Lithium hydroxide, monohydrate → 5-Fluoro-3-phenyl-2-{(S)-1-[9-(tetrahydropyran-2-yl)-9H-purin-6-ylamino]ethyl}-3H-benzoimidazole-4-carboxylic acid

HRID 243068Notes

Reaction equation

C[O:2][C:3]([C:5]1[C:13]2[N:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:11]([C@@H:20]([NH:22][C:23]3[N:31]=[CH:30][N:29]=[C:28]4[C:24]=3[N:25]=[CH:26][N:27]4[CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)[CH3:21])=[N:10][C:9]=2[CH:8]=[CH:7][C:6]=1[F:38])=[O:4].O.[OH-].[Li+]>CO.O>[F:38][C:6]1[CH:7]=[CH:8][C:9]2[N:10]=[C:11]([C@@H:20]([NH:22][C:23]3[N:31]=[CH:30][N:29]=[C:28]4[C:24]=3[N:25]=[CH:26][N:27]4[CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)[CH3:21])[N:12]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:13]=2[C:5]=1[C:3]([OH:4])=[O:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 5-fluoro-3-phenyl-2-{(S)-1-[9-(tetrahydro-pyran-2-yl)-9H-purin-6-ylamino]ethyl}-3H-benzoimidazole-4-carboxylic acid methyl ester (1.34 g, 2.66 mmol) in methanol (40 mL) and water (4 mL) was added lithium hydroxide monohydrate (0.166 g, 15. 9 mmol) and the reaction mixture heated at 80° C. for 16 h. The reaction mixture was concentrated in vacuo to remove methanol and the residual aqueous solution acidified to ph˜4 by addition of HCl (1 M) causing a precipitate to form. The product was collected by filtration and dried in vacuo to give the title compound as an off white solid (564 mg, 43%). LCMS (Method C): RT=2.44 min, [M+H]+=502.

Workup

concentrationThe reaction mixture was concentrated in vacuo
customto remove methanol
additionthe residual aqueous solution acidified to ph˜4 by addition of HCl (1 M)
customto form
filtrationThe product was collected by filtration
customdried in vacuo

Sources & evidence

ORD record: ord-3fdf10f183544a9b8f8e62a9bdd17b6c
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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