tert-Butyl (5-bromothiophen-3-yl)carbamate → HCID 121261628, compound

HRID 530433Notes

Reaction equation

HRID 530433 reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:6]=1.[C:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[NH:23][C:24]([NH2:26])=[O:25])#[CH:16]>C(N(CC)CC)C.CN(C=O)C.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:11]([O:10][C:8](=[O:9])[NH:7][C:5]1[CH:6]=[C:2]([C:16]#[C:15][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[NH:23][C:24]([NH2:26])=[O:25])[S:3][CH:4]=1)([CH3:14])([CH3:13])[CH3:12]

Participants

9

Reactant 2

HCID 15759194tert-Butyl (5-bromothiophen-3-yl)carbamateHCID 20280881HCID 20280881, compound

Product 1

HCID 121261628HCID 121261628, compoundYield 57.7%

Reagents, catalysts & solvents 6

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 2-bromo-4-(N-tert-butyloxycarbonylamino)thiophene (261 mg, 0.94 mmol, 1 eq), 1-(2-ethynylphenyl)urea (200 mg, 1.5 eq), and triphenylphosphine (6.2 mg, 0.025 eq) in anhydrous triethylamine (2 mL) and DMF (0.5 mL) was added bis(triphenylphosphine)palladium(II) dichloride (66 mg, 0.1 eq) and copper(I) iodide (18 mg, 0.1 eq). The mixture was stirred and heated at 80° C. for 30 minutes, then cooled to room temperature and diluted with ethyl acetate. It was washed sequentially with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, brine, and lastly dried with anhydrous sodium sulfate. The upper solution was decanted, concentrated, and the solid residue was subject to a gradient column chromatography (EtOAc-Hex from 1;100 to 1:1) to yield tert-butyl[5-({2-[(aminocarbonyl)amino]phenyl}ethynyl)-3-thienyl]carbamate as a yellow oil (194 mg) which was converted to a foam after dried in vacuo.

Workup

  1. temperaturecooled to room temperature
  2. washIt was washed sequentially with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, brine
  3. dry with materiallastly dried with anhydrous sodium sulfate
  4. customThe upper solution was decanted
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-5821b36928cc47959ba70d3f671a4db7
Source dataset
uspto-grants-2016_05
Patent number
US09353093B2

Reaction notes

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