2-Amino-5-cyanopyridine → 2-(5-Bromofuran-2-yl)-imidazo[1,2-a]pyridine-6-carbonitrile
Reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=1.Br[CH2:11][C:12]([C:14]1[O:15][C:16]([Br:19])=[CH:17][CH:18]=1)=O>>[Br:19][C:16]1[O:15][C:14]([C:12]2[N:1]=[C:2]3[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]3[CH:11]=2)=[CH:18][CH:17]=1Participants
Procedure
Referring now to Scheme 2, the acetate salt of 2-[5-(4-Amidinophenyl)-furan-2-yl]-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridine-6-carboxamidine (7) was synthesized from 2-[5-(4-Cyanophenyl)-furan-2-yl]-imidazo[1,2-a]pyridine-6-carbonitrile (4a), through the bis-O-acetoxyamidoxime followed by hydrogenation in glacial acetic acid. Compound 4a was obtained in four steps starting with two successive brominations of 2-acetylfuran first with N-bromosuccinimide, and second with bromine to form 2-Bromo-1-(5-bromofuran-2-yl)-ethanone (2) in a moderate yield. A condensation reaction between 6-Amino-nicotinonitrile and compound 2 gave 2-(5-Bromofuran-2-yl)-imidazo[1,2-a]pyridine-6-carbonitrile (3a). A subsequent Suzuki coupling of 3a with 4-Cyanophenyl boronic acid furnished 4a in good yield. Interestingly, 2-[5-(4-Amidinophenyl)-furan-2-y]-imidazo[1,2-a]pyridine-6-carbox-amidine acetate salt (8a) was obtained from 4a, through the bis-O-acetoxyamidoxime followed by hydrogenation in a mixture of ethanol/ethylacetate. Thus, by choice of hydrogenation solvent the saturated or unsaturated imidazo[1,2-a]pyridine can be obtained.
Sources & evidence
- ORD record
- ord-a21b8479c83f40d1add5c1bb8a59c927
- Source dataset
- uspto-grants-2008_10
- Patent number
- US07432278B2
Reaction notes
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