Methyl iodide → 5-Azaindole

Temperature

0 °C

4-tert-Butoxycarbonylamino-3-methylpyridine A solution of 4-tert-butoxycarbonylaminopyridine (10.0 g, 51.5 mmol) in tetrahydrofuran (150 ml) was cooled to -30° C. and n-butyllithium (45.3 ml, 2.5M in hexane, 113.3 mmol) was added at such a rate as to keep the temperature below -20° C. The mixture was stirred at 0° C. for 3 hours, the slurry cooled to -70° C. and a solution of methyl iodide (8.77 g, 61.8 mmol) in tetrahydrofuran (25 ml) added. The mixture was warmed to 20° C. and stirred for 1 hour. The mixture was quenched with water (100 ml) and extracted with ethyl acetate (2×100 ml). The combined ethyl acetate fractions were washed with saturated brine (100 ml), dried (Na2SO4), filtered and concentrated in vacuo. The crude product was chromatographed on silica gel (95% methylene chloride/5% methanol) and then swished in hot hexane to afford the title compound as a pale yellow solid; yield: 5.75 g (54%). mp 124°-126° C.; Analysis Found: C, 63.35; H, 7.72; N, 13.44. C11H16N2O2 : requires C, 63.44; H, 7.74; N, 13.45%; 1H NMR (CD2Cl1 /TMS) δ1.52 (9H, s), 2.22 (3H, s), 6.92 (1H, br.s), 7.97 (1H, d, J=5.6 Hz), 8.28 (1H, s), 8.33 (1H, d, J=5.6 Hz).

1. customthe temperature below -20° C
2. temperaturethe slurry cooled to -70° C.
3. temperatureThe mixture was warmed to 20° C.
4. stirringstirred for 1 hour
5. customThe mixture was quenched with water (100 ml)
6. extractionextracted with ethyl acetate (2×100 ml)
7. washThe combined ethyl acetate fractions were washed with saturated brine (100 ml)
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude product was chromatographed on silica gel (95% methylene chloride/5% methanol)

ORD record

ord-5bf3934016d44439967e2bbb8e23fc25

Source dataset

uspto-grants-1997_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05681959