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

HRID 634305Notes

Reaction equation

HRID 634305 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](B3OC(C)(C)C(C)(C)O3)=[CH:7][N:8]2[S:11]([C:14]2[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[CH:4][C:3]=1[C:30]1[O:34][C:33]([NH:35][CH:36]([CH3:38])[CH3:37])=[N:32][N:31]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Br[C:74]1[CH:79]=[N:78][CH:77]=[C:76]([CH:80]2[CH2:82][CH2:81]2)[N:75]=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:80]1([C:76]2[N:75]=[C:74]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([F:1])=[C:3]([C:30]5[O:34][C:33]([NH:35][CH:36]([CH3:37])[CH3:38])=[N:32][N:31]=5)[CH:4]=4)[N:8]([S:11]([C:14]4[CH:15]=[CH:16][C:17]([CH3:18])=[CH:19][CH:20]=4)(=[O:13])=[O:12])[CH:7]=3)[CH:79]=[N:78][CH:77]=2)[CH2:82][CH2:81]1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 457883052-Bromo-6-cyclopropylpyrazineHCID 683280445-(6-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine

Product 1

HCID 683283495-(3-(6-cyclopropylpyrazin-2-yl)-6-fluoro-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amineYield 36.3%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
130 °C

Procedure

A 20 mL microwave vial was charged with 5-(6-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (185 mg, 0.342 mmol), Xphos (Strem Chemicals, Newburyport, Mass., 9.8 mg, 0.021 mmol), Pd2(dba)3 (Strem Chemicals, Newburyport, Mass., 9.4 mg, 10.27 μmol), 2-bromo-6-cyclopropylpyrazine (CombiPhos Catalyst Inc., Princeton, N.J., 82 mg, 0.411 mmol) and potassium phosphate (218 mg, 1.03 mmol) followed by purging with argon. The solids were then treated with dioxane (4.0 mL) and water (1.0 mL) and heated in the microwave at 130° C. for 20 min. The reaction mixture was treated with water and extracted with EtOAc, dried over MgSO4, filtered and concentrated. Purification of the crude residue on the ISCO Combiflash Rf (12 g Redisep column, using a gradient of 0-100% EtOAc in hexanes) afforded 5-(3-(6-cyclopropylpyrazin-2-yl)-6-fluoro-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (65.8 mg, 0.124 mmol, 36.1% yield) as an off-white solid. MS (ESI, pos. ion) m/z: 533.0 (M+H)+. The material was used in the subsequent step without further purification.

Workup

  1. customby purging with argon
  2. additionThe solids were then treated with dioxane (4.0 mL) and water (1.0 mL)
  3. additionThe reaction mixture was treated with water
  4. extractionextracted with EtOAc
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the crude residue on the ISCO Combiflash Rf (12 g Redisep column

Sources & evidence

ORD record
ord-0f13af6cab73471b8ac9b316af53ba10
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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