Dichloromethane → 2-(1-(4-amino-3-(2-aminopyrimidin-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-(3-fluorophenyl)-4H-chromen-4-one

HRID 1476228Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1476228
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16]4[C:21]([C:22](=[O:31])[C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:13])[N:9]=[C:10](I)[C:3]=12.[NH2:32][C:33]1[N:38]=[CH:37][C:36](B(O)O)=[CH:35][N:34]=1.C(=O)([O-])[O-].[Na+].[Na+].ClCCl>CN(C=O)C.C(O)C.O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16]4[C:21]([C:22](=[O:31])[C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:13])[N:9]=[C:10]([C:36]3[CH:35]=[N:34][C:33]([NH2:32])=[N:38][CH:37]=3)[C:3]=12

Komponenten

8

Edukt 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 17750211(2-Aminopyrimidin-5-yl)boronic acidHCID 665799322-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-(3-fluorophenyl)-4H-chromen-4-one

Produkt 1

HCID 582691762-(1-(4-amino-3-(2-aminopyrimidin-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-(3-fluorophenyl)-4H-chromen-4-oneAusbeute 14 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of Example 57c (0.350 g, 0.663 mmoles) in DMF (4 ml), ethanol (2 ml) and water (2 ml), 2-aminopyrimidine-5-boronic acid (0.184 g, 1.327 mmoles) and sodium carbonate (0.351 g, 3.318 mmoles) were added and the system is degassed for 30 min Tetrakistriphenylphosphine Palladium (0.151 g, 0.130 mmoles) was added under nitrogen atmosphere and heated to 80° C. After 12 h, the reaction mixture was celite filtered, concentrated and extracted with ethyl acetate. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The crude product was purified by column chromatography with methanol: dichloromethane to afford the title compound as brown solid (0.045 g, 14% yield). MP: 264-268° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 8.38(s,2H), 8.05(s,1H), 8.03(d, J=7.9,Hz, 1H), 7.85(m,1H), 7.68(d, J=8.3Hz, 1H), 7.52(t, J=7.3Hz, 1H), 7.29(br s, 1H), 7.07-6.93(m, 5H), 5.99(q, J=7.0Hz, 1H),1.88 (d, J=7.0Hz, 3H). Mass: 494.86(M+).

Aufarbeitung

  1. additionwas added under nitrogen atmosphere
  2. concentrationconcentrated
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography with methanol

Quellen und Nachweise

ORD-Eintrag
ord-46a09831b91d4698b6e428b9199f168a
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09018375B2

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