N,N-Diethylaniline → Methyl 5-chloroimidazo[1,2-c]pyrimidine-7-carboxylate
Reaction equation
O[C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[CH:5]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[N:3]=1.C(N(CC)C1C=CC=CC=1)C.O=P(Cl)(Cl)[Cl:28]>>[Cl:28][C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[CH:5]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[N:3]=1Participants
Conditions
- Temperature
- 50 °C
Procedure
Methyl 5-hydroxyimidazo[1,2-c]pyrimidine-7-carboxylate (4.0 g, 21 mmol) and N,N-diethylaniline (6.6 mL, 41 mmol) were suspended in POCl3 (80 mL, 870 mmol) and heated at 50° C. for 30 minutes. The reaction mixture remained heterogeneous, so the temperature was raised to 100° C. After 30 minutes, LCMS analysis showed mostly the title compound, along with 5,7-dichloroimidazo[1,2-c]pyrimidine (which was presumably formed from 7-chloroimidazo[1,2-c]pyrimidin-5-ol carried through from the previous step). The reaction mixture was cooled to ambient temperature and concentrated down to remove the POCl3. The residue was cooled in an ice bath and quenched carefully with water. Solid K2CO3 was added to neutralize the solution to pH 7, which was then extracted with DCM. The combined organic layers were filtered through a Biotage phase separator cartridge and washed with DCM. The filtrate was concentrated down to a thick dark greenish brown residue. While sitting overnight, a precipitate formed. The resultant solid was triturated in DCM and Et2O to give afford methyl 5-chloroimidazo[1,2-c]pyrimidine-7-carboxylate (6.4 g, 21 mmol, 100% yield) as a brick-red solid. The solid was 70% pure, but could not be purified at this stage due to its insolubility. The crude material was used directly in the next step. MS (apci) m/z=212.2 (M+H).
Workup
- temperatureso the temperature was raised to 100° C
Sources & evidence
- ORD record
- ord-d527ec45a35742d396766b9f7ba6a432
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08962596B2
Reaction notes
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