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

HRID 1052877노트

반응식

HRID 1052877 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 1049Pyridine용매2회HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-73b79b3438a54693b37e01f6393e29d3
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09388464B2

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