2-Thiophenecarbonyl chloride → N-(4-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)thiazol-2-yl)-N-(3-morpholinopropyl)thiophene-2-carboxamide

HRID 1713973ノート

反応式

HRID 1713973 の反応式
Br[CH2:2][C:3]([C:5]1[CH:6]=[N:7][N:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:9]=1[CH3:10])=O.[N:17]1([CH2:23][CH2:24][CH2:25][NH:26][C:27]([NH2:29])=[S:28])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.C(N(CC)C(C)C)(C)C.[S:39]1[CH:43]=[CH:42][CH:41]=[C:40]1[C:44](Cl)=[O:45]>O1CCOCC1>[CH3:10][C:9]1[N:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:7]=[CH:6][C:5]=1[C:3]1[N:29]=[C:27]([N:26]([CH2:25][CH2:24][CH2:23][N:17]2[CH2:18][CH2:19][O:20][CH2:21][CH2:22]2)[C:44]([C:40]2[S:39][CH:43]=[CH:42][CH:41]=2)=[O:45])[S:28][CH:2]=1

参加物

6

反応物 4

HCID 789282-Thiophenecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 2760135N-[3-(4-Morpholinyl)propyl]thioureaHCID 27764392-Bromo-1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethan-1-one

生成物 1

HCID 68407246N-(4-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)thiazol-2-yl)-N-(3-morpholinopropyl)thiophene-2-carboxamide収率 65.2%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

A mixture of 2-bromo-1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-1-ethanone (167 mg, 0.6 mmol) and (3-morpholin-4-yl-propyl)-thiourea (122 mg, 0.6 mmol) in dry dioxane (5 ml) was heated at 80° C. for 2 h, cooled to room temperature, and concentrated in vacuo. The resulting residue was suspended in dichloromethane (5 mL) followed by the addition of N,N-diisopropylethylamine (209 μL, 1.2 mmol) and thiophene-2-carbonyl chloride (96 μL, 0.9 mmol). The reaction mixture was maintained at room temperature overnight, then concentrated in vacuo. The resulting residue was dissolved in DMSO (2.5 mL) and subjected to HPLC purification (Method Y). The resulting free amine was dissolved in MeOH (1 mL) and 1M HCl/ether (50 mL) was added. The precipitate was filtered and dried in vacuo to provide the title compound (193 mg) as an yellow solid as the hydrochloride salt. LC/MS (ESI) m/z 494.3 [M+H]. HPLC retention time (Method B)=2.72 min.

後処理

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. temperatureThe reaction mixture was maintained at room temperature overnight
  4. concentrationconcentrated in vacuo
  5. dissolutionThe resulting residue was dissolved in DMSO (2.5 mL)
  6. customsubjected to HPLC purification (Method Y)
  7. dissolutionThe resulting free amine was dissolved in MeOH (1 mL)
  8. addition1M HCl/ether (50 mL) was added
  9. filtrationThe precipitate was filtered
  10. customdried in vacuo

出典と根拠

ORDレコード
ord-958df25e38934dd18284f7bfea6fedea
出典データセット
uspto-grants-2010_09
特許番号
US07795290B2

反応ノート

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