Tetrabutylammonium Fluoride → 2-chloro-7-cyclopentyl-6-diethoxymethyl-7H-pyrrolo[2,3-d]pyrimidine

HRID 1853154Notes

Reaction equation

HRID 1853154 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[C:5]([C:14]#[C:15][CH:16]([O:20][CH2:21][CH3:22])[O:17][CH2:18][CH3:19])=[CH:4][N:3]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[CH:14]=[C:15]([CH:16]([O:20][CH2:21][CH3:22])[O:17][CH2:18][CH3:19])[N:8]([CH:9]3[CH2:13][CH2:12][CH2:11][CH2:10]3)[C:6]=2[N:7]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 58315397[2-Chloro-5-(3,3-diethoxy-prop-1-ynyl)-pyrimidin-4-yl]cyclopentylamine

Product 1

HCID 583154492-chloro-7-cyclopentyl-6-diethoxymethyl-7H-pyrrolo[2,3-d]pyrimidineYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of [2-chloro-5-(3,3-diethoxy-prop-1-ynyl)-pyrimidin-4-yl]-cyclopentyl-amine (7.50 g, 23.3 mmol) in THF (45 mL) is added 1N TBAF in THF (100 mL, 116 mmol) at room temperature. The reaction mixture is heated under reflux overnight. After cooling the mixture is partitioned between H2O and dichloromethane. The phases are separated and the aqueous layer is extracted with dichloromethane (×2). The combined organic extracts are dried (MgSO4), filtered and concentrated. The residue is purified by SiO2 chromatography eluting with a gradient of 10% EtOAc/petrol to 30% EtOAc/petrol to give 2-chloro-7-cyclopentyl-6-diethoxymethyl-7H-pyrrolo[2,3-d]pyrimidine, (5.68 g, 76%). MS (ESI) m/z 324.1 (M+H)+

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureunder reflux overnight
  3. temperatureAfter cooling the mixture
  4. customis partitioned between H2O and dichloromethane
  5. customThe phases are separated
  6. extractionthe aqueous layer is extracted with dichloromethane (×2)
  7. dry with materialThe combined organic extracts are dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue is purified by SiO2 chromatography
  11. washeluting with a gradient of 10% EtOAc/petrol to 30% EtOAc/petrol

Sources & evidence

ORD record
ord-1a0f46704a904ba4b97680fb4eafabaa
Source dataset
uspto-grants-2015_02
Patent number
US08962630B2

Reaction notes

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