4-Methylmorpholine → Benzyl [(1R)-2-({(2R)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropyl}amino)-1-methyl-2-oxoethyl]carbamate

HRID 1849986Notes

Reaction equation

HRID 1849986 reaction equation
[CH2:1]([O:8][C:9](=[O:21])[NH:10][C@H:11]([CH2:14]C1C=CC=CC=1)[CH2:12][NH2:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:22]([NH:29][C@@H:30]([C:32](O)=O)[CH3:31])([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].Cl.CN(C)CCCN=C=NCC.O.ON1[C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][C:52]=2N=N1.CN1CC[O:62]CC1>CN(C=O)C.C(OCC)(=O)C>[C:25]([O:24][C:22]([NH:29][C@H:30]([CH2:31][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[CH2:32][NH:13][C:12](=[O:62])[C@H:11]([NH:10][C:9](=[O:21])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH3:14])=[O:23])([CH3:26])([CH3:27])[CH3:28]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 637606BOC-D-alanineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 69740353(R)-Benzyl 1-amino-3-phenylpropan-2-ylcarbamate

Product 1

HCID 86717649Benzyl [(1R)-2-({(2R)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropyl}amino)-1-methyl-2-oxoethyl]carbamateYield 104.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Benzyl-[(1R)-2-amino-1-benzylethyl]carbamate (described in J. Med. Chem., 2010, p 106; 200 mg, 0.71 mmol) and N—BOC-D-alanine (134 mg, 0.71 mmol) were added to a stirred solution of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride salt (163 mg, 0.85 mmol), 1-hydroxybenzotriazole monohydrate (115 mg, 0.75 mmol) and N-methylmorpholine (72 mg, 0.71 mmol) in DMF (3 mL) at room temperature under a nitrogen atmosphere. After 16 h the mixture was treated with 8 mL of ethyl acetate (creating a suspension) and washed with 12 mL of a 10% aqueous citric acid solution, 12 mL of water, 12 mL of a 3% aqueous solution of sodium bicarbonate, and another 10 mL of a saturated aqueous brine solution. The organic layer was dried over sodium sulfate and evaporated under reduced pressure to give 338 mg (93%) of a white foam of the title compound, which was used with no further purification.

Workup

  1. washwashed with 12 mL of a 10% aqueous citric acid solution, 12 mL of water, 12 mL of a 3% aqueous solution of sodium bicarbonate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-5a1b8a05696c4932a99af03a4221e4c3
Source dataset
uspto-grants-2015_02
Patent number
US08957025B2

Reaction notes

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