Triethylamine → 4-((2-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)morpholin-3-one

A mixture of 2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde (intermediate 41, 1.50 g, 5.40 mmol), ethyl 2-(2-aminoethoxyl)acetate hydrochloride (intermediate 105, 1.24 g, 6.75 mmol) and triethylamine (0.97 ml, 7.02 mmol) in 1,2-dichloroethane (25 ml) at room temperature was stirred for 1 h and then sodium triacetoxyborohydride (1.83 g, 8.63 mmol) was added. The reaction mixture was stirred for 18 h at room temperature and additional sodium triacetoxyborohydride (0.92 g, 4.32 mmol) was added. After a further 5 h stirring at room temperature the reaction mixture was partitioned between saturated aqueous NaHCO3 solution and DCM, the mixture extracted with DCM (3×), the combined organic layers dried over Na2SO4 and evaporated. The residue was applied to a 80 g RediSep® silica and purified by normal phase chromatography, eluting with a gradient from DCM to 10% MeOH in DCM. Product containing fractions were combined and evaporated to give the title compound as an yellow solid. (UPLC-MS 6) tR 0.42; ESI-MS 322.2 [M+H]+.

1. stirringThe reaction mixture was stirred for 18 h at room temperature
2. stirringAfter a further 5 h stirring at room temperature the reaction mixture
3. customwas partitioned between saturated aqueous NaHCO3 solution and DCM
4. extractionthe mixture extracted with DCM (3×)
5. dry with materialthe combined organic layers dried over Na2SO4
6. customevaporated
7. custompurified by normal phase chromatography
8. washeluting with a gradient from DCM to 10% MeOH in DCM
9. additionProduct containing fractions
10. customevaporated

ORD record

ord-584202700c9d44eba4aa6c18f2533c04

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266883B2