Ammonium Chloride → Ethyl 3-{[(5-{[cyclohexyl(5-fluoro-3-methyl-1-benzofuran-2-yl)methyl]amino}pyridin-2-yl)carbonyl](methyl)amino}propanoate

HRID 2091067Notes

Reaction equation

HRID 2091067 reaction equation
C1([CH:7]([NH:19][C:20]2[CH:21]=[CH:22][C:23]([C:26]([OH:28])=O)=[N:24][CH:25]=2)[C:8]2[O:9][C:10]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:11]=3[C:12]=2[CH3:13])CCCCC1.[CH3:29][NH:30][CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34].O.ON1[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[Cl-].[NH4+]>CN(C)C=O.C(N(CC)CC)C>[CH:43]1([CH:7]([NH:19][C:20]2[CH:21]=[CH:22][C:23]([C:26]([N:30]([CH3:29])[CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])=[O:28])=[N:24][CH:25]=2)[C:8]2[O:9][C:10]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:11]=3[C:12]=2[CH3:13])[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 541480Ethyl 3-(methylamino)propanoateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 667777375-{[Cyclohexyl(5-fluoro-3-methyl-1-benzofuran-2-yl)methyl]amino}pyridine-2-carboxylic acid

Product 1

HCID 66777498Ethyl 3-{[(5-{[cyclohexyl(5-fluoro-3-methyl-1-benzofuran-2-yl)methyl]amino}pyridin-2-yl)carbonyl](methyl)amino}propanoateYield 82%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of 5-{[cyclohexyl(5-fluoro-3-methyl-1-benzofuran-2-yl)methyl]amino}pyridine-2-carboxylic acid (300 mg) synthesized in Example A55(2), ethyl 3-(methylamino)propanoate (155 mg), 1-hydroxybenzotriazole monohydrate (181 mg), triethylamine (328 μL) and N,N-dimethylformamide (10 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (226 mg), and the mixture was stirred at room temperature. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the reaction mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (20-60% ethyl acetate/hexane) to give the title object compound (318 mg, 82%) as a pale-yellow oil.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe reaction mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (20-60% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-6d7636ea27b44d289f071e874a7ece67
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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