1,2-Dichloroethane → N1-(3-fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-phenylmalonamide

HRID 418566

Reaction equation

HRID 418566 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:18])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[CH:16][S:17][C:10]=12.[O:19]=[C:20]([NH:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:21][C:22](O)=[O:23].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([NH:18][C:22](=[O:23])[CH2:21][C:20]([NH:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[O:19])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[CH:16][S:17][C:10]=12

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 2565932-(Phenylcarbamoyl)acetic acidHCID 594244303-Fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)aniline

Product 1

HCID 45488043N1-(3-fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-phenylmalonamideYield 10.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3 (660 mg, 2.27 mmol) in MeOH (10 ml) was added conc. HCl (1 ml) and Fe (1.91 g, 34.8 mmol), and the reaction mixture was stirred at 0° C. for 3 hrs, neutralized with aqueous NaHCO3 solution and extracted with EtOAc, producing 3-fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)-phenylamine (4) as a dark oil (500 mg, 83%), which was used directly in the next step. To a solution of the amine 4 (200 mg, 0.69 mmol) in DMF (10 ml) was added 3-oxo-3-(phenylamino)propanoic acid (1, 155 mg, 0.89 mmol), HOBT (121 mg, 0.89 mmol) and EDC (198 mg, 1.035 mmol). The reaction mixture was stirred at room temperature overnight, evaporated to dryness and the residue was dissolved in EtOAc and washed with water. The organic phase was dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography (eluent EtOAc:hexane 3:1) to afford the title compound 5a (30 mg, 10% yield) as a white solid (after trituration with Et2O). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.5 (s, 1H), 10.2 (s, 1H), 8.49 (d, J=5.48 Hz, 1H), 8.14 (d, J=5.48 Hz, 1H), 7.85 (dd, J=2.35 and 13.01 Hz, 1H), 7.59 (m, 3H), 7.42 (m, 2H), 7.30 (dt, J=1.96 and 7.43 Hz, 2H), 7.05 (t, J=7.24 Hz, 1H), 6.65 (d, J=5.28 Hz, 1H), 3.51 (s, 2H).

Workup

  1. customevaporated to dryness
  2. dissolutionthe residue was dissolved in EtOAc
  3. washwashed with water
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe residue was purified by column chromatography (eluent EtOAc:hexane 3:1)

Sources & evidence

ORD record
ord-550f95af80794869bb62978bd53ca2ff
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Linked notes

Loading…