Benzene → HCID 69348685, 화합물

HRID 23188노트

반응식

HRID 23188 반응식
[NH2:1][C:2]1[CH:3]=[C:4]([N:8]2[CH:12]=[CH:11][N:10]=[CH:9]2)[CH:5]=[CH:6][CH:7]=1.[CH2:13]([O:15][C:16](=[O:25])[CH2:17][C:18](=O)[CH2:19][CH2:20][CH2:21][CH2:22]Cl)[CH3:14].II.[CH:28]1C=CC=CC=1>>[CH2:13]([O:15][C:16](=[O:25])[CH:17]=[CH:18][CH:19]1[CH2:20][CH2:21][CH2:22][CH2:28][N:1]1[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N:8]2[CH:12]=[CH:11][N:10]=[CH:9]2)[CH:3]=1)[CH3:14]

참가 물질

5

반응물 4

HCID 241BenzeneHCID 807Iodine2회HCID 3212253-(1H-imidazol-1-yl)anilineHCID 13612450Ethyl 7-chloro-3-oxoheptanoate

생성물 1

HCID 69348685HCID 69348685, 화합물수율 8%

실험 절차

The above synthesis may be carried out as follows: To benzene (20 mL) was added 1-(3-aminophenyl)imidazole (755 mg, 4.7 mmol), 7-chloro-3-oxoheptanoic acid ethyl ester (982 mg, 4.7 mmol), Na2HPO4 (667 mg, 4.7 mmol), I2 (60 mg, 0.23 mmol), and 4 Å molecular sieves (500 mg). After refluxing for 6 hours, more I2 (60 mg) was added. After stirring for 16 hours, the reaction was filtered, the solvent was removed in vacuo, and the residues chromatographed (CH2Cl2/MeOH, 98/2) to give 120 mg (8%) of 1-[3-(1H-imidazol-1-yl)phenyl]piperidine-2-acrylic acid ethyl ester (1H NMR (CDCl3) δ 7.85 (s, 1), 7.05-7.50 (m, 6), 4.80 (s, 1), 4.15 (q, 2), 3.45 (t, 2), 2.4 (t, 2), 1.5-1.8 (m, 6), 1.30 (t, 3)). This ester (120 mg, 0.38 mmol) was dissolved in MeOH (20 mL) and reacted with 10% Pd/C (60 mg) and 1 atm of H2. After reacting for 60 hours, the reaction was filtered, the solvent removed in vacuo, and the residue chromatographed (ethyl acetate/hexanes, 1/1) to give 24 mg of 1-[3-(1H-imidazol-1-yl)phenyl]piperidine-2-acetic acid ethyl ester (compound of formula (XV)). This ester (24 mg, 0.076 mmol) was dissolved in 5% methanolic NaOH. After stirring for 16 hours, the reaction was acidified with methanolic HCl, the solvent removed in vacuo, and the residue dissolved in DMF. Piperonylamine (1 eq), Hünig's base (2 eq) and HATU (1 eq) were added. After reaction completion the reaction mixture was partitioned with water and ethyl acetate. The organic layer was separated, washed with water, and dried. The solvent was removed in vacuo and the residue was chromatographed (ethyl acetate/MeOH, 98/2) to give 6 mg of the compound of formula (Ibb), N-[(1,3-benzodioxol-5-yl)methyl]-1-[3-(1H-imidazol-1-yl)phenyl]piperidine-2-acetamide: 1H NMR (CDCl3) δ 7.80 (s, 1), 7.10-7.30 (m, 4), 6.50-6.70 (m, 5), 5.90 (s, 2), 4.20-4.35(m, 2, 3.85 (br s, 1), 3.50 (t, 2), 2.95 (d, 1), 2.35-2.55 (m, 2), 1.4-1.9 (m, 6); MS: (419 M+H)+.

후처리

  1. customThe above synthesis
  2. temperatureAfter refluxing for 6 hours
  3. filtrationthe reaction was filtered
  4. customthe solvent was removed in vacuo
  5. customthe residues chromatographed (CH2Cl2/MeOH, 98/2)

출처 및 근거

ORD 기록
ord-81f198b3132f42968c73b84bd07ee0a6
출처 데이터셋
uspto-grants-2005_02
특허 번호
US06849739B2

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