Sodium Hydroxide → (+/-)-6-((cyclopentyl(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methyl)amino)nicotinic acid

HRID 1892790Notes

Reaction equation

HRID 1892790 reaction equation
[CH:1]1([CH:6]([NH:24][C:25]2[CH:34]=[CH:33][C:28]([C:29]([O:31]C)=[O:30])=[CH:27][N:26]=2)[C:7]2[CH:12]=[C:11]([CH3:13])[C:10]([N:14]3[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[N:15]3)=[C:9]([CH3:23])[CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+]>O1CCCC1.CO>[CH:1]1([CH:6]([NH:24][C:25]2[CH:34]=[CH:33][C:28]([C:29]([OH:31])=[O:30])=[CH:27][N:26]=2)[C:7]2[CH:8]=[C:9]([CH3:23])[C:10]([N:14]3[CH:18]=[C:17]([C:19]([F:21])([F:22])[F:20])[CH:16]=[N:15]3)=[C:11]([CH3:13])[CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 68178658methyl (+/-)-6-((cyclopentyl(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methyl)amino)nicotinate

Product 1

HCID 68178659(+/-)-6-((cyclopentyl(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methyl)amino)nicotinic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl (+/−)-6-((cyclopentyl(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methyl)amino)nicotinate (753 mg, 1.59 mmol) in tetrahydrofuran (7.97 mL) and methanol (7.97 mL) was added 1 N aq sodium hydroxide (7.97 mL, 7.97 mmol). After 16 h, the solution was concentrated under reduced pressure to remove tetrahydrofuran and methanol. 1 N aq hydrochloric acid was added until the mixture was at pH 4. The mixture was diluted with sat. aq sodium chloride (30 mL) and extracted with ethyl acetate (3×50 mL). The combined organics were dried (Na2SO4) and filtered, and the filtrate was concentrated under reduced pressure to provide (+/−)-6-((cyclopentyl(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methyl)amino)nicotinic acid. 1H NMR (400 MHz, CDCl3, δ): 8.68 (s, 1H), 8.14 (d, J=9.2 Hz, 1H), 7.94 (s, 1H), 7.75 (s, 1H), 7.15 (s, 2H), 6.39 (d, J=9.2 Hz, 1H), 4.28-4.18 (m, 1H), 2.44-2.31 (m, 1H), 2.12-2.05 (m, 1H), 2.01 (s, 6H), 1.78-1.40 (m, 6H), 1.36-1.28 (m, 1H). MS (M+1): 459.5.

Workup

  1. concentrationthe solution was concentrated under reduced pressure
  2. customto remove tetrahydrofuran and methanol
  3. addition1 N aq hydrochloric acid was added until the mixture
  4. additionThe mixture was diluted with sat. aq sodium chloride (30 mL)
  5. extractionextracted with ethyl acetate (3×50 mL)
  6. dry with materialThe combined organics were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-6c6e781b2b4b41239f01ce813807e6d6
Source dataset
uspto-grants-2013_08
Patent number
US08507533B2

Reaction notes

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