Pyridine → HCID 76684688、化合物

HRID 1752807ノート

反応式

HRID 1752807 の反応式
[CH3:1][CH2:2][C:3](=O)[CH2:4][C:5](=O)[CH2:6][CH3:7].[NH2:10][C:11]1[NH:15][N:14]=[C:13]([CH2:16][CH2:17][CH2:18][N:19]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:20][CH2:21][OH:22])[N:12]=1.N1C=CC=CC=1>C(Cl)(Cl)Cl.CO.C(O)(=O)C>[CH2:2]([C:3]1[CH:4]=[C:5]([CH2:6][CH3:7])[N:15]2[N:14]=[C:13]([CH2:16][CH2:17][CH2:18][N:19]([C:23]3[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=3)[CH2:20][CH2:21][OH:22])[N:12]=[C:11]2[N:10]=1)[CH3:1]

参加物

5

反応物 3

HCID 1049PyridineHCID 819233,5-Heptanedione2 回HCID 178508400HCID 178508400、化合物

生成物 1

HCID 76684688HCID 76684688、化合物収率 72.1%

試薬・触媒・溶媒 1

HCID 21866353chloroform methanol HOAc溶媒

反応条件

温度
125 °C

実験手順

A mixture of 3,5-heptanedione (216 mg, 1.68 mmol), 2-{[3-(5-amino-1H-1,2,4-triazol-3-yl)propyl](4-fluorophenyl)amino}ethan-1-ol (470 mg, 1.68 mmol), and pyridine (3 mL) was added to a 50 mL RBF with a magnetic stirring bar. The flask was fitted with a condenser, and warmed in an oil bath to a gentle reflux at 125° C. Progress of the reaction was monitored by TLC using chloroform:methanol:acetic acid (9:1:0.2) (Rf starting material=0.1, Rf product=0.7). The solution was heated for 17 hours, and an additional portion of 3,5-heptanedione (95 mg, 0.74 mmol) was added. After an additional 6 hours of heating, the reaction was complete by TLC disappearance of the starting material. The mixture was allowed to cool to room temperature, concentrated under reduced pressure, and the crude material was purified by silica gel column chromatography using a gradient elution of 65-100% ethyl acetate in hexanes to afford the title compound as an oil (450 mg, 72% yield). 1H NMR (DMSO-d6, 400 MHz) δ ppm: 7.11 (s, 1H), 6.95 (m, 2H), 6.70 (m, 2H), 4.66 (t, 1H), 3.50 (q, 2H), 3.40 (t, 2H), 3.35 (m, 2H), 3.09 (q, 2H), 2.86 (q, 4H), 1.99 (m, 2H), 1.34 (t, 3H), 1.28 (t, 3H). EM (calc.): 371.2; MS (ESI) m/e: 372.3 (M+H)+.

後処理

  1. additionwas added to a 50 mL RBF with a magnetic stirring bar
  2. customThe flask was fitted with a condenser
  3. temperaturewarmed in an oil bath to
  4. temperatureThe solution was heated for 17 hours
  5. temperatureAfter an additional 6 hours of heating
  6. temperatureto cool to room temperature
  7. concentrationconcentrated under reduced pressure
  8. customthe crude material was purified by silica gel column chromatography
  9. washa gradient elution of 65-100% ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-60e9acfe2cda42eaafc75b59feb60f96
出典データセット
uspto-grants-2015_10
特許番号
US09163027B2

反応ノート

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