Triethylamine → 3-{4-[({[2-Fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenyl}prop-2-ynamide

HRID 631770Notes

Reaction equation

HRID 631770 reaction equation
[C:1]([NH2:5])(=[O:4])[C:2]#[CH:3].[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][C:8]=1[NH:17][C:18]([NH:20][C:21]1[CH:26]=[CH:25][C:24](I)=[CH:23][CH:22]=1)=[O:19].C(N(CC)CC)C>CN(C=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>[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][C:8]=1[NH:17][C:18]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([C:3]#[C:2][C:1]([NH2:5])=[O:4])=[CH:23][CH:22]=1)=[O:19]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 101445PropynamideHCID 690085641-[2-Fluoro-5-(trifluoromethyl)phenyl]-3-(4-iodophenyl)urea

Product 1

HCID 903870243-{4-[({[2-Fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenyl}prop-2-ynamideYield 81.1%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a mixture of propynoic acid amide (41.4 mg, 0.60 mmol), 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-(4-iodophenyl)urea (169.7 mg, 0.40 mmol), triethylamine (0.167 mL, 1.2 mmol), dichlorobis(triphenylphosphine)palladium(II) (22.5 mg, 0.032 mmol), and triphenylphosphine (5.2 mg, 0.020 mmol) in 3.0 mL DMF (degassed) was added copper(I)iodide (7.6 mg, 0.04 mmol) and the reaction stirred at rt for 17 hours. The reaction was combined with a prior test reaction (36.5 mg theoretical yield) and partitioned between EtOAc and H2O/brine mixture. The EtOAc layer was washed 3 times with H2O/brine mixture, then brine, dried with anhydrous Na2SO4 and rotary evaporated to a solid. The solid was chromatographed eluting with EtOAc/CHCl3 and then triturated with EtOAc/hexane to give the title compound as a light tan solid (118.5 mg, 65%). 1H NMR (DSMO-d6) δ: 9.45 (s, 1H), 8.98 (d, J=2.9 Hz, 1H), 8.59 (dd, J=7.3, 2.1 Hz, 1H), 8.07 (br. s, 1H), 7.59 (br. s., 1H), 7.47-7.58 (m, 5H), 7.38-7.45 (m, 1H).

Workup

  1. customtest reaction (36.5 mg theoretical yield)
  2. custompartitioned between EtOAc and H2O/brine mixture
  3. washThe EtOAc layer was washed 3 times with H2O/brine mixture
  4. dry with materialbrine, dried with anhydrous Na2SO4
  5. customrotary evaporated to a solid
  6. customThe solid was chromatographed
  7. washeluting with EtOAc/CHCl3
  8. customtriturated with EtOAc/hexane

Sources & evidence

ORD record
ord-5d829500fb7a426bb1d41878360d6138
Source dataset
uspto-grants-2016_04
Patent number
US09321721B2

Reaction notes

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