Glycolic Acid → (E)-1'-(2-hydroxyacetyl)-6-(3-oxo-3-(4-(thiazol-2-ylmethyl)-5,6-dihydropyridin-1(2H)-yl)prop-1-en-1-yl)-1H-spiro[[1,8]naphthyridine-3,4'-piperidin]-2(4H)-one

Temperatur

27.5 °C

DIPEA (0.38 mL, 2.13 mmol) was added to a stirred solution of (E)-6-(3-oxo-3-(4-(thiazol-2-ylmethyl)-5,6-dihydropyridin-1(2H)-yl)prop-1-en-1-yl)-1H-spiro[[1,8]naph-thyridine-3,4′-piperidin]-2(4H)-one 2,2,2-trifluoroacetate (Compound 34) (200 mg, 0.35 mmol), Glycolic acid (80 mg, 1.06 mmol), HOBt (96 mg, 0.70 mmol) and EDC.HCl (170 mg, 0.88 mmol) in dry DMF (4 mL) at 20-35° C. and the reaction mixture was allowed to stir at 20-35° C. for 16 h. Then the reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (2×30 mL). The organic layer was washed with brine (30 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was rotary evaporated under vacuum to get residue which was purified by column chromatography using mixture of 4% methanol/dichloromethane as an eluent to get the desired compound as a light yellow solid (40 mg, 22%); 1H NMR (400 MHz, DMSO-d6) δ 10.75 (s, 1H), 8.38 (d, J=2.0 Hz, 1H), 8.09 (s, 1H), 7.71 (d, J=3.4 Hz, 1H), 7.61 (d, J=3.5 Hz, 1H), 7.45 (d, J=15.7 Hz, 1H), 7.28-7.14 (m, 1H), 5.68-5.66 (m, 1H), 4.50 (t, J=5.4 Hz, 1H), 4.28-4.22 (m, 1H), 4.10-4.04 (m, 3H), 3.78-3.74 (m, 3H), 3.74-3.62 (m, 3H), 3.54-3.38 (m, 2H), 2.96 (s, 2H), 2.20-2.06 (m, 2H), 1.86-1.68 (m, 2H), 0.46-0.32 (m, 2H); ES-MS: 508.2 (M+1)+.

1. extractionextracted with ethyl acetate (2×30 mL)
2. washThe organic layer was washed with brine (30 mL)
3. dry with materialdried over anhydrous Na2SO4
4. filtrationfiltered
5. customThe filtrate was rotary evaporated under vacuum
6. customto get residue which
7. customwas purified by column chromatography
8. additionmixture of 4% methanol/dichloromethane as an eluent

ORD-Eintrag

ord-0dd8405b2c0d4861a497985bb66226cd

Quelldatensatz

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09062075B2