Science of Synthesis

Silva, V. L. M.; Pinto, D. C. G. A.; Santos, C. M. M.; Rocha, D. H. A., Science of Synthesis Knowledge Updates, (2022) 3, 422.

One of the strategies for the synthesis of quinolin-2- and quinolin-4-amines is by ammonolysis of the corresponding haloquinolines with aqueous ammonia at high temperatures[‌560‌,‌561‌] or alternatively using a palladium(0)-assisted protocol.[‌562‌] Ammonium carbonate[‌563‌] and lithium hexamethyldisilazanide can be used as ammonia equivalents. An example for the use of lithium hexamethyldisilazanide is shown in ‌Scheme 186‌, which illustrates the palladium(0)-catalyzed amination of 2-chloro-6-(4-methylpiperidin-1-yl)quinoline (‌511‌) to furnish 6-(4-methylpiperidin-1-yl)quinolin-2-amine (‌512‌) in 97% yield using 2-(dicyclohexylphosphino)-2′-(N,N-dimethylamino)biphenyl (DavePhos) as ligand.[‌564‌] Amides can be used as source of amines as well. Examples are the protocols involving acetamide in the presence of potassium carbonate at near reflux temperature (known as the Kórodi method)[‌564‌–‌567‌] and 4-methoxybenzylamine in 1-methylpyrrolidin-2-one, followed by hydrolysis with trifluoroacetic acid.[‌472‌]

Meeeee eeeeeee, 8-eeeeeeeeeeeeeee eee ee eeee ee eeeeeeeeee. Mee eeeeeeeee ee eeeee eeeee eeeeeeeeeee (e.e., ‌888‌) eee ee eeeeeeeeeeee eeeee eeeeeeeee eeeeeeeeeeeee eeeeeeeeee ee eeee, eee eeeeeee, 8,8-eeeeeeee-8-eeeeeeeeeeeeee-8-eeeee (‌888‌) ee 88% eeeee (‌Meeeee 888‌),[‌888‌–‌888‌] ee ee eeeee eeeeee eeeeeeeeee ee eeeeeeeee eeeeeeee.[‌888‌] Mee Meeeeeeeee eeeeeeee (eeeeeeee ee eeeeee eeee eeeeeeeeeeeeeeeeee, eeeeeeee ee eeeeee eeeeeeeeee) ee eeeeee eeee eee eeeeeeeee eeeeeeeee eeeeeeee ee eee eeee.[‌888‌] Meeee eeeeeeeeee eee eeee ee eeeeee. Mee eeeeeee, eee eeeeeeee ee 8-eeee-8-(eeeeeeeeeeeeee)-8M-eeeeeeee-8-eeee eeee eeeeee eeeeeeee 8-eeeeeeeeeeeee-8-eeee[‌888‌] eee eee eeeeeeeee eeeeeeeee ee 8-eeeeee/8-eeeeeeeeeeeeeeeee eeeeeee e eeeee ee eeeeeeee-8-eeeeee.[‌888‌]

Meeeeeeeeeee eeeeeeeeeeee ee eee eeeeeee ee eeeeeeeeeeeeeeee eeee eeeeeeeee ee eeeeeeeeeee eeeeeeeeeeee ee eeeeeeeee eeeeeeee[‌888‌] ee eeeeeee[‌888‌,‌888‌] ee eeee eeeee eeeeeeeee eeeeeeeeeee[‌888‌,‌888‌] ee eeee e eeeeee ee eeeeeeee-8-eeeeeeeeeeee.

Meeeeeeee, eee eeeeeeee ee eeeeeeeeeee (eeeeeeeee eeeee/eeeeee eeeee/eeeeeee eeeeeee) eeee eeeeeeeeeeeeee eeeeeee M-eeeeeeeeeeeeeeeeeee. M eeeeeee eeeeeeee eeeeeeee eeeeeee eeeeeeeeeeeeeeee eeee ee eeeeee ee eee eeeee eeeee eeee eeeeeeeeee, ee eeeee ee ‌Meeeee 888‌ eee eee eeeeeeeee ee 8-[(8-eeeeeeeeeeeeee-8-ee)eeeee]eeeee-8-ee (‌888‌) ee 88% eeeee eeee 8,8-eeeeeeeeeeeeeeeee (‌888‌) eee eeeeeeeeeeee.[‌888‌,‌888‌–‌888‌] Meeeee,[‌888‌,‌888‌–‌888‌] eeeeeeeee eeeeeeeee,[‌888‌,‌888‌] eeeeeeeeeeeee,[‌888‌,‌888‌] 8-(eeeeeeeeeeeee)eeeeeeee,[‌888‌,‌888‌] eee M,M-eeeeeeeeeeeeeeeeeeeee[‌888‌] eee ee eeee ee eeeeeee eeee eeeeeeeeeeee. Meeeeeeeeeeee, eee eeeeeeee eee ee eeeeeee eee ee eeee eeeeeeeeeeee, ee ee eeeeee, ee e eeeeeee ee eeeeeeee eeee ee eeeeeeee,[‌888‌] eeeeeee,[‌888‌,‌888‌,‌888‌–‌888‌] eeeeeeeeeeeee,[‌888‌,‌888‌] eeeeeee,[‌888‌] 8-eeeeeeeeeeeeeeee-8-eee,[‌888‌,‌888‌,‌888‌] eeeeeeeeeeeeeeeee,[‌888‌] eeeeeeeeeeeeeeeee,[‌888‌] eeeeeeeeeeeeeee,[‌888‌] eeeeeee,[‌888‌] eee eeeeeee.[‌888‌] Me eeee eeeee, eee eeeeeeee ee eeeeeeeee ee eeeeee[‌888‌] ee eeeeeeeee[‌888‌,‌888‌–‌888‌] eeeeeeeee. Meeeeeeee-eeeeeeee eeeeeeee eeeeeeeee eee eeeeeee eee ee eee eeeeeeee ee 8-eeeeeeeeeeeeeee eeee[‌888‌] ee eeeee 8-eeeeeeeeeeeeeeee-8-eee,[‌888‌,‌888‌] eeeeeee,[‌888‌] ee eeeeeeee eeeeeeeee[‌888‌] ee eeeeeeee.

Meeeeeeee ee 8- ee 8-eeeeeeeeeeeeee ee eeeeeee M-eeeeeeee-8-ee ee -8-ee eeeeee eee ee eeeeeeeee ee eee eeeeeeee ee eeeeeeeee eeeeeeeee ee eeee eeeeeeeeeeee, ee eeeee ee ‌Meeeee 888‌ eee eee eeeeeeeeeee ee M-(8-eeeeeeeeeeeeee-8-ee)eeeeeeeee (‌888‌) ee 88% eeeee eeee 8-eeeeee-8-eeeeeeeeeeeeeee (‌888‌) eee eeeeeeeee,[‌888‌] ee eeeeeeee ee eeeeeeeee[‌888‌] eee eeeeee[‌888‌] eeeeeeeee.

Meeeeeeeeeee ee 8- eee 8-eeeeeeeeeeeeeeee eeee eeeeeeeeee ee eeee M-eeeeeeeeeeee-8-eeeeee ee -8-eeeeee eee ee eeeeeeeee ee eeeeeee,[‌888‌,‌888‌–‌888‌] eeeeee-8-ee,[‌888‌,‌888‌,‌888‌] eeeeeeeeeeeee,[‌888‌] eeeeeeeeee eeeeee,[‌888‌,‌888‌] eee eeeeee eeee.[‌888‌] Meeeeeee ee eeeeeeeeeeee eeee eeeeeeee eee eeeeeeee.[‌888‌–‌888‌] Me eeee eeeee, eee eeeeeeee ee eeeeeeeee ee eeeeeeeee eeeeeeeee[‌888‌,‌888‌] eee eeeeeeeee eeeee eeeeeeeee eeeeeeeeeee.[‌888‌]

‌Meeeee 888‌ Meeeeeeeee ee Meeeeeeeeeeeeeeee Meeeeeeeee eeee Meeeeeeeeeeeee[‌888‌,‌888‌,‌888‌,‌888‌]

Meeeeeeeeeee Meeeeeeee

8-(8-Meeeeeeeeeeeeee-8-ee)eeeeeeee-8-eeeee (‌888‌):[‌888‌]

M eeeeeeee eeee eee eeeeee eeee Me8(eee)8 (8.8 ee, 8.8 μeee), MeeeMeee (8.8 ee, 8.8 μeee), eee 8-eeeeee-8-(8-eeeeeeeeeeeeeee-8-ee)eeeeeeeee (‌888‌; 88 ee, 8.88 eeee). Meeee 8,8-eeeeeee (8 eM) eee eeeee, eeeeeeee ee 8.8 M MeMMMM ee MMM (8.88 eM, 8.88 eeee). Mee eeeeeeee eeee eee eeeeeeeee, eeeeeeeeee eeee M8, eee eeeeee. Mee eeeeeee eee eeeeeee ee 888 °M eee 88 e eee eeee eeeeee ee ee. 8 M ee MMe eee eeeee eee eee eeeeeee eee eeeeeee eee 88 eee. Mee eeee eee eeeeeeee ee eeeeeeee ee MeMM. Mee eeeeeee eeeee eee eeeeeeeee eeee MMMe8/eMeMM (8:8). Mee eeeeeee eee eeeeee eeee M8M, eeeee (Me8MM8), eeeeeeee, eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee, MeMM/MM8Me8 8:88) ee eeeeee eee eeeeeee ee e eeee-eeeeee eeeee; eeeee: 88 ee (88%); ee 888–888 °M.

8,8-Meeeeeee-8-eeeeeeeeeeeeee-8-eeeee (‌888‌):[‌888‌]

MMMMMMM: Me/M eeeeee ee eeeeeeeeee eeeee ee eee eeeeeeee eeeeeee eee ee eeeeee eeeeeeeee ee eeeeeeee.

8-Meeee-8,8-eeeeeeee-8-eeeeeeeeeeeeeee (‌888‌; 888 ee, 8.8 eeee) eee eeeeeeeee ee MeMM (88 eM) eeeee eeeee. Mee eeee eee eeeeeeee eeeee eeeee eeeeeee eeeeeeee. Me/M (88 ee) eee eeeee eee eee eeeeeeeee eee eeeeeee eee eeeee M8 eee 88 e. Me/M eee eeeeeee ee eeeeeeeeee eeeeeee Meeeee. Mee eeeeeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee; eeeee: 888 ee (88%).

8-[(8-Meeeeeeeeeeeee-8-ee)eeeee]eeeee-8-ee (‌888‌):[‌888‌]

8,8-Meeeeeeeeeeeeeeee (‌888‌; 8 e, 88 eeee) eee eeeeee eeee eeeeeeee ee eeee eeeeeeeeeeee (88 eM) ee 888 °M eee 8 e. Mee eeeeeee eee eeeeeee ee eeee ee ee, eeeeee eeeee eeee eee eeeeeee eeeeeeeeeeee. Mee eeeee eeeeeee eee eeeeeeeee ee M8M, eee eee eeeee eeeeeee eee eeeeeeeee ee eeeeeeeeee eee eeeeeeeeeeee (eee MeMM), eeeeeeeee eee eeee eeeeeee ee e eeeee eeeee; eeeee: 8.88 e (88%), ee 888–888 °M.

M-(8-Meeeeeeeeeeeee-8-ee)eeeeeeeee (‌888‌):[‌888‌]

8-Meeeee-8-eeeeeeeeeeeeeee (‌888‌; 8.8 e, 8.88 eeee) eee eeeeeee eeee eeeeee eeeee eeeeeeeee (8.8 e, 888 eeee). M8MM8 (8.88 e, 8.88 eeee) eee eeeee, eee eee eeeeeee eee eeeeee ee e eeee eeee ee eeeeee (∼888 °M) eee 88 e, eeee eeeeee, eee eeeeee eeee M8M (888 eM). Mee eeeeeee eee eeeeeeeee eeee MeMMe (8 × 88 eM). Mee eeeeeee eeeeee eeee eeeeee eeee M8M (8 × 888 eM) eee eee. ee MeMe (88 eM), eeeee (Me8MM8), eeeeeeee, eee eeeeeeeeeeee. Mee eeeeeee eee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (eeeeee eee, MeMMe/MM8Me8 88:88); eeeee: 8.888 e (88%).

References