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

HRID 515039

反応式

HRID 515039 の反応式
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

参加物

9

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 681533(2H)-PyridazinoneHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 684254651-[2-(4-bromo-phenyl)-(1R,2R)-cyclopropylmethyl]-(2S)-2-methyl-pyrrolidine

生成物 1

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

試薬・触媒・溶媒 4

HCID 83717Copper iodide触媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 3776Isopropanol溶媒

反応条件

温度
110 °C

実験手順

A solution of the product from Example 4A (47 mg, 0.16 mmol; 1-[2-(4-bromophenyl)-(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)+.

後処理

  1. customcapped vial for 16 hours
  2. temperatureThe mixture was cooled to ambient temperature
  3. extractionextracted with ethyl acetate (2×25 mL)
  4. customThe organic layer was 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

出典と根拠

ORDレコード
ord-7378d7a2ce3148f6ba88418defe6d841
出典データセット
uspto-grants-2015_08
特許番号
US09108948B2

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