2-(4-Bromo-2-fluorophenylamino)-6-formylaminomethylnicotinic acid methyl ester → 5-(4-Bromo-2-fluorophenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid methyl ester

HRID 1500681Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][NH:11][CH:12]=O)=[N:6][C:5]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[F:22].O(Cl)Cl.[P+5]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]2[N:6]([CH:12]=[N:11][CH:10]=2)[C:5]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[F:22])=[O:23]

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of 2-(4-Bromo-2-fluorophenylamino)-6-formylaminomethylnicotinic acid methyl ester (11.8 g, 30.9 mmol) in toluene (550 mL) was added phosphorous (V) oxychloride (3.16 mL, 34 mmol) and the reaction mixture heated at 95° C. for 1 hour. The reaction mixture was concentrated in vacuo and treated with aqueous saturated sodium hydrogen carbonate solution then extracted twice with ethyl acetate. The combined organic fractions were washed with brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0-30% ethyl acetate in DCM) to yield the title compound as a brown oil (5.4 g, 49%). LCMS (Method B): RT=3.56 min, M+H+=364/366.

Workup

concentrationThe reaction mixture was concentrated in vacuo
additiontreated with aqueous saturated sodium hydrogen carbonate solution
extractionthen extracted twice with ethyl acetate
washThe combined organic fractions were washed with brine
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-8762685b39e5427c876f4711fd08e141
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206174B2

Reaction notes

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