Potassium Carbonate → HCID 86597699, compound

HRID 547811Notes

Reaction equation

HRID 547811 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.C(=O)([O-])[O-].[K+].[K+].Cl.FC(F)(F)C([NH:48][C@@H:49]1[CH2:53][CH2:52][NH:51][CH2:50]1)=O>CS(C)=O.COC(C)(C)C>[NH2:48][C@@H:49]1[CH2:53][CH2:52][N:51]([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)[CH2:50]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 235027842-(3,5-Bis(trifluoromethyl)phenyl)-N-(6-chloro-4-(4-fluoro-2-methylphenyl)pyrid-3-yl)-N,2-dimethylpropanamideHCID 426145702,2,2-Trifluoro-N-[(3R)-pyrrolidin-3-yl]acetamide--hydrogen chloride (1/1)

Product 1

HCID 86597699HCID 86597699, compoundYield 65.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 939 mg (1.76 mmol) 2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-chloro-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-isobutyramide, 1.22 g (8.81 mmol) potassium carbonate and 770 mg (3.52 mmol) (R)-3-(trifluoro-acetamido)pyrrolidine hydrochloride in 20 ml dimethyl sulfoxide was stirred at 130° C. for 52 h. After cooling to room temperature the reaction mixture was diluted with 30 ml tert-butyl methyl ether and washed with 20 ml of water and 10 ml of a saturated aqueous solution of sodium carbonate. The combined organic layers were dried over sodium sulfate, concentrated and dissolved in 25 ml of a 2 N solution of ammonia in ethanol. The solution was stirred at room temperature for 18 h. The reaction mixture was concentrated and purified by flash chromatography to give 670 mg (65%) of the title compound as a light brown foam.

Workup

  1. temperatureAfter cooling to room temperature the reaction mixture
  2. washwashed with 20 ml of water and 10 ml of a saturated aqueous solution of sodium carbonate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrated
  5. dissolutiondissolved in 25 ml of a 2 N solution of ammonia in ethanol
  6. stirringThe solution was stirred at room temperature for 18 h
  7. concentrationThe reaction mixture was concentrated
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-f0c6b2aa34b24dbdb639fdb36b30ea04
Source dataset
uspto-grants-2011_05
Patent number
US07939533B2

Reaction notes

Loading…