N-methylcyclopentanamine;hydrochloride

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 9-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene (360 mg, 0.81 mmol), Pd(OAc)2 (58 mg, 0.26 mmol), Cyclopentyl-methylamine HCl salt (236 mg, 1.74 mmol), 2,8,9-tributyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (99 mg, 0.29 mmol), tert-butoxide (256 mg, 2.61 mmol) in dioxane (2 mL) was bubbled N2 for 10 min and then stirred at 130° C. for 5 min under the irradition of microwave. The mixture was filtered over ceilite. The filtrate was concentrated to dryness and purified by pre-TLC (EtOAc:hexanes=1:1) to afford 51 mg of 123. (yield=13%). 1H NMR (CDCl3, 400 MHz) δ: 8.01 (s, 1H), 7.50-7.44 (m, 1H), 7.04-6.98 (m, 4H), 6.18-6.15 (d, J=8.8 Hz, 1H), 4.16-4.14 (m, 2H), 3.12-3.03 (m, 4H), 2.09-2.02 (m, 1H), 1.77-1.70 (m, 2H), 1.60-1.47 (m, 4H), 1.24-1.18 (m, 2H). LC-MS (ESI): m/z=480 [M+H]+ was bubbled N2 for 10 min The mixture was filtered over ceilite The filtrate was concentrated to dryness purified by pre-TLC (EtOAc:hexanes=1:1)

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 9-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene (360 mg, 0.81 mmol), Pd(OAc)2 (58 mg, 0.26 mmol), Cyclopentyl-methylamine HCl salt (236 mg, 1.74 mmol), 2,8,9-tributyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (99 mg, 0.29 mmol), tert-butoxide (256 mg, 2.61 mmol) in dioxane (2 mL) was bubbled N2 for 10 min and then stirred at 130° C. for 5 min under the irradition of microwave. The mixture was filtered over ceilite. The filtrate was concentrated to dryness and purified by pre-TLC (EtOAc:hexanes=1:1) to afford 51 mg of 123. (yield=13%). 1H NMR (CDCl3, 400 MHz) δ: 8.01 (s, 1H), 7.50-7.44 (m, 1H), 7.04-6.98 (m, 4H), 6.18-6.15 (d, J=8.8 Hz, 1H), 4.16-4.14 (m, 2H), 3.12-3.03 (m, 4H), 2.09-2.02 (m, 1H), 1.77-1.70 (m, 2H), 1.60-1.47 (m, 4H), 1.24-1.18 (m, 2H). LC-MS (ESI): m/z=480 [M+H]+ was bubbled N2 for 10 min The mixture was filtered over ceilite The filtrate was concentrated to dryness purified by pre-TLC (EtOAc:hexanes=1:1)

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 9-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene (360 mg, 0.81 mmol), Pd(OAc)2 (58 mg, 0.26 mmol), Cyclopentyl-methylamine HCl salt (236 mg, 1.74 mmol), 2,8,9-tributyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (99 mg, 0.29 mmol), tert-butoxide (256 mg, 2.61 mmol) in dioxane (2 mL) was bubbled N2 for 10 min and then stirred at 130° C. for 5 min under the irradition of microwave. The mixture was filtered over ceilite. The filtrate was concentrated to dryness and purified by pre-TLC (EtOAc:hexanes=1:1) to afford 51 mg of 123. (yield=13%). 1H NMR (CDCl3, 400 MHz) δ: 8.01 (s, 1H), 7.50-7.44 (m, 1H), 7.04-6.98 (m, 4H), 6.18-6.15 (d, J=8.8 Hz, 1H), 4.16-4.14 (m, 2H), 3.12-3.03 (m, 4H), 2.09-2.02 (m, 1H), 1.77-1.70 (m, 2H), 1.60-1.47 (m, 4H), 1.24-1.18 (m, 2H). LC-MS (ESI): m/z=480 [M+H]+ was bubbled N2 for 10 min The mixture was filtered over ceilite The filtrate was concentrated to dryness purified by pre-TLC (EtOAc:hexanes=1:1)

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 9-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene (360 mg, 0.81 mmol), Pd(OAc)2 (58 mg, 0.26 mmol), Cyclopentyl-methylamine HCl salt (236 mg, 1.74 mmol), 2,8,9-tributyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (99 mg, 0.29 mmol), tert-butoxide (256 mg, 2.61 mmol) in dioxane (2 mL) was bubbled N2 for 10 min and then stirred at 130° C. for 5 min under the irradition of microwave. The mixture was filtered over ceilite. The filtrate was concentrated to dryness and purified by pre-TLC (EtOAc: hexanes=1:1) to afford 51 mg of 123. (yield=13%). 1H NMR (CDCl3, 400 MHz) δ: 8.01 (s, 1H), 7.50-7.44 (m, 1H), 7.04-6.98 (m, 4H), 6.18-6.15 (d, J=8.8 Hz, 1H), 4.16-4.14 (m, 2H), 3.12-3.03 (m, 4H), 2.09-2.02 (m, 1H), 1.77-1.70 (m, 2H), 1.60-1.47 (m, 4H), 1.24-1.18 (m, 2H). LC-MS (ESI): m/z=480 [M+H]+ was bubbled N2 for 10 min The mixture was filtered over ceilite The filtrate was concentrated to dryness purified by pre-TLC (EtOAc: hexanes=1:1)

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 9-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene (360 mg, 0.81 mmol), Pd(OAc)2 (58 mg, 0.26 mmol), Cyclopentyl-methylamine HCl salt (236 mg, 1.74 mmol), 2,8,9-tributyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (99 mg, 0.29 mmol), tert-butoxide (256 mg, 2.61 mmol) in dioxane (2 mL) was bubbled N2 for 10 min and then stirred at 130° C. for 5 min under the irradition of microwave. The mixture was filtered over ceilite. The filtrate was concentrated to dryness and purified by pre-TLC (EtOAc: hexanes=1:1) to afford 51 mg of 123. (yield=13%). 1H NMR (CDCl3, 400 MHz) δ: 8.01 (s, 1H), 7.50-7.44 (m, 1H), 7.04-6.98 (m, 4H), 6.18-6.15 (d, J=8.8 Hz, 1H), 4.16-4.14 (m, 2H), 3.12-3.03 (m, 4H), 2.09-2.02 (m, 1H), 1.77-1.70 (m, 2H), 1.60-1.47 (m, 4H), 1.24-1.18 (m, 2H). LC-MS (ESI): m/z=480 [M+H]+ was bubbled N2 for 10 min The mixture was filtered over ceilite The filtrate was concentrated to dryness purified by pre-TLC (EtOAc: hexanes=1:1)

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 9-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene (360 mg, 0.81 mmol), Pd(OAc)2 (58 mg, 0.26 mmol), Cyclopentyl-methylamine HCl salt (236 mg, 1.74 mmol), 2,8,9-tributyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (99 mg, 0.29 mmol), tert-butoxide (256 mg, 2.61 mmol) in dioxane (2 mL) was bubbled N2 for 10 min and then stirred at 130° C. for 5 min under the irradition of microwave. The mixture was filtered over ceilite. The filtrate was concentrated to dryness and purified by pre-TLC (EtOAc: hexanes=1:1) to afford 51 mg of 123. (yield=13%). 1H NMR (CDCl3, 400 MHz) δ: 8.01 (s, 1H), 7.50-7.44 (m, 1H), 7.04-6.98 (m, 4H), 6.18-6.15 (d, J=8.8 Hz, 1H), 4.16-4.14 (m, 2H), 3.12-3.03 (m, 4H), 2.09-2.02 (m, 1H), 1.77-1.70 (m, 2H), 1.60-1.47 (m, 4H), 1.24-1.18 (m, 2H). LC-MS (ESI): m/z=480 [M+H]+ was bubbled N2 for 10 min The mixture was filtered over ceilite The filtrate was concentrated to dryness purified by pre-TLC (EtOAc: hexanes=1:1)

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 9-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene (360 mg, 0.81 mmol), Pd(OAc)2 (58 mg, 0.26 mmol), Cyclopentyl-methylamine HCl salt (236 mg, 1.74 mmol), 2,8,9-tributyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (99 mg, 0.29 mmol), tert-butoxide (256 mg, 2.61 mmol) in dioxane (2 mL) was bubbled N2 for 10 min and then stirred at 130° C. for 5 min under the irradition of microwave. The mixture was filtered over ceilite. The filtrate was concentrated to dryness and purified by pre-TLC (EtOAc: hexanes=1:1) to afford 51 mg of 123. (yield=13%). 1H NMR (CDCl3, 400 MHz) δ: 8.01 (s, 1H), 7.50-7.44 (m, 1H), 7.04-6.98 (m, 4H), 6.18-6.15 (d, J=8.8 Hz, 1H), 4.16-4.14 (m, 2H), 3.12-3.03 (m, 4H), 2.09-2.02 (m, 1H), 1.77-1.70 (m, 2H), 1.60-1.47 (m, 4H), 1.24-1.18 (m, 2H). LC-MS (ESI): m/z=480 [M+H]+ was bubbled N2 for 10 min The mixture was filtered over ceilite The filtrate was concentrated to dryness purified by pre-TLC (EtOAc: hexanes=1:1)