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

HRID 2218503Notes

Reaction equation

HRID 2218503 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

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.

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-ffcfe112815343018d06c3fdd19dbb5b
Source dataset
uspto-grants-2008_08
Patent number
US07410988B2

Reaction notes

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