Dimethylformamide → 5-Fluoro-3-methyl-pyrrolo[3,2-b]pyridin-1-ylamine

Temperature

0 °C

A solution of 5-fluoro-3-methyl-1H-pyrrolo[3,2-b]pyridine (10.7 mmol) in anhydrous DMF (15 mL) is added drop-wise to a stirred solution of NaH (60%, 160 mmol) in anhydrous DMF (25 mL) under N2 at 0° C. for 20 min and stirred at 0° C. under N2 for 30 minutes. HOSA (53.5 mmol) is added portion-wise for 30 minutes at 0° C., and stirred at 0° C. for 1.5 hours. After quenching with ice-water (400 mL), the mixture is extracted with ether (3×60 mL). The combined organic layer is washed with water (2×30 mL) and brine (20 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue is purified by silica gel column chromatography eluting with 0-60% EtOAc in heptane to afford 5-fluoro-3-methyl-pyrrolo[3,2-b]pyridin-1-ylamine (570 mg). MS: 166 (M+H); 1H NMR (300 MHz, CDCl3) δ 2.32 (s, 3H), 4.82 (br, 2N—H), 6.76 (d, H), 7.17 (s, H), 7.77 (dd, H).

1. additionHOSA (53.5 mmol) is added portion-wise for 30 minutes at 0° C.
2. stirringstirred at 0° C. for 1.5 hours
3. customAfter quenching with ice-water (400 mL)
4. extractionthe mixture is extracted with ether (3×60 mL)
5. washThe combined organic layer is washed with water (2×30 mL) and brine (20 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue is purified by silica gel column chromatography
10. washeluting with 0-60% EtOAc in heptane

ORD record

ord-d652396f997d4b5d902a7c0336192ee8

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258130B2