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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
ノート
印刷プレビュー

反応式

HRID 1058235 の反応式
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]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-a6ff06d5ad6f41d1851c3c2bd8530a22
出典データセット
uspto-grants-2003_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06515011B2

反応ノート

読み込み中…

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