2-Thiophenecarbonyl chloride → Methyl 4-(2-(N-(3-morpholinopropyl)thiophene-2-carboxamido)thiazol-4-yl)benzoate

HRID 1713969ノート

反応式

HRID 1713969 の反応式
[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([C:10](=O)[CH2:11]Br)=[CH:6][CH:5]=1.[N:15]1([CH2:21][CH2:22][CH2:23][NH:24][C:25]([NH2:27])=[S:26])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1.C(N(CC)C(C)C)(C)C.[S:37]1[CH:41]=[CH:40][CH:39]=[C:38]1[C:42](Cl)=[O:43]>C(O)C>[O:18]1[CH2:17][CH2:16][N:15]([CH2:21][CH2:22][CH2:23][N:24]([C:25]2[S:26][CH:11]=[C:10]([C:7]3[CH:8]=[CH:9][C:4]([C:3]([O:2][CH3:1])=[O:14])=[CH:5][CH:6]=3)[N:27]=2)[C:42]([C:38]2[S:37][CH:41]=[CH:40][CH:39]=2)=[O:43])[CH2:20][CH2:19]1

参加物

6

反応物 4

HCID 789282-Thiophenecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 2760135N-[3-(4-Morpholinyl)propyl]thioureaHCID 13612771Methyl 4-(2-bromoacetyl)benzoate

生成物 1

HCID 68405969Methyl 4-(2-(N-(3-morpholinopropyl)thiophene-2-carboxamido)thiazol-4-yl)benzoate収率 36.8%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

A mixture of 4-(2-bromo-acetyl)-benzoic acid methyl ester (77 mg, 0.3 mmol) and (3-morpholin-4-yl-propyl)-thiourea (61 mg, 0.3 mmol) in dry ethanol (3 mL) was heated at reflux for 10 min, cooled to room temperature, and concentrated in vacuo. The resulting residue was suspended in dichloromethane (3 mL) followed by the addition of N,N-diisopropylethylamine (105 μL, 0.6 mmol) and thiophene-2-carbonyl chloride (34 μL, 0.32 mmol). The reaction mixture was maintained at room temperature overnight, then concentrated in vacuo. The resulting residue was dissolved in DMSO (1.5 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 (52 mg) as an off-white solid as the hydrochloride salt. LC/MS (ESI) m/z 472.3 [M+H]. HPLC retention time (Method A)=2.80 min.

後処理

  1. temperaturewas heated
  2. temperatureat reflux for 10 min
  3. concentrationconcentrated in vacuo
  4. temperatureThe reaction mixture was maintained at room temperature overnight
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resulting residue was dissolved in DMSO (1.5 mL)
  7. customsubjected to HPLC purification (Method Y)
  8. dissolutionThe resulting free amine was dissolved in MeOH (1 mL)
  9. addition1M HCl/ether (50 mL) was added
  10. filtrationThe precipitate was filtered
  11. customdried in vacuo

出典と根拠

ORDレコード
ord-2b5236f5460647c896704f2a0e27cfef
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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