Sodium Methoxide → {(S)-1-[6-Fluoro-1-(6-methoxypyridin-3-yl)-1H-benzoimidazol-2-yl]ethyl}carbamic acid tert-butyl ester

HRID 242994Notes

Reaction equation

[C:1]([O:5][C:6](=[O:28])[NH:7][C@H:8]([C:10](=O)[NH:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[NH:19][C:20]1[CH:21]=[N:22][C:23](F)=[CH:24][CH:25]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2].[CH3:29][O-:30].[Na+]>CO>[C:1]([O:5][C:6](=[O:28])[NH:7][C@H:8]([C:10]1[N:19]([C:20]2[CH:21]=[N:22][C:23]([O:30][CH3:29])=[CH:24][CH:25]=2)[C:13]2[CH:14]=[C:15]([F:18])[CH:16]=[CH:17][C:12]=2[N:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 120 °C

Procedure

A suspension of {(S)-1-[4-fluoro-2-(6-fluoropyridin-3-ylamino)phenylcarbamoyl]ethyl}carbamic acid tert-butyl ester (196 mg, 0.50 mmol) in 0.5M NaOMe in MeOH (2.0 mL, 1.0 mmol) was heated at 120° C. using microwave irradiation for 15 min. The crude reaction mixture was diluted with MeOH and loaded onto an Isolute®SCX-2 cartridge then washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined and concentrated in vacuo and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-5% MeOH in DCM) to afford the title compound as a pink oil (52 mg, 27%). LCMS (Method C): RT 3.42 min [M+H]+ 387.2.

Workup

custommicrowave irradiation for 15 min
customThe crude reaction mixture
washthen washed with MeOH
concentrationconcentrated in vacuo
customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-5% MeOH in DCM)

Sources & evidence

ORD record: ord-116067c0e8bb46caa2f34236fcadcafc
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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