Sodium borohydride → 1-[5-Benzylamino-6-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

To a slurry of 1-[5-(benzylidene-amino)-6-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (0.177 g, 0.366 mmol) in ethanol (7 mL) was added sodium borohydride (41.6 mg, 1.10 mmol) at 0° C. The yellow slurry was warmed to 23° C. over 24 h. The reaction mixture was concentrated and saturated aqueous sodium bicarbonate (25 mL) was added to the residue. The reaction mixture was extracted with EtOAc (3×25 mL) and the combined organic layers were washed with brine (20 mL), dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (10-45% EtOAc/hexanes) to yield the titled compound as a 6:5 mixture of regioisomers (0.144 g, 81% yield). MS (ESI/CI): mass calcd. for C24H26ClN5O4, 483.2; m/z found, 484.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.79 (s, 1H), 8.14 (s, 1H), 7.58 (s, 1H), 7.43-7.27 (m, 5H), 6.92 (s, 1H), 6.03 (s, 2H), 4.75 (t, J=6.0 Hz, 1H), 4.49-4.43 (m, 2H), 4.34 (q, J=7.2 Hz, 2H), 3.65-3.61 (m, 2H), 3.47-3.44 (m, 2H), 3.32 (s, 1H), 1.36 (t, J=7.1 Hz, 3H).

1. concentrationThe reaction mixture was concentrated
2. additionsaturated aqueous sodium bicarbonate (25 mL) was added to the residue
3. extractionThe reaction mixture was extracted with EtOAc (3×25 mL)
4. washthe combined organic layers were washed with brine (20 mL)
5. customdried
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified (FCC) (10-45% EtOAc/hexanes)

ORD 기록

ord-e80beaec6ef24c7a9a9ca3ba47597976

출처 데이터셋

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09073923B2