Water → n-[4-Acetyl-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1h-pyrazole-5-carboxamide

HRID 1268895Notes

Reaction equation

HRID 1268895 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]([NH:15][C:16]3[C:25]([C:26]([NH:28][CH:29]([CH3:31])[CH3:30])=[O:27])=[CH:24][C:19]([C:20](OC)=[O:21])=[CH:18][C:17]=3[CH3:32])=[O:14])=[CH:11][C:10]([C:33]([F:36])([F:35])[F:34])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[CH2:37]([Sn](CCCC)(CCCC)C(OCC)=C)CCC.O>CN(C=O)C.C1(P([Pd](Cl)(Cl)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:20]([C:19]1[CH:24]=[C:25]([C:26]([NH:28][CH:29]([CH3:30])[CH3:31])=[O:27])[C:16]([NH:15][C:13]([C:12]2[N:8]([C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=3)[N:9]=[C:10]([C:33]([F:34])([F:36])[F:35])[CH:11]=2)=[O:14])=[C:17]([CH3:32])[CH:18]=1)(=[O:21])[CH3:37]

Participants

6

Reactant 3

HCID 962WaterHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 10165112Methyl 4-[[[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1h-pyrazol-5-yl]carbonyl]amino]-3-methyl-5-[[(1-methylethyl)amino]carbonyl]benzoate

Product 1

HCID 10207609n-[4-Acetyl-2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1h-pyrazole-5-carboxamide

Reagents, catalysts & solvents 2

HCID 178479802HCID 178479802, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

The title compound of Example 2, Step C (0.7 g, 1.3 mmol) was dissolved in DMF (10 mL) and treated with tributyl-(1-ethoxyvinyl)tin (0.47 g, 1.3 mmol) and bis(triphenyl-phosphino)palladium dichloride (50 mg). The mixture was heated at 80° C. for 4 hours. The mixture was poured into water (50 mL) and extracted with ether (3×50 mL). The combined organic layers were washed with water (50 mL) and saturated brine (50 mL). The mixture was dried over magnesium sulfate and concentrated under reduced pressure. The residue was filtered through a silica gel cartridge using dichloromethane as eluent. The appropriate fractions were pooled and evaporated. The residue (400 mg) was dissolved in acetone (20 mL) and treated with 1N hydrochloric acid (5 mL). After 1 hour at 25° C. the reaction mixture was partitioned between ethyl acetate (50 ml) and water (50 ml). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to chromatography on silica gel using ethyl acetate/hexanes (40:60) as eluent. Pooling appropriate fractions and evaporation of solvent provided the title compound, a compound of the invention, (150 mg) as a yellow solid, m.p.: 135–137° C. 1H NMR (CDCl3): δ 10.8 (NH), 8.42 (1H), 7.89 (1H), 7.87 (2H), 7.42 (1H), 7.31 (1H), 6.15 (1H), 4.21 (1H), 2.59 (3H), 2.27 (3H), 1.28 (6H).

Workup

  1. extractionextracted with ether (3×50 mL)
  2. washThe combined organic layers were washed with water (50 mL) and saturated brine (50 mL)
  3. dry with materialThe mixture was dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. filtrationThe residue was filtered through a silica gel cartridge
  6. customevaporated
  7. dissolutionThe residue (400 mg) was dissolved in acetone (20 mL)
  8. additiontreated with 1N hydrochloric acid (5 mL)
  9. customAfter 1 hour at 25° C. the reaction mixture was partitioned between ethyl acetate (50 ml) and water (50 ml)
  10. dry with materialThe organic layer was dried over magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customPooling appropriate fractions and evaporation of solvent

Sources & evidence

ORD record
ord-8b06ae39b8d842568b731fbe2e6a215c
Source dataset
uspto-grants-2007_04
Patent number
US07199138B2

Reaction notes

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