2-Chloro-5-fluoro-3-nitropyridine → 7-Chloro-4-fluoro-1H-pyrrolo[2,3-C]pyridine
Reaction equation
[Cl:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][C:5]([F:11])=[CH:4][N:3]=1.[CH:12]([Mg]Br)=[CH2:13]>>[F:11][C:5]1[CH:4]=[N:3][C:2]([Cl:1])=[C:7]2[C:6]=1[CH:12]=[CH:13][NH:8]2Participants
Procedure
The chemistry in Scheme 3 provided the derivatives which corresponds to general formula 5 and has a 6-aza ring and R2=F and R4=Cl. In particular, reaction of 2-chloro-5-fluoro-3-nitro pyridine with 3 equivalents of vinyl Magnesium bromide using the typical conditions described herein will provide 4-fluoro-7-chloro-6-azaindole in high yield. Addition of this compound to a solution of aluminum trichloride in dichloromethane stirring at ambident temperature followed 30 minutes later with chloromethyl or chloroethyl oxalate provided an ester. Hydrolysis with KOH as in the standard procedures herein provided an acid salt which reacted with piperazines 4 (for example 1-benzoyl piperazine) in the presence of DEPBT under the standard conditions described herein to provide the compound 5 described just above. The compound with the benzoyl piperazine is N-(benzoyl)-N′-[(4-fluoro-7-chloro-6-azaindol-3-yl)-oxoacetyl]-piperazine and is compound 5av. The compound with the (R)-methyl benzoyl piperazine is 5av′ (R)-N-(benzoyl)-3-methyl-N′-[(4-fluoro-7-chloro-6-azaindol-3-yl)-oxoacetyl]-piperazine and is compound 5av′.
Workup
- customThe chemistry in Scheme 3 provided the derivatives which
Sources & evidence
- ORD record
- ord-50bd4169dfe44ab68dcf5427254448f9
- Source dataset
- uspto-grants-2003_10
- Patent number
- US06632819B1
Reaction notes
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