4-Methylmorpholine → benzyl[(R)-5-tert-butoxycarbonylamino-5-((S)-1-carbamoyl-2-methyl-propylcarbamoyl)-pentyl]-carbamate

HRID 1943300Notes

Reaction equation

HRID 1943300 reaction equation
CN1CCOCC1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH2:30]([O:37][C:38]([NH:40][CH2:41][CH2:42][CH2:43][CH2:44][C@@H:45]([NH:49][C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[C:46]([OH:48])=O)=[O:39])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.Cl.[NH2:58][C@@H:59]([CH:63]([CH3:65])[CH3:64])[C:60]([NH2:62])=[O:61]>C(Cl)Cl.CN(C=O)C.C(Cl)Cl.CO.CCCCCCC.CCOC(C)=O>[CH2:30]([O:37][C:38](=[O:39])[NH:40][CH2:41][CH2:42][CH2:43][CH2:44][C@@H:45]([NH:49][C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[C:46](=[O:48])[NH:58][C@H:59]([C:60](=[O:61])[NH2:62])[CH:63]([CH3:65])[CH3:64])[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

10

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7269335(2R)-6-{[(benzyloxy)carbonyl]amino}-2-{[(tert-butoxy)carbonyl]amino}hexanoic acidHCID 13689583L-Valinamide--hydrogen chloride (1/1)

Product 1

HCID 131730274benzyl[(R)-5-tert-butoxycarbonylamino-5-((S)-1-carbamoyl-2-methyl-propylcarbamoyl)-pentyl]-carbamateYield 79.4%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolventHCID 21899848Ethylacetate heptaneSolvent

Procedure

N-Methylmorpholine (0.87 ml, 7.9 mmol), 1-hydroxybenzotriazole (0.46 g, 3.41 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.65 g, 3.41 mmol) were added in this sequence to a solution of commercially available (R)-6-benzyloxycarbonylamino-2-tert-butoxycarbonylamino-hexanoic acid (1 g, 2.63 mmol) and commercially available (S)-2-amino-3-methylbutyramide hydrochloride (0.40 g, 2.63 mmol) in 12 ml of CH2Cl2 and 4 ml of DMF, and the mixture was stirred at RT for about 14 h. Flash chromatography (gradient heptane/AcOEt to CH2Cl2/MeOH) afforded 1 g of the product (79%).

Sources & evidence

ORD record
ord-29f9437d2d854641b2d1c59d65dcfdc1
Source dataset
uspto-grants-2013_03
Patent number
US08389764B2

Reaction notes

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