Cesium carbonate → 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide

HRID 1045951Notes

Reaction equation

HRID 1045951 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:21]([F:24])([F:23])[F:22])=[CH:4][N:3]=1.[CH3:25][N:26]1[C:30]([NH2:31])=[CH:29][C:28]([CH3:32])=[N:27]1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:25][N:26]1[C:30]([NH:31][C:2]2[CH:7]=[C:6]([NH:8][C:9]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[C:10]=3[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:21]([F:24])([F:23])[F:22])=[CH:4][N:3]=2)=[CH:29][C:28]([CH3:32])=[N:27]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5207211,3-Dimethyl-1H-pyrazol-5-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866551442-(2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide

Product 1

HCID 569512912-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamideYield 32%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

2-(2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide (305 mg, 0.85 mmol), 1,3-dimethylpyrazol-5-amine (94 mg, 0.85 mmol), palladium(II) acetate (15.23 mg, 0.07 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (78 mg, 0.14 mmol) and cesium carbonate (331 mg, 1.02 mmol) were mixed together in dioxane (6 mL). The reaction mixture was degassed with argon and was stirred at 90° C. for 8 hours under argon. After cooling, the reaction mixture was filtered and washed with DCM. The filtrate was concentrated to dryness and was purified by flash chromatography on silica gel eluting with 1 to 5% MeOH in DCM. The solvent was evaporated to dryness to afford the title compound (118 mg, 32%) as a pale beige-pink solid.

Workup

  1. customThe reaction mixture was degassed with argon
  2. temperatureAfter cooling
  3. filtrationthe reaction mixture was filtered
  4. washwashed with DCM
  5. concentrationThe filtrate was concentrated to dryness
  6. customwas purified by flash chromatography on silica gel eluting with 1 to 5% MeOH in DCM
  7. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-f2346c0f751343a0b04cde8b102f620b
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Reaction notes

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