Cesium carbonate → 2-[2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino]-N-methylbenzamide

HRID 1045910Notes

Reaction equation

C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:7][C:8]1[CH:13]=[C:12](I)[C:11]([C:15]([F:18])([F:17])[F:16])=[CH:10][N:9]=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.[NH2:61][C:62]1[CH:71]=[CH:70][CH:69]=[CH:68][C:63]=1[C:64]([NH:66][CH3:67])=[O:65]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:7][C:8]1[CH:13]=[C:12]([NH:61][C:62]2[CH:71]=[CH:70][CH:69]=[CH:68][C:63]=2[C:64]([NH:66][CH3:67])=[O:65])[C:11]([C:15]([F:18])([F:17])[F:16])=[CH:10][N:9]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Cesium carbonate (3.40 g, 10.43 mmol) was added to 2-chloro-4-iodo-5-(trifluoromethyl)pyridine (1.604 g, 5.22 mmol), palladium(II) acetate (0.094 g, 0.42 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.362 g, 0.63 mmol) and 2-amino-N-methylbenzamide (0.784 g, 5.22 mmol) in dioxane (40 mL). The resulting suspension was heated at 80° C. for 24 hours under an argon atmosphere. The mixture was filtered through Celite and then purified directly by chromatography on silica eluting with a mixture of 50% EtOAc in isohexane. Fractions containing product were combined and evaporated to leave 2-[[2-chloro-5-(trifluoromethyl)pyridin-4-yl]amino]-N-methylbenzamide (1.168 g, 68% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 2.76 (3H, d), 7.24 (2H, dd), 7.57 (2H, ddd), 7.74 (1H, dd), 8.49 (1H, d), 8.71 (1H, d), 10.54 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+=329.99 and 331.95.

Workup

filtrationThe mixture was filtered through Celite
custompurified directly by chromatography on silica eluting with a mixture of 50% EtOAc in isohexane
additionFractions containing product
customevaporated

Sources & evidence

ORD record: ord-b9585607274c453aa06aa412b634c6e0
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569298B2

Reaction notes

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