Potassium Carbonate → 2-chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester

HRID 2189333Notes

Reaction equation

HRID 2189333 reaction equation
Br[C:2]1[C:3]([NH:9][CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[Cl-].[Li+].C(=O)([O-])[O-].[K+].[K+].[CH3:23][O:24][C:25](=[O:29])[C:26]#[C:27][CH3:28]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:23][O:24][C:25]([C:26]1[N:9]([CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[C:3]2[N:4]=[C:5]([Cl:8])[N:6]=[CH:7][C:2]=2[C:27]=1[CH3:28])=[O:29]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 141019Methyl but-2-ynoateHCID 433294Lithium ChlorideHCID 442482475-Bromo-2-chloro-N-cyclopentyl-4-pyrimidinamine

Product 1

HCID 866373522-chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl esterYield 25%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A solution of (5-Bromo-2-chloro-pyrimidin-4-yl)cyclopentylamine (8 g, 28.93 mmol), lithium chloride (1.23 g, 28.9 mmol), potassium carbonate (10 g, 72 mmol) and palladium acetate (324.68 mg, 1.45 mmol) in DMF (300 mL) is degassed and back-filled filled with nitrogen three times. Methyl-2-butynoate (8.5 mL, 87 mmol) is added and the reaction solution is heated at 120° C. for 5 h. LC-MS indicated the formation of two regioisomers and no starting material remaining. After cooling to room temperature the solution is filtered through Celite, diluted with water and extracted with ethyl acetate three times. The organic layers are combined, washed with brine and dried over anhydrous sodium sulfate. The solvent is evaporated and the crude product is purified using silica gel chromatography (˜20% ethyl acetate/80% hexane) to give 2-chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester as a yellow solid (2.11 g, 25%). [M+H]+=294.04.

Workup

  1. additionback-filled
  2. additionfilled with nitrogen three times
  3. temperatureAfter cooling to room temperature the solution
  4. filtrationis filtered through Celite
  5. additiondiluted with water
  6. extractionextracted with ethyl acetate three times
  7. washwashed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent is evaporated
  10. customthe crude product is purified

Sources & evidence

ORD record
ord-a4a11c94133249618454438801db53cc
Source dataset
uspto-grants-2012_12
Patent number
US08324225B2

Reaction notes

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