Water → N-(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-6-methoxybenzene-1,3-diamine

A mixture of 5-chloro-N-{4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl}-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 19, 145 mg, 0.28 mmol), iron (95 mg, 1.71 mmol) and NH4Cl (11.4 mg, 0.21 mmol) was heated at reflux in ethanol (6 mL) and water (2 mL) for 1.5 h. The mixture was then cooled and concentrated in vacuo. The resulting residue was triturated using 10% CH3OH in CH2Cl2 (15 mL) for 15 minutes and the mixture was then filtered. The residues were triturated again using 10% CH3OH in CH2Cl2 (15 mL) and the mixture was filtered. The combined filtrates were washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification by FCC, eluting with 2% 7N methanolic ammonia in CH2Cl2 gave the title compound (112 mg, 82%) as a yellow gum; 1H NMR: (CDCl3) 1.83-1.96 (1H, m), 2.08-2.23 (1H, m), 2.30 (6H, s), 2.82-2.92 (1H, m), 2.99-3.13 (2H, m), 3.17-3.28 (2H, m), 3.65 (2H, s), 3.84 (3H, s), 6.72 (1H, s), 6.96 (1H, td), 7.38 (1H, ddd), 7.52 (1H, s), 7.90 (1H, s), 8.36 (1H, s), 8.55-8.60 (1H, m), 8.65 (1H, dd), 8.94 (1H, s); m/z: ES+ MH+ 479.5.

1. temperaturewas heated
2. temperatureThe mixture was then cooled
3. concentrationconcentrated in vacuo
4. customThe resulting residue was triturated
5. customfor 15 minutes
6. filtrationthe mixture was then filtered
7. customThe residues were triturated again
8. filtrationthe mixture was filtered
9. washThe combined filtrates were washed with brine
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated in vacuo
12. customPurification by FCC
13. washeluting with 2% 7N methanolic ammonia in CH2Cl2

ORD record

ord-00c1ee85292d4745a516ab35266fedbc

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946235B2