1,2-Dichloroethane → N1-(4-(2-(1-Ethyl-1H-imidazol-5-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-fluorophenyl)malonamide

HRID 2193703Notes

Reaction equation

HRID 2193703 reaction equation
[CH2:1]([N:3]1[C:7]([C:8]2[S:16][C:15]3[C:10](=[N:11][CH:12]=[CH:13][C:14]=3[O:17][C:18]3[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][C:19]=3[F:25])[CH:9]=2)=[CH:6][N:5]=[CH:4]1)[CH3:2].[F:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[NH:33][C:34](=[O:39])[CH2:35][C:36](O)=[O:37].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[CH2:1]([N:3]1[C:7]([C:8]2[S:16][C:15]3[C:10](=[N:11][CH:12]=[CH:13][C:14]=3[O:17][C:18]3[CH:24]=[CH:23][C:21]([NH:22][C:36](=[O:37])[CH2:35][C:34]([NH:33][C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=4[F:26])=[O:39])=[CH:20][C:19]=3[F:25])[CH:9]=2)=[CH:6][N:5]=[CH:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 164811562-[(2-Fluorophenyl)carbamoyl]acetic acidHCID 587904254-(2-(1-Ethyl-1H-imidazol-5-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroaniline

Product 1

HCID 58790094N1-(4-(2-(1-Ethyl-1H-imidazol-5-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-fluorophenyl)malonamideYield 60.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the amino compound 120 (400 mg, 1.08 mmol) in DMF (10 mL), 3-(2-fluorophenylamino)-3-oxopropanoic acid (444 mg, 2.25 mmol), EDC (519 mg, 2.70 mmol) was added HOBT (364 mg, 2.70 mmol). The reaction mixture was allowed to stir for 1 hr. The solution was extracted with EtOAc and the extract was washed with water, aqueous ammonium chloride and brine then dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography (eluents DCM-MeOH, 98:2, 95:5) to afford title compound 117 (348 mg, 58% yield) as a white solid. 1H NMR (DMSO-d6). δ ppm: 10.58 (s, 1H), 10.06 (s, 1H), 8.52 (d, J=5.6 Hz, 1H), 8.10-7.76 (m, 1H), 7.94 (d, J=1.2 Hz, 1H), 7.88 (dd, J=2.4 and 13.2 Hz, 1H), 7.74 (s, 1H)), 7.51 (t, J=8.8 Hz, 1H), 7.43 (dd, J=1.6 and 8.8 Hz, 1H), 7.39 (d, J=1.2 Hz, 1H), 7.32-7.25 (m, 1H), 7.21-7.14 (m, 2H), 6.66 (d, J=5.6 Hz, 1H), 4.29 (q, J=7.2 Hz, 2H), 3.62 (s, 2H), 1.34 (t, J=7.2 Hz, 3H). MS (m/z): 534.1 (M+H).

Workup

  1. extractionThe solution was extracted with EtOAc
  2. washthe extract was washed with water, aqueous ammonium chloride and brine
  3. dry with materialthen dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe residue was purified by flash chromatography (eluents DCM-MeOH, 98:2, 95:5)

Sources & evidence

ORD record
ord-af877f6163e34d63bf87afd58e6d6185
Source dataset
uspto-grants-2012_12
Patent number
US08329726B2

Reaction notes

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