Potassium Phosphate, Tribasic → N-[6-(3,6-Dihydro-2H-pyran-4-yl)-5-methylpyridin-3-yl]-5-methyl-1-[4-(trifluoromethyl)-phenyl]-1H-pyrazole-4-carboxamide

HRID 1748634Notes

Reaction equation

HRID 1748634 reaction equation
[CH3:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:17]([NH2:19])=[O:18].Br[C:21]1[CH:22]=[C:23]([CH3:33])[C:24]([C:27]2[CH2:28][CH2:29][O:30][CH2:31][CH:32]=2)=[N:25][CH:26]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(O)(C)(C)C.C(Cl)(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>[O:30]1[CH2:31][CH:32]=[C:27]([C:24]2[N:25]=[CH:26][C:21]([NH:19][C:17]([C:3]3[CH:4]=[N:5][N:6]([C:7]4[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:14])[F:15])=[CH:9][CH:8]=4)[C:2]=3[CH3:1])=[O:18])=[CH:22][C:23]=2[CH3:33])[CH2:28][CH2:29]1

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 178227615-methyl-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-4-carboxamideHCID 866925085-Bromo-2-(3,6-dihydro-2H-pyran-4-yl)-3-methylpyridine

Product 1

HCID 86692571N-[6-(3,6-Dihydro-2H-pyran-4-yl)-5-methylpyridin-3-yl]-5-methyl-1-[4-(trifluoromethyl)-phenyl]-1H-pyrazole-4-carboxamideYield 58%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphaneCatalystHCID 6212ChloroformSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of 5-methyl-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-4-carboxamide (212 mg), 5-bromo-2-(3,6-dihydro-2H-pyran-4-yl)-3-methylpyridine (200 mg) described in Reference Example 135, 2-(di-tert-butylphosphino)-3,4,5,6-tetramethyl-2′,4′,6′-triisopropyl-1,1′-biphenyl (19 mg), tris(dibenzylideneacetone)dipalladium (0) (7.2 mg) and tripotassium phosphate (200 mg) in tert-butanol (3 ml) was stirred at 110° C. After the reaction, the reaction solution was left stand, diluted with chloroform and filtered through Celite. The organic layer was washed with water and saturated brine successively, dried over anhydrous sodium sulfate and concentrated. The resulting residue was purified with a silica gel column chromatography (chloroform/methanol), washed with hot ethanol and the resulting solid was filtered and dried at 60° C. in vacuo to give the titled compound (202 mg) as a white solid.

Workup

  1. customAfter the reaction
  2. waitthe reaction solution was left stand
  3. filtrationfiltered through Celite
  4. washThe organic layer was washed with water and saturated brine successively
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe resulting residue was purified with a silica gel column chromatography (chloroform/methanol)
  8. washwashed with hot ethanol
  9. filtrationthe resulting solid was filtered
  10. customdried at 60° C. in vacuo

Sources & evidence

ORD record
ord-0436c03475aa45f292880c1dbd83ddd1
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

Loading…