Bicarbonate Ion → TFA-ap-dC

HRID 500306ノート

反応式

HRID 500306 の反応式
I[C:2]1[C:3]([NH2:17])=[N:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1.C(N(CC)CC)C.[F:25][C:26]([F:34])([F:33])[C:27]([NH:29][CH2:30][C:31]#[CH:32])=[O:28].N(CO[C@@H]1[C@@H](CO)O[C@@H](N2C=C(C#CCNC(=O)C(F)(F)F)C(=O)NC2=O)C1)=[N+]=[N-].C(=O)(O)[O-]>CN(C=O)C.[Cu]I>[F:25][C:26]([F:34])([F:33])[C:27]([NH:29][CH2:30][C:31]#[C:32][C:2]1[C:3]([NH2:17])=[N:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1)=[O:28]

参加物

8

反応物 5

HCID 769Bicarbonate IonHCID 8471TriethylamineHCID 65050IbacitabineHCID 110948052,2,2-trifluoro-N-(prop-2-yn-1-yl)acetamideHCID 866136103'-O-Azidomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridine

生成物 1

HCID 14768553TFA-ap-dC

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 5-iodo-2′-deoxycytidine (10 g, 28.32 mmol) in DMF (200 ml) in a light protected round bottom flask under Argon atmosphere, was added CuI (1.08 g, 5.67 mmol), triethylamine (7.80 ml, 55.60 mmol), 2,2,2-trifluoro-N-prop-2-ynyl-acetamide (12.8 g, 84.76 mmol) and at last Pd(PPh)3)4 (3.27 g, 2.83 mmol). After 18 hours at room temperature, dowex bicarbonate (20 mg) was added and the mixture was stirred for a further 1 h. Filtration and evaporation of the volatiles under reduced pressure gave a residue that was purified by flash chromatography on silica gel (CH2Cl2, CH2Cl2:EtOAc 1:1, EtOAc:MeOH 9:1). The expected product (7) was obtained as a beige solid in quantitative yield. 1H NMR (D2O) δ 2.24-2.17 (m, 1H, H-2′), 2.41-2.37 (m, 1H, H-2′), 3.68 (dd, J=12.5, 5.0 Hz, 1H, H-5′), 3.77 (dd, J=12.5, 3.2 Hz, 1H, H-5′), 3.99 (m, 1H, H-4′), 4.27 (s, 2H, CH2N), 4.34 (m, 1H, H-3′), 6.11 (t, J=6.3 Hz, 1H, H-1′), 8.1 (br s, 1H, NH); MS (ES): m/z (%) (M−H) 375 (100).

後処理

  1. filtrationFiltration and evaporation of the volatiles under reduced pressure
  2. customgave a residue that
  3. customwas purified by flash chromatography on silica gel (CH2Cl2, CH2Cl2:EtOAc 1:1, EtOAc:MeOH 9:1)

出典と根拠

ORDレコード
ord-fa8eae02176b43f4a37a1176455d1e05
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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