Palladium-Catalyzed Highly Regioselective C6 Arylation of Pyrrolo[2,3-d]pyrimidine Derivatives with Arylboronic Acids

Abstract

A mild and selective C6 arylation strategy for pyrrolo­[2,3-d]­pyrimidine derivatives with arylboronic acids at room temperature is described. This unified protocol has been achieved by the synergistic combination of Pd­(II)/TEMPO catalysis and CF3CO2H promotion under silver-, base-, and additive-free conditions. The broad substrate scope, good functional group tolerance, excellent regioselectivity, and air and moisture tolerant conditions make this process attractive for the effective synthesis and modification of targeted small molecule drugs.

Palladium Catalysis: Dependence of the Efficiency of C−C Bond Formation on Carboxylate Ligand and Alkali Metal Carboxylate or Carboxylic Acid Additive. Part A: the C(sp2)−C(sp2), C(sp2)−C(sp3) and C(sp3)−C(sp3) Bonds

“…[36] The recently reported phenylation of 7-methyl-N-phenyl-7H-pyrrolo- [2,3-d]pyrimidine-4-amine with phenylboronic acid used Pd(OAc) 2 catalyst and K 2 S 2 O 8 or TEMPO in CF 3 CO 2 H under air atmosphere (Scheme 3f). [37] The similar yield obtained with Pd(OCOCF 3 ) 2 catalyst as well as the absence of reaction in AcOH and t-BuCO 2 H led Tang, Zhang and co-workers to assume catalysis with Pd(OCOCF 3 ) 2 under the former conditions.…”

Visible-Light-Induced Highly Site-Selective Direct C–H Phosphorylation of Pyrrolo[2,3-d]pyrimidine Derivatives with H-Phosphine Oxides

“…The luminescence quenching experiment was taken using an F-7000 pro fluorescence spectrophotometer (Shanghai, China). Pyrrolo­[2,3- d ]­pyrimidine substrates 1 were synthesized according to the literature ,− (Supporting Information S8).…”

“…Owing to their high biological activities, our group is also actively involved in the late-stage of pyrrolo­[2,3- d ]­pyrimidines. In our previous work, we have developed Pd-catalyzed C–H arylation, C–H mono- and bis-acetoxylation, and Ru-catalyzed C–H amidation of pyrrolo­[2,3- d ]­pyrimidine derivatives. In the continuation of further functionalization of pyrrolo­[2,3- d ]­pyrimidine, herein, we will report a visible-light-induced highly regioselective C–H phosphorylation of pyrrolo­[2,3- d ]­pyrimidine derivatives with various H-phosphine oxides promoted by dilauroyl peroxide (LPO) at room temperature (Scheme d).…”

Promotion of Water as Solvent in Amination of 4-Chloropyrrolopyrimidines and Related Heterocycles under Acidic Conditions

“…282 °C (decomp.) (lit, 282–283 °C), 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.71 (s, 1H), 9.18 (s, 1H), 8.23 (s, 1H), 7.59 (d, J = 2.2 Hz, 1H), 7.23–7.19 (m, 2H), 6.89 (d, J = 8.4 Hz, 1H), 6.71 (dd, J = 3.5, 1.9 Hz, 1H), 6.00 (s, 2H). The spectroscopic data correspond to those previously reported …”