Isopropanol → 1-(3-((1-(Quinolin-2-YL)piperidin-4-YL)oxy)pyrazin-2-YL)piperidin-4-OL

HRID 2207811ノート

反応式

HRID 2207811 の反応式
Cl[C:2]1[C:3]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:24]=[CH:23][C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[N:16]=3)[CH2:11][CH2:10]2)=[N:4][CH:5]=[CH:6][N:7]=1.[NH:25]1[CH2:30][CH2:29][CH:28]([OH:31])[CH2:27][CH2:26]1.C([O-])([O-])=O.[K+].[K+].C(O)(C)C>O>[N:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:23]=[CH:24][C:15]=1[N:12]1[CH2:13][CH2:14][CH:9]([O:8][C:3]2[C:2]([N:25]3[CH2:30][CH2:29][CH:28]([OH:31])[CH2:27][CH2:26]3)=[N:7][CH:6]=[CH:5][N:4]=2)[CH2:10][CH2:11]1

参加物

6

反応物 4

HCID 3776IsopropanolHCID 11430Potassium CarbonateHCID 79341Piperidin-4-olHCID 585476872-(4-((3-Chloropyrazin-2-yl)oxy)piperidin-1-yl)quinoline

生成物 1

HCID 585478291-(3-((1-(Quinolin-2-YL)piperidin-4-YL)oxy)pyrazin-2-YL)piperidin-4-OL収率 17%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
160 °C

実験手順

To a mixture of 2-(4-((3-chloropyrazin-2-yl)oxy)piperidin-1-yl)quinoline (see PREPARATION P1.1; 0.1 g, 0.29 mmol) and piperidin-4-ol (0.029 g, 0.29 mmol) and K2CO3 (0.08 g, 0.58 mmol) was added isopropyl alcohol (i-PrOH) (2 mL) and water (0.5 ml). The solution was heated to 160° C. under microwave for 5 hours. Then the mixture was concentrated and extracted with EtOAc (2×20 mL). The combined organic extracts were washed with water (10 mL) and brine (10 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (20% to 60% EtOAc in petroleum ether) to give the title product (0.02 g, 0.04 mmol, 17% yield) as white solid. ESI-MS (M+1): 406 calc. for C23H27N5O2 405.

後処理

  1. concentrationThen the mixture was concentrated
  2. extractionextracted with EtOAc (2×20 mL)
  3. washThe combined organic extracts were washed with water (10 mL) and brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customThe filtrate was evaporated in vacuo
  7. customthe residue was purified by flash column chromatography on silica gel (20% to 60% EtOAc in petroleum ether)

出典と根拠

ORDレコード
ord-5c4f79f8fb764d1f8f25a4c26e219355
出典データセット
uspto-grants-2016_06
特許番号
US09376450B2

反応ノート

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