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

HRID 500308ノート

反応式

HRID 500308 の反応式
[Si:1]([O:8][CH2:9][C@H:10]1[O:14][C@@H:13]([N:15]2[CH:22]=[C:21]([C:23]#[C:24][CH2:25][NH:26][C:27](=[O:32])[C:28]([F:31])([F:30])[F:29])[C:19]([NH2:20])=[N:18][C:16]2=[O:17])[CH2:12][C@@H:11]1[OH:33])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl[Si](C)(C)C.[C:39](Cl)(=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C([O-])(O)=O.[Na+]>N1C=CC=CC=1.C(Cl)Cl>[C:39]([NH:20][C:19]1[C:21]([C:23]#[C:24][CH2:25][NH:26][C:27](=[O:32])[C:28]([F:30])([F:31])[F:29])=[CH:22][N:15]([C@@H:13]2[O:14][C@H:10]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2])[C@@H:11]([OH:33])[CH2:12]2)[C:16](=[O:17])[N:18]=1)(=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

参加物

7

反応物 4

HCID 6397ChlorotrimethylsilaneHCID 7412Benzoyl chlorideHCID 516892Sodium BicarbonateHCID 866136115'-O-(tert-Butyldimethylsilyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxycytidine

生成物 1

HCID 866136124-N-Benzoyl-5'-O-(tert-butyldimethylsilyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxycytidine収率 74%

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒2 回HCID 6344Dichloromethane溶媒

実験手順

The starting material (8) (10 g, 20.43 mmol) was azeotroped in dry pyridine (2×100 ml) then dissolved in dry pyridine (160 ml) under N2 atmosphere. Chlorotrimethylsilane (10 ml, 79.07 mmol) added drop wise to the solution and stirred for 2 hours at room temperature. Benzoyl chloride (2.6 ml, 22.40 mmol) was then added to solution and stirred for one further hour. The reaction mixture was cooled to 0° C., distilled water (50 ml) added slowly to the solution and stirred for 30 minutes. Pyridine and water were evaporated from mixture under high vacuum to yield a brown gel that was portioned between 100 ml of sat. aq. NaHCO3 (100 ml) solution DCM. The organic phase was separated and the aqueous phase extracted with a further (2×100 ml) of DCM. The organic layers were combined, dried (MgSO4), filtered and the volatiles evaporated under reduced pressure. The resulting brown oil was purified by flash chromatography on silica gel (DCM:MeOH 99:1 to 95:5) to yield a light yellow crystalline solid (13) (8.92 g, 74%) 1H NMR (d6 DMSO): δ 0.00 (s, 6H, CH3), 0.78 (s, 9H, tBu), 1.94 (m, 1H, H-2′), 2.27 (m, 1H, H-2′), 3.64 (d, 1H, J=11.6 Hz, H-5′), 3.75 (d, 1H, J=11.6 Hz, H-5′), 3.91 (m, 1H, H-4′), 4.09 (br m, 3H, CH2NH, H-3′), 5.24 (s, 1H, 3′—OH), 6.00 (m, 1H, H-1′), 7.39 (m, 2H, Ph), 7.52 (m, 2H, Ph), 7.86 (m, 1H, Ph), 8.0 (s, 1H, H-6), 9.79 (t, 1H, J=5.4 Hz, NHCH2), 12.67 (br s, 1H, NH). Mass (+ve electrospray) calcd for C27H33F3N4O6Si 594.67, found 595.

後処理

  1. stirringstirred for one further hour
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. distillationdistilled water (50 ml)
  4. additionadded slowly to the solution
  5. stirringstirred for 30 minutes
  6. customPyridine and water were evaporated from mixture under high vacuum
  7. customto yield a brown gel that
  8. customThe organic phase was separated
  9. extractionthe aqueous phase extracted with a further (2×100 ml) of DCM
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. customthe volatiles evaporated under reduced pressure
  13. customThe resulting brown oil was purified by flash chromatography on silica gel (DCM:MeOH 99:1 to 95:5)

出典と根拠

ORDレコード
ord-d507759260cc401d95a2c0d4f19132b4
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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