POTASSIUM DIPHOSPHATE → 2-[4-((1R,2R)-2-{[(2S)-2-Methylpyrrolidin-1-yl]methyl}cyclopropyl)phenyl]pyridazin-3(2H)-one

HRID 73291

反应方程式

HRID 73291 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.CN[C@@H]1CCCC[C@H]1NC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C(O)(C)C.[Cu](I)I.O>[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

9

反应物 4

HCID 62657POTASSIUM DIPHOSPHATEHCID 681533-哒嗪酮HCID 2733821(1R,2R)-(-)-N,N'-二甲基-1,2-环己二胺HCID 684254651-[2-(4-bromo-phenyl)-(1R,2R)-cyclopropylmethyl]-(2S)-2-methyl-pyrrolidine

产物 1

HCID 441973232-[4-((1R,2R)-2-{[(2S)-2-Methylpyrrolidin-1-yl]methyl}cyclopropyl)phenyl]pyridazin-3(2H)-one

试剂、催化剂与溶剂 4

HCID 83717碘化铜催化剂HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 1140甲苯溶剂HCID 3776异丙醇溶剂

反应条件

温度
110 °C

实验过程

A solution of the product from Example 4A (47 mg, 0.16 mmol; 1-[2-(4-bromo-phenyl)-(1R,2R)-cyclopropylmethyl]-(2S)-2-methyl-pyrrolidine), 3(2H)-pyridazinone (CAS #504-30-3, 20 mg, 0.2 mmol), copper iodide (1.5 mg, 0.008 mmol), N,N′-trans-dimethyl-cyclohexane-1,2-diamine (2.3 mg, 0.016 mmol) and potassium phosphate (75 mg, 0.35 mmol) in a mixture of toluene and isopropanol (4 ml, 1.1) was heated to 110° C. in a screw capped vial for 16 hours. The mixture was cooled to ambient temperature, treated with H2O and extracted with ethyl acetate (2×25 mL) The organic layer was separated, washed with brine and dried with magnesium sulfate. After filtration, the organic layer was concentrated under reduced pressure and the resulting oil was purified on silica gel with 1% to 3% methanol (containing 10% concentrated NH4OH) in dichloromethane to provide the title compound. 1H NMR (300 MHz, CD3OD) δ 1.07 (m, 1H), 1.14 (m, 1H), 1.26 (d, J=6 Hz, 3H), 1.40 (m, 1H), 1.58 (m, 1H), 1.90 (m, 3H), 2.13 (m, 1H), 2.58 (m, 1H), 2.70 (q, J=9 Hz, 1H), 2.89 (m, 1H), 3.14 (dd, J=12 Hz, J=6 Hz, 1H), 3.44 (m, 1H), 7.07 (d, J=9 Hz, 1H), 7.24 (d, J=9 Hz, 2H), 7.44 (d, J=9 Hz, 2H), 7.47 (m, 1H), 8.03 (m, 1H), MS (DCl—NH3) m/z 310 (M+H)+.

后处理

  1. customcapped vial for 16 hours
  2. temperatureThe mixture was cooled to ambient temperature
  3. extractionextracted with ethyl acetate (2×25 mL) The organic layer
  4. customwas separated
  5. washwashed with brine
  6. dry with materialdried with magnesium sulfate
  7. filtrationAfter filtration
  8. concentrationthe organic layer was concentrated under reduced pressure
  9. customthe resulting oil was purified on silica gel with 1% to 3% methanol (containing 10% concentrated NH4OH) in dichloromethane

来源与证据

ORD记录
ord-3285dc2904e94f4595151fcbb05b077d
来源数据集
uspto-grants-2014_09
专利号
US08829041B2

关联笔记

加载中…