Triethylamine → tert-Butyl 4-(5-((4-(2-(1-(methoxycarbonyl)cyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

HRID 592373ノート

反応式

HRID 592373 の反応式
[CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]#[C:15][C:16]2[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]3[CH:28]=[CH:29][C:30]([CH:33]4[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]4)=[N:31][CH:32]=3)[N:17]=2)[CH2:7][CH2:6]1)=[O:4].CCN(CC)CC>CN(C=O)C.CCOC(C)=O.[Pd]>[CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[CH2:14][CH2:15][C:16]2[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]3[CH:28]=[CH:29][C:30]([CH:33]4[CH2:34][CH2:35][N:36]([C:39]([O:41][C:42]([CH3:44])([CH3:45])[CH3:43])=[O:40])[CH2:37][CH2:38]4)=[N:31][CH:32]=3)[N:17]=2)[CH2:7][CH2:6]1)=[O:4]

参加物

6

反応物 2

HCID 8471TriethylamineHCID 86712291tert-Butyl 4-(5-((4-((2-(1-(methoxycarbonyl)cyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

生成物 1

HCID 86712292tert-Butyl 4-(5-((4-(2-(1-(methoxycarbonyl)cyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

試薬・触媒・溶媒 3

HCID 23938Palladium触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A suspension of tert-butyl 4-(5-((4-((2-(1-(methoxycarbonyl)cyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate (A10) (134 mg, 0.216 mmol), 10% Pd/C (100 mg) and Et3N (1.0 mL) in DMF (10 mL) was stirred under an atmosphere of hydrogen for 16 hours. The resulting mixture was diluted with EtOAc (60 mL) and filtered through Celite. The filtrate was evaporated in vacuo and the resulting residue was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 10-50% EtOAc in petroleum benzine 40-60° C.) to give the title compound A11 as a colourless oil (117 mg, 87%); 1H NMR (400 MHz, CDCl3) δ 8.65 (d, J=2.6 Hz, 1H), 8.57 (s, 1H), 8.15 (dd, J=8.5, 2.7 Hz, 1H), 7.45 (s, 1H), 7.34-7.27 (m, 3H), 7.24-7.15 (m, 2H), 4.26 (s, 2H), 3.60 (s, 3H), 3.22-3.07 (m, 4H), 2.92-2.76 (m, 3H), 1.92 (d, J=11.4 Hz, 2H), 1.79-1.65 (m, 4H), 1.48 (s, 9H), 1.22-1.18 (m, 2H). LCMS-A: rt 5.971 min; m/z 626 [M+H]+.

後処理

  1. filtrationfiltered through Celite
  2. customThe filtrate was evaporated in vacuo
  3. custompurified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 10-50% EtOAc in petroleum benzine 40-60° C.)

出典と根拠

ORDレコード
ord-ecf8b0827de241d7b5c68c0c416e26fb
出典データセット
uspto-grants-2016_01
特許番号
US09238644B2

反応ノート

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