Triphenylphosphine → HCID 24829863, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 5-(6-chloro-5-fluoro-1H-benzimidazol-1-yl)-3-{[(1R)-1-(2-chloro-3-hydroxyphenyl)ethyl]oxy}-2-thiophenecarboxylate (Example 69, Step E, 0.10 g, 0.21 mmol) and 1-methyl-4-piperidinol (0.05 g, 0.42 mmol) in DCM (2 mL) was added polymer-supported triphenylphosphine (0.19 g, 0.42 mmol), di-tert-butylazodicarboxylate (0.10 g, 0.42 mmol). The reaction mixture was stirred for 8 h. The reaction was filtered with DCM washings and the volatiles were evaporated under reduced pressure. To the residue was added a solution of 7 N ammonia in MeOH (8 mL). The mixture was heated in a sealed tube to 70° C. for 48 h and then cooled to rt. Silica; was added and the volatiles evaporated under reduced pressure and the residue was purified by flash chromatography ((0 to 100% 89/10/1 DCM/MeOH/ammonium hydroxide:DCM) to afford 0.72 g (61%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.65 (s, 1H), 7.86 (d, J=9.7 Hz, 1H), 7.84 (s, 1H), 7.72 (d, J=6.4 Hz, 1H), 7.33 (t, J=8.0 Hz, 1H), 7.20 (d, J=7.5 Hz, 1H), 7.17 (s, 1H), 7.15 (d, J=8.2 Hz, 1H), 7.13 (s, 1H), 6.00 (q, J=6.0 Hz, 1H), 4.45 (s, 1H), 2.51-2.62 (m, 2H), 2.15-2.25 (m, 2H), 2.13 (s, 3H), 1.78-1.93 (m, 2H), 1.70 (d, J=6.4 Hz, 3H), 1.56-1.67 (m, 2H). MS (ESI): 564 [M+H]+.

Provenance & Evidence