Piperidine → N-(7-(piperidin-1-yl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 468739ノート

反応式

HRID 468739 の反応式
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[NH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.O1CCOCC1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:18]1([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]4[CH2:17][CH2:16]4)=[O:14])[N:8]=[CH:9]3)=[CH:4][CH:3]=2)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1

参加物

8

反応物 5

HCID 8082PiperidineHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 634876Binap, (A+-)-HCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

生成物 1

HCID 67974711N-(7-(piperidin-1-yl)isoquinolin-3-yl)cyclopropanecarboxamide収率 6%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

A solution was made of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (66.6 mg, 0.229 mmol) and piperidine (46 uL, 0.46 mmol) in 1,4-dioxane (1.5 mL, 19 mmol). Nitrogen gas was bubbled through the mixture for 10 minutes, and then palladium (II) acetate (6.0 mg, 0.027 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (15.2 mg, 0.0244 mmol), and cesium carbonate (231 mg, 0.709 mmol) were added. The reaction mixture was stirred in a sealed vial at 100° C. for 18 hours. The reaction mixture was then cooled to room temperature, diluted in ethyl acetate, filtered through celite, washed with saturated aqueous NaHCO3, dried over MgSO4, and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 3.8 mg (6%) of N-(7-(piperidin-1-yl)isoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): RT=3.481, M+H=416.2, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.64 (s, 1H), 8.89 (s, 1H), 8.27 (s, 1H), 7.67 (d, J=9.1 Hz, 1H), 7.55 (dd, J=9.1, 2.4 Hz, 1H), 7.25 (d, J=2.1 Hz, 1H), 3.27-3.20 (m, 4H), 2.03 (m, 1H), 1.66 (d, J=4.6 Hz, 4H), 1.58 (d, J=4.7 Hz, 2H), 0.81 (m, 4H).

後処理

  1. customNitrogen gas was bubbled through the mixture for 10 minutes
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. filtrationfiltered through celite
  4. washwashed with saturated aqueous NaHCO3
  5. dry with materialdried over MgSO4
  6. customevaporated in vacuo
  7. customThe crude product was purified via reverse phase HPLC

出典と根拠

ORDレコード
ord-febe4f3cd1a5469caa170d235079fc08
出典データセット
uspto-grants-2014_01
特許番号
US08623889B2

反応ノート

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