Methyl chloroformate → 5,8-Dimethoxy-[1,2,4]triazolo[1,5-c]pyrimidin-2-amine

온도

45 °C

To a 25 mL three-neck round bottom flask were added 1.11 g (5.55 mmol) of 90 wt % 2,5-dimethoxy-4-cyanoaminopyrimidine (2), 463 mg (6.66 mmol) of hydroxylamine hydrochloride, and 9.8 g of acetonitrile. To this mixture was added 681 mg (6.72 mmol) of triethylamine in one portion. The reaction mixture was heated to a gentle reflux (˜45° C.) for 2 h. The reaction mixture was cooled in an ice water bath to about 5.8° C. at which time an additional 716 mg (7.08 mmol) of triethylamine was added in one portion. To this mixture was added 662 mg (7.01 mmol) of methyl chloroformate in one portion at which time the internal reaction temperature rose from 5.8° C. to 12.1° C. The ice water bath was removed and the mixture was stirred at ambient temperature for 1 h and then at reflux (˜76° C.) for about 3 h. The reaction mixture was cooled to ambient temperature and an additional 100 μL of triethylamine was added to adjust the reaction pH to about 7-8. To this mixture was added 11.3 g of water; the mixture was transferred to a 100 mL round bottom flask; and the acetonitrile was removed in vacuo at 60 mm Hg and 30° C. The aqueous slurry was then suction filtered over a medium glass frit and the residue from the flask was transferred with ˜2 g of water. After the cake de-liquored, another 1 g displacement water wash was passed through the cake. After suction air drying the cake for 30 min, the mixture was allowed to dry over a nitrogen pad overnight. This afforded 588 mg (˜97% pure by liquid chromatography (LC) analysis) of 2-amino-5,8-dimethoxy-[1,2,4]-triazolo[1,5-c]pyrimidine (I) as a light yellow solid in 52.8% yield from starting 2,5-dimethoxy-4-cyanoaminopyrimidine (2). 1H NMR (DMSO-d6, 400 MHz) δ 3.90 (s, 3H), 4.06 (s, 3H), 6.28 (br s, 2H), 7.48 (s, 1H); 13C NMR (DMSO-d6, 100 MHz) δ 55.37, 57.04, 123.07, 138.60, 143.73, 148.50, 166.02.

1. temperatureThe reaction mixture was heated to
2. additionwas added in one portion
3. customrose from 5.8° C. to 12.1° C
4. customThe ice water bath was removed
5. temperatureat reflux (˜76° C.) for about 3 h
6. temperatureThe reaction mixture was cooled to ambient temperature
7. additionan additional 100 μL of triethylamine was added
8. customthe reaction pH to about 7-8
9. customthe mixture was transferred to a 100 mL round bottom flask
10. customand the acetonitrile was removed in vacuo at 60 mm Hg and 30° C
11. filtrationsuction filtered over a medium glass frit
12. washwash
13. customAfter suction air drying the cake for 30 min
14. customto dry over a nitrogen pad overnight

ORD 기록

ord-6a2312ce96414cd8b400bc6bf883acef

출처 데이터셋

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09000160B2