Reaktion #68956

Reaktionsgleichung

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

1H-pyrazol-3-yl boronic acid

sodium carbonate

→

required product

Ausbeute 30.0%

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

Ausbeute 30.0%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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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