Morpholine → N-(3-(4-fluorophenyl)-1-(2-morpholinoethyl)-4-(phenylethynyl)-1H-pyrazol-5-yl)acetamide

HRID 1775579ノート

反応式

HRID 1775579 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:11]([NH:21][C:22](=[O:24])[CH3:23])[N:10]([CH2:25][CH2:26]O)[N:9]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[NH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:11]([NH:21][C:22](=[O:24])[CH3:23])[N:10]([CH2:25][CH2:26][N:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)[N:9]=2)=[CH:4][CH:3]=1

参加物

6

反応物 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 70983184N-(3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(phenylethynyl)-1H-pyrazol-5-yl)acetamide

生成物 1

HCID 70983554N-(3-(4-fluorophenyl)-1-(2-morpholinoethyl)-4-(phenylethynyl)-1H-pyrazol-5-yl)acetamide収率 44.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a suspension of N-(3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(phenylethynyl)-1H-pyrazol-5-yl)acetamide (269 mg, 0.74 mmol) in CH2Cl2 (9 mL) and triethylamine (155 μl, 1.11 mmol) was added methanesulphonyl chloride (65 μl, 0.81 mmol and the reaction stirred at room temperature for 16 h. The reaction mixture was poured onto ice/water and the organic layer was dried over MgSO4, filtered and evaporated. The crude product was dissolved in THF (10 ml) and morpholine (320 μl, 3.7 mmol) was added. The reaction was heated to 55° C. for 24 h before evaporating the solvent in vacuo. The crude was partitioned between CH2Cl2 and dilute aqueous NaHCO3 and the organic layer was dried over MgSO4, filtered and evaporated. Purification using chromatography (silica gel, gradient 0 to 10% methanol/CH2Cl2) gave N-(3-(4-fluorophenyl)-1-(2-morpholinoethyl)-4-(phenylethynyl)-1H-pyrazol-5-yl)acetamide as a white solid (141 mg) which was used as such in the subsequent step.

後処理

  1. additionThe reaction mixture was poured onto ice/water
  2. dry with materialthe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. dissolutionThe crude product was dissolved in THF (10 ml)
  6. temperatureThe reaction was heated to 55° C. for 24 h
  7. custombefore evaporating the solvent in vacuo
  8. customThe crude was partitioned between CH2Cl2 and dilute aqueous NaHCO3
  9. dry with materialthe organic layer was dried over MgSO4
  10. filtrationfiltered
  11. customevaporated
  12. customPurification

出典と根拠

ORDレコード
ord-2a194821dd404537aaba0ec96dee2c26
出典データセット
uspto-grants-2016_02
特許番号
US09260381B2

反応ノート

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