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

HRID 592373노트

반응식

HRID 592373 반응식
[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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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]+.

후처리

  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.)

출처 및 근거

ORD 기록
ord-ecf8b0827de241d7b5c68c0c416e26fb
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238644B2

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