1,2-Dimethoxyethane → 3-cyclopropyl-3-(4-(7-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile

HRID 1852990

Reaktionsgleichung

Reaktionsgleichung von HRID 1852990
Cl[C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[CH:5]=[C:4]([C:11]2[CH:12]=[N:13][N:14]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:15]=2)[N:3]=1.[CH:24]1([CH:27]([N:31]2[CH:35]=[C:34](B3OC(C)(C)C(C)(C)O3)[CH:33]=[N:32]2)[CH2:28][C:29]#[N:30])[CH2:26][CH2:25]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].COCCOC>O.CCOCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:24]1([CH:27]([N:31]2[CH:35]=[C:34]([C:2]3[N:7]4[CH:8]=[CH:9][N:10]=[C:6]4[CH:5]=[C:4]([C:11]4[CH:12]=[N:13][N:14]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:15]=4)[N:3]=3)[CH:33]=[N:32]2)[CH2:28][C:29]#[N:30])[CH2:26][CH2:25]1

Komponenten

8

Edukt 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 674580563-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrileHCID 866853115-chloro-7-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine

Produkt 1

HCID 674584153-cyclopropyl-3-(4-(7-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrileAusbeute 75,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel2×HCID 3283Diethyl EtherLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A flask was charged with 5-chloro-7-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (Step C, 150 mg, 0.429 mmol), 3-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrile (Preparation P; 185 mg, 0.643 mmol) and K3PO4 (273 mg, 1.29 mmol). DME (2.5 mL) and H2O (1.5 mL) were added and the resulting solution was purged with N2 for 15 minutes. Pd(PPh3)4 (49.5 mg, 0.0429 mmol) was added, the flask sealed, and the mixture stirred at 80° C. for 3.5 hours. The mixture was cooled to ambient temperature and was diluted with H2O (5 mL). The mixture was extracted with 50% EtOAc/hexanes and the combined extracts were washed with saturated NaCl and dried over MgSO4/activated carbon. The dried solution was eluted through a SiO2 column eluting with 50% EtOAc/hexanes, EtOAc and 10% MeOH/EtOAc. The EtOAc and 10% MeOH/EtOAc pools were combined and concentrated to give a gold syrup. The syrup was dissolved in Et2O and concentrated to give the title compound (153 mg, 75.0% yield) as a brittle, light beige foam. MS (apci) m/z=475.3 (M+H).

Aufarbeitung

  1. customthe resulting solution was purged with N2 for 15 minutes
  2. customthe flask sealed
  3. temperatureThe mixture was cooled to ambient temperature
  4. extractionThe mixture was extracted with 50% EtOAc/hexanes
  5. washthe combined extracts were washed with saturated NaCl
  6. dry with materialdried over MgSO4/activated carbon
  7. washThe dried solution was eluted through a SiO2 column
  8. washeluting with 50% EtOAc/hexanes, EtOAc and 10% MeOH/EtOAc
  9. concentrationconcentrated
  10. customto give a gold syrup
  11. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-f2731bf75bf74b50a70eb747840a71e9
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08962596B2

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