Pyrazole → HCID 178524326, 화합물

HRID 1093744노트

반응식

HRID 1093744 반응식
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]

참가 물질

6

반응물 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

생성물 1

HCID 178524326HCID 178524326, 화합물수율 48.4%

시약·촉매·용매 1

HCID 21892291Methanol tetrahydrofuran water용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-63c0970b568b4603807751c62b2f9cda
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129376B2

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