Process for synthesizing oxidized lactam compounds

Patent metadata

Field	Value
Publication number	US-10011569-B2
Application number	US-201715483331-A
Country	US
Kind code	B2
Filing date	Apr 10, 2017
Priority date	May 4, 2010
Publication date	Jul 3, 2018
Grant date	Jul 3, 2018

Abstract

The invention provides a method for the synthesis of dehydrogenated lactam drugs of Formula I:

First claim

What is claimed:

1. A method for preparing a compound of Formula V, comprising the step of reacting a compound of Formula VA:

with a compound of Formula II:

in the presence of an acid, wherein
Each R A , R B , R C , and R D is independently selected from hydrogen, halogen, —CN, NH 2 , NR 100 R 101 , SR 100 , OR 100 , aliphatic, substituted aliphatic, aryl and substituted aryl; wherein R 100 and R 101 , are independently selected from hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
X is —S— or —O—;
X 2 is selected from CH and N;
R 1 , is selected from H, —C(R J )(R K )—OR 20 , —C(R J )(R K )—OC(O)OR 20 , —C(R J )(R K )—OC(O)R 20 , —C(R J )(R K )—OC(O)NR 20 R 21 , —(C(R J )(R K ))—OPO 3 MY, —(C(R J )(R K ))—OP(O)(OR 20 )(OR 21 ), —[C(R J )(R K )O] z —R 20 , —[C(R J )(R K )O] z —C(O)OR 20 , —[C(R J )(R K )O] z —C(O)R 20 , —[C(R J )(R K )O] z —C(O)NR 20 R 21 , —[C(R J )(R K )O] z —OPO 3 MY, —[C(R J )(R K )O] z —P(O) 2 (OR 20 )M and —[C(R J )(R K )O] z —P(O)(OR 20 )(OR 21 );
wherein each R J and R K is independently selected from hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
each R 20 and R 21 is independently selected from hydrogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
Y and M are the same or different and each is a monovalent cation; or M and Y together is a divalent cation; and
z is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R 2 is hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
n is selected from 0, 1, 2 or 3;
q is 0, 1, 2, 3, 4, 5, 6, 7, 8, or 9;
R 6 is independently absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl or substituted heterocyclyl;
R 7 and R 8 are independently selected from absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; and
wherein said compound of Formula VA contain a primary, secondary or tertiary amine having a pKa of about 6 to about 45.

2. The method according to claim 1 , wherein R 6 is selected from:

wherein R 100 R 101 , and R 103 are independently selected from hydrogen, halogen, optionally substituted C 1 -C 8 alkyl, optionally substituted C 2 -C 8 alkenyl, optionally substituted C 2 -C 8 alkynyl, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted C 1 -C 8 alkoxy, optionally substituted C 1 -C 8 alkylamino and optionally substituted C 1 -C 8 aryl.

3. The method according to claim 2 , wherein R 6 is selected from

4. A method according to claim 1 , wherein R 1 is selected from Tables 1-4.

TABLE 1

Assignees

• Alkermes Pharma Ireland Ltd

Inventors

• Remenar Julius F
• Blumberg Laura Cook
• Zeidan Tarek A

Classifications

• C07F9/65583

  each of the hetero rings containing nitrogen as ring hetero atom · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D215/22

  attached in position 2 or 4 · CPC title

• C07F9/650952

  having the nitrogen atoms in the positions 1 and 4 · CPC title