Phosphorus oxychloride → tert-butyl 4-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl)piperidine-1-carboxylate

HRID 1616088Notes

Reaction equation

HRID 1616088 reaction equation
O=[C:2]1[NH:7][CH:6]=[N:5][C:4]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:3]1=2.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.P(Cl)(Cl)([Cl:41])=O>O>[Cl:41][C:2]1[C:3]2[NH:10][CH:9]=[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 90495Di-tert-butyl dicarbonateHCID 136359803tert-butyl 4-(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)piperidine-1-carboxylate

Product 1

HCID 86681880tert-butyl 4-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl)piperidine-1-carboxylateYield 43.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl 4-(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)piperidine-1-carboxylate (466 mg, 1.38 mmol) was dissolved in phosphorus oxychloride (2 mL) and stirred at 100° C. for 5 hours. The reaction liquid was concentrated under a reduced pressure, a 2 N aqueous sodium hydroxide solution (pH=14) was added, and then di-tert-butyl dicarbonate (602 mg, 2.76 mmol) was added to the aqueous solution, followed by stirring at room temperature for 2 hours. The reaction liquid was diluted with water, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under a reduced pressure. The obtained residue was purified by using silica gel chromatography (chloroform:methanol=10:1) to give tert-butyl 4-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl)piperidine-1-carboxylate (201 mg, 43.1%) as a pale yellow amorphous.

Workup

  1. customThe reaction liquid
  2. concentrationwas concentrated under a reduced pressure
  3. additiona 2 N aqueous sodium hydroxide solution (pH=14) was added
  4. stirringby stirring at room temperature for 2 hours
  5. customThe reaction liquid
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under a reduced pressure
  10. customThe obtained residue was purified

Sources & evidence

ORD record
ord-094885f6d5cb42848982f09b51e413d7
Source dataset
uspto-grants-2014_07
Patent number
US08765771B2

Reaction notes

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