Diisopropylethylamine → N-((2'-Cyano(1,1'-biphenyl)-4-yl)methyl)-L-valine methyl ester

HRID 875171Notes

Reaction equation

HRID 875171 reaction equation
CCCCC([N:7]([C@H:26]([C:30]([OH:32])=[O:31])[CH:27]([CH3:29])[CH3:28])[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=2[C:21]2NN=N[N:25]=2)=[CH:13][CH:14]=1)=O.Br[CH2:34]C1C=CC(C2C=CC=CC=2C#N)=CC=1.Cl.COC(=O)[C@H](C(C)C)N.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH3:34][O:32][C:30](=[O:31])[C@H:26]([CH:27]([CH3:28])[CH3:29])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=2[C:21]#[N:25])=[CH:11][CH:10]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111190Methyl valinate hydrochlorideHCID 15019124'-(Bromomethyl)-2-cyanobiphenylHCID 178447302HCID 178447302, compound

Product 1

HCID 16744794N-((2'-Cyano(1,1'-biphenyl)-4-yl)methyl)-L-valine methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Bioorganic & Medicinal Chemistry Letters (1994), 4(1), 29-34, reported a process for the preparation of Valsartan by reacting 4′-bromomethyl-2-cyanobiphenyl (II) with (L)-valine methyl ester hydrochloride (V) in the presence of diisopropylethylamine in methylenechloride to produce N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester (VI), followed by reacting with valeryl chloride in the presence of diisopropylethylamine in methylenechloride to produce N-valeryl-N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester (VII), which is further reacted with tributyltin azide in xylene to produce N-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-N-valeryl-(L)-valine methyl ester (VIII), followed by hydrolysis with aqueous base to produce Valsartan of formula (I).

Sources & evidence

ORD record
ord-5634e96350e143768c8515802b7759c6
Source dataset
uspto-grants-2015_03
Patent number
US08981109B2

Reaction notes

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