Potassium Phosphate, Tribasic → 5-(3-Bromo-1,2,4-thiadiazol-5-yl)-2-(2-methylpropyl)benzonitrile

HRID 1942632Notes

Reaction equation

HRID 1942632 reaction equation
[CH3:1][CH:2]([CH3:21])[CH2:3][C:4]1[CH:11]=[CH:10][C:9](B2OC(C)(C)C(C)(C)O2)=[CH:8][C:5]=1[C:6]#[N:7].[Br:22][C:23]1[N:27]=[C:26](Cl)[S:25][N:24]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.O.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Br:22][C:23]1[N:27]=[C:26]([C:9]2[CH:10]=[CH:11][C:4]([CH2:3][CH:2]([CH3:1])[CH3:21])=[C:5]([CH:8]=2)[C:6]#[N:7])[S:25][N:24]=1

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27250533-Bromo-5-chloro-1,2,4-thiadiazoleHCID 51358167Benzonitrile, 2-(2-methylpropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-

Product 1

HCID 669817585-(3-Bromo-1,2,4-thiadiazol-5-yl)-2-(2-methylpropyl)benzonitrileYield 88.5%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-(2-methylpropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (D59) (500 mg), 3-bromo-5-chloro-1,2,4-thiadiazole (699 mg) and tripotassium phosphate (1116 mg) in N,N-dimethylformamide (DMF) (6 mL) and water (1.500 mL) stirred under nitrogen was added PdCl2(dppf) (154 mg). The reaction mixture was sealed and heated under microwave at 80° C. for 1 h. After cooling the reaction, the mixture was diluted with ethyl acetate, the organic phase was washed with water, dried and concentrated, the residue was purified by column chromatography to afford 5-(3-bromo-1,2,4-thiadiazol-5-yl)-2-(2-methylpropyl)benzonitrile (D60) (500 mg). δH (CDCl3, 400 MHz): 0.99 (6H, d), 2.04 (1H, m), 2.80 (2H, d), 7.46 (1H, d), 8.05 (1H, dd), 8.22 (1H, d). MS (ES): C13H12BrN3S requires 321. found 322.0 (M+H+).

Workup

  1. customThe reaction mixture was sealed
  2. temperatureAfter cooling
  3. customthe reaction
  4. washthe organic phase was washed with water
  5. customdried
  6. concentrationconcentrated
  7. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-8ec5e75776284223949eebea1236fcc3
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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