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

HRID 1879113

반응식

HRID 1879113 반응식
[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]

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-0e63bfbbd08547d4bf830891d0501af1
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08314147B2

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