Triacetoxyborohydride → 1-{2-[4-({[5-chloro-6-(hydroxymethyl)-3-pyridinyl]methyl}amino)-1-piperidinyl]ethyl}-7-(methyloxy)-1,5-naphthyridin-2(1H)-one

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Reaction Steps

1-[2-(4-amino-1-piperidinyl)ethyl]-7-(methyloxy)-1,5-naphthyridin-2(1H)-one (Intermediate 29: 100 mg, 0.331 mmol) was dissolved in a mixture of Dichloromethane (DCM) (4 mL) and Methanol (0.444 mL). Aldehyde 5-chloro-6-(hydroxymethyl)-3-pyridinecarbaldehyde (Intermediate 39: 56.7 mg, 0.331 mmol) was added and the mixture was left at room temp. for 3 hours. Then sodium triacetoxy borohydride (210 mg, 0.992 mmol) was added and after 2 hours 2 more eq. of triacetoxy borohydride were added leaving the reaction under stirring overnight. LCMS overnight showed still imine remaining so 3 eq more of sodium triacetoxy borohydride were added and 2 eq more after 3 hours leaving the reaction overnight. Next morning 2 more eq. of sodium triacetoxy borohydride were added and after 3H reaction was stopped. Volatiles were removed under vacuum and the corresponding crude was diluted with DCM and washed with NaHCO3 several times. Organic layers were dried over Na2SO4, filtered and volatiles removed under vacuum. Corresponding crude was purified by flash master chromatography. Si II, 5 g. DCM/MeOH (0-30%), to obtain a solid which was left in the oven overnight to afford 45 mg of the final compound as a pale yellow solid.

Provenance & Evidence