Tributyltin azide → Valsartan benzyl ester

HRID 901310Notes

Reaction equation

[CH2:1]([O:8][C:9](=[O:36])[C@H:10]([CH:33]([CH3:35])[CH3:34])[N:11]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]#[N:32])=[CH:21][CH:20]=1)[C:12](=[O:17])[CH2:13][CH2:14][CH2:15][CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Sn]([N:50]=[N+:51]=[N-:52])(CCCC)CCCC)CCC>>[CH3:16][CH2:15][CH2:14][CH2:13][C:12]([N:11]([C@H:10]([C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:36])[CH:33]([CH3:35])[CH3:34])[CH2:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[C:26]([C:31]3[N:52]=[N:51][NH:50][N:32]=3)=[CH:27][CH:28]=[CH:29][CH:30]=2)=[CH:23][CH:24]=1)=[O:17]

Participants

Reactant 2

HCID 4984872Tributyltin azide

HCID 46912012Benzyl(S)-2-((2'-cyanobiphenyl-4-ylmethyl)pentanoylamino)-3-methylbutyrate

Product 1

HCID 11283894Valsartan benzyl ester

Procedure

L-valine benzyl ester hydrochoride is N-alkylated with 4-bromomethyl-2′-cyanobiphenyl, the product 4-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine benzyl ester so formed is N-acylated with valeryl chloride to give N-[(2′-cyanobiphenyl-4-yl)methyl]-N-valeryl-(L)-valine benzyl ester. N-[(2′-cyanobiphenyl-4-yl)methyl]-N-valeryl-(L)-valine benzyl ester is treated with tributyltin azide to give valsartan benzyl ester. Valsartan benzyl ester is subjected to catalytic hydrogenation using for example palladium-charcoal as catalyst to give valsartan.

Sources & evidence

ORD record: ord-2f02965b3d5b4cbf8478d61e8af9f06a
Source dataset: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07361770B2

Reaction notes

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