Cesium fluoride → 3-(4-amino-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-5-fluorophenol

HRID 243327Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 243327
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]=[C:33]([OH:35])[CH:34]=1.[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]=[C:33]([OH:35])[CH:34]=[C:29]([F:28])[CH:30]=3)[C:10]=12

Komponenten

7

Edukt 3

HCID 25953Cesium fluorideHCID 447173083-Fluoro-5-hydroxybenzeneboronic acidHCID 681579743-iodo-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Produkt 1

HCID 681581243-(4-amino-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-5-fluorophenolAusbeute 31,1 %

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 (1.0 g, 2.14 mmol), 3-fluoro-5-hydroxyphenylboronic acid (0.4 g, 2.56 mmol), Pd(dppf)Cl2 (0.2 g) and CsF (0.65 g, 4.3 mmol) in DME (20 mL) and H2O (2 mL) was refluxed overnight. Then the mixture was cooled to room temperature, added H2O (50 mL) and extracted with EtOAc (20 mL×3). The combined organic layers were washed with brine, dried over Na2SO4 and then concentrated in vacuo. The residue was treated with CH2Cl2 and filtered to give 153 (300 mg, yield 31%) as a grey solid. LCMS (ESI), M+H+=450.16. 1HNMR (400 MHz, DMSO) δ 5.795 (s, 2H), 6.606-6.633 (d, J=10.8 Hz, 1H), 6.720-6.724 (d, J=8.8 Hz, 1H), 6.800 (s, 2H), 7.065-7.083 (d, J=7.2 Hz, 1H), 7.213-7.260 (m, 2H), 7.400 (s, 5H), 7.657-7.676 (d, J=7.6 Hz, 1H), 8.119 (s, 1H), 10.139 (s, 1H)

Aufarbeitung

  1. temperaturewas refluxed overnight
  2. extractionextracted with EtOAc (20 mL×3)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. additionThe residue was treated with CH2Cl2
  7. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-0dd9f859ec344753b9598a6c2a5d30f4
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653089B2

Notizen zur Reaktion

Wird geladen…