2-Nitropyridine → (3,4-Dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methanol

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 (for a preparation see Example 5A(j)) (0.075 g, 0.201 mmol) in dichloromethane (5 ml) and methanol (1 ml) at rt under argon was treated with 3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde (prepared by (1) reduction of 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxaldehyde (for a synthesis see WO2003087098, Example 301(d)) with LiAlH4 to give 3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethanol and then (2) oxidation with MnO2)) (0.036 g, 0.201 mmol), sodium bicarbonate (0.150 g, 1.786 mmol) and sodium sulfate (0.300 g, 2.112 mmol) and stirred at rt for 5 h. The solution was then treated with sodium triacetoxyborohydride (0.128 g, 0.603 mmol) and stirred over weekend for 65 hours. The solution was evaporated, taken up in CH3OH, adsorbed onto silica gel and chromatographed on silica (0-15% CH3OH in DCM (with 1% NH4OH)) to give the title compound as the free base (59 mg, 63%) as a beige solid.

ORD record

ord-df2a9d47245e4d61ab2c013295274baf

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08389524B2