Hydrochloric Acid → 4-Vinylsulfonyl-morpholine

Temperatur

22 °C

7H-Indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-3-methoxy-6-(4-morpholinylsulfonyl)-. To a solution of 7H-Indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-3-methoxy-6-(4-morpholinylsulfonyl)-, 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 (1.0 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 (1.0 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 (50 mg, 71%) as a yellow paste. MS 643 m/z (MH+). 1H NMR (300 MHz, CDCl3) δ ppm 1.15-1.60 (m, 4H), 1.80 (m, 1H), 1.91-2.12 (m, 5H), 2.81 (m, 3H), 3.08 (broad s, 8H), 3.22 (m, 2H), 3.41 (m, 2H), 3.92 (s, 3H), 4.4 (broad d, 1H), 5.36 (broad d, 1H), 7.02 (d, 1H), 7.15 (m, 1H), 7.40 (m, 1H), 7.51 (m, 1H), 7.68 (s, 1H), 7.90 (m, 1H), 8.11 (s, 1H), 8.58 (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-9005c5b5ea0849baadd1aedd86b42931

Quelldatensatz

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07456167B2