Triethylamine → Ethyl (3-chloro-4-{[(2-chloro-5-{[(3-chlorophenyl)methyl]oxy}phenyl)carbonyl]amino}-2-fluorophenyl)acetate

HRID 1879113

反応式

HRID 1879113 の反応式
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[NH2:33][C:34]1[CH:39]=[CH:38][C:37]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])=[C:36]([F:46])[C:35]=1[Cl:47]>ClCCl.CN(C=O)C.C(#N)C>[Cl:47][C:35]1[C:36]([F:46])=[C:37]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH:38]=[CH:39][C:34]=1[NH:33][C:4]([C:3]1[CH:7]=[C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[CH:9]=[CH:10][C:2]=1[Cl:1])=[O:6]

参加物

8

反応物 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 59163335Ethyl (4-amino-3-chloro-2-fluorophenyl)acetateHCID 597600492-Chloro-5-{[(3-chlorophenyl)methyl]oxy}benzoic acid

生成物 1

HCID 59163365Ethyl (3-chloro-4-{[(2-chloro-5-{[(3-chlorophenyl)methyl]oxy}phenyl)carbonyl]amino}-2-fluorophenyl)acetate収率 32.1%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide触媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

A solution of 2-chloro-5-{[(3-chlorophenyl)methyl]oxy}benzoic acid (200 mg, 0.67 mmol) in dichloromethane (3 ml) was treated with oxalyl chloride (90 ul, 1.0 mmol) and DMF (1 drop). Effervescence was observed and the mixture was stirred at room temperature for 30 minutes. The solvent was then evaporated in vacuo and azeotroped with toluene. The resulting solid was dissolved in dichloromethane (3 ml) and treated with triethylamine (140 ul, 1.0 mmol) and a solution of ethyl (4-amino-3-chloro-2-fluorophenyl)acetate (230 mg, 1.0 mmol) in dichloromethane (2 ml). The mixture was stirred at room temperature for 2 hours. The mixture was then diluted with acetonitrile and purified by SCX cartridge eluting with acetonitrile. Fractions combined and evaporated, residue purified by MDAP to give the title compound as a white solid (110 mg). MS (ES+) m/z 510 [M+H]+ (C24H1935Cl3FNO4). 1H-NMR (400 MHz, d6-DMSO) δ 1.20 (3H, t, J 7.2), 3.81 (2H, s), 4.12 (2H, q, J 7.2), 5.20 (2H, s), 7.16-7.55 (9H, m).

後処理

  1. customThe solvent was then evaporated in vacuo
  2. customazeotroped with toluene
  3. dissolutionThe resulting solid was dissolved in dichloromethane (3 ml)
  4. stirringThe mixture was stirred at room temperature for 2 hours
  5. custompurified by SCX cartridge
  6. washeluting with acetonitrile
  7. customevaporated
  8. customresidue purified by MDAP

出典と根拠

ORDレコード
ord-0e63bfbbd08547d4bf830891d0501af1
出典データセット
uspto-grants-2012_11
特許番号
US08314147B2

関連ノート

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