Water → Tert-butyl 4-azido-5-hydroxyazepane-1-carboxylate

HRID 1244305노트

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HRID 1244305 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH:13]2[CH:11]([O:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[Cl-].[NH4+].[N-:19]=[N+:20]=[N-:21].[Na+]>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH:13]([OH:12])[CH:11]([N:19]=[N+:20]=[N-:21])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

6

반응물 4

HCID 962WaterHCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 58717040Tert-butyl 8-oxa-4-azabicyclo[5.1.0]octane-4-carboxylate

생성물 1

HCID 58717042Tert-butyl 4-azido-5-hydroxyazepane-1-carboxylate

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
75 °C

실험 절차

According to scheme 10, to a stirred solution of 2,3,6,7-tetrahydro-azepine-1-carboxylic acid tert-butyl ester (XXX) in dichloromethane was added at −60° C. m-chloroperbenzoic acid (MCPBA). The mixture was allowed to slowly warm to room temperature overnight and 8-oxa-4-aza-bicyclo[5.1.0]octane-4-carboxylic acid tert-butyl ester (XXXI) was obtained. To a solution of 8-oxa-4-aza-bicyclo[5.1.0]octane-4-carboxylic acid tert-butyl ester in ethanol was added water, ammonium chloride and sodium azide. The mixture was stirred at 75° C. over night, to give 4-azido-5-hydroxy-azepane-1-carboxylic acid tert-butyl ester (XXXII). 4-Azido-5-hydroxy-azepane-1-carboxylic acid tert-butyl ester in methanol was hydrogenated in the presence of palladium on charcoal (10%) to yield 4-amino-5-hydroxy-azepane-1-carboxylic acid tert-butyl ester (XXXIII). 4-Methoxy-7-morpholin-4-yl-benzothiazole-2-carboxylic acid and 1,1′-carbonyl-diimidazole in dimethylformamide are stirred at room temperature for about 16 hours. 4-Amino-5-hydroxy-azepane-1-carboxylic acid tert-butyl ester was added and stirring was continued for 16 hours at room temperature. It was obtained 4-hydroxy-5-[(4-methoxy-7-morpholin-4-yl-benzothiazole-2-carbonyl)-amino]-azepane-1-carboxylic acid tert-butyl ester (XXXIV). To a solution of 4-hydroxy-5-[(4-methoxy-7-morpholin-4-yl-benzothiazole-2-carbonyl)-amino]-azepane-1-carboxylic acid tert-butyl ester in dimethylsulfoxide was added triethylamine, dichloromethane and a solution of sulfur trioxide pyridine complex in dimethylsulfoxide. The mixture was stirred for 18 hours at room temperature. After purification 4-[(4-methoxy-7-morpholin-4-yl-benzothiazole-2-carbonyl)-amino]-5-oxo-azepane-1-carboxylic acid tert-butyl ester (VIII) was obtained.

출처 및 근거

ORD 기록
ord-aaeb1797619f4232b140e28ea016180d
출처 데이터셋
uspto-grants-2006_10
특허 번호
US07122545B2

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