Hydrochloric Acid → Ethyl 3-{[(4-{[(5-cyano-3-methyl-1-benzofuran-2-yl)(cyclohexyl)methyl]amino}phenyl)carbonyl]amino}propanoate

HRID 2091158Notes

Reaction equation

HRID 2091158 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([CH:11]([NH:18][C:19]3[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=3)[CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]3)=[C:8]([CH3:28])[C:7]=2[CH:29]=1)#[N:2].Cl.[CH2:31]([O:33][C:34](=[O:38])[CH2:35][CH2:36][NH2:37])[CH3:32].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl>CN(C)C=O.C(N(CC)CC)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([CH:11]([NH:18][C:19]3[CH:27]=[CH:26][C:22]([C:23]([NH:37][CH2:36][CH2:35][C:34]([O:33][CH2:31][CH3:32])=[O:38])=[O:24])=[CH:21][CH:20]=3)[CH:12]3[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]3)=[C:8]([CH3:28])[C:7]=2[CH:29]=1)#[N:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 667776914-{[(5-Cyano-3-methyl-1-benzofuran-2-yl)(cyclohexyl)methyl]amino}benzoic acid

Product 1

HCID 66778037Ethyl 3-{[(4-{[(5-cyano-3-methyl-1-benzofuran-2-yl)(cyclohexyl)methyl]amino}phenyl)carbonyl]amino}propanoateYield 62.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of 4-{[(5-cyano-3-methyl-1-benzofuran-2-yl)(cyclohexyl)methyl]amino}benzoic acid (250 mg) synthesized above, β-alanine ethyl ester hydrochloride (148 mg), 1-hydroxybenzotriazole monohydrate (148 mg), triethylamine (269 μL) and N,N-dimethylformamide (10 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (185 mg), and the mixture was stirred overnight at room temperature. 1N Hydrochloric acid was added to quench the reaction, and the 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 (50% ethyl acetate/hexane) to give the title object compound (195 mg, 62%) as a colorless oil.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe 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 (50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b55435916a4040e0bd23444e52d32717
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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