Phosphorus oxychloride → 2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carbonitrile

To the mixture of 2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carboxamide, prepared as described in Example 33 (0.4 g, 0.999 mmol) in Dichloromethane (DCM) (50 mL) was added in POCl3 (0.931 mL, 9.99 mmol) and followed by the addition of ten drops of DMF. The reaction was stirred at rt for 1 h. The mixture was quenched with aqueous sodium bicarbonate solution. The aqueous phase was extracted with DCM (100 mL). The combined organic phase was washed with Brine then dried (MgSO4), filtered and the solvent removed in-vacuo. The crude was purified on silica (20˜50% EtOAc/Hexane) to give the product (0.246 g, 64%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.45 (s, 3H), 2.96-3.15 (m, 4H), 3.62-3.72 (m, 4H), 6.05 (s, 2H), 6.32 (d, J=7.07 Hz, 1H), 7.29-7.44 (m, 3H), 7.57-7.74 (m, 2H), 7.86 (d, J=8.08 Hz, 1H), 8.02 (d, J=7.83 Hz, 1H) 8.22 (d, 1H). MS (ES+) m/z 383.2 [M+H]+.

1. customprepared
2. customThe mixture was quenched with aqueous sodium bicarbonate solution
3. extractionThe aqueous phase was extracted with DCM (100 mL)
4. washThe combined organic phase was washed with Brine
5. dry with materialthen dried (MgSO4)
6. filtrationfiltered
7. customthe solvent removed in-vacuo
8. customThe crude was purified on silica (20˜50% EtOAc/Hexane)

ORD record

ord-06e3663ce94b464ba155a5f80b58f6be

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08541411B2