1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Biphenyl-4-carboxylic acid {2-[4-(2-fluoro-6-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide

HRID 1177985

반응식

HRID 1177985 반응식
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[C:12]=1[C:13]([OH:15])=O.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[O:45]=[C:46]([N:63]1[CH2:68][CH2:67][NH:66][CH2:65][CH2:64]1)[CH2:47][NH:48][C:49]([C:51]1[CH:56]=[CH:55][C:54]([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)=[CH:53][CH:52]=1)=[O:50]>CN(C=O)C.O>[F:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[C:12]=1[C:13]([N:66]1[CH2:65][CH2:64][N:63]([C:46](=[O:45])[CH2:47][NH:48][C:49]([C:51]2[CH:56]=[CH:55][C:54]([C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)=[CH:53][CH:52]=2)=[O:50])[CH2:68][CH2:67]1)=[O:15]

참가 물질

8

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 6881232-Fluoro-6-(trifluoromethyl)benzoic acidHCID 57855677Biphenyl-4-carboxylicacid (2-oxo-2-piperazin-1-yl-ethyl)-amide

생성물 1

HCID 59559608Biphenyl-4-carboxylic acid {2-[4-(2-fluoro-6-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide수율 50.8%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

DIPEA (118 mg, 0.16 mL, 0.92 mmol) was added to a stirred solution of 2-fluoro-6-trifluoromethyl-benzoic acid (48 mg, 0.23 mmol) in DMF (2 mL). HOBT (46 mg, 0.35 mmol) and EDCI (100 mg, 0.57 mmol) were then added at room temperature. After 2 minutes, Biphenyl-4-carboxylic acid (2-oxo-2-piperazin-1-yl-ethyl)-amide (75 mg, 0.23 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the product was extracted with EtOAc and the organic layer was washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure to get the residue. The obtained residue was purified by column chromatography (using basic alumina and 10% MeOH in CHCl3 as eluent) to afford 60 mg (50.8% yield) of biphenyl-4-carboxylic acid {2-[4-(2-fluoro-6-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LCMS Purity: 96.5%. 1H NMR (CDCl3): δ 7.9 (m, 2H), 7.6 (m, 6H), 7.4 (m, 4H), 4.3 (m, 2H), 3.8 (m, 3H), 3.8 (m, 3H), 3.6-(m, 2H), 3.5 (m, 1H) 3.3 (m, 2H).

후처리

  1. extractionthe product was extracted with EtOAc
  2. washthe organic layer was washed with brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto get the residue
  6. customThe obtained residue was purified by column chromatography (using basic alumina and 10% MeOH in CHCl3 as eluent)

출처 및 근거

ORD 기록
ord-3e3e9d6215ae4248a770f42918e1ca4b
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07842696B2

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