Hydrogen Cyanide → 5-Amino-4-(beta-amino-alpha-hydroxyethyl)-1-methylpyrazole
Reaction equation
[NH2:1][C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[CH:8]=[O:9].[CH:10]#[N:11]>[Ni].C(O)(=O)C>[NH2:1][C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[CH:8]([OH:9])[CH2:10][NH2:11]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Procedure
The objective was to build the 3,4,5-trihydro-1,3-diazepin-5-ol moiety using as a template the 5-amino-1-methylpyrazole-4-carboxaldehyde, 6. This aldehyde may be readily prepared from the partial reduction and in situ hydrolysis of the corresponding nitrile, compound 5. ##STR5## The presentation of the aldehyde 6 involved the reduction of nitrile 5 with an activated form of Raney nickel (see Dominquez et al, J. Org. Chem. 1961, 26, 1625; T-1 Raney Nickel) in 70% aqueous acetic acid. Through a modification of the Kiliani-Fischer cyanohydrin homologation sequence, it was proposed to add hydrogen cyanide in this aldehyde and subsequently to reduce the nitrile portion of the resulting cyanohydrin 7. ##STR6## This transformation would provide the 5-amino-4-(β-amino-α-hydroxyethyl)-1-methylpyrazole, intermediate 8. This intermediate would be subsequently ring closed with triethylorthoformate to afford the requisite 4,5,6-trihydro-1-methylpyrazolo[5,4-d] [1,2] diazepin-4-ol, compound 9. ##STR7##
Sources & evidence
- ORD record
- ord-e9c769b65584499d8937c2f50990667f
- Source dataset
- uspto-grants-1990_06
- Patent number
- US04935505
Reaction notes
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