Triethylamine → HCID 67326296, compound

HRID 339484Notes

Reaction equation

HRID 339484 reaction equation
[CH3:1][C:2]([NH:9][C:10](=[O:35])[CH:11]([OH:34])[C@@H:12]([NH:22][C:23](=[O:33])[C@@H:24]([NH2:32])[CH2:25][CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)[CH2:13][O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([CH3:8])[CH2:3][C:4]([CH3:7])([CH3:6])[CH3:5].C(N(CC)CC)C.[N:43]1([C:49](Cl)=[O:50])[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1>CN(C=O)C>[CH2:15]([O:14][CH2:13][C@H:12]([NH:22][C:23](=[O:33])[C@@H:24]([NH:32][C:49]([N:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1)=[O:50])[CH2:25][CH:26]1[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]1)[CH:11]([OH:34])[C:10](=[O:35])[NH:9][C:2]([CH3:1])([CH3:8])[CH2:3][C:4]([CH3:5])([CH3:6])[CH3:7])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 848104-Morpholinecarbonyl chlorideHCID 67326187HCID 67326187, compound

Product 1

HCID 67326296HCID 67326296, compoundYield 66.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N1-(1,1,3,3-tetramethylbutyl)-(3S)-3-[(2S)-2-amino-3-cyclohexylpropanoyl]amino-4-(benzyloxy)-2-hydroxybutanamide (360 mg, 0.7 mmole) was dissolved in DMF (7 mL), followed by addition of addition of triethylamine (205 ul, 1.5 mmole) and stirring under N2 for 15 min. 4-Morpholinecarbonyl chloride (93 ul, 0.8 mmole) was added. Stirring was continued overnight and DMF was removed under reduced pressure. The solution was diluted with EtOAc and washed with water. The organic layer was dried over MgSO4, filtered, and concentrated by rotary evaporation. Purification by chromatography (silica, Hexane/EtOAc with 10% MeOH, Rf=0.5) afforded N4-[(1S)-2-((1S)-1-[(benzyloxy)methyl]-2-hydroxy-3-oxo-3-[(1,1,3,3-tetramethylbutyl)amino]propylamino)-1-(cyclohexylmethyl)-2-oxoethyl]-4-Morpholinecarboxamide as a white solid (280 mg, 63%).

Workup

  1. stirringStirring
  2. waitwas continued overnight
  3. customDMF was removed under reduced pressure
  4. additionThe solution was diluted with EtOAc
  5. washwashed with water
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated by rotary evaporation
  9. customPurification by chromatography (silica, Hexane/EtOAc with 10% MeOH, Rf=0.5)

Sources & evidence

ORD record
ord-f7b6ff4a48564ca6a5b6ba0c973ad3d7
Source dataset
uspto-grants-2014_11
Patent number
US08895497B2

Reaction notes

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