4-Nitrophenyl chloroformate → (R)-tert-Butyl 3-(3-(4-(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazine-1-carbonyl)-2-fluorophenyl)ureido)pyrrolidine-1-carboxylate

HRID 1807760ノート

反応式

HRID 1807760 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])([C:28]([F:31])([F:30])[F:29])[C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[F:40].[C:41](Cl)(=O)[O:42]C1C=CC([N+]([O-])=O)=CC=1.[NH2:54][C@@H:55]1[CH2:59][CH2:58][N:57]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[CH2:56]1>ClCCl>[Si:33]([O:32][C:23]([C:20]1[CH:19]=[CH:18][C:17]([CH2:16][N:13]2[CH2:14][CH2:15][N:10]([C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:41](=[O:42])[NH:54][C@@H:55]4[CH2:59][CH2:58][N:57]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[CH2:56]4)=[C:3]([F:40])[CH:4]=3)=[O:9])[CH2:11][CH2:12]2)=[CH:22][CH:21]=1)([C:24]([F:25])([F:26])[F:27])[C:28]([F:31])([F:29])[F:30])([C:36]([CH3:37])([CH3:39])[CH3:38])([CH3:34])[CH3:35]

参加物

5

反応物 3

HCID 821294-Nitrophenyl chloroformateHCID 854070(R)-(+)-1-Boc-3-aminopyrrolidineHCID 59175907(4-Amino-3-fluorophenyl)(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazin-1-yl)methanone

生成物 1

HCID 59175827(R)-tert-Butyl 3-(3-(4-(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazine-1-carbonyl)-2-fluorophenyl)ureido)pyrrolidine-1-carboxylate収率 55.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A solution of (4-amino-3-fluorophenyl)(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazin-1-yl)methanone (0.674 mmol, 400 mg) and 4-nitrophenyl carbonochloridate (0.674 mmol, 136 mg) in dichloromethane (10 mL) was stirred at room temperature for 30 minutes. (R)-tert-Butyl 3-aminopyrrolidine-1-carboxylate (2.021 mmol, 0.353 mL, 376 mg) was added and the reaction stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane (10 mL) and washed with saturated aqueous sodium hydrogen carbonate solution (10 mL). The organic phase was concentrated and the resulting residue was purified by column chromatography on silica gel (eluting with dichloromethane—5% methanol/95% dichloromethane gradient) to afford the title compound (300 mg).

後処理

  1. washwashed with saturated aqueous sodium hydrogen carbonate solution (10 mL)
  2. concentrationThe organic phase was concentrated
  3. customthe resulting residue was purified by column chromatography on silica gel (eluting with dichloromethane—5% methanol/95% dichloromethane gradient)

出典と根拠

ORDレコード
ord-7115370cfd714b01923d037e302d54c2
出典データセット
uspto-grants-2013_01
特許番号
US08357679B2

反応ノート

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