반응 #68956

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5-(8-bromoisoquinolin-3-ylamino)pyrazine-2-carbonitrile

1H-pyrazol-3-yl boronic acid

sodium carbonate

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required product

수율 30.0%

5-(8-(1H-pyrazol-3-yl)isoquinolin-3-ylamino)pyrazine-2-carbonitrile

수율 30.0%

용매

DMF

반응 조건

후처리

1. 1
   기타The mixture was further degassed for 5 minutes
2. 2
   기타The cooled mixture was partitioned between ethyl acetate and water
3. 3
   추출The aqueous layer was further extracted with ethyl acetate
4. 4
   세척the combined organics were washed with water and brine
5. 5
   건조dried (Na2SO4)
6. 6
   농축The eluent was concentrated to a yellow solid which
7. 7
   workup.DISSOLUTIONwas dissolved in methanol
8. 8
   기타purified by SPE on a MP-TsOH cartridge
9. 9
   세척eluting with 2 M ammonia in methanol

실험 절차

A mixture of 5-(8-bromoisoquinolin-3-ylamino)pyrazine-2-carbonitrile (65 mg, 0.20 mmol), 1H-pyrazol-3-yl boronic acid (33 mg, 0.30 mmol) and aqueous sodium carbonate (0.5M, 0.60 mL, 0.30 mmol) in DMF (2 mL) was degassed for 15 minutes before the addition of tetrakis(triphenylphosphine)palladium(0) (12 mg, 0.10 mmol). The mixture was further degassed for 5 minutes and then heated to 140° C. for 20 minutes in a microwave reactor. The cooled mixture was partitioned between ethyl acetate and water. The aqueous layer was further extracted with ethyl acetate and the combined organics were washed with water and brine, dried (Na2SO4), and passed sequentially through two PS-Thiol cartridges. The eluent was concentrated to a yellow solid which was dissolved in methanol and purified by SPE on a MP-TsOH cartridge, eluting with 2 M ammonia in methanol. Concentration of the eluent gave the required product as a light yellow solid (18 mg, 0.06 mmol, 29%). 1H NMR (DMSO, 400 MHz) δ 13.25 (br s, 1H), 11.10 (br s, 1H), 10.00 (s, 1H), 8.84 (s, 1H), 8.72 (s, 1H), 8.55 (s, 1H), 7.80-8.00 (m, 2H), 7.70-7.80 (m, 2H), 6.80 (s, 1H). LCMS (2) Rt=2.46 min, m/z (ESI+) 314 (MH+).

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