Potassium Phosphate, Tribasic → N-(4-methoxybenzyl)-5-(3-(6-(2-methylpiperidin-1-yl)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine

HRID 634091Notes

Reaction equation

HRID 634091 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[CH3:43][CH:44]1[CH2:49][CH2:48][CH2:47][CH2:46][N:45]1[C:50]1[CH:55]=[N:54][CH:53]=[C:52](B2OC(C)(C)C(C)(C)O2)[N:51]=1.I[C:66]1[C:74]2[C:69](=[CH:70][CH:71]=[C:72]([C:75]3[O:79][C:78]([NH:80][CH2:81][C:82]4[CH:87]=[CH:86][C:85]([O:88][CH3:89])=[CH:84][CH:83]=4)=[N:77][N:76]=3)[CH:73]=2)[N:68]([S:90]([C:93]2[CH:99]=[CH:98][C:96]([CH3:97])=[CH:95][CH:94]=2)(=[O:92])=[O:91])[CH:67]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:89][O:88][C:85]1[CH:86]=[CH:87][C:82]([CH2:81][NH:80][C:78]2[O:79][C:75]([C:72]3[CH:73]=[C:74]4[C:69](=[CH:70][CH:71]=3)[N:68]([S:90]([C:93]3[CH:94]=[CH:95][C:96]([CH3:97])=[CH:98][CH:99]=3)(=[O:91])=[O:92])[CH:67]=[C:66]4[C:52]3[CH:53]=[N:54][CH:55]=[C:50]([N:45]4[CH2:46][CH2:47][CH2:48][CH2:49][CH:44]4[CH3:43])[N:51]=3)=[N:76][N:77]=2)=[CH:83][CH:84]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 457862286-(2-Methylpiperidin-1-yl)pyrazine-2-boronic acid pinacol esterHCID 683283255-(3-iodo-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine

Product 1

HCID 68328232N-(4-methoxybenzyl)-5-(3-(6-(2-methylpiperidin-1-yl)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amineYield 53.1%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

K3PO4 (327 mg, 1.539 mmol) (Reidel-de Haen), XPhos (14.67 mg, 0.031 mmol) (Strem), Pd2(dba)3 (14.09 mg, 0.015 mmol) (Strem), 2-(2-methylpiperidin-1-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazine (194 mg, 0.641 mmol) (CombiPhos Catalysts Inc.) and 5-(3-iodo-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine (308 mg, 0.513 mmol) were weighed into a 5 mL glass microwave tube. The tube was purged with argon and the contents were treated with dioxane (3.0 mL) and water (0.5 mL). The tube was sealed and the suspension was heated at 120° C. for 10 min in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden). An additional 50 mg of the boronic ester were added, the tube was sealed and the mixture was heated at 120° C. for an additional 10 min. The mixture was treated with 1N NaOH and extracted with EtOAc (50 mL). The organic layer was dried over MgSO4, filtered and concentrated. Purification by flash chromatography (eluent: 20% MeOH in DCM) afforded N-(4-methoxybenzyl)-5-(3-(6-(2-methylpiperidin-1-yl)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (177 mg, 0.272 mmol, 53.1%) as a dark yellow solid. MS (ESI, pos. ion) m/z: 650.0 (M+1).

Workup

  1. customThe tube was purged with argon
  2. additionthe contents were treated with dioxane (3.0 mL) and water (0.5 mL)
  3. customThe tube was sealed
  4. additionAn additional 50 mg of the boronic ester were added
  5. customthe tube was sealed
  6. temperaturethe mixture was heated at 120° C. for an additional 10 min
  7. additionThe mixture was treated with 1N NaOH
  8. extractionextracted with EtOAc (50 mL)
  9. dry with materialThe organic layer was dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by flash chromatography (eluent: 20% MeOH in DCM)

Sources & evidence

ORD record
ord-e04ba10bfb414b5c8efffa91059957e2
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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