Binap, (A+-)- → HCID 90041496, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-bromo-3-methyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (0.110 g, 0.25 mmol), 1-methyl-1H-pyrazol-4-ylamine 1.35-HCl salt (0.073 g, 0.5 mmol), tris(dibenzylideneacetone)dipalladium (0.011 g, 0.0125 mmol), racemic BINAP [rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl](0.023 g, 0.038 mmol) and sodium tert-butoxide (0.094 g, 0.98 mmol) in toluene (2½ mL), under an argon atmosphere, was heated and stirred in a sealed vessel at 110° C. for 18.5 h. The cooled reaction mixture was diluted with ethyl acetate, washed once with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by chromatography (silica, 70% ethyl acetate in hexanes) gave 0.104 g of slightly impure 3-methyl-2-(1-methyl-1H-pyrazol-4-ylamino)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a yellow-brown solid. This material was combined with 0.022 g of partially purified product obtained from a separate, lower yielding, coupling reaction (palladium acetate was used in place of tris(dibenzylideneacetone)dipalladium), and purified by chromatography (silica, ethyl acetate) to give 3-methyl-2-(1-methyl-1H-pyrazol-4-ylamino)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (0.112 g) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm −0.08 (s, 9H), 0.83 (t, J=8.2 Hz, 2H), 1.38 (s, 9H), 2.54 (s, 3H), 3.51 (t, J=8.2 Hz, 2H), 3.80 (s, 3H), 5.55 (s, 2H), 7.61 (s, 1H), 7.68 (s, 1H), 7.85 (s, 1H), 8.01 (s, 1H), 8.19 (s, 1H); MS (EI/CI) m/z: 458 [M+H].

Provenance & Evidence