Diisopropylethylamine → HCID 56608208, compound

HRID 365436

Reaction equation

HRID 365436 reaction equation
Cl.CN(C)CCCN=C=NCC.[C:13]([O:17][C:18]([N:20]([C@H:22]([CH2:26][C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=1)[C:23]([OH:25])=O)[CH3:21])=[O:19])([CH3:16])([CH3:15])[CH3:14].ON1C2N=CC=CC=2N=N1.[CH3:47][NH:48][C:49](=[O:72])[C@@H:50]([NH:59][C:60](=[O:71])[C@H:61]([NH:69][CH3:70])[CH2:62][C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[CH2:51][CH2:52][CH2:53][CH2:54][NH:55][C:56](=[O:58])[CH3:57].C(N(C(C)C)C(C)C)C>ClCCl.CN(C)C=O.C(OCC)(=O)C>[C:13]([O:17][C:18](=[O:19])[N:20]([C@@H:22]([C:23](=[O:25])[N:69]([C@@H:61]([C:60](=[O:71])[NH:59][C@H:50]([C:49](=[O:72])[NH:48][CH3:47])[CH2:51][CH2:52][CH2:53][CH2:54][NH:55][C:56](=[O:58])[CH3:57])[CH2:62][C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[CH3:70])[CH2:26][C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=1)[CH3:21])([CH3:15])([CH3:16])[CH3:14]

Participants

9

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 53795766HCID 53795766, compound

Product 1

HCID 56608208HCID 56608208, compoundYield 68.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (313 mg, 1.63 mmol) was added at 0° C. to a solution of (2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)propionic acid (537 mg, 1.63 mmol) and 1-hydroxy-7-azabenzotriazole (222 mg, 1.63 mmol) in dichloromethane (20 ml) and N,N-dimethylformamide (10 ml). The reaction mixture was stirred for 20 min at 0° C. A solution of the crude hydrochloride salt of (2S)-6-acetylamino-2-((2R)-2-(methylamino)-3-phenylpropionylamino)hexanoic acid methylamide (710 mg, 1.63 mmol) and ethyldiisopropylamine (0.84 ml, 4.89 mmol) were added subsequently, The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (70 ml) and washed with a 1 0% aqueous solution of sodium hydrogen sulfate (70 ml). The aqueous solution was extracted with ethyl acetate (2×60 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (70 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (80 g), using dichloromethane./methanol (1 0: 1) as eluent to give 748 mg of N-((1R)-1-{N-[(1R)-1-((1S)-5-(acetylamino)-1-(methylcarbamoyl)pentylcarbamoyl)-2-phenylethyl]-N-methylcarbamoyl}-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butyl ester.

Workup

  1. stirringThe reaction mixture was stirred for 16 h, while it
  2. temperaturewas warming up to room temperature
  3. washwashed with a 1 0% aqueous solution of sodium hydrogen sulfate (70 ml)
  4. extractionThe aqueous solution was extracted with ethyl acetate (2×60 ml)
  5. washThe combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (70 ml)
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. customThe crude product was purified by flash chromatography on silica (80 g)

Sources & evidence

ORD record
ord-cb2d6f3e0b764bb3a088d7cfa6789211
Source dataset
uspto-grants-2000_10
Patent number
US06127341

Linked notes

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