Trifluoroacetic acid → 6-bromo-2,2,3-trimethyl-2,3-dihydro-1H-imidazo[4,5-b]pyridine

5-bromo-N2-methylpyridine-2,3-diamine (54.4 mg, 0.269 mmol) was dissolved in isopropyl acetate (1.5 ml) and acetone (23 μl, 0.31 mmol), trifluoroacetic acid (0.045 ml, 0.58 mmol), and sodium triacetoxyborohydride (64 mg, 0.30 mmol) were added. The reaction was stirred under nitrogen at room temperature for 4 hours, and then more acetone was added (0.040 ml) along with TFA (0.090 ml) and isopropyl acetate (0.5 ml). The reaction was then stirred overnight. This reaction was repeated on a larger scale using 5-bromo-N2-methylpyridine-2,3-diamine (288 mg, 1.43 mmol), 2,2,2-trifluoroacetic acid (0.30 ml, 3.9 mmol), acetone (0.13 ml, 1.8 mmol), and sodium triacetoxyborohydride (352 mg, 1.66 mmol). Then, both reactions were poured into water (25 ml), and solid sodium hydroxide was added to raise the pH to about 10. The layers were separated, and the aqueous phase was extracted with EtOAc. The organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and dried under high vacuum. To afford 5-bromo-N3-isopropyl-N2-methylpyridine-2,3-diamine and 6-bromo-2,2,3-trimethyl-2,3-dihydro-1H-imidazo[4,5-b]pyridine (399 mg, 97% combined yield).

1. stirringThe reaction was then stirred overnight
2. additionwas added
3. temperatureto raise the pH to about 10
4. customThe layers were separated
5. extractionthe aqueous phase was extracted with EtOAc
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customdried under high vacuum

ORD record

ord-74bb07374504460eb0fa44a4b867d9a4

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07928140B2