2-methoxy-4-(morpholin-4-ylmethyl)aniline

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

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

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

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into an 8-dram vial, Trifluoro-methanesulfonic acid 7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester (88.0 mg, 0.195 mmol), 2-Methoxy-4-morpholin-4-ylmethyl-phenylamine (0.174 g, 0.782 mmol), N,N-Diisopropylethylamine (0.136 mL, 0.782 mmol), and 1-Methoxy-2-propanol (0.880 mL, 9.00 mmol) were added. The reaction mixture was heated at 120° C. for 4 hours. The solvent was removed under vacuum. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN. The collected fractions were concentrated under vacuum to give a glassy solid. The solid was triturated with Et2O to give N-{2-[2-(2-Methoxy-4-morpholin-4-ylmethyl-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-phenyl}-N-methyl-methanesulfonamide as a yellow solid (46 mg, 37%). LCMS (E/I+) 523.15 (M+H). NMR 1H (DMSO-d6)-9.61 (s, 1H), 8.13 (d, 1H, J=8.58 Hz), 7.95-8.00 (m, 1H), 7.86 (s, 1H), 7.66-7.70 (m, 1H), 7.53-7.58 (m, 1H), 7.16 (d, 1H, J=1.72 Hz), 7.04 (d, 1H, J=4.66 Hz), 7.01 (d, 1H, J=4.66 Hz), 6.96 (d, 1H, J=8.58 Hz), 4.29 (d, 2H, J=3.50 Hz), 3.86-4.04 (m, 5H), 3.61 (t, 2H, J=11.67 Hz), 3.20 (d, 2H, J=12.84 Hz), 3.00-3.15 (m, 5H), 2.88 (s, 3H). The solvent was removed under vacuum The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN The collected fractions were concentrated under vacuum to give a glassy solid The solid was triturated with Et2O

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 8-dram vial, Trifluoro-methanesulfonic acid 7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester (72.9 mg, 0.195 mmol), 2-Methoxy-4-morpholin-4-ylmethyl-phenylamine (0.174 g, 0.782 mmol), N,N-Diisopropylethylamine (0.136 mL, 0.782 mmol), and 1-Methoxy-2-propanol (0.250 mL, 2.56 mmol). The reaction mixture was heated at 120° C. for 60 minutes. HPLC suggested little if any triflate SM. The solvent was removed under vacuum. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN. The collected fractions were lyophilized to give (2-Methoxy-4-morpholin-4-ylmethyl-phenyl)-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine a brown solid (11 mg, 10%). LCMS (E/I+) 445.19 (M+H). NMR 1H (DMSO-d6)-9.81 (s, 1H), 8.99 (s, 1H), 8.24 (d, 1H, J=8.32 Hz), 7.73-7.82 (m, 2H), 7.48 (dt, 1H, JJ=1.19, 8.92 Hz), 7.22 (d, 1H, J=8.11 Hz), 7.17 (, s, 1H), 7.11 (t, 1H, J=7.40 Hz), 6.85-7.05 (m, 3H), 4.28 (bs, 2H), 3.90-4.02 (m, 5H), 3.79 (s, 3H), 3.62 (t, 2H, J=11.67 Hz), 3.26 (d, 2H, J=13.80 Hz), 3.08 (bs, 2H). The solvent was removed under vacuum The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN