Ethyl Acetate → 5-(4-(methylthio)phenoxy)-3-(quinolin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

HRID 2047040Notes

Reaction equation

HRID 2047040 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]2[C:10]([N:11]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])=[CH:9][C:8]([O:28][C:29]3[CH:34]=[CH:33][C:32]([S:35][CH3:36])=[CH:31][CH:30]=3)=[N:7][C:6]=12.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1[CH2:50][CH2:49]OCC1.CCO[C:54]([CH3:56])=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]>[CH3:36][S:35][C:32]1[CH:33]=[CH:34][C:29]([O:28][C:8]2[CH:9]=[C:10]([N:11]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[N:5]3[N:4]=[CH:3][C:2]([C:9]4[CH:10]=[N:5][C:6]5[C:49]([CH:50]=4)=[CH:56][CH:54]=[CH:3][CH:2]=5)=[C:6]3[N:7]=2)=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 667354123-iodo-5-(4-(methylthio)phenoxy)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

Product 1

HCID 667454745-(4-(methylthio)phenoxy)-3-(quinolin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
90 °C

Procedure

3-iodo-5-(4-(methylthio)phenoxy)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (180 mg, 0.26 mmol) under Argon, was mixed with Pd(dppf)Cl2 (21 mg, 0.26 mmol, K3PO4 (106 mg, 0.5 mmol), 3-quinoline bornic acid (55 mg, 0.31 mmol) and dioxane (10 mL with 1 ml water). The resulting mixture was heated at 90° C. and stirred over night. After cooled to room temperature, the mixture was diluted with EtOAc (60 mL) and filtered through celite. After concentration, the crude was purified with column (silica gel, 0˜30% EtOAc/Hexane) gave the product 5-(4-(methylthio)phenoxy)-3-(quinolin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (150 mg). HPLC-MS tR=2.85 min (UV254 nm); mass calculated for formula C34H45N5O3SSi2 659.3, observed LCMS m/z 660.1 (M+H).

Workup

  1. temperatureAfter cooled to room temperature
  2. filtrationfiltered through celite
  3. concentrationAfter concentration
  4. customthe crude was purified with column (silica gel, 0˜30% EtOAc/Hexane)

Sources & evidence

ORD record
ord-e37f5cd22802456186fb701e98c4d887
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

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