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

HRID 1052872ノート

反応式

HRID 1052872 の反応式
[F:1][C:2]([F:26])([F:25])[C:3]([NH:5][CH2:6][C:7]#[C:8][C:9]1[C:10](=[O:24])[NH: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].[Si:27](Cl)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28].N1C=CN=C1>CN(C=O)C>[Si:27]([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](=[O:24])[NH:11][C:12]2=[O:23])[CH2:15][C@@H:16]1[OH:17])([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]

参加物

5

反応物 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 10894132TFA-ap-dU

生成物 1

HCID 866642615'-O-(tert-butydimethylsilyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridine

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of (1) (656 mg, 1.74 mmol) in dry DMF (15 ml) was added t-butyldimethylsilylchloride (288 mg, 1.91 mmol) in small portions, followed by imidazole (130 mg, 1.91 mmol). The reaction was followed by TLC and was completed after stirring for 8 h at room temperature. The reaction was quenched with sat. aq. NaCl solution. EtOAc (25 ml) was added to the reaction mixture and the aqueous layer was extracted with EtOAc three times. After drying the combined organics (MgSO4), the solvent was removed under vacuum. Purification by chromatography on silica (EtOAc:petroleum ether 8:2) gave (2) as slightly yellow crystals (676 mg, 83%). 1H NMR (d6 DMSO) δ 0.00 (s, 6H, CH3), 0.79 (s, 9H, tBu), 1.93-2.00 (m, 1H, H-2′), 2.06-2.11 (m, 1H, H-2′), 3.63-3.75 (m, 2H, H-5′), 3.79-3.80 (m, 1H, H-4′), 4.12-4.14 (m, 3H, H-3′, CHO, 5.22 (d, J=4.1 Hz, 1H, OH), 6.03 (t, J=6.9 Hz, 1H, H-1′), 7.86 (s, 1H, H-6), 9.95 (t, J=5.4 Hz, 1H, NH), 11.61 (br s, 1H, NH). Mass (−ve electrospray) calcd for C20H28F3N3O6Si, 491.17. found 490.

後処理

  1. customThe reaction was quenched with sat. aq. NaCl solution
  2. additionEtOAc (25 ml) was added to the reaction mixture
  3. extractionthe aqueous layer was extracted with EtOAc three times
  4. dry with materialAfter drying the combined organics (MgSO4)
  5. customthe solvent was removed under vacuum
  6. customPurification by chromatography on silica (EtOAc:petroleum ether 8:2)

出典と根拠

ORDレコード
ord-5d057c9c2f9d4be79ff9bac23e89ada7
出典データセット
uspto-grants-2016_07
特許番号
US09388464B2

反応ノート

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