Diisopropylethylamine → 6-Azido-2-fluoro-9-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)purine

HRID 1646666노트

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HRID 1646666 반응식
[CH2:1]([O:8][C@H:9]1[C@H:25]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:24]([CH2:34][O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[O:23][CH:10]1OC(=O)C1C=CC([N+]([O-])=O)=CC=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[N:52]([C:55]1[N:63]=[C:62]([F:64])[N:61]=[C:60]2[C:56]=1[NH:57][CH:58]=[N:59]2)=[N+:53]=[N-:54]>ClCCCl.ClCCl>[N:52]([C:55]1[N:63]=[C:62]([F:64])[N:61]=[C:60]2[C:56]=1[N:57]=[CH:58][N:59]2[C@@H:10]1[O:23][C@H:24]([CH2:34][O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C@@H:25]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:9]1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[N+:53]=[N-:54]

참가 물질

6

반응물 3

HCID 81531Diisopropylethylamine2회HCID 970762,3,5-Tri-O-benzyl-1-O-(4-nitrobenzoyl)-D-arabinofuranoseHCID 198012676-azido-2-fluoro-7H-purine

생성물 1

HCID 544897616-Azido-2-fluoro-9-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)purine수율 24.6%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 6344Dichloromethane용매

실험 절차

A solution of 2,3,5-tri-O-benzyl-1-α-D-arabinofuranosylchloride (freshly prepared from 1.9 g of 2,3,5-tri-O-benzyl-1-O-p-nitrobenzoyl-D-arabinofuranose), N,N-diisopropylethylamine (0.58 mL) and 6-azido-2-fluoropurine (0.50 g) in 10 mL of anhydrous 1,2-dichloroethane was heated at reflux overnight. Additional N,N-diisopropylethylamine (0.26 mL) was added and heating was continued for an additional 24 hours. The mixture was cooled to ambient temperature and diluted with dichloromethane (60 mL) and washed sequentially with 10% aqueous sodium hydroxide (NaOH), water, 1N phosphoric acid (H3PO4), saturated NaCl and then dried over MgSO4 along with decolorizing carbon. The dried solution was filtered through celite and concentrated in vacuo. The residue was purified by silica gel chromatography with gradient elution from 3:1 Hexane:ethyl acetate to 100% ethyl acetate to obtain 0.40 g of the title compound as a colorless oil; IR (neat) 3031, 2922, 2867, 2126, 1608 cm-1 ; 1H NMR (DMSO-d6, 360 MHz) δ3.65-3.75 (m, 2H), 4.16 (q, J=5 Hz, 1H), 4.22 (d, J=11.8 Hz), 4.42 (t, J=5.5 Hz, 1H), 4.47 (d, J=11.8 Hz, 1H), 4.51 (s, 2H), 4.58 (t, J=5.5 Hz, 1H), 4.62 (d, J=12.0 Hz, 1H), 4.68 (d, J=12.0 Hz, 1H), 6.41 (d, J=5.5 Hz, 1H), 6.9-6.95 (m, 2H) 7.1-7.2 (m, 3H), 7.25-7.4 (m, 10H), 8.48 (s, 1H); UV (MeOH) λmax, 286 nm; MS (EI+, m/z) 582 (M+H)+.

후처리

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. temperatureheating
  4. washwashed sequentially with 10% aqueous sodium hydroxide (NaOH), water, 1N phosphoric acid (H3PO4), saturated NaCl
  5. dry with materialdried over MgSO4 along with decolorizing carbon
  6. filtrationThe dried solution was filtered through celite and
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography with gradient elution from 3:1 Hexane

출처 및 근거

ORD 기록
ord-c2e760113de6479bb1270021495b60a8
출처 데이터셋
uspto-grants-1993_01
특허 번호
US05180824

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