1,4-Dioxane → Methyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)benzoate

HRID 2047034Notes

Reaction equation

HRID 2047034 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[N:5]2[N:25]=[CH:26][CH:27]=[C:4]2[N:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C(C)(C)OB([C:44]2[CH:53]=[CH:52][C:47]([C:48]([O:50][CH3:51])=[O:49])=[CH:46][CH:45]=2)O1.O1CCOCC1>CCOC(C)=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]>[CH3:14][Si:13]([CH3:16])([CH3:15])[CH2:12][CH2:11][O:10][CH2:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:6]1[N:5]2[N:25]=[CH:26][CH:27]=[C:4]2[N:3]=[C:2]([C:44]2[CH:53]=[CH:52][C:47]([C:48]([O:50][CH3:51])=[O:49])=[CH:46][CH:45]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 2773500Methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 772312195-chloro-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

Product 1

HCID 67494225Methyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)benzoateYield 86.8%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Under Ar, compound, 5-chloro-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine, (430 mg, 1.0 mmol) was mixed with Pd(dppf)Cl2 (82 mg, 0.1 mmol, K3PO4 (636 mg, 3.0 mmol), methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (200 mg, 1.1 mmol) and dioxane (20 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, methyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)benzoate (459 mg). HPLC-MS tR=2.89 min (UV254 nm); mass calculated for formula C26H40N4O4Si2 528.3, observed LCMS m/z 529.2 (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-4727d380b8c04aa7993d864fb3ffad77
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

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