Sodium triacetoxyborohydride → 1-(2-{4-[(2,3-Dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]piperidin-1-yl}ethyl)-7-methoxyquinolin-2(1H)-one

HRID 255157

反応式

HRID 255157 の反応式
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:22])[CH2:4][CH2:3]1.[O:23]1[C:32]2[CH:31]=[C:30]([CH:33]=O)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.CO>[O:23]1[C:32]2[CH:31]=[C:30]([CH2:33][NH:1][CH:2]3[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]4[C:19]5[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=5)[CH:13]=[CH:12][C:11]4=[O:22])[CH2:4][CH2:3]3)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1

参加物

5

反応物 3

HCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 593982891-[2-(4-aminopiperidin-1-yl)ethyl]-7-methoxyquinolin-2(1H)-one2 回

生成物 1

HCID 119833621-(2-{4-[(2,3-Dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]piperidin-1-yl}ethyl)-7-methoxyquinolin-2(1H)-one

試薬・触媒・溶媒 1

HCID 21584188Chloroform methanol溶媒

反応条件

温度
0 °C

実験手順

A solution of 1-[2-(4-aminopiperidin-1-yl)ethyl]-7-methoxyquinolin-2(1H)-one (Intermediate 1, crude, 60 mg, 0.20 mmol) and 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde (WO 2004/058144) (33 mg, 0.20 mmol) in dry chloroform/methanol (5 mL, 1:1) was heated over 3 Å molecular sieves at 70° C. for 3 hours. The reaction mixture was cooled to 0° C., and sodium triacetoxy borohydride (127 mg, 0.6 mmol) was added. The resulting reaction mixture was stirred at room temperature for 30 minutes and then was filtered through a 0.45 μm membrane and concentrated to dryness under reduced pressure. The residue was taken up in dichloromethane (50 mL) and saturated aqueous sodium hydrogen carbonate solution (5 mL). The pH of the aqueous phase was adjusted to a pH of 10 with 1M aqueous sodium hydroxide solution. The aqueous phase was back extracted twice with dichloromethane (2×20 mL) and the combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. Chromatography on silica gel with dichloromethane/methanol (8:1 to 4:1) gave the free base of the title compound as a colorless oil. The free base was taken up in dichloromethane (2 mL), ethanol (7 mL) was added, followed by addition of 1M HCl in ether (0.3 mL). The colorless precipitate was collected by filtration and gave 50 mg (48%) of the bis-hydrochloride salt of the product, mp 243° C.

後処理

  1. customThe resulting reaction mixture
  2. filtrationwas filtered through a 0.45 μm membrane
  3. concentrationconcentrated to dryness under reduced pressure
  4. extractionThe aqueous phase was back extracted twice with dichloromethane (2×20 mL)
  5. dry with materialthe combined organic phases were dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-90af062bafae42dea72df5fa27bafacc
出典データセット
uspto-grants-2011_01
特許番号
US07875715B2

関連ノート

読み込み中…