Formaldehyde → HCID 86727556, Verbindung

To a solution of 7-(2-fluoro-phenyl)-4-methyl-6-(3-methyl-azetidin-3-ylamino)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.216 g, 0.545 mmol) in MeOH (10 mL) and acetic acid (1 mL) was added paraformaldehyde (0.05 g, 1.635 mmol) followed by NaBH3CN (0.068 g, 1.090 mmol). The mixture was stirred at ambient temperature for 30 min. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (30 mL×3). The combined organic phase was washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and evaporated in vacuo to give the residue, which was purified by chromatography on silica gel (eluting with 50% EtOAc in petroleum ether to 10% methanol in EtOAc) to give 6-(1,3-dimethyl-azetidin-3-ylamino)-7-(2-fluoro-phenyl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.150 g, 67%). 1H NMR (CDCl3, 400 MHz): δ 7.37 (m, 2H), 7.24 (m, 2H), 6.78 (s, 1H), 6.02 (s, 1H), 4.78 (m, 1H), 4.55 (m, 2H), 3.90 (m, 2H), 3.80 (m, 2H), 2.75 (s, 3H), 1.59 (s, 3H), 1.48 (d, J=6.8 Hz, 3H). LC/MS (Table 1, Method 25) Rt=0.715 min.; MS m/z: 410 [M+H]+.

1. extractionthe reaction mixture was extracted with EtOAc (30 mL×3)
2. washThe combined organic phase was washed with brine (10 mL)
3. dry with materialdried over anhydrous Na2SO4
4. filtrationfiltered
5. customevaporated in vacuo
6. customto give the residue, which
7. customwas purified by chromatography on silica gel (eluting with 50% EtOAc in petroleum ether to 10% methanol in EtOAc)

ORD-Eintrag

ord-416700b743c8428eafaa563ca5370b41

Quelldatensatz

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09115151B2