1-(1-Benzyl-2,5-diMethyl-1h-pyrrol-3-yl)-2-chloroethan-1-one synthesis

Yield:870762-83-7 27%

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide at 70; for 48 h;

Steps:

2.6.3 (CYM- 5478)

General procedure: To a stirred solution of 1-(1-benzyl-2,5-dimethyl-1H-pyrrol-3-yl)-2-chloroethanone (50 mg, 0.191 mmol) in DMF (2.5mL) were added sequentially DIPEA (66 μL, 0.38 mmol) and 2-hydroxy-5-trifluoromethyl pyridine (62 mg, 0.38 mmol). The reaction was stirred 48 h at 70°C. The mixture was diluted in water and extracted with ethyl acetate (4×50ml). The combined organic phase was washed with brine (2×50mL) and concentrated under reduced pressure. The mixture was purified by column chromatography using DCM/MeOH to yield 20 mg (0.052 mmol, 27%) of product as a pale yellow powder. ¹H NMR (400MHz, CDCl₃): δ 7.63 (br s, 1H), 7.48 (dd, J=9.5, 2.4Hz, 1H), 7.34-7.26 (m, 3H), 6.89 (d, J=7.2Hz, 2H), 6.66 (d, J=9.5Hz, 1H), 6.40 (s, 1H), 5.18 (s, 2H), 5.06 (s, 2H), 2.48 (s, 3H), 2.16 (s, 3H); ¹³C NMR (125MHz, CDCl₃): δ 187.07, 162.26, 138.86 (q, J³=5Hz), 137.71, 136.59, 135.77 (q, J³=2Hz), 129.47, 129.37, 128.00, 125.89, 123.77 (q, J¹=268Hz), 121.48, 117.25, 109.65 (q, J²=35Hz), 107.17, 55.44, 47.11, 12.62, 12.27. IR (cm^-1): 1740 s, 1675 s, 1330 s. MS (EI) m/z: 389 (M+H).

References:

Satsu, Hideo;Schaeffer, Marie-Therese;Guerrero, Miguel;Saldana, Adrian;Eberhart, Christina;Hodder, Peter;Cayanan, Charmagne;Schürer, Stephan;Bhhatarai, Barun;Roberts, Ed;Rosen, Hugh;Brown, Steven J. [Bioorganic and Medicinal Chemistry,2013,vol. 21,# 17,p. 5373 - 5382]