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

HRID 2189333ノート

反応式

HRID 2189333 の反応式
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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-a4a11c94133249618454438801db53cc
出典データセット
uspto-grants-2012_12
特許番号
US08324225B2

反応ノート

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