Triethylamine → HCID 56614268, compound

HRID 974267Notes

Reaction equation

HRID 974267 reaction equation
[CH:1]1([CH2:4][NH:5][C:6]2[N:14]=[CH:13][N:12]=[C:11]3[C:7]=2[N:8]=[CH:9][N:10]3[C@H:15]2[CH2:19][CH2:18][C@@H:17]([CH2:20][OH:21])[O:16]2)[CH2:3][CH2:2]1.C(N(CC)CC)C.[C:29](Cl)(=[O:32])[CH2:30][CH3:31]>CN(C)C1C=CN=CC=1.C(#N)C>[CH:1]1([CH2:4][NH:5][C:6]2[N:14]=[CH:13][N:12]=[C:11]3[C:7]=2[N:8]=[CH:9][N:10]3[C@H:15]2[CH2:19][CH2:18][C@@H:17]([CH2:20][O:21][C:29](=[O:32])[CH2:30][CH3:31])[O:16]2)[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 62324Propionyl chlorideHCID 18649770HCID 18649770, compound

Product 1

HCID 56614268HCID 56614268, compoundYield 39.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

6-(Cyclopropylmethylamino)-9-[(2R,5S)-tetrahydro-5-(hydroxymethyl)-2-furyl]-9H-purine (0.369 g, 1.3 mmoles), 4-dimethylaminopyridine (10 mg, 0.1 mmoles, Aldrich Chemical Co., Madison, Wis.), and triethylamine (2.0 mL, 14 mmoles, Aldrich Chemical Co., Madison, Wis.) were dissolved in 50 mL acetonitrile. Propionyl chloride (450 μl, 5.2 mmoles, Aldrich Chemical Co., Madison, Wis.) was added and the reaction was stirred at room temperature for 2 hours. The reaction was quenched with methanol and solvents were evaporated in vacuo. Ethyl acetate was added to the residue and undissolved salts were removed by filtration. The filtrate was then applied to a silica gel column (4.8×13 cm) and eluted with methanol. After evaporation of the solvent, the product was eluted to a Chromatotron plate (4 mm silica gel) with a mixture of hexane:acetone (75:25). The product containing fractions were combined, concentrated, and further chromatographed on the Chromatotron (2 mm silica gel plate) with a mixture of chloroform:acetone (95:5). Product containing fractions were applied to preparative silica gel plates (20×20×0.2 cm) which were then developed in chloroform:acetone (85:15). Final purification was achieved by a third run on the Chromatotron (2 mm silica gel plate) with a mixture of hexane:acetone (80:20). Lyophilization afforded 0.178 g of 6-(cyclopropylmethylamino)-9-((2R,5S)-5-((propanoyloxy)methyl)-tetrahydro-2-furyl)-9H-purine as an oil (39% yield).

Workup

  1. customThe reaction was quenched with methanol and solvents
  2. customwere evaporated in vacuo
  3. additionEthyl acetate was added to the residue and undissolved salts
  4. customwere removed by filtration
  5. washeluted with methanol
  6. customAfter evaporation of the solvent
  7. washthe product was eluted to a Chromatotron plate (4 mm silica gel) with a mixture of hexane:acetone (75:25)
  8. additionThe product containing fractions
  9. concentrationconcentrated
  10. customfurther chromatographed on the Chromatotron (2 mm silica gel plate) with a mixture of chloroform:acetone (95:5)
  11. additionProduct containing fractions
  12. customFinal purification
  13. additionwas achieved by a third run on the Chromatotron (2 mm silica gel plate) with a mixture of hexane:acetone (80:20)

Sources & evidence

ORD record
ord-63bda10ee32d46a987aa1976d68f81eb
Source dataset
uspto-grants-1991_11
Patent number
US05068320

Reaction notes

Loading…