Water → (R)-5-Methyl-N-{5-methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridin-3-yl}-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide

HRID 1748625Notes

Reaction equation

HRID 1748625 reaction equation
S(Cl)(Cl)=O.[CH3:5][N:6]([CH3:9])C=O.[CH3:10][C:11]1[N:15]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][N:17]=2)[N:14]=[CH:13][C:12]=1[C:26]([OH:28])=O.[CH2:29]([N:31]([CH2:34][CH3:35])[CH2:32][CH3:33])[CH3:30].[OH2:36]>C1(C)C=CC=CC=1>[CH3:10][C:11]1[N:15]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:23])([F:24])[F:25])=[CH:18][N:17]=2)[N:14]=[CH:13][C:12]=1[C:26]([NH:14][C:13]1[CH:5]=[N:6][C:9]([C:19]2[CH2:20][CH2:21][C@@H:29]([N:31]3[CH2:34][CH2:35][O:36][CH2:33][CH2:32]3)[CH2:30][CH:18]=2)=[C:11]([CH3:10])[CH:12]=1)=[O:28]

Participants

7

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 162278455-methyl-1-(5-(trifluoromethyl)pyridin-2-yl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 72700481(R)-5-Methyl-N-{5-methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridin-3-yl}-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Thionyl chloride (6.6 ml) and N,N-dimethylformamide (catalytic amounts) were added at room temperature to a solution of 5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxylic acid (8.17 g) described in Reference Example 8 in toluene (150 ml), and stirred at 80° C. for an hour. The solvent and an excess amount of thionyl chloride were evaporated. Pyridine (200 ml) was added to the resulting reaction mixture, and a pyridine (250 ml) solution of (R)-5-methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridine-3-amine (7.5 g), which was derived from the first peak fractions when 5-methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridine-3-amine of Reference Example 108 was optically fractionated with a chiral column, was added and stirred at 50° C. for two hours. After the reaction, the reaction solution was left stand, triethylamine and water were added and the precipitate was filtered. The resulting solid was dissolved in acetic acid (7.5 ml), water (7.5 ml) and ethanol (750 ml), activated charcoal was added and stirred at 40° C. for an hour. The mixture was filtered through Celite, pH was adjusted to 8 by the addition of 1N aqueous solution of sodium hydroxide and the precipitate was collected by filtration. The resulting solid was washed with water and dried at 60° C. under current of air to give the titled compound (11.4 g) as a white solid.

Workup

  1. customThe solvent and an excess amount of thionyl chloride were evaporated
  2. additionPyridine (200 ml) was added to the resulting reaction mixture
  3. additionwas added
  4. stirringstirred at 50° C. for two hours
  5. customAfter the reaction
  6. additionwere added
  7. filtrationthe precipitate was filtered
  8. dissolutionThe resulting solid was dissolved in acetic acid (7.5 ml)
  9. additionwater (7.5 ml) and ethanol (750 ml), activated charcoal was added
  10. stirringstirred at 40° C. for an hour
  11. filtrationThe mixture was filtered through Celite, pH
  12. additionwas adjusted to 8 by the addition of 1N aqueous solution of sodium hydroxide
  13. filtrationthe precipitate was collected by filtration
  14. washThe resulting solid was washed with water
  15. customdried at 60° C. under current of air

Sources & evidence

ORD record
ord-b15f1532147b4ba0a782fcf838c0c4b9
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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