Ammonia → [1-(4-Amino-pyrimidin-2-yl)-cyclopropyl]-carbamic acid tert-butyl ester

3-Dimethylamino-acrylonitrile (0.05 mL, 0.50 mmol) was dissolved in EtOH (1 mL) and NaOEt solution (21 wt % in EtOH, 0.19 mL, 0.50 mmol) was added. This was stirred for 1 h and then (1-Carbamimidoyl-cyclopropyl)-carbamic acid tert-butyl ester hydrochloride (50 mg, 0.25 mmol) was added. The reaction was stirred for 1.5 h at 60° C. and then solid NH4Cl (27 mg, 0.50 mmol) and NH3 (7 M in MeOH, 0.50 mL, 3.5 mmol) were added and stirring was continued at 60° C. for 1 h and then at 100° C. for 17 h. Additional 3-dimethylamino-acrylonitrile (0.1 mL, 0.87 mmol) was added to the reaction and stirring was continued at 100° C. for 22 h. The solvent was removed under a stream of N2 and the residue was directly purified by reversed phase HPLC (20% MeCN/H2O+0.1% TFA) to give a red semisolid that was neutralized by dissolving in EtOAc (5 mL) and washing with saturated aqueous NaHCO3 (2×5 mL). The organic phase was dried with Na2SO4 and concentrated to give 29 mg of the title compound as a red semisolid, m/z 251.44 [M+1]+.

1. stirringThe reaction was stirred for 1.5 h at 60° C.
2. stirringstirring
3. waitwas continued at 60° C. for 1 h
4. waitat 100° C. for 17 h
5. stirringstirring
6. waitwas continued at 100° C. for 22 h
7. customThe solvent was removed under a stream of N2
8. customthe residue was directly purified by reversed phase HPLC (20% MeCN/H2O+0.1% TFA)
9. customto give a red semisolid that
10. washwashing with saturated aqueous NaHCO3 (2×5 mL)
11. dry with materialThe organic phase was dried with Na2SO4
12. concentrationconcentrated

ORD record

ord-baedb3f43c164857927a67e608fa4cfe

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08552205B2