Methane → N-Cyclopropyl-4-oxazol-5-yl-N-piperidin-4-yl-benzamide

HRID 1424523Notes

Reaction equation

HRID 1424523 reaction equation
F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[O:23]1[C:27]([C:28]2[CH:36]=[CH:35][C:31]([C:32]([OH:34])=O)=[CH:30][CH:29]=2)=[CH:26][N:25]=[CH:24]1.C(N(C(C)C)C(C)C)C.C(OC([N:53]1[CH2:58][CH2:57][CH:56]([NH:59][CH:60]2[CH2:62][CH2:61]2)[CH2:55][CH2:54]1)=O)(C)(C)C.C>CN(C)C=O>[CH:60]1([N:59]([CH:56]2[CH2:57][CH2:58][NH:53][CH2:54][CH2:55]2)[C:32](=[O:34])[C:31]2[CH:30]=[CH:29][C:28]([C:27]3[O:23][CH:24]=[N:25][CH:26]=3)=[CH:36][CH:35]=2)[CH2:62][CH2:61]1

Participants

7

Reactant 5

HCID 297MethaneHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 2769591tert-Butyl 4-(cyclopropylamino)piperidine-1-carboxylateHCID 27764144-(1,3-Oxazol-5-yl)benzoic Acid

Product 1

HCID 68289931N-Cyclopropyl-4-oxazol-5-yl-N-piperidin-4-yl-benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (6.10 g) is added to a solution of 4-oxazol-5-yl-benzoic acid (3.00 g) and ethyldiisopropylamine (5.56 mL) in N,N-dimethylformamide (50 mL) at room temperature. The solution is stirred for 10 min prior to the addition of 4-cyclopropylamino-piperidine-1-carboxylic acid tert-butyl ester (4.57 g). The resulting mixture is kept at room temperature over night. The mixture is treated with activated charcoal and filtered through a pad of basic aluminum oxide. The pad is washed with N,N-dimethylformamide/methanol (9:1) and the combined filtrates are concentrated in vacuo. The residue is dissolved in 1,4-dioxane (35 mL), a 4 M solution of hydrogen chloride in 1,4-dioxane (20 mL) is added and the resulting mixture is stirred at room temperature for 2 h. The solvent is evaporated and the residue is taken up in water. The resulting mixture is washed with dichloromethane, basified with NaOH solution and extracted with dichloromethane.

Workup

  1. waitThe resulting mixture is kept at room temperature over night
  2. filtrationfiltered through a pad of basic aluminum oxide
  3. washThe pad is washed with N,N-dimethylformamide/methanol (9:1)
  4. concentrationthe combined filtrates are concentrated in vacuo
  5. dissolutionThe residue is dissolved in 1,4-dioxane (35 mL)
  6. additiona 4 M solution of hydrogen chloride in 1,4-dioxane (20 mL) is added
  7. stirringthe resulting mixture is stirred at room temperature for 2 h
  8. customThe solvent is evaporated
  9. washThe resulting mixture is washed with dichloromethane
  10. extractionextracted with dichloromethane

Sources & evidence

ORD record
ord-a4c88af9a14c4343a819cf53c05d3a33
Source dataset
uspto-grants-2015_01
Patent number
US08927726B2

Reaction notes

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