Diisopropylethylamine → Methyl 2-((4-(4-(3-cyclobutylureido)benzoyl)piperazin-1-yl)methyl)oxazole-4-carboxylate

HRID 408846Notes

Reaction equation

HRID 408846 reaction equation
FC(F)(F)C(O)=O.[N:8]1([CH2:14][C:15]2[O:16][CH:17]=[C:18]([C:20]([O:22][CH3:23])=[O:21])[N:19]=2)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.[CH:24]1([NH:28][C:29](=[O:40])[NH:30][C:31]2[CH:39]=[CH:38][C:34]([C:35](O)=[O:36])=[CH:33][CH:32]=2)[CH2:27][CH2:26][CH2:25]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH:24]1([NH:28][C:29](=[O:40])[NH:30][C:31]2[CH:32]=[CH:33][C:34]([C:35]([N:11]3[CH2:12][CH2:13][N:8]([CH2:14][C:15]4[O:16][CH:17]=[C:18]([C:20]([O:22][CH3:23])=[O:21])[N:19]=4)[CH2:9][CH2:10]3)=[O:36])=[CH:38][CH:39]=2)[CH2:25][CH2:26][CH2:27]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 624152074-(3-Cyclobutylureido)benzoic acidHCID 66661413Methyl 2-(piperazin-1-yl-methyl)oxazole-4-carboxylate 2,2,2-trifluoroacetate

Product 1

HCID 58055798Methyl 2-((4-(4-(3-cyclobutylureido)benzoyl)piperazin-1-yl)methyl)oxazole-4-carboxylateYield 15%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a N,N-dimethylformamide (3 mL) solution of methyl 2-(piperazin-1-yl-methyl)oxazole-4-carboxylate 2,2,2-trifluoroacetate (174 mg, 513 μmol) and 4-(3-cyclobutylureido)benzoic acid (120 mg, 513 μmol) in N,N-dimethylformamide (5 mL) was added N,N-diisopropylethylamine (357 μL, 2.05 mmol), followed by O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyl uronium hexafluorophosphate (293 mg, 770 μmol; HATU). The mixture was stirred at room temperature for 22 hours and was then concentrated under vacuum. The residue was taken up in ethyl acetate and washed with saturated aqueous ammonium chloride and brine. The organic phase was dried on magnesium sulfate, filtered and concentrated under vacuum. The crude residue was applied to a silica gel column and eluted with 25% ethyl acetate in n-hexanes to give the title compound (34 mg). MS (ESI) m/z 442.1 [M+H]+

Workup

  1. concentrationwas then concentrated under vacuum
  2. washwashed with saturated aqueous ammonium chloride and brine
  3. customThe organic phase was dried on magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. washeluted with 25% ethyl acetate in n-hexanes

Sources & evidence

ORD record
ord-19183c09759242dc89f96965b528b391
Source dataset
uspto-grants-2014_06
Patent number
US08759352B2

Reaction notes

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