Hydrochloric Acid → 5-(8-Aminoisoquinolin-3-ylamino)pyrazine-2-carbonitrile

HRID 40682

Reaktionsgleichung

Reaktionsgleichung von HRID 40682
CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.Br[C:44]1[CH:45]=[CH:46][CH:47]=[C:48]2[C:53]=1[CH:52]=[N:51][C:50]([NH:54][C:55]1[N:56]=[CH:57][C:58]([C:61]#[N:62])=[N:59][CH:60]=1)=[CH:49]2.C(=[NH:76])(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl>C1(C)C=CC=CC=1.CN(C=O)C.C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:76][C:44]1[CH:45]=[CH:46][CH:47]=[C:48]2[C:53]=1[CH:52]=[N:51][C:50]([NH:54][C:55]1[N:56]=[CH:57][C:58]([C:61]#[N:62])=[N:59][CH:60]=1)=[CH:49]2

Komponenten

10

Edukt 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 136809Benzophenone imineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 442046545-(8-Bromoisoquinolin-3-ylamino)pyrazine-2-carbonitrile

Produkt 1

HCID 442045585-(8-Aminoisoquinolin-3-ylamino)pyrazine-2-carbonitrileAusbeute 11 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

A mixture of tris(dibenzylideneacetone)dipalladium (0) (18 mg, 0.020 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (23 mg, 0.040 mmol) in toluene (1 mL) and DMF (1 mL) was degassed under a stream of nitrogen gas with stirring for 15 minutes. 5-(8-Bromoisoquinolin-3-ylamino)pyrazine-2-carbonitrile (65 mg, 0.20 mmol), benzophenone imine (36 mg, 0.20 mmol) and caesium carbonate (130 mg, 0.40 mmol) were added and the mixture was degassed for a further 5 minutes, then heated at 140° C. for 40 minutes in a microwave reactor. Upon cooling the reaction mixture was diluted with ethyl acetate and filtered through celite, washed sequentially with water and brine then dried (Na2SO4) and concentrated to dryness to afford a brown oil. The residue was dissolved in THF (2 mL) and treated with aqueous hydrogen chloride (2 mL, 2M) for 30 minutes and then concentrated to dryness. Preparative HPLC gave the title compound (5.64 mg, 0.022 mmol, 11%). 1H NMR (d6-DMSO, 400 MHz) δ 10.90 (br s, 1H), 9.35 (s, 1H), 8.80 (s, 1H), 8.70 (s, 1H), 8.25 (s, 1H), 7.40 (t, 1H, J=7.8, 6.8 Hz), 6.95 (d, 1H, J=7.8 Hz), 6.60 (d, 1H, J=6.8 Hz), 6.25 (s, 1H). LC-MS (2) Rt=2.32 min; m/z (ESI+) 263 (M+H).

Aufarbeitung

  1. customwas degassed under a stream of nitrogen gas
  2. customthe mixture was degassed for a further 5 minutes
  3. temperatureUpon cooling the reaction mixture
  4. additionwas diluted with ethyl acetate
  5. filtrationfiltered through celite
  6. washwashed sequentially with water and brine
  7. dry with materialthen dried (Na2SO4)
  8. concentrationconcentrated to dryness
  9. customto afford a brown oil
  10. concentrationconcentrated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-24a2b8616ddb46b188b6cbc8c0b22a6b
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08530468B2

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