4-Methylmorpholine → 3-(4-Cylcohexyl-4-[1,2,4]triazol-1-ylmethyl-piperidin-1-yl)-2-(4-fluorobenzyl)-3-oxo-propionic acid methyl ester

HRID 1795184Notes

Reaction equation

HRID 1795184 reaction equation
[CH3:1][O:2][C:3](=[O:16])[CH:4]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=1)[C:5]([OH:7])=O.[CH:17]1([C:23]2([CH2:29][N:30]3[CH:34]=[N:33][CH:32]=[N:31]3)[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.CN(C)CCCN=C=NCC.[Cl-].[NH4+]>CN(C)C=O>[CH3:1][O:2][C:3](=[O:16])[CH:4]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=1)[C:5]([N:26]1[CH2:25][CH2:24][C:23]([CH:17]2[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]2)([CH2:29][N:30]2[CH:34]=[N:33][CH:32]=[N:31]2)[CH2:28][CH2:27]1)=[O:7]

Participants

8

Reactant 6

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 129914504-Cyclohexyl-4-[(1H-1,2,4-triazol-1-yl)methyl]piperidineHCID 210237472-(4-Fluoro-benzyl)-malonic acid monomethyl ester

Product 1

HCID 210237643-(4-Cylcohexyl-4-[1,2,4]triazol-1-ylmethyl-piperidin-1-yl)-2-(4-fluorobenzyl)-3-oxo-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(4-fluoro-benzyl)-malonic acid monomethyl ester, 56, (47.5 mg, 0.21 mmol), 4-cyclohexyl-4-[1,2,4]triazol-1-ylmethyl-piperidine, 18, (50 mg, 0.20 mmol), 1-hydroxybenzotriazole (54 mg, 0.40 mmol), 4-methylmorpholine (88 □l, 0.80 mmol) in N,N-dimethylformamide (7 mL) is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (50 mg, 0.26 mmol). The reaction mixture is stirred overnight and then aqueous ammonium chloride is added. The reaction is extracted with ethyl acetate, and the organics are separated dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product is purified by preparative HPLC to afford the desired compound.

Workup

  1. extractionThe reaction is extracted with ethyl acetate
  2. customthe organics are separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product is purified by preparative HPLC

Sources & evidence

ORD record
ord-7b7ce7f0e7af46c985e98b4dcd12c931
Source dataset
uspto-grants-2006_04
Patent number
US07026335B2

Reaction notes

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