Sodium hydride → 4-((5-methyl-3-phenylisoxazol-4-yl)methyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Participants

Reaction Conditions

Reaction Steps

To a flask charged with N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIATE M) (0.104 g, 0.25 mmol) was added DMF (0.7 ml), and cooled in an ice water bath prior to the addition of NaH (60% in mineral oil) (10 mg, 0.25 mmol). The mixture was stirred for 45 min at 0° C., then 30 min at rt. To a separate vial charged with 4-(bromomethyl)-5-methyl-3-phenylisoxazole (Sigma Aldrich) (35 mg, 0.25 mmol) was added DMF (0.3 ml), then the solution of deprotonated amine. The resulting mixture was sealed and shaken at room temperature overnight. The mixture was quenched with the addition of MeOH, then concentrated under reduced pressure and purified with NH4OH modified reverse-phase-HPLC affording 4-((5-methyl-3-phenylisoxazol-4-yl)methyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (14.6 mg, 12%). 1H NMR (500 MHz, DMSO-d6) δ=12.50 (br. s., 1 H), 7.60 (dd, J=1.7, 7.7 Hz, 2 H), 7.48-7.40 (m, 3 H), 7.21 (d, J=4.6 Hz, 1 H), 7.15 (dd, J=2.1, 8.5 Hz, 1 H), 6.99 (d, J=2.2 Hz, 1 H), 6.82-6.75 (m, 2 H), 4.37 (s, 2 H), 4.03-3.95 (m, 2 H), 3.13-3.07 (m, 2 H), 2.47 (s, 3 H); m/z (ESI) 469.0 (M+H)+.

Provenance & Evidence