4-Methylmorpholine → Ethyl 9-{(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-[(acetyloxy)methyl]tetrahydro-2-furanyl}-6-[(2,2-diphenylethyl)amino]-9H-purine-2-carboxylate

HRID 10467

반응식

HRID 10467 반응식
[C:1]1([CH:7]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:8][NH:9][C:10]2[N:18]=[C:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[N:16]=[C:15]3[C:11]=2[N:12]=[CH:13][NH:14]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN1CCOCC1.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.C(O[C@@H:53]1[O:65][C@H:64]([CH2:66][O:67][C:68](=[O:70])[CH3:69])[C@@H:59]([O:60][C:61](=[O:63])[CH3:62])[C@H:54]1[O:55][C:56](=[O:58])[CH3:57])(=O)C.C(=O)(O)[O-].[Na+]>COCCOC.C(OCC)(=O)C>[C:56]([O:55][C@@H:54]1[C@H:59]([O:60][C:61](=[O:63])[CH3:62])[C@@H:64]([CH2:66][O:67][C:68](=[O:70])[CH3:69])[O:65][C@H:53]1[N:14]1[CH:13]=[N:12][C:11]2[C:15]1=[N:16][C:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[N:18][C:10]=2[NH:9][CH2:8][CH:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)(=[O:58])[CH3:57]

참가 물질

8

반응물 5

HCID 79724-MethylmorpholineHCID 65367Trimethylsilyl triflateHCID 830641,2,3,5-Tetraacetyl-beta-D-ribofuranoseHCID 516892Sodium BicarbonateHCID 178419102HCID 178419102, 화합물

생성물 1

HCID 10122270Ethyl 9-{(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-[(acetyloxy)methyl]tetrahydro-2-furanyl}-6-[(2,2-diphenylethyl)amino]-9H-purine-2-carboxylate

시약·촉매·용매 2

HCID 80711,2-Dimethoxyethane용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
55 °C

실험 절차

To a suspension of ethyl 6-[(2,2-diphenylethyl)amino]-9H-purine-2-carboxylate (Preparation 63) (40.0 g, 0.103 moles) in anhydrous 1,2-dimethoxyethane (240 ml) under an atmosphere of nitrogen was added 4-methylmorpholine (11.5 g, 12.5 ml, 0.114 moles) and the resultant mixture was heated to 45° C. with stirring. To this mixture was then added trimethylsilyl trifluoromethanesulphonate (27.5 g, 22.4 ml, 0.124 moles) over a period of 10 minutes. The resultant orange solution was then heated to 55° C., and a solution of 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose (36.1 g, 0.113 moles) in 1,2-dimethoxyethane (100 ml plus 20 ml to rinse through) was added over a period of 10 minutes. The reaction was then stirred at 57–60° C. for 2 hours after which time the mixture was cooled to ambient temperature. The reaction mixture was then cautiously added to a mixture of saturated aqueous sodium bicarbonate solution (400 ml) and ethyl acetate (400 ml) with vigorous stirring. The layers were separated and the aqueous phase was extracted with ethyl acetate (400 ml). The combined organic phases were dried over anhydrous magnesium sulphate and were then concentrated in vacuo to give the crude product as an orange foam (74.9 g) that could be used as such for the next step. This crude product can be purified using flash chromatography on silica gel eluting with a gradient system of 10% v/v diethyl ether in dichloromethane changing to 25% v/v diethyl ether in dichloromethane to give the title compound as a colourless foam.

후처리

  1. stirringThe reaction was then stirred at 57–60° C. for 2 hours after which time the mixture
  2. temperaturewas cooled to ambient temperature
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with ethyl acetate (400 ml)
  5. dry with materialThe combined organic phases were dried over anhydrous magnesium sulphate
  6. concentrationwere then concentrated in vacuo
  7. customto give the crude product as an orange foam (74.9 g) that
  8. customThis crude product can be purified

출처 및 근거

ORD 기록
ord-24077634027d402792edb18726eda7e5
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07094769B2

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