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

HRID 634201Notes

Reaction equation

HRID 634201 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[N:43]=[C:42]([CH:44]2[CH2:46][CH2:45]2)[CH:41]=[CH:40][N:39]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>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: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:22]=[CH:23][C:24]([CH3:25])=[CH:26][CH:27]=3)(=[O:19])=[O:20])[CH:13]=[C:12]4[C:38]3[N:43]=[C:42]([CH:44]4[CH2:46][CH2:45]4)[CH:41]=[CH:40][N:39]=3)=[N:7][N:8]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 49758247HCID 49758247, compoundHCID 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 683281792-cyclopropyl-5-(3-(4-cyclopropylpyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazoleYield 23.5%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

To a 20 mL glass microwave tube containing 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 (340 mg, 0.673 mmol) was added 2-bromo-4-cyclopropylpyrimidine (154 mg, 0.774 mmol) (CombiPhos Catalysts Inc.), potassium phosphate (428 mg, 2.018 mmol) (Sigma-Aldrich), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (19.24 mg, 0.040 mmol) (Strem), and Pd2(dba)3 (18.48 mg, 0.020 mmol) (Strem). The tube was purged with argon, the solids were treated with dioxane (6.0 mL) and water (0.600 mL), the tube was sealed, and the contents were heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 100° C. for 20 min. The mixture was treated with water and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by flash chromatography (20-70% EtOAc in Hex) affording 2-cyclopropyl-5-(3-(4-cyclopropylpyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazole (78.6 mg, 0.158 mmol, 23.48%) as an amorphous, rust-coloured solid. MS (ESI, pos. ion) m/z: 498.1 (M+1).

Workup

  1. customThe tube was purged with argon
  2. additionthe solids were treated with dioxane (6.0 mL) and water (0.600 mL)
  3. customthe tube was sealed
  4. additionThe mixture was treated with water
  5. extractionextracted with EtOAc
  6. washThe organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by flash chromatography (20-70% EtOAc in Hex)

Sources & evidence

ORD record
ord-1cbdf395ed2c426c9618b9828daa5622
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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