Potassium Phosphate, Tribasic → 2-cyclopropyl-5-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazole

HRID 634203Notes

Reaction equation

HRID 634203 reaction equation
[CH:1]1([C:4]2[O:5][C:6]([C:9]3[CH:10]=[C:11]4[C:15](=[CH:16][CH:17]=3)[N:14]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[CH:13]=[C:12]4B3OC(C)(C)C(C)(C)O3)=[N:7][N:8]=2)[CH2:3][CH2:2]1.Br[C:38]1[CH:43]=[N:42][CH:41]=[C:40]([CH:44]2[CH2:46][CH2:45]2)[N:39]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>[CH:1]1([C:4]2[O:5][C:6]([C:9]3[CH:10]=[C:11]4[C:15](=[CH:16][CH:17]=3)[N:14]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[CH:13]=[C:12]4[C:38]3[CH:43]=[N:42][CH:41]=[C:40]([CH:44]4[CH2:46][CH2:45]4)[N:39]=3)=[N:7][N:8]=2)[CH2:3][CH2:2]1

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 457883052-Bromo-6-cyclopropylpyrazineHCID 683286632-cyclopropyl-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazole

Product 1

HCID 683289342-cyclopropyl-5-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazoleYield 78.3%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A brown mixture of 2-cyclopropyl-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazole (298.4 mg, 0.590 mmol), 2-bromo-6-cyclopropylpyrazine (CombiPhos Catalysts, Inc., Princeton, N.J.; 129 mg, 0.649 mmol), Pd2(dba)3 (16.22 mg, 0.018 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (XPhos; 16.89 mg, 0.035 mmol), and potassium phosphate (376 mg, 1.771 mmol) in a mixture of dioxane (5.0 mL) and water (0.500 mL) was sparged with argon then heated at 100° C. for 2 h. The reaction was then cooled to RT, diluted with DCM (20 mL), and concentrated onto silica gel. Chromatographic purification (silica gel, 0-100% EtOAc/Hex) furnished 2-cyclopropyl-5-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazole (230 mg, 0.462 mmol, 78%) as a light-yellow solid: MS (ESI, pos. ion) m/z: 498.6 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.99 (1H, s), 8.75 (1H, s), 8.43 (1H, s), 8.18 (1H, s), 8.12 (2H, s), 7.84 (2H, d, J=8.4 Hz), 7.28 (2H, s), 2.36 (3H, s), 2.24-2.32 (1H, m), 2.12-2.21 (1H, m), 1.25-1.31 (4H, m), 1.15-1.23 (4H, m).

Workup

  1. customwas sparged with argon
  2. temperatureThe reaction was then cooled to RT
  3. additiondiluted with DCM (20 mL)
  4. concentrationconcentrated onto silica gel
  5. customChromatographic purification (silica gel, 0-100% EtOAc/Hex)

Sources & evidence

ORD record
ord-2d51b2fac628494cb874c15fa370a8b5
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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