Reaktion #68963

Reaktionsgleichung

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

N-(2-aminoethyl)morpholine

triphenylphosphine

sodium acetate

→

title compound

Ausbeute 32.5%

3-(5-Cyanopyrazin-2-ylamino)-N-(2-morpholinoethyl)isoquinoline-8-carboxamide

Ausbeute 32.5%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas degassed
2. 2
   Sonstigeby bubbling N2 through the solution for 5 mins
3. 3
   Sonstigethe mixture degassed for a further 5 minutes
4. 4
   SonstigeCarbon monoxide was then bubbled through the solution for 5 minutes, before the reaction vessel
5. 5
   Sonstigewas sealed
6. 6
   Sonstigepartitioned between ethyl acetate and aqueous sodium hydrogen carbonate (2.5%)
7. 7
   SonstigeThe phases were separated
8. 8
   Waschenthe aqueous phase washed with ethyl acetate
9. 9
   WaschenThe combined organic phases were washed with aqueous sodium hydrogen carbonate (2.5%)
10. 10
    Trocknenbefore being dried (Na2SO4)
11. 11
    Einengenconcentrated to dryness

Vorschrift

A mixture of 5-(8-bromoisoquinolin-3-ylamino)pyrazine-2-carbonitrile (33 mg, 0.10 mmol), N-(2-aminoethyl)morpholine (26 mg, 0.20 mmol), triphenylphosphine (8 mg, 0.030 mmol), and sodium acetate (3.3 mg, 0.040 mmol) in DMF (1 mL) was degassed by bubbling N2 through the solution for 5 mins. Palladium (II) acetate (6.8 mg, 0.030 mmol) was added and the mixture degassed for a further 5 minutes. Carbon monoxide was then bubbled through the solution for 5 minutes, before the reaction vessel was sealed. The solution was stirred at 80° C. under a balloon of carbon monoxide for 90 minutes and then partitioned between ethyl acetate and aqueous sodium hydrogen carbonate (2.5%). The phases were separated and the aqueous phase washed with ethyl acetate. The combined organic phases were washed with aqueous sodium hydrogen carbonate (2.5%) before being dried (Na2SO4) and then passed sequentially through two PS-Thiol cartridges and concentrated to dryness. Preparative HPLC gave the title compound (5.1 mg, 0.013 mmol, 12%). 1H NMR (d6-DMSO, 400 MHz) δ 11.05 (s, 1H), 9.58 (s, 1H), 8.83 (d, 1H, J=1.2 Hz), 8.73 (d, 1H, J=1.2 Hz), 8.63 (br t, 1H, J=5.8 Hz), 8.56 (s, 1H), 8.00 (d, 1H, J=8.4 Hz), 7.75 (dd, 1H, J=7.1, 8.3 Hz), 7.57 (d, 1H, J=6.8 Hz), 3.62-3.68 (m, 4H), 3.46-3.52 (m, 2H), 2.52-2.58 (m, 2H), 2.46-2.52 (m, 4H, partially obscured by DMSO). LC-MS (2) Rt=1.95 min; m/z (ESI+) 404 (M+H).

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