Diisopropylethylamine → (2-((((1R)-1-(((1R)-2-(4-fluorophenyl)-1-methylcarbamoylethyl)-methylcarbamoyl)-2-(2-naphthyl)ethyl)methylcarbamoyl)-methoxy)-1,1-dimethylethyl)carbamic acid tert-butylester

HRID 495795Notes

Reaction equation

HRID 495795 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:17])([CH3:16])[CH2:10][O:11][CH2:12][C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[F:40][C:41]1[CH:46]=[CH:45][C:44]([CH2:47][C@@H:48]([N:53]([CH3:70])[C:54](=[O:69])[C@H:55]([NH:67][CH3:68])[CH2:56][C:57]2[CH:66]=[CH:65][C:64]3[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=3)[CH:58]=2)[C:49](=[O:52])[NH:50][CH3:51])=[CH:43][CH:42]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]([CH3:17])([CH3:16])[CH2:10][O:11][CH2:12][C:13](=[O:15])[N:67]([C@@H:55]([C:54](=[O:69])[N:53]([C@@H:48]([C:49](=[O:52])[NH:50][CH3:51])[CH2:47][C:44]1[CH:43]=[CH:42][C:41]([F:40])=[CH:46][CH:45]=1)[CH3:70])[CH2:56][C:57]1[CH:66]=[CH:65][C:64]2[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=2)[CH:58]=1)[CH3:68])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10717074(2R)-N-((1R)-2-(4-Fluorophenyl)-1-(methylcarbamoyl)ethyl)-N-methyl-2-methylamino-3-(2-naphthyl)propionamideHCID 10776871(2-Bocamino-2-methyl-propoxy)-acetic acid

Product 1

HCID 54329951(2-((((1R)-1-(((1R)-2-(4-fluorophenyl)-1-methylcarbamoylethyl)-methylcarbamoyl)-2-(2-naphthyl)ethyl)methylcarbamoyl)-methoxy)-1,1-dimethylethyl)carbamic acid tert-butylesterYield 91.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(2-tert-Butoxycarbonylamino-2-methylpropoxy)acetic acid (0.22 g; 0.89 mmol) was dissolved in methylene chloride (10 mL). 1-Hydroxy-7-azabenzotriazole (0.13 g; 0.98 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.20 g; 1.02 mmol) were added and the reaction mixture was stirred for 15 min at room temperature. (2R)-N-((1R)-2-(4-Fluorophenyl)-1-(methylcarbamoyl)ethyl)-N-methyl-2-methylamino-3-(2-naphthyl)propionamide (0.38 g; 0.89 mmol) and diisopropylethylamine (0.17 mL; 0.98 mmol) were added and the reaction mixture was stirred for 12 hours at room temperature. Methylene chloride (50 mL) was added and the reaction mixture was washed with water (50 mL), an aqueous solution of sodium hydrogen carbonate/sodium carbonate (pH 9; 50 mL), an aqueous solution of sodium hydrogen sulfate (10%; 50 mL) and water (50 mL) and dried (magnesium sulfate). The solvent was removed in vacuo to afford 0.53 g of (2-((((1R)-1-(((1R)-2-(4-fluorophenyl)-1-methylcarbamoylethyl)-methylcarbamoyl)-2-(2-naphthyl)ethyl)methylcarbamoyl)-methoxy)-1,1-dimethylethyl)carbamic acid tert-butylester.

Workup

  1. stirringthe reaction mixture was stirred for 12 hours at room temperature
  2. washthe reaction mixture was washed with water (50 mL)
  3. dry with materialan aqueous solution of sodium hydrogen carbonate/sodium carbonate (pH 9; 50 mL), an aqueous solution of sodium hydrogen sulfate (10%; 50 mL) and water (50 mL) and dried (magnesium sulfate)
  4. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-7b947202b5a64fbfbff4a4cc1bdd54b8
Source dataset
uspto-grants-2005_09
Patent number
US06939880B2

Reaction notes

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