2-Nitropyridine → (7-chloro-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methanol

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Reaction Steps

To a 10 mL round-bottomed flask were added (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)) (45 mg, 0.134 mmol), 7-chloro-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehyde (prepared by (1) reduction of 7-chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehyde (for a synthesis see WO2003064421 Example 15(c)) with LiAlH4 to give (7-chloro-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methanol and then (2) oxidation with MnO2) (29.2 mg, 0.147 mmol), and NaHCO3 (100 mg, 1.190 mmol) in dichloromethane (DCM) (4 ml) and methanol (1 ml) to give a brown suspension. Sodium sulfate (200 mg, 1.408 mmol) was added and the reaction was stirred at rt overnight. After 15 h sodium triacetoxyborohydride (56.6 mg, 0.267 mmol) was added and the reaction was stirred at 25° C. under nitrogen for 4 h. The reaction mixture was adsorbed onto silica and purified using 0-10% MeOH/DCM (1% NH4OH) to give the title compound as a free base (9.4 mg, 0.019 mmol, 14.57% yield).

Provenance & Evidence