Lithium hydroxide, monohydrate → Lithium 2-(2-(2-(2-((4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate

HRID 1485136노트

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HRID 1485136 반응식
O[Li:2].O.C[O:5][C:6](=[O:46])[CH2:7][C:8]1[CH:45]=[CH:44][CH:43]=[CH:42][C:9]=1[CH2:10][CH2:11][C:12]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][N:15]=[C:14]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]3)=[CH:25][CH:24]=2)[N:13]=1>C1COCC1.O.CO>[C:38]([O:37][C:35]([N:32]1[CH2:31][CH2:30][N:29]([C:26]2[CH:27]=[CH:28][C:23]([NH:22][C:14]3[N:13]=[C:12]([CH2:11][CH2:10][C:9]4[CH:42]=[CH:43][CH:44]=[CH:45][C:8]=4[CH2:7][C:6]([O-:46])=[O:5])[C:17]([C:18]([F:19])([F:20])[F:21])=[CH:16][N:15]=3)=[CH:24][CH:25]=2)[CH2:34][CH2:33]1)=[O:36])([CH3:41])([CH3:39])[CH3:40].[Li+:2]

참가 물질

6

반응물 2

HCID 168937Lithium hydroxide, monohydrateHCID 68282913tert-Butyl 4-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate

생성물 1

HCID 68282842Lithium 2-(2-(2-(2-((4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate수율 96%

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매HCID 8028Tetrahydrofuran용매

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온도
40 °C

실험 절차

LiOH.H2O (0.044 g, 1.06 mmol) was added to tert-butyl 4-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate (I6) (0.211 g, 0.352 mmol) in THF (10 mL), water (2.5 mL) and methanol (1 mL). The resulting mixture was allowed to stir for 3 hours at 40° C. The volatiles were removed in vacuo and the residue was diluted with EtOAc (100 mL) and 2 M aq. NaOH (100 mL). The layers were separated and the aqueous layer was extracted with EtOAc (70 mL), the organic layers were combined, washed with brine (100 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give the title compound (I7) (0.195 g, 96% yield) as a yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 10.02 (s, 1H), 8.61 (s, 1H), 7.64-7.55 (m, 2H), 7.26-7.14 (m, 4H), 6.97-6.91 (m, 2H), 3.65 (s, 2H), 3.50-3.41 (m, 4H), 3.10-2.93 (m, 8H), 1.42 (s, 9H). LCMS Method C: rt 6.32 min; m/z 586.3 [M+H]+.

후처리

  1. customThe volatiles were removed in vacuo
  2. additionthe residue was diluted with EtOAc (100 mL) and 2 M aq. NaOH (100 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (70 mL)
  5. washwashed with brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-1bfa8e5896b74bd29b08a35b8261a66c
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09421205B2

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