Triethylamine → 4-(1,3-Dioxo-1,3dihydrobenzo[f]isoindol-2-yl)-2-{1-[2-(4-methoxyphenyl)-1-(methylcarbamoyl)-ethylcarbamoyl]cyclohexylamino}butyric acid tert-butyl ester

HRID 1459895Notes

Reaction equation

HRID 1459895 reaction equation
[C:1]([O:5][C:6]([CH:8]([NH:26][C:27]1([C:33]([OH:35])=O)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[CH2:9][CH2:10][N:11]1[C:19](=[O:20])[C:18]2[CH:17]=[C:16]3[CH:21]=[CH:22][CH:23]=[CH:24][C:15]3=[CH:14][C:13]=2[C:12]1=[O:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.C[NH-].[CH3:39][O:40][C:41]1[CH:52]=[CH:51][C:44]([CH2:45][C@@H:46]([C:48](O)=[O:49])[NH2:47])=[CH:43][CH:42]=1.O.O[N:55]1[C:59]2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[CH:8]([NH:26][C:27]1([C:33](=[O:35])[NH:47][CH:46]([C:48](=[O:49])[NH:55][CH3:59])[CH2:45][C:44]2[CH:51]=[CH:52][C:41]([O:40][CH3:39])=[CH:42][CH:43]=2)[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]1)[CH2:9][CH2:10][N:11]1[C:12](=[O:25])[C:13]2[CH:14]=[C:15]3[CH:24]=[CH:23][CH:22]=[CH:21][C:16]3=[CH:17][C:18]=2[C:19]1=[O:20])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 700859441-[1-Tert-butoxycarbonyl-3-(1,3-dioxo-1,3-dihydrobenzo[f]isoindol-2-yl)propylamino]cyclohexanecarboxylic acidHCID 131721053L-tyrosine methyl ether N-methylamide hydrochloride

Product 1

HCID 700834344-(1,3-Dioxo-1,3dihydrobenzo[f]isoindol-2-yl)-2-{1-[2-(4-methoxyphenyl)-1-(methylcarbamoyl)-ethylcarbamoyl]cyclohexylamino}butyric acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-[1-tert-butoxycarbonyl-3-(1,3-dioxo-1,3-dihydrobenzo[f]isoindol-2-yl)propylamino]cyclohexanecarboxylic acid (298 mg,0.62 mmol) in methylene chloride (10 mL) were added successively L-tyrosine methyl ether N-methylamide hydrochloride (180 mg, 0.74 mmol), 1-hydroxybenztriazole hydrate (95 mg, 0.62 mmol), triethylamine (0.12 mL, 0.86 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (142 mg, 0.74 mmol). The resulting mixture was stirred for 3 days at room temperature. After dilution with methylene chloride, the mixture was washed successively with saturated aqueous sodium bicarbonate, water, 0.5M aqueous hydrochloric acid and brine. The solution was dried over magnesium sulfate. The solvent was removed by evaporation under vacuum leaving an oil which was chromatographed on silica gel eluting with 45% hexane in ethyl acetate to afford 4-(1,3-dioxo-1,3dihydrobenzo[f]isoindol-2-yl)-2-{1-[2-(4-methoxyphenyl)-1-(methylcarbamoyl)-ethylcarbamoyl]cyclohexylamino}butyric acid tert-butyl ester, diastereomer A (91 mg, 22%) and diastereomer B (85 mg, 20%), in addition to a mixture of diastereomers A and B (169 mg, 41%).

Workup

  1. washAfter dilution with methylene chloride, the mixture was washed successively with saturated aqueous sodium bicarbonate, water, 0.5M aqueous hydrochloric acid and brine
  2. dry with materialThe solution was dried over magnesium sulfate
  3. customThe solvent was removed by evaporation under vacuum
  4. customleaving an oil which
  5. customwas chromatographed on silica gel eluting with 45% hexane in ethyl acetate

Sources & evidence

ORD record
ord-4679a9c9e122419abd9eeff3fab7cdb4
Source dataset
uspto-grants-1998_12
Patent number
US05854275

Reaction notes

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