2-Amino-4,6-dichloropyrimidine → 4-(2-Amino-6-chloro-4-pyrimidinyl)-3-morpholinecarboxamide
Reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH:2]1[C:7]([NH2:9])=[O:8].[NH2:10][C:11]1[N:16]=[C:15](Cl)[CH:14]=[C:13]([Cl:18])[N:12]=1.CCN(C(C)C)C(C)C>CC#N.CCOC(C)=O>[NH2:10][C:11]1[N:16]=[C:15]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH:2]2[C:7]([NH2:9])=[O:8])[CH:14]=[C:13]([Cl:18])[N:12]=1Participants
6
Conditions
- Temperature
- 100 °C
Procedure
A mixture of 3-morpholinecarboxamide (830 mg, 3.40 mmol), 2-amino-4,6-dichloropyrimidine (502 mg, 3.06 mmol), and Hunig's base (1.6 mL, 9.16 mmol) in CH3CN (12 mL) was stirred at 100° C. in a sealed tube for 40 hours. The mixture was diluted with EtOAc (100 mL), and washed with saturated aqueous NaHCO3 (2×50 mL) and brine (50 mL). The combined aqueous phases were further extracted with CH2Cl2 (3×50 mL) and EtOAc (3×50 mL). All of the organic phases were combined, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (34 g SiO2, CH2Cl2 to 90/10/1 CH2Cl2/CH3OH/NH4OH gradient) to give the title compound (394 mg) as a white solid. LC-MS (ES) m/z=258, 260 [M+H]+.
Workup
- washwashed with saturated aqueous NaHCO3 (2×50 mL) and brine (50 mL)
- extractionThe combined aqueous phases were further extracted with CH2Cl2 (3×50 mL) and EtOAc (3×50 mL)
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue was purified by silica gel chromatography (34 g SiO2, CH2Cl2 to 90/10/1 CH2Cl2/CH3OH/NH4OH gradient)
Sources & evidence
- ORD record
- ord-873fc21636dd41f3bf8f37ebea1c67fc
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08697685B2
Reaction notes
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