반응 #359729

반응 방정식

NaOH

7H-Indolo[2,1-a][2]benzazepine-10-carboxamide

MeOH THF

HCl

oxalyl chloride

HCl

BEMP

dimethylsulfamide

→

title compound

수율 69.0%

Methyl 11-cyclohexyl-6-hydroxy-6H-isoindolo[2,1-a]indole-3-carboxylate

수율 69.0%

용매

CH2Cl2

CH2Cl2

반응 조건

후처리

1. 1
   추출the aqueous layer was extracted with CHCl3 (2×15 mL)
2. 2
   건조The organic phase was dried over Na2SO4
3. 3
   여과filtered
4. 4
   농축concentrated under reduced pressure
5. 5
   기타to afford a white solid
6. 6
   workup.STIRRINGThis solution was stirred at 22° C. for 2 hr
7. 7
   농축concentrated under reduced pressure
8. 8
   workup.DISSOLUTIONThe resulting yellow oil was redissolved in CH2Cl2 (1.5 mL)
9. 9
   workup.ADDITIONwas added
10. 10
    추출the aqueous layer was extracted with CHCl3 (2×30 mL)
11. 11
    농축The organic phase was concentrated under reduced pressure
12. 12
    기타This oil was purified by reverse-phase prep HPLC

실험 절차

7H-Indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-(ethylsulfonyl)-To a solution of 7H-Indolo[2,1-a][2]benzazepine-10-carboxylic acid,13-cyclohexyl-6-(ethylsulfonyl)-, methyl ester (80 mg, 0.17 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 (1.5 mL) and 2M oxalyl chloride (1.5 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 (1.5 mL); BEMP (94 mg, 0.34 mmol) and dimethylsulfamide (107 mg, 0.86 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 (67 mg, 69%) as a yellow paste. MS m/z 556 (MH+). 1H NMR (300 MHz, CDCl3) δ ppm 1.18-1.70 (m, 5H), 1.35 (t, 3H), 1.77 (m, 2H), 1.87-2.16 (m, 3H), 2.88 (m, 1H), 3.08 (s, 6H), 3.15 (q, 2H), 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), 8.54 (broad s, 1H).

출처