2-Chloro-4-iodo-5-(trifluoromethyl)pyridine → 2-(2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide

HRID 163Notes

Reaction equation

HRID 163 reaction equation
CNC(=O)c1c(N)cccc1OC.FC(F)(F)c1cnc(Cl)cc1I>C1COCCO1.CC(=O)O.CC(=O)O.CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.O=C([O-])[O-].[Cs+].[Cs+].[Pd]>CNC(=O)c1c(Nc2cc(Cl)ncc2C(F)(F)F)cccc1OC

Participants

7

Reactant 2

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 66.13%

Reagents, catalysts & solvents 4

HCID 10796Cesium carbonateReagentHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 4144353Palladium (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), diacetoxypalladium (24.54 mg, 0.11 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (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. Reaction was filtered, washed with CH2Cl2 and the filtrate was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 10 to 30% ethyl acetate 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, 66.1 %) as a white solid.

Sources & evidence

ORD record
ord-67600027c34a4dbf95ee52ac1b8cec86
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Reaction notes

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