Dichloromethane → tert-butyl 2-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-5-methoxy-1H-indole-1-carboxylate

HRID 2047171

Reaktionsgleichung

Reaktionsgleichung von HRID 2047171
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=2)[CH:10]=[C:9]1B(O)O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(Cl)Cl.Cl[C:34]1[CH:39]=[C:38]([N:40]([CH2:49][O:50][CH2:51][CH2:52][Si:53]([CH3:56])([CH3:55])[CH3:54])[CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[N:37]2[N:57]=[CH:58][C:59]([C:60]3[CH:61]=[N:62][C:63]([C:66]4[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=4)=[CH:64][CH:65]=3)=[C:36]2[N:35]=1>O1CCOCC1.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]>[CH3:54][Si:53]([CH3:56])([CH3:55])[CH2:52][CH2:51][O:50][CH2:49][N:40]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[C:38]1[N:37]2[N:57]=[CH:58][C:59]([C:60]3[CH:61]=[N:62][C:63]([C:66]4[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=4)=[CH:64][CH:65]=3)=[C:36]2[N:35]=[C:34]([C:9]2[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:16]3[C:11]([CH:10]=2)=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[CH:39]=1

Komponenten

8

Edukt 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 27947161-Boc-5-methoxyindole-2-boronic acidHCID 866647885-chloro-3-(6-phenylpyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

Produkt 1

HCID 66738101tert-butyl 2-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-5-methoxy-1H-indole-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittel2×HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

1-(tert-butoxycarbonyl)-5-methoxy-1H-indol-2-ylboronic acid (0.24 mmol, 70 mg), K3PO4 (0.36 mmol, 77 mg), and PdCl2(dppf).CH2Cl2 (0.012 mmol, 9.8 mg) were added to a solution of 5-chloro-3-(6-phenylpyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (0.12 mmol, 72 mg) in dioxane (4 mL) and H2O (0.5 mL). The resulting solution was stirred at 90° C. under argon overnight. The mixture was diluted with H2O and then extracted with ethyl acetate (×2). The combined organic layers were washed with brine and dried with Na2SO4. Evaporation and purification by column chromatography afforded tert-butyl 2-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-5-methoxy-1H-indole-1-carboxylate, LCMS tR=3.48 Min (5 min run, UV254nm). Mass calculated for, M+ 792.3, observed LC/MS m/z 793.2 (M+H).

Aufarbeitung

  1. extractionextracted with ethyl acetate (×2)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried with Na2SO4
  4. customEvaporation and purification by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-542236fc6aca40ca871435bf4b50cecf
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08591943B2

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