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These compounds were reacted with acyl chlorides 3, 4 and 5. Compound 3 is commercially
available and compounds 4 and 5 were obtained from commercially available di-esters by
monohydrolysis with MeOH/H 2 O/KOH followed by treatment of the resulting carboxylic acids with
Cl 2 SO (Figure 2).
Figure 2. Formula 3 and synthesis of compounds 4 and 5
O
O
Cl
OMe
Commercially available
3
O
O O O
MeO OR Cl OR
R 1
R 1 R 2
R 2
i) KOH,
ii) Cl 2 SO
i)
ii)
4: R=R 1 =Et, R 2 =H (88%)
5: R=Me, R 1 =R 2 =Et (86%)
The reaction of acyl chlorides 3, 4 and 5 with the amines 1 and 2 in CH 2 Cl 2 in the presence of
Et 3 N at room temperature gave the ester derivatives 6-10 (Figure 3).
Figure 3. Synthesis of esters 6-10
NH 2 t-Bu t-Bu
Cl
O O
OR
R 1 R 2
O
O
OR
R 2
HN R 1 t-Bu t-Bu
OMe OMe OMe
1
t-Bu NH 2
2
Cl
3: R=Me, R 1 =R 2 =H
4: R=R 1 =Et, R 2 =H
5: R=Me, R 1 =R 2 =Et
i)
O O
OR
R 1 R 2
t-Bu
OMe OMe OMe
6: R=Me, R 1 =R 2 =H (71%)
7: R=R 1 =Et, R 2 =H (51%)
8: R=Me, R 1 =R 2 =Et (36%)
O
HN
O
OR
R 1
R 2
2
OMe
2
OMe
3
3: R=Me, R 1 =R 2 =H
4: R=R 1 =Et, R 2 =H
i)
OMe
OMe
9: R=Me, R 1 =R 2 =H (23%)
10: R=R 1 =Et, R 2 =H (57%)
3
i) Et 3 N, CH 2 Cl 2 , r.t.
Aminolysis of these compounds with butylamine at reflux temperature gave malonamide
derivatives 11-15, as described in Figure 4.
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