Science of Synthesis

Herr, R. J., Science of Synthesis, (2004) 17, 954.

A variant of the previous method involves the preparation of hetareno[2,3-b][1,5]benzodiazepin-5-ones by bis-coupling reactions between benzene-1,2-diamines and 2-chloronicotinic acids or their heterocyclic derivatives (‌Scheme 26‌). Reaction of substituted benzene-1,2-diamines ‌89‌ with 2-chloronicotinic acid (‌90‌) at high temperatures (140–150°C) in inert solvents provides 6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-5-ones ‌91‌ in synthetically useful yields, as shown in ‌Scheme 26‌.[‌106‌–‌108‌] This transformation involves addition of one amino group of ‌89‌ to the α-chloropyridine center, followed by intramolecular amide formation by condensation to ‌91‌.[‌106‌–‌111‌] In an analogous fashion, 2-nitrophenylamines ‌92‌ may be condensed with 2-chloro-3-carboxyl nitrogen heterocycles [such as the 2,4-dichloro-5-pyrimidinecarbonyl chloride (‌93‌)] to provide the 2-nitro­phenyl­amide ‌94‌. Dichloropyrimidine (2-nitrophenyl)amide ‌94‌ is reduced with iron in acidic media to provide a 2-aminophenyl intermediate, which upon heating with a resin-bound base generates 2-chloro-9-(trifluoromethyl)-6,11-dihydro-5H-pyrimido[4,5-b][1,5]benzodiazepin-5-one (‌95‌) in an acceptable yield for the three-step process.[‌111‌]

‌Meeeee 88‌ Meeeeeee ee Meeeeee-8,8-eeeeeeee eeee 8-Meeeeeeeeeeeeee Meeee[‌888‌–‌888‌]

‌Meeeeeeeeee 88‌

Meeeeeeeeeee Meeeeeeeee

8-Meeeee-8,88-eeeeeee-8M-eeeeee[8,8-e][8,8]eeeeeeeeeeeee-8-eee (‌88‌, M8 = Me; M8 = M8 = M); Meeeeee Meeeeeeee:[‌888‌]

M eeeeeee ee 8-eeeeeeeeeeeee-8,8-eeeeeee (‌88‌, M8 = Me; M8 = M8 = M; 88.8 e, 888 eeee) eee 8-eeeeeeeeeeeeeee eeee (‌88‌; 88.8 e, 888 eeee) ee 8-eeeeeeeeeeeee (888 eM) eee eeeeee ee 888°M eeeee M8 eee 8 e. Mee eeeeee eeeeeee eee eeeeee eeee eeeeeee eee eee eee eeeeeeeee eeeeee eeee eeeeeeeee ee eeeeeeeeee. Mee eeeeee eeee eeeeee eeee M8M, eeeee eee eeeeeeeeeeeeee (8,8-eeeeeee/M8M 8:8) eeee e eeeeeeee eeeeeeeee ee eeeeeee (M8 = Me; M8 = M8 = M) ee e eeeee eeeeee eeeee; eeeee: 88.8 e (88%).

8,8-Meeeeeee-M-[8-eeeee-8-(eeeeeeeeeeeeeee)eeeeee]-8-eeeeeeeeeeeeeeeeeeeee (‌88‌); Meeeeee Meeeeeeee:[‌888‌]

M eeee ee 8-eeeee-8-eeeeeeeeeeeeeeeeeeeeee (‌88‌, 888 ee, 8.8 eeee) eee 8,8-eeeeeeee-8-eeeeeeeeeeeeeeeeee eeeeeeee (‌88‌; 888 ee, 8.8 eeee) ee MMM (88 eM) eee eeeeeeee eeeee M8 eee 88 e. Mee eeeeeee eee eeeeeee eeee eee eeeeee eeeeeee eeeee eeeeeee eeeeeeee eee eee eeeeeee eee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (eeeeee eee, MMMe8/eeeeeee 8:8) ee eeeeeee ‌88‌ ee e eeeee eeeee; eeeee: 888 ee (88%).

8-Meeeee-8-(eeeeeeeeeeeeeee)-8,88-eeeeeee-8M-eeeeeeee[8,8-e][8,8]eeeeeeeeeeeee-8-eee (‌88‌); Meeeeee Meeeeeeee:[‌888‌]

M eeee ee ‌88‌ (88 ee, 8.88 eeee), Me eeeeee (88 ee) eee eeeee MMe (8.8 eM) ee MeMM (8.8 eM) eee eeeeeee ee ee eeeee M8 eee 88 e. Mee eeeeee eeee eeeeeee ee eeeeeeeeee eee eee eeeeeeee eeeeeeee eeee eeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeeee ee MMM (8 eM), eeeeeee eeee Meeeeeeee M-88 (888 ee) eee eee eeeeeeeeee eee eeeeeee ee ee eeeee M8 eee 88 e. Mee eeeeee eeee eeeeeee ee eeeeeeeeee eee eee eeeeeeee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeeee 88:88) ee eeeeeee ‌88‌ ee e eeeee; eeeee: 88 ee (88%).

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) M 88e8, 888.