Sodium hydride → HCID 14221930, compound

HRID 1651079Notes

Reaction equation

HRID 1651079 reaction equation
[H-].[Na+].[Cl:3][C:4]1[N:9]=[CH:8][NH:7][C:6]2=[N:10][CH:11]=[CH:12][C:5]=12.[H][H].[C:15]([O:18][CH2:19][CH2:20][O:21][CH2:22]Br)(=[O:17])[CH3:16]>CN(C=O)C.O>[Cl:3][C:4]1[C:5]2[CH:12]=[CH:11][N:10]([CH2:22][O:21][CH2:20][CH2:19][O:18][C:15](=[O:17])[CH3:16])[C:6]=2[N:7]=[CH:8][N:9]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 3676562-(Bromomethoxy)ethyl acetateHCID 178418361HCID 178418361, compoundHCID 178418725HCID 178418725, compound

Product 1

HCID 14221930HCID 14221930, compoundYield 40.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (0.09 g, 60% in mineral oil) was added to a solution of 4-chloropyrrolo[2,3-d]pyrimidine (1) in dry DMF (6 mL) in small portions at 0-5 degrees C under a nitrogen atomosphere. When all hydrogen evolution has ceased, 2-acetoxyethoxymethyl bromide (2) (0.45 g) was added, dropwise with stirring, at room temperature. The reaction mixture was then stirred at room temperature for an additional 3 hours. After that period of time, water (50 mL) was added and the product was extracted with ethylacetate. The ethylacetate layer was separated, washed with cold water, dried over anhydrous, Na2SO4 and the solvent then evaporated under reduced pressure and temperature to afford a thick syrup. This syrup was applied to the top of a silica gel column (20×2 cm) and the column was eluted with 1% MeOH in CHCl3. All the fractions containing UV absorbing material were combined and the solvent from these fractions was evaporated to yield a colorless syrup was crystallized from methanol as colorless needles to yield 0.21 g of 3 (40.2%), mp 67-88 degrees C. 1H-NMR (DMSO-d6) δ: 8.5 (s, 1, C2-H), 7.88 (d, 1, J=3.5 Hz, C6-H), 6.72 (d, 1, J=3.6 Hz, C5-H), 5.7 (s, 2, N7-CH2), 4.03 (m, 2, OCH2), 3.52 (m, 2, CH2), 1.92 (s, 3, OAc): UVλmax nm (ε×104); (pH 7) 223 (1.2), 276 (2.4); (pH 1) 225 (1.2), 274 (0.25); (pH 11) 227 (0.8), 276 (0.2).

Workup

  1. stirringThe reaction mixture was then stirred at room temperature for an additional 3 hours
  2. extractionthe product was extracted with ethylacetate
  3. customThe ethylacetate layer was separated
  4. washwashed with cold water
  5. dry with materialdried over anhydrous, Na2SO4
  6. customthe solvent then evaporated under reduced pressure and temperature
  7. customto afford a thick syrup
  8. washthe column was eluted with 1% MeOH in CHCl3
  9. additionAll the fractions containing UV
  10. customabsorbing material
  11. customthe solvent from these fractions was evaporated
  12. customto yield a colorless syrup
  13. customwas crystallized from methanol as colorless needles

Sources & evidence

ORD record
ord-c8aee39f1a684b958d9bd4ec2a69684d
Source dataset
uspto-grants-1990_05
Patent number
US04927830

Reaction notes

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