Benzyl 4-{2-[(di-tert-butoxyphosphoryl)oxy]ethyl}-3-oxopiperazine-1-carboxylate → Di-tert-butyl 2-(2-oxopiperazin-1-yl)ethyl phosphate

HRID 640026Notes

Reaction equation

HRID 640026 reaction equation
[C:1]([O:5][P:6]([O:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][N:19](C(OCC2C=CC=CC=2)=O)[CH2:18][C:17]1=[O:32])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2]>[Pd].CO>[P:6]([O:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][NH:19][CH2:18][C:17]1=[O:32])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7]

Participants

4

Reactant 1

HCID 68638741Benzyl 4-{2-[(di-tert-butoxyphosphoryl)oxy]ethyl}-3-oxopiperazine-1-carboxylate

Product 1

HCID 68640146Di-tert-butyl 2-(2-oxopiperazin-1-yl)ethyl phosphate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Benzyl 4-{2-[(di-tert-butoxyphosphoryl)oxy]ethyl}-3-oxopiperazine-1-carboxylate (1.20 g, 2.55 mmol) and 10% palladium on carbon (100 mg) in methanol (25 ml) were stirred at room temperature under an atmosphere of hydrogen for 2 hours and then filtered through Celite. The filtrate was evaporated to give di-tert-butyl 2-(2-oxopiperazin-1-yl)ethyl phosphate as a colourless oil which was dissolved in dimethylacetamide(4.0 ml) containing 2-(4-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-1-yl)-N-(2,3-difluorophenyl)acetamide hydrochloride (326 mg, 0.64 mmol) and potassium iodide (213 mg, 1.28 mmol) and the mixture was then heated at 90° C. for 3 hours. The mixture was cooled to room temperature, poured into dilute aqueous sodium hydrogen carbonate solution and then extracted with a solution of 10% isopropanol in dichloromethane. The organic layer was dried over magnesium sulphate and then evaporated to leave an orange oil. The crude product was purified by silica gel chromatography eluting with 5% methanol in dichloromethane containing 0-4% 7N ammonia in methanol to give di-tert-butyl 2-{4-[3-({4-[(1-{2-[(2,3-difluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)propyl]-2-oxopiperazin-1-yl}ethyl phosphate (211 mg, 43% yield) as a pale yellow solid: MS (+ve ESI): 773 (M+H)+.

Workup

  1. filtrationfiltered through Celite
  2. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-b9be4bd85a094b55bc972e1158f4e748
Source dataset
uspto-grants-2010_04
Patent number
US07691867B2

Reaction notes

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