2-Thiophenecarbonyl chloride → N-(4-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)thiazol-2-yl)-N-(3-morpholinopropyl)thiophene-2-carboxamide

HRID 2218504Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2218504
[CH2:1]1[CH2:14][O:13][C:12]2[CH:11]=[CH:10][C:5]([C:6](=O)[CH2:7]Br)=[CH:4][C:3]=2[O:2]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:13]1[CH2:14][CH2:1][O:2][C:3]2[CH:4]=[C:5]([C:6]3[N:27]=[C:25]([N:24]([CH2:23][CH2:22][CH2:21][N:15]4[CH2:16][CH2:17][O:18][CH2:19][CH2:20]4)[C:42]([C:38]4[S:37][CH:41]=[CH:40][CH:39]=4)=[O:43])[S:26][CH:7]=3)[CH:10]=[CH:11][C:12]1=2

Komponenten

6

Edukt 4

HCID 789282-Thiophenecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 2760135N-[3-(4-Morpholinyl)propyl]thioureaHCID 27761712-Bromo-1-(2,3-dihydro-1,4-benzodioxin-6-yl)ethan-1-one

Produkt 1

HCID 68406166N-(4-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)thiazol-2-yl)-N-(3-morpholinopropyl)thiophene-2-carboxamideAusbeute 50,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Versuchsvorschrift

A mixture of 3,4-(ethylenedioxy)phenacyl bromide (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 (72 mg) as an off-white solid as the hydrochloride salt. LC/MS (ESI) m/z 472.3 [M+H]. HPLC retention time (Method A)=2.72 min.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-524616086db74ea3998d5cafb08506e6
Quelldatensatz
uspto-grants-2008_08
Patentnummer
US07410988B2

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