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

HRID 547832Notes

Reaction equation

HRID 547832 reaction equation
C([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[CH:18][C:17]([N:20]([CH3:40])[C:21](=[O:39])[C:22]([C:25]3[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([C:35]([F:38])([F:37])[F:36])[CH:26]=3)([CH3:24])[CH3:23])=[C:16]([C:41]3[CH:46]=[CH:45][C:44]([F:47])=[CH:43][C:42]=3[CH3:48])[CH:15]=2)[C@H:10]([CH3:49])[CH2:9]1)C1C=CC=CC=1>C(O)(=O)C>[F:38][C:35]([F:36])([F:37])[C:27]1[CH:26]=[C:25]([C:22]([CH3:23])([CH3:24])[C:21]([N:20]([C:17]2[CH:18]=[N:19][C:14]([N:11]3[CH2:12][CH2:13][NH:8][CH2:9][C@H:10]3[CH3:49])=[CH:15][C:16]=2[C:41]2[CH:46]=[CH:45][C:44]([F:47])=[CH:43][C:42]=2[CH3:48])[CH3:40])=[O:39])[CH:30]=[C:29]([C:31]([F:32])([F:33])[F:34])[CH:28]=1

Participants

3

Reactant 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-isobutyramide

Product 1

HCID 86597714(R)-2-(3,5-Bis-trifluoromethyl-phenyl)-N-[4-(4-fluoro-2-methyl-phenyl)-6-(2-methyl-piperazin-1-yl)-pyridin-3-yl]-N-methyl-isobutyramideYield 98%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 0.11 g (0.17 mmol) (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 in 3 ml acetic acid was deoxygenated by three cycles of evacuation and flushing with argon. After addition of 0.02 g palladium on charcoal (10%) the reaction vessel was evacuated and filled with hydrogen gas. The reaction mixture was stirred at room temperature under an atmosphere of hydrogen for 3 h. The reaction mixture was filtered over decalite followed by washing with tert-butyl methyl ether. The filtrate was washed with a 2 M aqueous solution of sodium hydroxide. The aqueous layer was extracted with three portions of tert-butyl methyl ether. The combined organic layers were dried over sodium sulfate and concentrated in vacuo to give 98 mg (98%) of the crude title compound as an off-white solid, which was used in the next step without further purification.

Workup

  1. customflushing with argon
  2. additionAfter addition of 0.02 g palladium on charcoal (10%) the reaction vessel
  3. customwas evacuated
  4. additionfilled with hydrogen gas
  5. filtrationThe reaction mixture was filtered over decalite
  6. washby washing with tert-butyl methyl ether
  7. washThe filtrate was washed with a 2 M aqueous solution of sodium hydroxide
  8. extractionThe aqueous layer was extracted with three portions of tert-butyl methyl ether
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-22d28741b0794ca3a1a3c66976805b4d
Source dataset
uspto-grants-2011_05
Patent number
US07939533B2

Reaction notes

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