Imidazole → 5'-O-(tert-Butyldimethylsilyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxycytidine

HRID 2273459Notes

Reaction equation

HRID 2273459 reaction equation
[F:1][C:2]([F:26])([F:25])[C:3]([NH:5][CH2:6][C:7]#[C:8][C:9]1[C:10]([NH2:24])=[N:11][C:12](=[O:23])[N:13]([CH:22]=1)[C@@H:14]1[O:21][C@H:18]([CH2:19][OH:20])[C@@H:16]([OH:17])[CH2:15]1)=[O:4].N1C=CN=C1.[CH3:32][C:33]([Si:36](Cl)([CH3:38])[CH3:37])([CH3:35])[CH3:34]>CN(C=O)C>[Si:36]([O:20][CH2:19][C@H:18]1[O:21][C@@H:14]([N:13]2[CH:22]=[C:9]([C:8]#[C:7][CH2:6][NH:5][C:3](=[O:4])[C:2]([F:25])([F:1])[F:26])[C:10]([NH2:24])=[N:11][C:12]2=[O:23])[CH2:15][C@@H:16]1[OH:17])([C:33]([CH3:35])([CH3:34])[CH3:32])([CH3:38])[CH3:37]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 14768553TFA-ap-dC

Product 1

HCID 866136115'-O-(tert-Butyldimethylsilyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxycytidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the starting material (7) (1.0 g, 2.66 mmol) and imidazole (200 mg, 2.93 mmol) in DMF (3.0 ml) at 0° C., was slowly added TBDMSCl (442 mg, 2.93 mmol) in four portions over 1 h. After 2 h, the volatiles were evaporated under reduced pressure and the residue was adsorbed on silica gel and purified by flash chromatography (EtOAc, EtOAc:MeOH 9.5:0.5). The expected product (8) was isolated as a crystalline solid (826 mg, 64%). 1H NMR (d6 DMSO) δ 0.00 (s, 1H, CH3); 0.01 (s, 1H, CH3), 0.79 (s, 9H, tBu), 1.87-1.80 (m, 1H, H-2′), 2.12 (ddd, J=13.0, 5.8 and 3.0 Hz, 1H, H-2′), 3.65 (dd, J=11.5, 2.9 Hz, 1H, H-5′), 3.74 (dd, J=11.5, 2.5 Hz, 1H, H-5′), 3.81-3.80 (m, 1H, H-4′), 4.10-4.09 (m, 1H, H-3′), 4.17 (d, 2H, J=5.1 Hz, NCH2), 5.19 (d, 1H, J=4.0 Hz, 3′-OH), 6.04 (t, J=6.6 Hz, 1H, H-1′), 6.83 (br s, 1H, NHH), 7.78 (br s, 1H, NHH), 7.90 (s, 1H, H-6), 9.86 (t, J=5.1 Hz, 1H, —H2CNH); MS (ES): m/z (%) (MH)+ 491 (40%).

Workup

  1. customat 0° C.
  2. customover 1 h
  3. customthe volatiles were evaporated under reduced pressure
  4. custompurified by flash chromatography (EtOAc, EtOAc:MeOH 9.5:0.5)

Sources & evidence

ORD record
ord-5c395f3065a34475ade2f43774b814da
Source dataset
uspto-grants-2015_09
Patent number
US09121060B2

Reaction notes

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