Potassium Phosphate, Tribasic → 4-Fluoro-2-(6-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenylamino)-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-purin-2-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)benzyl Acetate

HRID 1024092Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1024092
[C:1]([O:4][CH2:5][C:6]1[C:11](B2OC(C)(C)C(C)(C)O2)=[CH:10][C:9]([F:21])=[CH:8][C:7]=1[N:22]1[CH2:34][CH2:33][C:32]2[N:31]3[C:26]([CH2:27][CH2:28][CH2:29][CH2:30]3)=[CH:25][C:24]=2[C:23]1=[O:35])(=[O:3])[CH3:2].I[C:37]1[N:45]=[C:44]2[C:40]([N:41]=[CH:42][N:43]2[CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])=[C:39]([NH:54][C:55]2[CH:60]=[CH:59][C:58]([N:61]3[CH2:66][CH2:65][N:64]([CH:67]4[CH2:70][O:69][CH2:68]4)[CH2:63][CH2:62]3)=[CH:57][CH:56]=2)[N:38]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>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].O.C(#N)C>[C:1]([O:4][CH2:5][C:6]1[C:7]([N:22]2[CH2:34][CH2:33][C:32]3[N:31]4[C:26]([CH2:27][CH2:28][CH2:29][CH2:30]4)=[CH:25][C:24]=3[C:23]2=[O:35])=[CH:8][C:9]([F:21])=[CH:10][C:11]=1[C:37]1[N:45]=[C:44]2[C:40]([N:41]=[CH:42][N:43]2[CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:51])([CH3:52])[CH3:53])=[C:39]([NH:54][C:55]2[CH:56]=[CH:57][C:58]([N:61]3[CH2:66][CH2:65][N:64]([CH:67]4[CH2:68][O:69][CH2:70]4)[CH2:63][CH2:62]3)=[CH:59][CH:60]=2)[N:38]=1)(=[O:3])[CH3:2]

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866841532-Iodo-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-purin-6-amineHCID 866841614-Fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl Acetate

Produkt 1

HCID 866841604-Fluoro-2-(6-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenylamino)-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-purin-2-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)benzyl AcetateAusbeute 67,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 120f (400 mg, 0.82 mmol), 2-iodo-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-purin-6-amine 117f (604 mg, 0.99 mmol), PdCl2(dppf) (33 mg, 0.040 mmol), K3PO4 (347 mg, 1.64 mmol), and sodium acetate (134 mg, 1.64 mmol), acetonitrile (15 mL), and water (1 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 100° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford 120g (460 mg, 66%) as a green solid. MS-ESI: [M+H]+ 836.4.

Aufarbeitung

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. temperatureIt was then cooled to room temperature
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica-gel column chromatography
  8. washeluting with 30:1 dichloromethane/methanol

Quellen und Nachweise

ORD-Eintrag
ord-fa199e2702b845e5aee46718d831107d
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08722676B2

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