Potassium Carbonate → 4-((3-((4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)carbamoyl)benzyl)thio)benzoic acid

HRID 926892노트

반응식

HRID 926892 반응식
Cl[CH2:2][C:3]1[CH:4]=[C:5]([CH:39]=[CH:40][CH:41]=1)[C:6]([NH:8][C:9]1[CH:32]=[CH:31][C:30]([N:33]2[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]2)=[CH:29][C:10]=1[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)[N:15]=1)=[O:12])=[O:7].[SH:42][C:43]1[CH:51]=[CH:50][C:46]([C:47]([OH:49])=[O:48])=[CH:45][CH:44]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[N:33]1([C:30]2[CH:31]=[CH:32][C:9]([NH:8][C:6]([C:5]3[CH:4]=[C:3]([CH:41]=[CH:40][CH:39]=3)[CH2:2][S:42][C:43]3[CH:51]=[CH:50][C:46]([C:47]([OH:49])=[O:48])=[CH:45][CH:44]=3)=[O:7])=[C:10]([C:11](=[O:12])[NH:13][C:14]3[CH:18]=[CH:17][N:16]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:27])([F:28])[F:26])[CH:20]=4)[N:15]=3)[CH:29]=2)[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]1

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 957384-Mercaptobenzoic acidHCID 665882652-(3-(chloromethyl)benzamido)-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide

생성물 1

HCID 566443444-((3-((4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)carbamoyl)benzyl)thio)benzoic acid수율 83.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

Into a round bottom flask was placed a solution of intermediate 21a (0.0580 mmol, 1 equiv), 4-mercaptobenzoic acid (11 mg, 0.0696 mmol, 1.2 equiv), potassium carbonate (24 mg, 3 equiv), and DMF (1 mL). The solution was stirred at room temperature overnight. The solvent was evaporated at reduced pressure and the residue was partitioned between dichloromethane and water. The organic phase was dried (Na2SO4). The solvent was evaporated and the residue was purified by reverse phase HPLC eluting with 0.05% TFA in a water/acetonitrile gradient to give 34 mg of product. 1H-NMR (400 MHz, DMSO, ppm): δ 11.55(s, 1H), 11.48(s, 1H), 8.67(d, J=2.6 Hz, 1H), 8.32(d, J=8.3 Hz, 1H), 8.19(S, 1H), 8.16(d, J=7.8 Hz, 1H), 8.01(s, 1H), 7.85-7.71(m, 5H), 7.65(d, J=7.5 Hz, 3H), 7.52(t, J=7.7 Hz, 1H), 7.44(d, J=8.7 Hz, 2H), 7.04(d, J=2.7 Hz, 1H), 4.46(s, 2H), 3.30(s, 4H), 1.70(s, 4H), 1.59(s, 2H). MS (ES, m/z) 700 [M+H]+.

후처리

  1. customInto a round bottom flask was placed
  2. customThe solvent was evaporated at reduced pressure
  3. customthe residue was partitioned between dichloromethane and water
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. customThe solvent was evaporated
  6. customthe residue was purified by reverse phase HPLC
  7. washeluting with 0.05% TFA in a water/acetonitrile gradient

출처 및 근거

ORD 기록
ord-578344074c03493aaede22acae98d217
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09289430B2

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