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

HRID 2273462Notes

Reaction equation

HRID 2273462 reaction equation
[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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-a4e4369f89c5426692039af8ef5f76f2
Source dataset
uspto-grants-2015_09
Patent number
US09121060B2

Reaction notes

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