1-Hydroxybenzotriazole → ((1R)-1-((1R)-1-(4-Carbamoyl-5-phenyl-1,3-thiazol-2-yl)-2-(2-naphthyl)ethylcarbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butylester

HRID 849888

Reaction equation

HRID 849888 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[NH2:46][C@@H:47]([C:59]1[S:60][C:61]([C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)=[C:62]([C:64]([NH2:66])=[O:65])[N:63]=1)[CH2:48][C:49]1[CH:58]=[CH:57][C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH:50]=1>C(Cl)Cl.CN(C)C=O>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([C:10](=[O:12])[NH:46][C@@H:47]([C:59]1[S:60][C:61]([C:67]2[CH:68]=[CH:69][CH:70]=[CH:71][CH:72]=2)=[C:62]([C:64](=[O:65])[NH2:66])[N:63]=1)[CH2:48][C:49]1[CH:58]=[CH:57][C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH:50]=1)[CH2:13][C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2734481(2R)-2-(((tert-butoxy)carbonyl)amino)-3-(naphthalen-2-yl)propanoic acidHCID 540396812-((1R)-1-amino-2-(2-naphthyl)ethyl)-5-phenyl-1,3-thiazole-4-carboxylic acid amide

Product 1

HCID 53997581((1R)-1-((1R)-1-(4-Carbamoyl-5-phenyl-1,3-thiazol-2-yl)-2-(2-naphthyl)ethylcarbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butylesterYield 115.5%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

(2R)-2-tert-Butoxycarbonylamino-3-(2-naphthyl)propionic acid (0.107 g; 0.341 mmol) was dissolved in methylene chloride/dimethyl formamide (5:1; 20 ml). 1-Hydroxybenzotriazole (0.046 g; 0.341 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.071 g; 0.369 mmol) were added. The reaction mixture was stirred 15 min at room temperature and 2-((1R)-1-amino-2-(2-naphthyl)ethyl)-5-phenyl-1,3-thiazole-4-carboxylic acid amide (0.106 g; 0.284 mmol) was added. The reaction mixture was stirred 12 hours at room temperature. The reaction mixture was washed with water (20 ml), sodium hydrogensulfate (10%; 20 ml), sodium hydrogencarbonate (satd; 20 ml), water (20 ml) and dried (magnesium sulfate). The solvent was removed in vacuo and the residue was chromatographed on silica (2×15 cm) using ethyl acetate/heptane (2:1) as eluent to afford 0.22 g of ((1R)-1-((1R)-1-(4-carbamoyl-5-phenyl-1,3-thiazole-2-yl)-2-(2-naphthyl)ethylcarbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butyl ester.

Workup

  1. stirringThe reaction mixture was stirred 12 hours at room temperature
  2. washThe reaction mixture was washed with water (20 ml), sodium hydrogensulfate (10%; 20 ml), sodium hydrogencarbonate (satd; 20 ml), water (20 ml)
  3. dry with materialdried (magnesium sulfate)
  4. customThe solvent was removed in vacuo
  5. customthe residue was chromatographed on silica (2×15 cm)

Sources & evidence

ORD record
ord-ed73bb3ec8a9422f8ef0403255ca0592
Source dataset
uspto-grants-2000_01
Patent number
US06013658

Linked notes

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