Sodium hydride → Methyl 2-(4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yloxy)phenyl)acetate

HRID 2047028Notes

Reaction equation

HRID 2047028 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:16]1[CH:21]=[C:20]([N:22]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[N:19]2[N:39]=[CH:40][CH:41]=[C:18]2[N:17]=1.[NH4+].[Cl-]>CN(C=O)C>[CH3:36][Si:35]([CH3:38])([CH3:37])[CH2:34][CH2:33][O:32][CH2:31][N:22]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:20]1[N:19]2[N:39]=[CH:40][CH:41]=[C:18]2[N:17]=[C:16]([O:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:6][CH:7]=2)[CH:21]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 518900Benzeneacetic acid, 4-hydroxy-, methyl esterHCID 772312195-chloro-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

Product 1

HCID 66736440Methyl 2-(4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yloxy)phenyl)acetateYield 876.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The compound methyl 2-(4-hydroxyphenyl)acetate (330 mg, 0.2 mmol) was dissolved in dry DMF (3 mL) and NaH (80 mg, 60% in oil, 0.2 mmol) was added and the mixture was stirred at room temperature for 5 min. Then, 5-chloro-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (430 mg, 0.1 mmol) was added and the resulting mixture was heated up to 130° C. with microwave and stirred for 30 min. After cooling to room temperature, NH4Cl (aq) was added to quench the reaction and extracted with EtOAc (50 mL×3). The combined organics were washed with water and brine and dried over Na2SO4. After concentration, the residue was purified with column (silica gel, 20% EtOAc/Hexane) gave the product, methyl 2-(4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yloxy)phenyl)acetate, (490 mg) as clear oil. HPLC-MS tR=2.77 min (UV254 nm); mass calculated for formula C27H42N4O5Si2 558.3, observed LCMS m/z 559.3 (M+H).

Workup

  1. temperaturethe resulting mixture was heated up to 130° C. with microwave
  2. stirringstirred for 30 min
  3. temperatureAfter cooling to room temperature
  4. customto quench
  5. customthe reaction
  6. extractionextracted with EtOAc (50 mL×3)
  7. washThe combined organics were washed with water and brine
  8. dry with materialdried over Na2SO4
  9. concentrationAfter concentration
  10. customthe residue was purified with column (silica gel, 20% EtOAc/Hexane)

Sources & evidence

ORD record
ord-c813691929184a378ec34f93fe1565f4
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

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