2-Thiophenecarbonyl chloride → N-(4-(5-Chlorothiophen-2-yl)thiazol-2-yl)-N-(3-morpholinopropyl)thiophene-2-carboxamide

HRID 2218502Notes

Reaction equation

HRID 2218502 reaction equation
Br[CH2:2][C:3]([C:5]1[S:6][C:7]([Cl:10])=[CH:8][CH:9]=1)=O.[N:11]1([CH2:17][CH2:18][CH2:19][NH:20][C:21]([NH2:23])=[S:22])[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.C(N(CC)C(C)C)(C)C.[S:33]1[CH:37]=[CH:36][CH:35]=[C:34]1[C:38](Cl)=[O:39]>C(O)C>[Cl:10][C:7]1[S:6][C:5]([C:3]2[N:23]=[C:21]([N:20]([CH2:19][CH2:18][CH2:17][N:11]3[CH2:12][CH2:13][O:14][CH2:15][CH2:16]3)[C:38]([C:34]3[S:33][CH:37]=[CH:36][CH:35]=3)=[O:39])[S:22][CH:2]=2)=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 789282-Thiophenecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 20636342-(Bromoacetyl)-5-chlorothiopheneHCID 2760135N-[3-(4-Morpholinyl)propyl]thiourea

Product 1

HCID 68406816N-(4-(5-Chlorothiophen-2-yl)thiazol-2-yl)-N-(3-morpholinopropyl)thiophene-2-carboxamideYield 44.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2-bromo-1-(5-chloro-thiophen-2-yl)-ethanone (72 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 (61 mg) as an yellow solid as the hydrochloride salt. LC/MS (ESI) m/z 453.9 [M+H]. HPLC retention time (Method A)=2.93 min.

Workup

  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

Sources & evidence

ORD record
ord-66ddb412d4fb4039be68a8406bd5ff7b
Source dataset
uspto-grants-2008_08
Patent number
US07410988B2

Reaction notes

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