Sodium Carbonate → (S)-2-amino-4-((1-(8-(5-methoxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile

HRID 1626913

Reaktionsgleichung

Reaktionsgleichung von HRID 1626913
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:12]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:13](=[O:22])[C:14]3[C:19]([CH:20]=2)=[CH:18][CH:17]=[CH:16][C:15]=3Cl)[CH3:10])[C:5]([C:29]#[N:30])=[CH:4][N:3]=1.[CH3:31][O:32][C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[N:37][CH:38]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:12]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:13](=[O:22])[C:14]3[C:19]([CH:20]=2)=[CH:18][CH:17]=[CH:16][C:15]=3[C:35]2[CH:36]=[N:37][CH:38]=[C:33]([O:32][CH3:31])[CH:34]=2)[CH3:10])[C:5]([C:29]#[N:30])=[CH:4][N:3]=1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 27630875-Methoxypyridine-3-boronic AcidHCID 67950671(S)-2-amino-4-((1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile

Produkt 1

HCID 71270277(S)-2-amino-4-((1-(8-(5-methoxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a mixture of (S)-2-amino-4-(1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile 8 (50 mg, 0.12 mmol) and (5-methoxypyridin-3-yl)boronic acid (37 mg, 0.24 mmol) in anhydrous 1,4-dioxane (4 mL), PdCl2(dppf) (9.8 mg, 0.012 mmol) and aqueous Na2CO3 solution (1 M, 0.6 mL, 0.6 mmol) were added and the resulting mixture was stirred at 120° C. for 3 h. The reaction mixture was allowed to cool to RT, quenched with water, and then extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel eluting with 0-10% MeOH-DCM to afford the product, (S)-2-amino-4-((1-(8-(5-methoxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile 9. ESI-MS m/z: 490.2 [M+H]+. Compound 2-amino-4-((S)-1-(8-(5-methoxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethylamino)pyrimidine-5-carboxamide 10 was also formed in the above reaction and it was isolated by column chromatography. ESI-MS m/z: 508.2 [M+H]+.

Aufarbeitung

  1. additionwere added
  2. temperatureto cool to RT
  3. customquenched with water
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by flash column chromatography on silica gel eluting with 0-10% MeOH-DCM

Quellen und Nachweise

ORD-Eintrag
ord-8c0c55a447514cd497f128c9dd0d2f8a
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785470B2

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