Acetic Acid → 6-Bromo-2-(2-cyclopropyl-4-pyrimidinyl)-1h-imidazo[4,5-b]pyrazine

HRID 931231Notes

Reaction equation

[Br:1][C:2]1[N:3]=[C:4]([NH2:9])[C:5]([NH2:8])=[N:6][CH:7]=1.[CH:10]1([C:13]2[N:18]=[C:17]([C:19](=N)OCC)[CH:16]=[CH:15][N:14]=2)[CH2:12][CH2:11]1.C(N(CC)CC)C.C(O)(=O)C>C(O)C>[Br:1][C:2]1[N:3]=[C:4]2[NH:9][C:19]([C:17]3[CH:16]=[CH:15][N:14]=[C:13]([CH:10]4[CH2:12][CH2:11]4)[N:18]=3)=[N:8][C:5]2=[N:6][CH:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 5-bromopyrazine-2,3-diamine (50 mg, 0.3 mmol) and ethyl 2-cyclopropylpyrimidine-4-carbimidate (Intermediate 19, 50.7 mg, 0.3 mmol), triethylamine (73.8 μL, 0.5 mmol), acetic acid (244 μL, 4.2 mmol) and ethanol (0.8 mL) was heated to 100° C. for 30 min. The mixture was concentrated and diluted with water. Then a saturated aqueous solution of sodium bicarbonate was added and the mixture was extracted with ethyl acetate. The organics were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The crude material was purified via flash chromatography (0-5% methanol in dichloromethane) to afford 6-bromo-2-(2-cyclopropylpyrimidin-4-yl)-1H-imidazo[4,5-b]pyrazine (21 mg, 25%).

Workup

concentrationThe mixture was concentrated
additiondiluted with water
additionThen a saturated aqueous solution of sodium bicarbonate was added
extractionthe mixture was extracted with ethyl acetate
washThe organics were washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated under reduced pressure
customThe crude material was purified via flash chromatography (0-5% methanol in dichloromethane)

Sources & evidence

ORD record: ord-9bc4a801e7794d64b45e16619e18ba17
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296745B2

Reaction notes

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