Hydrochloric Acid → 4-Vinylsulfonyl-morpholine

Temperatur

22 °C

7H-Indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-(4-morpholinylsulfonyl)-. To a solution of 7H-Indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6-(4-morpholinylsulfonyl)-, methyl ester (60 mg, 0.12 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 (1.0 mL) and 2M oxalyl chloride (0.24 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 (1.0 mL); BEMP (0.14, 0.47 mmol) and dimethylsulfamide (59 mg, 0.47 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 (50 mg, 68%) as a yellow paste. MS m/z 613 (MH+). 1H NMR (300 MHz, CDCl3) δ ppm 1.18-1.70 (m, 5H), 1.77 (m, 2H), 1.87-2.16 (m, 3H), 2.88 (m, 1H), 3.08 (s, 6H), 3.93 (s, 3H), 4.18 (broad m, 1H), 5.67 (broad m, 1H), 7.38 (s, 1H), 7.47 (m, 2H), 7.51 (dd, J=7.6, 8.4 Hz ,1H), 7.61 (d, J=7.6 Hz, 1H), 7.75 (d, J=8.4 Hz, 1H), 7.87 (d, J=8.4 Hz, 1H), 8.31 (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 (1.0 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-Eintrag

ord-0b45743fafd94f049f9792fd08bba93c

Quelldatensatz

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07456167B2