Hydrochloric Acid → Irbesartan hydrochloride

HRID 1715730

Reaction equation

HRID 1715730 reaction equation
[ClH:1].[CH2:2]([C:6]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[CH:24]3[N:28](C)[N:27](C4C=CC=CC=4)[N:26](C4C=CC=CC=4)[N:25]3C3C=CC=CC=3)=[CH:14][CH:13]=2)[C:9](=[O:48])[C:8]2([CH2:52][CH2:51][CH2:50][CH2:49]2)[N:7]=1)[CH2:3][CH2:4][CH3:5].BrCC1C=CC(C2C=CC=CC=2C2N(C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)N=NN=2)=CC=1.C(C1NC(=O)C2(CCCC2)N=1)CCC.Cl>O.C1(C)C=CC=CC=1>[CH3:5][CH2:4][CH2:3][CH2:2][C:6]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:24]4[N:25]=[N:26][NH:27][N:28]=4)=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:14][CH:13]=2)[C:9](=[O:48])[C:8]2([CH2:49][CH2:50][CH2:51][CH2:52]2)[N:7]=1.[ClH:1]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 100534615-(4'-(Bromomethyl)(1,1'-biphenyl)-2-yl)-1-trityl-1H-tetraazoleHCID 101765112-Butyl-1,3-diazaspiro[4.4]non-1-en-4-oneHCID 86630707HCID 86630707, compound

Product 1

HCID 11568906Irbesartan hydrochloride

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
25 °C

Procedure

A synthetic one-pot process as provided by the present invention preferably involves the preparation of 2n-butyl-3-[2′(triphenyl methyl tetrazol-5yl)-biphenyl-4-yl-methyl]-1,3-diazaspiro[4,4]non-1-en-4-one hydrochloride of formula (IV) as shown above by the reaction of 5-(4′-bromomethyl biphenyl-2-yl)-1-trityl-1H-tetrazole of formula (III) and 2n-butyl-1,3-diazaspiro[4,4]-non-1-en-4-one of formula (II) as the HCl in presence of a base, with a phase transfer catalyst, in the presence of a hydrocarbon solvent, preferably toluene, optionally in presence of water as a second phase of the one-pot reaction system. The condensation of intermediate compounds of formulae (II) and (III) is preferably carried out at a temperature from about 20° C. to about 95° C., preferably at about 85° C. The reaction is allowed to proceed for a time that the skilled artisan will know to adjust according to the reaction temperature. For example, when the reaction temperature is about 90° C., a reaction time of between about 1 and 2 hours is usually sufficient. The reaction can be easily monitored using Thin Layer Chromatography. After reaction completion, the reaction is cooled to about 25° C. and the aqueous layer, if present, is separated, the reaction mass is washed with water and the layers are separated. A suitable acid, such as HCl (4N) is added to the reaction mass and stirred at about 55° C. for 40 minutes to 1 hour. The reaction can again be easily monitored by Thin Layer Chromatography and after reaction completion, the product can be filtered. Upon filtration, the product is washed with water and dried to yield irbesartan hydrochloride in hydrated form.

Workup

  1. customA synthetic one-pot process as provided by the present invention
  2. customis preferably carried out at a temperature from about 20° C. to about 95° C., preferably at about 85° C
  3. customis about 90° C.
  4. customa reaction time of between about 1 and 2 hours
  5. customThe reaction
  6. customAfter reaction completion
  7. customthe aqueous layer, if present, is separated
  8. washthe reaction mass is washed with water
  9. customthe layers are separated
  10. additionA suitable acid, such as HCl (4N) is added to the reaction mass
  11. customThe reaction
  12. customafter reaction completion
  13. filtrationthe product can be filtered
  14. filtrationUpon filtration
  15. washthe product is washed with water
  16. customdried

Sources & evidence

ORD record
ord-055652ad144b4f9db3cd3196caca8e60
Source dataset
uspto-grants-2010_09
Patent number
US07799928B2

Linked notes

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