Lamotrigine → HCID 178511371, compound

HRID 2270885Notes

Reaction equation

HRID 2270885 reaction equation
[CH:1]1[CH:6]=[C:5]([Cl:7])[C:4]([Cl:8])=[C:3]([C:9]2[N:14]=[N:13][C:12]([NH2:15])=[N:11][C:10]=2[NH2:16])[CH:2]=1.ClC1C(Cl)=CC=CC=1C(C#N)=O.ClC1C(Cl)=CC=CC=1C(OC(=O)C1C=CC=C(Cl)C=1Cl)=O.C(=O)(O)O.NNC(N)=N>S(=O)(=O)(O)O>[Cl:8][C:4]1[C:5]([Cl:7])=[CH:6][CH:1]=[CH:2][C:3]=1/[C:9](=[N:14]/[NH:13][C:12]([NH2:15])=[NH:11])/[C:10]#[N:16]

Participants

6

Reactant 4

HCID 3878LamotrigineHCID 2735968(2,3-Dichlorophenyl)oxoacetonitrile2×HCID 20714991Benzoic acid, 2,3-dichloro-, anhydride with 2,3-dichlorobenzoic acidHCID 178513185HCID 178513185, compound

Product 1

HCID 178511371HCID 178511371, compound

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Procedure

The synthesis of lamotrigine is illustrated in Reference Example 1. 2,3-Dichlorobenzoyl cyanide, which is intermediate 1.4 in that synthesis, may contain up to 10% of 2,3-dichlorobenzoic anhydride as a contaminant. When the 2,3-dichlorobenzoyl cyanide is treated with a solution of aminoguanidine bicarbonate in sulphuric acid, which is step (d) in Reference Example 1, the adduct (Z)-2-(2,3-dichlorophenyl)-2-(guanidinoimino)acetonitrile (intermediate 1.5) is produced. The anhydride contaminant can then react with the latter adduct to form (Z)-2-(2,3-dichlorophenyl)-2-[N′-(2,3-dichlorobenzoyl)guanidinoimino]acetonitrile, which is the direct precursor to compound B. Cyclisation of the precursor in propan-1-ol under reflux yields compound B.

Workup

  1. customin that synthesis

Sources & evidence

ORD record
ord-52efb0685c5e40b7bbd602fafabebd66
Source dataset
uspto-grants-2001_12
Patent number
US06333198B1

Reaction notes

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