Sodium hydride → HCID 68312871, Verbindung

To a suspension of 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-ol from Example 4 (100 mg, 0.307 mmol) in DMF (2 mL) was added sodium hydride (12.3 mg, 60% in oil, 0.307 mmol). The mixture was stirred at RT for 15 min, then 2-bromo-2-cyclopropylmethylmalonic acid diethyl ester (135 mg, 0.46 mmol) was added. The reaction mixture was stirred at RT for 1 h, and then at 70° C. for 6 h. The reaction was repeated with 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-ol from Example 4 (400 mg, 1.23 mmol), DMF (8 mL), sodium hydride (49.2 mg, 1.23 mmol) and 2-bromo-2-cyclopropylmethylmalonic acid diethyl ester (540 mg, 1.84 mmol). The cooled reaction mixtures were combined and partitioned between water and EtOAc. The aqueous phase was extracted with EtOAc. The combined organic phases were washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-10% MeOH in DCM) affording the title compound (0.309 g, 37%). LCMS (Method B): RT 3.77 min [M+H]+ 538.

1. stirringThe reaction mixture was stirred at RT for 1 h
2. waitat 70° C. for 6 h
3. customThe cooled reaction mixtures
4. custompartitioned between water and EtOAc
5. extractionThe aqueous phase was extracted with EtOAc
6. washThe combined organic phases were washed with water
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated in vacuo
9. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 2-10% MeOH in DCM)

ORD-Eintrag

ord-603fd0d9df5c46068003fd529a84b6c3

Quelldatensatz

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09090628B2