Methanol → HCID 89761989, compound

Participants

Reaction Steps

To a solution of 4-(2-(1,2-dihydroxyethyl)-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (from EXAMPLE 204, intermediate in Step 2; 0.100 g, 0.161 mmol) in THF (0.619 ml)/water (0.619 ml) was added sodium periodate (0.052 g, 0.241 mmol). The reaction mixture was stirred at RT for 2 h. Upon completion, the reaction was filtered and washed well with THF. The filtrate was concentrated in vacuo and 4-(2-formyl-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide was carried on without purification. To a solution of 4-(2-formyl-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.095 g, 0.161 mmol, 100% yield) in methanol (1.609 ml, 0.161 mmol) was added sodium borohydride (0.012 g, 0.322 mmol) at 0° C. (turned from yellow to clear solution upon addition), and the reaction was stirred in the ice-bath for 30 minutes until completion. The reaction was quenched with sat ammonium chloride solution (aq) and washed with DCM (×2). After drying via phase separator (Radley's Discovery Technology), the organics were concentrated in vacuo to yield an orange oil. The oil was taken up in DCM, and TFA was added (color change from orange solution to light pink). The reaction was stirred for 1 h until complete deprotection. The material was concentrated in vacuo and purified via silica gel chromatography, eluting with 0-100% ethyl acetate in heptane to yield 4-(2-(hydroxymethyl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.017 g, 0.036 mmol, 22.41% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.58 (br. s., 1 H) 3.66-3.79 (m, 1 H) 4.30-4.37 (m, 2 H) 4.38-4.58 (m, 2 H) 5.42 (t, J=5.48 Hz, 1H) 6.12 (d, J=8.51 Hz, 1 H) 6.78 (d, J=4.50 Hz, 1 H) 7.10 (dd, J=8.46, 2.10 Hz, 1H) 7.15 (d, J=2.05 Hz, 1 H) 7.21 (d, J=4.60 Hz, 1 H) 7.53 (d, J=8.31 Hz, 1 H) 7.73 (d, J=8.22 Hz, 1 H) 7.92 (s, 1 H) 12.55 (br. s., 1 H). m/z (ESI) 472.0 (M+H)+.

Provenance & Evidence