Controllable Site-Selective Construction of 2- and 4-Substituted Pyrimido[1,2-b]indazole from 3-Aminoindazoles and Ynals

Abstract

A straightforward and novel controllable siteselective construction of 2-and 4-substituted pyrimido[1,2b]indazole from 3-aminoindazoles and ynals has been developed. The high regioselectivity of this reaction could be easily switched by converting different catalytic systems. In this way, a series of 2and 4-substituted pyrimido[1,2-b]indazole derivatives were obtained in moderate to good yields. In addition, the photophysical properties of compound 3a prepared by the present method were discussed.

Synthesis of Substituted Pyrimido[1,2‐b]indazoles through (3+2+1) Cyclization of 3‐Aminoindazoles, Ketones, and N,N‐Dimethylaminoethanol as One‐Carbon Synthon

“…As shown in Scheme 1d, 2‐ and 4‐aryl substituted pyrimido[1,2‐ b ]indazoles could be afforded theoretically when 3‐aminoindazole ( 1 a ) reacts with aryl methyl ketones ( 2 b ) in DMEA. However, only 2‐aryl substituted product ( 3 b ) was isolated and the experimental NMR data are agreement with those from the literature report [12] . Moreover, there is a significant difference of the coupling constant between C3‐H/C4‐H (about 7.2 Hz) and C2‐H/C3‐H (about 4.0 Hz) [12] .…”

“…3 – 2‐( p ‐Tolyl)pyrimido[1,2‐b]indazole (3 b) [12] Yellow solid, (213 mg, 88%); mp 157.7–158.9 °C. 1 H NMR (400 MHz, CDCl 3 ): δ 8.96 (d, J= 7.2 Hz, 1H), 8.37 (d, J =8.4 Hz, 1H), 8.12 (d, J= 8.0 Hz, 2H), 7.82 (d, J =8.8 Hz, 1H), 7.66–7.61 (m, 2H), 7.35 (d, J= 8.0 Hz, 2H), 7.30 (t, J =7.2 Hz, 1H), 2.45 (s, 3H).…”

“…2‐(2‐Methoxyphenyl)pyrimido[1,2‐b]indazole (3 o) [12] Yellow solid, (187 mg, 60%); mp 157.1–157.9 °C. 1 H NMR (400 MHz, CDCl 3 ): δ 8.92 (d, J =7.2 Hz, 1H), 8.38 (d, J =8.4 Hz, 1H), 8.15 (dd, J =1.6, 7.6 Hz, 1H), 7.92 (d, J =7.2 Hz, 1H), 7.84 (d, J= 8.8 Hz, 1H), 7.63 (t, J =7.6 Hz, 1H), 7.48 (t, J =7.6 Hz, 1H), 7.30 (t, J= 7.6 Hz, 1H), 7.17 (t, J =7.6 Hz, 1H), 7.04 (d, J= 8.4 Hz, 1H), 3.94 (s, 3H).…”

“…Very recently, Cao et al. demonstrated their fantastic finding that 2‐ and 4‐substituted pyrimido[1,2‐ b ]indazoles could be selectively constructed from 3‐aminoindazoles and ynals by using different catalytic systems (Scheme 1c) [12] . However, ynals are not commercially available and need to be synthesized from aryl iodides and prop‐2‐yn‐1‐ol via two‐step reactions [13] .…”

“…Very recently, Cao et al demonstrated their fantastic finding that 2and 4-substituted pyrimido [1,2-b]indazoles could be selectively constructed from 3-aminoindazoles and ynals by using different catalytic systems (Scheme 1c). [12] However, ynals are not commercially available and need to be synthesized from aryl iodides and prop-2-yn-1-ol via two-step reactions. [13] Thus, a convenient chemoselective strategy for the synthesis of pyrimido [1,2-b]indazoles from easily accessible starting materials is highly desirable.…”