Cyclopropanemethanamine → 5-bromo-2-(cyclopropylmethylamino)-3-methylpyrimidin-4(3H)-one
Reaction equation
[Br:1][C:2]1[C:3](=[O:10])[N:4]([CH3:9])[C:5](Cl)=[N:6][CH:7]=1.[CH:11]1([CH2:14][NH2:15])[CH2:13][CH2:12]1.C([O-])(O)=O.[Na+]>CCCCO.CCOC(C)=O>[Br:1][C:2]1[C:3](=[O:10])[N:4]([CH3:9])[C:5]([NH:15][CH2:14][CH:11]2[CH2:13][CH2:12]2)=[N:6][CH:7]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 60 °C
Procedure
A mixture of 5-bromo-2-chloro-3-methylpyrimidin-4(3H)-one (0.100 g, 0.45 mmol), cyclopropylmethanamine (0.051 mL, 0.58 mmol) and NaHCO3 (0.150 g, 1.79 mmol) in n-BuOH (3 mL) was stirred at 60° C. for 1 hour. The reaction mixture was cooled to room temperature and then diluted with EtOAc. The EtOAc layer washed with H2O and saturated aqueous NaCl. The aqueous phase was re-extracted with EtOAc (1×). The combined EtOAc layers were dried (Na2SO4), filtered and concentrated to yield the desired product (0.114 g, 98%) as a pale yellow solid that was used without further purification. 1H NMR (400 MHz, DMSO-d6) δ 7.93 (s, 1H), 7.46 (t, J=5.5 Hz, 1H), 3.33 (s, 3H), 3.19 (t, J=6.2 Hz, 2H), 1.12 (m, 1H), 0.43 (m, 2H), 0.24 (m, 2H). LRMS (ESI pos) m/e 258, 260 (M+1, Br pattern).
Workup
- temperatureThe reaction mixture was cooled to room temperature
- washThe EtOAc layer washed with H2O and saturated aqueous NaCl
- extractionThe aqueous phase was re-extracted with EtOAc (1×)
- dry with materialThe combined EtOAc layers were dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-11a21765cc9243509ba21a2aafd09c8b
- Source dataset
- uspto-grants-2010_05
- Patent number
- US07723330B2
Reaction notes
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