Dimethylformamide → 5-(5-{5-fluoro-2-(methyloxy)-3-[(E)-2-(methyloxy)ethenyl]phenyl}-1,3,4-thiadiazol-2-yl)-2-(2-methylpropyl)benzonitrile

HRID 1942612Notes

Reaction equation

HRID 1942612 reaction equation
Br[C:2]1[S:3][C:4]([C:7]2[CH:12]=[CH:11][C:10](OC(C)C)=[C:9](C(F)(F)F)[CH:8]=2)=[N:5][N:6]=1.[F:21][C:22]1[CH:23]=[C:24](/[CH:39]=[CH:40]/[O:41][CH3:42])[C:25]([O:37][CH3:38])=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:27]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C[N:52]([CH3:55])C=O>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:21][C:22]1[CH:23]=[C:24](/[CH:39]=[CH:40]/[O:41][CH3:42])[C:25]([O:37][CH3:38])=[C:26]([C:2]2[S:3][C:4]([C:7]3[CH:8]=[CH:9][C:10]([CH2:4][CH:7]([CH3:12])[CH3:8])=[C:11]([CH:12]=3)[C:55]#[N:52])=[N:5][N:6]=2)[CH:27]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 669817782-Bromo-5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazoleHCID 669817982-{5-fluoro-2-(methyloxy)-3-[(E)-2-(methyloxy)ethenyl]phenyl}-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 669817285-(5-{5-fluoro-2-(methyloxy)-3-[(E)-2-(methyloxy)ethenyl]phenyl}-1,3,4-thiadiazol-2-yl)-2-(2-methylpropyl)benzonitrile

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
120 °C

Procedure

To a suspension of 2-bromo-5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazole (D26) (400 mg), 2-{5-fluoro-2-(methyloxy)-3-[(E)-2-(methyloxy)ethenyl]phenyl}-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (459 mg) and tripotassium phosphate (659 mg) in N,N-dimethylformamide (DMF) (8 mL) and water (2 mL) under nitrogen was added Pd(Ph3P)4 (71.7 mg). The reaction vessel was sealed and heated under microwave at 120° C. for 10 min. Water was added. The reaction mixture was extracted with EA for 3 times, the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, the dried solution was concentrated, and purified by column chromatography to afford 5-(5-{5-fluoro-2-(methyloxy)-3-[(E)-2-(methyloxy)ethenyl]phenyl}-1,3,4-thiadiazol-2-yl)-2-(2-methylpropyl)benzonitrile (D36) (140 mg) as a yellow solid. MS (ES): C23H22FN3O2S requires 423. found 424.1 (M+H+).

Workup

  1. customThe reaction vessel was sealed
  2. extractionThe reaction mixture was extracted with EA for 3 times
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationthe dried solution was concentrated
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-486a383382334555bcdf024fa13fd7bd
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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