Stannane, hydroxytrimethyl- → 5-(2-Fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid

HRID 2064031Notes

Reaction equation

C[O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]2[N:9]([CH:20]=[N:21][CH:22]=2)[C:10]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=1[F:19])=[O:4].[OH-].C[Sn+](C)C>ClCCCl>[F:19][C:13]1[CH:14]=[C:15]([I:18])[CH:16]=[CH:17][C:12]=1[NH:11][C:10]1[N:9]2[CH:20]=[N:21][CH:22]=[C:8]2[CH:7]=[N:6][C:5]=1[C:3]([OH:4])=[O:2]

Participants

Conditions

Temperature: 85 °C

Procedure

To a solution of 5-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid methyl ester (140 mg, 0.34 mmol) in anhydrous 1,2-dichloroethane (2.5 mL) was added trimethyltin hydroxide (215 mg, 1.19 mmol, 3.5 eq.). The reaction mixture was heated at 85° C. for 1 hour and then cooled to RT. The reaction mixture was concentrated in vacuo, and the crude residue was diluted with ethyl acetate. The organic layer was washed with 1N HCl (3×), water and brine, dried (Na2SO4), filtered and concentrated in vacuo. Crystallization from dichloromethane—ether—hexane afforded the title compound as a yellow solid (132.1 mg, 97.7%). 1H NMR (MeOD, 400 MHz) δ ppm 8.76 (s, 1H), 7.92 (s, 1H), 7.86 (s, 1H), 7.64 (dd, J=10.13, 1.84 Hz, 1H), 7.55-7.50 (m, 1H), 6.72 (t, J=8.49 Hz, 1H); LCMS (method D1): RT=0.77 min, [M+H]+=399.

Workup

temperaturecooled to RT
concentrationThe reaction mixture was concentrated in vacuo
additionthe crude residue was diluted with ethyl acetate
washThe organic layer was washed with 1N HCl (3×), water and brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customCrystallization from dichloromethane—ether—hexane

Sources & evidence

ORD record: ord-be9b1fdfa88b4f01982fd98f9ce3ecb8
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08288408B2

Reaction notes

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