Isopropanol → Methyl 1-(3-((1-(quinolin-2-YL)piperidin-4-YL)oxy)pyrazin-2-YL)piperidine-4-carboxylate

HRID 2207823ノート

反応式

HRID 2207823 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]([C:31]([O:33][CH3:34])=[O:32])[CH2:27][CH2:26]1.C([O-])([O-])=O.[K+].[K+].CC(O)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]([C:31]([O:33][CH3:34])=[O:32])[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 424914Methyl isonipecotateHCID 585476872-(4-((3-Chloropyrazin-2-yl)oxy)piperidin-1-yl)quinoline

生成物 1

HCID 58547953Methyl 1-(3-((1-(quinolin-2-YL)piperidin-4-YL)oxy)pyrazin-2-YL)piperidine-4-carboxylate収率 27%

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-chloro-pyrazin-2-yloxy)-piperidin-1-yl]-quinoline (see PREPARATION P2.1; 0.34 g, 1.0 mmol) and methyl piperidine-4-carboxylate (0.14 g, 1.0 mmol) and K2CO3 (0.27 g, 2.0 mmol) was added 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 (0.12 g, 0.27 mmol, 27% yield) as white solid. ESI-MS (M+1): 448 calc. for C25H29N5O3 447.

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-7f027545cef74e92be2b032abc6124db
出典データセット
uspto-grants-2016_06
特許番号
US09376450B2

反応ノート

読み込み中…