HCID 54362776, compound → (+/-)1,1-dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate

HRID 1735626Notes

Reaction equation

HRID 1735626 reaction equation
C[Si](C)(C)[N:3]=[CH:4][C:5]#[C:6][Si:7]([CH3:10])([CH3:9])[CH3:8].[C:13]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:15])[CH3:14].[Li]>>[NH2:3][CH:4]([C:5]#[C:6][Si:7]([CH3:10])([CH3:9])[CH3:8])[CH2:14][C:13]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]

Participants

3

Reactant 2

HCID 54362776HCID 54362776, compoundHCID 86586795Lithium Tert-butyl Acetate

Product 1

HCID 11064560(+/-)1,1-dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate

Procedure

The present invention relates to a novel process for the preparation of ethyl 3S-[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-4-pentynoate having the following structural formula ##STR1## and the pharmaceutically acceptable acid addition salt thereof which comprises treating (trimethylsilyl) acetylene sequentially with n-butyllithium and 4-formylmorpholine in the presence of an aprotic solvent followed by acid hydrolysis to give 3-(trimethylsilyl)-2-propynal; treating 3-(trimethylsilyl)-2-propynal with lithium bis(trimethylsilyl)amide in the presence of an aprotic solvent to give N,3-bis(trimethylsilyl)-2-propyn-1-imine in situ; condensation of N,3-bis(trimethylsilyl)-2-propyn-1-imine with lithium t-butyl acetate followed by hydrolytic cleavage to give (±)1,1-dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate; treating (±)1,1-dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate with p-toluenesulfonic acid in the presence of aprotic solvents to give (±)1,1-dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate, mono p-toluenesulfonic acid salt; treatment of the resulting salt with ethanol in the presence of p-toluenesulfonic acid, followed by neutralization to give (±)ethyl 3-amino-5-(trimethylsilyl)-4-pentynoate; desilylation of (±)ethyl 3-amino-5-(trimethylsilyl)-4-pentynoate in the presence of a catalytic amount of base and an alkanol solvent to give in situ (±)ethyl 3-amino-4-pentynoate; resolution of (±)ethyl 3-amino-4-pentynoate using (R)-(-)-mandelic acid and treatment of the resolved product with gaseous hydrochloric acid to give ethyl 3S-amino-4-pentynoate, monohydrochloride; coupling the ethyl 3S-amino-4-pentynoate, monohydrochloride to 4-[[4-(aminoiminomethyl)phenyl]amino]-4-oxobutanoic acid, monohydrochloride in the presence of isobutyl chloroformate and N-methylmorpholine to give ethyl 3S-[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-4-pentynoate, monohydrochloride.

Sources & evidence

ORD record
ord-898f50db51364b3587cb660aefac872d
Source dataset
uspto-grants-1996_07
Patent number
US05536869

Reaction notes

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