[5-(2-Amino-phenyl)-thiophen-2-yl]-acetic acid methyl ester → (5-{2-[(3',4',5'-Trimethoxy-biphenyl-2-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid methyl ester

HRID 383612

反応式

HRID 383612 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[C:14]([C:19](Cl)=[O:20])=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[CH3:22][O:23][C:24](=[O:38])[CH2:25][C:26]1[S:27][C:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[NH2:37])=[CH:29][CH:30]=1>C(Cl)Cl.N1C=CC=CC=1>[CH3:22][O:23][C:24](=[O:38])[CH2:25][C:26]1[S:27][C:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[NH:37][C:19]([C:14]2[C:13]([C:5]3[CH:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][CH3:10])=[C:7]([O:11][CH3:12])[CH:6]=3)=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:20])=[CH:29][CH:30]=1

参加物

5

反応物 2

HCID 16116160[5-(2-Amino-phenyl)-thiophen-2-yl]-acetic acid methyl esterHCID 161162893',4',5'-Trimethoxy-biphenyl-2-carbonyl chloride

生成物 1

HCID 59785699(5-{2-[(3',4',5'-Trimethoxy-biphenyl-2-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid methyl ester収率 62.3%

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

Add a solution of 3′,4′,5′-Trimethoxy-biphenyl-2-carbonyl chloride (84) (0.18 mmol) in DCM (1.0 mL) to an ice cooled solution of [5-(2-Amino-phenyl)-thiophen-2-yl]-acetic acid methyl ester (46) (46 mg, 0.18 mmol) in anhydrous DCM (2.0 mL) and anhydrous pyridine (0.5 mL). Stir the reaction mixture for 1 h at 0° C. and additional 20 h at rt. Pour the reaction mixture into ice cooled 1M aqu. HCl, extract with EtOAc (2×) and DCM (2×), wash the combined organic layer with brine and dry with Na2SO4. Purify the crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+2) to obtain (5-{2-[(3′,4′,5′-Trimethoxy-biphenyl-2-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid methyl ester (85) as a light brown solid (58 mg, 59%). 1H NMR (400 MHz, CDCl3): 3.70 (s, 3H); 3.76 (s, 6H); 3.78 (s, 2H); 3.80 (s, 3H); 6.29 (d, 1H, J=3.4 Hz); 6.60 (s, 2H); 6.75 (d, 1H, J=3.4 Hz); 7.07 (t, 1H, J=7.6 Hz); 7.23 (d, 1H, J=7.6 Hz); 7.31 (t, 1H, J=8.0 Hz); 7.37-7.43 (m, 2H); 7.48 (t, 1H, J=7.6 Hz); 7.52 (s, 1H); 7.69 (d, 1H, J=8.0 Hz); 8.45 (d, 1H, J=8.0 Hz).

後処理

  1. customadditional 20 h
  2. customat rt
  3. additionPour the reaction mixture into ice
  4. temperaturecooled 1M aqu
  5. extractionHCl, extract with EtOAc (2×) and DCM (2×)
  6. washwash the combined organic layer with brine
  7. dry with materialdry with Na2SO4
  8. customPurify the crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+2)

出典と根拠

ORDレコード
ord-57e1d6ed7de84142bc2189d07694f4cf
出典データセット
uspto-grants-2013_02
特許番号
US08367677B2

関連ノート

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