2-Thiophenecarbonyl chloride → N-(3-Morpholinopropyl)-N-(4-(3-phenylisoxazol-5-yl)thiazol-2-yl)thiophene-2-carboxamide

HRID 1713972Notes

Reaction equation

HRID 1713972 reaction equation
Br[CH2:2][C:3]([C:5]1[O:9][N:8]=[C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:6]=1)=O.[N:16]1([CH2:22][CH2:23][CH2:24][NH:25][C:26]([NH2:28])=[S:27])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C(N(CC)C(C)C)(C)C.[S:38]1[CH:42]=[CH:41][CH:40]=[C:39]1[C:43](Cl)=[O:44]>O1CCOCC1>[O:19]1[CH2:18][CH2:17][N:16]([CH2:22][CH2:23][CH2:24][N:25]([C:26]2[S:27][CH:2]=[C:3]([C:5]3[O:9][N:8]=[C:7]([C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=4)[CH:6]=3)[N:28]=2)[C:43]([C:39]2[S:38][CH:42]=[CH:41][CH:40]=2)=[O:44])[CH2:21][CH2:20]1

Participants

6

Reactant 4

HCID 789282-Thiophenecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 27355325-(Bromoacetyl)-3-phenylisoxazoleHCID 2760135N-[3-(4-Morpholinyl)propyl]thiourea

Product 1

HCID 59769689N-(3-Morpholinopropyl)-N-(4-(3-phenylisoxazol-5-yl)thiazol-2-yl)thiophene-2-carboxamideYield 53.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-bromo-1-(3-phenylisoxazol-5-yl)ethan-1-one (160 mg, 0.6 mmol) and (3-morpholin-4-yl-propyl)-thiourea (122 mg, 0.6 mmol) in dry dioxane (5 ml) was heated at 80° C. for 2 h, 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 (209 μL, 1.2 mmol) and thiophene-2-carbonyl chloride (96 μL, 0.9 mmol). The reaction mixture was maintained at room temperature overnight, then concentrated in vacuo. The resulting residue was dissolved in DMSO (2.5 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 (155 mg) as an off-white solid as the hydrochloride salt. LC/MS (ESI) m/z 481.1 [M+H]. HPLC retention time (Method B)=2.94 min.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. temperatureThe reaction mixture was maintained at room temperature overnight
  4. concentrationconcentrated in vacuo
  5. dissolutionThe resulting residue was dissolved in DMSO (2.5 mL)
  6. customsubjected to HPLC purification (Method Y)
  7. dissolutionThe resulting free amine was dissolved in MeOH (1 mL)
  8. addition1M HCl/ether (50 mL) was added
  9. filtrationThe precipitate was filtered
  10. customdried in vacuo

Sources & evidence

ORD record
ord-0d95d6129f614471822fbaaf9c876d53
Source dataset
uspto-grants-2010_09
Patent number
US07795290B2

Reaction notes

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