N,N-Dimethylaniline → 7-Chloro-5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazolo[1,5-a]pyrimidine
Reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[C:15](O)[N:14]4[N:18]=[CH:19][CH:20]=[C:13]4[N:12]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.CN(C)C1C=CC=CC=1.O=P(Cl)(Cl)[Cl:32]>>[Cl:32][C:15]1[N:14]2[N:18]=[CH:19][CH:20]=[C:13]2[N:12]=[C:11]([CH:8]2[CH2:9][CH2:10][C:5]3([O:4][CH2:3][CH2:2][O:1]3)[CH2:6][CH2:7]2)[CH:16]=1Participants
Procedure
5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazolo[1,5-a]pyrimidin-7-ol (11.7 mmol) is charged to 250 mL roundbottom flask. To this flask is added 4 mL N,N-dimethylaniline, followed by 40 mL POCl3. This suspension was sonicated to break up the starting material and stirred at room temperature for 18 hours. After 18 hours, a solution formed. The solution was reduced in vacuo and cooled to 0° C. in ice bath. The reaction is then quenched with sat. NaHCO3(aq) and extracted with DCM (×3). The combined organics are dried with Na2SO4 and the solvent was removed in vacuo. The resulting oil was purified via silica gel column on 20% to 100% ethyl acetate in hexanes gradient to yield 7-chloro-5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazolo[1,5-a]pyrimidine (2.65 grams, 77% across 2 steps) as white solid.
Workup
- customThis suspension was sonicated
- waitAfter 18 hours
- customa solution formed
- temperaturecooled to 0° C. in ice bath
- customThe reaction is then quenched with sat. NaHCO3(aq)
- extractionextracted with DCM (×3)
- dry with materialThe combined organics are dried with Na2SO4
- customthe solvent was removed in vacuo
- customThe resulting oil was purified via silica gel column on 20% to 100% ethyl acetate in hexanes gradient
Sources & evidence
- ORD record
- ord-854089970b5e4e7291ae65092cf2c3ef
- Source dataset
- uspto-grants-2013_11
- Patent number
- US08591943B2
Reaction notes
Loading…