1-(azetidin-3-yl)-2-methylpropan-1-ol

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: A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (125 mg, 0.32 mmol), 1-azetidin-3-yl-2-methylpropan-1-ol (50 mg, 0.38 mmol) and 4 Å molecular sieves (1.0 g) in 1,2-dichloroethane (5 mL) was stirred at RT under nitrogen atmosphere for 5 h. Sodium triacetoxyborohydride (102 mg, 0.48 mmol) was added and the resulting reaction mixture was stirred at RT for 16 h. The solvent was reduced in vacuo and the residue was loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was washed with DCM/MeOH, the desired product was subsequently eluted using a mixture of 2M NH3 in MeOH and DCM. The solvents were reduced in vacuo to afford 313 as an off-white foam (60 mg, 37%). LCMS (Method G): RT 6.95 min, [M+H]+ 505. 1H NMR (400 MHz, CDCl3): δ 7.99-7.95 (1 H, m), 7.72-7.71 (1 H, m), 7.23 (2 H, m), 4.32 (4 H, br s), 3.85-3.78 (9 H, m), 3.47-3.45 (3 H, m), 3.32 (2 H, q, J=7.48 Hz), 3.25 (1 H, t, J=6.66 Hz), 3.13 (1 H, t, J=6.66 Hz), 2.66-2.65 (1 H, m), 1.62-1.60 (2 H, m), 1.41 (3 H, t, J=7.48 Hz), 0.87 (6 H, dd, J=11.85, 6.78 Hz) the resulting reaction mixture was stirred at RT for 16 h The cartridge was washed with DCM/MeOH the desired product was subsequently eluted a mixture of 2M NH3 in MeOH and DCM

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

Procedure: Trifluoroacetic acid (3 mL) was added to a solution of 3-(1-hydroxy-2-methylpropyl)azetidine-1-carboxylic acid tert-butyl ester (0.84 g, 3.66 mmol) in dichloromethane (12 mL). The resulting reaction mixture was stirred at RT for 40 min. The solvents were reduced in vacuo. The resulting residue was loaded onto an Isolute® SCX-2 cartridge (5 g). The cartridge was washed with DCM/MeOH, the desired product was subsequently eluted using a mixture of 2M NH3 in MeOH and DCM. The solvents were reduced in vacuo to afford 1-Azetidin-3-yl-2-methylpropan-1-ol as a white solid (0.42 g, 88%). 1H NMR (400 MHz, CDCl3): δ 3.63-3.62 (3 H, m), 3.53-3.51 (2 H, m), 2.88-2.87 (1 H, m), 1.62-1.62 (1 H, m), 0.89 (6 H, dd, J=6.84, 4.72 Hz) The resulting reaction mixture The cartridge was washed with DCM/MeOH the desired product was subsequently eluted a mixture of 2M NH3 in MeOH and DCM

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

Procedure: A mixture of 242-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (125 mg, 0.32 mmol), 1-azetidin-3-yl-2-methylpropan-1-ol (50 mg, 0.38 mmol) and 4 Å molecular sieves (1.0 g) in 1,2-dichloroethane (5 mL) was stirred at RT under nitrogen atmosphere for 5 h. Sodium triacetoxyborohydride (102 mg, 0.48 mmol) was added and the resulting reaction mixture was stirred at RT for 16 h. The solvent was reduced in vacuo and the residue was loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was washed with DCM/MeOH, the desired product was subsequently eluted using a mixture of 2M NH3 in MeOH and DCM. The solvents were reduced in vacuo to afford 313 as an off-white foam (60 mg, 37%). LCMS (Method G): RT 6.95 min, [M+H]+ 505. 1H NMR (400 MHz, CDCl3): δ 7.99-7.95 (1 H, m), 7.72-7.71 (1 H, m), 7.23 (2 H, m), 4.32 (4 H, br s), 3.85-3.78 (9 H, m), 3.47-3.45 (3 H, m), 3.32 (2 H, q, J=7.48 Hz), 3.25 (1 H, t, J=6.66 Hz), 3.13 (1 H, t, J=6.66 Hz), 2.66-2.65 (1 H, m), 1.62-1.60 (2 H, m), 1.41 (3 H, t, J=7.48 Hz), 0.87(6 H, dd, J=11.85, 6.78 Hz) the resulting reaction mixture was stirred at RT for 16 h The cartridge was washed with DCM/MeOH the desired product was subsequently eluted a mixture of 2M NH3 in MeOH and DCM

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

Procedure: Trifluoroacetic acid (3 mL) was added to a solution of 3-(1-hydroxy-2-methylpropyl)azetidine-1-carboxylic acid tert-butyl ester (0.84 g, 3.66 mmol) in dichloromethane (12 mL). The resulting reaction mixture was stirred at RT for 40 min. The solvents were reduced in vacuo. The resulting residue was loaded onto an Isolute® SCX-2 cartridge (5 g). The cartridge was washed with DCM/MeOH, the desired product was subsequently eluted using a mixture of 2M NH3 in MeOH and DCM. The solvents were reduced in vacuo to afford 1-Azetidin-3-yl-2-methylpropan-1-ol as a white solid (0.42 g, 88%). 1H NMR (400 MHz, CDCl3): δ 3.63-3.62 (3H, m), 3.53-3.51 (2H, m), 2.88-2.87 (1H, m), 1.62-1.62 (1H, m), 0.89 (6H, dd, J=6.84, 4.72 Hz) The resulting reaction mixture The cartridge was washed with DCM/MeOH the desired product was subsequently eluted a mixture of 2M NH3 in MeOH and DCM