Triethylamine → HCID 67491274, compound

HRID 403209Notes

Reaction equation

HRID 403209 reaction equation
C(OC(N[C@H](C(NC[C@@H](NC(OC(C)(C)C)=O)C(C)C)=O)CC1C=CC=CC=1)=O)C1C=CC=CC=1.Cl.[NH2:37][C@:38](NC(OC(C)(C)C)=O)([CH:62]([CH3:64])[CH3:63])[CH2:39][NH:40][C:41](=[O:61])[C@H:42]([CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)[NH:43][C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45].C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.[C:90]([NH:97][C@H:98]([C:103](O)=[O:104])[CH2:99][CH:100]([CH3:102])[CH3:101])([O:92][C:93]([CH3:96])([CH3:95])[CH3:94])=[O:91].C1CCC(N=C=NC2CCCCC2)CC1>Cl.O1CCOCC1.CN(C=O)C.C(Cl)Cl>[CH2:47]([O:46][C:44]([NH:43][C@H:42]([C:41]([NH:40][CH2:39][C@@H:38]([NH:37][C:103](=[O:104])[C@H:98]([CH2:99][CH:100]([CH3:101])[CH3:102])[NH:97][C:90]([O:92][C:93]([CH3:94])([CH3:95])[CH3:96])=[O:91])[CH:62]([CH3:64])[CH3:63])=[O:61])[CH2:54][C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1)=[O:45])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 67491245HCID 67491245, compoundHCID 67491279HCID 67491279, compound

Product 1

HCID 67491274HCID 67491274, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

(2S)-1-(N-benzyloxycarbonyl-L-phenylalanylamino)-2-(tert-butoxycarbonylamino)-3-methylbutane (0.730 g, 1.51 mmol) was dissolved in 15 ml of 4N solution of anhydrous hydrochloride in dioxane. The reaction mixture was stirred during 0.5 h at room temperature, then evaporated under reduced pressure. The residual oil was triturated with anhydrous diethyl ether (50 ml). The obtained solid was filtered off under reduced pressure, washed with anhydrous diethyl ether (3×10 ml) and dried under vacuum over potassium hydroxide. The resulted (2S)-2-amino-1-(N-benzyloxycarbonyl-L-phenylalanylamino)-2-(tert-butoxycarbonyl-amino)-3-methylbutane hydrochloride (0.622 g, 1.48 mmol) was dissolved in 14 ml DMF/DCM (5:9 v/v) mixture, then triethylamine (412 μl, 2.96 mmol), HOBt (0.200 g, 1.48 mmol) and Boc-L-leucine (0.342 g, 1.48 mmol) were added to the solution. The mixture was cooled on ice bath and DCC (0.336 g, 1.63 mmol) was added in small portions during 0.5 h, with vigorous stirring. Stirring on ice bath was continued during additional 1 h, then the reaction mixture was left at room temperature overnight. The precipitated DCU was filtered off, washed with DMF (5 ml) and the combined filtrates were evaporated under reduced pressure. The solid residue was dissolved in 250 ml of ethyl acetate and the solution was washed with 1 M hydrochloric acid (3×80 ml), water (100 ml), 1 M sodium bicarbonate (3×80 ml) and saline (3×80 ml). The organic layer was dried over anhydrous magnesium sulphate and evaporated to dryness. The residue was dissolved in hot toluene and precipitated with petroleum ether, yielding 0.795 g (90%) of (2S)-1-(N-benzyloxycarbonyl-L-phenylalanylamino)-2-(N-tert-butoxycarbonyl-L-leucylamino)-3-methylbutane.

Workup

  1. customevaporated under reduced pressure
  2. customThe residual oil was triturated with anhydrous diethyl ether (50 ml)
  3. filtrationThe obtained solid was filtered off under reduced pressure
  4. washwashed with anhydrous diethyl ether (3×10 ml)
  5. dry with materialdried under vacuum over potassium hydroxide
  6. temperatureThe mixture was cooled on ice bath
  7. stirringStirring on ice bath
  8. waitwas continued during additional 1 h
  9. waitthe reaction mixture was left at room temperature overnight
  10. filtrationThe precipitated DCU was filtered off
  11. washwashed with DMF (5 ml)
  12. customthe combined filtrates were evaporated under reduced pressure
  13. dissolutionThe solid residue was dissolved in 250 ml of ethyl acetate
  14. washthe solution was washed with 1 M hydrochloric acid (3×80 ml), water (100 ml), 1 M sodium bicarbonate (3×80 ml) and saline (3×80 ml)
  15. dry with materialThe organic layer was dried over anhydrous magnesium sulphate
  16. customevaporated to dryness
  17. dissolutionThe residue was dissolved in hot toluene
  18. customprecipitated with petroleum ether

Sources & evidence

ORD record
ord-c036272946d34316805042f97cb1a0e0
Source dataset
uspto-grants-2014_06
Patent number
US08748370B2

Reaction notes

Loading…