1-Hydroxybenzotriazole → (E)-3,3,3-trifluoro-N-((4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methyl)propanamide

HRID 587743노트

반응식

HRID 587743 반응식
[F:1][C:2]([F:28])([F:27])[CH:3]([C:18]1[CH:23]=[C:22]([Cl:24])[C:21]([Cl:25])=[C:20]([Cl:26])[CH:19]=1)/[CH:4]=[CH:5]/[C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([CH2:16][NH2:17])=[CH:8][CH:7]=1.[F:29][C:30]([F:36])([F:35])[CH2:31][C:32](O)=[O:33].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C>C(Cl)Cl.O>[F:29][C:30]([F:36])([F:35])[CH2:31][C:32]([NH:17][CH2:16][C:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:6](/[CH:5]=[CH:4]/[CH:3]([C:18]2[CH:19]=[C:20]([Cl:26])[C:21]([Cl:25])=[C:22]([Cl:24])[CH:23]=2)[C:2]([F:1])([F:27])[F:28])=[CH:7][CH:8]=1)=[O:33]

참가 물질

8

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27779723,3,3-Trifluoropropionic acidHCID 86675189(E)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methanamine

생성물 1

HCID 86675210(E)-3,3,3-trifluoro-N-((4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methyl)propanamide

시약·촉매·용매 2

HCID 962Water용매2회HCID 6344Dichloromethane용매

실험 절차

To a stirred solution of (E)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methanamine (0.1 g, 0.22 mmol) in CH2Cl2 (8 mL) were added 3,3,3-trifluoropropanoic acid (0.032 g, 0.24 mmol), HOBt.H2O (52 mg, 0.33 mmol), EDC.HCl (0.065 g, 0.33 mmol) and DIPEA (0.044 g, 0.45 mmol), and the resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with water and extracted with EtOAc (3×30 mL). The combined EtOAc layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. Purification by flash column chromatography (SiO2, 100-200 mesh; 15% EtOAc in n-hexane) afforded the title compound as a gummy material (60 mg, 50%): mp 151-153° C.; 1H NMR (400 MHz, CDCl3) δ 8.06 (m, 1H), 7.61 (m, 4H), 7.48 (s, 2H), 7.44 (d, J=8.0 Hz, 1H), 7.38 (m, 1H), 6.42 (m, 1H), 5.92 (br s, 1H), 4.92 (m, 2H), 4.24 (m, 1H), 3.12 (m, 2H); ESIMS m/z 554.04 ([M−H]−).

후처리

  1. extractionextracted with EtOAc (3×30 mL)
  2. washThe combined EtOAc layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (SiO2, 100-200 mesh; 15% EtOAc in n-hexane)

출처 및 근거

ORD 기록
ord-6c81fbe4ee6f4dfb90b84c8f49172e88
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09226501B2

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