Formamidine acetate → HCID 178432632, compound

Temperature

100 °C

2-Methyl-4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-amine, trifluoroacetate salt (103.0 g, 353.7 mmol) and formamidine acetate (98%, 131 g, 1.23 mol) were combined in 2-butanol (350 mL). The reaction was heated to 100° C. for 3 hours, at which time it was allowed to cool to room temperature and diluted with a 2:1 mixture of 10 N sodium hydroxide solution/saturated aqueous sodium chloride solution (300 mL). After vigorous stirring, the layers were separated, and the aqueous layer was extracted with 2-butanol (4×250 mL). The combined organic layers were concentrated in vacuo, and the resulting solid was slurried with acetonitrile (550 mL), stirred for 2 hours at room temperature and filtered. The collected solids were washed with dry acetonitrile (3×100 mL), then dried in vacuo at 40° C. for 2 hours to provide the product as an off-white solid. Yield: 61.5 g, 301 mmol, 85%. The mother liquor was concentrated to dryness, then dissolved in acetonitrile (200 mL) and allowed to stand for 18 hours. The resulting solid was isolated by filtration to provide additional product as an off-white solid. Combined yield: 64.8 g, 317 mmol, 90%. 1H NMR (500 MHz, CD3OD), presumed to be a mixture of rotamers or tautomers: δ 2.25 and 2.29 (2 s, 3H), 3.88 and 3.88 (2 s, 3H), 7.03 and 7.19 (2 s, 1H), 7.39 and 7.94 (2 s, 1H), 7.69 and 7.67 (2 s, 1H), 7.77 and 7.75 (2 s, 1H).

1. temperatureto cool to room temperature
2. customAfter vigorous stirring, the layers were separated
3. extractionthe aqueous layer was extracted with 2-butanol (4×250 mL)
4. concentrationThe combined organic layers were concentrated in vacuo
5. filtrationfiltered
6. washThe collected solids were washed with dry acetonitrile (3×100 mL)
7. customdried in vacuo at 40° C. for 2 hours

ORD record

ord-b6aa73bc339e4cb3ad9cb4cf2453c9b5

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598155B2