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1,2-Dichloroethane → N-(5-chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}benzyl)-1-(tert-butoxycarbonyl)-L-prolinamide

HRID 1058235
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HRID 1058235 반응식
C(Cl)CCl.[NH2:5][CH2:6][C:7]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:8]=1[CH:14]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1)[CH:15]([F:17])[F:16].[C:27]([N:34]1[CH2:41][CH2:40][CH2:39][C@H:35]1[C:36](O)=[O:37])([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].C1C=NC2N(O)N=NC=2C=1>CN(C=O)C>[Cl:13][C:11]1[CH:10]=[CH:9][C:8]([CH:14]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=2)[CH:15]([F:17])[F:16])=[C:7]([CH:12]=1)[CH2:6][NH:5][C:36](=[O:37])[C@@H:35]1[CH2:39][CH2:40][CH2:41][N:34]1[C:27]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:28]
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참가 물질

6

반응물 4

HCID 111,2-DichloroethaneHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 181649HOAtHCID 18672348N-{1-[2-(aminomethyl)-4-chlorophenyl]-2,2-difluoroethyl}-N-(4-methoxyphenyl)amine

생성물 1

HCID 69939286N-(5-chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}benzyl)-1-(tert-butoxycarbonyl)-L-prolinamide수율 50.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

EDC (0.171 g, 1.25 mmol) was added to a stirred mixture of N-{1-[2-(aminomethyl)-4-chlorophenyl]-2,2-difluoroethyl}-N-(4-methoxyphenyl)amine (0.314 g, 0.96 mmol), N-BOC-L-proline (0.207 g, 0.96 mmol) and HOAT (0.171, 1.25 mmol) in DMF (2.0 mL). After 18 h the mixture was partitioned between EtOAc and water. The organic layer was washed with 1M citric acid, saturated aqueous NaHCO3 and brine, dried (Na2SO4) and reduced in vacuo and the residue was purified by flash column chromatography on silica (eluting with 5% methylene chloride, 10-50% ethyl acetate/hexanes gradient) to give N-(5-chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}benzyl)-1-(tert-butoxycarbonyl)-L-prolinamide (0.256 g) as a foam; LC-MS m/z=524.3.

후처리

  1. customAfter 18 h the mixture was partitioned between EtOAc and water
  2. washThe organic layer was washed with 1M citric acid, saturated aqueous NaHCO3 and brine
  3. dry with materialdried (Na2SO4)
  4. customthe residue was purified by flash column chromatography on silica (eluting with 5% methylene chloride, 10-50% ethyl acetate/hexanes gradient)

출처 및 근거

ORD 기록
ord-a6ff06d5ad6f41d1851c3c2bd8530a22
출처 데이터셋
uspto-grants-2003_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06515011B2

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