Hydrogen Bromide → 7-(Trifluoromethyl)imidazo(1,2-a)pyrimidine

HRID 478220Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=1.[CH2:12](OC(OCC)CBr)[CH3:13].Br>C(O)C>[F:10][C:8]([F:11])([F:9])[C:6]1[CH:5]=[CH:4][N:3]2[CH:12]=[CH:13][N:1]=[C:2]2[N:7]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 2-amino-4-(trifluoromethyl)pyrimidine (prepared according to Zanatta et al. in J. Heterocyclic Chem., 1997, 34(2), 509-513) (500 mg, 3.1 mmol) and bromoacetaldehyde diethyl acetal (1.38 ml, 9.2 mmol) in ethanol (10 ml) was treated with hydrobromic acid (0.5 ml of a 48% aqueous solution) and then heated at 70° C. for 12 h. The reaction was cooled to ambient temperature then pre-adsorbed onto silica. Purification by chromatography on silica eluting with dichloromethane (containing 1% conc. ammonia) on a gradient of methanol (1-5%) afforded 7-trifluoromethylimidazo[1,2-a]pyrimidine (500 mg, 87%) as a cream-coloured solid: δH (400 MHz, CDCl3) 7.22 (1H, d, J 7), 7.74 (1H, d, J 1), 8.03 (1H, d, J 1), 8.67 (1H, d, J 7).

Workup

temperatureThe reaction was cooled to ambient temperature
customPurification by chromatography on silica eluting with dichloromethane (containing 1% conc. ammonia) on a gradient of methanol (1-5%)

Sources & evidence

ORD record: ord-6bafdda426bd4d58807f0e31f585fc3a
Source dataset: uspto-grants-2003_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06642229B2

Reaction notes

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