2-Fluoro-5-iodobenzonitrile → N-[3-(3-Cyano-4-fluorophenyl)prop-2-yn-1-yl]-N-(2,4-dimethoxybenzyl)-1H-pyrrole-2-carboxamide

HRID 1172787Notes

Reaction equation

HRID 1172787 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:4]=1[CH2:5][N:6]([CH2:14][C:15]#[CH:16])[C:7]([C:9]1[NH:10][CH:11]=[CH:12][CH:13]=1)=[O:8].[F:23][C:24]1[CH:31]=[CH:30][C:29](I)=[CH:28][C:25]=1[C:26]#[N:27]>CN(C=O)C.CCN(CC)CC.CCOC(C)=O.[Cu]I.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>[C:26]([C:25]1[CH:28]=[C:29]([C:16]#[C:15][CH2:14][N:6]([CH2:5][C:4]2[CH:17]=[CH:18][C:19]([O:21][CH3:22])=[CH:20][C:3]=2[O:2][CH3:1])[C:7]([C:9]2[NH:10][CH:11]=[CH:12][CH:13]=2)=[O:8])[CH:30]=[CH:31][C:24]=1[F:23])#[N:27]

Participants

8

Reactant 2

HCID 27789282-Fluoro-5-iodobenzonitrileHCID 86633422N-(2,4-dimethoxybenzyl)-N-prop-2-yn-1-yl-1H-pyrrole-2-carboxamide

Product 1

HCID 68688798N-[3-(3-Cyano-4-fluorophenyl)prop-2-yn-1-yl]-N-(2,4-dimethoxybenzyl)-1H-pyrrole-2-carboxamide

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of A1 (1 eq) in a mixture of DMF and Et3N (1:1) was added 2-fluoro-5-iodobenzonitrile (2 eq), CuI (0.2 eq) and Pd(PPh3)4 (0.05 eq). The resulting mixture was stirred at RT overnight. The reaction mixture was diluted with EtOAc, washed with 0.1N HCl (2×) and then with brine; dried (Na2SO4) and concentrated. The resulting crude was purified by on silica gel eluting with EtOAc/petrol ether to obtain the desired compound. MS (ES) C24H20FN3O3 requires: 417, found: 418 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ: 11.59 (1H, bs), 7.93 (1H, dd, J=6.3, 2.0 Hz), 7.78-7.73 (1H, m), 7.53 (1H, t, J=9.1 Hz), 7.13 (1H, d, J=8.3 Hz), 6.93 (1H, s), 6.60 (1H, d, J=2.3 Hz), 6.53 (1H, dd, J=8.3, 2.3 Hz), 6.50-6.38 (1H, m), 6.10 (1H, s), 4.77 (2H, s), 4.50 (2H, s), 3.78 (3H, s), 3.76 (3H, s).

Workup

  1. washwashed with 0.1N HCl (2×)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe resulting crude was purified by on silica gel eluting with EtOAc/petrol ether

Sources & evidence

ORD record
ord-bafd89f6352b450d86ae6d56c0bc2fbd
Source dataset
uspto-grants-2010_11
Patent number
US07834015B2

Reaction notes

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