1,1'-Carbonyldiimidazole → 3-chloro-2-hydroxy-N-(3-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-phenyl)-benzamide

HRID 403364노트

반응식

HRID 403364 반응식
[Cl:1][C:2]1[C:3]([OH:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=O.C1N=CN(C(N2C=NC=C2)=O)C=1.[NH2:24][C:25]1[CH:26]=[C:27]([CH:31]2[CH2:36][CH2:35][N:34]([C:37](=[O:49])[CH2:38][N:39]3[C:43]([CH3:44])=[CH:42][C:41]([C:45]([F:48])([F:47])[F:46])=[N:40]3)[CH2:33][CH2:32]2)[CH:28]=[CH:29][CH:30]=1.N1(C2CCCCCCCCCC2)CCCN=CCCCCC1>C(#N)C>[Cl:1][C:2]1[C:3]([OH:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH:31]2[CH2:32][CH2:33][N:34]([C:37](=[O:49])[CH2:38][N:39]3[C:43]([CH3:44])=[CH:42][C:41]([C:45]([F:48])([F:47])[F:46])=[N:40]3)[CH2:35][CH2:36]2)[CH:26]=1)=[O:7]

참가 물질

6

반응물 4

HCID 682631,1'-CarbonyldiimidazoleHCID 745853-Chlorosalicylic acidHCID 682800461-[4-(3-Amino-phenyl)-piperidin-1-yl]-2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethanoneHCID 1296629601,8-Diazabicycloundec-7ene

생성물 1

HCID 601424163-chloro-2-hydroxy-N-(3-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-phenyl)-benzamide

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
60 °C

실험 절차

To a solution of 3-chloro-2-hydroxy-benzoic acid (0.11 g, 0.65 mmol) in acetonitrile (10 mL) is added carbodiimidazole (0.11 g, 0.71 mmol). After stirring the reaction mixture at 60° C. for 2 h, 1-[4-(3-amino-phenyl)-piperidin-1-yl]-2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethanone (0.20 g, 055 mmol) is added, followed by 1,8-diazabicycloundec-7-ene (0.1 mL, 0.82 mmol). After stirring overnight at 60° C., the reaction mixture is cooled down to RT and then solvent is evaporated and the resulting yellow oil is dissolved in ethylacetate (20 mL), washed with saturated aqueous sodium bicarbonate solution (20 mL), 1N HCl (20 mL) and brine (20 mL). The organic layer is dried over sodium sulfate, filtered, and evaporated under reduced pressure. Cyclohexane is added dropwise to a solution of crude mixture in 1 mL ethylacetate to give after filtration 3-chloro-2-hydroxy-N-(3-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-phenyl)-benzamide (Compound No. I.u.003) (0.148 g, 43%). 1H-NMR (400 MHz, MeOD): δ=1.61-1.76 (m, 1H), 1.77-1.90 (m, 1H), 1.92-2.03 (m, 2H), 2.33 (s, 3H), 2.81-2.99 (m, 2H), 3.31-3.41 (m, 1H), 4.09-4.16 (m, 1H), 4.61-4.70 (m, 1H), 5.62-5.81 (q, 2H), 6.45 (s, 1H), 6.95-7.01 (t, 1H), 7.11-7.18 (m, 1H), 7.33-7.39 (t, 1H), 7.51-7.60 (m, 2H), 7.63 (s, 1H), 7.91-7.92 (m, 1H). MS: m/z=521 (M+1).

후처리

  1. stirringAfter stirring overnight at 60° C.
  2. temperaturethe reaction mixture is cooled down to RT
  3. customsolvent is evaporated
  4. dissolutionthe resulting yellow oil is dissolved in ethylacetate (20 mL)
  5. washwashed with saturated aqueous sodium bicarbonate solution (20 mL), 1N HCl (20 mL) and brine (20 mL)
  6. dry with materialThe organic layer is dried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. additionCyclohexane is added dropwise to a solution of crude mixture in 1 mL ethylacetate
  10. customto give
  11. filtrationafter filtration 3-chloro-2-hydroxy-N-(3-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-phenyl)-benzamide (Compound No

출처 및 근거

ORD 기록
ord-910e19e53d464718a1ec0f56c1df0caa
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08748432B2

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