Methylamine → 1-(2-(Cyclopropylthio)-5-nitrophenyl)-N-methylmethanamine

Temperature

25 °C

To a stirred solution of 2-(cyclopropylthio)-5-nitrobenzaldehyde (5 g, 22.40 mmol, see WO 2008/079759 for preparation) in MeOH (50 mL) was added methylamine (6.32 g, 67.2 mmol) dropwise and stirred for 1 h at 25° C. The reaction mixture was cooled to 0° C. and sodium borohydride (1.695 g, 44.8 mmol) was added portionwise with stirring. The reaction mixture was allowed to warm to rt and stirred overnight. The reaction mixture was concentrated under reduced pressure, diluted with EtOAc (250 mL), washed with water (2×100 mL), brine (1×100 mL) and dried (Na2SO4). Solvent was removed under reduced pressure to give Intermediate 6A (5 g, 20.98 mmol, 94% yield) as a orange oil. It was utilized in the subsequent step without any further purification. 1H NMR (400 MHz, chloroform-d) δ 8.11 (d, J=2.6 Hz, 1H), 8.04 (dd, J=8.8, 2.6 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 3.69 (s, 2H), 2.40 (s, 3H), 2.13-2.09 (m, 1H), 1.18-1.12 (m, 2H), 0.73-0.67 (m, 2H); MS (ESI) m/z: 239.2 (M+H)+.

1. temperatureThe reaction mixture was cooled to 0° C.
2. stirringwith stirring
3. temperatureto warm to rt
4. stirringstirred overnight
5. concentrationThe reaction mixture was concentrated under reduced pressure
6. additiondiluted with EtOAc (250 mL)
7. washwashed with water (2×100 mL), brine (1×100 mL)
8. dry with materialdried (Na2SO4)
9. customSolvent was removed under reduced pressure

ORD record

ord-4c02375f6dbf402c8e49893b200ee7bd

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09174974B2