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

Reaction equation

HRID 1896228 reaction equation
[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

Participants

8

Reactant 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

Product 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-diolYield 91%

Reagents, catalysts & solvents 3

HCID 24462Copper SulfateCatalystHCID 962WaterSolventHCID 18914702t-Butanol dichloromethaneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-d8d1652af8344f9396dd9d39766493eb
Source dataset
uspto-grants-2013_08
Patent number
US08518957B2

Linked notes

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