Water → (1S,2R,3S,4R,5S)-4-(2-Chloro-6-((1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide

HRID 1896231ノート

反応式

HRID 1896231 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].[Cl:14][C:15]1[N:23]=[C:22]2[C:18]([N:19]=[CH:20][N:21]2[C@@H:24]2[C@@H:29]3[C@@:27]([C:30]([NH:32][CH3:33])=[O:31])([CH2:28]3)[C@@H:26]([OH:34])[C@H:25]2[OH:35])=[C:17]([NH:36][CH2:37][C:38]#[CH:39])[N:16]=1.O.O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>C(O)(C)(C)C.S([O-])([O-])(=O)=O.[Cu+2].CCCC[Sn](OC(C)=O)(CCCC)CCCC>[Cl:14][C:15]1[N:23]=[C:22]2[C:18]([N:19]=[CH:20][N:21]2[C@@H:24]2[C@@H:29]3[C@@:27]([C:30]([NH:32][CH3:33])=[O:31])([CH2:28]3)[C@@H:26]([OH:34])[C@H:25]2[OH:35])=[C:17]([NH:36][CH2:37][C:38]2[N:10]=[N:9][N:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[C:3]([N+:11]([O-:13])=[O:12])[CH:4]=3)[CH:39]=2)[N:16]=1

参加物

8

反応物 4

HCID 962WaterHCID 931211-Fluoro-2-nitro-4-azidobenzeneHCID 23667548Sodium AscorbateHCID 86672501(1S,2R,3S,4R,5S)-4-(2-Chloro-6-(prop-2-ynylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide

生成物 1

HCID 86672500(1S,2R,3S,4R,5S)-4-(2-Chloro-6-((1-(4-fluoro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide収率 92%

試薬・触媒・溶媒 3

HCID 24462Copper Sulfate触媒HCID 16682741Tributyltin acetate触媒HCID 6386tert-Butanol溶媒

実験手順

4-Fluoro-3-nitro-phenylazide (9.7 mg, 0.053 mmol) and TBTA (1 mg, 0.001 mmol) were added to a solution of compound 218 (14.4 mg, 0.038 mmol) in t-butanol (0.8 mL)-water (0.8 mL) at room temperature. Freshly prepared 1M solution of sodium ascorbate (38.2 μL) followed by 7.5% solution of copper sulfate (63 μL, 0.019 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=30:1) to give compound 219a (19 mg, 92%) as a syrup. 1H NMR (CD3OD, 400 MHz) δ 8.62-8.61 (m, 2H), 8.27-8.24 (m, 1H), 8.06 (s, 1H), 7.69-7.64 (m, 1H), 5.08 (d, J=6.8 Hz, 1H), 4.94 (br s, 2H), 4.81 (s, 1H), 4.01 (d, J=6.0 Hz, 1H), 2.87 (s, 3H), 2.07-2.04 (m, 1H), 1.82 (t, J=4.8 Hz, 1H), 1.39-1.37 (m, 1H). HRMS calculated for C22H21ClFN10O5 (M+H)+: 559.1369. Found 559.1346.

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=30:1)

出典と根拠

ORDレコード
ord-568fab321a654552875384824a02f29e
出典データセット
uspto-grants-2013_08
特許番号
US08518957B2

反応ノート

読み込み中…