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

HRID 1058237
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HRID 1058237 반응식
C(Cl)CCl.[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([CH:21]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[CH:22]([F:24])[F:23])=[C:10]([CH:20]=1)[CH2:11][NH:12][C:13](=[O:19])[C@@H:14]1[CH2:18][CH2:17][CH2:16][NH:15]1.[C:34](O)(=[O:43])[C@@H:35]([CH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1)[OH:36].C1C=NC2N(O)N=NC=2C=1>CN(C=O)C>[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([CH:21]([NH:25][C:26]2[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=2)[CH:22]([F:24])[F:23])=[C:10]([CH:20]=1)[CH2:11][NH:12][C:13](=[O:19])[C@@H:14]1[CH2:18][CH2:17][CH2:16][N:15]1[C:34](=[O:43])[C@@H:35]([CH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1)[OH:36]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 819914(2R)-2-cyclohexyl-2-hydroxyacetic acidHCID 69939410N-(5-Chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}benzyl)-L-prolinamide

생성물 1

HCID 69937977N-(5-chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}benzyl)-1-[(2R)-2-cyclohexyl-2-hydroxyethanoyl]-L-prolinamide수율 36.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

EDC (0.0469 g, 0.24 mmol was added to a stirred mixture of N-(5-chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}benzyl)-L-prolinamide (0.0691 g, 0.16 mmol), (R)-hexahydromandelic acid (0.0258 g, 0.16 mmol) and HOAT (0.0111 g, 0.08 mmol) in DMF (2.0 mL). After 2 h the mixture was partitioned between EtOAc and water. The organic layer was washed with brine, dried (Na2SO4) and evaporated in vacuo and the residue was purified by flash column chromatography on silica (eluting with 5% methylene chloride, 10-70% ethyl acetate/hexanes gradient) to give N-(5-chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}benzyl)-1-[(2R)-2-cyclohexyl-2-hydroxyethanoyl]-L-prolinamide (0.0332 g) as a white solid; LC-MS m/z=564.4.

후처리

  1. customAfter 2 h the mixture was partitioned between EtOAc and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried (Na2SO4)
  4. customevaporated in vacuo
  5. customthe residue was purified by flash column chromatography on silica (eluting with 5% methylene chloride, 10-70% ethyl acetate/hexanes gradient)

출처 및 근거

ORD 기록
ord-d9e1fa7738b34fea994409aae23b1568
출처 데이터셋
uspto-grants-2003_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06515011B2

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