Hydrochloric Acid → 6-(1H-Indol-4-yl)-4-{5-[(phenylsulfonyl)methyl]-1,3,4-oxadiazol-2-yl}-1H-indazole

HRID 520627Notes

Reaction equation

HRID 520627 reaction equation
Cl[CH2:2][C:3]1[O:7][C:6]([C:8]2[CH:16]=[C:15]([C:17]3[CH:25]=[CH:24][CH:23]=[C:22]4[C:18]=3[CH:19]=[CH:20][NH:21]4)[CH:14]=[C:13]3[C:9]=2[CH:10]=[N:11][N:12]3S(C2C=CC=CC=2)(=O)=O)=[N:5][N:4]=1.O.O.[C:37]1([S:43]([O-:45])=[O:44])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.[Na+].[OH-].[Na+].Cl>C(O)C.C(O)(C)C.CO.ClCCl>[NH:21]1[C:22]2[C:18](=[C:17]([C:15]3[CH:14]=[C:13]4[C:9]([CH:10]=[N:11][NH:12]4)=[C:8]([C:6]4[O:7][C:3]([CH2:2][S:43]([C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=5)(=[O:45])=[O:44])=[N:4][N:5]=4)[CH:16]=3)[CH:25]=[CH:24][CH:23]=2)[CH:19]=[CH:20]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 23681562Benzenesulfinic acid, sodium salt, dihydrateHCID 667769544-[5-(Chloromethyl)-1,3,4-oxadiazol-2-yl]-6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazole

Product 1

HCID 667769046-(1H-Indol-4-yl)-4-{5-[(phenylsulfonyl)methyl]-1,3,4-oxadiazol-2-yl}-1H-indazoleYield 16%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 887MethanolSolventHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

4-[5-(Chloromethyl)-1,3,4-oxadiazol-2-yl]-6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazole (60 mg, 0.110 mmol) and sodium benzenesulfinate dihydrate (33.1 mg, 0.165 mmol, available from TCI Europe) in ethanol (0.8 ml) were heated under microwave irradiation to 100° C. for 30 mins then 150° C. for 20 mins. The mixture was treated with dichloromethane (3 ml) and methanol (3 ml) and absorbed onto Florisil. This was placed on top a silica cartridge (10 g) and eluted with 0-100% ethyl acetate/cyclohexane and then 0-20% methanol/ethyl acetate. Appropriate fractions were combined and concentrated to give a yellow solid, 33 mg. The solid was treated with isopropanol (1 ml) and 2M aqueous sodium hydroxide (0.999 ml, 1.998 mmol) and stirred at 20° C. for 22 h. The mixture was neutralised with 2M aqueous hydrochloric acid, blown to dryness and purified by Mass Directed Automated Preparative H PLC. Appropriate fraction was evaporated, then azeotroped with methanol to give the title compound as a white solid (8 mg).

Workup

  1. customabsorbed onto Florisil
  2. washeluted with 0-100% ethyl acetate/cyclohexane
  3. concentrationconcentrated
  4. customto give a yellow solid, 33 mg
  5. custompurified by Mass Directed Automated Preparative H PLC
  6. customAppropriate fraction was evaporated
  7. customazeotroped with methanol

Sources & evidence

ORD record
ord-47b2c6f52e3041dc805d0abe7aae2ee3
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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