4-Methylmorpholine → N-(tert-butoxycarbonyl)-2,6-dimethyl-L-tyrosyl-N-{(2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropyl}-D-alaninamide

HRID 1849984

Reaction equation

HRID 1849984 reaction equation
[C:1]([O:5][C:6](=[O:23])[NH:7][C@@H:8]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:9][NH:10][C:11](=[O:15])[C@@H:12]([CH3:14])[NH2:13])([CH3:4])([CH3:3])[CH3:2].[C:24]([O:28][C:29]([NH:31][C@H:32]([C:43](O)=[O:44])[CH2:33][C:34]1[C:39]([CH3:40])=[CH:38][C:37]([OH:41])=[CH:36][C:35]=1[CH3:42])=[O:30])([CH3:27])([CH3:26])[CH3:25].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[C:24]([O:28][C:29]([NH:31][C@H:32]([C:43]([NH:13][C@@H:12]([C:11]([NH:10][CH2:9][C@@H:8]([NH:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:23])[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)=[O:15])[CH3:14])=[O:44])[CH2:33][C:34]1[C:35]([CH3:42])=[CH:36][C:37]([OH:41])=[CH:38][C:39]=1[CH3:40])=[O:30])([CH3:26])([CH3:27])[CH3:25]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 13656657(S)-2-tert-Butoxycarbonylamino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionic acidHCID 58403568tert-Butyl-[(1S)-2-(D-alanylamino)-1-benzylethyl]carbamate

Product 1

HCID 71229494N-(tert-butoxycarbonyl)-2,6-dimethyl-L-tyrosyl-N-{(2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropyl}-D-alaninamideYield 109.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl-[(1S)-2-(D-alanylamino)-1-benzylethyl]carbamate (described in PC33903A Preparation 36; 3.43 g, 9.94 mmol) and N-(tert-butoxycarbonyl)-2,6-dimethyl-L-tyrosine (described in BioOrg. Med. Chem. Letts, 2003, p 599; 2.92 g, 9.25 mmol) were added sequentially to a stirred solution of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride salt (2.29 g, 11.9 mmol), 1-hydroxybenzotriazole monohydrate (1.57 g, 10.2 mmol) and N-methylmorpholine (1.01 g, 9.94 mmol) in DMF (70 mL) at room temperature under a nitrogen atmosphere. The mixture was stirred at room temperature for 16 h and then diluted with 280 mL of EtOAc and washed with 280 mL of a 10% aqueous solution of citric acid, 280 mL of water, 280 mL of a 3% aqueous solution of sodium bicarbonate, and finally 200 mL of a saturated aqueous brine solution. The organic layer was dried over sodium sulfate and evaporated under reduced pressure to give 6.2 g (92%) of a white foam of the title compound, which was used with no further purification.

Workup

  1. washwashed with 280 mL of a 10% aqueous solution of citric acid, 280 mL of water, 280 mL of a 3% aqueous solution of sodium bicarbonate, and finally 200 mL of a saturated aqueous brine solution
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-e317decea0734c44bbad695ec1133a1c
Source dataset
uspto-grants-2015_02
Patent number
US08957025B2

Linked notes

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