Acetic Acid → HCID 89762090, compound

Participants

Reaction Steps

To a vial charged with N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIATE M) (50 mg, 0.120 mmol) was added DCE (479 n1), acetic acid (10.28 μl, 0.180 mmol) and benzaldehyde (18.24 μl, 0.180 mmol). The mixture was shaken at room temperature for 10 min prior to the addition of sodium triacetoxyborohydride (76 mg, 0.359 mmol). The mixture was shaken at rt overnight yielding product (PMB protected) as the major species. To the mixture was added TFA (100 n1) and the mixture shaken at room temperature for 1 hr then at 80° C. for 1 hr. The mixture was concentrated under reduced pressure and purified with a 25 g HP spherical silica column (15 nm spherical, Interchim) ramping DCM:MeOH (90:10) in DCM (0-50%), monitoring at 215 nm providing product which had coeluted with minor impurities (51 mg). The material was repurified with Gilson RP-HPLC dissolving in DMSO/MeOH ramping ACN in H2O (10-90%, 0.1% TFA throughout). The product containing eluents were filtered through a 2 g SCX-2 column washing with MeOH, then 2 M NH3 in MeOH. The basic wash was dried under reduced pressure and lyophilized from MeOH/H2O providing product as an off-white solid, 4-benzyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (6 mg, 0.015 mmol, 12.93% yield). 1H NMR (500 MHz, DMSO-d6) ppm 3.45-3.50 (m, 2 H) 4.23 (t, J=4.33 Hz, 2 H) 4.56 (s, 2 H) 6.68 (d, J=8.55 Hz, 1 H) 6.75 (d, J=4.49 Hz, 1 H) 7.03 (d, J=2.24 Hz, 1 H) 7.14 (dd, J=8.49, 2.08 Hz, 1 H) 7.19 (d, J=4.49 Hz, 1 H) 7.26 (d, J=7.37 Hz, 3 H) 7.31-7.36 (m, 2 H) 12.48 (br. s., 1 H). m/z (ESI) 388.2 (M+H)+.

Provenance & Evidence