Ultrasound assisted synthesis of pyrazolo[1,5-a]pyrimidine-antipyrine hybrids and their anti-inflammatory and anti-cancer activities

Abstract

A series of antipyrinyl-pyrazolo[1,5-a]pyrimidines have been synthesized by reactions of aminopyrazole (4) with various formylated active proton compounds in the presence of KHSO4 (aqueous media), under ultrasound irradiation. The structures of the compounds have been established with the help of spectral and analytical data. N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-7-phenylpyrazolo[1,5-a]pyrimidine-3-carboxamide (6a) was further subjected to X-ray crystallographic studies to avoid any ambiguity of the derived structures. Crystal data for compound 6a, C51H46N12O5 (M =907.00 g/mol): triclinic, space group P-1 (no. 2), a = 9.9554(3) Å, b = 14.0875(4) Å, c = 17.4572(4) Å, α = 79.676(2)°, β = 85.283(2)°, γ = 72.647(2)°, V = 2297.97(11) Å3, Z = 2, T = 296.15 K, μ(MoKα) = 0.088 mm-1, Dcalc = 1.311 g/cm3, 29732 reflections measured (4.174° ≤ 2Θ ≤ 57.068°), 10681 unique (Rint = 0.0400, Rsigma = 0.0533) which were used in all calculations. The final R1 was 0.0566 (I > 2σ(I)) and wR2 was 0.1663 (all data). The novel compounds were also screened for their biological activities.

Efficient synthesis of diversely substituted pyrazolo[1,5-a]pyrimidine derivatives promoted by ultrasound irradiation in water and their antibacterial activities

“…The other aromatic protons of compounds 3a-n and 3ii appeared in their usual range. Furthermore, 13 C NMR, FT-IR, and mass spectroscopy were in support of the structure.…”

“…The structures of the above compounds were confirmed by their spectral and analytical data ( 1 H NMR, 13 C NMR, FT-IR, and Mass spectrometry). For further confirmation of their structures, the selected compound was subjected to X-ray crystallography.…”

“…They have been reported to have the advantages of rapid absorption, rapid onset, adequate duration of action, and no residual effect on daytime performance [4][5][6][7][8]. Inspired by this, our group has reported various pyrazolo[1,5-a]pyrimidine hybrids (4a-b, 5, 6, 7, 8(a-c)) all of which exhibit various bio-efficiencies ( Figure 1) [9][10][11][12][13]. Motivated by this notable significance of pyrazolo[1, 5a]pyrimidine and in continuation with our research activities, we settled to further add on to this class of compounds.…”

Efficient synthesis of diversely substituted pyrazolo[1,5-a]pyrimidine derivatives promoted by ultrasound irradiation in water and their antibacterial activities

“…The other aromatic protons of compounds 3a-n and 3ii appeared in their usual range. Furthermore, 13 C NMR, FT-IR, and mass spectroscopy were in support of the structure.…”

“…The structures of the above compounds were confirmed by their spectral and analytical data ( 1 H NMR, 13 C NMR, FT-IR, and Mass spectrometry). For further confirmation of their structures, the selected compound was subjected to X-ray crystallography.…”

“…They have been reported to have the advantages of rapid absorption, rapid onset, adequate duration of action, and no residual effect on daytime performance [4][5][6][7][8]. Inspired by this, our group has reported various pyrazolo[1,5-a]pyrimidine hybrids (4a-b, 5, 6, 7, 8(a-c)) all of which exhibit various bio-efficiencies ( Figure 1) [9][10][11][12][13]. Motivated by this notable significance of pyrazolo[1, 5a]pyrimidine and in continuation with our research activities, we settled to further add on to this class of compounds.…”

Insights into the medicinal chemistry of heterocycles integrated with a pyrazolo[1,5- a ]pyrimidine scaffold

“…Kaping's group [89][90][91][92][93] have recently specified the synthesis of pyrazolopyrimidine analogs from the reactions of aminopyrazoles with enaminones or enaminonitriles through Accordingly, these tosylate derivatives 59a-c and 62a-d reacted with n-Bu 4 NF to yield the investigated fluorine-based 60a-c and 63a-d in 81-96% yields (Scheme 10). 79 Kwon et al 94 3.1.2.…”

“…84 Kaping et al 92 have investigated the synthesis of compounds 136-139 by reactions of the corresponding 3-amino-N-phenyl-1H-pyrazole-4-carboxamide with enaminones under ultrasonic irradiation conditions. In addition, Kaping et al 93 have also Two series of pyrazolopyrimidines were prepared by reactions of aminopyrazoles with unsaturated ketones under reflux conditions as stated by Abdallah et al 105 The compounds of both series were assessed as antimicrobial agents against Gram-positive bacteria, i.e. B. subtilis, S. aureus, Gram-negative bacteria, i.e.…”

Efficient synthesis of diversely substituted pyrazolo[1,5-a]pyrimidine derivatives promoted by ultrasound irradiation in water and their antibacterial activities

“…The other aromatic protons of compounds 3a-n and 3ii appeared in their usual range. Furthermore, 13 C NMR, FT-IR, and mass spectroscopy were in support of the structure.…”

“…The structures of the above compounds were confirmed by their spectral and analytical data ( 1 H NMR, 13 C NMR, FT-IR, and Mass spectrometry). For further confirmation of their structures, the selected compound was subjected to X-ray crystallography.…”

“…They have been reported to have the advantages of rapid absorption, rapid onset, adequate duration of action, and no residual effect on daytime performance [4][5][6][7][8]. Inspired by this, our group has reported various pyrazolo[1,5-a]pyrimidine hybrids (4a-b, 5, 6, 7, 8(a-c)) all of which exhibit various bio-efficiencies ( Figure 1) [9][10][11][12][13]. Motivated by this notable significance of pyrazolo[1, 5a]pyrimidine and in continuation with our research activities, we settled to further add on to this class of compounds.…”

Insights into the medicinal chemistry of heterocycles integrated with a pyrazolo[1,5- a ]pyrimidine scaffold

“…Kaping's group [89][90][91][92][93] have recently specified the synthesis of pyrazolopyrimidine analogs from the reactions of aminopyrazoles with enaminones or enaminonitriles through Accordingly, these tosylate derivatives 59a-c and 62a-d reacted with n-Bu 4 NF to yield the investigated fluorine-based 60a-c and 63a-d in 81-96% yields (Scheme 10). 79 Kwon et al 94 3.1.2.…”

“…84 Kaping et al 92 have investigated the synthesis of compounds 136-139 by reactions of the corresponding 3-amino-N-phenyl-1H-pyrazole-4-carboxamide with enaminones under ultrasonic irradiation conditions. In addition, Kaping et al 93 have also Two series of pyrazolopyrimidines were prepared by reactions of aminopyrazoles with unsaturated ketones under reflux conditions as stated by Abdallah et al 105 The compounds of both series were assessed as antimicrobial agents against Gram-positive bacteria, i.e. B. subtilis, S. aureus, Gram-negative bacteria, i.e.…”

Efficient synthesis of diversely substituted pyrazolo[1,5-a]pyrimidine derivatives promoted by ultrasound irradiation in water and their antibacterial activities

“…The other aromatic protons of compounds 3a-n and 3ii appeared in their usual range. Furthermore, 13 C NMR, FT-IR, and mass spectroscopy were in support of the structure.…”

“…The structures of the above compounds were confirmed by their spectral and analytical data ( 1 H NMR, 13 C NMR, FT-IR, and Mass spectrometry). For further confirmation of their structures, the selected compound was subjected to X-ray crystallography.…”

“…They have been reported to have the advantages of rapid absorption, rapid onset, adequate duration of action, and no residual effect on daytime performance [4][5][6][7][8]. Inspired by this, our group has reported various pyrazolo[1,5-a]pyrimidine hybrids (4a-b, 5, 6, 7, 8(a-c)) all of which exhibit various bio-efficiencies ( Figure 1) [9][10][11][12][13]. Motivated by this notable significance of pyrazolo[1, 5a]pyrimidine and in continuation with our research activities, we settled to further add on to this class of compounds.…”

Insights into the medicinal chemistry of heterocycles integrated with a pyrazolo[1,5- a ]pyrimidine scaffold

“…Kaping's group [89][90][91][92][93] have recently specified the synthesis of pyrazolopyrimidine analogs from the reactions of aminopyrazoles with enaminones or enaminonitriles through Accordingly, these tosylate derivatives 59a-c and 62a-d reacted with n-Bu 4 NF to yield the investigated fluorine-based 60a-c and 63a-d in 81-96% yields (Scheme 10). 79 Kwon et al 94 3.1.2.…”

“…84 Kaping et al 92 have investigated the synthesis of compounds 136-139 by reactions of the corresponding 3-amino-N-phenyl-1H-pyrazole-4-carboxamide with enaminones under ultrasonic irradiation conditions. In addition, Kaping et al 93 have also Two series of pyrazolopyrimidines were prepared by reactions of aminopyrazoles with unsaturated ketones under reflux conditions as stated by Abdallah et al 105 The compounds of both series were assessed as antimicrobial agents against Gram-positive bacteria, i.e. B. subtilis, S. aureus, Gram-negative bacteria, i.e.…”