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

온도

22 °C

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).

1. extractionthe aqueous layer was extracted with CHCl3 (2×15 mL)
2. dry with materialThe organic phase was dried over Na2SO4
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. customto afford a white solid
6. stirringThis solution was stirred at 22° C. for 2 hr
7. concentrationconcentrated under reduced pressure
8. dissolutionThe resulting yellow oil was redissolved in CH2Cl2 (110 mL)
9. stirringto stir at 22° C. for 6 hr
10. extractionthe aqueous layer was extracted with CHCl3 (2×30 mL)
11. concentrationThe organic phase was concentrated under reduced pressure
12. customThis oil was purified by reverse-phase prep HPLC

ORD 기록

ord-b89676e591234712922f7f7a73bacaf1

출처 데이터셋

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07456167B2