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 403364Notes

Reaction equation

HRID 403364 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-910e19e53d464718a1ec0f56c1df0caa
Source dataset
uspto-grants-2014_06
Patent number
US08748432B2

Reaction notes

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