Diisopropylethylamine → 3-((E)-2-(methyl((1R)-1-(methyl((1R)-1-(methylcarbamoyl)-2-phenylethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)vinyl)azetidine-1-carboxylic acid tert-butyl ester

HRID 1268552

Reaction equation

HRID 1268552 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10](/[CH:12]=[CH:13]/[C:14]([OH:16])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:39][N:40]([CH:57]([C:65](=[O:68])[NH:66][CH3:67])[CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)[C:41](=[O:56])[CH:42]([NH:54][CH3:55])[CH2:43][C:44]1[CH:53]=[CH:52][C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH:45]=1.C(N(C(C)C)C(C)C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10](/[CH:12]=[CH:13]/[C:14](=[O:16])[N:54]([CH3:55])[C@@H:42]([C:41](=[O:56])[N:40]([CH3:39])[C@@H:57]([C:65](=[O:68])[NH:66][CH3:67])[CH2:58][C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[CH2:43][C:44]2[CH:53]=[CH:52][C:51]3[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=3)[CH:45]=2)[CH2:11]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10799312HCID 10799312, compoundHCID 22326951N-methyl-2-methylamino-N-(1-methylcarbamoyl-2-phenylethyl)-3-(2-naphthyl)propionamide

Product 1

HCID 590572573-((E)-2-(methyl((1R)-1-(methyl((1R)-1-(methylcarbamoyl)-2-phenylethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)vinyl)azetidine-1-carboxylic acid tert-butyl esterYield 64.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

3-((E)-2-Carboxyvinyl)azetidine-1-carboxylic acid tert-butyl ester (0.28 g; 1.24 mmol) was dissolved in methylene chloride (3 mL). 1-Hydroxy-7-azabenzotriazole (0.17 g; 1.24 mmol) and N-(3dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.26 g; 1.36 mmol) were added and the reaction mixture was stirred for 15 min at room temperature. N-Methyl-2-methylamino-N-(1-(methylcarbamoyl)-2-phenylethyl)-3-(2-naphthyl)propionamide (0.50 g; 1.24 mmol) (prepared as in example 1) was dissolved in methylene chloride (3 mL) and added to the reaction mixture. Ethyldiisopropylamine (0.21 mL; 1.24 mmol) was added and the reaction mixture was stirred for 12 hours at room temperature. Methylene chloride (20 mL) was added and the reaction mixture was washed with water (10 mL), an aqueous solution of sodium hydrogen sulfate (10 mL; 10%), an aqueous solution of sodium hydrogen carbonate (10 mL; sat.) and water (10 mL). The organic phase was dried (magnesium sulfate) and evaporated in vacuo. The residue was chromatographed on silica (2.5×20 cm) using 2.5% (7% ammonia in ethanol) in methylene chloride as eluent to afford 0.49 g of 3-((E)-2-(methyl((1R)-1-(methyl((1R)-1-(methylcarbamoyl)-2-phenylethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)vinyl)azetidine-1-carboxylic acid tert-butyl ester.

Workup

  1. additionadded to the reaction mixture
  2. stirringthe reaction mixture was stirred for 12 hours at room temperature
  3. washthe reaction mixture was washed with water (10 mL)
  4. dry with materialThe organic phase was dried (magnesium sulfate)
  5. customevaporated in vacuo
  6. customThe residue was chromatographed on silica (2.5×20 cm)

Sources & evidence

ORD record
ord-d86c56e03df943e9a96b813a2a71aade
Source dataset
uspto-grants-2003_04
Patent number
US06555570B2

Linked notes

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