Diisopropylethylamine → tert-butyl ((2S,3S)-3-hydroxy-1-(((S)-3-(4-methoxyphenyl)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)amino)-1-oxobutan-2-yl)carbamate

HRID 58924Notes

Reaction equation

HRID 58924 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@@H:13]([OH:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.OC(C(F)(F)F)=O.[NH2:47][C@@H:48]([CH2:66][C:67]1[CH:72]=[CH:71][C:70]([O:73][CH3:74])=[CH:69][CH:68]=1)[C:49]([NH:51][C@@H:52]([CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)[C:53]([C@@:55]1([CH3:58])[CH2:57][O:56]1)=[O:54])=[O:50].CCN(C(C)C)C(C)C>CN(C=O)C>[OH:15][C@@H:13]([CH3:14])[C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:10]([NH:47][C@@H:48]([CH2:66][C:67]1[CH:68]=[CH:69][C:70]([O:73][CH3:74])=[CH:71][CH:72]=1)[C:49]([NH:51][C@@H:52]([CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)[C:53]([C@@:55]1([CH3:58])[CH2:57][O:56]1)=[O:54])=[O:50])=[O:12]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 6992538(2S,3S)-2-{[(tert-butoxy)carbonyl]amino}-3-hydroxybutanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131737036HCID 131737036, compound

Product 1

HCID 117608239tert-butyl ((2S,3S)-3-hydroxy-1-(((S)-3-(4-methoxyphenyl)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)amino)-1-oxobutan-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To (2S,3S)-2-((tert-butoxycarbonyl)amino)-3-hydroxybutanoic acid (453 mg, 2.07 mmol) in DMF (10 mL) at 0° C. was added HATU (865 mg, 2.28 mmol). The mixture was stirred for 5 min to dissolve the solids at which time (S)-2-amino-3-(4-methoxyphenyl)-N-((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)propanamide TFA salt (2.07 mmol assumed) and DIEA (1.71 mL, 10.35 mmol) was added. The reaction mixture was stirred at ambient temperature for 30 min then quenched with sodium bicarbonate (sat.), extracted with ethyl acetate (2×), dried with sodium sulfate, filtered, and concentrated to provide crude tert-butyl ((2S,3S)-3-hydroxy-1-(((S)-3-(4-methoxyphenyl)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)amino)-1-oxobutan-2-yl)carbamate as a yellow oil that was carried forward without further purification.

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at ambient temperature for 30 min
  3. customthen quenched with sodium bicarbonate (sat.)
  4. extractionextracted with ethyl acetate (2×)
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-ea51544fb6c8439da1113c452df8fee2
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Reaction notes

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