2,4-Dimethoxy-3-iodopyrimidine → (s)-n-Methyl-n-(tert-butoxycarbonyl)-5-(2,4-dimethoxy-5-pyrimidinyl)-4-penten-2-amine
Reaction equation
CN[C@H](CC=CC1C(O)=NC(O)=NC=1)C.[CH3:16][N:17]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@H:18]([CH2:20][CH:21]=[CH2:22])[CH3:19].[CH3:30][O:31][CH:32]1[N:37](I)[C:36]([O:39][CH3:40])=[CH:35][CH:34]=[N:33]1>[Pd]>[CH3:16][N:17]([C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])[C@H:18]([CH2:20][CH:21]=[CH:22][C:35]1[C:36]([O:39][CH3:40])=[N:37][C:32]([O:31][CH3:30])=[N:33][CH:34]=1)[CH3:19]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
Scheme I shows the synthesis of (S)-N-methyl-5-(2,4-dihydroxy-5-pyrimidinyl)-4-penten-2-amine. In this synthesis, the previously described (S)-N-methyl-N-(tert-butoxycarbonyl)-4-penten-2-amine is subjected to Heck-type coupling conditions by reaction with a 2,4-dimethoxy-3-iodopyrimidine in the presence of a palladium catalyst to form (S)-N-methyl-N-(tert-butoxycarbonyl)-5-(2,4-dimethoxy-5-pyrimidinyl)-4-penten-2-amine. The methoxy groups can be converted to hydroxy groups, concurrent with the cleavage of the amine protecting group, by reaction with trimethylsilyl iodide in methanol/dichloromethane to yield the desired N-methyl-5-(2,4-dihydroxy-5-pyrimidinyl)-4-penten-2-amine compound as a hydroiodide salt. Alternately, the tert-butoxycarbonyl protecting group can be selectively removed by trifluoroacetic acid, as described previously, to give the (S)-N-methyl-5-(2,4-dimethoxy-5-pyrimidinyl)-4-penten-2-amine. Cleavage of the methyl ethers using 48% HBr then provides (S)-N-methyl-5-(2,4-dihydroxy-5-pyrimidinyl)-4-penten-2-amine.
Workup
- customIn this synthesis
Sources & evidence
- ORD record
- ord-2b912c6f3c5d40369c0701a2a49bac8a
- Source dataset
- uspto-grants-2006_05
- Patent number
- US07045538B2
Reaction notes
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