2-Bromo-3'-chloroacetophenone → N-(4-(3-Chlorophenyl)thiazol-2-yl)-N-(3-morpholinopropyl)thiophene-2-carboxamide

HRID 1713967Notes

Reaction equation

HRID 1713967 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5](=O)[CH2:6]Br.[N:12]1([CH2:18][CH2:19][CH2:20][NH:21][C:22]([NH2:24])=[S:23])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.C(N(CC)C(C)C)(C)C.[S:34]1[CH:38]=[CH:37][CH:36]=[C:35]1[C:39](Cl)=[O:40]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[N:24]=[C:22]([N:21]([CH2:20][CH2:19][CH2:18][N:12]3[CH2:13][CH2:14][O:15][CH2:16][CH2:17]3)[C:39]([C:35]3[S:34][CH:38]=[CH:37][CH:36]=3)=[O:40])[S:23][CH:6]=2)[CH:9]=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 387382-Bromo-3'-chloroacetophenoneHCID 789282-Thiophenecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 2760135N-[3-(4-Morpholinyl)propyl]thiourea

Product 1

HCID 68407178N-(4-(3-Chlorophenyl)thiazol-2-yl)-N-(3-morpholinopropyl)thiophene-2-carboxamideYield 54.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 3-chlorophenacyl bromide (467 mg, 2 mmol) and (3-morpholin-4-yl-propyl)-thiourea (407 mg, 2 mmol) in dry ethanol (4 ml) was heated at reflux for 2 min, 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 (554 μL, 3 mmol) and thiophene-2-carbonyl chloride (160 μL, 1.5 mmol). The reaction mixture was maintained at room temperature overnight, then concentrated in vacuo. The resulting residue was dissolved in DMSO (3 mL) and subjected to HPLC purification (Method Y). The resulting free amine was dissolved in MeOH (2 mL) and 1M HCl/ether (75 mL) was added. The precipitate was filtered and dried in vacuo to provide the title compound (367 mg) as an off-white solid as the hydrochloride salt. LC/MS (ESI) m/z 447.9 [M+H]. HPLC retention time (Method A)=2.95 min.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 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 (3 mL)
  7. customsubjected to HPLC purification (Method Y)
  8. dissolutionThe resulting free amine was dissolved in MeOH (2 mL)
  9. addition1M HCl/ether (75 mL) was added
  10. filtrationThe precipitate was filtered
  11. customdried in vacuo

Sources & evidence

ORD record
ord-6db2836bceb54006890ef24bf76a5943
Source dataset
uspto-grants-2010_09
Patent number
US07795290B2

Reaction notes

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