Methylamine → HCID 69286786, compound

To a solution of (S)-6-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)ethylamino)nicotinaldehyde (Example 73, 0.10 g, 0.26 mmol) in THF (5 ml) was added methylamine (2.0 M in THF, 0.52 mmol) and NaBH(OAc)3 (0.82 g, 0.39 mmol). The reaction was stirred for 3 hours, quenched with water, and extracted with DCM (2×20 ml). The combined organic fractions were dried over Na2SO4, filtered, and then concentrated. The resulting crude imine was dissolved in MeOH (5 ml) and NaBH4 (0.06 g, 0.4 mmol) was added. The reaction was stirred for 10 min, quenched with aq. Na2CO3 (10 ml), and extracted with DCM (2×20 ml). The combined organic fractions were dried over Na2SO4, filtered, and then concentrated. The resulting oil was purified by reverse phase column chromatography (5-35% ACN) to give the title compound (0.05 g, 48%). 1H NMR (400 MHz, CD3OD) δ 7.41-7.38 (m, 2H), 7.10 (d, J=9.2 Hz, 1H), 7.02-6.98 (m, 2H), 6.00-5.52 (br s, 1H), 5.05 (s, 1H), 3.63 (s, 2H), 2.37 (s, 3H), 1.87-1.82 (m, 1H), 1.51 (d, J=6.9 Hz, 3H), 0.93-0.91 (m, 2H), 0.67-0.63 (m, 2H). MS: Calcd.: 398. Found: [M+H]+399.

1. customquenched with water
2. extractionextracted with DCM (2×20 ml)
3. dry with materialThe combined organic fractions were dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. dissolutionThe resulting crude imine was dissolved in MeOH (5 ml)
7. stirringThe reaction was stirred for 10 min
8. customquenched with aq. Na2CO3 (10 ml)
9. extractionextracted with DCM (2×20 ml)
10. dry with materialThe combined organic fractions were dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. customThe resulting oil was purified by reverse phase column chromatography (5-35% ACN)

ORD record

ord-cc60204040ba40548fe0a494f087bf50

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08835465B2