Hydrochloric Acid → 1-Methyl-4-(vinylsulfonyl)piperazine

Participants

Reaction Conditions

Reaction Steps

7H-Indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-3-methoxy-6-[(4-methyl-1-piperazinyl)sulfonyl]-. To a solution of 7H-Indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-3-methoxy-6-[(4-methyl-1-piperazinyl)sulfonyl]-, methyl ester (60 mg, 0.11 mmol) in 1:1 MeOH/THF (2.0 mL) was added 1M NaOH (2.0 mL). The resulting mixture was stirred at 22° C. for 16 hr. 1M HCl (15 mL) was added and the aqueous layer was extracted with CHCl3 (2×15 mL). The organic phase was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford a white solid. This solid was dissolved in CH2Cl2 (110 mL) and 2M oxalyl chloride (1.0 mL) in CH2Cl2 was added. This solution was stirred at 22° C. for 2 hr and concentrated under reduced pressure. The resulting yellow oil was redissolved in CH2Cl2 (110 mL); BEMP (60 mg, 0.22 mmol) and dimethylsulfamide (68 mg, 0.55 mmol) were added. The resulting mixture was allowed to stir at 22° C. for 6 hr. 1M HCl (15 mL) was added and the aqueous layer was extracted with CHCl3 (2×30 mL). The organic phase was concentrated under reduced pressure. This oil was purified by reverse-phase prep HPLC to afford the title compound (48 mg, 68%) as a yellow paste. MS m/z 643 (MH+). 1H NMR (300 MHz, CDCl3) δ ppm 1.13-1.52 (m, 4H), 1.79 (m, 1H), 1.90-2.11 (m, 5H), 2.56 (s, 3H), 2.79 (m, 1H), 2.87-3.16 (m, 5H), 3.05 (s, 6H), 3.36 (m, 1H), 3.58 (m, 1H), 3.70 (m, 1H), 3.92 (s, 3H), 4.41 (broad d, 1H), 5.28 (broad d, 1H), 7.01 (d, 1H), 7.12 (m, 1H), 7.52 (m, 2H), 7.65 (s, 1H), 7.89 (m, 1H), 8.10 (s, 1H), 9.60 (s, 1H).

Provenance & Evidence