Tert-butyl 4-(4-((4-((3-(2-methoxy-2-oxoethyl)pyridin-2-yl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate → tert-Butyl 4-(4-((4-(2-(3-(2-methoxy-2-oxoethyl)pyridin-2-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

HRID 1485259ノート

反応式

HRID 1485259 の反応式
[CH3:1][O:2][C:3](=[O:43])[CH2:4][C:5]1[C:6]([C:11]#[C:12][C:13]2[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([CH:30]4[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]4)=[CH:26][CH:25]=3)[N:14]=2)=[N:7][CH:8]=[CH:9][CH:10]=1>CN(C=O)C.[Pd]>[CH3:1][O:2][C:3](=[O:43])[CH2:4][C:5]1[C:6]([CH2:11][CH2:12][C:13]2[C:18]([C:19]([F:22])([F:20])[F:21])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([CH:30]4[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:41])([CH3:40])[CH3:42])=[O:37])[CH2:32][CH2:31]4)=[CH:26][CH:25]=3)[N:14]=2)=[N:7][CH:8]=[CH:9][CH:10]=1

参加物

4

反応物 1

HCID 71209391Tert-butyl 4-(4-((4-((3-(2-methoxy-2-oxoethyl)pyridin-2-yl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

生成物 1

HCID 71208998tert-Butyl 4-(4-((4-(2-(3-(2-methoxy-2-oxoethyl)pyridin-2-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate収率 75%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 6228Dimethylformamide溶媒2 回

実験手順

A solution of tert-butyl 4-(4-((4-((3-(2-methoxy-2-oxoethyl)pyridin-2-yl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I121) (81.5 mg, 0.137 mmol) in DMF (10 mL) was added to a solution of 10% Pd/C (170 mg) in DMF (7 mL). The reaction was stirred at room temperature for 24 hours under an atmosphere of hydrogen. The reaction was filtered through a pad of celite, washing with EtOAc (100 mL). The solvent was removed in vacuo to afford an oil which was purified on by column chromatography on silica gel (0-40% EtOAc in petroleum benzine 40-60° C.) to yield the title compound (I122) (61.4 mg, 75%) as a viscous oil; 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 8.46 (dd, J=4.8, 1.7 Hz, 1H), 7.56-7.50 (m, 3H), 7.49 (s, 1H), 7.19-7.14 (m, 2H), 7.12 (dd, J=7.7, 4.8 Hz, 1H), 4.23 (bs, 2H), 3.72 (s, 2H), 3.70 (s, 3H), 3.40-3.33 (m, 2H), 3.32-3.23 (m, 2H), 2.80 (t, J=12.1 Hz, 2H), 2.62 (tt, J=12.1, 3.5 Hz, 1H), 1.81 (d, J=12.9 Hz, 2H), 1.65-1.55 (m, 2H), 1.48 (s, 9H). LCMS Method C: rt 6.01 min; m/z 622 [M+Na]+, 600 [M+H]+, 544 [M-tButyl+2H]+.

後処理

  1. filtrationThe reaction was filtered through a pad of celite
  2. washwashing with EtOAc (100 mL)
  3. customThe solvent was removed in vacuo
  4. customto afford an oil which
  5. customwas purified on by column chromatography on silica gel (0-40% EtOAc in petroleum benzine 40-60° C.)

出典と根拠

ORDレコード
ord-73f56da3a32f45d298fadcfc3abba696
出典データセット
uspto-grants-2016_08
特許番号
US09421205B2

反応ノート

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