Piperazine Dihydrochloride → Irbesartan

HRID 659752

Reaktionsgleichung

Reaktionsgleichung von HRID 659752
[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]#[N:24])=[CH:13][CH:12]=2)[C:8](=[O:25])[C:7]2([CH2:29][CH2:28][CH2:27][CH2:26]2)[N:6]=1)[CH2:2][CH2:3][CH3:4].[N-:30]=[N+:31]=[N-:32].[Na+].Cl.Cl.N1CCNCC1.[OH-].[Na+]>CN(C)C=O.O>[CH3:4][CH2:3][CH2:2][CH2:1][C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]3[N:32]=[N:31][NH:30][N:24]=3)=[CH:13][CH:12]=2)[C:8](=[O:25])[C:7]2([CH2:26][CH2:27][CH2:28][CH2:29]2)[N:6]=1

Komponenten

7

Edukt 4

HCID 8893Piperazine DihydrochlorideHCID 14798Sodium HydroxideHCID 33557Sodium AzideHCID 98431164'-((2-Butyl-4-oxo-1,3-diazaspiro(4.4)non-1-ene-3-yl)methyl)(1,1'-biphenyl)-2-carbonitrile

Produkt 1

HCID 3749IrbesartanAusbeute 92,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of 2-n-butyl-3-[(2′-cyanobiphenyl-4-yl)methyl]-1,3-diazaspiro-[4,4]-non-1-en-4-one (10g), sodium azide (7.7 g) and piperazine dihydrochloride (7.5 g) in N,N-dimethylformamide (30 ml) was refluxed for 7 hours under stirring. The reaction was cooled to room temperature and 20 ml water was added. The reaction mixture was adjusted to pH of about 12 using 10% NaOH solution. The alkaline solution was washed with toluene (15 ml) and the aqueous phase was neutralized to pH of 6.0 using concentrated HCl. The resulting suspension was stirred for 3 hours at room temperature and filtered to obtain irbesartan (6.0 g, 92.7% purity by HPLC) and content of the impurity 2-n-butyl-3-[(2′-carboxamidobiphenyl-4-yl)methyl]-1,3-diazaspiro-[4,4]-non-1-en-1-one 0.07%. When the pH was adjusted to 5.6, the yield remained same but the purity was further reduced to 90.2% and content of the impurity 2-n-butyl-3-[(2′-carboxamidobiphenyl-4-yl)methyl]-1,3-diazaspiro-[4,4]-non-1-ene-4-one; 0.09%.

Aufarbeitung

  1. temperaturewas refluxed for 7 hours
  2. washThe alkaline solution was washed with toluene (15 ml)
  3. stirringThe resulting suspension was stirred for 3 hours at room temperature
  4. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-2502363ac3154beea3f0de68607d37ba
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08080670B2

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