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

HRID 162

Reaction equation

HRID 162 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 63.83%

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 (790 mg, 2.57 mmol), 2-amino-6-methoxy-N-methylbenzamide (477 mg, 2.65 mmol), diacetoxypalladium (46.2 mg, 0.21 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (238 mg, 0.41 mmol) and cesium carbonate (1005 mg, 3.08 mmol) were mixed together in dioxane (15 mL). Reaction was degassed with argon and was stirred at 90 °C overnight under argon. Reaction was filtered, washed with CH2Cl2 and filtrate was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 50% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide (590 mg, 63.8 %) as a white foam.

Sources & evidence

ORD record
ord-1a5e116509544433b15ed4392cd63699
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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