Pyrazole → HCID 178524326, compound

HRID 1093744Notes

Reaction equation

HRID 1093744 reaction equation
O[Li].O.C[O:5][C:6](=[O:41])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2[CH:17]=[C:16]([C:18](=[O:40])[NH:19][CH2:20][C:21](=[O:39])[N:22]3[CH2:27][CH2:26][CH:25]([O:28][C:29]4[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=4)[CH2:24][CH2:23]3)[NH:15][N:14]=2)[CH:8]=1.C(C1C=C(C=CC=1)C(OC)=O)(=O)C.N1C=CC=N1>C1COCC1.CO.O>[O:39]=[C:21]([N:22]1[CH2:23][CH2:24][CH:25]([O:28][C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:36])([F:37])[F:38])[CH:30]=2)[CH2:26][CH2:27]1)[CH2:20][NH:19][C:18]([C:16]1[CH:17]=[C:13]([C:9]2[CH:8]=[C:7]([CH:12]=[CH:11][CH:10]=2)[C:6]([OH:41])=[O:5])[NH:14][N:15]=1)=[O:40]

Participants

6

Reactant 4

HCID 1048PyrazoleHCID 168937Lithium hydroxide, monohydrateHCID 15094405Methyl 3-acetylbenzoateHCID 665915813-(5-{2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethylcarbamoyl}-1H-pyrazol-3-yl)-benzoic acid methyl ester

Product 1

HCID 178524326HCID 178524326, compoundYield 48.4%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

LiOH.H2O (32 mg, 0.76 mmol) was added to a stirred mixture of 3-(5-{2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethylcarbamoyl}-1H-pyrazol-3-yl)-benzoic acid methyl ester (99 mg, 0.2 mmol) (prepared by the method used for the synthesis of Example 102, starting, alternatively from methyl 3-acetylbenzoate to generate the 1H-pyrazole intermediate) in THF:MeOH:H2O (3:2:1, 38 mL) was added, and the resulting mixture was stirred at ambient temperature overnight. The reaction mixture was concentrated under reduced pressure Cold water was then added and the contents were acidified with 10% aqueous HCl, the precipitate was filtered. The solid obtained was purified by recrystallisation form methanol to afford 50 mg (38.1% Yield) of 3-(5-{2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethylcarbamoyl}-2H-pyrazol-3-yl)-benzoic acid. LC/MS [M+H]+: 517, 95.29%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 13.2 (s, 1H), 8.38 (s, 1H), 8.04 (d, 1H), 7.9 (d, 1H), 7.5 (m, 2H), 7.26 (t, 3H), 7.18 (bs, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.4 (m, 2H), 1.9 (m, 2H), 1.6 (m, 2H).

Workup

  1. customprepared by the method
  2. customused for the synthesis of Example 102
  3. additionwas added
  4. concentrationThe reaction mixture was concentrated under reduced pressure Cold water
  5. additionwas then added
  6. filtrationthe precipitate was filtered
  7. customThe solid obtained
  8. customwas purified by recrystallisation
  9. customform methanol

Sources & evidence

ORD record
ord-63c0970b568b4603807751c62b2f9cda
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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