Ethylamine hydrochloride → 7-bromo-1-ethyl-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

Temperature

105 °C

A mixture of ethyl 2-(3,5-dibromopyrazin-2-ylamino)acetate (See Example 6.B) (1 equiv), ethylamine hydrochloride (3.1 equiv), N,N-diisopropylethylamine (4 equiv) in N-methyl pyrrolidinone was heated at 105° C. under nitrogen for 14 h. Standard ethyl acetate/water work up gave the crude product in 77% yield. This material was used without further purification. Crude ethyl 2-(5-bromo-3-(ethylamino)pyrazin-2-ylamino)acetate and acetic acid were combined in methanol. The reaction mixture was refluxed at 60-62° C. under nitrogen for 16 h. The reaction was concentrated under reduced pressure and the resultant residue was diluted with methanol and concentrated. The resultant residue was dissolved in ethyl acetate, treated with sodium carbonate and stirred for 10 min until pH˜7. The mixture was filtered and washed with ethyl acetate. The filtrate was concentrated and purification by a silica gel plug purification using (0-40% ethyl acetate in hexanes) gave the product as a tan solid. Additionally the filter-cake was suspended in water to remove potassium carbonate. The remaining solid product was collected by filtration. The process afforded product in a combined yield of 75%.

1. customThis material was used without further purification
2. temperatureThe reaction mixture was refluxed at 60-62° C. under nitrogen for 16 h
3. concentrationThe reaction was concentrated under reduced pressure
4. additionthe resultant residue was diluted with methanol
5. concentrationconcentrated
6. dissolutionThe resultant residue was dissolved in ethyl acetate
7. additiontreated with sodium carbonate
8. filtrationThe mixture was filtered
9. washwashed with ethyl acetate
10. concentrationThe filtrate was concentrated
11. custompurification
12. customby a silica gel plug purification

ORD record

ord-64eb8cdcda704cd19a2c8c31ccb8f61f

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507492B2