Diisopropylethylamine → 6-[({1-[2-(7-Methoxy-2-oxo-2H-3,1-benzoxazin-1(4H)-yl)ethyl]piperidin-4-yl}amino)methyl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

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Reaction Steps

1-[2-(4-Aminopiperidin-1-yl)ethyl]-7-methoxy-1,4-dihydro-2H-3,1-benzoxazin-2-one trifluoro acetate (Intermediate 106) (324 mg, 0.78 mmol) was converted to the free base using N,N-diisopropylethylamine for 30 minutes and reacted with 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehyde (WO 2004/058144) (153 mg, 0.86 mmol) and sodium cyanoborohydride (98 mg, 1.56 mmol) as described under Example 21. The reaction mixture was filtered through a 0.45 μm membrane and concentrated to dryness under reduced pressure. Chromatography on silica gel with dichloromethane/methanol (9:1) gave the free base of the title compound as a colorless foam. The free base was taken up in 1,4 dioxane (2 mL), followed by addition of 4M HCl in 1,4-dioxane (0.30 mL). The resulting precipitate was collected by filtration and gave 75 mg (48%) of the bis-hydrochloride salt of the product.

Provenance & Evidence