N-methyl-2-methylsulfonylethanamine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Following the general procedure of example 1, 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(3-formylphenyl)-1H-indole-7-carboxamide (42.0 mg, 0.096 mmol), N-methyl-2-(methylsulfonyl)ethanamine (12.0 mg, 0.087 mmol) and NaBH(OAc)3 (58.0 mg, 0.261 mmol) were reacted to give the title compound (15.1 mg, 28.0%). were reacted

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

Procedure: Following the general procedure of example 1, 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(3-formylphenyl)-1H-indole-7-carboxamide (42.0 mg, 0.096 mmol), N-methyl-2-(methylsulfonyl)ethanamine (12.0 mg, 0.087 mmol) and NaBH(OAc)3 (58.0 mg, 0.261 mmol) were reacted to give the title compound (15.1 mg, 28.0%). were reacted

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

Procedure: In an analogous manner to Example 10, 5-(4-(4-Benzyloxy-phenylamino)-quinazolin-6-yl)-furan-2-carbaldehyde hydrochloride (0.217 g, 0.474 mmol) was reacted with N-methyl-N-(2-methanesulphonyl-ethyl)amine (0.411 g, 3.0 mmol). Purification by silica gel chromatography, eluting with 2-3% MeOH/CHCl3, followed by trituration with ether, gave the title compound as a pale yellow solid (0.100 g, 0.184 mmol, 39%); δH [2H6]DMSO 9.84 (1H, s), 8.63 (1H, s), 8.48 (1H, s), 8.12 (1H, d), 7.78 (1H, d), 7.68 (2H, d), 7.13-7.52 (5H, m), 7.02-7.10 (3H, m), 6.55 (1H, d), 5.14 (2H, s), 3.70 (2H, s), 3.35-3.44 (2H, obscured by water), 3.05 (3H, s), 2.84 (2H, t), 2.28 (3H, s). Purification by silica gel chromatography eluting with 2-3% MeOH/CHCl3

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

Procedure: In an analogous manner to Example 10, 5-(4-(4-Benzyloxy-phenylamino)-quinazolin-6-yl)-furan-2-carbaldehyde hydrochloride (0.217 g, 0.474 mmol) was reacted with N-methyl-N-(2-methanesulphonyl-ethyl)amine (0.411 g, 3.0 mmol). Purification by silica gel chromatography, eluting with 2-3% MeOH/CHCl3, followed by trituration with ether, gave the title compound as a pale yellow solid (0.100 g, 0.184 mmol, 39%); δH [2H6]DMSO 9.84 (1H, s), 8.63 (1H, s), 8.48 (1H, s), 8.12 (1H, d), 7.78 (1H, d), 7.68 (2H, d), 7.13-7.52 (5H, m), 7.02-7.10 (3H, m), 6.55 (1H, d), 5.14 (2H, s), 3.70 (2H, s), 3.35-3.44 (2H, obscured by water), 3.05 (3H, s), 2.84 (2H, t), 2.28 (3H, s). Purification by silica gel chromatography eluting with 2-3% MeOH/CHCl3

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

Procedure: (R)-2-(6-Fluoro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoic acid (15 mg, 0.051 mmol), HOBt hydrate (9.46 mg, 0.062 mmol), and EDC hydrochloride (14.81 mg, 0.077 mmol) were combined in DMF (2 mL). N-methyl-2-(methylsulfonyl)ethanamine (10.60 mg, 0.077 mmol) and 4-methylmorpholine (0.023 mL, 0.206 mmol) were added, and the reaction mixture was stirred at room temperature for 2 h. The product was purified by preparative HPLC (10-45% AcCN/H2O with 0.035% TFA), concentrated in vacuo, and lyophilized to afford the title compound as a white solid (12 mg, 57% yield). 1H NMR (500 MHz, CD3OD) δ 0.77 (d, J=6.5 Hz, 3H), 0.95 (d, J=6.5 Hz, 3H), 2.41-2.49 (m, 1H), 2.97 (s, 3H), 3.05 (s, 3H), 3.36 (t, J=6.5 Hz, 2H), 3.78 (t, J=6.5 Hz, 2H), 4.81-4.96 (m, 2H), 5.36 (d, J=11.0 Hz, 1H), 7.97 (d, J=2.5 Hz, 1H), 8.23 (d, J=2.5 Hz, 1H), 12.39 (s, 1H). [M+H] calc'd for C18H23FN4O4S, 411; found, 411. The product was purified by preparative HPLC (10-45% AcCN/H2O with 0.035% TFA) concentrated in vacuo

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

Procedure: In an analogous manner to Example 10, 5-(4-(4-Benzyloxy-phenylamino)-quinazolin-6-yl)-furan-2-carbaldehyde hydrochloride (0.217 g, 0.474 mmol) was reacted with N-methyl-N-(2-methanesulphonyl-ethyl)amine (0.41 1g, 3.0 mmol). Purification by silica gel chromatography, eluting with 2-3% MeOH/CHCl3, followed by trituration with ether, gave the title compound as a pale yellow solid (0.100 g, 0.184 mmol, 39%); δH [2H6]DMSO 9.84 (1H,s), 8.63 (1H,s), 8.48 (1H,s), 8.12 (1H,d), 7.78 (1H,d), 7.68 (2H,d), 7.13-7.52 (5H,m), 7.02-7.10 (3H,m), 6.55 (1H,d), 5.14 (2H,s), 3.70 (2H,s), 3.35-3.44 (2H, obscured by water), 3.05 (3H,s), 2.84 (2H,t), 2.28 (3H,s). Purification by silica gel chromatography eluting with 2-3% MeOH/CHCl3

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

Procedure: Following the general procedure of example 1, 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(3-formylphenyl)-1H-indole-7-carboxamide (42.0 mg, 0.096 mmol), N-methyl-2-(methylsulfonyl)ethanamine (12.0 mg, 0.087 mmol) and NaBH(OAc)3 (58.0 mg, 0.261 mmol) were reacted to give the title compound (15.1 mg, 28.0%). were reacted

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

Procedure: (R)-2-(6-Fluoro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoic acid (15 mg, 0.051 mmol), HOBt hydrate (9.46 mg, 0.062 mmol), and EDC hydrochloride (14.81 mg, 0.077 mmol) were combined in DMF (2 mL). N-methyl-2-(methylsulfonyl)ethanamine (10.60 mg, 0.077 mmol) and 4-methylmorpholine (0.023 mL, 0.206 mmol) were added, and the reaction mixture was stirred at room temperature for 2 h. The product was purified by preparative HPLC (10-45% AcCN/H2O with 0.035% TFA), concentrated in vacuo, and lyophilized to afford the title compound as a white solid (12 mg, 57% yield). 1H NMR (500 MHz, CD3OD) δ 0.77 (d, J=6.5 Hz, 3H), 0.95 (d, J=6.5 Hz, 3H), 2.41-2.49 (m, 1H), 2.97 (s, 3H), 3.05 (s, 3H), 3.36 (t, J=6.5 Hz, 2H), 3.78 (t, J=6.5 Hz, 2H), 4.81-4.96 (m, 2H), 5.36 (d, J=11.0 Hz, 1H), 7.97 (d, J=2.5 Hz, 1H), 8.23 (d, J=2.5 Hz, 1H), 12.39 (s, 1H). [M+H] calc'd for C18H23FN4O4S, 411; found, 411. The product was purified by preparative HPLC (10-45% AcCN/H2O with 0.035% TFA) concentrated in vacuo

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

Procedure: Following the general procedure of example 1, 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(3-formylphenyl)-1H-indole-7-carboxamide (42.0 mg, 0.096 mmol), N-methyl-2-(methylsulfonyl)ethanamine (12.0 mg, 0.087 mmol) and NaBH(OAc)3 (58.0 mg, 0.261 mmol) were reacted to give the title compound (15.1 mg, 28.0%). were reacted