Hydrochloric Acid → 4-Chloro-7-(1-methylethyl)-N-propyl-7H-pyrrolo[2,3-d]pyrimidin-2-amine

HRID 530087Notes

Reaction equation

HRID 530087 reaction equation
[Si]([NH:8][C:9]1[N:10]=[C:11]([Cl:21])[C:12]2[CH:17]=[CH:16][N:15]([CH:18]([CH3:20])[CH3:19])[C:13]=2[N:14]=1)(C(C)(C)C)(C)C.I[CH2:23][CH2:24][CH3:25].[H-].[Na+].Cl>CN(C=O)C.CCOCC.O>[CH2:23]([NH:8][C:9]1[N:10]=[C:11]([Cl:21])[C:12]2[CH:17]=[CH:16][N:15]([CH:18]([CH3:19])[CH3:20])[C:13]=2[N:14]=1)[CH2:24][CH3:25]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 336431-IodopropaneHCID 86665994HCID 86665994, compound

Product 1

HCID 735546564-Chloro-7-(1-methylethyl)-N-propyl-7H-pyrrolo[2,3-d]pyrimidin-2-amine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

Under nitrogen atmosphere, 2-(t-butyl-dimethylsilanyl)amino-4-chloro-7-i-propyl-pyrrolo[2,3-d]pyrimidine (5.7 g, 17.6 mmol) and 1-iodopropane (4.5 g (26.4 mmol) were dissolved in DMF (20 mL). The reaction mixture was cooled to 0° C. with vigorous stirring, and NaH (1.06 g of a 60% dispersion in mineral oil, 26.4 mmol) of (60%) was added. The mixture was stirred for 10 min, and then water (50 mL) was slowly added to quench the reaction. The mixture was extracted with EtOAc (300 mL) and the organic layer was washed with water (50 mL) and then with a brine solution (50 mL), and lastly, dried over anhydrous Na2SO4. After evaporation of the solvents, a yellow oily residue was isolated (6.5 g). The residue was dissolved in Et2O (50 mL), concentrated hydrochloric acid (10 mL) was added at 0° C. with stirring, and the mixture was stirred for an additional 10 min. After the reaction was completed, the solution was extracted with EtOAc (200 mL) and 1N NaOH (200 mL). The organic layer was washed with H2O (150 mL) and then with a brine solution (150 mL) and dried over Na2SO4. The solvents in vacuo and the residue was purified by flash column chromatography (PE/EtOAc=10/1 to 5/1) to yield 2-(n-propyl)amino-4-chloro-7-i-propyl-pyrrolo[2,3-d]pyrimidine (CXXXIV, 4.5 g, !00%) as a yellow solid. LCMS (ESI) m/z=253 (M+H)+.

Workup

  1. additionwas added
  2. customto quench
  3. customthe reaction
  4. extractionThe mixture was extracted with EtOAc (300 mL)
  5. washthe organic layer was washed with water (50 mL)
  6. dry with materialwith a brine solution (50 mL), and lastly, dried over anhydrous Na2SO4
  7. customAfter evaporation of the solvents
  8. customa yellow oily residue was isolated (6.5 g)
  9. stirringwith stirring
  10. stirringthe mixture was stirred for an additional 10 min
  11. extractionthe solution was extracted with EtOAc (200 mL) and 1N NaOH (200 mL)
  12. washThe organic layer was washed with H2O (150 mL)
  13. dry with materialwith a brine solution (150 mL) and dried over Na2SO4
  14. customThe solvents in vacuo and the residue was purified by flash column chromatography (PE/EtOAc=10/1 to 5/1)

Sources & evidence

ORD record
ord-1f66d18858ac408080106d8f7add1e4f
Source dataset
uspto-grants-2016_05
Patent number
US09351972B2

Reaction notes

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