Potassium Carbonate → methyl (+/-)-6-((cyclopentyl(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methyl)amino)nicotinate

HRID 537571Notes

Reaction equation

HRID 537571 reaction equation
Cl.[CH:2]1([CH:7]([C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([N:16]3[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[N:17]3)=[C:11]([CH3:25])[CH:10]=2)[NH2:8])[CH2:6][CH2:5][CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].F[C:33]1[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][N:34]=1>CN(C)C=O.O>[CH:2]1([CH:7]([NH:8][C:33]2[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][N:34]=2)[C:9]2[CH:10]=[C:11]([CH3:25])[C:12]([N:16]3[CH:20]=[C:19]([C:21]([F:23])([F:24])[F:22])[CH:18]=[N:17]3)=[C:13]([CH3:15])[CH:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 13758765Methyl 6-fluoropyridine-3-carboxylateHCID 68279202(+/-)-cyclopentyl(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methanamine hydrochloride

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of (+/−)-cyclopentyl(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methanamine hydrochloride (1.002 g, 2.680 mmol) and potassium carbonate (1.51 g, 10.7 mmol) in N,N-dimethylformamide (5.36 mL) was added methyl 6-fluoronicotinate (472 mg, 2.95 mmol). The reaction was heated to 85° C. After 15 h, the reaction was cooled to room temperature, diluted with water (50 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. Purification by column chromatography (ethyl acetate/heptane) gave methyl (+/−)-6-((cyclopentyl(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methyl)amino)nicotinate. 1H NMR (400 MHz, CDCl3, δ): 8.67 (d, J=1.6 Hz, 1H), 7.99 (dd, J=9.0, 2.0 Hz, 1H), 7.93 (s, 1H), 7.75 (s, 1H), 7.12 (s, 2H), 6.28 (d, J=9.0 Hz, 1H), 4.43-4.33 (m, 1H), 3.87 (s, 3H), 2.36-2.23 (m, 1H), 2.04-1.97 (m, 7H), 1.77-1.41 (m, 6H), 1.37-1.28 (m, 1H). MS (M+1): 4732.

Workup

  1. temperaturethe reaction was cooled to room temperature
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined organics were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customPurification by column chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-9204f0d0ef3f4a0da4aac4c2fb133d90
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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