N,N'-二甲基乙二胺 → 2-(4-((1S,2S)-2-(((S)-2-methylpyrrolidin-1-yl)methyl)cyclopropyl)phenyl)pyridazin-3(2H)-one

HRID 73314

反应方程式

HRID 73314 反应方程式
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:10][C@@H:9]2[CH2:11][N:12]2[CH2:16][CH2:15][CH2:14][C@@H:13]2[CH3:17])=[CH:4][CH:3]=1.[N:18]1[NH:19][C:20](=[O:24])[CH:21]=[CH:22][CH:23]=1.CNCCNC>N1C=CC=CC=1.C(Cl)Cl.[Cu]I>[CH3:17][C@H:13]1[CH2:14][CH2:15][CH2:16][N:12]1[CH2:11][C@H:9]1[CH2:10][C@@H:8]1[C:5]1[CH:6]=[CH:7][C:2]([N:19]2[C:20](=[O:24])[CH:21]=[CH:22][CH:23]=[N:18]2)=[CH:3][CH:4]=1

参与物

7

反应物 3

HCID 8070N,N'-二甲基乙二胺HCID 681533-哒嗪酮HCID 575153751-{[(1S,2S)-2-(4-bromophenyl)cyclopropyl]methyl}-(2S)-2-methylpyrrolidine

产物 1

HCID 236359352-(4-((1S,2S)-2-(((S)-2-methylpyrrolidin-1-yl)methyl)cyclopropyl)phenyl)pyridazin-3(2H)-one

试剂、催化剂与溶剂 3

HCID 24350碘化亚铜催化剂HCID 1049吡啶溶剂HCID 6344二氯甲烷溶剂

实验过程

A solution of the product from Example 34F, 1{[(1S,2S)-2-(4-bromophenyl)cyclopropyl]methyl}-(2S)-2-methylpyrrolidine (100 mg, 0.340 mmol), pyridazin-3(2H)-one (52.3 mg, 0.544 mmol), N1,N2-dimethylethane-1,2-diamine (0.088 mL, 0.816 mmol) and copper(I) iodide (78 mg, 0.408 mmol) in pyridine (2 mL) under a nitrogen atmosphere in a sealed vial was heated in an oil bath to 135° C. for 16 hours. The reaction mixture was cooled and diluted with DCM (10 mL), filtered through diatomaceous earth and washed with DCM. The filtrate was washed sequentially with H2O, 28-30% NH4OH (10 mL×2), and H2O, dried with MgSO4 and concentrated under reduced pressure. The residue was chromatographed on silica gel eluting with concentrated concentrated NH4OH/MeOH/DCM (0.4/4/96) to provide the title compound. 1H NMR (300 MHz, CD3OD), δ 0.90-0.97 (m, 1H), 1.03-1.09 (m, 1H), 1.15 (d, J=6 Hz, 3H), 1.23-1.33 (m, 1H), 1.39-1.49 (m, 1H), 1.70-1.80 (m, 2H), 1.82-2.05 (m, 3H), 2.26-2.42 (m, 2H), 3.16 (dd, J=12 Hz, J=6 Hz, 1H), 3.21-3.28 (m, 1H), 7.07 (d, J=6 Hz, 2H), 7.21 (dd, J=6 Hz, J=1.5 Hz, 2H), 7.43 (d, J=6 Hz, 2H), 7.47 (dd, J=9 Hz, J=3 Hz, 1H), 8.02 (dd, J=6 Hz, J=1.5 Hz, 1 HK) MS (DCl—NH3) m/z 310 (M+H)+.

后处理

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered through diatomaceous earth
  3. washwashed with DCM
  4. washThe filtrate was washed sequentially with H2O, 28-30% NH4OH (10 mL×2), and H2O
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was chromatographed on silica gel eluting
  8. concentrationwith concentrated concentrated NH4OH/MeOH/DCM (0.4/4/96)

来源与证据

ORD记录
ord-1b7cb71aeeb84404b927a718dbf1819a
来源数据集
uspto-grants-2014_09
专利号
US08829041B2

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