Synthesis of lactams
View Patent ↗Methods for the synthesis of lactams are presented whereby a carboxylic acid of the formula HOOC—OR—NH-LG, wherein OR is an organic moiety and LG is a leaving group, is reacted with an acid, such as an organic acid, in particular a strong acid, and a dehydrating agent, which may be one in the same such as a strong acid anhydride, such that the amount of acid added allows for the desired transformation to take place without the loss of the leaving group (LG) before the cyclization, and recovering the lactam.
1. A compound of the formulae (QQQ):
wherein
R 37 is H, C 1 -C 3 alkyl, halogen, or haloalkyl;
R 31 is aryl, alkyl, cycloalkyl, or haloalkyl, wherein each of said alkyl, cycloalkyl, and haloalkyl groups optionally includes O or N heteroatoms and two R 31 s on adjacent ring atoms or on the same ring atom together with the ring atom(s) to which they are attached optionally form a 3-8-membered cycle;
yy is 0, 1, 2, 3, or 4;
ZZ is (CH 2 ) xx — wherein xx is 1, 2, 3, or 4, or —O—(CH 2 ) xx — wherein xx is 2, 3, or 4;
Y is —N—;
L, as allowed by valance, is hydrogen, aryl, heteroaryl, C 1 -C 8 alkoxy, aryloxy, heteroaryloxy, C 1 -C 8 alkyl, cycloalkylalkyl, -TT-RR, C 3 -C 8 cycloalkyl, or cycloalkyl containing one or more heteroatoms selected from N, O, and S;
TT is an C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl linker;
RR is a hydroxyl, C 1 -C 6 alkoxy, amino, C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, C 6 -C 10 aryl, heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O, and S, C 3 -C 10 carbocycle, or heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S; and
R 65 is Br, I, F, SMe, Saryl, Sheteroaryl, SOMe, SO 2 Me, SOalkyl, SO 2 alkyl, SOcycloalkyl, SO 2 cycloalkyl, SOaryl, SO 2 aryl, hydroxy, hydroxyalkyl, hydroxyaryl, or hydroxyheteroaryl.
2. The compound of claim 1 , wherein R 65 is SMe, SOMe, SO 2 Me, SOalkyl, SO 2 alkyl, SOaryl, or SO 2 aryl.
3. The compound of claim 1 , wherein L is hydrogen.
4. The compound of claim 1 , wherein xx is 2.
5. The compound of claim 1 , wherein R 37 is hydrogen.
6. The compound of claim 1 , wherein R 65 is SMe or SOMe.
7. The compound of claim 1 , wherein R 65 is SOalkyl or SOaryl.
8. The compound of claim 1 , wherein R 65 is SO 2 alkyl.
9. The compound of claim 1 , wherein R 65 is SO 2 Me.
10. The compound of claim 9 , wherein L is hydrogen.
11. The compound of claim 10 , wherein xx is 2.
12. The compound of claim 11 , wherein R 37 is hydrogen.
13. The compound of claim 1 , wherein the compound is
14. The compound of claim 1 , wherein the compound is
15. The compound of claim 1 , wherein the compound is
16. The compound of claim 1 , wherein the compound is
17. The compound of claim 1 , wherein the compound is