Cesium carbonate → 2-(2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide

HRID 1045953Notes

Reaction equation

HRID 1045953 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[NH2:13][C:14]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:15]=1[C:16]([NH:18][CH3:19])=[O:17].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>[Cl:1][C:2]1[CH:7]=[C:6]([NH:13][C:14]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:15]=2[C:16]([NH:18][CH3:19])=[O:17])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27737912-Chloro-4-iodo-5-(trifluoromethyl)pyridineHCID 122648202-amino-6-methoxy-N-methylbenzamide

Product 1

HCID 866551442-(2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamideYield 66%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

2-Chloro-4-iodo-5-(trifluoromethyl)pyridine (420 mg, 1.37 mmol), 2-amino-6-methoxy-N-methylbenzamide (246 mg, 1.37 mmol), palladium(II) acetate (24.54 mg, 0.11 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (126 mg, 0.22 mmol) and cesium carbonate (534 mg, 1.64 mmol) were mixed together in dioxane (8 mL). Reaction was degassed with argon and was stirred at 90° C. overnight (15 hours) under argon. The reaction mixture was filtered, washed with DCM and the filtrate was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 10 to 30% EtOAc in petroleum ether. The solvent was evaporated to dryness to afford 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide (325 mg, 66%) as a white solid. 1H NMR spectrum (500 MHz, DMSO): 2.68 (d, 3H), 3.83 (s, 3H), 6.84 (s, 1H), 7.03 (d, 1H), 7.08 (d, 1H), 7.47 (dd, 1H), 8.19 (q, 1H), 8.42 (s, 1H), 9.15 (s, 1H); Mass spectrum: ESI+ MH+ 360.

Workup

  1. customReaction
  2. customwas degassed with argon
  3. filtrationThe reaction mixture was filtered
  4. washwashed with DCM
  5. concentrationthe filtrate was concentrated to dryness
  6. customThe crude product was purified by flash chromatography on silica gel eluting with 10 to 30% EtOAc in petroleum ether
  7. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-1a13ca36001746eab4b19f21511b9aab
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Reaction notes

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