Malononitrile → 3-amino-5-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile

HRID 1750307Notes

Reaction equation

HRID 1750307 reaction equation
O(C1C=CC(C(O)=O)=CC=1)C1C=CC=CC=1.C(#N)CC#N.[C:22]([C:24]([C:40]#[N:41])=[C:25](O)[C:26]1[CH:31]=[CH:30][C:29]([O:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:28][CH:27]=1)#[N:23].C[Si](C=[N+:47]=[N-:48])(C)C.O.NN>>[NH2:23][C:22]1[C:24]([C:40]#[N:41])=[C:25]([C:26]2[CH:31]=[CH:30][C:29]([O:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:28][CH:27]=2)[NH:48][N:47]=1

Participants

6

Reactant 5

HCID 8010MalononitrileHCID 24654Hydrazine hydrate (1:1)HCID 751824-Phenoxybenzoic acidHCID 167693TrimethylsilyldiazomethaneHCID 223471552-(Hydroxy-(4-phenoxyphenyl)methylene)propanedinitrile

Product 1

HCID 223467843-amino-5-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile

Procedure

First, 4-amino-3-(4-phenoxyphenyl)-1H-pyrazole[3,4-d]pyrimidine may be prepared in accordance with procedures described in WO 2008/039218, for instance by converting 4-phenoxybenzoic acid to the corresponding acyl chloride (by using thionyl chloride), which latter product may be reacted with malononitrile to prepare 1,1-dicyano-2-hydroxy-2-(4-phenoxyphenyl)ethene. The methoxy moiety is then methylated using trimethylsilyldiazomethane, and that methylated product is the treated with hydrazine hydrate to provide 3-amino-4-cyano-5-(4-phenoxyphenyl)pyrazole, which is reacted with formamide to provide 4-amino-3-(4-phenoxyphenyl)-1H-pyrazole[3,4-d]pyrimidine, as illustrated in the following scheme:

Sources & evidence

ORD record
ord-a7d1086aa96e4c3f8bf91b263dfca458
Source dataset
uspto-grants-2015_10
Patent number
US09156847B2

Reaction notes

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