Dimethylphosphinic acid → [6-({3-(Aminocarbonyl)-5-[2-fluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-thienyl}amino)pyridin-2-yl]methyl dimethylphosphinate

Participants

Reaction Steps

5-[2-Fluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-{[6-(hydroxymethyl)pyridin-2-yl]amino}thiophene-3-carboxamide (Example 43) (125 mg, 0.31 mmol), dimethylphosphinic acid (32.2 mg, 0.34 mmol), BOP (207 mg, 0.47 mmol) and DIPEA (48.3 mg, 0.37 mmol) were stirred in DMF (1 mL) at room temperature for 6 hours. Additional dimethylphosphinic acid (11.71 mg, 0.13 mmol), BOP (68.9 mg, 0.16 mmol) and DIPEA (0.033 mL, 0.19 mmol) were added and the reaction mixture was maintained at room temperature overnight. Saturated sodium bicarbonate was added and the mixture was extracted with EtOAc (×5). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by silica gel column chromatography (0-10% MeOH-EtOAc) gave the title compound as a pale yellow solid.

Provenance & Evidence