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

HRID 2193710Notes

Reaction equation

HRID 2193710 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17]([C:19]3[N:20]=[CH:21][N:22]([CH2:24][CH2:25][CH3:26])[CH:23]=3)[S:18][C:11]=12)[NH2:5].[F:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[NH:34][C:35](=[O:40])[CH2:36][C:37](O)=[O:38].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:37](=[O:38])[CH2:36][C:35]([NH:34][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[F:27])=[O:40])[CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17]([C:19]3[N:20]=[CH:21][N:22]([CH2:24][CH2:25][CH3:26])[CH:23]=3)[S:18][C:11]=12

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 164811562-[(2-Fluorophenyl)carbamoyl]acetic acidHCID 587904093-Fluoro-4-(2-(1-propyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)aniline

Product 1

HCID 16042164N1-(3-Fluoro-4-(2-(1-propyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-(2-fluorophenyl)malonamideYield 36.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the amino compound 133 (400 mg, 1.08 mmol) in DMF (20 mL), 3-(2-fluorophenylamino)-3-oxopropanoic acid (29) (427 mg, 2.17 mmol), EDC (352 mg, 2.60 mmol) was added HOBT (499 mg, 2.60 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 130 (215 mg, 36% yield) as a yellow solid. 1H NMR (DMSO-d6). δ (ppm): 10.56 (s, 1H), 10.06 (s, 1H), 8.43 (d, J=5.6 Hz, 1H), 8.10-7.96 (m, 1H), 7.94 (d, J=1.2 Hz, 1H), 7.87 (dd, J=1.6 and 12.8 Hz, 1H), 7.77 (d, J=1.2 Hz, 1H), 7.68 (s, 1H), 7.49 (t, J=8.8 Hz, 1H), 7.42 (dd, J=2.0 and 8.8 Hz, 1H), 7.32-7.25 (m, 1H), 7.22-7.14 (m, 2H), 6.58 (d, J=5.6 Hz, 1H), 3.98 (t, J=7.2 Hz, 2H), 3.62 (s, 2H), 1.78 (sex, J=7.2 Hz, 2H), 0.87 (t, J=7.2 Hz, 3H). MS (m/z): 548.1 (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-6e980c78e312426ba948163303e9cb83
Source dataset
uspto-grants-2012_12
Patent number
US08329726B2

Reaction notes

Loading…