[CH3:1][C:2]1[C:3]([C:11]#[N:12])=[CH:4][C:5]2[N:9]=[CH:8][NH:7][C:6]=2[CH:10]=1.C1COCC1.[O:18]1[CH:23]=[CH:22][CH2:21][CH2:20][CH2:19]1.CC1C=CC(S(O)(=O)=O)=CC=1.O>CCOC(C)=O>[CH3:1][C:2]1[C:3]([C:11]#[N:12])=[CH:4][C:5]2[N:9]=[CH:8][N:7]([CH:19]3[CH2:20][CH2:21][CH2:22][CH2:23][O:18]3)[C:6]=2[CH:10]=1To a stirred solution of 6-methyl-1H-benzo[d]imidazole-5-carbonitrile (7.9 g, 50 mmol, CASRN 952511-47-6) and THF (85 mL) at RT under nitrogen was added 3,4-dihydro-2H-pyran (34 g, 0.4 mol) and p-TsOH.H2O (0.9 g, 5 mmol) and the resulting mixture was heated at 75° C. for 3 h. The reaction mixture was cooled to RT, diluted with EtOAc (200 mL), and washed sequentially with sat'd. aq. Na2CO3 (300 mL) and brine (300 mL). The organic phase was dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with a MeOH/DCM gradient (0 to 5% MeOH) to afford 7.2 g (60%) of 6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole-5-carbonitrile (176) as a yellow oil: MS (ESI) m/z=242 [M+1]+.
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