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

HRID 2193640

反応式

HRID 2193640 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-1b0dce1ccdc248b2897fa5181344a330
出典データセット
uspto-grants-2012_12
特許番号
US08329726B2

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