4-Methylmorpholine → HCID 86625803, compound

HRID 1924000Notes

Reaction equation

HRID 1924000 reaction equation
CN1CCOCC1.[C:8]([O:12][C:13]([NH:15][CH2:16][CH2:17][N:18]([CH2:34][CH2:35][NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C:19]([CH2:21][C@H:22]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:23]([OH:25])=O)=[O:20])=[O:14])([CH3:11])([CH3:10])[CH3:9].[NH2:44][C@@H:45]([CH2:65][CH2:66][C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)[C:46]([N:48]([CH3:64])[CH2:49][CH2:50][NH:51][C:52]([C:54]1[CH:59]=[CH:58][C:57]([C:60]([F:63])([F:62])[F:61])=[CH:56][CH:55]=1)=[O:53])=[O:47]>C(Cl)Cl>[C:40]([O:39][C:37]([NH:36][CH2:35][CH2:34][N:18]([CH2:17][CH2:16][NH:15][C:13]([O:12][C:8]([CH3:9])([CH3:11])[CH3:10])=[O:14])[C:19]([CH2:21][C@H:22]([NH:26][C:27](=[O:28])[O:29][C:30]([CH3:31])([CH3:33])[CH3:32])[C:23](=[O:25])[NH:44][C@H:45]([C:46](=[O:47])[N:48]([CH3:64])[CH2:49][CH2:50][NH:51][C:52]([C:54]1[CH:55]=[CH:56][C:57]([C:60]([F:62])([F:63])[F:61])=[CH:58][CH:59]=1)=[O:53])[CH2:65][CH2:66][C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)=[O:20])=[O:38])([CH3:41])([CH3:43])[CH3:42]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 59366638HCID 59366638, compoundHCID 59366646HCID 59366646, compound

Product 1

HCID 86625803HCID 86625803, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of CDMT (0.22 g, 1.26 mmol) in DCM (30 mL) was cooled to 0° C. before adding N-methylmorpholine (0.3 mL, 2.62 mmol). After 15 min, (2S)-3-[bis(2-{[(tert-butoxy)carbonyl]amino}ethyl)carbamoyl]-2-{[(tert-butoxy)carbonyl]amino}propanoic acid CXXIV (0.62 g, 1.20 mmol) was added and the solution was stirred for additional 40 min. After that time, (2S)-2-amino-N-methyl-4-phenyl-N-(2-{[4-(trifluoromethyl)phenyl]formamido}ethyl)butanamide CXXIII (0.56 g, 1.26 mmol) was added and the mixture stirred at r.t. overnight. The mixture was washed with 1 M HCl (5×), 1 M K2CO3 (5×), brine and dried over MgSO4. The solvent was evaporated under vacuum and the residue was purified on a silica gel column (50:1 DCM/methanol) to give tert-butyl N-[(1S)-2-[bis(2-{[(tert-butoxy)carbonyl]amino}ethyl)carbamoyl]-1-{[(1S)-1-[methyl(2-{[4-(trifluoromethyl)phenyl]formamido}ethyl)carbamoyl]-3-phenylpropyl]carbamoyl}ethyl]carbamate as yellow solid (0.78 g, 0.86 mmol, 68% yield). ESIMS found for C44H64F3N7O10 m/z 908 (M+H).

Workup

  1. stirringthe mixture stirred at r.t. overnight
  2. washThe mixture was washed with 1 M HCl (5×), 1 M K2CO3 (5×), brine
  3. dry with materialdried over MgSO4
  4. customThe solvent was evaporated under vacuum
  5. customthe residue was purified on a silica gel column (50:1 DCM/methanol)

Sources & evidence

ORD record
ord-5ad761f9f3eb443882c06e8c236f3385
Source dataset
uspto-grants-2012_05
Patent number
US08178490B2

Reaction notes

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