4-ethenylsulfonylmorpholine

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). the aqueous layer was extracted with CHCl3 (2×15 mL) The organic phase was dried over Na2SO4 filtered concentrated under reduced pressure to afford a white solid This solution was stirred at 22° C. for 2 hr concentrated under reduced pressure The resulting yellow oil was redissolved in CH2Cl2 (1.0 mL) to stir at 22° C. for 6 hr 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

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5H-Indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6,7-dihydro-3-methoxy-6-(4-morpholinylsulfonyl)-. To a solution of 5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6,7-dihydro-3-methoxy-6-(4-morpholinylsulfonyl)-(45 mg, 0.084 mmol) in CH2Cl2 (1.0 mL) was added 2M oxalyl chloride (0.20 mL) in CH2Cl2. 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 (0.10 mL, 0.33 mmol) and dimethylsulfamide (42 mg, 0.33 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 (2×20 mL). The organic phase was concentrated under reduced pressure. This oil was purified by reverse-phase prep HPLC to afford the title compound (34 mg, 64%) as a yellow paste. MS m/z 645 (MH+). Two rotomers present in NMR. 1H NMR (300 MHz, CDCl3) δ ppm 1.26 (m, 1H), 1.32-1.49 (m, 2H), 1.64 (m, 1H), 1.78 (m, 2H), 1.88-2.10 (m, 4H), 2.89 (m, 1H), 2.97-3.15 (m, 9H), 3.36 (m, 2.6H), 3.45 (m, 1.4H), 3.66-3.81 (m, 4H), 3.92 (d, 3H), 3.96 (m, 0.65H), 4.07 (m, 0.35H), 4.72 (m, 0.35H), 4.97 (d, J=15 Hz, 0.65H), 6.92 (m, 0.65H), 6.97 (m, 1.35H), 7.33-7.47 (m, 2H), 7.87 (m, 1H), 7.99 (m, 1H), 8.55 (broad s, 1H). concentrated under reduced pressure The resulting yellow oil was redissolved in CH2Cl2 (1.0 mL) to stir at 22° C. for 6 hr the aqueous layer was extracted with CHCl3 (2×20 mL) The organic phase was concentrated under reduced pressure This oil was purified by reverse-phase prep HPLC

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5H-Indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6,7-dihydro-3-methoxy-6-(4-morpholinylsulfonyl)-. To a solution of 5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6,7-dihydro-3-methoxy-6-(4-morpholinylsulfonyl)-(45 mg, 0.084 mmol) in CH2Cl2 (1.0 mL) was added 2M oxalyl chloride (0.20 mL) in CH2Cl2. 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 (0.10 mL, 0.33 mmol) and dimethylsulfamide (42 mg, 0.33 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 (2×20 mL). The organic phase was concentrated under reduced pressure. This oil was purified by reverse-phase prep HPLC to afford the title compound (34 mg, 64%) as a yellow paste. MS m/z 645 (MH+). Two rotomers present in NMR. 1H NMR (300 MHz, CDCl3) δ ppm 1.26 (m, 1H), 1.32-1.49 (m, 2H), 1.64 (m, 1H), 1.78 (m, 2H), 1.88-2.10 (m, 4H), 2.89 (m, 1H), 2.97-3.15 (m, 9H), 3.36 (m, 2.6H), 3.45 (m, 1.4H), 3.66-3.81 (m, 4H), 3.92 (d, 3H), 3.96 (m, 0.65H), 4.07 (m, 0.35H), 4.72 (m, 0.35H), 4.97 (d, J=15 Hz, 0.65H), 6.92 (m, 0.65H), 6.97 (m, 1.35H), 7.33-7.47 (m, 2H), 7.87 (m, 1H), 7.99 (m, 1H), 8.55 (broad s, 1H). concentrated under reduced pressure The resulting yellow oil was redissolved in CH2Cl2 (1.0 mL) to stir at 22° C. for 6 hr the aqueous layer was extracted with CHCl3 (2×20 mL) The organic phase was concentrated under reduced pressure This oil was purified by reverse-phase prep HPLC

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). the aqueous layer was extracted with CHCl3 (2×15 mL) The organic phase was dried over Na2SO4 filtered concentrated under reduced pressure to afford a white solid This solution was stirred at 22° C. for 2 hr concentrated under reduced pressure The resulting yellow oil was redissolved in CH2Cl2 (1.0 mL) to stir at 22° C. for 6 hr 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

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). the aqueous layer was extracted with CHCl3 (2×15 mL) The organic phase was dried over Na2SO4 filtered concentrated under reduced pressure to afford a white solid This solution was stirred at 22° C. for 2 hr concentrated under reduced pressure The resulting yellow oil was redissolved in CH2Cl2 (1.0 mL) to stir at 22° C. for 6 hr 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

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). the aqueous layer was extracted with CHCl3 (2×15 mL) The organic phase was dried over Na2SO4 filtered concentrated under reduced pressure to afford a white solid This solution was stirred at 22° C. for 2 hr concentrated under reduced pressure The resulting yellow oil was redissolved in CH2Cl2 (1.0 mL) to stir at 22° C. for 6 hr 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

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5H-Indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6,7-dihydro-3-methoxy-6-(4-morpholinylsulfonyl)-. To a solution of 5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6,7-dihydro-3-methoxy-6-(4-morpholinylsulfonyl)-(45 mg, 0.084 mmol) in CH2Cl2 (1.0 mL) was added 2M oxalyl chloride (0.20 mL) in CH2Cl2. 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 (0.10 mL, 0.33 mmol) and dimethylsulfamide (42 mg, 0.33 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 (2×20 mL). The organic phase was concentrated under reduced pressure. This oil was purified by reverse-phase prep HPLC to afford the title compound (34 mg, 64%) as a yellow paste. MS m/z 645 (MH+). Two rotomers present in NMR. 1H NMR (300 MHz, CDCl3) δ ppm 1.26 (m, 1H), 1.32-1.49 (m, 2H), 1.64 (m, 1H), 1.78 (m, 2H), 1.88-2.10 (m, 4H), 2.89 (m, 1H), 2.97-3.15 (m, 9H), 3.36 (m, 2.6H), 3.45 (m, 1.4H), 3.66-3.81 (m, 4H), 3.92 (d, 3H), 3.96 (m, 0.65H), 4.07 (m, 0.35H), 4.72 (m, 0.35H), 4.97 (d, J=15 Hz, 0.65H), 6.92 (m, 0.65H), 6.97 (m, 1.35H), 7.33-7.47 (m, 2H), 7.87 (m, 1H), 7.99 (m, 1H), 8.55 (broad s, 1H). concentrated under reduced pressure The resulting yellow oil was redissolved in CH2Cl2 (1.0 mL) to stir at 22° C. for 6 hr the aqueous layer was extracted with CHCl3 (2×20 mL) The organic phase was concentrated under reduced pressure This oil was purified by reverse-phase prep HPLC

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). the aqueous layer was extracted with CHCl3 (2×15 mL) The organic phase was dried over Na2SO4 filtered concentrated under reduced pressure to afford a white solid This solution was stirred at 22° C. for 2 hr concentrated under reduced pressure The resulting yellow oil was redissolved in CH2Cl2 (1.0 mL) to stir at 22° C. for 6 hr 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

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). the aqueous layer was extracted with CHCl3 (2×15 mL) The organic phase was dried over Na2SO4 filtered concentrated under reduced pressure to afford a white solid This solution was stirred at 22° C. for 2 hr concentrated under reduced pressure The resulting yellow oil was redissolved in CH2Cl2 (1.0 mL) to stir at 22° C. for 6 hr 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

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (3R)-3-(4-iodo-phenyl)-cyclopentanone (286 mg, 1 mmol), 4-(vinylsulfonyl)morpholine (265 mg, 1.5 mmol), tri(o-tolyl)-phosphin (20 mg), Pd(OAc)2 (8 mg) and NaOAc (164 mg) in DMF (4 mL) was heated at 130 C for 1.5 h. After cooling, the mixture 1H NMR (300 MHz, DMSO) δ 7.73 (d, J=8.2 Hz, 2H), 7.45-7.36 (m, 3H), 7.26 (d, J=15.5 Hz, 1H), 3.71-3.61 (m, 4H), 3.52-3.37 (m, 1H), 3.10-3.02 (m, 4H), 2.61-2.49 (m, 1H), 2.41-2.21 (m, 4H), 2.01-1.84 (m, 1H). was heated at 130 C for 1.5 h After cooling

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). the aqueous layer was extracted with CHCl3 (2×15 mL) The organic phase was dried over Na2SO4 filtered concentrated under reduced pressure to afford a white solid This solution was stirred at 22° C. for 2 hr concentrated under reduced pressure The resulting yellow oil was redissolved in CH2Cl2 (1.0 mL) to stir at 22° C. for 6 hr 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

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5H-Indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6,7-dihydro-3-methoxy-6-(4-morpholinylsulfonyl)-. To a solution of 5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6,7-dihydro-3-methoxy-6-(4-morpholinylsulfonyl)-(45 mg, 0.084 mmol) in CH2Cl2 (1.0 mL) was added 2M oxalyl chloride (0.20 mL) in CH2Cl2. 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 (0.10 mL, 0.33 mmol) and dimethylsulfamide (42 mg, 0.33 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 (2×20 mL). The organic phase was concentrated under reduced pressure. This oil was purified by reverse-phase prep HPLC to afford the title compound (34 mg, 64%) as a yellow paste. MS m/z 645 (MH+). Two rotomers present in NMR. 1H NMR (300 MHz, CDCl3) δ ppm 1.26 (m, 1H), 1.32-1.49 (m, 2H), 1.64 (m, 1H), 1.78 (m, 2H), 1.88-2.10 (m, 4H), 2.89 (m, 1H), 2.97-3.15 (m, 9H), 3.36 (m, 2.6H), 3.45 (m, 1.4H), 3.66-3.81 (m, 4H), 3.92 (d, 3H), 3.96 (m, 0.65H), 4.07 (m, 0.35H), 4.72 (m, 0.35H), 4.97 (d, J=15 Hz, 0.65H), 6.92 (m, 0.65H), 6.97 (m, 1.35H), 7.33-7.47 (m, 2H), 7.87 (m, 1H), 7.99 (m, 1H), 8.55 (broad s, 1H). concentrated under reduced pressure The resulting yellow oil was redissolved in CH2Cl2 (1.0 mL) to stir at 22° C. for 6 hr the aqueous layer was extracted with CHCl3 (2×20 mL) The organic phase was concentrated under reduced pressure This oil was purified by reverse-phase prep HPLC