Diethyl Ether → Ethyl 5-chloropyrazolo(1,5-a)pyrimidine-3-carboxylate
Reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]2[CH:14]=[CH:13][C:12](=O)[NH:11][C:10]=12)=[O:5])[CH3:2].C(N(C(C)C)CC)(C)C.C(OCC)C.P(Cl)(Cl)([Cl:32])=O>>[Cl:32][C:12]1[CH:13]=[CH:14][N:9]2[N:8]=[CH:7][C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[C:10]2[N:11]=1Participants
Conditions
- Temperature
- 90 °C
Procedure
To a suspension of 5-oxo-4,5-dihydro-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid ethyl ester (prepared according to Gavrin, L. K. et al, J. Org. Chem. 2007, 72, 1043-1046) (3.00 g, 14.5 mmol, 1 equiv) in phosphorus oxychloride (30 mL) was added diisopropylethylamine (2.00 mL, 11.6 mmol, 0.8 equiv). The mixture was heated to 90° C. for 4.5 hours. After cooling, the mixture was carefully quenched with ice-water and extracted with dichloromethane. The organic extract was washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous sodium sulphate, filtered, and concentrated under vacuum to give a solid. Trituration (diethyl ether) afforded 2.38 g (73%) of ethyl 5-chloropyrazolo[1,5-a]pyrimidine-3-carboxylate as a solid. LCMS (ESI) m+H=226.2 (mono chlorinated isotope pattern); 1H NMR (400 MHz, CDCl3) δ: 8.63 (d, 1H), 8.56 (s, 1H), 6.99 (d, 1H), 4.43 (q, 2H), 1.42 (t, 3H).
Workup
- temperatureAfter cooling
- customthe mixture was carefully quenched with ice-water
- extractionextracted with dichloromethane
- extractionThe organic extract
- washwas washed with saturated aqueous sodium bicarbonate solution
- dry with materialdried over anhydrous sodium sulphate
- filtrationfiltered
- concentrationconcentrated under vacuum
- customto give a solid
Sources & evidence
- ORD record
- ord-29c6d0884e20401784eca3d3106bb6d2
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08637526B2
Reaction notes
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