Methyl bromoacetate → HCID 15851016, compound
Reaction equation
[I:1][C:2]1[C:3](=[O:9])[NH:4][C:5](=[O:8])[NH:6][CH:7]=1.Br[CH2:11][C:12]([O:14][CH3:15])=[O:13]>>[I:1][C:2]1[C:3](=[O:9])[NH:4][C:5](=[O:8])[N:6]([CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH:7]=1Participants
Procedure
Astoundingly, as can be seen from FIG. 2, it was the use of a modification of the Heck reaction (Heck, J. Am. Chem. Soc. 90 (1968), 5518), of all possible options, which led to the desired C—C linkage. 5-Iodouracil (5) was first of all alkylated with methyl bromoacetate to give methyl 5-iodouracil-1-acetate (6). The Heck reaction of 6 with Z-protected allylamine in the presence of Pd(OAc)2 and triphenylphosphine in absolute acetonitrile was carried out with the exclusion of air and at a superelevated temperature (bath temperature of 110° C.), and yielded the compound (7) together with a small portion of the oxidized byproduct (8). The methyl ester (7) was then hydrolyzed to give the free acid (9), which was reacted with methyl 2-Boc-aminoethylglycine (10) in analogy with the method of Dueholm et al., (J. Org. Chem. 59 (1994), 5767). The desired amino-modified thymine PNA building block (11) was obtained after the ester had been subjected to alkaline hydrolysis.
Workup
- customthe use of a modification of the Heck reaction (Heck, J. Am. Chem. Soc. 90 (1968), 5518)
Sources & evidence
- ORD record
- ord-f4b3b776298d4c1b823873a293a59133
- Source dataset
- uspto-grants-2002_05
- Patent number
- US06388061B1
Reaction notes
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