2-Amino-4,6-dichloropyrimidine → (3S)-1-(2-amino-6-chloro-4-pyrimidinyl)-3-piperidinecarboxylic acid
Reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([NH2:9])[N:3]=1.[NH:10]1[CH2:15][CH2:14][CH2:13][C@H:12]([C:16]([OH:18])=[O:17])[CH2:11]1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[NH2:9][C:4]1[N:3]=[C:2]([N:10]2[CH2:15][CH2:14][CH2:13][C@H:12]([C:16]([OH:18])=[O:17])[CH2:11]2)[CH:7]=[C:6]([Cl:8])[N:5]=1Participants
Conditions
- Temperature
- 140 °C
Procedure
A mixture of 4,6-dichloro-2-pyrimidinamine (1.397 g, 8.52 mmol), (3S)-3-piperidinecarboxylic acid (1 g, 7.74 mmol) and Hunig's base (2.70 ml, 15.49 mmol) in NMP (10 mL) was heated in the microwave at 140° C. for 90 minutes. LCMS showed mainly desired product. The reaction was cooled down to room temperature, and poured onto water (160 mL). The formed solid was filtered, and the filtered solid was identified as the SM 4,6-dichloro-2-pyrimidinamine. The product stayed in the aqueous solution. 1N HCl was added to adjust the pH=7. Then the aqueous solution was extracted 3× with a mixture of CHCl3 and isopropanol (200:10 mL). The organic layers were combined and evaporated to afford the title compound (1.99 g) as a yellow solid. LC-MS (ES) m/z=257 [M+H]+.
Sources & evidence
- ORD record
- ord-217279fa057d4d6ca6f6942535e06b5c
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08697685B2
Reaction notes
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