Cesium fluoride → 4-(4-amino-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-fluorophenol

HRID 243329Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 243329
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH2:12][C:13]2[N:17]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:16]3[CH:24]=[CH:25][CH:26]=[CH:27][C:15]=3[N:14]=2)[N:3]=1.[F:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][C:34]=1[OH:35].[F-].[Cs+]>COCCOC.O.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]>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH2:12][C:13]3[N:17]([C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:16]4[CH:24]=[CH:25][CH:26]=[CH:27][C:15]=4[N:14]=3)[N:3]=[C:2]([C:31]3[CH:32]=[CH:33][C:34]([OH:35])=[C:29]([F:28])[CH:30]=3)[C:10]=12

Komponenten

7

Edukt 3

HCID 25953Cesium fluorideHCID 23005361(3-Fluoro-4-hydroxyphenyl)boronic acidHCID 681579743-iodo-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Produkt 1

HCID 1361661304-(4-amino-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-fluorophenolAusbeute 34,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittel2×HCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

A mixture of 3-iodo-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 141 (1.5 g, 3.2 mmol), 3-fluoro-4-hydroxyphenylboronic acid (0.6 g, 3.8 mmol), Pd(dppf)Cl2 (0.3 g) and CsF (1.0 g, 6.4 mmol) in DME (30 mL) and H2O (3 mL) was refluxed overnight. Then the mixture was cooled to room temperature, added H2O (50 mL) and extracted with EtOAc (30 mL×3). The combined organic layers were washed with brine and concentrated in vacuo. The residue was treated with CH2Cl2 and filtered to give 155 (500 mg, yield 34%) as a white solid. LCMS (ESI), M+H+=450.16. 1HNMR (400 MHz, DMSO) δ 5.875 (s, 2H), 7.046-7.120 (m, 2H), 7.175-7.200 (d, J=1.6 Hz, 1H), 7.242-7.307 (m, 3H), 7.432-7.472 (m, 5H), 7.687-7.708 (d, J=1.2 Hz, 1H), 8.335 (s, 1H)

Aufarbeitung

  1. temperaturewas refluxed overnight
  2. extractionextracted with EtOAc (30 mL×3)
  3. washThe combined organic layers were washed with brine
  4. concentrationconcentrated in vacuo
  5. additionThe residue was treated with CH2Cl2
  6. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-1e0826944b4e45a2b1d406495c36873f
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653089B2

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