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

HRID 500310ノート

反応式

HRID 500310 の反応式
[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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

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 to 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

後処理

  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)

出典と根拠

ORDレコード
ord-6ca99fe46c4445bb8837d336c918c64b
出典データセット
uspto-grants-2010_08
特許番号
US07771973B2

反応ノート

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