1-Fluoro-2-nitro-4-azidobenzene → (1R,2R,3S,4R,5S)-4-(2-Chloro-6-(3-(5-(1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)pent-1-ynyl)benzylamino)-9H-purin-9-yl)-bicyclo[3.1.0]hexane-2,3-diol

HRID 1896228노트

반응식

HRID 1896228 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[N+:9]=[N-:10])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].CCCC[Sn](OC(C)=O)(CCCC)CCCC.[Cl:31][C:32]1[N:40]=[C:39]2[C:35]([N:36]=[CH:37][N:38]2[C@@H:41]2[C@@H:46]3[C@@H:44]([CH2:45]3)[C@@H:43]([OH:47])[C@H:42]2[OH:48])=[C:34]([NH:49][CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[C:53]([C:57]#[C:58][CH2:59][CH2:60][CH2:61][C:62]#[CH:63])[CH:52]=2)[N:33]=1.O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>C(Cl)Cl.C(O)(C)(C)C.S([O-])([O-])(=O)=O.[Cu+2].O>[Cl:31][C:32]1[N:40]=[C:39]2[C:35]([N:36]=[CH:37][N:38]2[C@@H:41]2[C@@H:46]3[C@@H:44]([CH2:45]3)[C@@H:43]([OH:47])[C@H:42]2[OH:48])=[C:34]([NH:49][CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[C:53]([C:57]#[C:58][CH2:59][CH2:60][CH2:61][C:62]3[N:10]=[N:9][N:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[C:3]([N+:11]([O-:13])=[O:12])[CH:4]=4)[CH:63]=3)[CH:52]=2)[N:33]=1

참가 물질

8

반응물 4

HCID 931211-Fluoro-2-nitro-4-azidobenzeneHCID 16682741Tributyltin acetateHCID 23667548Sodium AscorbateHCID 86672495(1R,2R,3S,4R,5S)-4-(2-Chloro-6-(3-(hepta-1,6-diynyl)benzylamino)-9H-purin-9-yl) bicyclo[3.1.0]hexane-2,3-diol

생성물 1

HCID 86672494(1R,2R,3S,4R,5S)-4-(2-Chloro-6-(3-(5-(1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)pent-1-ynyl)benzylamino)-9H-purin-9-yl)-bicyclo[3.1.0]hexane-2,3-diol수율 91%

시약·촉매·용매 3

HCID 24462Copper Sulfate촉매HCID 962Water용매HCID 18914702t-Butanol dichloromethane용매

실험 절차

4-Fluoro-3-nitro-phenylazide (7.5 mg, 0.041 mmol) and TBTA (1 mg, 0.001 mmol) were added to a solution of compound 211 (13.5 mg, 0.029 mmol) in CH2Cl2-t-butanol (0.6 mL)-water (0.6 mL) at room temperature. Freshly prepared 1M solution of sodium ascorbate (29.2 μL) followed by 7.5% solution of copper sulfate (48 μL, 0.015 mmol) was also added into the reaction mixture stirred at room temperature overnight. Solvent was evaporated, and the residue was purified on flash silica gel column chromatography (CH2Cl2:MeOH=45:1) to give compound 214 (17 mg, 91%) as a syrup. 1H NMR (CD3OD, 400 MHz) δ 861-8.59 (m, 1H), 8.49 (s, 1H), 8.23-8.19 (m, 1H), 8.14 (s, 1H), 7.65 (t, J=9.2 Hz, 1H), 7.39 (s, 1H), 7.33-7.24 (m, 3H), 4.79 (s, 1H), 4.72-4.70 (m, 3H), 3.90 (d, J=6.4 Hz, 1H), 2.99 (t, J=7.6 Hz, 2H), 2.53 (t, J=6.8 Hz, 2H), 2.08-1.96 (m, 3H), 1.69-1.65 (m, 1H), 1.33-1.30 (m, 1H), 0.79-0.75 (m, 1H). HRMS calculated for C31H28ClFN9O4 (M+H)+: 644.1937. Found 644.1962.

후처리

  1. additionwas also added into the reaction mixture
  2. customSolvent was evaporated
  3. customthe residue was purified on flash silica gel column chromatography (CH2Cl2:MeOH=45:1)

출처 및 근거

ORD 기록
ord-d8d1652af8344f9396dd9d39766493eb
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08518957B2

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