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

HRID 592342노트

반응식

HRID 592342 반응식
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

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 3007855Zincchloride촉매HCID 111,2-Dichloroethane용매HCID 6386tert-Butanol용매

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-a5bd20942bdc4285a46639e9bfb4d746
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238644B2

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