Hydrochloric Acid → 3-(4-Hydroxybutyl)-1H-indole-5-carbonitrile

HRID 1056542Notes

Reaction equation

HRID 1056542 reaction equation
[CH:1]1[C:6]([C:7]#[N:8])=[CH:5][C:4]2[C:9]([CH2:12][CH2:13][CH2:14][CH2:15]N3CCN(C4C=CC5OC(C(N)=O)=CC=5C=4)CC3)=[CH:10][NH:11][C:3]=2[CH:2]=1.ClCCCC(C1C2C(=CC=C(C#N)C=2)NC=1)=[O:39].[BH4-].[Na+].Cl>C(O)(C)C>[OH:39][CH2:15][CH2:14][CH2:13][CH2:12][C:9]1[C:4]2[C:3](=[CH:2][CH:1]=[C:6]([C:7]#[N:8])[CH:5]=2)[NH:11][CH:10]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 6918314VilazodoneHCID 102205283-(4-chlorobutanoyl)-1H-indole-5-carbonitrile

Product 1

HCID 121509853-(4-Hydroxybutyl)-1H-indole-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

As per the process described in CN'932 publication, vilazodone is prepared by reacting 3-(4-chlorobutyryl)-1H-indole-5-carbonitrile with sodium borohydride in isopropanol at reflux temperature, followed by treating the reaction mass with dilute hydrochloric acid and subsequent workup and then subjecting to column chromatography purifications to produce 3-(4-hydroxybutyl)-1H-indole-5-carbonitrile. The hydroxylbutyl intermediate obtained is then subjected to sulfonylation using a sulfonylating agent selected from p-toluenesulfonyl chloride, benzenesulfonyl chloride, methanesulfonyl chloride and trifluoromethanesulfonyl chloride to produce corresponding sulfonylated intermediate, which is then condensed with 5-(1-piperazinyl)benzofuran-2-carboxamide in acetonitrile to produce vilazodone.

Workup

  1. customis prepared
  2. temperatureat reflux temperature

Sources & evidence

ORD record
ord-fc0bc80133bf4187b039efd2db85355e
Source dataset
uspto-grants-2016_07
Patent number
US09399630B2

Reaction notes

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