Phosphorus oxychloride → 4-Chloro-2-(trifluoromethyl)pyrimidine

To 2-(trifluoromethyl)pyrimidin-4-ol (2 g, 12 mmol) was added POCl3 (15 mL). It was refluxed overnight. The solvent was removed. 1N NaOH was added to the reaction mixture slowly until pH=10. The mixture was extracted with DCM (3×80 mL). Combined DCM layer dried over Na2SO4 and taken to dryness. The crude product was vacuum distilled. 4-chloro-2(trifluromethyl)pyrimidine was obtained as a clear oil. (94%). 1H NMR (400 MHz, DCM) δ: 7.60 (d, J=3 Hz, 1H), 8.80 (d, J=3 Hz, 1H), To a mixture of compound 30a (137 mg, 0.75 mmol) and compound 4b (235 mg, 0.75 mmol) in IPA (1 mL), was added TEA (210 mL, 1.5 mmol). The reaction was heated in microwave oven at 140° C. for 20 min. HPLC yielded the desired product as a white powder (28 mg, 6.4%). 1H NMR (400 MHz, DMSO) δ: 1.04 (m, 2 H), 1.62 (m, 6 H), 1.88 (m, 1 H), 2.73 (m,1 H), 4.34 (m, 2 H), 7.09-7.37 (m, 6 H), 8.41 (s, 1 H). Anal. (C22H22N7OF3.0.52TFA.0.54H2O) C, H, N. APCI-MS:[M+H] 458.

1. temperatureIt was refluxed overnight
2. customThe solvent was removed
3. addition1N NaOH was added to the reaction mixture slowly until pH=10
4. extractionThe mixture was extracted with DCM (3×80 mL)
5. dry with materialCombined DCM layer dried over Na2SO4
6. distillationdistilled

ORD record

ord-5299c18f9ed0457e8a0263ed6e07be6e

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08067591B2