Diisopropylethylamine → (S)-tert-Butyl 4-(4-(3-cyclobutylureido)benzoyl)-3-methylpiperazine-1-carboxylate

HRID 1878378Notes

Reaction equation

HRID 1878378 reaction equation
[CH3:1][C@@H:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[CH:15]1([NH:19][C:20](=[O:31])[NH:21][C:22]2[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=2)[CH2:18][CH2:17][CH2:16]1.C(N(C(C)C)C(C)C)C>CN(C)C=O>[CH:15]1([NH:19][C:20](=[O:31])[NH:21][C:22]2[CH:23]=[CH:24][C:25]([C:26]([N:7]3[CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])[CH2:3][C@@H:2]3[CH3:1])=[O:27])=[CH:29][CH:30]=2)[CH2:16][CH2:17][CH2:18]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 7023035(S)-1-Boc-3-methylpiperazineHCID 624152074-(3-Cyclobutylureido)benzoic acid

Product 1

HCID 57917669(S)-tert-Butyl 4-(4-(3-cyclobutylureido)benzoyl)-3-methylpiperazine-1-carboxylateYield 69.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-tert-butyl 3-methylpiperazine-1-carboxylate (0.10 g, 0.50 mmol) in N,N-dimethylformamide (5 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyl uronium hexafluorophosphate (0.190 g, 0.50 mmol, HATU), 4-(3-cyclobutylureido)benzoic acid (0.117 g, 0.50 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.13 mL, 0.75 mmol). The reaction mixture was stirred at room temperature for 20 hours and concentrated under vacuum. The residue was diluted with dichloromethane (15 mL) and washed with saturated ammonium chloride (aqueous) and brine. The organic layer was dried (sodium sulfate), filtered and concentrated under vacuum. The crude material was purified by column chromatography on silica (using a solvent gradient of dichloromethane/methanol) to afford the title compound (0.145 g) as a white solid.

Workup

  1. concentrationconcentrated under vacuum
  2. additionThe residue was diluted with dichloromethane (15 mL)
  3. washwashed with saturated ammonium chloride (aqueous) and brine
  4. dry with materialThe organic layer was dried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude material was purified by column chromatography on silica (

Sources & evidence

ORD record
ord-d1f0272c1762443583994f8763e4f808
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

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