Sodium Hydroxide → (R)-N-[6-(4-Benzyl-2-methyl-piperazin-1-yl)-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-isobutyramide

HRID 1951739Notes

Reaction equation

HRID 1951739 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]([CH3:34])([CH3:33])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21](Cl)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH2:37]([N:44]1[CH2:49][CH2:48][NH:47][C@H:46]([CH3:50])[CH2:45]1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.[OH-].[Na+]>[Br-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.C1(C)C=CC=CC=1>[CH2:37]([N:44]1[CH2:49][CH2:48][N:47]([C:21]2[N:20]=[CH:19][C:18]([N:16]([CH3:17])[C:14](=[O:15])[C:13]([C:5]3[CH:4]=[C:3]([C:2]([F:36])([F:35])[F:1])[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=3)([CH3:34])[CH3:33])=[C:23]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=3[CH3:31])[CH:22]=2)[C@H:46]([CH3:50])[CH2:45]1)[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 6923226(R)-1-Benzyl-3-methylpiperazineHCID 235027842-(3,5-Bis(trifluoromethyl)phenyl)-N-(6-chloro-4-(4-fluoro-2-methylphenyl)pyrid-3-yl)-N,2-dimethylpropanamide

Product 1

HCID 86597713(R)-N-[6-(4-Benzyl-2-methyl-piperazin-1-yl)-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-isobutyramideYield 37%

Reagents, catalysts & solvents 3

HCID 5974Hexadecyltrimethylammonium BromideCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 0.20 g (0.38 mmol) 2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-chloro-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-isobutyramide, 93 mg (0.49 mmol) (R)-1-benzyl-3-methyl-piperazine, 0.01 g (0.03 mmol) cetyltrimethyl-ammonium bromide, 0.038 g (0.074 mmol) bis(tri-t-butylphosphine)palladium(0), 0.05 ml NaOH 50% and 2 ml toluene was degassed by two freeze-thaw cycles. The reaction mixture was heated under argon at 90° C. for 48 h. After cooling to room temperature the mixture was diluted with water and brine and extracted with three portions of tert-butyl methyl ether. The combined organic layers were dried over sodium sulphate and concentrated in vacuo. Flash column chromatography gave 95 mg (37%) of the title compound as a light yellow solid. MS m/e (%): 687 (M+H+, 100)

Workup

  1. customwas degassed by two freeze-thaw cycles
  2. temperatureAfter cooling to room temperature the mixture
  3. additionwas diluted with water and brine
  4. extractionextracted with three portions of tert-butyl methyl ether
  5. dry with materialThe combined organic layers were dried over sodium sulphate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1d98c958849141669446ff7de1bfc7ed
Source dataset
uspto-grants-2013_03
Patent number
US08404708B2

Reaction notes

Loading…