1-aminocyclopentane-1-carboxamide;hydrochloride

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

Procedure: A solution of 2,6-dichloro-3-cyano-5-fluoropyridine (250 mg, 1.30 mmol), 1-aminocyclopentanecarboxamide hydrochloride (214 mg, 1.30 mmol) and DIEA (0.650 mL, 3.73 mmol) in DMSO (3 mL) was stirred at 95 C for 4 h. Water and EtOAc were added. The organic phase was separated, dried over Na2SO4, concentrated in vacuo. The residue was purified by a silica gel column, eluted with 50-100% EtOAc in hexane to give 1-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)cyclopentanecarboxamide (180 mg). The organic phase was separated dried over Na2SO4 concentrated in vacuo The residue was purified by a silica gel column eluted with 50-100% EtOAc in hexane

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

Procedure: A solution of tert-butyl 1-carbamoylcyclopentylcarbamate (305 mg, 1.33 mmol) in 4N HCl in dioxane (5 mL) and aq. 6N HCl (3 mL) was stirred at room temperature for 3 h. It was then concentrated in vacuo to give 1-aminocyclopentanecarboxamide hydrochloride as a solid (214 mg). It was then concentrated in vacuo

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

Procedure: To a stirred solution of 1-aminocyclopentanecarboxamide hydrochloride (0.46 g, 2.79 mmol) in DCM (4 mL), cooled to 0° C., were added 2-chlorobenzoyl chloride (0.73 g, 4.19 mmol) and triethylamine (0.97 mL, 6.99 mmol). After stirring for 3 h, the precipitate in the reaction mixture was filtered to give the title compound. the precipitate in the reaction mixture was filtered

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

Procedure: Compound 25 was synthesized from 4a (251 mg, 0.66 mmol) and 5j (140 mg, 0.98 mmol) as a white solid (140 mg, 45%) in a manner similar to that described in Example 53. 1H NMR (400 MHz, CDCl3) δ 7.40 (d, 1H), 7.32˜7.26 (m, 3H), 7.12 (s, 1H), 7.02 (d, 2H), 2.49 (m, 2H), 2.36 (s, 3H), 2.17 (m, 2H), 1.86 (m, 4H); ESMS m/z: 473.1 (M+1).

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

Procedure: A solution of 2,6-dichloro-3-cyano-5-fluoropyridine (250 mg, 1.30 mmol), 1-aminocyclopentanecarboxamide hydrochloride (214 mg, 1.30 mmol) and DIEA (0.650 mL, 3.73 mmol) in DMSO (3 mL) was stirred at 95 C for 4 h. Water and EtOAc were added. The organic phase was separated, dried over Na2SO4, concentrated in vacuo. The residue was purified by a silica gel column, eluted with 50-100% EtOAc in hexane to give 1-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)cyclopentanecarboxamide (180 mg). The organic phase was separated dried over Na2SO4 concentrated in vacuo The residue was purified by a silica gel column eluted with 50-100% EtOAc in hexane

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

Procedure: A solution of tert-butyl 1-carbamoylcyclopentylcarbamate (305 mg, 1.33 mmol) in 4N HCl in dioxane (5 mL) and aq. 6N HCl (3 mL) was stirred at room temperature for 3 h. It was then concentrated in vacuo to give 1-aminocyclopentanecarboxamide hydrochloride as a solid (214 mg). It was then concentrated in vacuo