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

HRID 634217Notes

Reaction equation

HRID 634217 reaction equation
[C:1]1([C:7]([NH:10][C:11]2[O:12][C:13]([C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[N:21]([S:25]([C:28]3[CH:34]=[CH:33][C:31]([CH3:32])=[CH:30][CH:29]=3)(=[O:27])=[O:26])[CH:20]=[C:19]4B3OC(C)(C)C(C)(C)O3)=[N:14][N:15]=2)([CH3:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.Br[C:79]1[CH:84]=[N:83][CH:82]=[C:81]([CH:85]2[CH2:87][CH2:86]2)[N:80]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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]>[CH:85]1([C:81]2[N:80]=[C:79]([C:19]3[C:18]4[C:22](=[CH:23][CH:24]=[C:16]([C:13]5[O:12][C:11]([NH:10][C:7]([C:1]6[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=6)([CH3:8])[CH3:9])=[N:15][N:14]=5)[CH:17]=4)[N:21]([S:25]([C:28]4[CH:29]=[CH:30][C:31]([CH3:32])=[CH:33][CH:34]=4)(=[O:27])=[O:26])[CH:20]=3)[CH:84]=[N:83][CH:82]=2)[CH2:87][CH2:86]1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 457883052-Bromo-6-cyclopropylpyrazineHCID 68328199N-(2-phenylpropan-2-yl)-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine

Product 1

HCID 683281825-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(2-phenylpropan-2-yl)-1,3,4-oxadiazol-2-amineYield 29%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

To a 20 mL microwave vial was added N-(2-phenylpropan-2-yl)-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (86 mg, 0.167 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (4.8 mg, 9.99 μmol), Pd2(dba)3 (4.6 mg, 5.00 μmol), 2-bromo-6-cyclopropylpyrazine (CombiPhos Catalyst Inc., 36.5 mg, 0.183 mmol) and potassium phosphate (106 mg, 0.500 mmol) followed by purging with argon. The solids were treated with dioxane (3.0 mL) and water (0.3 mL) and heated in the microwave at 120° C. for 20 min. The mixture was treated with water and extracted with EtOAc, dried over MgSO4, filtered and concentrated. Purification (10-100% EtOAc in Hex) afforded 5-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(2-phenylpropan-2-yl)-1,3,4-oxadiazol-2-amine (28.1 mg, 29%) as a pale yellow solid. MS (ESI, pos. ion) m/z: 591.2 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.64-8.71 (2H, m), 8.39 (1H, s), 8.13 (1H, s), 8.03 (1H, d, J=8.8 Hz), 7.81 (2H, d, J=8.4 Hz), 7.78 (1H, dd, J=8.7, 1.5 Hz), 7.54 (2H, d, J=7.6 Hz), 7.35 (2H, t, J=7.7 Hz), 7.22-7.29 (3H, m), 6.01 (1H, s), 2.35 (3H, s), 2.09-2.16 (1H, m), 1.86 (6H, s), 1.20-1.24 (2H, m), 1.08-1.14 (2H, m).

Workup

  1. customby purging with argon
  2. additionThe solids were treated with dioxane (3.0 mL) and water (0.3 mL)
  3. additionThe mixture was treated with water
  4. extractionextracted with EtOAc
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification (10-100% EtOAc in Hex)

Sources & evidence

ORD record
ord-fd73def145b345538aafd8e30c828bc1
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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