Synthetic Route of 7752-82-1 ,Some common heterocyclic compound, 7752-82-1, molecular formula is C4H4BrN3, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
[00159] Scheme 1. Preparation of relevant pyri(mi)dyl halides A-H. Key: (a) NBS, NH4OAc, MeCN, rt, 5 min, pyr: 85-90%; pym: quant; (b) pyr: RCHO, Na(CN)BH3, MeCN, reflux, 1-12h (82%, R = C5Hn); pym: NaH, Rl, THF, rt, overnight (85%, R = Me); (c) Me3(Bn)NBr, f-BuONO, CH2Br2, rt, overnight, pyr: 77-83%; pym: 30- 40%; (d) pym: HI, CH2CI2, 0C, 80-85%; (e) i. NaOH, Br2, H20, rt, 50-60%, ii. POCI3, PhNEt2, reflux, 4h, 75-85%, iii. HI, CH2CI2, 0C, 80-85%; (f) ROH, Na, rt, 1-12 h, quant.; (g) RZnl, CI2Pd(PPh3)2, DMF/THF, rt, overnight, pyr (Br): 72% (R = C6H13), pym (I) 81 %, (R = C6H13); (h) alkyne, Cul, CI2Pd(PPh3)2, Et3N, MeCN, rt, 1-12 h, quant. [00161] The pyrimidyl bromides were prepared in a similar manner, beginning with bromination of 2-aminopyrimidine. N-Alkylation could not be achieved by reductive amination (presumably due to the decreased nucleophilicity of the amine) and was instead accomplished using NaH and an appropriate alkyl halide to give (B). Nonaqueous diazotization/halo-dediazoniation was used to prepare 5-bromo-2- halopyrimidines, but in diminished yield relative to the analogous reaction with the 2- aminopyridine (again, presumably due to the decreased nucleophilicity of the amine group). Alternatively, 2-pyrimidinone could serve as a precursor to 5-bromo-2- halopyrimidines (Lutz, F.; Kawasaki, T.; Soai, K. Tetrahedron-Asymmetry 2006, 17, 486.) or as a substrate for alkylation to generate 5-bromo-2-alkoxypyrimidines (D) (Kokatla, H. P.; Lakshman, M. K. Org. Lett. 2010, 12, 4478.) Introduction of an alkyne substituent at the 2-position to give ( proceeded satisfactorily under Sonogoshira conditions, but alkylation using Negishi conditions was unselective. Since reduction of the 2- alkynylpyrimidyl bromide (F) to the corresponding 2-alkyl pyrimidyl bromide (H) was complicated by competing removal of the bromine, we turned to 5-bromo-2- iodopyrimidine as a precursor for the cross coupling reactions and saw a dramatic improvement in selectivity and yields.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,7752-82-1, its application will become more common.
Reference:
Patent; QUEEN’S UNIVERSITY AT KINGSTON; UNIVERSITA DI BOLOGNA; PRATT, Derek A.; HANTHORN, Jason, J.; VALGIMIGLI, Luca; WO2012/162818; (2012); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia