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 1896231노트

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HRID 1896231 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].[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

참가 물질

8

반응물 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

생성물 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-carboxamide수율 92%

시약·촉매·용매 3

HCID 24462Copper Sulfate촉매HCID 16682741Tributyltin acetate촉매HCID 6386tert-Butanol용매

실험 절차

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.

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=30:1)

출처 및 근거

ORD 기록
ord-568fab321a654552875384824a02f29e
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08518957B2

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