Efficient acid catalytic synthesis of pyrazolopyrimidines from 1H-pyrazol-5-yl-N,N-dimethylformamidines with cyanamide

Tsai, Shu-Yao; Yen, Wan-Ping; Tseng, Ching‐Chun; Xie, Jia-Jun; Liou, Ming Yu; Li, Yiting; Uramaru, Naoto; Wong, Fung Fuh

doi:10.1016/j.tet.2018.04.048

Cited by 8 publications

(14 citation statements)

References 36 publications

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“…A similar result and mechanism has been predicted and demonstrated by the LC-MS analysis technique. 36 According to the predicted mechanism, 5-amino-1Hpyrazole-4-carbaldehyde 8a 38 was considered to be the deprotected form of compound 1a. Theoretically, compound 8a could be used to react with cyanamide (NH 2 CN) in methanesulfonylchloride solution at ∼55 °C with 100 W of microwave energy within 50 min to give the same 6aminopyrazolo [3,4-d] In further investigations, the timed programming of the acidpromoted heterocyclization reaction was conducted under microwave irradiation to demonstrate the mechanism and is shown in Figure 1.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Initially, we investigated the possibility of the amination cyclization reaction of 1 H -pyrazol-5-yl- N , N -dimethylformamidines 1 with NH 2 CN under different acid-mediated solvents, such as conc. HCl, HCl (aq) /AcOH co-solvent, acetic acid (AcOH), trifluoroacetic acid (TFA), methanesulfonic acid, methanesulfonylchloride, and p -toluenesulfonylchloride.…”

Section: Resultsmentioning

confidence: 99%

“…Subsequently, the decyanation reaction took place by nucleophiles (e.g., water or excess cyanamide) to generate the pyrazolo[3,4- d ]pyrimidine product 3a . A similar result and mechanism has been predicted and demonstrated by the LC-MS analysis technique …”

Section: Resultsmentioning

confidence: 99%

“…The residue solution was purified by short column chromatography on silica gel (hexane/EtOAc = 6:4) to give pure 8e; 84% yields (1.23 g), yellow solid; mp 128−129 °C. (36), 297 (M + , 100), 296 (53), 177 (11), 128 (12) 5-Amino-1-(4-chlorophenyl)-3-phenyl-1H-pyrazole-4-carbaldehyde (8g). A solution of N′-[1-(4-chlorophenyl)-4-formyl-3-phenyl-1H-pyrazol-5-yl-N,N-dimethyl-methanimidamide (1g, 1.73 g, 4.90 mmol, 1.0 equiv) and NaOH (0.39 g, 9.80 mmol, 2.0 equiv) in MeOH solution (45 mL) at reflux within 2−3 h. When the reaction was completed, the reaction mixture was concentrated to remove solvent, added to water (10 mL), and extracted with CH 2 Cl 2 (3 × 20 mL).…”

Section: The Journal Of Organic Chemistrymentioning

confidence: 99%

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One-Pot Acid-Promoted Synthesis of 6-Aminopyrazolopyrimidines from 1H-Pyrazol-5-yl-N,N-dimethylformamidines or 5-Amino-1H-pyrazole-4-carbaldehydes with Cyanamide

Tseng

Tsai

et al. 2019

J. Org. Chem.

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A convenient and efficient one-pot acidpromoted synthesis of 6-aminopyrazolo [3,4-d]pyrimidine has been developed by treatment of 1H-pyrazol-5-yl-N,N-dimethylformamidines or 5-amino-1H-pyrazole-4-carbaldehydes with cyanamide (NH 2 CN) in an acid-mediated solution. This synthetic route involves four steps of deprotection, imination, the key acid-promoted heterocyclization, and aromatization. On the basis of optimized studies, methanesulfonylchloride is considered to be the best solvent. Furthermore, the microwave-assisted synthetic technique was also carried out to improve the major product 6-aminopyrazolo [3,4d]pyrimidines in this method. Moreover, our proposed mechanism was confirmed in this study, which demonstrates that N-[(5amino-1,3-diaryl-1H-pyrazol-4-yl)methylene]cyanamide is the intermediate.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: The Journal Of Organic Chemistrymentioning

confidence: 99%

See 2 more Smart Citations

One-Pot Acid-Promoted Synthesis of 6-Aminopyrazolopyrimidines from 1H-Pyrazol-5-yl-N,N-dimethylformamidines or 5-Amino-1H-pyrazole-4-carbaldehydes with Cyanamide

Tseng

Tsai

et al. 2019

J. Org. Chem.

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“…On the other hand, the reaction of triphenylphosphanimines 38 with acyl chlorides 50 gave the corresponding pyrazolo [3,4-d]pyrimidinium salts 51 (Scheme 15). 66 The intermolecular heterocyclization from N'-(4-formylpyrazol-5-yl)formimidamide 52 with various amines 67 or cyanamide (NH2CN) in acidic solution at reflux 68 Cyclization of 5-aminopyrazole-4-carbaldehyde 11 with formamide 69,70 or benzamide 70 and phosphorus tribromide (PBr3) 69 afforded pyrazolo [3,4-d] Gondek et al 83 [4,3-c]pyrazole. Under a Cu(0)/Selectfluor catalyzed system, a range of 3-methyl-1,5diphenyl-1H-pyrazole-4-carbaldehydes 116 could be intramolecularly lactonized to chromeno [4,3-c]pyrazoles 117 in moderate to good yields (55-72%, 117a-e, Scheme 40, Table 1).…”

Section: Synthesis Of Fused Pyrazolesmentioning

confidence: 99%

Synthesis of various pyrazole-fused heterocyclic systems using pyrazole-4-carbaldehydes as versatile precursors

Abdelhamid¹,

Hawass²,

Sanad³

et al. 2021

Arkivoc

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The discovery of intriguing properties shown by a large number of pyrazole derivatives has sparked a surge in interest in pyrazole chemistry over the last decade. They exist in a variety of natural products, dyes, and as scaffolds in a variety of drugs and pharmaceutical active ingredients. This review demonstrated various methods for the construction of pyrazole-fused heterocycles using pyrazole-4-carbaldehydes as effective precursors. Heterocyclic compounds mentioned in this review are arranged into categories based on the size of the heterocyclic ring as well as the position and number of the heteroatoms..

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One‐pot Microwave‐assisted Synthesis of Pyrazolopyrimidines from 5‐Amino‐4‐thiocyanato‐pyrazoles with Vilsmeier Reagent

Zeng,

Chung

et al. 2024

ChemistrySelect

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A facile one‐pot microwave‐assisted synthesis of pyrazolopyrimidines and pyrazolothiazoles was developed by reacting 5‐amino‐4‐thiocyanato‐pyrazoles with Vilsmeier Reagent (PBr3/foramide). The reaction gave the corresponding pyrazolopyrimidines as major products in good yields (61–85 %) and pyrazolothiazoles as minor products (11–23 % yields). The plausible reaction mechanism was proposed to account for the transformation of pyrazolopyrimidines and pyrazolothiazoles through two paths A and B. In path A, the reaction leading to the formation of pyrazolopyrimidines proceeded through four sequential steps, including acidic catalyzed cascade dethiocyanation/cyclization, Vilsmeier reaction, ring expansion, and deamination. The formation of the pyrazolothiazole in path B was caused by the nucleophilic heterocyclization reaction involving the sulfur nucleophilic reaction of thiocyanate (R−SC≡N) and the departure of a cyanamide. Based on the experimental results, we observed that the path A for the formation of pyrazolopyrimidines was more favorable.

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Efficient acid catalytic synthesis of pyrazolopyrimidines from 1H-pyrazol-5-yl-N,N-dimethylformamidines with cyanamide

Cited by 8 publications

References 36 publications

One-Pot Acid-Promoted Synthesis of 6-Aminopyrazolopyrimidines from 1H-Pyrazol-5-yl-N,N-dimethylformamidines or 5-Amino-1H-pyrazole-4-carbaldehydes with Cyanamide

One-Pot Acid-Promoted Synthesis of 6-Aminopyrazolopyrimidines from 1H-Pyrazol-5-yl-N,N-dimethylformamidines or 5-Amino-1H-pyrazole-4-carbaldehydes with Cyanamide

Synthesis of various pyrazole-fused heterocyclic systems using pyrazole-4-carbaldehydes as versatile precursors

One‐pot Microwave‐assisted Synthesis of Pyrazolopyrimidines from 5‐Amino‐4‐thiocyanato‐pyrazoles with Vilsmeier Reagent

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