Sodium Iodide → 4-(5-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-6-(1H-indol-4-yl)-1H-indazole

HRID 520611Notes

Reaction equation

HRID 520611 reaction equation
[CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][NH:4][CH2:3]1.Cl[CH2:10][C:11]1[O:15][C:14]([C:16]2[CH:24]=[C:23]([C:25]3[CH:33]=[CH:32][CH:31]=[C:30]4[C:26]=3[CH:27]=[CH:28][NH:29]4)[CH:22]=[C:21]3[C:17]=2[CH:18]=[N:19][N:20]3S(C2C=CC=CC=2)(=O)=O)=[N:13][N:12]=1.C(N(CC)C(C)C)(C)C.[I-].[Na+].[OH-].[Na+]>C(#N)C.C(O)(C)C>[CH3:8][C@H:6]1[O:7][C@@H:2]([CH3:1])[CH2:3][N:4]([CH2:10][C:11]2[O:15][C:14]([C:16]3[CH:24]=[C:23]([C:25]4[CH:33]=[CH:32][CH:31]=[C:30]5[C:26]=4[CH:27]=[CH:28][NH:29]5)[CH:22]=[C:21]4[C:17]=3[CH:18]=[N:19][NH:20]4)=[N:13][N:12]=2)[CH2:5]1

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 6415002,6-Dimethylmorpholine, cis-HCID 667769544-[5-(Chloromethyl)-1,3,4-oxadiazol-2-yl]-6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazole

Product 1

HCID 667768284-(5-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-6-(1H-indol-4-yl)-1H-indazoleYield 9%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

(2R,6S)-2,6-Dimethylmorpholine (12.57 mg, 0.11 mmol) and 4-[5-(chloromethyl)-1,3,4-oxadiazol-2-yl]-6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazole (51 mg, 0.104 mmol) were dissolved in acetonitrile (0.5 ml) and N,N-diisopropylethylamine (0.0262 ml, 0.15 mmol) was added, followed by sodium iodide (14.99 mg, 0.1 mmol). The solution was stirred at 70° C. for 18 h and blown to dryness under a stream of nitrogen. Isopropanol (0.5 ml) was added followed by 2M sodium hydroxide (0.5 ml) and stirred for 18 h when the mixture was neutralised and the solvent removed under a stream of nitrogen. The crude product was dissolved in dimethylsulphoxide (0.5 ml) and purified by Mass Directed Automated Preparative HPLC (Method F) and the solvent was evaporated in vacuo using Genevac to give the title compound (4 mg).

Workup

  1. stirringstirred for 18 h when the mixture
  2. customthe solvent removed under a stream of nitrogen
  3. dissolutionThe crude product was dissolved in dimethylsulphoxide (0.5 ml)
  4. custompurified by Mass Directed Automated Preparative HPLC (Method F)
  5. customthe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-dec0e5153cc1499999d34c86643e1632
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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