Trimethylaluminum → 3-ethyl-2-{[2-(6-fluoropyridin-2-yl)-1H-imidazol-1-yl]methyl)-6-propyl-3H-imidazo[4,5-c]pyridine

HRID 895561노트

반응식

HRID 895561 반응식
[CH2:1]([NH:3][C:4]1[CH:5]=[N:6][C:7]([CH2:11][CH2:12][CH3:13])=[CH:8][C:9]=1[NH2:10])[CH3:2].C[Al](C)C.CO[C:20](=O)[CH2:21][N:22]1[CH:26]=[CH:25][N:24]=[C:23]1[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[N:28]=1>ClCCCl>[CH2:1]([N:3]1[C:4]2[CH:5]=[N:6][C:7]([CH2:11][CH2:12][CH3:13])=[CH:8][C:9]=2[N:10]=[C:20]1[CH2:21][N:22]1[CH:26]=[CH:25][N:24]=[C:23]1[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[N:28]=1)[CH3:2]

참가 물질

5

반응물 3

HCID 16682925TrimethylaluminumHCID 68499258[2-(2-Fluoropyridin-6-yl)-imidazol-1-yl]acetic acid methyl esterHCID 86587614N3-ethyl-6-propyl-pyridine-3,4-diamine

생성물 1

HCID 223798763-ethyl-2-{[2-(6-fluoropyridin-2-yl)-1H-imidazol-1-yl]methyl)-6-propyl-3H-imidazo[4,5-c]pyridine

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매2회

실험 절차

A solution of N3-ethyl-6-propyl-pyridine-3,4-diamine (82 mg, ˜0.45 mmol, contaminated with ˜10% of N-(4-amino-6-propyl-pyridin-3-yl)-acetamide) in 1,2-dichloroethane (4 mL) at room temperature under N2 is treated with 2.0 M AlMe3 (0.69 mL, 1.37 mmol). The resulting solution is stirred at room temperature for 30 min and then treated with a solution of [2-(6-fluoro-pyridin-2-yl)-imidazol-1-yl]-acetic acid methyl ester (97 mg, 0.41 mmol) in 1,2-dichloroethane via cannula, followed by a 1 mL rinse. The reaction mixture is then stirred at reflux overnight. After cooling, it is treated with MeOH (˜2 mL) and then further diluted with saturated aq NaHCO3 (˜10 mL) and some H2O. The mixture is stirred vigorously for 15 min and then extracted thrice with CHCl3 containing some (˜5%) MeOH. The combined extracts are dried over K2CO3 and concentrated. The crude material is purified by preparative thin layer chromatography. Developing with 15:1 CHCl3-MeOH yields 3-ethyl-2-{[2-(6-fluoropyridin-2-yl)-1H-imidazol-1-yl]methyl}-6-propyl-3H-imidazo[4,5-c]pyridine as an off-white solid. 1H NMR (CDCl3, 300 MHz) δ 8.70 (d, J=0.9 Hz, 1H), 8.17 (dd, J=8.0, 2.6 Hz, 1H), 7.89 (q, J=7.8 Hz, 1H), 7.47 (s, 1H), 7.22 (d, J=0.9 Hz, 1H), 7.18 (d, J=1.5 Hz, 1H), 6.88 (dd, J=8.6, 2.9 Hz, 1H), 6.27 (s, 2H), 4.42 (q, J=7.2 Hz, 2H), 2.86 (m, 2H), 1.78 (sextet, J=7.2 Hz, 2H), 1.30 (t, J=7.2 Hz, 3H), 0.97 (t, J=7.2 Hz, 3H) ppm. Electrospray MS: m/z 365 [M+1].

후처리

  1. washrinse
  2. stirringThe reaction mixture is then stirred
  3. temperatureat reflux overnight
  4. temperatureAfter cooling
  5. additionit is treated with MeOH (˜2 mL)
  6. additionfurther diluted with saturated aq NaHCO3 (˜10 mL)
  7. stirringThe mixture is stirred vigorously for 15 min
  8. extractionextracted thrice with CHCl3 containing some (˜5%) MeOH
  9. dry with materialThe combined extracts are dried over K2CO3
  10. concentrationconcentrated
  11. customThe crude material is purified by preparative thin layer chromatography

출처 및 근거

ORD 기록
ord-38b4396315a3456585175ec7c9f8df8c
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06916819B2

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