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

HRID 1500677Notes

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]([I: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]([I:21])=[CH:17][C:16]=1[F:22])=[O:23]

Participants

Conditions

Temperature: 95 °C

Procedure

To a suspension of 2-(2-fluoro-4-iodophenylamino)-6-formylaminomethylnicotinic acid methyl ester (11.6 g, 27.4 mmol) in toluene (160 mL) was added phosphorous (V) oxychloride (5.1 mL, 54.8 mmol) and the reaction mixture heated at 95° C. for 1 hour. The reaction mixture was concentrated in vacuo and the resultant residue poured onto ice. The mixture was washed with aqueous saturated sodium hydrogen carbonate solution (40 mL) and the aqueous layer extracted twice with ethyl acetate (2×30 mL). The combined organic extracts were washed with brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-70% ethyl acetate in DCM) to yield the title compound as a brown oil (5.6 g, 50%). LCMS (Method B): RT=3.62 min, M+H+=412.

Workup

concentrationThe reaction mixture was concentrated in vacuo
additionthe resultant residue poured onto ice
washThe mixture was washed with aqueous saturated sodium hydrogen carbonate solution (40 mL)
extractionthe aqueous layer extracted twice with ethyl acetate (2×30 mL)
washThe combined organic extracts were washed with brine (30 mL)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-5754bff5f0714da6bb6f01ae53a9c163
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206174B2

Reaction notes

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