N-propylmethanesulfonamide

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: N-(4-[(2-amino-2-methyl-3-phenylpropoxy)methyl]-6-{[(2-methylcyclopropyl)methyl]amino}pyridin-2-yl)-N-propylmethanesulfonamide was prepared from intermediate VI and [(2-methylcyclopropyl)methyl]amine (prepared from N-benzyl-1-(2-trans-methylcyclopropyl)methenamine by hydrogenation on Pd(OH)2, in EtOH, in the presence of TFA), following a similar procedure as described for the preparation of N-4-[(2-amino-2-methyl-3-phenylpropoxy)methyl]-6-{benzyl[(2-methylcyclopropyl)methyl]amino}pyridin-2-yl)-N-propylmethanesulfonamide. HRMS (ES, M+H) calcd. for C25H38N4O3S: 475.2737, found: 475.2719.

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

Procedure: N-(4-[(2-amino-2-methyl-3-phenylpropoxy)methyl]-6-{[(2-methylcyclopropyl)methyl]amino}pyridin-2-yl)-N-propylmethanesulfonamide was prepared from intermediate VI and [(2-methylcyclopropyl)methyl]amine (prepared from N-benzyl-1-(2-trans-methylcyclopropyl)methenamine by hydrogenation on Pd(OH)2, in EtOH, in the presence of TFA), following a similar procedure as described for the preparation of N-4-[(2-amino-2-methyl-3-phenylpropoxy)methyl]-6-{benzyl[(2-methylcyclopropyl)methyl]amino}pyridin-2-yl)-N-propylmethanesulfonamide. HRMS (ES, M+H) calcd. for C25H38N4O3S: 475.2737, found: 475.2719.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 2,6-dichloroisonicotinate (4.8 g, 23.3 mmol) and N-propylmethanesulfonamide (3.8 g, 28.0 mmol) in dioxane (190 mL) was degassed with argon. Potassium phosphate tribasic (6.9 g, 32.6 mmol), xantphos (810 mg, 1.40 mmol) and Pd2 dba3 (427 mg, 0.47 mmol) were added, and the reaction mixture was stirred at 100° C., sealed, for 16 h. The reaction mixture was filtered on cellite, concentrated in vacuo, and purified by flash chromatography (2×300 g silica gel, 0 to 35% EtOAc in hexane) to give methyl 2-chloro-6-[(methylsulfonyl)(propyl)amino]isonicotinate. 1H NMR (400 MHz, CD3OD) δ 7.87 (s, 1H), 7.72 (s, 1H), 3.97 (s, 3H), 3.91 (t, J=7.2 Hz, 2H), 3.14 (s, 3H), 1.68-1.52 (m, 2H), 0.94 (t, J=7.4 Hz, 3H). sealed, for 16 h The reaction mixture was filtered on cellite concentrated in vacuo purified by flash chromatography (2×300 g silica gel, 0 to 35% EtOAc in hexane)

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

Procedure: N-(4-[(2-amino-2-methyl-3-phenylpropoxy)methyl]-6-{[(2-methylcyclopropyl)methyl]amino}pyridin-2-yl)-N-propylmethanesulfonamide was prepared from intermediate VI and [(2-methylcyclopropyl)methyl]amine (prepared from N-benzyl-1-(2-trans-methylcyclopropyl)methenamine by hydrogenation on Pd(OH)2, in EtOH, in the presence of TFA), following a similar procedure as described for the preparation of N-4-[(2-amino-2-methyl-3-phenylpropoxy)methyl]-6-{benzyl[(2-methylcyclopropyl)methyl]amino}pyridin-2-yl)-N-propylmethanesulfonamide. HRMS (ES, M+H) calcd. for C25H38N4O3S: 475.2737, found: 475.2719.