Triethylamine → 2-Hydroxy-5-methyl-3-[[2-[[3-(1-naphthalenyl)-2-(1-naphthalenylmethyl)-1-oxopropyl]amino]-1-oxo-6-[[(phenylmethoxy)carbonyl]amino]hexyl]amino]hexanoic acid, 1-methylethyl ester

HRID 846471Notes

Reaction equation

HRID 846471 reaction equation
[C:1]1([CH2:11][CH:12]([CH2:35][C:36]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[CH:39]=[CH:38][CH:37]=2)[C:13]([NH:15][C@H:16]([C:32](O)=[O:33])[CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl.[NH2:47][CH:48]([CH2:57][CH:58]([CH3:60])[CH3:59])[CH:49]([OH:56])[C:50]([O:52][CH:53]([CH3:55])[CH3:54])=[O:51].ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O>[OH:56][CH:49]([CH:48]([NH:47][C:32](=[O:33])[CH:16]([NH:15][C:13](=[O:14])[CH:12]([CH2:11][C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)[CH2:35][C:36]1[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH:39]=[CH:38][CH:37]=1)[CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:22]([O:24][CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)=[O:23])[CH2:57][CH:58]([CH3:60])[CH3:59])[C:50]([O:52][CH:53]([CH3:54])[CH3:55])=[O:51]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 15177038N-[3-(1-Naphthalenyl)-2-(1-naphthalenylmethyl)-1-oxopropyl]-N6-[(phenylmethoxy)carbonyl]-L-lysineHCID 1317174863-Amino-2-hydroxy-5-methylhexanoic acid, 1-methylethyl ester, monohydrochloride2×

Product 1

HCID 765099312-Hydroxy-5-methyl-3-[[2-[[3-(1-naphthalenyl)-2-(1-naphthalenylmethyl)-1-oxopropyl]amino]-1-oxo-6-[[(phenylmethoxy)carbonyl]amino]hexyl]amino]hexanoic acid, 1-methylethyl esterYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-10 °C

Procedure

N-[3-(1-naphthalenyl)-2-(1-naphthalenylmethyl)-1-oxopropyl]-N6 -[(phenylmethoxy)carbonyl]-L-lysine, 4 g (6.6 mmol), 1.58 g (6.6 mmol) of [2R-(2R*,3S*)]-3-amino-2-hydroxy-5-methylhexanoic acid, 1-methylethyl ester, monohydrochloride, and 1.79 g (13.2 mmol) of 1-hydroxybenzotriazole are combined in 80 ml of dimethylformamide. The [2R-(2R*,3S*)]-3-amino-2-hydroxy-5-methylhexanoic acid, 1-methylethyl ester, monohydrochloride is neutralized with 1.4 ml (10.1 mmol) of triethylamine. The solution is cooled to -10° C. and 1.36 g (6.6 mmol) of dicyclohexylcarbodiimide is added with stirring. The reaction mixture is kept cold for 8 hours while stirring under nitrogen, allowed to warm to room temperature overnight, filtered, the filtrate concentrated and the residue partitioned between ethyl acetate and water. The organic layer is separated and extracted with saturated solution of sodium bicarbonate, dried (sodium sulfate), filtered and concentrated. The residue is flash chromatographed over silica gel 60 (230-400 mesh), eluted with hexane-ethyl acetate (2:3), the eluates collected, dissolved in diethyl ether, filtered and the filtrate concentrated to afford 4.01 g (77%) of the title compound as a white amorphous solid.

Workup

  1. stirringwhile stirring under nitrogen
  2. temperatureto warm to room temperature overnight
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated
  5. customthe residue partitioned between ethyl acetate and water
  6. customThe organic layer is separated
  7. extractionextracted with saturated solution of sodium bicarbonate
  8. dry with materialdried (sodium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customchromatographed over silica gel 60 (230-400 mesh)
  12. washeluted with hexane-ethyl acetate (2:3)
  13. customthe eluates collected
  14. dissolutiondissolved in diethyl ether
  15. filtrationfiltered
  16. concentrationthe filtrate concentrated

Sources & evidence

ORD record
ord-b1ee39934a6e42a19ac772767f876d2a
Source dataset
uspto-grants-1992_08
Patent number
US05135914

Reaction notes

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