Trifluoroacetic acid → (4E)-N-methyl-5-(6-oxazolo[4,5-b]pyridinyl)-4-penten-2-amine
Reaction equation
Br[C:2]1[CH:3]=[C:4]2[O:10][CH:9]=[N:8][C:5]2=[N:6][CH:7]=1.[CH3:11][N:12](C(OC(C)(C)C)=O)[CH:13]([CH2:15][CH:16]=[CH2:17])[CH3:14].FC(F)(F)C(O)=O>[Pd]>[CH3:11][NH:12][CH:13]([CH2:15]/[CH:16]=[CH:17]/[C:2]1[CH:3]=[C:4]2[O:10][CH:9]=[N:8][C:5]2=[N:6][CH:7]=1)[CH3:14]Participants
Procedure
In another example, 6-bromooxazolo[4,5-b]pyridine, when submitted sequentially to palladium catalyzed coupling to N-methyl-N-(tert-butoxycarbonyl)-4-penten-2-amine and deprotection with trifluoroacetic acid, gives (4E)-N-methyl-5-(6-oxazolo[4,5-b]pyridinyl)-4-penten-2-amine. The requisite 6-bromooxazolo[4,5-b]pyridine can be produced from 2-amino-5-bromo-3-pyridinol by condensation with formic acid or a trialkyl orthoformate, using methodology similar to that of M-C. Viaud et al., Heterocycles 41: 2799-2809 (1995). The use of other carboxylic acids produces 2-substituted-6-bromooxazolo[4,5-b]pyridines, which are also substrates for the Heck reaction. The synthesis of 2-amino-5-bromo-3-pyridinol proceeds from furfurylamine (Aldrich Chemical Company). Thus, 5-bromo-3-pyridinol (produced from furfurylamine according to U.S. Pat. No. 4,192,946) can be chlorinated, using methods described by V. Koch et al., Synthesis, 499 (1990), to give 2-chloro-5-bromo-3-pyridinol, which in turn can be converted to 2-amino-5-bromo-3-pyridinol by treatment with ammonia.
Sources & evidence
- ORD record
- ord-362782627e644aed9dd974786157d8d5
- Source dataset
- uspto-grants-2008_12
- Patent number
- US07459469B2
Reaction notes
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