert-butyl dicarbonate (1 equivalent). The mixture was stirred for 10 minutes AT-10 C and was then quenched with saturated aqueous NAHC03. The two phases were separated, and the organic layer was extracted with methylene chloride. The organic extracts were collected, dried (NA2SO4), and concentrated to give the desired tert-butyl 3-methylpiperazine-carboxylate (LC/MS M/Z 201.0 (MH +), Rt 1.67 minutes). Conversion to tert-butyl 4- [2- (4-AMINO-5-FLUORO-2-OXO (3- hydroquinolyl)) benzimidazol-6-yl]-3-methylpiperazinecarboxylate was performed according to the procedure in Example 8 (LC/MS M/Z 493.3 (MH+), Rt 2.45 minutes). Subsequent removal of the Boc group was preformed by bubbling HCI gas into a MeOH solution until saturated (LC/MS M/Z 393.2 (MH +), Rt 1.95 minutes). The free amine was subsequently reacted with paraformaldehyde (5 equivalents) in MeOH: AcOH (5: 1) and NaCNBH4 (4 equivalents) over molecular sieves at 80 C. After 10 hours, the mixture was cooled, filtered, and concentrated. The residue was dissolved in CH2CI2, washed with saturated NAHC03, and dried with NA2SO4 to give the desired 4- AMINO-3-[6-(2, 4-DIMETHYLPIPERAZINYL) BENZIMIDAZOL-2-YL]-5-FLUOROHYDROQUINOLIN- 2-one (LC/MS M/Z 407.3 (MH +), Rt 2.03 minutes). Further purification was performed via reverse phase prep. HPLC.

Reference： [1]Patent: WO2004/18419,2004,A2 .Location in patent: Page 339

27
[ 34619-03-9 ]
[ 63839-24-7 ]
tert-butyl 6-bromoindoline-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With triethylamine; In tetrahydrofuran; water;	(53-1) 1-t-butoxycarbonyl-<strong>[63839-24-7]6-bromoindoline</strong> Di-t-butyl carbonate (6.7 g) was added to a solution of <strong>[63839-24-7]6-bromoindoline</strong> (5.1 g) and triethylamine (3.1 g) in tetrahydrofuran (50 ml) followed by stirring the resultant mixture at room temperature overnight. After adding water and ethyl acetate thereto, the layers were separated and the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The residue was then purified by silica gel column chromatography (hexane/ethyl acetate system) to give the title compound (5.5 g) as a colorless oil (yield: 71percent). 1H-NMR (400 MHz, CDCl3): delta(ppm) 1.56(9H, s), 3.04(2H, t, J=8Hz), 3.99(2H, t, J=8Hz), 6.98(1H, d, J=8Hz), 7.03(1H, d, J=8Hz), 8.04(1H, s).

Reference： [1]Patent: US2002/19531,2002,A1

28
[ 34619-03-9 ]
[ 64051-79-2 ]
[ 85275-45-2 ]
3-(3,4-dichlorophenyl)-3-hydroxy piperidine-1-carboxylic acid {4-[(2,2-dimethyl-propionylamino)-methyl]-phenyl}-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In 1,4-dioxane; hexane; ethyl acetate;	EXAMPLE 9 3-(3,4-dichlorophenyl)-3-hydroxy piperidine-1-carboxylic acid {4-[(2,2-dimethyl-propionylamino)-methyl]-phenyl}-amide To a solution of <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> (827 mg, 6 mmol) in dioxane (12 ml) and water (6 ml) cooled to 0 C. is added 1 N NaOH (12 ml, 12 mmol) and dit-butyl carbonate (827 mg, 6 mmol) in dioxane (35 ml) and the reaction mixture is stirred at 25 C. for 1 hr. The reaction mixture is diluted with ethyl acetate, washed with aqueous sodium bicarbonate, 1 N KHSO4, water and brine, dried over sodium sulfate and concentrated in vacuo. The crude product is purified by flash chromatography (silica gel, 50% ethyl acetate in hexane) to give N-t-butoxycarbonyl-3-hydroxypiperidine (1.07 g).

Reference： [1]Patent: US2001/44454,2001,A1

29
(1S,4R) 4-[[(1,1,-dimethylethoxy)carbonyl]amino]-cyclopent-2-ene-1-carboxylate [ No CAS ]
(1S,4R) methyl 4-aminocyclopent-2-ene-1-carboxylate L-tartrate [ No CAS ]
[ 34619-03-9 ]
[ 168683-02-1 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In methanol; water;	EXAMPLE 3 (1S,4R) Methyl 4-[[(1,1,-dimethylethoxy)carbonyl]amino]-2-cyclopentene-1-carboxylate from (1S,4R) Methyl 4-aminocyclopent-2-ene-1-carboxylate L-tartrate (1S,4R)-Methyl 4-aminocyclopent-2-ene-1-carboxylate L-tartrate (100.0 g, 0.343 mol) and di-tert-butyl carbonate (78.7 g, 0.361 mol) were suspended in methanol (130.0 g). Triethylamine (80.0 g, 0.791 mol) was added to the suspended solution, at 30-35 C. Following addition of approximately half of the amine, the mixture turned into a solution and gas evolution (CO2) started. After complete addition of the amine, the solution was stirred for 1 h without heating. The solution was cooled to 5-10 C. and water (375 ml) was added over 10-15 min. A few crystals of (1S,4R) 4-[[(1,1,-dimethylethoxy)carbonyl]amino]-cyclopent-2-ene-1-carboxylate were added as seeds to yield a white precipitate. The mixture was stirred for 2 h at 5-10 C. and then filtered. The solid was washed with water (50 ml) and dried at 35-40 C. under vacuum (<50 mbar).

Reference： [1]Patent: US2002/52524,2002,A1

30
(1S,4R) methyl 4-aminocyclopent-2-ene-1-carboxylate L-tartrate [ No CAS ]
[ 34619-03-9 ]
[ 168683-02-1 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium hydroxide; triethylamine; In methanol; water;	Step 2 Wet (1S,4R)-methyl 4-aminocyclopent-2-ene-1-carboxylate L-tartrate (285 g, about 0.95 mol) and di-tert-butyl carbonate (231.2 g, 1.06 mol) were suspended in methanol (124.2 g). Triethylamine (200.0 g, 1.98 mol) was added to the suspension, at 30-37 C. During addition of the triethylamine, strong gas evolution (CO2) was observed. By the end of the addition, the reaction mixture became a clear, slightly yellowish solution. The solution was then stirred for 1.5 h without heating. Ammonium hydroxide 25% weight solution in water (14.4 g, 0.21 mol) was added and the solution was seeded with a few crystals of (1S,4R) methyl 4-[[(1,1,-dimethylethoxy)carbonyl]amino]cyclopent-2-ene-1-carboxylate. The solution was cooled to 0-5 C. and water (675 g) was added slowly, resulting in the formation of a white precipitate. The mixture was stirred for an additional 1 h at 0-5 C. and then filtered. The solid was washed with water (200 g) and dried at 35-40 C. under vacuum (<50 mbar) to yield the title product. Yield: 212 g, 80%

Reference： [1]Patent: US2002/52524,2002,A1

31
[ 34619-03-9 ]
[ 40064-34-4 ]
[ 79099-07-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water;	(1) Water (250 ml) was added to <strong>[40064-34-4]4-piperidone monohydrate hydrochloride</strong> salt (75 g) for dissolution, and 1 N aqueous solution of sodium hydroxide (1000 ml) was added thereto. To the solution, ditertiarybutylcarbonate (120 g) was added dropwise with stirring under cooling on ice, and the mixture was vigorously stirred for 6 hours at room temperature. The reaction mixture was subjected to extraction with ethyl acetate, and the extract was evaporated to dryness under reduced pressure to thereby yield a pale yellow solid. By recrystallization of the solid from hexane, N-t-butyloxycarbonyl-4-piperidone (3) (38.9 g) was obtained in the form of white needle-shaped crystals. mp.: 74.4-75.2 C.

Reference： [1]Patent: US6306882,2001,B1

32
[ 34619-03-9 ]
(R)-piperidin-3-ol hydrochloride [ No CAS ]
[ 143900-43-0 ]

Yield	Reaction Conditions	Operation in experiment
6.6 g (92%)	With potassium carbonate; In tetrahydrofuran; water; ethyl acetate;	EXAMPLE 6 344738 R-3-[1-(4-chlorophenyl)cyclopropylmethoxy]-4-(3-piperidinyloxy)-1,2,5-thiadiazole (lot #M52-FBA-212). R-3-hydroxy-1-t-butoxycarbonylpiperidine. Di-t-butylcarbonate (9.5 g, 0.044 m) was added to a solution of R-3-hydroxypiperidine hydrochloride (5.0 g, 0.036 m) and potassium carbonate (12.0 g,.086 m) in 140 ml of a 50% solution of THF in water and stirred for 4 hr. EtOAc was added and the solution washed with water, dried and condensed to yield 6.6 g (92%) of R-3-hydroxy-1-t-butoxycarbonylpiperidine. 3-(N-t-Butyloxycarbonyl-3-piperidyloxy)-4-n-propylthiothiadiazole. 3 g of R-3-hydroxy-1-t-BOC-piperidine (0.015 m) was added to a stirred solution of potassium t-butoxide (1.66 g, 0.015 m) in 80 ml THF and cooled to 0-5 C.

Reference： [1]Patent: US6117883,2000,A

33
[ 34619-03-9 ]
[ 1197-17-7 ]
[ 27687-14-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; magnesium oxide; In 1,4-dioxane; CH3 COOC2 H5; water;	a) (N, N-dimethyl)-4-[aminomethyl]cyclohexylmethylamine (trans) 63.6 ml of an N aqueous NaOH solution and 1.28 g of MgO are introduced, at 0° C., into 50 ml of dioxane containing 5 g of trans-4-(aminomethyl)cyclohexylcarboxylic acid, followed, slowly, by 6.94 g of di(t-butyl)carbonate in solution in 20 ml of dioxane. After 20 hours at room temperature, the mixture is filtered, the solvent is removed and the residue is taken up in 100 ml of H2 O and the aqueous phase is washed with (C2 H5)2 O before acidifying it up to pH 2 by addition of KHSO)4; it is then extracted in CH3 COOC2 H5 to yield 7.3 g of trans-N-(t-butoxycarbonyl)-4-(aminomethyl)cyclohexylcarboxylic acid which melts at 125° C.

Reference： [1]Patent: US5506258,1996,A

34
[ 487-89-8 ]
aqueous potassium hydroxide [ No CAS ]
[ 34619-03-9 ]
[ 57476-50-3 ]

Yield	Reaction Conditions	Operation in experiment
97.7%	With tetrabutylammomium bromide; In tetrahydrofuran;	(1) 1-(tert-Butyloxycarbonyl)-3-formylindole Indole-3-carboxaldehyde (4.53 g, 30 mmol) was dissolved in tetrahydrofuran (100 mL) (dissolved at about 40 C.). Aqueous potassium hydroxide (1N, 30 mL) and tetrabutylammonium bromide (0.97 g, 3 mmol) were added. Then di-t-butylcarbonate (7.2 g, 33 mmol) was added (the temperature should not rise about 25 C.). The resulting mixture was stirred at room temperature until the starting material was not detected by TLC (CH2 CL2 /CH3 OH 9:1). The reaction mixture was separated, and the aqueous layer was extracted with ethyl acetate (2*50 mL). The combined organic layer was dried with MgSO4 and evaporated to give crude product. The product was recrystallized from methylene chloride/hexane (20 mL/100 mL) to obtain needle crystals (7.19 g, 97.7%). m.p. 124-125 C.

Reference： [1]Patent: US5554753,1996,A

35
[ 776-41-0 ]
[ 34619-03-9 ]
[ 177200-90-7 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; In hexane; ethyl acetate; acetonitrile;	e Ethyl 1-(tert-butoxycarbonyl)indole-3-carboxylate A solution of 3.15 g of <strong>[776-41-0]ethyl indole-3-carboxylate</strong>, 4.36 g of di-tert-butylcarbonate and 0.02 g of 4-DMAP in 30 ml of acetonitrile is stirred at room temperature for 15 min. The reaction mixture is then diluted with 200 ml of ethyl acetate. The organic phase is washed with dilute hydrochloric acid, water and saturated sodium chloride solution in succession, dried over sodium sulfate and concentrated. Purification by means of FC over 80 g of silica gel with a 15:1 mixture of hexane and ethyl acetate as the mobile phase gives 5.1 g of the title compound: Rf (G)=0.41.

Reference： [1]Patent: US5719141,1998,A

36
[ 34619-03-9 ]
[ 6276-54-6 ]
[ 497-19-8 ]
[ 116861-31-5 ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-dioxane; water;	(a) N-[(tert-butoxy)carbonyl]-3-chloro-propylamine The compound of the title, employed as the starting material in example 1, is prepared by slowly adding a solution of 3-chloro-propylamine hydrochloride (12.98 g, 0.1 mol) in dioxane/water (100 ml 2/1 v/v) to a vigorously stirred mixture of di-(tert-butyl)carbonate (24 g, 0.11 mol), 1N Na2 CO3 (100 ml) and dioxane/water (200 ml, 2/1 v/v) cooled to 0 C. When the addition is over, the reaction mixture is stirred at room temperature for an additional hour, dioxane is removed under vacuum and the aqueous phase is extracted a few times with ethyl acetate. From the organic solution an oily product (19.2 g) is recovered, whose structure is confirmed by NMR spectroscopy. This compound can be used as such for the preparation of example 1.

Reference： [1]Patent: US4914226,1990,A

37
[ 34619-03-9 ]
[ 2799-07-7 ]
[ 101-83-7 ]
[ 77-92-9 ]
[ 26988-59-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In 1,4-dioxane;	A. N-boc-S-trityl-cysteine, dicyclohexylammonium salt (XX) To a solution of S-trityl cysteine (see Hiskey and Adams, J. Org. Chem., 30:1340, (1965)) (36.3 g, 0.10 mol) in dioxane (200 ml) and 1M aqueous NaOH (100 ml, 0.10 mol) was added di-t-butyl carbonate (25.36 g, 0.12 mol). The resulting opaque solution became warm and effervesced and the pH fell from 12 to 8 over one hour. After stirring for 90 min, 50percent aqueous citric acid (40 ml) was added and the resulting mixture (pH 4) was extracted with ether. The ether was washed with water, then saturated brine, dried (MgSO4), filtered and evaporated to give N-BOC-S-(triphenylmethyl)-cysteine as an oil. Half of this material was dissolved in ether (200 ml) and treated with dicyclohexylamine (10 ml, 50 mmol) to give compound (XX) as a white precipitate which was filtered off, washed with ether and dried (25.1 g, 78percent), mp 205°-207°.

Reference： [1]Patent: US4673562,1987,A

38
ter.-butanol [ No CAS ]
aqueous KHCO₃ [ No CAS ]
[ 34619-03-9 ]
[ 2566-30-5 ]
[ 37553-65-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water;	(a) Boc-MePhe-OH 3.6 g of H-MePhe-OH are dissolved in a mixture of ter.-butanol, 25 ml of 10% aqueous KHCO3 solution and 5 ml of 4 N sodium hydroxide. 8 ml of di-tert.-butylcarbonate are added and the mixture stirred for 2 days at room temperature. The reaction mixture is diluted with ca. 100 ml of water and extracted with ether. The aqueous phase is acidified, with stirring to pH 2. The precipitated product is extracted with acetic acid, the extract washed with water and dried over Na2 SO4. The liquid is evaporated and the product crystallized from ether/petroleum ether to yield Boc-MePHe-OH. M.P. 87. [alpha]D20 =-65 (c=1 in methanol).

Reference： [1]Patent: US4261888,1981,A

39
[ 34619-03-9 ]
[ 26395-99-3 ]
7-tert-butoxycarbonylamino-2-carboxy-3-methyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate;ethyl acetate; In 1,4-dioxane; water;	7-Amino-2-carboxy-3-methyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene (371 g) is dissolved in a solution of sodium bicarbonate (307 g) in a mixture of distilled water (2 liters) and dioxane (2 liters). A solution of di-tert.-butyl carbonate (421 g) in dioxane (2 liters) is added in the course of 10 minutes. The reaction mixture is stirred for 48 hours at 25° C. The suspension obtained is concentrated under reduced pressure (20 mm Hg) at 50° C. to a residual volume of about 2 liters, and is then diluted with ethyl acetate (1 liter) and distilled water (2 liters). The aqueous phase is decanted, washed with ethyl acetate (500 cc) and acidified to pH 2 with 6 N hydrochloric acid in the presence of ethyl acetate (1500 cc). The aqueous phase is extracted with ethyl acetate (21 liter). The combined organic phases are washed with a saturated sodium chloride solution (2250 cc) and dried over sodium sulphate. After filtration, the solvent is evaporated under reduced pressure (20 mm Hg) at 50° C. 7-tert.-Butoxycarbonylamino-2-carboxy-3-methyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene (486 g) is obtained in the form of yellow crystals (m.p.=190° C., with decomposition).

Reference： [1]Patent: US4307230,1981,A

40
[ 34619-03-9 ]
[ 1991-81-7 ]
[ 210962-68-8 ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; thionyl chloride; sodium borohydrid; In tetrahydrofuran; methanol; dichloromethane;	Step 1 Synthesis of t-butyl [(1S)-2-hydroxy-1-(4-iodobenzyl)ethyl]carbamate: 0.56 ml (7.13 mmol) of thionyl chloride was added to 3 ml of methanol under cooling with ice. 450 mg (1.56 mmol) of L-4-iodophenylalanine was added to the resultant mixture, and they were heated under reflux for 2 hours. The solvent was evaporated. 0.52 ml (4.68 mmol) of N-methylmorpholine, 443 mg (2.03 mmol) of di-t-butyl carbonate and 10 ml of dichloromethane were added to the residue, and they were stirred for 19 hours. The reaction liquid was diluted with water. After the extraction with dichloromethane, the organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and then with saturated aqueous NaCl solution, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. 3 ml of methanol and 3 ml of tetrahydrofuran were added to the residue. 143 mg (3.78 mmol) of sodium borohydride was added to the resultant mixture, and they were stirred for 17 hours. The reaction liquid was slowly poured into 1 N hydrochloric acid. After the extraction with ethyl acetate, the organic layer was successively washed with water, 1 N hydrochloric acid, 1 N sodium hydroxide and saturated aqueous NaCl solution, and dried over anhydrous magnesium sulfate. The solvent was evaporated. The residue was purified by the silica gel column chromatography to obtain the title compound. Yield: 240 mg (0.64 mmol) (41 percent) H-NMR (CDCl3) delta 1.42 (9H, s), 3.48-3.77 (2H, m), 2.59 (2H, d), 3.79-3.91 (2H, m), 4.63-4.78 (1H, m), 6.97 (2H, d), 7.64 (2H, d)

Reference： [1]Patent: EP976722,2000,A1

41
[ 33588-64-6 ]
[ 34619-03-9 ]
[ 172226-77-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	With dmap; In dichloromethane; at 20℃; for 2h;	To a solution of <strong>[33588-64-6]ethyl 2-(1H-indol-2-yl)acetate</strong> (14.7 g, 72.2 mmol) in dichloromethane (150 mL) was added 4-dimethylaminopyridine (8.83 g, 72.2 mmol) and di-tert-butyl carbonate (23.7 g, 108 mmol) in portions. After stirring for 2 h at room temperature, the mixture was diluted with dichloromethane, washed with water, dried over magnesium sulfate and purified by silica gel chromatography (0 to 20% EtOAc in hexane) to give tert-butyl 2-((ethoxycarbonyl)methyl)-1H-indole-1-carboxylate (20.0 g, 91%).
91%	With dmap; In hexane; dichloromethane; ethyl acetate;	tert-Butyl 2-((ethoxycarbonyl)methyl)-1H-indole-1-carboxylate To a solution of <strong>[33588-64-6]ethyl 2-(1H-indol-2-yl)acetate</strong> (14.7 g, 72.2 mmol) in dichloromethane (150 mL) was added 4-dimethylaminopyridine (8.83 g, 72.2 mmol) and di-tert-butyl carbonate (23.7 g, 108 mmol) in portions. After stirring for 2 h at room temperature, the mixture was diluted with dichloromethane, washed with water, dried over magnesium sulfate and purified by silica gel chromatography (0 to 20% EtOAc in hexane) to give tert-butyl 2-((ethoxycarbonyl)methyl)-1H-indole-1-carboxylate (20.0 g, 91%).

Reference： [1]Patent: US2007/244159,2007,A1 .Location in patent: Page/Page column 133
[2]Patent: US2011/98311,2011,A1

42
[ 593-77-1 ]
[ 34619-03-9 ]
[ 19689-97-5 ]

Reference： [1]Patent: WO2008/57235,2008,A2 .Location in patent: Page/Page column 4/7

43
[ 34619-03-9 ]
[ 134997-74-3 ]
[ 134997-81-2 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium tetrahydroborate;nickel(II) chloride hexahydrate; In methanol; at 0 - 20℃; for 2h;	To an ice cooled solution of the title compound from Step A above (5.6 g), di-tert-butyl dicarbonate (14.06 g) and NiCl2-OH2O (1.53 g) in MeOH, NaBH4 (8.51 g) was added in portions. The mixture was vigorously stirred for Ih at O0C and Ih at room temperature. After the addition of diethylenetriamine (3.5 mL) the mixture was concentrated, diluted with EtOAc, washed subsequently with IN HCl, saturated aqueous NaHCO3 and saturated aqueous NaCl, dried (MgSO4), concentrated to afford the title compound as an off-white solid (7.91 g, 88%). [M+Na]+ = 397.

Reference： [1]Patent: WO2008/63667,2008,A1 .Location in patent: Page/Page column 70

44
[ 504-29-0 ]
[ 34619-03-9 ]
[ 38427-94-0 ]

Yield	Reaction Conditions	Operation in experiment
	In tert-butyl alcohol; at 20℃; for 24h;	To a solution of tert-butyl alcohol (650 mL) and di-tert-butyl carbonate (24 g) was added 2-Aminopyridine (9.4 g) slowly. This mixture was stirred at room temperature for 24 hours. This reaction solution was concentrated under a reduced pressure, and the residue thereof was purified by silica gel column chromatography (heptane:ethyl acetate=1:1) to obtain the title compound (18 g). 1H-NMR Spectrum (DMSO-d6) delta (ppm): 1.47 (9H, s), 6.99-7.03 (1H, m), 7.70-7.74 (1H, m), 7.77-7.80 (1H, m), 8.23-8.24 (1H, m), 9.72 (1H, brs).

Reference： [1]Patent: US2008/275244,2008,A1 .Location in patent: Page/Page column 12

45
[ 109162-29-0 ]
[ 34619-03-9 ]
[ 478832-21-2 ]

Yield	Reaction Conditions	Operation in experiment
70%		Ammonium formate (900 mg) and 10% Pd-C (200 mg) were added to a solution of 1-benzyl-4-azepanol (450 mg, 2.19 mmol) in ethanol (10 ml), and the resulting mixture was refluxed for 1 hour. The reaction mixture was filtered by the use of Celite and the filtrate was concentrated. To a solution of the resulting residue in dichloromethane (10 ml) was added di-tert-butyl dicarbonate (0.504 ml, 2.19 mmol) at room temperature, and stirred for 19 hours. A saturated aqueous sodium hydrogencarbonate solution and then water were added to the reaction mixture, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent, and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate = 2/1) to obtain tert-butyl 4-hydroxyazepane-1-carboxylate (333 mg, 70%).1H-NMR (CDCl3) delta; 1.50-1.92 (6H, m), 2.39 (1H, s), 3.11-3.42 (4H, m), 3.77 (1H, m).

Reference： [1]Patent: EP1403255,2004,A1 .Location in patent: Page 93-94

46
[ 34619-03-9 ]
[ 540-37-4 ]
[ 159217-89-7 ]

Reference： [1]Organic Letters,2008,vol. 10,p. 3207 - 3210

47
[ 504-29-0 ]
[ 34619-03-9 ]
[ 75-65-0 ]
[ 38427-94-0 ]

Yield	Reaction Conditions	Operation in experiment
	at 20℃;	Manufacturing Example 1-7-1 Pyridin-2-yl-carbamic acid tent-butyl ester To a solution of tert-butyl alcohol (650 mL) and di-tert-butylcarbonate (24 g) was added 2-aminopyridine (9.4 g) slowly. This mixture was stirred at room temperature for 24 hours. The reaction solution was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=1:1) to obtain the title compound (18 g). 1H-NMR Spectrum (DMSO-d6) delta (ppm): 1.47 (9H, s), 6.99-7.03 (1H, m), 7.70-7.74 (1H, m), 7.77-7.80 (1H, m), 8.23-8.24 (1H, m), 9.72 (1H, brs).

Reference： [1]Patent: US2010/105737,2010,A1 .Location in patent: Page/Page column 16

48
[ 540-88-5 ]
[ 34619-03-9 ]
[ 34622-39-4 ]
[ 144403-08-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1910 - 1912

49
[ 34619-03-9 ]
[ 60-19-5 ]
[ 64318-28-1 ]

Reference： [1]Journal of Organic Chemistry,2010,vol. 75,p. 8333 - 8336

50
[ 34619-03-9 ]
[ 704-15-4 ]
[ 14296-92-5 ]

Reference： [1]Chemistry - A European Journal,2010,vol. 16,p. 13479 - 13486

51
[ 34619-03-9 ]
[ 231958-14-8 ]

Reference： [1]Patent: WO2010/144345,2010,A1

52
[ 34619-03-9 ]
[ 66607-27-0 ]
[ 290368-00-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1852 - 1856

53
[ 34619-03-9 ]
[ 86770-74-3 ]
[ 106984-09-2 ]

Reference： [1]Tetrahedron Letters,2011,vol. 52,p. 2906 - 2909

54
[ 34619-03-9 ]
[ 123-30-8 ]
[ 54840-15-2 ]

Reference： [1]Molecular Crystals and Liquid Crystals,2010,vol. 531,p. 47 - 54
[2]Journal of the American Chemical Society,2012,vol. 134,p. 1847 - 1852

55
[ 34619-03-9 ]
[ 62037-46-1 ]
[ 570390-94-2 ]

Reference： [1]Synlett,2011,p. 1831 - 1834

56
[ 34619-03-9 ]
[ 615-36-1 ]
[ 78839-75-5 ]

Reference： [1]Chemical Communications,2011,vol. 47,p. 11703 - 11705
[2]Journal of labelled compounds and radiopharmaceuticals,2011,vol. 54,p. 239 - 246

57
[ 33588-64-6 ]
[ 34619-03-9 ]
[ 172226-78-7 ]

Reference： [1]Patent: US2011/98311,2011,A1

58
[ 34619-03-9 ]
[ 121786-39-8 ]
(R)-2-((tert-butoxycarbonyl)amino)-3-cyclopropylpropanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In tetrahydrofuran; ethanol; water; at 20℃; for 15h;	[0390] Synthesis of (R)-2-amino-3-cyclopropylpropanamide hydrochloride salt:[0391] To a solution of <strong>[121786-39-8](R)-2-amino-3-cyclopropylpropanoic acid</strong> (1.0 g, 7.7.4 mmol) in Ethanol (15 mL) and water (8 mL) was added IN NaOH (10 mL) and Di-tert-butyl carbonate (1.86 g, 8.52 mmol) in THF (8 mL). After stirring at room temperature for 15 h, the solution was diluted with water, extracted with ether, the aqueous layer was separated and was acidified to pH 2 with cone. HCl, the aqueous layer was extracted with EtOAc, organic layer was separated, washed with brine, dried and concentrated to give (R)-2-(tert- butoxycarbonylamino)-3-cyclopropylpropanoic acid (1.0 g)

Reference： [1]Patent: WO2012/61418,2012,A2 .Location in patent: Page/Page column 106

59
[ 34619-03-9 ]
[ 121786-39-8 ]
(R)-tert-butyl-1-amino-3-cyclopropyl-1-oxopropan-2-ylcarbamate [ No CAS ]

Reference： [1]Patent: WO2012/61418,2012,A2

60
[ 34619-03-9 ]
[ 19733-56-3 ]
[ 875798-79-1 ]

Reference： [1]Organic Process Research and Development,2011,vol. 15,p. 831 - 840

61
[ 34619-03-9 ]
[ 220199-85-9 ]

Reference： [1]Bulletin of the Korean Chemical Society,2012,vol. 33,p. 2971 - 2975

62
3,6-dithiophen-2-yl-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione [ No CAS ]
[ 34619-03-9 ]
[ 1046864-83-8 ]

Reference： [1]Advanced Functional Materials,2012,vol. 22,p. 4128 - 4138

63
[ 34619-03-9 ]
[ 6276-54-6 ]
[ 116861-31-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With triethylamine; In chloroform; at 20℃;	[0086] Under stirring, a solution of di-tert-butyl di-carbonate (23.79 g, 110 mmol) in chloroform (50 mL) is slowly addedinto a solution of 3-chloropropylamine hydrochloride (11.0 g, 110 mmol) and triethylamine (18.42 mL, 130 mmol) inchloroform (50 mL). After stirring overnight at room temperature, a brown oil is obtained as a crude product. Thencompound (8-2) (22 g, 95%) as a colorless solid is produced by Kugelrohr distillation at a temperatures of less than 48 C.

Reference： [1]Advanced Materials,2012,vol. 24,p. 6193 - 6198
[2]Patent: EP2615092,2013,A1 .Location in patent: Paragraph 0085; 0086

64
[ 1192-07-0 ]
[ 34619-03-9 ]
[ 1421706-23-1 ]

Reference： [1]European Journal of Organic Chemistry,2013,p. 95 - 104

65
[ 34619-03-9 ]
[ 22348-44-3 ]
[ 400899-99-2 ]

Yield	Reaction Conditions	Operation in experiment
87%	In acetonitrile; at 20℃;	tert-butyl (trans-4-hydroxycyclohexyl)methylcarbamate To a solution of <strong>[22348-44-3]trans-4-(methylamino)cyclohexanol</strong> (intermediate 2, 5.3 g, 0.04 mol) in acetonitrile (92 mL) was added in portions di-tert-butyl dicarbonate (9.9 g, 0.04 mol). The mixture was stirred overnight at room temperature. The solvent was removed under reduced pressure and the crude was purified by column chromatography with silica gel, eluting with a mixture of chloroform/methanol (from 75:1 to 4:1)) to give the title compound as a colourless oil (87%). 1H NMR (300 MHz, CHLOROFORM-d) delta ppm 1.34 - 1.43 (m, 2 H) 1.46 (s, 9 H) 1.49 - 1.57 (m, 2 H) 1.70 (d, J=9.89 Hz, 2 H) 2.03 (br. s., 3 H) 2.71 (br. s., 3 H) 3.57 (br. s., 1 H)

Reference： [1]Patent: EP2386555,2011,A1 .Location in patent: Paragraph 0075

66
[ 909036-46-0 ]
[ 34619-03-9 ]
[ 234108-74-8 ]

Yield	Reaction Conditions	Operation in experiment
56%	In tetrahydrofuran; for 1h;Cooling with ether-dry ice;	PREPARATION 42 tert-Butyl (2-chloro-3-iodopyridin-4-yl)carbamate The title compound of Preparation 41 (6.4 g, 25 mmol) was dissolved in 25 ml tetrahydrofuran and the mixture was cooled in an ice-bath. Di-tert-butylcarbonate (6.0 g, 27.5 mmol) was added and the mixture was stirred for 1 h. The mixture was partitioned between saturated ammonium chloride solution and ethyl acetate. The organics were washed sequentially with 0.1 N hydrochloric acid, water and brine. The organics were dried over sodium sulphate, filtered and evaporated under reduced pressure. The solid was recrystallised from ethanol and was dried in the oven to give 5.0 g (14 mmol, 56%) of the title compound. Purity 100%. 1 H NMR (400 MHz, CH LOROFORM-d) delta ppm 8.15 (1 H , d, J=5.5 Hz), 8.03 (1 H, d, J=5.5 Hz), 7.32 (1 H, br. s.), 1 .55 (9 H, s). UPLC/MS (3 min) retention time 1 .92 min. LRMS: m/z 355 (M+1 ).

Reference： [1]Patent: WO2013/10880,2013,A1 .Location in patent: Page/Page column 94-95

67
[ 34619-03-9 ]
[ 68-41-7 ]
[ 128346-20-3 ]

Yield	Reaction Conditions	Operation in experiment
157 g	With triethylamine; In tetrahydrofuran; water; at 10℃;	30 D-<strong>[68-41-7]cycloserine</strong> (100 g) was dissolved in tetrahydrofuran (1000 ml) and water (1000 ml) then triethylamine (144 ml) was added. The stuffed solution was cooled to 10C then a solution of ditert-butylcarbonate (224 g) in tetrahydrofuran (1000 ml) was added dropwise over a period of 1hour and the resulting reaction mixture was stirred overnight at room temperature.The solventwas removed in vacuo then the residue was acidified to pH 2-3 with a 2N hydrochloric acid solution. A precipitate was obtained, which was filtered to obtain a white solid. The filtrate was extracted with dichloromethane (6*200 ml). The combined organic layers were dried oversodium sulphate and the solvent evaporated in vacuo.The combined solids were triturated with diethyl ether then filtered and rinsed with cold diethyl ether and dried to afford the title product as a white solid (157 g). ?H-NMR (CDC13, 400 MHz): 5.20 (m, 1H), 4.80 (m, 1H), 4.60 (m, 1H), 4.10 (m, 1H), 1.50 (s, 9H).

Reference： [1]Patent: WO2013/50302,2013,A1 .Location in patent: Page/Page column 119; 220

68
[ 61272-71-7 ]
[ 34619-03-9 ]
[ 1093307-36-8 ]

Yield	Reaction Conditions	Operation in experiment
84%	With dmap; In tetrahydrofuran; at 20℃; for 18.0h;	A. To a solution of <strong>[61272-71-7]5-bromo-1H-indazol-3-amine</strong> (1.5 g, 7.1 mmol) (prepared according to PCT Published Patent Application No. WO 2008/154241) in tetrahydrofuran (50 mL) was added 4-(N,N-dimethylamino)pyridine (0.17 g, 1.4 mmol) and di-ferf-butyl dicarbonate (4.80 g, 22.1 mmol). The reaction was stirred at ambient temperature for 18 h and concentrated in vacuo. The residue was diluted with ethyl acetate (30 mL), washed with water (2 x 15 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a 30-60% gradient of ethyl acetate in hexanes to afford ferf-butyl 3-[bis(te/f-butoxycarbonyl)amino]-5-bromo-1 - -indazole-1 -carboxylate as a colorless solid in 84% yield (3.06 g): 1H NMR (300 MHz, DMSO-d6) £7.80 (d, J = 8.7 Hz, 1 H), 7.70 (s, 1 H), 7.63 (d, J = 9.0 Hz, 1 H); MS (ES+) m/z 51 1.9 (M + 1), 513.9 (M + 1).

Reference： [1]Patent: WO2013/64984,2013,A1 .Location in patent: Page/Page column 71

69
[ 61272-71-7 ]
[ 34619-03-9 ]
[ 1432912-66-7 ]

Reference： [1]Patent: WO2013/64984,2013,A1

70
[ 34619-03-9 ]
[ 128502-56-7 ]
[ 142335-42-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In tetrahydrofuran; water; for 12h;Inert atmosphere;	To a solution of crude L-7-hydroxy- 1,2,3, 4-tetrahydroisoquinoline-3- carboxylic acid (0.87 g, 4.5 mmol) and NaHC03 (0.76 g, 9.0 mmol) in THF (26 mL) and H2O (26 mL) was added B0C2O (1.1 mL, 4.9 mmol). After 12 h the reaction mixture was concentrated in vacuo to remove the volatiles and acidified to pH = 4 with IN HC1, resulting in a cloudy yellow solution. The solution was then partitioned in CH2CI2, and the layers were separated. The aqueous layer was extracted with CH2CI2 (3x), and the combined organic layer was dried over MgS04, filtered, and concentrated in vacuo to give crude (5)-2-(tert-butoxycarbonyl)-7-hydroxy-l,2,3,4-tetrahydroisoquinoline-3- carboxylic acid, which was used directly in the next step. MS(ESI+) m/z 294.3 (M+H)+

Reference： [1]Patent: WO2013/192286,2013,A1 .Location in patent: Paragraph 00163

71
[ 34619-03-9 ]
[ 74-89-5 ]
[ 16066-84-5 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 3998 - 4000

72
[ 34619-03-9 ]
[ 40350-83-2 ]

Reference： [1]European Journal of Organic Chemistry,2014,vol. 2014,p. 5351 - 5355

73
[ 41339-17-7 ]
[ 34619-03-9 ]
tert-butyl (5-nitro-1H-indazol-3-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.8 g	With dmap; triethylamine; In tetrahydrofuran; for 0.333333h;Cooling with ice;	1st Step Di-tert-butyl carbonate (1.76 g), triethylamine (1.13 ml), and DMAP (10 mg) were added to a THF (8.2 ml) solution containing <strong>[41339-17-7]5-nitro-1H-indazol-3-amine</strong> (1.45 g) under ice cooling, followed by stirring for 20 minutes. A saturated ammonium chloride aqueous solution was added to the reaction solution, followed by extraction with ethyl acetate. The organic layers were extracted with water and saturated saline and dried over sodium sulfate and the solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=1:0 to 3:2) and a yellow solid of tert-butyl (5-nitro-1H-indazol-3-yl)carbamate (1.8 g) was thus obtained.

Reference： [1]Patent: US2014/309225,2014,A1 .Location in patent: Paragraph 0656

74
[ 41339-17-7 ]
[ 34619-03-9 ]
[ 574729-25-2 ]
tert-butyl 3-((tert-butoxycarbonyl)amino)-5-nitro-1H-indazol-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.8 g	With dmap; triethylamine; In tetrahydrofuran; for 0.333333h;Cooling with liquid nitrogen;	1st Step di-tert-Butyl carbonate (1.76 g), triethylamine (1.13 ml), and DMAP (10 mg) were added to a THF (8.2 ml) solution containing <strong>[41339-17-7]5-nitro-1H-indazol-3-amine</strong> (1.45 g), followed by stirring for 20 minutes under ice cooling. A saturated ammonium chloride aqueous solution was added to the reaction solution, followed by extraction with ethyl acetate and washing with water and saturated saline. The obtained solution was dried over sodium sulfate and the solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=1:0 to 3:2) and a yellow solid mixture (1.8 g) of tert-butyl 3-((tert-butoxycarbonyl)amino)-5-nitro-1H-indazol-1-carboxylate, tert-butyl (5-nitro-1H-indazol-3-yl)carbamate, and tert-butyl 3-amino-5-nitro-1H-indazol-1-carboxylate was thus obtained.

Reference： [1]Patent: US2014/309225,2014,A1 .Location in patent: Paragraph 0667

75
[ 61367-07-5 ]
[ 34619-03-9 ]
[ 146307-51-9 ]

Yield	Reaction Conditions	Operation in experiment
86%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 1h;	Step 1 trans-Methyl 4-((tert-butoxycarbonyl)amino)cyclohexanecarboxylate To a suspension of trans-methyl 4-aminocyclohexanecarboxylate hydrochloride (1.5 g, 7.7 mmol) in DCM (80 mL) was added DIEA (4 g, 31mmol) and (Boc)20 (3 g, 13.9 mmol) at room temperature. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated in vacuum to give crude product. The crude product was purified by silica gel chromatography (PE / EtOAc = 8 : 1 to 3 : 1) to give trans-methyl 4-((iert-butoxycarbonyl)amino)cyclohexanecarboxylate (1.7 g, yield 86%) as a white solid. 1H NMR (400 MHz, Methanol-d4) delta 4.38 (br, 1H), 3.66 (s, 3H), 3.47- 3.40 (m, 1H), 2.22-2.19 (m, 1H), 2.07-1.98 (m, 4H), 1.56-1.50 (m, 2H), 1.43 (s, 9H), 1.15-1.12 (m, 2H).

Reference： [1]Patent: WO2015/188051,2015,A1 .Location in patent: Page/Page column 139

76
[ 63927-22-0 ]
[ 40899-73-8 ]
[ 34619-03-9 ]
C₂₈H₃₅BrN₂O₂Si [ No CAS ]
C₂₈H₃₅BrN₂O₂Si [ No CAS ]

Reference： [1]ACS Catalysis,2016,vol. 6,p. 5290 - 5294

77
[ 4720-64-3 ]
[ 34619-03-9 ]
[ 128372-93-0 ]

Yield	Reaction Conditions	Operation in experiment
42%	With dmap; In dichloromethane; at 20℃; for 16h;	Di-tertiary-butyl carbonate (4.2 g, 24 mmol) and 4-dimethylaminopyridine (3 g, 24 mmol) were added to a stirred solution of <strong>[4720-64-3]4-methylpiperidin-2-one</strong> (2.5 g, 22 mmol) in dichloromethane (25 ml) at room temperature and the resulting mixture stirred for 16 hours. Water was added and theresulting mixture extracted with dichloromethane (3 x 400 ml). The combined organic extracts were washed with 1 N hydrochloric acid (40 ml) and water, dried over sodium sulfate and concentrated under reduced pressure to provide tert-butyl 4-methyl-2-oxo-piperidine-1- carboxylate (2 g, 42 percent).1H NMR (400 MHz, CDCI3) oe 3.82-3.75 (m, 1H), 3.52-3.46 (m, 1H), 2.62-2.56 (m, 1H), 2.15-2.07(m, 1H), 1.94-1.90 (m, 2H), 1.52 (s, 9H), 1.48-1.42 (m, 1H), 1.02 (d, 3H) ppm.

Reference： [1]Patent: WO2016/207083,2016,A1 .Location in patent: Page/Page column 94

78
[ 34619-03-9 ]
[ 15996-76-6 ]
[ 66389-80-8 ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 3718 - 3722
Angew. Chem.,2017,vol. 129,p. 3772 - 3776,5

79
[ 34619-03-9 ]
[ 132414-81-4 ]

Reference： [1]Patent: WO2017/21920,2017,A1

80
[ 34619-03-9 ]
[ 132414-50-7 ]
[ 132414-80-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	In dichloromethane; at 20℃; for 4.0h;	A solution of Di-tert-butyl dicarbonate (1.8 g, 8.28 mmol) in DCM (10 mL) was added to a solution of <strong>[132414-50-7]1-benzyl-octahydropyrrolo[2,3-c]pyrrole</strong> (p69, 1.4 g, 6.9 mmol) in DCM (20 mL). The solution was stirred at RT for 4hrs. Solvent was removed under vacuum and the residue was purified by FC on 5i02 cartridge (eluting from cHex to 35% EtOAc) to afford 1.68 g of title compound (p70, y= 80%) as colourless oil. MS (m/z): 303.3 [IVIH]t

Reference： [1]Patent: WO2017/21920,2017,A1 .Location in patent: Paragraph 0635; 0636

81
[ 34619-03-9 ]
[ 1029413-55-5 ]

Reference： [1]Patent: CN106478651,2017,A
[2]Patent: CN106478607,2017,A

82
[ 133081-24-0 ]
[ 34619-03-9 ]
[ 133081-25-1 ]

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2017,vol. 60,p. 431 - 438

83
[ 552331-16-5 ]
[ 34619-03-9 ]
[ 552331-49-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine; In dichloromethane; at 20℃; for 3h;	500 ml three-neck bottle in adding compound 1 (50g, 237mmol, 1eq), triethylamine (72g, 713mmol, 3eq), di-t-n-butyl carbonate (51.7g, 237mmol, 1.0eq), methylene chloride (250 ml, 5V), the reaction mixture at room temperature 3 hours, TLC detection raw material the reaction is complete. Water is added to the reaction system (500 ml), stirring 5 minutes, standing, separating the organic phase, the aqueous phase is dichloromethane (200 ml) then extracting 1 time, combined with the organic phase, saturated salt water (500 ml) and water (500 ml) all washed, dried with anhydrous sodium sulfate, concentrated to obtain black liquid (73g, Y=100%).

Reference： [1]Patent: CN104610229,2017,B .Location in patent: Paragraph 0069-0071

84
[ 51-67-2 ]
[ 34619-03-9 ]
[ 64318-28-1 ]

Yield	Reaction Conditions	Operation in experiment
91%	With triethylamine; In tetrahydrofuran; methanol; at 0 - 20℃;	Tyramine(10 g, 72.90 mmol) slowly dissolved in THF (ie tetrahydrofuran, 140 ml)Triethylamine (7.36 g, 72.90 mmol) was added to methanol (20 ml). The solution was cooled to 0[deg.] with an ice-salt bath and di-tert-butyl carbonate (8.20 g, 87.48 mmol) was added in portions. After the addition is complete, it is stirred at 0C for 1 hour and then at room temperature overnight. Spin-drying solvent product 18.0g (91%) ?

Reference： [1]Patent: CN104341347,2018,B .Location in patent: Paragraph 0097; 0098

85
[ 34619-03-9 ]
[ 1500-85-2 ]
tert-butyl 4-amino-7H-pyrrolo[2,3-d]pyrimidine-7-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%		A mixture of 7H-pyrrolo[2,3-d]pyrimidin-4-amine (GAS 1500-85-2, 1 .50 g, 11 .2 mmol) inpyridine (30 mL) was treated with N,N-dimethylpyridin-4-amine (273 mg, 2.24 mmol) andstirred at RT for 15 minutes. Di-tert-butyl dicarbonate (GAS 24424-99-5, 2.44 g, 11 .2 mmol)was added and it was stirred at RT over night. The mixture was concentrated and the residue purified by flash chromatography (Biotage SNAP cartridge silica 100 g, methanol:dichloromethane) to give 2.30 g (88% yield) of the title compound.LG-MS: m/z = 235.5 [M÷H].1HNMR (400 MHz, DMSO-d6), 6 [ppm]= 1.58 (9H), 6.74 (1H), 7.22 (2H), 7.44 (1H), 8.17 (1H).

Reference： [1]Patent: WO2018/134148,2018,A1 .Location in patent: Page/Page column 161

86
[ 3775-73-3 ]
[ 34619-03-9 ]
[ 159991-23-8 ]

Yield	Reaction Conditions	Operation in experiment
93.5%	With sodium carbonate; In water; at 25℃;Green chemistry;	Sequentially put 103g of R-3-aminobutyric acid,105g sodium carbonate,218g di-tert-butyl carbonate,Add to the reaction flask containing 500 mL of water,React at 25 C for 2-6 hours,After the reaction is completed, adjust the pH to 3-4 with 2N hydrochloric acid.The product was extracted twice with 500 mL of ethyl acetate.Spin dry,That is, N-Boc-(R)-3-aminobutyric acid (I),The white solid was 190 g, the yield was 93.5%, and the content was 98% (HPLC method).

Reference： [1]Patent: CN108424370,2018,A .Location in patent: Paragraph 0087; 0088

87
[ 3470-54-0 ]
[ 34619-03-9 ]
[ 1116358-96-3 ]

Yield	Reaction Conditions	Operation in experiment
7.45 g	In toluene; at 90℃; for 24h;	5-Amino-1-indanone () (5.00 g) was suspended in toluene (50 mL), and bis(2-methyl-2-propanyl)carbonate (16.31 g) () was added thereto, followed by stirring at 90 C for 14 hours. To the reaction mixture, bis(2-methyl-2-propanyl)carbonate (16.31 g) was added, followed by stirring at 90C for 10 hours. The reaction mixture was concentrated under reduced pressure, and hexane was added to the resulting residue, and then, the solid was collected by filtration, whereby the title compound having the following physical property values was obtained (7.45 g). TLC: Rf 0.76 (hexane:ethyl acetate = 1:1); 1H-NMR (CDCl3): delta 1.54, 2.65-2.66, 3.08-3.11, 6.73, 7.10-7.13, 7.66-7.69, 7.75.

Reference： [1]Patent: EP3447045,2019,A1 .Location in patent: Paragraph 0209

88
[ 19798-81-3 ]
[ 34619-03-9 ]
[ 344331-90-4 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; at 20℃;	Di-tert-butyldicarbonate (Boc anhydride) (2 eq) was added to a solution of 6-bromopyridine-2-amine of Formula (XII) and triethyl amine (2 M. eq.) in MDC (5 vol.). The resulting mixture was then stirred at ambient temperature. After reaction complies water was added and the product was extracted with organic layer. The organic layers were dried over anhydrous MgSO4 and evaporated under vacuum to give compound of Formula (XIII).

Reference： [1]Patent: US2020/62744,2020,A1 .Location in patent: Paragraph 0090-0091

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	34619-03-9	MDL No. :	MFCD14560560
Formula :	C₉H₁₈O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ODCCJTMPMUFERV-UHFFFAOYSA-N
M.W :	174.24	Pubchem ID :	10219638
Synonyms :

Num. heavy atoms :	12
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.89
Num. rotatable bonds :	4
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	48.21
TPSA :	35.53 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.59 cm/s

Log Po/w (iLOGP) :	2.99
Log Po/w (XLOGP3) :	2.49
Log Po/w (WLOGP) :	2.74
Log Po/w (MLOGP) :	1.8
Log Po/w (SILICOS-IT) :	1.31
Consensus Log Po/w :	2.27

[ CAS No. 34619-03-9 ] {[proInfo.proName]}

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[ 34619-03-9 ] Synthesis Path-Downstream 1~88

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

Log S (ESOL) :	-2.22
Solubility :	1.04 mg/ml ; 0.00596 mol/l
Class :	Soluble
Log S (Ali) :	-2.88
Solubility :	0.229 mg/ml ; 0.00131 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.73
Solubility :	3.27 mg/ml ; 0.0187 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.13

Signal Word:	Warning	Class:
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338	UN#:
Hazard Statements:	H302-H315-H319-H335	Packing Group:
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