Methods for preparing diazonamides
View Patent ↗This invention relates to novel macrocyclic lactams intermediates useful for the preparation of diazonamide analogs. This invention also relates to a novel electrochemical oxidative cyclization for the preparation of such macrocyclic lactams, and their further elucidation to provide diazonamide analogs.
1. A compound of formula (I):
or a salt thereof; wherein:
R 1 is C1-C4 alkyl;
R 2 is H or Me;
R 3 is —NR 4 R 5 ;
R 4 is H, or C1-C4 alkyl;
R 5 is H, or C1-C8 alkyl, C1-C8 heteroalkyl, C6-C14 arylalkyl, C6-C14 heteroarylalkyl, arylsulfonyl, trialkylsilyl, or alkoxycarbonyl, each of which may be optionally substituted; or —C(═X)R′ where X is O, S, or NH, and R′ is optionally fluorinated C1-C8 alkyl, C2-C8 alkenyl, C5-C12 aryl, or C6-C14 arylalkyl, each of which may be optionally substituted;
R 6 is H, or an arylalkyl, arylsulfonyl, acyl or alkoxycarbonyl;
R 7 is H, or halo, —CN, optionally substituted C1-C6 acyl, —COOR 8 , or —C(O)NR 9 2 ;
R 8 is H, or C1-C8 alkyl, C2-C8 alkenyl, C5-C6 aryl, C6-C14 arylalkyl, or trialkylsilyl;
R 9 is H, or C1-C8 alkyl, C2-C8 alkenyl, C5-C6 aryl, C6-C14 arylalkyl, C6-C14 heteroarylalkyl, —OH, or C1-C4 alkoxy, each of which may be optionally substituted; or two R 9 on the same N can optionally cyclize to form a ring; and
Y′ is H or halo, and Y is halo or —OR 10 , where R 10 is H, or is optionally fluorinated alkylsulfonyl or arylsulfonyl.
2. The compound of claim 1 wherein:
R 1 is isopropyl;
R 2 is H;
R 4 is H;
R 6 is H; and
Y′ is H, and Y is bromo or triflate (-OTf).
3. The compound of claim 1 wherein:
R 7 is H, or halo, —CN, or optionally substituted C1-C6 acyl.
4. The compound of claim 1 wherein:
R 1 is isopropyl;
R 2 is H;
R 4 is H;
R 6 is H;
R 7 is H, or halo, —CN, or optionally substituted C1-C6 acyl; and
Y′ is H, and Y is bromo or triflate (—OTf).
5. The compound of claim 1 having the structure:
wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Y and Y′ are defined as for formula (I).
6. A compound of a formula selected from the group consisting of:
7. The compound of claim 6 wherein the formula is:
8. The compound of claim 6 wherein the formula is:
9. The compound of claim 6 wherein the formula is:
10. The compound of claim 6 wherein the formula is:
11. The compound of claim 6 wherein the formula is:
12. A compound of a formula selected from the group consisting of:
13. The compound of claim 12 wherein the formula is:
14. The compound of claim 12 wherein the formula is: