Triethylamine → (1R)-1-({4-[(2,3-Dihydro[1,4]oxathiino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione hydrochloride

Participants

Reaction Steps

A suspension of (1R)-1-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione dihydrochloride (511 mg, 1.369 mmol) (for a preparation see Example 5(j)) in chloroform (20 ml) and methanol (1 ml) at rt under argon was treated with triethylamine (0.572 ml, 4.11 mmol) and stirred at rt for 0.25 h. The solution was then treated with 2,3-dihydro[1,4]oxathiino[2,3-c]pyridine-7-carbaldehyde (for a synthesis see WO2004058144, Example 60) (248 mg, 1.369 mmol) and stirred for a further 0.5 h. The solution was then treated with NaBH(OAc)3 (870 mg, 4.11 mmol) and stirred at rt for 0.5 h. The reaction was then treated with saturated aqueous NaHCO3 (100 ml) and extracted with 20% methanol/DCM (3×200 ml). The combined organic extracts were dried (MgSO4), filtered, evaporated and chromatographed (0-20% methanol/DCM) to give the free base of the title compound as a light brown solid (499 mg, 78%).

Provenance & Evidence