Phosgene → 2-Chloro-1-[2-(1-methylethyl)pyrazolo[1,5-a]pyridin-3-yl]-1-propanone
Reaction equation
[CH3:1][CH:2]([C:4]1[C:12]([C:13]([CH:15](N)[CH3:16])=[O:14])=[C:11]2[N:6]([CH:7]=[CH:8][CH:9]=[CH:10]2)[N:5]=1)[CH3:3].C(C1C=C2C=CC=CN2N=1)(C)C.[Cl:30]C(C)C=O.ClC(Cl)=O.ClC(C)C(Cl)=O.[Cl-].[Al+3].[Cl-].[Cl-]>>[Cl:30][CH:15]([CH3:16])[C:13]([C:12]1[C:4]([CH:2]([CH3:3])[CH3:1])=[N:5][N:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=12)=[O:14]Participants
Reactant 6
Product 1
Procedure
The second step in the synthesis of AV1013 involves reacting the intermediate (IPPP), with 2-chloro-propan-1-one under Friedel-Craft conditions to synthesize the corresponding chloroketone. Thus, reaction of isopropylpyrazolo[1,5-a]pyridine (IPPP) with 2-chloropropionyl chloride in the presence of aluminum chloride (Example 1, Step 2), gave 2-chloro-1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)propan-1-one (i.e., 2-chloro-desmethylibudilast). In an alternate strategy as described in Example 8, IPPP is allowed to react with propanoyl chloride under Friedel-Crafts acylation conditions to give desmethylibudilast. It should be noted that the terms desmethylibudilast and Nor-methyl ibudilast are used interchangeably throughout the specification. The obtained Nor-methyl ibudilast is then converted to the corresponding alpha-chloroketone (2-chloro-desmethylibudilast), by techniques known in the chemical art, for example, via chlorination.
Sources & evidence
- ORD record
- ord-b27c89131407423cb3094b00b7421b0d
- Source dataset
- uspto-grants-2012_02
- Patent number
- US08119657B2
Reaction notes
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