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 1896228ノート

反応式

HRID 1896228 の反応式
[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

参加物

8

反応物 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

生成物 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-diol収率 91%

試薬・触媒・溶媒 3

HCID 24462Copper Sulfate触媒HCID 962Water溶媒HCID 18914702t-Butanol dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-d8d1652af8344f9396dd9d39766493eb
出典データセット
uspto-grants-2013_08
特許番号
US08518957B2

反応ノート

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