US 11,981,688 B2
Methods of preparing cytotoxic benzodiazepine derivatives
Michael Reardon, North Attleboro, MA (US); and Richard A. Silva, Needham, MA (US)
Assigned to IMMUNOGEN, INC., Waltham, MA (US)
Filed by IMMUNOGEN, INC., Waltham, MA (US)
Filed on Jun. 15, 2022, as Appl. No. 17/841,046.
Application 17/841,046 is a continuation of application No. 17/060,611, filed on Oct. 1, 2020, granted, now 11,396,519.
Application 17/060,611 is a continuation of application No. 16/679,563, filed on Nov. 11, 2019, granted, now 10,851,117, issued on Dec. 1, 2020.
Claims priority of provisional application 62/758,814, filed on Nov. 12, 2018.
Prior Publication US 2023/0045079 A1, Feb. 9, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 487/04 (2006.01); C07C 231/12 (2006.01); C07C 233/07 (2006.01); C07C 319/20 (2006.01); C07C 321/20 (2006.01); C07D 519/00 (2006.01)
CPC C07D 519/00 (2013.01) [C07C 231/12 (2013.01); C07C 233/07 (2013.01); C07C 319/20 (2013.01); C07C 321/20 (2013.01); C07D 487/04 (2013.01)] 20 Claims
 
1. A method of preparing a compound of formula (IVA′):

OG Complex Work Unit Chemistry
comprising the steps of:
1) reacting a compound of formula (IA′):

OG Complex Work Unit Chemistry
with cyanuric chloride to form a compound of formula (IIA′):

OG Complex Work Unit Chemistry
2) reacting the compound of formula (IIA′) with a compound of formula (b):

OG Complex Work Unit Chemistry
to form a compound of formula (VILA′):

OG Complex Work Unit Chemistry
3) reacting the compound of formula (VITA′) with a sulfonating agent to form a compound of formula (VIIIA′):

OG Complex Work Unit Chemistry
 and
4) reacting the compound of formula (VIIIA′) with a compound of formula (a):

OG Complex Work Unit Chemistry
to form the compound of formula (IVA′), wherein X1 is a sulfonate ester.