Acetonitrile → 4-Fluoro-6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one methanesulfonate

HRID 2061499Notes

Reaction equation

[F:1][C:2]1[C:10]2[NH:9][C:8](=[O:11])[N:7]([CH:12]3[CH2:17][CH2:16][N:15]([CH:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[C:4]([CH3:24])[CH:3]=1.C(#N)C.[CH3:28][S:29]([OH:32])(=[O:31])=[O:30]>C(O)CC>[CH3:28][S:29]([OH:32])(=[O:31])=[O:30].[F:1][C:2]1[C:10]2[NH:9][C:8](=[O:11])[N:7]([CH:12]3[CH2:17][CH2:16][N:15]([CH:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[C:4]([CH3:24])[CH:3]=1

Participants

Conditions

Temperature: 35 °C

Procedure

4-Fluoro-6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one free base (1.499 mmol, 500 mg, 1 wt) was weighed into a 250 ml round bottomed flask, acetonitrile (95 vol., 47.5 ml) and n-propanol (80 vol., 40 ml) were added, giving a white slurry. Methanesulfonic acid (1 eq, 1.499 mmol, 97 μl) was pipetted into the flask. The contents of the flask were heated using a hot air gun—the slurry dissolved and a white precipitate formed. The precipitate was magnetically stirred at 35° C. for four days under nitrogen. After cooling to ambient temperature, the solid was isolated by vacuum filtration and washed with acetonitrile (10 vol. 5 ml). The white solid was dried under high vacuum at 60° C. for 25 hours. 561 mg, 87%, white solid.

Workup

customgiving a white slurry
temperatureThe contents of the flask were heated
dissolutiondissolved
customa white precipitate formed
temperatureAfter cooling to ambient temperature
customthe solid was isolated by vacuum filtration
washwashed with acetonitrile (10 vol. 5 ml)
customThe white solid was dried under high vacuum at 60° C. for 25 hours

Sources & evidence

ORD record: ord-63d67a3201b04a1289dc68631abc0053
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08283364B2

Reaction notes

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