Potassium Phosphate, Tribasic → HCID 58928326, Verbindung

HRID 851913

Reaktionsgleichung

Reaktionsgleichung von HRID 851913
Br[C:2]1[NH:19][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:10][C:11]3[CH:12]=[CH:13][C:14]([CH3:18])=[C:15]([OH:17])[CH:16]=3)[C:4]=2[CH:3]=1.[NH2:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[CH:25][CH:26]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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]>[NH2:20][C:21]1[CH:26]=[C:25]([C:2]2[NH:19][C:5]3[N:6]=[CH:7][N:8]=[C:9]([NH:10][C:11]4[CH:12]=[CH:13][C:14]([CH3:18])=[C:15]([OH:17])[CH:16]=4)[C:4]=3[CH:3]=2)[CH:24]=[CH:23][CH:22]=1

Komponenten

6

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 922693-Aminophenylboronic acidHCID 694901645-(6-bromo-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-methyl-phenol

Produkt 1

HCID 58928326HCID 58928326, VerbindungAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

5-(6-bromo-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-methyl-phenol (14 mg, 0.0448 mmol) is mixed with 3-aminophenylboronic acid (13 mg, 0.0896 mmol), Pd(dppf)Cl2∩CH2Cl2 (7.5 mg, 0.009 mmol), and K3PO4 (19 mg, 0.0896 mmol) in anhydrous dioxane (0.8 mL) under an argon atmosphere. The mixture is heated to 80° C. for 18 hours, with stirring. The reaction is then cooled to ambient temperature and filtered through a pad of silica with 10% MeOH in DCM. The filtrate is concentrated and the resulting crude product is purified by reverse phase HPLC using a C18 column and 0-95% acetonitrile/water gradient to give 5-[6-(3-amino-phenyl)-7H-pyrrolo[2,3-d]primidin-4-ylamino]-2-methyl-phenol (8.6 mg, 59%); 1H NMR (500 MHz, DMSO): δ 8.16 (s, 1H), 7.27 (s, 1H), 7.17 (t, J=8.1 Hz, 1H), 7.09-7.10 (m, 2H), 7.04 (d, J=8.1 Hz, 1H), 6.92 (d, J=8.1 Hz, 1H), 6.81 (s, 1H), 6.70 (d, J=7.4 Hz, 1H), 2.19 (s, 3H); LC-ESMS observed [M+H]+ 332.1.

Aufarbeitung

  1. temperatureThe reaction is then cooled to ambient temperature
  2. filtrationfiltered through a pad of silica with 10% MeOH in DCM
  3. concentrationThe filtrate is concentrated
  4. customthe resulting crude product is purified by reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-0c5885cdf5114ec2bd6e6fe57a99a353
Quelldatensatz
uspto-grants-2007_08
Patentnummer
US07253166B2

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