Methyl 4-amino-2,5-dimethylbenzoate → Methyl 4-{3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionylamino}-2,5-dimethylbenzoate

HRID 2113260Notes

Reaction equation

HRID 2113260 reaction equation
[C:1]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([O:10][CH:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19](O)=[O:20])[CH2:13][CH2:12]1)=[O:9].[NH2:28][C:29]1[C:38]([CH3:39])=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[C:31]([CH3:40])[CH:30]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>ClCCl.C(N(C(C)C)CC)(C)C>[C:1]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([O:10][CH:11]1[CH2:12][CH2:13][N:14]([CH2:17][CH2:18][C:19]([NH:28][C:29]2[C:38]([CH3:39])=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[C:31]([CH3:40])[CH:30]=2)=[O:20])[CH2:15][CH2:16]1)=[O:9]

Participants

6

Reactant 3

HCID 273299Methyl 4-amino-2,5-dimethylbenzoateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 218806073-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic Acid

Product 1

HCID 46239621Methyl 4-{3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionylamino}-2,5-dimethylbenzoateYield 59%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 81531DiisopropylethylamineSolvent

Procedure

To a stirred solution of 3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic acid (670 mg, 1.82 mmol) and methyl 4-amino-2,5-dimethylbenzoate (390 mg, 2.18 mmol) in dichloromethane (3.6 mL) and diisopropylethylamine (0.413 mL) was added O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) (829 mg, 2.18 mmol). The resulting mixture was stirred at room temperature overnight. The mixture was then washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with dichloromethane containing from 3% to 5% methanol to provide methyl 4-{3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionylamino}-2,5-dimethylbenzoate (568 mg, 59% yield). LCMS (10-70) Rt=4.55; [M+H+] found 530.4.

Workup

  1. washThe mixture was then washed with saturated aqueous sodium bicarbonate
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with dichloromethane containing from 3% to 5% methanol

Sources & evidence

ORD record
ord-2bd0dab6092a4183af266f187993a26f
Source dataset
uspto-grants-2009_04
Patent number
US07524965B2

Reaction notes

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