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 926892Notizen

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Reaktionsgleichung von HRID 926892
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

Komponenten

5

Edukt 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

Produkt 1

HCID 566443444-((3-((4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)carbamoyl)benzyl)thio)benzoic acidAusbeute 83,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

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]+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-578344074c03493aaede22acae98d217
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09289430B2

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