Cyclohexene → 4-N-Benzoyl-5'-O-(tert-butyldimethylsilyl)-3'-O-azidomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxycytidine

HRID 1907097Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1907097
[C:1]([NH:9][C:10]1[C:33]([C:34]#[C:35][CH2:36][NH:37][C:38](=[O:43])[C:39]([F:42])([F:41])[F:40])=[CH:32][N:13]([C@@H:14]2[O:31][C@H:21]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C@@H:16]([O:17][CH2:18]SC)[CH2:15]2)[C:12](=[O:44])[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1CCCCC=1.[N-:51]=[N+:52]=[N-:53].[Na+]>C(Cl)Cl.CN(C=O)C>[C:1]([NH:9][C:10]1[C:33]([C:34]#[C:35][CH2:36][NH:37][C:38](=[O:43])[C:39]([F:42])([F:41])[F:40])=[CH:32][N:13]([C@@H:14]2[O:31][C@H:21]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C@@H:16]([O:17][CH2:18][N:51]=[N+:52]=[N-:53])[CH2:15]2)[C:12](=[O:44])[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

6

Edukt 3

HCID 8079CyclohexeneHCID 33557Sodium AzideHCID 866642624-N-Benzoyl-5'-O-(tert-butyldimethylsilyl)-3'-O-methylthiomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxycytidine

Produkt 1

HCID 866136144-N-Benzoyl-5'-O-(tert-butyldimethylsilyl)-3'-O-azidomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxycytidineAusbeute 55 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

The starting material (14) (1.65 g, 2.99 mmol) was dissolved in DCM (18 ml) and cooled to 0° C. Cyclohexene (1.5 ml, 14.95 mmol) and SO2Cl2 (0.72 ml, 8.97 mmol) were added and stirred 1 h in ice bath. TLC indicated starting material still to be present whereupon a further aliquot of SO2Cl2 (0.24 ml) was added and the mixture stirred for 1 h at 0° C. Volatiles were removed by evaporation to yield a light brown solid that was redissolved in 18 ml of dry DMF (18 ml) under N2. Sodium azide (0.97 g, 14.95 mmol) was then added to the solution and stirred for 2.5 h at room temperature. The reaction mixture was passed through a pad of silica and eluted with EtOAc and the volatiles removed by high vacuum evaporation. The resulting brown gel was purified by flash chromatography (petroleum ether:EtOAc 4:1 to 2:1) to yield the desired product as a white crystalline solid (15) (0.9 g, 55%). 1H NMR (d6 DMSO): δ 0.00 (s, 6H, CH3), 0.78 (s, 9H, tBu), 2.16 (m, 1H, H-2′), 2.22 (m, 1H, H-2′), 3.70 (d, 1H, J=11.5 Hz, H-5′), 3.75 (d, 1H, J=11.3 Hz, H-5′), 4.01 (m, 1H, H-4′), 4.10 (m, 1H, CH2NH), 4.23 (m, 1H, H-3′), 4.76 (s, 2H, CH2S), 5.99 (m, 1H, H-1′), 7.37 (m, 2H, Ph), 7.50 (m, 2H, Ph), 7.81 (d, 1H, J=7.4 Hz, Ph), 7.95 (s, 1H, H-6), 9.78 (br s, 1H, NHCH2), 12.64 (br s, 1H, NH). Mass (−ve electrospray) calcd for C28H34F3N7O6Si 649.71. Found 648.2

Aufarbeitung

  1. additionwas added
  2. stirringthe mixture stirred for 1 h at 0° C
  3. customVolatiles were removed by evaporation
  4. customto yield a light brown solid that
  5. stirringstirred for 2.5 h at room temperature
  6. washeluted with EtOAc
  7. customthe volatiles removed by high vacuum evaporation
  8. customThe resulting brown gel was purified by flash chromatography (petroleum ether:EtOAc 4:1 to 2:1)

Quellen und Nachweise

ORD-Eintrag
ord-662574a9961f4675b589d1a277abba70
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08597881B2

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