Diisobutylaluminum hydride → HCID 86693114, compound

Participants

Reaction Conditions

Reaction Steps

Into a 8-mL sealed tube, was placed a solution of ethyl 3-(2-[4-carbamoyl-12-fluoro-9-oxa-3,6-diazatricyclo[8.4.0.0[2,6]]tetradeca-1(14),2,4,10,12-pentaen-13-yl]ethynyl)-3-hydroxycyclobutane-1-carboxylate (140 mg, 0.34 mmol, 1.00 equiv) in tetrahydrofuran (5 mL). Then added DIBAL-H (1.0M in THF, 7 mL, 2.00 equiv) dropwise with stirring at −70° C. The resulting solution was stirred for 4 h at −70° C. The reaction was then quenched by the addition of 2 mL of 10% sodium potassium tartrate. The solids were filtered out. The mixture was diluted with 40 mL of ethyl acetate, and washed with 20 mL of brine, dried over sodium sulfate. Filtered and concentrated, the residue was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-016(Waters)): Column, Xbridge Prep C18, 5 um, 19*150 mm; mobile phase, water with 0.03% NH4CO3 and CH3CN (10% CH3CN up to 29% in 13 min); Detector, uv 254/220 nm. This resulted in 25 mg (20%) of 8-Fluoro-9-(1-hydroxy-3-hydroxymethyl-cyclobutylethynyl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a white solid. (single undetermined diastereomer). LC-MS: (ES, m/z):372[M+H]+ 1H-NMR: (400 MHz, DMSO-d6, ppm) δ 8.602 (d, 1H), 7.785 (s, 1H), 7.596 (s, 1H), 7.142 (s, 1H), 7.033 (d, 1H), 5.907 (s, 1H), 4.559-4.410 (m, 4H), 3.422 (t, 2H), 2.449 (t, 2H), 2.238-2.100 (m, 1H), 2.029 (t, 2H).

Provenance & Evidence