3-Pentyn-2-ol → 1-(2-Chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-ethanol

HRID 2189330Notes

Reaction equation

HRID 2189330 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)C.[K+].[CH3:22][CH:23]([OH:27])[C:24]#[C:25][CH3:26]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:8][C:5]1[N:6]=[CH:7][C:2]2[C:25]([CH3:26])=[C:24]([CH:23]([OH:27])[CH3:22])[N:9]([CH:10]3[CH2:14][CH2:13][CH2:12][CH2:11]3)[C:3]=2[N:4]=1

Participants

7

Reactant 4

HCID 1413443-Pentyn-2-olHCID 433294Lithium ChlorideHCID 517044Potassium AcetateHCID 442482475-Bromo-2-chloro-N-cyclopentyl-4-pyrimidinamine

Product 1

HCID 866373501-(2-Chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-ethanolYield 14.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (5-Bromo-2-chloro-pyrimidin-4-yl)cyclopentylamine (1 g, 3.616 mmol) is added lithium chloride (153.7 mg, 3.616 mmol) and potassium acetate (887.12 mg, 9.03 mmol) in DMF (50 mL). The solution is degassed and back-filled with N2. Palladium(II) acetate (40.6 mg, 0.18 mmol) is added and the solution is degassed and back-filled with nitrogen three times. 3-pentyn-2-ol (1.0 mL, 10.8 mmol) is added and the reaction solution is heated at 120° C. for 5 hours. LC-MS analysis indicated the absence of starting material and the formation of a pair of regio-isomeric products. After cooling to room temperature, the mixture is filtered through Celite, diluted with water, and extracted with ethyl acetate EtOAc three times. The organic layers are combined, washed with brine and dried over anhydrous sodium sulfate. The solvent is evaporated and the crude material is purified using silica gel chromatography (30% ethyl acetate/70% hexanes to give 1-(2-Chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-ethanol as a pale powder (150 mg, 14.8%). [M+H]+=280.07.

Workup

  1. customThe solution is degassed
  2. additionback-filled with N2
  3. customthe solution is degassed
  4. additionback-filled with nitrogen three times
  5. temperatureAfter cooling to room temperature
  6. filtrationthe mixture is filtered through Celite
  7. additiondiluted with water
  8. extractionextracted with ethyl acetate EtOAc three times
  9. washwashed with brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. customThe solvent is evaporated
  12. customthe crude material is purified

Sources & evidence

ORD record
ord-f32479f8778e4211ae1c4838b2993f29
Source dataset
uspto-grants-2012_12
Patent number
US08324225B2

Reaction notes

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