Diethyl Ether → Tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

HRID 592342ノート

反応式

HRID 592342 の反応式
Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.CCOCC.[C:18]([N:25]1[CH2:30][CH2:29][CH:28]([C:31]2[CH:36]=[CH:35][C:34]([NH2:37])=[CH:33][CH:32]=2)[CH2:27][CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].CCN(CC)CC>[Cl-].[Cl-].[Zn+2].ClCCCl.CC(O)(C)C>[Cl:8][C:6]1[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=[C:2]([NH:37][C:34]2[CH:35]=[CH:36][C:31]([CH:28]3[CH2:27][CH2:26][N:25]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:30][CH2:29]3)=[CH:32][CH:33]=2)[N:7]=1

参加物

8

反応物 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 21940085tert-Butyl 4-(4-aminophenyl)piperidine-1-carboxylate

生成物 1

HCID 86675716Tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

試薬・触媒・溶媒 3

HCID 3007855Zincchloride触媒HCID 111,2-Dichloroethane溶媒HCID 6386tert-Butanol溶媒

実験手順

2,4-Dichloro-5-(trifluoromethyl)pyrimidine (4.122 g, 19.00 mmol) was stirred in a 1:1 t-BuOH:DCE mixture (400 mL) at room temperature. A 1.0 M ZnCl2 solution in Et2O (21.71 mL, 21.71 mmol) was added cautiously and the resulting mixture was stirred for 10 minutes. 1-Boc-4-(4-aminophenyl)piperidine (5.00 g, 18.1 mmol) was added followed by Et3N (6.052 mL, 43.42 mmol) and stirring continued at room temperature overnight. The volatiles were evaporated to dryness and the resulting residue was suspended in water (500 mL). After sonication for 30 minutes the suspension was filtered and the filter cake was washed with water (2×100 mL) and dried under a high vacuum to yield the title compound K3 as a tan solid (8.11 g, 98%); 1H NMR (400 MHz, d6-DMSO) δ 10.61 (s, 1H), 8.78 (s, 1H), 7.59 (d, J=8.4 Hz, 2H), 7.23 (d, J=8.5 Hz, 2H), 4.07 (d, J=11.1 Hz, 2H), 2.80 (s, 2H), 2.65 (t, J=12.0 Hz, 1H), 1.74 (d, J=12.3 Hz, 2H), 1.42 (s, 11H). LCMS-A: rt 6.834 min; m/z 457 [M+H]+.

後処理

  1. customat room temperature
  2. stirringstirring
  3. waitcontinued at room temperature overnight
  4. customThe volatiles were evaporated to dryness
  5. customAfter sonication for 30 minutes the suspension
  6. filtrationwas filtered
  7. washthe filter cake was washed with water (2×100 mL)
  8. customdried under a high vacuum

出典と根拠

ORDレコード
ord-a5bd20942bdc4285a46639e9bfb4d746
出典データセット
uspto-grants-2016_01
特許番号
US09238644B2

反応ノート

読み込み中…