Cesium fluoride → N-tert-butyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamide

HRID 886755Notes

Reaction equation

HRID 886755 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([NH:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[CH:4][CH:3]=1.[CH:14]1([NH:17][C:18](=[O:35])[C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[C:21](B3OC(C)(C)C(C)(C)O3)[CH:20]=2)[CH2:16][CH2:15]1.[F-].[Cs+].O1CCOCC1>CCOC(C)=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.O>[C:10]([NH:9][C:7]([C:5]1[S:6][C:2]([C:21]2[CH:20]=[C:19]([C:18](=[O:35])[NH:17][CH:14]3[CH2:16][CH2:15]3)[CH:24]=[CH:23][C:22]=2[CH3:25])=[CH:3][CH:4]=1)=[O:8])([CH3:13])([CH3:12])[CH3:11]

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 312751,4-DioxaneHCID 8450905-bromo-N-tert-butylthiophene-2-carboxamideHCID 21914577N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide

Product 1

HCID 68559715N-tert-butyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamideYield 59.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A 15 ml glass microwave reaction vessel was charged with 5-Bromo-N-tert-butylthiophene-2-carboxamide (1.5 g, 5.7 mmol), N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (1.7 g, 5.7 mmol), cesium fluoride (0.63 g, 17 mmol), tetrakis(triphenylphosphine)palladium(0) (0.46 g, 0.40 mmol), 1,4-dioxane (4 ml, 57 mmol) and water (4 ml). The reaction mixture was heated in a Smith Synthesizer microwave reactor (Personal Chemistry, Inc., Upssala, Sweden) at 150° C. for 20 min. The reaction mixture was diluted with EtOAc and filtered through Celite and the Celite was washed with DCM. The combined organic solutions were evaporated under reduced pressure. The crude residue was suspended in DCM and washed with saturated sodium bicarbonate followed by brine, water and dried over MgSO4. The organic solutions were evaporated under reduced pressure and the crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 5% to 95% MeOH in DCM to provide N-tert-butyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamide (1.2 g). MS (ES+): 357 (M+H)+.

Workup

  1. filtrationfiltered through Celite
  2. washthe Celite was washed with DCM
  3. customThe combined organic solutions were evaporated under reduced pressure
  4. washwashed with saturated sodium bicarbonate
  5. dry with materialdried over MgSO4
  6. customThe organic solutions were evaporated under reduced pressure
  7. customchromatographed through a Redi-Sep pre-packed silica gel column (40 g)
  8. washeluting with a gradient of 5% to 95% MeOH in DCM

Sources & evidence

ORD record
ord-d9e003cbf4074d41a2c247923d6f86a6
Source dataset
uspto-grants-2012_08
Patent number
US08247409B2

Reaction notes

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