Diisopropylethylamine → N-Methyl-N-[(1R)1-(N-methyl-N-{(1R)-1-[N-methyl-N-(2-(pyridinyl)ethyl)carbamoyl]-2-phenylethyl}carbamoyl)-2-(2-naphthyl)ethyl]carbamic acid tert-butyl ester

HRID 413491Notes

Reaction equation

HRID 413491 reaction equation
[C:1]([O:5][C:6]([N:8]([C@H:10]([CH2:14][C:15]1[CH:24]=[CH:23][C:22]2C(=CC=C[CH:21]=2)[CH:16]=1)[C:11](O)=[O:12])[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1[C:30]2N=C[CH:33]=[CH:34][C:29]=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)C(C)C)C.[CH3:56][N:57]([CH2:70][CH2:71][C:72]1[CH:77]=[CH:76][CH:75]=[CH:74][N:73]=1)[C:58](=[O:69])[C@H:59]([NH:67][CH3:68])[CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1>ClCCl>[C:1]([O:5][C:6](=[O:7])[N:8]([CH3:9])[C@@H:10]([C:11](=[O:12])[N:67]([CH3:68])[C@@H:59]([C:58](=[O:69])[N:57]([CH3:56])[CH2:70][CH2:71][C:72]1[CH:77]=[CH:76][CH:75]=[CH:74][N:73]=1)[CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[CH2:14][C:15]1[CH:16]=[CH:33][C:34]2[C:23](=[CH:22][CH:21]=[CH:30][CH:29]=2)[CH:24]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10065151(2R)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3-naphthalen-2-ylpropanoic acidHCID 53710542(2R)-N-Methyl-2-(methylamino)-3-phenyl-N-(2-(2-pyridyl)ethyl)propionamide

Product 1

HCID 59063565N-Methyl-N-[(1R)1-(N-methyl-N-{(1R)-1-[N-methyl-N-(2-(pyridinyl)ethyl)carbamoyl]-2-phenylethyl}carbamoyl)-2-(2-naphthyl)ethyl]carbamic acid tert-butyl esterYield 90.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-(2-naphthyl) propionic acid (11.2 g, 34 mmol), 1-hydroxy-7-azabenzotriazole (5.2 g, 38 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (6.9 g, 36 mmol) were dissolved in dichloromethane (100 mL). The reaction mixture was stirred for 15 min. Ethyldiisopropylamine (7.0 mL, 41 mmol) was added. (2R)-N-Methyl-2-(methylamino)-3-phenyl-N-(2-(2-pyridyl)ethyl)propionamide (7.9 g, 27 mmol) dissolved in dichloromethane (20 mL) was added. The reaction mixture was stirred for 16 h. The reaction mixture was added to aminomethylresin (17.3 g, 13.5 mmol). The reaction mixture was stirred for 6 h. The reaction mixture was filtrated. The organic layer was washed with sat. aqueous sodium hydrogen carbonate solution (2×150 mL). The organic layer was dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g), using ethyl acetate as eluent, to give 14.9 g N-Methyl-N-[(1R)1-(N-methyl-N-{(1R)-1-[N-methyl-N-(2-(pyridinyl)ethyl)carbamoyl]-2-phenylethyl}carbamoyl)-2-(2-naphthyl)ethyl]carbamic acid tertbutyl ester.

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred for 16 h
  3. additionThe reaction mixture was added to aminomethylresin (17.3 g, 13.5 mmol)
  4. stirringThe reaction mixture was stirred for 6 h
  5. filtrationThe reaction mixture was filtrated
  6. washThe organic layer was washed with sat. aqueous sodium hydrogen carbonate solution (2×150 mL)
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. customThe solvent was removed in vacuo
  9. customThe crude product was purified by flash chromatography on silica (400 g)

Sources & evidence

ORD record
ord-35c026e55bef4a38963d629b60b37633
Source dataset
uspto-grants-2003_05
Patent number
US06566337B1

Reaction notes

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