Triethylamine → HCID 56614268, 화합물

HRID 974267노트

반응식

HRID 974267 반응식
[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

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 62324Propionyl chlorideHCID 18649770HCID 18649770, 화합물

생성물 1

HCID 56614268HCID 56614268, 화합물수율 39.6%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6342Acetonitrile용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-63bda10ee32d46a987aa1976d68f81eb
출처 데이터셋
uspto-grants-1991_11
특허 번호
US05068320

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