반응 #359730

반응 방정식

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

NaOH

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

HCl

oxalyl chloride

HCl

BEMP

dimethylsulfamide

→

title compound

수율 71.0%

4-(Vinylsulfonyl)morpholine

수율 71.0%

용매

MeOH THF

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 (1.0 mL)
9. 9
   workup.STIRRINGto stir at 22° C. for 6 hr
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]-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).

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