Dimethylformamide → 4-(7-(Cyclopropylamino)-3-formylpyrazolo[1,5-a]pyrimidin-5-ylamino)benzonitrile
Reaction equation
Cl.[CH:2]1([NH:5][C:6]2[N:11]3[N:12]=[CH:13][CH:14]=[C:10]3[N:9]=[C:8]([NH:15][C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)[CH:7]=2)[CH2:4][CH2:3]1.O=P(Cl)(Cl)Cl.CN([CH:32]=[O:33])C>>[CH:2]1([NH:5][C:6]2[N:11]3[N:12]=[CH:13][C:14]([CH:32]=[O:33])=[C:10]3[N:9]=[C:8]([NH:15][C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)[CH:7]=2)[CH2:4][CH2:3]1Participants
Conditions
- Temperature
- 0 °C
Procedure
4-(7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-ylamino)benzonitrile hydrochloride (205 mg, 0.62 mmol) was dissolved in anhydrous DMF (1 mL) and the solution was cooled to 0° C. by an external ice bath. POCl3 (115 μL, 1.25 mmol) was added dropwise keeping the internal temperature <5° C. After addition, the ice bath was removed. After 5 h, the solution was poured into H2O (20 mL) and the pH was adjusted to 11 by the addition of 6N NaOH. The solution was allowed to stir for 1 h, and the precipitate was filtered off. The crude product was triturated with EtOH (7 mL), filtered, and dried under high vacuum (1 mmHg) to provide 4-(7-(cyclopropylamino)-3-formylpyrazolo[1,5-a]pyrimidin-5-ylamino)benzonitrile (129 mg, 64%) as an orange solid. LCMS (ES): >90% pure, m/z 319 [M+1]+.
Workup
- customthe internal temperature <5° C
- additionAfter addition
- customthe ice bath was removed
- additionthe solution was poured into H2O (20 mL)
- additionthe pH was adjusted to 11 by the addition of 6N NaOH
- filtrationthe precipitate was filtered off
- customThe crude product was triturated with EtOH (7 mL)
- filtrationfiltered
- customdried under high vacuum (1 mmHg)
Sources & evidence
- ORD record
- ord-d1a8e98b8ee64691915f5a8c67e621f7
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09303033B2
Reaction notes
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