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

HRID 634215Notes

Reaction equation

HRID 634215 reaction equation
[CH:1]1([NH:4][C:5]2[O:6][C:7]([C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[N:15]([S:19]([C:22]3[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=3)(=[O:21])=[O:20])[CH:14]=[C:13]4B3OC(C)(C)C(C)(C)O3)=[N:8][N:9]=2)[CH2:3][CH2:2]1.Cl[C:39]1[CH:44]=[N:43][CH:42]=[C:41]([CH:45]2[CH2:47][CH2:46]2)[N:40]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.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:1]1([NH:4][C:5]2[O:6][C:7]([C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[N:15]([S:19]([C:22]3[CH:23]=[CH:24][C:25]([CH3:26])=[CH:27][CH:28]=3)(=[O:20])=[O:21])[CH:14]=[C:13]4[C:39]3[CH:44]=[N:43][CH:42]=[C:41]([CH:45]4[CH2:47][CH2:46]4)[N:40]=3)=[N:8][N:9]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 649849712-Chloro-6-cyclopropylpyrazineHCID 68328967N-cyclopropyl-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 68328339N-cyclopropyl-5-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amineYield 19.5%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
130 °C

Procedure

To a 20 mL microwave vial was added N-cyclopropyl-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 (200 mg, 0.456 mmol), 2-chloro-6-cyclopropylpyrazine (CombiPhos Catalysts Inc., 78 mg, 0.502 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (13.05 mg, 0.027 mmol), Pd2(dba)3 (12.5 mg, 0.014 mmol), and potassium phosphate (291 mg, 1.369 mmol) followed by purging with argon. The solids were treated with dioxane (4.0 mL) and water (0.4 mL) and heated in the microwave at 130° C. for 20 min. The mixture was treated with H2O and extracted with EtOAc, dried over MgSO4, filtered and concentrated. Purification (0-100% EtOAc in Hex) afforded N-cyclopropyl-5-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (45.6 mg, 19%) as a pale yellow solid. MS (ESI, pos. ion) m/z: 513.1 (M+1).

Workup

  1. customby purging with argon
  2. additionThe solids were treated with dioxane (4.0 mL) and water (0.4 mL)
  3. additionThe mixture was treated with H2O
  4. extractionextracted with EtOAc
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification (0-100% EtOAc in Hex)

Sources & evidence

ORD record
ord-38f8414c7c6546f196110a7ad2b76f55
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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