Home Cart 0 Sign in  

[ CAS No. 288-13-1 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 288-13-1
Chemical Structure| 288-13-1
Structure of 288-13-1 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 288-13-1 ]

Related Doc. of [ 288-13-1 ]

Alternatived Products of [ 288-13-1 ]

Product Details of [ 288-13-1 ]

CAS No. :288-13-1 MDL No. :MFCD00005234
Formula : C3H4N2 Boiling Point : -
Linear Structure Formula :- InChI Key :WTKZEGDFNFYCGP-UHFFFAOYSA-N
M.W :68.08 Pubchem ID :1048
Synonyms :
1H-pyrazole

Calculated chemistry of [ 288-13-1 ]

Physicochemical Properties

Num. heavy atoms : 5
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 1.0
Num. H-bond donors : 1.0
Molar Refractivity : 18.59
TPSA : 28.68 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.56 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 0.22
Log Po/w (WLOGP) : 0.41
Log Po/w (MLOGP) : -0.52
Log Po/w (SILICOS-IT) : 1.36
Consensus Log Po/w : 0.3

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.14
Solubility : 4.92 mg/ml ; 0.0723 mol/l
Class : Very soluble
Log S (Ali) : -0.38
Solubility : 28.3 mg/ml ; 0.415 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.08
Solubility : 5.61 mg/ml ; 0.0824 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.0

Safety of [ 288-13-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P273-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335-H412 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 288-13-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 288-13-1 ]
  • Downstream synthetic route of [ 288-13-1 ]

[ 288-13-1 ] Synthesis Path-Upstream   1~106

  • 1
  • [ 288-13-1 ]
  • [ 60-29-7 ]
  • [ 591-51-5 ]
  • [ 1621-91-6 ]
Reference: [1] Justus Liebigs Annalen der Chemie, 1959, vol. 625, p. 55,60
  • 2
  • [ 103582-19-0 ]
  • [ 288-13-1 ]
  • [ 33689-29-1 ]
  • [ 15366-34-4 ]
Reference: [1] Heterocycles, 1985, vol. 23, # 10, p. 2619 - 2628
  • 3
  • [ 288-13-1 ]
  • [ 106-40-1 ]
  • [ 17635-45-9 ]
YieldReaction ConditionsOperation in experiment
91% With caesium carbonate In acetonitrile at 82℃; for 42 h; Example 1.22 [0670] Preparation of 1-(4?-aminophenyl)-1H-pyrazole [0671] General procedure B (82 C., 42 hours) was followed using 117 mg of Chxn-Py-Al (0.4 mmoles), 516 mg of 4-bromoaniline (3 mmoles), 136 mg of pyrazole (2 mmoles) and 1.2 ml of acetonitrile. [0672] The brown oil obtained after the filtration step was purified directly by alumina chromatography (eluent: hexane/dichloromethane, 100/0 to 50/50). [0673] 290 mg of an orange solid was obtained, corresponding to a yield of 91percent. [0674] The treatment and analyses were carried out as quickly as possible protected from the light as there was a risk that the compound would decompose. [0675] The compound obtained had the following formula: [CHEMMOL-00061] [0676] The characteristics were as follows: [0677] MPt: 42-43 C.; [0678] 1H NMR/CDCl3 (250 MHz):? 7.75 (dd, 1H, 3JHH=2.4 Hz, 4JHH=0.5 HZ, H5), 7.66 (dd, 1H, 3JHH=1.8 Hz, ??=0.5 Hz, H3), 7.40 (m, 2H, H6,7), 6.66 (m, 2H, H8,9), 6.38 (dd, 1H, 3JHH=?? Hz, 3JHH=2.4 Hz, H4) 3.79 (s, 2H, NH2). Purity=98percent; [0679] 13C NMR/CDCl3: ? 145.47 (C2), 140.22 (C3), 132.31 (Cl), 126.80 (C5), 121.10 (C6, C7), 115.43 (C8, C9), 106.83 (C4); [0680] GC/MS: Rt=17.77 min, M/Z=159; [0681] Rf=0.17 (eluent: dichloromethane/ethyl acetate, 95/5, silica) or 0.17 (eluent: dichloromethane/hexane, 50/50, alumina).
Reference: [1] European Journal of Organic Chemistry, 2004, # 4, p. 695 - 709
[2] Patent: US2003/236413, 2003, A1, . Location in patent: Page 26
  • 4
  • [ 288-13-1 ]
  • [ 540-37-4 ]
  • [ 17635-45-9 ]
YieldReaction ConditionsOperation in experiment
57% at 125℃; for 24 h; sealed tube Following General Procedure A (125 0C, 24 hours), 1 H-pyrazole (102 mg, 1.5 mmol) is coupled with 4-iodoaniline (220 mg, 1.0 mmol). The s crude brown oil is purified by flash chromatography on silica gel (eluent: dichloromethane/hexanes = 50/50) to provide 90 mg (57 percent isolated yield) of the desired product as an orange solid. <n="48"/>36- 47 -IdentificationMp: 42°C.1H NMR (400 MHz, CDCI3): δ 7.70 (dd, 1H, H7), 7.59 (d, 1 H, H9), 7.34-7.38 (m, 2H1 H2l6), 6.63-6.67 (m, 2H, H3,5), 6.33-6.34 (m, 1 H, H8), 3.67 (s, 2H, Hio). 13C NMR (100 MHz, CDCI3): δ 145.33 (C4), 140.24 (C9), 132.39 (C1), 126.76 (C7), 121.11 (C2,6), 115.46 (C3|5), 106.83 (C8).IR (KBr) : v (cm-1) = 3381 , 3298, 3192, 1632, 1525, 1398, 1280, 1176, 1126, 1051 , 1033, 943, 823, 751 , 612, 521. GC/MS: rt = 19.16 min, IWZ = 159. HRMS: 160.0873 (M+H). Theoretical: 160.0875.
Reference: [1] Angewandte Chemie - International Edition, 2007, vol. 46, # 6, p. 934 - 936
[2] Patent: WO2008/4088, 2008, A2, . Location in patent: Page/Page column 46-47
[3] Tetrahedron Letters, 2009, vol. 50, # 42, p. 5868 - 5871
[4] RSC Advances, 2015, vol. 5, # 130, p. 107547 - 107556
  • 5
  • [ 288-13-1 ]
  • [ 106-47-8 ]
  • [ 17635-45-9 ]
Reference: [1] European Journal of Organic Chemistry, 2011, # 24, p. 4523 - 4527
  • 6
  • [ 288-13-1 ]
  • [ 15878-00-9 ]
YieldReaction ConditionsOperation in experiment
74% With oxone; sodium chloride In water at 20℃; for 2.5 h; General procedure: 1-benzyl-4-chloro-3,5-dimethyl-1H-pyrazole. To a 16 mL vial containing 1-benzyl-3,5-dimethyl-1H-pyrazole (196 mg, 1.05 mmol) and a magnetic stir bar, 0.7 mL of water and 0.3 mL of ethyl acetate was added. Next, NaCl (123 mg, 2 mmol) was added and the vial was placed in a room temperature water bath to control exotherms. Finally, Oxone (322 mg, 0.52 mmol or 1.05 mmol KHSO5) was added and the vial was capped. The reaction proceeded with continuous and vigorous stirring until no starting material remained as indicated by TLC (1 h). The remaining oxidants were reduced with solid sodium bisulfite until starch iodide paper tested negative. Water (5 mL) was added and the mixture was extracted with 1:1 hexanes/diethyl ether (3 x 5 mL). The combined organic fractions were dried (MgSO4) and concentrated to yield crude product that was purified by flash chromatography (14 x 1 cm), 9:1 hexane/ethyl acetate eluent. Pure 1-benzyl-4-chloro-3,5-dimethyl-1H-pyrazole was obtained as a pale yellow oil (215 mg, 93percent yield).
Reference: [1] Canadian Journal of Chemistry, 1991, vol. 69, # 3, p. 432 - 439
[2] Journal of Heterocyclic Chemistry, 2014, vol. 51, # 6, p. 1621 - 1627
[3] Tetrahedron Letters, 2017, vol. 58, # 43, p. 4111 - 4114
[4] Advanced Synthesis and Catalysis, 2013, vol. 355, # 2-3, p. 499 - 507
[5] Angewandte Chemie - International Edition, 2016, vol. 55, # 52, p. 16132 - 16135[6] Angew. Chem., 2016, vol. 128, # 52, p. 16366 - 16369,4
[7] Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 1313 - 1316
[8] Chemische Berichte, 1895, vol. 28, p. 688[9] Journal fuer Praktische Chemie (Leipzig), 1896, vol. &lt;2&gt; 53, p. 127
[10] Atti della Accademia Nazionale dei Lincei, Classe di Scienze Fisiche, Matematiche e Naturali, Rendiconti, 1906, vol. &lt;5&gt; 15 I, p. 705[11] Gazzetta Chimica Italiana, 1906, vol. 36 II, p. 350
[12] Justus Liebigs Annalen der Chemie, 1956, vol. 598, p. 186,197
[13] Justus Liebigs Annalen der Chemie, 1956, vol. 598, p. 186,197
[14] Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 1313 - 1316
[15] Synthetic Communications, 2007, vol. 37, # 1, p. 137 - 147
[16] Patent: WO2003/105853, 2003, A1, . Location in patent: Page 63
[17] Chemistry - A European Journal, 2014, vol. 20, # 50, p. 16529 - 16535
[18] Patent: WO2017/21029, 2017, A1, . Location in patent: Sheet 1/1
  • 7
  • [ 288-13-1 ]
  • [ 56-23-5 ]
  • [ 7782-50-5 ]
  • [ 15878-00-9 ]
  • [ 27258-16-8 ]
Reference: [1] Chemische Berichte, 1970, vol. 103, p. 1942,1943, 1948
[2] Justus Liebigs Annalen der Chemie, 1956, vol. 598, p. 186,197
  • 8
  • [ 288-13-1 ]
  • [ 2075-45-8 ]
YieldReaction ConditionsOperation in experiment
100% With N-Bromosuccinimide In water at 20 - 25℃; Step 1[00249j To a slurry of 1H-pyrazole (10 g, 147 mmol) in water (150 mL) at room temperature was added NBS (26.1 g, 147 mmol) in one portion. Reaction became milky white and was allowed to stir at room temperature for 24 h. The reaction mixture was extracted with EtOAc (2 x 100 mL). The combined EtOAc extracts were washed with aqueous Na25203 and brine then dried over Na2504, and concentrated under reduced pressure to afford a light tan oil as 21.5 g (100percent) of as a light tan oil that solidified upon standing. HPLC Peak RT = 0.87 mm.
100% With N-Bromosuccinimide In water at 20℃; step 1To a solution of lH-pyrazole (10 g, 147 mmol)NBS (26.1 g, 147 mmol) was added to the slurry in water (150 mL) at one time (note: exotherm) and the mixture became milky white and stirred overnight at rt. The reaction mixture was then extracted with EtOAc (2 x 100 mL). The combined organic extracts were washed with aqueous Na2S2O3 and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to provide the desired product as 4-bromo-lH-pyrazole (21.5 g, 146 mmol, 100percent yield), which solidifies after standing.
99%
Stage #1: With bromine In water for 1 h; Heating / reflux
Stage #2: With sodium carbonate In water at 20℃;
A solution of 150 g (2.2 mol) of pyrazole and 703 g (4.4 mol, 2.0 eq.) of bromine in 3 L of water was refluxed for 1 h.
The resulting mixture was cooled to room temperature, diluted with saturated aqueous sodium bicarbonate solution and the product was extracted into ethyl acetate.
The organic layer was dried over sodium sulfate and concentrated.
The residue was triturated with hexanes to give 322 g (99percent) of 4-bromo-1H-pyrazole.
99% With tetrapropylammonium nonabromide In dichloromethane at 0 - 23℃; for 0.166667 h; Inert atmosphere General procedure: A round-bottom flask equipped with a magnetic stir bar and a rubber septum was charged with Pr4NBr9 (0.66 mmol, 0.33 molpercent) and CH2Cl2 (1 mL). The homogeneous solution was stirred and cooled to 0 °C if not described otherwise (partial precipitation of the nonabromide can occur at this point). The substrate (2.0 mmol, 1.0equiv) was added and the reaction allowed to warm to 23 °C (attention: exothermic reaction) After the reported reaction time the dark-red color of the nonabromide had vanished and TLC control showed completion of the reaction. The reaction was quenched by addition of sat. aq Na2S2O3 (2 mL) and transferred to a separation funnel. H2O was added (15 mL) followed by extraction with Et2O (4 × 20 mL) if not described otherwise. The organic layers were combined, washed with H2O (4 × 15 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure to give the crude product.
98% With N-Bromosuccinimide In water at 20℃; 4-Bromopyrazole (21).; Pyrazole (13, 34.0 g, 0.5 mol) and NBS (89.0 g, 0.5 mol, 1.0 equiv) were suspended in water (625 ml). The resulting suspension was stirred over night at room temperature. The reaction mixture was then extracted with EtOAc (2.x.100 mL). The combined EtOAc extracts was washed with aqueous Na2S2O3 and brine, dried over Na2SO4, and concentrated under reduced pressure to afford 4-bromopyrazole (21, 72.0 g, 73.5 g theoretical, 98percent yield) as a white solid (GC purity: >98percent).
98% With N-Bromosuccinimide In water at 20℃; 4-Bromopyrazole (22) [0163] Pyrazole (19, 34.0 g, 0.5 mol) and NBS (89.0 g, 0.5 mol, 1.0 equiv) were suspended in water (625 ml) at ambient temperature. The resulting suspension was stirred at ambient temperature for overnight. The reaction mixture was then extracted with EtOAc (2×100 mL). The combined EtOAc extracts were washed with aqueous Na2S2O3 and brine, dried over Na2SO4, and concentrated under reduced pressure to afford crude 4-bromopyrazole (72.0 g, 73.5 g theoretical, 98percent yield) as white solids (GC purity: >98percent), which was directly used in the subsequent reaction without further purification.
94%
Stage #1: With bromine In water at 15℃; for 3 h;
Stage #2: at 10℃;
4-bromo-l H-pyrazole (A)Bromine (76.4 mL, 1.49 mol) was added dropwise over a period of 2 h to a stirred and cooled (<15 0C; ice bath cooling) solution of pyrazole 3 (97.26 g, 1.43 mol) in water (450 mL). The mixture was stirred for additional 1 h, cooled to 10 0C. Excess of acid was neutralized with 50percent aqueous NaOH (total of about 120 mL) followed by saturated aqueous NaHCO3 (150 mL). The solid was filtered off, washed with cold water (300 mL) and dried in vacuum overnight to afford 4 (196.49 g, 94percent) as white-pink powder. 1H NMR (400 MHz, CDCl3) δ 7.60 (s, 2H), 11.70 (bs, IH).
80% With oxone; sodium bromide In water at 20℃; for 48 h; General procedure: 1-benzyl-4-chloro-3,5-dimethyl-1H-pyrazole. To a 16 mL vial containing 1-benzyl-3,5-dimethyl-1H-pyrazole (196 mg, 1.05 mmol) and a magnetic stir bar, 0.7 mL of water and 0.3 mL of ethyl acetate was added. Next, NaCl (123 mg, 2 mmol) was added and the vial was placed in a room temperature water bath to control exotherms. Finally, Oxone (322 mg, 0.52 mmol or 1.05 mmol KHSO5) was added and the vial was capped. The reaction proceeded with continuous and vigorous stirring until no starting material remained as indicated by TLC (1 h). The remaining oxidants were reduced with solid sodium bisulfite until starch iodide paper tested negative. Water (5 mL) was added and the mixture was extracted with 1:1 hexanes/diethyl ether (3 x 5 mL). The combined organic fractions were dried (MgSO4) and concentrated to yield crude product that was purified by flash chromatography (14 x 1 cm), 9:1 hexane/ethyl acetate eluent. Pure 1-benzyl-4-chloro-3,5-dimethyl-1H-pyrazole was obtained as a pale yellow oil (215 mg, 93percent yield).

Reference: [1] Heterocycles, 2010, vol. 81, # 6, p. 1509 - 1516
[2] Patent: WO2014/74661, 2014, A1, . Location in patent: Paragraph 00249
[3] Patent: TWI582077, 2017, B, . Location in patent: Page/Page column 81
[4] Patent: US2008/261975, 2008, A1, . Location in patent: Page/Page column 12
[5] Synthesis (Germany), 2014, vol. 46, # 6, p. 740 - 747
[6] Patent: US2010/190981, 2010, A1, . Location in patent: Page/Page column 105
[7] Patent: US2014/256941, 2014, A1, . Location in patent: Paragraph 0163
[8] Patent: WO2008/95944, 2008, A1, . Location in patent: Page/Page column 225
[9] Journal of Organic Chemistry, 2018, vol. 83, # 5, p. 2954 - 2958
[10] Tetrahedron Letters, 2017, vol. 58, # 43, p. 4111 - 4114
[11] Canadian Journal of Chemistry, 1991, vol. 69, # 3, p. 432 - 439
[12] Synthetic Communications, 2007, vol. 37, # 1, p. 137 - 147
[13] Chem.Abstr., 1961, # 23942,
[14] Patent: WO2015/69310, 2015, A1, . Location in patent: Paragraph 00173
[15] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 20, p. 4405 - 4411
[16] Oriental Journal of Chemistry, 2015, vol. 31, # 4, p. 2239 - 2245
[17] Oriental Journal of Chemistry, 2015, vol. 31, # 4, p. 2239 - 2245
[18] Organic and Biomolecular Chemistry, 2017, vol. 15, # 48, p. 10200 - 10211
[19] Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 626 - 630
  • 9
  • [ 288-13-1 ]
  • [ 600-00-0 ]
  • [ 2075-45-8 ]
  • [ 1040377-17-0 ]
Reference: [1] Patent: WO2014/140073, 2014, A1, . Location in patent: Page/Page column 13; 28
  • 10
  • [ 288-13-1 ]
  • [ 3469-69-0 ]
YieldReaction ConditionsOperation in experiment
91% With ammonium cerium(IV) nitrate; iodine In acetonitrile at 20℃; for 2.5 h; EXAMPLE 1; Preparation of 2-Amino-3-methyl-5-(1-methyl-1H-pyrazol-4-yl)-5-(3-pyrimidin-5-ylphenyl)-3,5-dihydro-4-imidazol-4-one; Step a); Preparation of Compound 2; A mixture of pyrazole (3.00 g, 44.0 mmol), iodine (6.71 g, 26.4 mmol) and ceric ammonium nitrate (14.5 g, 26.4 mmol) in acetonitrile (400 mL) was stirred at room temperature for 2.5 h. The reaction was concentrated and partitioned between ethyl acetate (250 mL) and 5percent aqueous sodium bisulfite (250 mL). Water (150 mL) was added and the organic layer was separated and washed with brine (250 mL), dried over magnesium sulfate, filtered and concentrated to afford 2 (7.80 g, 91percent) as a white solid: mp 105-108° C.; 1H NMR (300 MHz, CDCl3) δ7.63 (s, 2H).
90% at 70℃; for 1 h; Raw material Pyrazole (10g) was mixed with ethanol (10 g), and iodine (22.4 g) was added in portions, (20 ° C to 30 ° C), 30percent hydrogen peroxide (16.7 g) was added dropwise, the control temperature was not higher than 70 ° C, the stirring was continued for 1 hour, the TLC was followed by the reaction, 10 g of saturated aqueous sodium bisulfite solution was added, After filtration for 1 hour, the white solid was filtered and the cake was washed with water. The filtrate was concentrated, solidified and re-filtered. The filter cake was dried and weighed 25.7g, GC purity: 99percent
89%
Stage #1: With sulfuric acid; iodine; iodic acid In acetic acid at 60℃;
Stage #2: With sodium hydrogencarbonate; sodium carbonate In acetic acid
4-lodopyrazole (1); [00188] A mixture of iodic acid (3.6g 20mmole), iodine (10.2g 40mmole), 30percent w/w sulfuric acid (4ml_) and acetic acid (30ml_) was stirred to give a solution/suspension. About half of this mix was added in portions to a solution of pyrazole (6.8g, 100 mmole) in acetic acid (60ml_) maintained at 60°C. The colour was allowed to fade after each addition before adding the next aliquot. The rest of the solution/suspension was added in one portion and the mix stirred and heated at 60°C for another 1 .75 hours. The final mix still had an iodine colour. The reaction was cooled and added to saturated sodium hydrogen carbonate (100ml_). Sodium carbonate solution (200ml of a 15percent solution) was added carefully and then solid sodium carbonate was added until there was no more carbon dioxide evolved. The product was extracted with chloroform (3x60ml_) and the combined extracts were washed with water (50ml_). The extracts were dried and evaporated and the solid obtained was dried in vacuum over sodium hydroxide to give the title compound (17.4g, 89percent), spectroscopic data for which was consistent with data reported in G.Zoppellaro, A.Geiss, V.Enkelmann, M.Baumgarten, Eur. J.Org.Chem., 2004, 2367-2374.
89% at 60℃; for 1.75 h; 4-Iodopyrazole (1) [0622] A mixture of iodic acid (3.6 g 20 mmole), iodine (10.2 g 40 mmole), 30percent w/w sulfuric acid (4 mL) and acetic acid (30 mL) was stirred to give a solution/suspension. About half of this mix was added in portions to a solution of pyrazole (6.8 g, 100 mmole) in acetic acid (60 mL) maintained at 60° C. The colour was allowed to fade after each addition before adding the next aliquot. The rest of the solution/suspension was added in one portion and the mix stirred and heated at 60° C. for another 1.75 hours. The final mix still had an iodine colour. The reaction was cooled and added to saturated sodium hydrogen carbonate (100 mL). Sodium carbonate solution (200 ml of a 15percent solution) was added carefully and then solid sodium carbonate was added until there was no more carbon dioxide evolved. The product was extracted with chloroform (3×60 mL) and the combined extracts were washed with water (50 mL). The extracts were dried and evaporated and the solid obtained was dried in vacuum over sodium hydroxide to give the title compound (17.4 g, 89percent), spectroscopic data for which was consistent with data reported in G. Zoppellaro, A. Geiss, V. Enkelmann, M. Baumgarten, Eur. J. Org. Chem., 2004, 2367-2374.
89% With iodine; n-butyltriphenylphosphonium peroxodisulfate In water; acetonitrile at 20℃; for 2 h; n-Butyltriphenylphosphonium peroxodisulfate (0.5 mmol) was added in small portions to a solution of pyrazole (1 mmol) and iodine (0.6 mmol) in CH3CN/H2O (10 : 2 mL) in a 50 mL round-bottome flask equipped with a magnetic stirrer. The reaction mixture was stirred at ambient temperature for the appropriate time (see table). Upon completion of the reaction, as indicated by TLC, the reaction mixture was poured into an aqueous sodium thiosulfate solution (1 M) and extracted with diethyl ether (3 × 15 mL). The combined organic layers were dried over MgSO4. The solvent was concentrated in vacuo, the resulting product was purified on silica gel using column chromategraphy (diethyl ether : n-hexane = 1 : 4) to afford the pure compound. 4-Iodo-1H-pyrazole (1). Yield 89percent, mp 109–110°C. 13 NMR spectrum, δ, ppm: 57.6, 138.8. Found, percent:C 18.6, H 1.57, N 14.40. C3H3IN2. Calculated, percent. C18.57, H 1.56, N 14.43.
88.6% With N-iodo-succinimide In tetrahydrofuran at 10 - 20℃; Inert atmosphere 4-Iodopyrazole (14).; A flask equipped with a nitrogen inlet, addition funnel, thermowell, and mechanical stirrer was charged with pyrazole (13, 450 g, 6.62 mol) and tetrahydrofuran (5 L). The mixture was cooled to 10° C. and N-iodosuccinimide (NIS, 1490 g, 6.62 mol, 1.0 equiv) was added in portions as a solid. The reaction mixture (slight suspension) was stirred at room temperature for 1 hour (longer reaction times may be necessary depending on ambient temperature). The mixture was then filtered and the THF was removed under reduced pressure. The residue was suspended in ethyl acetate (6 L) and insoluble materials were filtered. The dark filtrate was sequentially washed with aqueous saturated sodium thiosulfate solution (2.x.3 L) (organic layer lightens to a pale yellow), water (2.x.3 L), and brine (2 L). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford 4-iodopyrazole (14, 1138 g, 1284.1 g theoretical, 88.6percent) as white to pale yellow solids after being dried in a vacuum oven at 30° C. overnight. For 14: 1H NMR (DMSO-d6, 400 MHz) δ ppm 13.17 (bs, 1H), 7.93 (bs,1H), 7.55 (bs,1H); C3H3IN2 (MW, 193.97), LCMS (EI) m/e 195 (M++H).
88.6% With N-iodo-succinimide In tetrahydrofuran at 10 - 20℃; for 1 h; 4-Iodopyrazole (20) [0159] A flask equipped with a nitrogen inlet, an addition funnel, a thermowell, and a mechanical stirrer was charged with pyrazole (1, 450 g, 6.62 mol) and tetrahydrofuran (THF, 5 L) at ambient temperature. The mixture was then cooled to 10° C. and N-iodosuccinimide (NIS, 1490 g, 6.62 mol, 1.0 equiv) was added to the mixture in portions as a solid at approximately 10° C. The resulting reaction mixture was then stirred at ambient temperature for 1 hour (longer reaction times may be necessary depending on ambient temperature). The mixture was then filtered and the THF was removed under reduced pressure. The residue was suspended in ethyl acetate (6 L) and insoluble materials were filtered. The dark filtrate was sequentially washed with saturated aqueous sodium thiosulfate solution (2×3 L) (organic layer lightens to a pale yellow), water (2×3 L), and brine (2 L). The resulting organic layer was then dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford 4-iodopyrazole (1138 g, 1284.1 g theoretical, 88.6percent) as a white to pale yellow solid after being dried in a vacuum oven at approximately 30° C. overnight. 1H NMR (400 MHz, DMSO-d6) δ 13.17 (bs, 1H), 7.93 (bs, 1H), 7.55 (bs, 1H) ppm; C3H31N2 (MW, 193.97), LCMS (EI) m/e 195 (M++H).
85% With dihydrogen peroxide; iodine In water at 20℃; To a solution of pyrazole 34d (25.53 g, 375 mmol) and iodine (47.6 g, 187.5 mmol) in water (135 mL) was added 30percent H202 (25.8 mL, 225 mmol). The mixture was stirred at room temperature overnight. A cold solution of 5percent NaHS03 (100 mL) was added to the reaction mixture, affording an off-white slurry. The product was filtered and washed with water to give 4-iodo-lH-pyrazole 34e (61.9 g 85 percent), as off-white solid; mp 86.8 °C; NMR (300 MHz, CDC13) δ 9.20 (bs, 1H), 7.63 (s, 2H); 13C NMR (75 MHz, CDC13) δ 138.75, 138.75, 56.50 ; Analysis: Calculated for C3H3rN2: C, 18.58; H, 1.56; N, 14.44; Found: C, 18.70; H, 1.49; N, 14.41.

Reference: [1] Tetrahedron Letters, 2001, vol. 42, # 5, p. 863 - 865
[2] Heterocycles, 2003, vol. 60, # 4, p. 879 - 886
[3] Journal of Organic Chemistry, 2003, vol. 68, # 21, p. 8075 - 8079
[4] Tetrahedron Letters, 2001, vol. 42, # 11, p. 2089 - 2092
[5] Russian Chemical Bulletin, 2014, vol. 63, # 2, p. 360 - 367[6] Izv. Akad. Nauk, Ser. Khim., 2014, # 2, p. 360 - 367
[7] Patent: US2007/4786, 2007, A1, . Location in patent: Page/Page column 13-14
[8] Chimia, 2016, vol. 70, # 10, p. 704 - 708
[9] Patent: CN103601749, 2016, B, . Location in patent: Paragraph 0021; 0025-0028
[10] Patent: WO2012/123745, 2012, A1, . Location in patent: Page/Page column 63
[11] Patent: US2013/345181, 2013, A1, . Location in patent: Paragraph 0621-0622
[12] Russian Journal of General Chemistry, 2016, vol. 86, # 8, p. 1931 - 1934[13] Zh. Obshch. Khim., 2016, vol. 86, # 8, p. 1931 - 1934,4
[14] Organic Letters, 2004, vol. 6, # 26, p. 4929 - 4932
[15] Patent: US2010/190981, 2010, A1, . Location in patent: Page/Page column 102-103
[16] Patent: US2014/256941, 2014, A1, . Location in patent: Paragraph 0159
[17] Synthetic Communications, 2011, vol. 41, # 16, p. 2430 - 2434
[18] Journal fuer Praktische Chemie (Leipzig), 1989, vol. 331, # 5, p. 799 - 805
[19] Patent: WO2011/31554, 2011, A2, . Location in patent: Page/Page column 148
[20] Molecules, 2005, vol. 10, # 2, p. 401 - 406
[21] Angewandte Chemie - International Edition, 2013, vol. 52, # 32, p. 8290 - 8294[22] Angew. Chem., 2013, vol. 125, # 32, p. 8448 - 8452,5
[23] Advanced Synthesis and Catalysis, 2013, vol. 355, # 2-3, p. 499 - 507
[24] Tetrahedron Letters, 2008, vol. 49, # 25, p. 4026 - 4028
[25] Chemistry - A European Journal, 2015, vol. 21, # 47, p. 16801 - 16806
[26] Russian Chemical Bulletin, 2010, vol. 59, # 8, p. 1549 - 1555
[27] Monatshefte fur Chemie, 2012, vol. 143, # 4, p. 619 - 623
[28] Chemical Communications, 2015, vol. 51, # 34, p. 7305 - 7308
[29] Synlett, 2003, # 12, p. 1895 - 1897
[30] Synthesis, 1995, # 8, p. 926 - 928
[31] Justus Liebigs Annalen der Chemie, 1955, vol. 593, p. 200 - 207
[32] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 18, p. 5164 - 5170
[33] Polyhedron, 2012, vol. 47, # 1, p. 151 - 164
[34] Russian Chemical Bulletin, 2013, vol. 62, # 4, p. 1044 - 1051[35] Izv. Akad. Nauk, Ser. Khim., 2013, vol. 62, # 4, p. 1043 - 1050,8
[36] Heterocycles, 2018, vol. 96, # 7, p. 1203 - 1215
  • 11
  • [ 288-13-1 ]
  • [ 3469-69-0 ]
  • [ 6645-70-1 ]
Reference: [1] Russian Journal of General Chemistry, 2016, vol. 86, # 8, p. 1931 - 1934[2] Zh. Obshch. Khim., 2016, vol. 86, # 8, p. 1931 - 1934,4
  • 12
  • [ 1134-81-2 ]
  • [ 288-13-1 ]
  • [ 13036-57-2 ]
  • [ 4472-44-0 ]
  • [ 14164-34-2 ]
Reference: [1] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 24, p. 3581 - 3585
  • 13
  • [ 288-13-1 ]
  • [ 67-56-1 ]
  • [ 1120-82-7 ]
YieldReaction ConditionsOperation in experiment
90% With formaldehyd In water at 25℃; for 4 h; A roundbottom flask comprising pyrazole (144 mmol, 100 g) and methanol (about 200 mL) was charged with formaldehyde (131 g, 37percent aq. solution). The reaction mixture was stirred at 25 °C for 4 hours to give a (0193) homogenous solution. The solvent was removed under reduced pressure and dried in vacuo hours, yielding the title compound (127 g, 90percent).
Reference: [1] Patent: WO2016/191677, 2016, A1, . Location in patent: Paragraph 0110
  • 14
  • [ 288-13-1 ]
  • [ 50-00-0 ]
  • [ 1120-82-7 ]
YieldReaction ConditionsOperation in experiment
98% for 120 h; Reflux The 1H-pyrazolyl-1-methanol as starting material were preparedin processes described in literature [1]. The CH2Cl2 solution(100 mL) of pyrazole (20.4 g, 0.30 mol) was added a CH2Cl2 solution(100 mL) of para-formaldehyde (9.00 g, 0.30 mol). The solutionwas reflux for 5 days and the filtrate solvent was removedunder reduced pressure to give white powder (28.5 g, 98.0percent). 1HNMR (CDCl3, 400 MHz) for 1H-pyrazolyl-1-methanol: d 7.71 (s,1H), 7.59 (d, 1H, J = 2.24 Hz), 7.56 (d, 1H, J = 1.48 Hz), 6.29 (t, 1H,J = 1.8 Hz), 5.51 (s, 2H).
96.6% at 60℃; for 4 h; After dissolving 20.4 g (0.300 mol) of pyrazole and 9.0 g (0.300 mol) of para-formaldehyde in 400 mL of methylene chloride, the reaction was carried out at 60 ° C. for 4 days using a reflux condenser . The reaction mixture was dried under reduced pressure, and the reaction mixture obtained after the removal was washed with 100 ml of hexane three times, followed by vacuum drying under reduced pressure.The yield of (1H-1-pyrazolyl-1-methanol) obtained was 34.8 g (96.6percent).
Reference: [1] Polyhedron, 2012, vol. 42, # 1, p. 135 - 141
[2] Journal of Molecular Structure, 2014, vol. 1063, # 1, p. 70 - 76
[3] Inorganica Chimica Acta, 2015, vol. 428, p. 193 - 202
[4] Recueil: Journal of the Royal Netherlands Chemical Society, 1982, vol. 101, # 12, p. 441 - 443
[5] Applied Organometallic Chemistry, 2014, vol. 28, # 6, p. 445 - 453
[6] Patent: KR2017/51867, 2017, A, . Location in patent: Paragraph 0078; 0079
[7] Medicinal Chemistry Research, 2012, vol. 21, # 10, p. 3035 - 3042,8
[8] Heterocycles, 1986, vol. 24, # 8, p. 2233 - 2237
[9] Chemische Berichte, 1952, vol. 85, p. 820,823
[10] Chemische Berichte, 1952, vol. 85, p. 820,823
[11] Patent: EP1710234, 2006, A1, . Location in patent: Page/Page column 40-41
[12] Patent: EP1422228, 2004, A1, . Location in patent: Page 223
[13] Dalton Transactions, 2009, # 35, p. 7029 - 7038
[14] Patent: WO2010/132999, 2010, A1, . Location in patent: Page/Page column 138
[15] European Journal of Medicinal Chemistry, 2014, vol. 73, p. 83 - 96
[16] Inorganic Chemistry, 2014, vol. 53, # 8, p. 4192 - 4201
[17] RSC Advances, 2015, vol. 5, # 41, p. 32369 - 32375
[18] Medicinal Chemistry, 2016, vol. 12, # 1, p. 83 - 89
  • 15
  • [ 1134-81-2 ]
  • [ 288-13-1 ]
  • [ 13036-57-2 ]
  • [ 4472-44-0 ]
  • [ 14164-34-2 ]
Reference: [1] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 24, p. 3581 - 3585
  • 16
  • [ 288-13-1 ]
  • [ 7119-95-1 ]
YieldReaction ConditionsOperation in experiment
92% With nitric acid; acetic anhydride In acetic acid at 55℃; Cooling with ice; Flow reactor; High pressure The acetic anhydride and fuming nitric acid are slowly mixed in an ice water bath at a volume ratio of 5.5:1 to obtain a nitrating agent, and the nitratingagent and the pyrazole acetic acid solution are respectively delivered to the microchannel reactor through a high-pressure constant-flow pump with precise flow control. The twoinlets control the molar ratio of nitric acid to pyrazole to be 1.1:1. At 45-70 °C, the two liquids are instantaneously mixed in the microchannel reactorand reacted. The reaction solution is poured into crushed ice and filtered. It was washed with ice water and dried under vacuum to give N-nitropyrazole; theflow rate of the acetic acid solution of the pyrazole was 0.1 mL/min.The yield and purity of N-nitropyrazole are shown in Table 1 and Figure 2.
78%
Stage #1: at -10℃;
Stage #2: at 20℃; for 1.5 h;
Fuming nitric acid (3.3 mL) was added dropwise to a stirred solution of pyrazole (4.5 g, 66 mmol) in glacial acetic acid (14.1 mL) that had been cooled to −10 °C using an ice-salt bath. A voluminous precipitate was formed. Acetic anhydride (9.45 mL) was added dropwise and the resultant mixture was stirred at ambient temperature for 1.5 h. The mixture was poured onto ice and was neutralized with potassium carbonate. The precipitate was isolated by filtration. The yield of the obtained white solid of N-nitropyrazole is 78percent.
Reference: [1] Patent: CN108570010, 2018, A, . Location in patent: Paragraph 0035; 0036; 0037; 0038; 0041-0070
[2] Archiv der Pharmazie, 1995, vol. 328, # 4, p. 349 - 358
[3] ChemPlusChem, 2018, vol. 83, # 8, p. 804 - 811
[4] Journal of Chemical Research - Part S, 1996, # 5, p. 244 - 245
[5] Beilstein Journal of Organic Chemistry, 2013, vol. 9, p. 1517 - 1525
[6] Chemische Berichte, 1955, vol. 88, p. 1586,1590
[7] Journal of the Chemical Society. Perkin Transactions 2, 2001, # 2, p. 197 - 200
[8] Patent: WO2006/40520, 2006, A1, . Location in patent: Page/Page column 122
[9] Patent: WO2007/99326, 2007, A1, . Location in patent: Page/Page column 103
[10] Patent: WO2007/99317, 2007, A1, . Location in patent: Page/Page column 101
[11] Patent: WO2007/99335, 2007, A1, . Location in patent: Page/Page column 94
[12] Patent: US2009/76075, 2009, A1, . Location in patent: Page/Page column 36-37
[13] Chemistry - A European Journal, 2010, vol. 16, # 35, p. 10778 - 10784
[14] Journal of Molecular Structure, 2013, vol. 1043, p. 121 - 131
[15] Zeitschrift fur Anorganische und Allgemeine Chemie, 2014, vol. 640, # 11, p. 2139 - 2148
[16] Patent: CN105669557, 2016, A, . Location in patent: Paragraph 0023
[17] Patent: WO2007/113548, 2007, A1, . Location in patent: Page/Page column 142
[18] Patent: WO2007/113565, 2007, A1, . Location in patent: Page/Page column 93
  • 17
  • [ 288-13-1 ]
  • [ 79-08-3 ]
  • [ 16034-48-3 ]
Reference: [1] European Journal of Inorganic Chemistry, 2005, # 5, p. 872 - 878
[2] Chemical Communications, 2015, vol. 51, # 16, p. 3438 - 3441
  • 18
  • [ 288-13-1 ]
  • [ 2075-46-9 ]
YieldReaction ConditionsOperation in experiment
91%
Stage #1: at 40℃;
Stage #2: at -5℃;
lH-Pyrazol-4-amine (Compound 0113-42)Pyrazole (2.04 g, 30 mmol) was added in portions to concentrated sulfuric acid (15 rnL) at below 4O0C followed by addition of concentrated nitric acid (2.08 g, 33 mmol) at -50C dropwise. After the reaction was completed, the mixture was poured onto ice and extracted with ethyl acetate. The separated organic layer was washed with saturated NaΗCO3 solution, brine, dried and concentrated to give the compound 4-nitro-l/f-pyrazole (3.09 g, 91percent) as a light yellow solid. LC-MS: 114 [M+l]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.59 (br s, 2H), 13.98 (br s, IH).
85.5%
Stage #1: With sulfuric acid; nitric acid In water at 55℃;
Stage #2: With sodium hydroxide In water at 0℃;
2a (5.Og, 73.5mmol) was added in portions to H2SO4 (35mL) while keeping the temperature below 400C, then 70percent HNO3 (5.06mL, 80.6mmol) was added dropwise while maintaining the temperature below 55 0C. The mixture was then heated at 550C for 5h and cooled to 00C. The mixture was neutralized with 50percent NaOH and the resulting slurry was diluted with ethyl acetate. The resulting precipitate was removed by filtration. The filtrate was separated and the organic phase was washed with water and brine, dried over MgSO4 and concentrated in vacuum. The residue was crystallized for ethanol to afford 2b (7.1g, 85.5percent)
74% at 55℃; for 3 h; EXAMPLE 1; SYNTHESIS OF REAGENTS 3-BROMO-7-CHLORO-5-METHYL-lH-PYRAZOLO[4,3-b]PYRiDiNEAND 7-BENZYLOXY-S-BROMO-S-METHYL- lH-PYRAZOLO[4,3-b]PYRIDINE; Step IA; Pyrazole (30.0 g, 441 mmol) was added portionwise to sulfuric acid (220 raL, 97percent) in an ice-bath. The mixture was heated at 55 0C and nitric acid (30 mL, 70percent, 0.5 mol) was added slowly. The reaction mixture was stirred at 55 °C for 3 hours, cooled down, poured into ice-water (600 mL) and neutralized with 6N NaOH solution (pH = 7). The reaction mixture was extracted with ethyl acetate (5x150 mL). The organic phases were combined, washed with water (100 mL) and brine (100 mL), dried with sodium sulfate, filtered and concentrated by vacuum to afford compound Ia as a white solid (37.0 g, 326 mmol, 74percent); GC/MS: m/z = 113 (100percent).
56% at 0℃; for 6 h; Reflux Pyrazole (8.5 g) and cold concentrated nitric acid (18 cm3, d = 1.4 g/mL) were added to concentrated sulfuric acid (15 cm3) that had been cooled to 0 °C using an ice–salt bath.The reaction mixture was heated under reflux for 3 h. The reaction mixture was cooled toroom temperature, and additional nitrating mixture (6 cm3 of concentrated sulfuric acid and 6 cm3 of nitric acid) was added dropwise. The mixture was heated under reflux for a further 3 h, cooled and left to stand overnight. The obtained solution was poured onto ice (80 g), and the precipitate was filtered under reduced pressure, washed with cold water and cold ethanol, and crystallized from toluene. 4-Nitropyrazole (56 percent yield) was obtained as a white solid.
42% at 60℃; for 4 h; Cooling with ice 4-nitro-1H-pyrazole
Pyrazole (10 g, 147 mmol), was added to concentrated sulfuric acid (100 mL), in portions, while maintaining the internal reaction temperature below 50° C. via an ice water bath.
Concentrated nitric acid (10 mL) was then added, dropwise, maintaining the internal reaction temperature below 50° C. via an ice water bath.
The ice water bath was removed and the reaction was heated to 60° C. and stirred for 4 hours.
The reaction was cooled via an ice water bath and made basic, to ˜pH 8, with 18 N aqueous NaOH solution (150 mL).
The product, which precipitated as a white solid, was collected by filtration, washed with H2O, and dried under high vacuum to afford 4-nitro-1H-pyrazole (7 g, 42percent) as a white solid. 13C NMR (100 MHz, CDCl3): δ 126.4, 137.0.
42% at 0 - 55℃; for 5 h; Example 41c
3,5-Dimethyl-4-((4-nitro-1H-pyrazol-1-yl)methyl)isoxazole
1H-Pyrazole (10 g, 147 mmol) was added in small portions to concentrated H2SO4 (100 mL), cooled to 0° C. via an ice/water bath, maintaining the internal reaction temperature below 40° C. Concentrated HNO3 (10 mL) was carefully added, dropwise, to the reaction mixture maintaining the internal reaction temperature below 55° C.
The reaction was then heated to 55° C. and stirred for 5 hours.
The mixture was cooled to 0° C. and carefully made basic (pH-8) with aqueous NaOH solution (110 g NaOH in 150 mL H2O) until a white precipitate formed, carefully ensuring the internal temperature of the solution remain below 40° C.
The white solid was collected by filtration and washed with ethyl acetate/hexanes (1/3) then dried en vacuo to afford 4-nitro-1H-pyrazole (7 g, 42percent, isolated yield).
13C NMR (DMSO-d6, 100 MHz) δ 137.0, 126.4.
To 4-nitro-1H-pyrazole (9 g, 80 mmol) in DMF (100 mL) was added cesium carbonate (26 g, 80 mmol) followed by the addition of 4-(chloromethyl)-3,5-dimethylisoxazole (12.3 g, 85 mmol).
The reaction mixture was stirred in DMF (100 mL) at 80° C. for 30 minutes, then cooled, diluted with H2O (150 mL) and extracted with ethyl acetate (3*, 75 mL).
The combined organic layers were dried over sodium sulfate, filtered and concentrated.
The residue was taken up in ethyl acetate (200 mL) and washed with H2O (2*, 100 mL).
The organic layer was dried over sodium sulfate, filtered and concentrated.
The solid product was triturated with ethyl acetate/hexanes (1/9) and collected by filtration.
The product was dried under high vacuum to afford 3,5-dimethyl-4-((4-nitro-1H-pyrazol-1-yl)methyl)isoxazole (12 g, 67percent) as a light yellow solid. 1H NMR (CDCl3, 400 MHz): δ 2.23 (s, 3H), 2.46 (s, 3H), 5.08 (s, 2H), 8.02 (s, 1H), 8.08 (s, 1H).

Reference: [1] Patent: WO2010/75542, 2010, A1, . Location in patent: Page/Page column 73
[2] Journal of Medicinal Chemistry, 2005, vol. 48, # 18, p. 5780 - 5793
[3] Patent: WO2009/154769, 2009, A1, . Location in patent: Page/Page column 36
[4] Patent: WO2006/44821, 2006, A1, . Location in patent: Page/Page column 22
[5] Beilstein Journal of Organic Chemistry, 2013, vol. 9, p. 1517 - 1525
[6] Journal of Heterocyclic Chemistry, 2014, vol. 51, # 6, p. 1621 - 1627
[7] Patent: US9247759, 2016, B2, . Location in patent: Page/Page column 87
[8] Patent: US2016/376263, 2016, A1, . Location in patent: Paragraph 0395; 0396
[9] Justus Liebigs Annalen der Chemie, 1893, vol. 273, p. 252
[10] Chemische Berichte, 1955, vol. 88, p. 1577,1583
[11] Journal of Chemical Research - Part S, 1996, # 5, p. 244 - 245
[12] Patent: WO2008/8375, 2008, A2, . Location in patent: Page/Page column 82-83
[13] Patent: WO2009/93012, 2009, A1, . Location in patent: Page/Page column 19-20; 33
[14] Polyhedron, 2012, vol. 47, # 1, p. 151 - 164
[15] Patent: CN106986860, 2017, A, . Location in patent: Paragraph 0030; 0031; 0032
[16] Patent: CN107098861, 2017, A, . Location in patent: Paragraph 0032; 0034
[17] Patent: CN107118157, 2017, A, . Location in patent: Paragraph 0029
[18] Chemical Biology and Drug Design, 2018, vol. 91, # 2, p. 567 - 574
[19] Patent: CN107880029, 2018, A, . Location in patent: Paragraph 0029
[20] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 14, p. 2382 - 2390
  • 19
  • [ 288-13-1 ]
  • [ 2075-46-9 ]
  • [ 26621-44-3 ]
Reference: [1] Catalysis Communications, 2012, vol. 19, p. 37 - 41
  • 20
  • [ 288-13-1 ]
  • [ 17635-44-8 ]
YieldReaction ConditionsOperation in experiment
81% With bromine; sodium hydroxide In water at 20℃; for 2 h; Step A:
Into a stirred solution of 1H-pyrazole (6.95 g, 0.1 mmol) and sodium hydroxide (16 g, 0.4 mol) in water (400 mL0 was added bromine (48 g, 0.3 mol) dropwise over 1 h.
The mixture was stirred for 1 h, and then filtered.
The cake was washed with water and dried to give 3,4,5-tribromo-1H-pyrazole (25.2 g, 81percent). MS m/z 302.9 [M+H]+.
Reference: [1] Journal of the Chemical Society, Dalton Transactions, 2002, # 11, p. 2297 - 2301
[2] Journal of Medicinal Chemistry, 2016, vol. 59, # 13, p. 6070 - 6085
[3] Patent: US9617268, 2017, B2, . Location in patent: Page/Page column 414; 415
[4] Journal of Organic Chemistry, 1986, vol. 51, # 24, p. 4656 - 4660
[5] Tetrahedron, 2007, vol. 63, # 1, p. 56 - 61
  • 21
  • [ 288-13-1 ]
  • [ 95-46-5 ]
  • [ 20157-44-2 ]
YieldReaction ConditionsOperation in experiment
35% With tetrabutylammomium bromide; copper; lithium hydroxide In water at 120℃; for 24 h; General procedure: General procedure: iodobenzene (1.0mmol), pyrazole (1.5 mmol), LiOH (2.0 mmol), TBAB(0.2 mmol), active Cu (0.1 mmol) and 2 mL H2O were added to a 10 mL flask. The mixture was heated in an oil bath at 120℃. When the reaction completed, the resulting mixture was cooled to room temperature and the product was extracted by ethyl acetate (10 mL×3). The combine dextracts were washed by brine (15 mL) , dried over MgSO4 and evaporated under reduced pressure. Further purification by silica gel column chromatography (5:1 petroleum ether/ethylacetate) give 1-phenyl-1H-pyrazole (2a, 0.126 g, 88percent) as a Colorless liquid.
Reference: [1] Advanced Synthesis and Catalysis, 2007, vol. 349, # 17-18, p. 2673 - 2676
[2] Journal of Organic Chemistry, 2004, vol. 69, # 17, p. 5578 - 5587
[3] Tetrahedron Letters, 2006, vol. 47, # 29, p. 5203 - 5205
[4] Chinese Journal of Chemistry, 2012, vol. 30, # 10, p. 2389 - 2393,5
[5] Tetrahedron Letters, 2013, vol. 54, # 15, p. 1994 - 1997
[6] European Journal of Organic Chemistry, 2004, # 4, p. 695 - 709
  • 22
  • [ 288-13-1 ]
  • [ 615-37-2 ]
  • [ 20157-44-2 ]
YieldReaction ConditionsOperation in experiment
94% at 82℃; for 70 h; 0535] Preparation of 1-(o-tolyl)-1H-pyrazole [0536] Operating protocol A (82 C., 70 hours) was followed using 117 mg of Chxn-Py-Al (0.4 mmoles), 383 ?l of 2-iodotoluene (3 mmoles), 136 mg of pyrazole (2 mmoles) and 1.2 ml of acetonitrile. [0537] The degree of transformation and selectivity for 1-(o-tolyl)-1H-pyrazole were 100percent. [0538] The residue obtained was purified by silica gel chromatography (eluent: hexane/dichloromethane, 100/0 to 0/100). [0539] 297 mg of a pale yellow oil was obtained, corresponding to a yield of 94percent by weight. [0540] The compound obtained had the following formula: [CHEMMOL-00045]
87% With 2,2'-biimidazole; copper(II) acetate monohydrate; caesium carbonate In dimethyl sulfoxide at 80℃; for 48 h; (1) The o-iodobenzene 0.218g (1.0mmol), pyrazole 0.069g (1.0mmol), Cu (OAc)2·H2O 0.030g (0.15mmol), 2,2- biimidazole 0.022g (0.15mmol), cesium carbonate 0.652g (2mmol), DMSO (2mL) was added the reaction tube with a piston, was heated to 80 deg.] C with stirring for 48 hours reaction.(2) TLC until the reaction was complete the reaction was followed ends.After the reaction was cooled to room temperature, diluted with water, extracted with ethyl acetate 3-4 was added, and the combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated to give the crude product.After the end of (3) to obtain the crude product was purified by column chromatography (petroleum ether / ethyl acetate elution) to give the desired product 4 (87percent yield).
83% With (N,N'-bis(salicylidenate)cyclohexane-1,2-diamine)copper(II); sodium hydroxide In dimethyl sulfoxide at 100℃; for 12 h; Sealed tube General procedure: Complex 2 (0.05 mmol) was added to a 5 mL of a sealed tube containing the aryl iodide or bromide (0.5 mmol), 1H-pyrazole (0.75 mmol), NaOH (1 mmol), and DMSO (1 mL). The mixture was stirred at 100 °C for 12 h. After being cooled to room temperature, the mixture was quenched with 10 mL H2O and extracted with EtOAc(3 × 20 mL). The combined EtOAc extracts were dried with anhydrous Na2SO4, filtered and the solvent was removed under reduced pressure.The residue was purified by flash column chromatography on silicagel with PE/EtOAc (from 10:1 to 5:1) as the eluent to afford the pure products. All N-aryl pyrazoles reported here are known products and were characterised by 1H NMR, and GC-MS.
65% With copper(l) iodide; tetrabutylammomium bromide; N-(2-aminoethyl)-N'-{2-[(2-aminoethyl)amino]ethyl}ethane-1,2-diamine In water at 125℃; for 12 h; General procedure: Iodobenzene (1.0 mmol), imidazole (1.5 mmol), TEPA (2.0 mmol), TBAB (0.3 mmol), CuI (0.1 mmol), and 3 mL H2O were added to a 10 mL flask, which was subsequently capped with a rubber balloon. The mixture was stirred in a preheated oil bath at 125 °C for 12 h. After cooling the mixture to the room temperature, 5 mL water was added and the product was extracted by ethyl acetate (10 mL×3). The combined organic layer was washed by brine (15 mL), dried over anhydrous MgSO4, and evaporated under the reduced pressure. Further purification by silica gel column chromatography (6:1 petroleum ether/ethyl acetate) give the 1-phenyl-1H-imidazole.
40% With copper diacetate; sodium hydroxide; 3-(diphenylphosphino)propionic acid In 1,4-dioxane at 100℃; for 24 h; Sealed tube General procedure: Cu(OAc)2 (0.03mmol), L2 (0.06mmol), aryl idione or bromide (0.5mmol), 1H-pyrazole (0.75mmol), NaOH (1mmol), and 1,4-dioxane (1mL) was added into a 5mL tube, then sealed. The mixture was stirred at 100°C for certain time. After cooling to room temperature, the mixture was quenched with 10mL H2O and extracted with EtOAc (3×20mL). The combined EtOAc extracts were dried with anhydrous Na2SO4 and filtrated and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel with PE/EtOAc, as the eluent, to afford the desired products.

Reference: [1] European Journal of Organic Chemistry, 2004, # 4, p. 695 - 709
[2] Patent: US2003/236413, 2003, A1, . Location in patent: Page 21
[3] Patent: CN104447557, 2017, B, . Location in patent: Paragraph 0050; 0051; 0052; 0053; 0054; 0055
[4] Journal of Chemical Research, 2013, vol. 37, # 10, p. 636 - 637
[5] Synlett, 2006, # 13, p. 2124 - 2126
[6] Tetrahedron Letters, 2009, vol. 50, # 42, p. 5868 - 5871
[7] Tetrahedron, 2013, vol. 69, # 30, p. 6230 - 6233
[8] Chinese Chemical Letters, 2014, vol. 25, # 5, p. 775 - 778
[9] Synlett, 2012, vol. 23, # 19, p. 2763 - 2767
  • 23
  • [ 288-13-1 ]
  • [ 16419-60-6 ]
  • [ 20157-44-2 ]
Reference: [1] Helvetica Chimica Acta, 2010, vol. 93, # 5, p. 974 - 979
  • 24
  • [ 288-13-1 ]
  • [ 95-53-4 ]
  • [ 20157-44-2 ]
Reference: [1] Chemistry - A European Journal, 2014, vol. 20, # 45, p. 14619 - 14623
  • 25
  • [ 288-13-1 ]
  • [ 603-76-9 ]
  • [ 61-70-1 ]
  • [ 1414867-74-5 ]
  • [ 1414867-88-1 ]
Reference: [1] Organic Letters, 2012, vol. 14, # 23, p. 5832 - 5835
  • 26
  • [ 288-13-1 ]
  • [ 603-76-9 ]
  • [ 61-70-1 ]
  • [ 1414867-74-5 ]
Reference: [1] Organic Letters, 2012, vol. 14, # 23, p. 5832 - 5835
  • 27
  • [ 288-13-1 ]
  • [ 288-32-4 ]
  • [ 75-09-2 ]
  • [ 84661-56-3 ]
  • [ 84661-55-2 ]
  • [ 27258-04-4 ]
Reference: [1] Journal of Heterocyclic Chemistry, 1982, vol. 19, p. 1141 - 1145
  • 28
  • [ 288-13-1 ]
  • [ 645-00-1 ]
  • [ 25688-18-0 ]
YieldReaction ConditionsOperation in experiment
88% With copper(I) oxide; caesium carbonate; N-phenyl-2-pyridincarboxamide-1-oxide In acetonitrile for 20 h; Inert atmosphere; Reflux General procedure: In 50 mL round bottom flask, aryl halide (1.0 mmol), pyrazole (1.2 mmol), ligand (0.04 mmol), Cu2O (0.10 mmol), cesium carbonate (2.0 mmol), and dry solvent (20 mL) were placed under nitrogen atmosphere. The reaction mixture was heated in oil bath up to specified temperature under constant stirring for 20 h and then allowed to cool to room temperature. The reaction mixture was filtered through a plug of Celite in a fritted filter funnel and washed with ethyl acetate. If DMSO is used as solvent, it is extracted by washing the filtrate with 25 mL water for three times. The organic phase was dried over anhydrous MgSO4 and was removed under reduced pressure to provide the crude product which was purified by column chromatography on silica gel, using hexane and ethyl acetate in 3:1 ratio, respectively, as an eluent.
70% With copper(l) iodide; manganese(II) fluoride; (1R,2R)-1,2-diaminocyclohexane; potassium hydroxide In water at 60℃; for 24 h; General procedure: The N-nucleophile (1.47 mmol), CuI (Sigma-Aldrich, 99.999percent purity, 0.147 mmol), MnF2 (Sigma-Aldrich, 98percent purity, 0.441 mmol), KOH (2.94 mmol), the aryl halide (2.21 mmol), trans-1,2-diaminocyclohexane (0.294 mmol) and water (0.75 mL) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 60C for 24 h. After cooling to room temperature, the mixture was diluted with dichloromethane and filtered through a pad of Celite. The combined organic extracts were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of known products was confirmed by 1H and 13C NMR spectroscopic analysis.
Reference: [1] Journal of Organic Chemistry, 2007, vol. 72, # 23, p. 8969 - 8971
[2] Tetrahedron Letters, 2016, vol. 57, # 20, p. 2197 - 2200
[3] Angewandte Chemie, International Edition, 2009, vol. 48, # 40, p. 7398 - 7401[4] Angewandte Chemie, 2009, vol. 121, # 40, p. 7534 - 7537
[5] Tetrahedron Letters, 2011, vol. 52, # 52, p. 7171 - 7174
  • 29
  • [ 288-13-1 ]
  • [ 402-67-5 ]
  • [ 25688-18-0 ]
YieldReaction ConditionsOperation in experiment
71% With caesium carbonate In 1-methyl-pyrrolidin-2-one at 100℃; for 17 h; A mixture of 3-fluoronitrobenzene (1.0 g, 7.1 mmol), pyrazole (0.58 g, 8.5 mmol), and cesium carbonate (2.8 g, 8.5 mmol) in 4 mL of N-methylpyrrolidinone was heated to 100°C for 17 h. After cooling to rt, the mixture was diluted with water (75 mL) and extracted with ethyl acetate (3 x 75 mL) and the combined extracts were washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to afford 1.7 g (71 percent) of 110A as a dark red oil. LCMS (M+H+) = 190.1. HPLC Ret. time: 2.42 min.
Reference: [1] Patent: WO2003/90912, 2003, A1, . Location in patent: Page/Page column 85-86
[2] Australian Journal of Chemistry, 1993, vol. 46, # 4, p. 417 - 425
  • 30
  • [ 288-13-1 ]
  • [ 121-73-3 ]
  • [ 25688-18-0 ]
YieldReaction ConditionsOperation in experiment
56% With copper(l) iodide; 1,10-phenanthroline N-oxide; caesium carbonate In N,N-dimethyl-formamide at 110 - 120℃; for 84 h; Inert atmosphere To the three-neck flask, CuI (19 mg, 0.1 mmol, 10 molpercent), 1,10-phenanthroline-N-oxide (39 mg, 0.2 mmol, 20 molpercent), Cs2CO3 (650 mg, 2.0mmol). The reaction flask was evacuated under argon. m-nitrochlorobenzene (157 mg, 1.0 mmol), pyrazole (102 mg, 1.5 mmol) and DMF (2 mL) were added under an atmosphere of argon gas. Reaction was carried out at 120 °C for 72 hours and at 110 °C for 12 hours until the reaction starting material was completely reacted (the reaction was complete by TLC). After completion of the reaction, a brown oil was obtained which was diluted with ethyl acetate. The inorganic salt was removed by filtration and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography using petroleum ether / ethyl acetate as eluant to give 1-(3-nitrophenyl)-1-hydropyrazole as a yellow solid in 56percent yield.
Reference: [1] Chinese Journal of Chemistry, 2014, vol. 32, # 8, p. 685 - 688
[2] Patent: CN104356131, 2016, B, . Location in patent: Paragraph 0355-0366
  • 31
  • [ 288-13-1 ]
  • [ 585-79-5 ]
  • [ 25688-18-0 ]
Reference: [1] Advanced Synthesis and Catalysis, 2007, vol. 349, # 17-18, p. 2673 - 2676
[2] ChemCatChem, 2014, vol. 6, # 8, p. 2373 - 2383
[3] European Journal of Organic Chemistry, 2004, # 4, p. 695 - 709
  • 32
  • [ 288-13-1 ]
  • [ 586-78-7 ]
  • [ 2301-25-9 ]
Reference: [1] ChemCatChem, 2014, vol. 6, # 8, p. 2373 - 2383
  • 33
  • [ 107073-66-5 ]
  • [ 75-26-3 ]
  • [ 288-13-1 ]
  • [ 49633-25-2 ]
Reference: [1] Heterocycles, 1986, vol. 24, # 4, p. 1075 - 1078
  • 34
  • [ 288-13-1 ]
  • [ 109-04-6 ]
  • [ 25700-11-2 ]
YieldReaction ConditionsOperation in experiment
87% for 8 h; Reflux (Pyr-N-PzH) Compound 3
To a 250 mL single-neck round bottomed flask were charged 15.0 g (95 mmol) of 2-bromopyridine, 25.0 g (367 mmol, 3.86 eq.) of pyrazole, and 45 mL of xylenes.
The mixture was heated at reflux for eight hours, then was cooled to room temperature.
The resulting mixture was dissolved in dichloromethane, and the organic layer washed four times with 250 mL of water (until no pyrazole was observed by GC).
Drying over magnesium sulfate, filtering and rotary evaporation gave 12.0 g (82.6 mmol, 87percent) of the product as a white solid. 1H NMR (400 MHz, CDCl3) 8.59 (m, 1H, Pyridyl 6-H), 8.39 (s, 1H, Pyrazole 5-H), 7.90 (d, 1H, Pyridyl 3-H), 7.80 (m, 1H, Pyridyl 4-H), 7.73 (s, 1H, Pyrazole 3-H), 7.15 (s, 1H, Pyridyl 5-H), 6.45 (m, 1H, Pyrazole 4-H).
75% With potassium hydroxide In dimethyl sulfoxide at 120℃; for 24 h; Dry DMSO (4 mL) was added to a mixture of 1H-pyrazole (340 mg, 5.00 mmol), 2-bromopyridine (790 mg, 5.00 mmol) and KOH (700 mg, 12.5 mmol) and heated at 120 °Cfor 24 h. The reaction mixture was quenched with saturated solution of NH4Cl and extractedwith EtOAc. The organic phase was dried over anhydrous Na2SO4, followed by evaporationunder reduced pressure to remove the solvent. Purification of the crude reaction mixture byflash column chromatography using 2.5percent acetone in petroleum ether afforded the titledcompound as low melting white solid (544 mg, 75percent).
Reference: [1] Tetrahedron, 2010, vol. 66, # 47, p. 9141 - 9144
[2] Organic and Biomolecular Chemistry, 2015, vol. 13, # 13, p. 4101 - 4114
[3] European Journal of Organic Chemistry, 2011, # 14, p. 2692 - 2696
[4] Journal of Organic Chemistry, 2005, vol. 70, # 13, p. 5164 - 5173
[5] Journal of Organic Chemistry, 2011, vol. 76, # 2, p. 654 - 660
[6] Patent: US2016/244860, 2016, A1, . Location in patent: Paragraph 0118-0119
[7] Organic and Biomolecular Chemistry, 2011, vol. 9, # 12, p. 4671 - 4684
[8] Journal of Organic Chemistry, 2018, vol. 83, # 12, p. 6408 - 6422
[9] Tetrahedron Letters, 2014, vol. 55, # 52, p. 7198 - 7202
[10] Green Chemistry, 2011, vol. 13, # 1, p. 42 - 45
[11] Chemical Communications, 2007, # 45, p. 4809 - 4811
[12] Chemistry - A European Journal, 2011, vol. 17, # 25, p. 6998 - 7006
[13] Chemical Communications, 2014, vol. 50, # 5, p. 530 - 532
[14] Dalton Transactions, 2015, vol. 44, # 18, p. 8521 - 8528
  • 35
  • [ 288-13-1 ]
  • [ 5029-67-4 ]
  • [ 25700-11-2 ]
YieldReaction ConditionsOperation in experiment
87% With copper(I) oxide; caesium carbonate In dimethyl sulfoxide at 100℃; for 24 h; Inert atmosphere General procedure: The N-nucleophile (0.735mmol), Cu2O (0.0735mmol), Cs2CO3 (1.47mmol), DMSO (0.3mL) and heteroaryl halide (1.103mmol) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 100°C for 24h. After cooling to room temperature, the mixture was diluted with dichloromethane and filtered through a pad of Celite. The combined organic extracts were dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of the products was confirmed by 1H, 13C NMR spectroscopic analysis and elemental analysis or mass spectroscopy.
Reference: [1] Advanced Synthesis and Catalysis, 2017, vol. 359, # 10, p. 1631 - 1636
[2] Tetrahedron Letters, 2009, vol. 50, # 42, p. 5868 - 5871
[3] Tetrahedron, 2013, vol. 69, # 35, p. 7279 - 7284
[4] Green Chemistry, 2011, vol. 13, # 1, p. 42 - 45
  • 36
  • [ 288-13-1 ]
  • [ 1120-90-7 ]
  • [ 25700-11-2 ]
YieldReaction ConditionsOperation in experiment
94% With copper(l) iodide; manganese(II) fluoride; (1R,2R)-1,2-diaminocyclohexane; potassium hydroxide In water at 100℃; for 48 h; General procedure: The N-nucleophile (1.47 mmol), CuI (Sigma-Aldrich, 99.999percent purity, 0.147 mmol), MnF2 (Sigma-Aldrich, 98percent purity, 0.441 mmol), KOH (2.94 mmol), the aryl halide (2.21 mmol), trans-1,2-diaminocyclohexane (0.294 mmol) and water (0.75 mL) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 60C for 24 h. After cooling to room temperature, the mixture was diluted with dichloromethane and filtered through a pad of Celite. The combined organic extracts were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of known products was confirmed by 1H and 13C NMR spectroscopic analysis.
Reference: [1] Tetrahedron Letters, 2011, vol. 52, # 52, p. 7171 - 7174
  • 37
  • [ 288-13-1 ]
  • [ 694-59-7 ]
  • [ 25700-11-2 ]
Reference: [1] Organic Letters, 2010, vol. 12, # 22, p. 5254 - 5257
[2] Organic Letters, 2011, vol. 13, # 7, p. 1840 - 1843
  • 38
  • [ 288-13-1 ]
  • [ 142-08-5 ]
  • [ 25700-11-2 ]
Reference: [1] Journal of Organic Chemistry, 2011, vol. 76, # 20, p. 8262 - 8269
[2] Chemistry of Materials, 2013, vol. 25, # 19, p. 3910 - 3920
  • 39
  • [ 288-13-1 ]
  • [ 109-09-1 ]
  • [ 25700-11-2 ]
Reference: [1] Chemische Berichte, 1996, vol. 129, # 5, p. 589 - 594
[2] Green Chemistry, 2011, vol. 13, # 1, p. 42 - 45
  • 40
  • [ 288-13-1 ]
  • [ 372-48-5 ]
  • [ 25700-11-2 ]
Reference: [1] Green Chemistry, 2011, vol. 13, # 1, p. 42 - 45
  • 41
  • [ 288-13-1 ]
  • [ 504-29-0 ]
  • [ 25700-11-2 ]
Reference: [1] Chemistry - A European Journal, 2014, vol. 20, # 45, p. 14619 - 14623
  • 42
  • [ 288-13-1 ]
  • [ 626-55-1 ]
  • [ 25700-12-3 ]
YieldReaction ConditionsOperation in experiment
93% With copper(I) oxide; salicylaldehyde-oxime; caesium carbonate In acetonitrile for 24 h; Inert atmosphere; Reflux To a solution of copper(I) oxide (0.906 g, 6.33 mmol), salicylaldoximine (3.47 g, 25.3 mmol), 1H-pyrazole (12.93 g, 190 mmol), and cesium carbonate (66.0 g, 203 mmol) in acetonitrile (50.6 ml) under a nitrogen stream was added 3-bromopyridine (20 g, 127 mmol).
The reaction mixture was heated at reflux for 24H.
The reaction mixture was allowed to cool to ambient temperature, and then diluted with EtOAc, filtered through celite, and washed with H2O and saturated brine solution.
The organics were separated, dried with MgSO4, filtered and concentrated in vacuo.
The residue was purified by column chromatography eluting with 0-50percent acetone in hexanes to afford 3-(1H-pyrazol-1-yl)pyridine as a yellow oil (17 g, 93percent): 1H NMR (400 MHz, acetone-d6) δ 9.14 (d, J=2.2 Hz, 1H), 8.54 (d, J=3.8 Hz, 1H), 8.45 (dd, J=2.5, 0.5 Hz, 1H), 8.24 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.79 (d, J=1.5 Hz, 1H), 7.53 (ddd, J=8.3, 4.7, 0.7 Hz, 1H), 6.59 (dd, J=2.5, 1.8 Hz, 1H); EIMS m/z 145.
43% With caesium carbonate In acetonitrile at 80℃; for 24 h; Inert atmosphere Step 1:
Preparation of 3-pyrazol-1-yl-pyridine
To a solution of 3-bromopyridine (5 g, 0.031 mol) in 50 ml of acetonitrile were added pyrazole (2.6 g, 0.038 mol), Cs2CO3 (16.5 g, 0.050 mol), Cu2O (0.226 g, 0.0016 mol), and salicylaldoxime (0.867 g, 0.006 mol) under N2 atmosphere.
The reaction mass was refluxed for 24 hrs at 80° C.
The reaction mass was concentrated and the crude was purified by column chromatography using ethyl acetate and hexane (1:1) to afford the pyrazolyl pyridine as a dark brown liquid (2 g, 43percent): 1H NMR (400 MHz, CDCl3) δ 8.99 (d, J=2.8 Hz, 1H), 8.48 (dd, J=4.8, 1.2 Hz, 1H), 8.11-8.08 (m, 1H), 7.99 (d, J=1.2 Hz, 1H), 7.78 (d, J=1.2 Hz, 1H), 7.38-7.35 (m, 1H), 6.53 (t, J=1.2 Hz, 1H); MS (m/z) 146 [M+1].
43% With copper(I) oxide; salicylaldehyde-oxime; caesium carbonate In acetonitrile at 80℃; for 24 h; Inert atmosphere To a solution of 3-bromopyridine (5 g, 0.031 mol) in 50 ml of acetonitrile were added pyrazole (2.6 g, 0.038 mol), Cs2CO(16.5 g, 0.050 mol), Cu2O (0.226 g, 0.0016 mol), and salicylaldoxime (0.867 g, 0.006 mol) under Natmosphere. The reaction mass was refluxed for 24 hrs at 80° C. The reaction mass was concentrated and the crude was purified by column chromatography using ethyl acetate and hexane (1:1) to afford the pyrazolyl pyridine as a dark brown liquid (2 g, 43percent): 1H NMR (400 MHz, CDCl3) δ 8.99 (d, J=2.8 Hz, 1H), 8.48 (dd, J=4.8, 1.2 Hz, 1H), 8.11-8.08 (m, 1H), 7.99 (d, J=1.2 Hz, 1H), 7.78 (d, J=1.2 Hz, 1H), 7.38-7.35 (m, 1H), 6.53 (t, J=1.2 Hz, 1H); MS (m/z) 146 [M+1].
43% With copper(I) oxide; salicylaldehyde-oxime; caesium carbonate In acetonitrile at 80℃; for 24 h; Inert atmosphere Step 1:
Preparation of 3-pyrazol-1-yl-pyridine
To a solution of 3-bromopyridine (5 g, 0.031 mol) in 50 ml of acetonitrile were added pyrazole (2.6 g, 0.038 mol), Cs2CO3 (16.5 g, 0.050 mol), Cu2O (0.226 g, 0.0016 mol), and salicylaldoxime (0.867 g, 0.006 mol) under N2 atmosphere.
The reaction mass was refluxed for 24 hrs at 80° C.
The reaction mass was concentrated and the crude was purified by column chromatography using ethyl acetate and hexane (1:1) to afford the pyrazolyl pyridine as a dark brown liquid (2 g, 43percent): 1H NMR (400 MHz, CDCl3) δ 8.99 (d, J=2.8 Hz, 1H), 8.48 (dd, J=4.8, 1.2 Hz, 1H), 8.11-8.08 (m, 1H), 7.99 (d, J=1.2 Hz, 1H), 7.78 (d, J=1.2 Hz, 1H), 7.38-7.35 (m, 1H), 6.53 (t, J=1.2 Hz, 1H); MS (m/z) 146 [M+1].
43% With copper(I) oxide; caesium carbonate; hydroxybenzaldoxime In acetonitrile at 80℃; for 24 h; Inert atmosphere Step 1:
Preparation of 3-pyrazol-1-yl-pyridine
To a solution of 3-bromopyridine (5 g, 0.031 mol) in 50 ml of acetonitrile were added pyrazole (2.6 g, 0.038 mol), Cs2CO3 (16.5 g, 0.050 mol), Cu2O (0.226 g, 0.0016 mol), and salicylaldoxime (0.867 g, 0.006 mol) under N2 atmosphere.
The reaction mass was refluxed for 24 hrs at 80° C.
The reaction mass was concentrated and the crude was purified by column chromatography using ethyl acetate and hexane (1:1) to afford the pyrazolyl pyridine as a dark brown liquid (2 g, 43percent): 1H NMR (400 MHz, CDCl3) δ 8.99 (d, J=2.8 Hz, 1H), 8.48 (dd, J=4.8, 1.2 Hz, 1H), 8.11-8.08 (m, 1H), 7.99 (d, J=1.2 Hz, 1H), 7.78 (d, J=1.2 Hz, 1H), 7.38-7.35 (m, 1H), 6.53 (t, J=1.2 Hz, 1H); MS (m/z) 146 [M+1].

Reference: [1] European Journal of Organic Chemistry, 2004, # 4, p. 695 - 709
[2] Patent: US2012/220453, 2012, A1, . Location in patent: Paragraph 0164; 0165
[3] Synthesis (Germany), 2012, vol. 44, # 13, p. 2041 - 2048
[4] Organic and Biomolecular Chemistry, 2015, vol. 13, # 13, p. 4101 - 4114
[5] Organic and Biomolecular Chemistry, 2011, vol. 9, # 12, p. 4671 - 4684
[6] Green Chemistry, 2011, vol. 13, # 1, p. 42 - 45
[7] Advanced Synthesis and Catalysis, 2010, vol. 352, # 18, p. 3158 - 3162
[8] Patent: US2012/110702, 2012, A1, . Location in patent: Page/Page column 15
[9] Patent: US2013/109566, 2013, A1, . Location in patent: Paragraph 0163; 0164
[10] Patent: US2013/288893, 2013, A1, . Location in patent: Paragraph 0191-0192
[11] Patent: US2016/60245, 2016, A1, . Location in patent: Paragraph 0191; 0192
  • 43
  • [ 288-13-1 ]
  • [ 1120-90-7 ]
  • [ 25700-12-3 ]
YieldReaction ConditionsOperation in experiment
83% With copper(I) oxide; caesium carbonate In dimethyl sulfoxide at 100℃; for 24 h; Inert atmosphere General procedure: The N-nucleophile (0.735mmol), Cu2O (0.0735mmol), Cs2CO3 (1.47mmol), DMSO (0.3mL) and heteroaryl halide (1.103mmol) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 100°C for 24h. After cooling to room temperature, the mixture was diluted with dichloromethane and filtered through a pad of Celite. The combined organic extracts were dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of the products was confirmed by 1H, 13C NMR spectroscopic analysis and elemental analysis or mass spectroscopy.
Reference: [1] Tetrahedron Letters, 2009, vol. 50, # 42, p. 5868 - 5871
[2] Green Chemistry, 2011, vol. 13, # 1, p. 42 - 45
[3] Tetrahedron, 2013, vol. 69, # 35, p. 7279 - 7284
  • 44
  • [ 288-13-1 ]
  • [ 1120-90-7 ]
  • [ 25700-12-3 ]
  • [ 25700-13-4 ]
Reference: [1] Journal of Organic Chemistry, 2011, vol. 76, # 2, p. 654 - 660
  • 45
  • [ 288-13-1 ]
  • [ 372-47-4 ]
  • [ 25700-12-3 ]
Reference: [1] Green Chemistry, 2011, vol. 13, # 1, p. 42 - 45
  • 46
  • [ 288-13-1 ]
  • [ 626-60-8 ]
  • [ 25700-12-3 ]
Reference: [1] Green Chemistry, 2011, vol. 13, # 1, p. 42 - 45
  • 47
  • [ 288-13-1 ]
  • [ 1194-02-1 ]
  • [ 25699-83-6 ]
YieldReaction ConditionsOperation in experiment
87% With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 7 h; 4-( 1 H-pyrazol- 1 -yl)- benzonitrile4-Fluorobenzonitrile (204.2 g), pyrazole (138.6 g, 1.22 eq) and potassium carbonate (281.5 g, 1.22 eq) in DMF (1110 ml) were heated at 120 0C for 7 hours. The suspension was cooled to 25 0C and water (2920 ml) added. The reaction was extracted with MTBE (3 x 1460 ml) and the combined extracts were washed with water (3 x 1460 ml) and saturated aqueous sodium chloride (1460 ml). The organic phase was concentrated at atmospheric pressure until the pot temperature rose to 65 0C. Heptane (1700 ml) was added over 30 minutes at 60-65 0C, and then a further 300 ml of distillate was collected. The solution was stirred at 60-65 0C for 15 minutes and then cooled to <5 0C. The slurry was filtered and washed with heptane (2 x 200 ml), and dried under vacuum to constant weight to give the title compound as a solid (245.3 g, 87percent). <n="47"/>1H NMR (400 MHz, CDCl3): 6.51 (q, IH), 7.71 (d, 2H), 7.75 (d, IH), 7.81 (d, 2H), 7.98 (d, IH).
83% With potassium carbonate In N,N-dimethyl-formamide at 115 - 120℃; for 7 - 8 h; Inert atmosphere 5f: 4-(1H-pyrazol-1-yl)benzonitrile N,N-dimethylformamide (123.25 L) was charged to the vessel and analysed for moisture content (target<0.5percent). Potassium carbonate (34.01 kg) was then charged to the vessel followed by pyrazole (16.76 kg) and 4-fluorobenzonitrile (24.65 kg). The reaction mixture was heated to 115 to 120° C. and stirred at this temperature for between seven and eight hours under a nitrogen atmosphere. The reaction was monitored by GC (target<10percent 4-fluorobenzonitrile). The reaction was then cooled to 20-25° C. and quenched with water (369.7 L). Methyl tert-butyl ether (246.5 L) was then charged and the layers allowed to separate. The aqueous layer was washed with methyl tert-butyl ether (2 x147.9 L) and the organic layers combined. The organic layer was then washed with water (2 x 172.55 L) and aqueous brine (123.25 L, 24 wt percent). The organic phase was then concentrated to approximately 100 L at 60° C. or below at atmospheric pressure. n-Heptane (209 L) was then charged and the mixture concentrated to approximately 100 L at 60° C. or below at atmospheric pressure. The reaction was cooled to 0° C. and stirred for three hours at this temperature. The slurry was then filtered washing the filter cake with n-heptane (24.65 L). The resulting solid was dried under vacuum at 40° C. to yield the title product (28.6 kg, 99.32percent purity, 83percent yield). 1H NMR (300 MHz, DMSO-d6): 6.61 (dd, J=2.4, 1.9 Hz, 1H), 7.83 (d, J=1.4 Hz 1H), 7.94 (d, J=8.7 Hz, 2H), 8.04 (d, J=9.0 Hz, 2H), 8.65 (d, J=2.4 Hz, 1H).
80% With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 16 h; Step 1. 4-(lH-Pyrazol-l-yl)benzonitrile (0847) [00269] A mixture of lH-pyrazole (15 g, 220.34 mmol), 4-fluorobenzonitrile (27 g, 222.93 mmol), potassium carbonate (60.7 g, 439.19 mmol) in DMF (200 mL) was stirred for 16 h at 110 °C. After cooling to ambient temperature, the reaction mixture was poured into water (500 mL) and the resulting solids were collected by filtration and dried under vacuum, resulting in 30 g (80percent) of 4-(lH-pyrazol-l-yl)benzonitrile. MS (ESI) m/z 170 [M+H]+.
62%
Stage #1: With sodium hydroxide In N,N-dimethyl-formamide at 80℃; for 0.5 h; Inert atmosphere
Stage #2: at 110℃; for 3 h;
Into a 50-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 1H-pyrazole (422 mg, 6.21 mmol, 1.50 equiv), sodium hydroxide (248 mg, 6.20 mmol, 1.50 equiv), and N,N-dimethylformamide (20 mL).
The mixture was stirred and heated to 80° C. for 30 min, then to this was added 4-fluorobenzonitrile (500 mg, 4.13 mmol, 1.00 equiv).
The resulting solution was stirred for 3 h at 110° C. in an oil bath.
The resulting solution was diluted with 50 mL of H2O.
The solids were collected by filtration and dried in an oven.
The product was obtained as 0.43 g (62percent) of a white solid.
47% With caesium carbonate In N,N-dimethyl-formamide for 2 h; Reflux A 100-mE round-bottom flask was charged with4-fluorobenzonitrile (2 g, 16.51 mmol), cesium carbonate (16 g, 49.11 mmol), N,N-dimethylformamide (20 mE) and 1 H-pyrazole (2.24 g, 32.90 mmol). The resulting solution was refluxed for 2 h. The solids were removed by filtration and the filtrate was concentrated under vacuum. The residue was purified by column chromatography eluting with ethyl acetate/petroleum ether (1:10 to 1:4 v/v) to afford 4-(1H- pyrazol-i-yl)benzonitrile as a yellow oil (1.3 g, 47percent). LCMS: (ESI) mlz 170 [M+H].
47% With caesium carbonate In N,N-dimethyl-formamide for 2 h; Reflux A 100-mL round-bottom flask was charged with 4-fluorobenzonitrile (2 g, 16.51 mmol), cesium carbonate (16 g, 49.11 mmol), N,N-dimethylformamide (20 mL) and 1H-pyrazole (2.24 g, 32.90 mmol). The resulting solution was refluxed for 2 h. The solids were removed by filtration and the filtrate was concentrated under vacuum. The residue was purified by column chromatography eluting with ethyl acetate/petroleum ether (1:10 to 1:4 v/v) to afford 4-(1H-pyrazol-1-yl)benzonitrile as a yellow oil (1.3 g, 47percent). LCMS: (ESI) m/z 170 [M+H].

Reference: [1] Patent: WO2009/61271, 2009, A1, . Location in patent: Page/Page column 45-46
[2] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 11, p. 2955 - 2959
[3] Patent: US2011/224229, 2011, A1, . Location in patent: Page/Page column 19
[4] Patent: WO2017/87837, 2017, A1, . Location in patent: Paragraph 00269
[5] Patent: US9301951, 2016, B2, . Location in patent: Page/Page column 231
[6] Patent: US2016/185785, 2016, A1, . Location in patent: Paragraph 2106; 2107
[7] Patent: US2016/185786, 2016, A1, . Location in patent: Paragraph 0629
  • 48
  • [ 288-13-1 ]
  • [ 623-03-0 ]
  • [ 25699-83-6 ]
YieldReaction ConditionsOperation in experiment
51% With copper(l) iodide; 1,10-phenanthroline N-oxide; caesium carbonate In N,N-dimethyl-formamide at 120℃; Inert atmosphere To the three-necked flask, CuI (19 mg, 0.1 mmol, 10 molpercent), 1,10-phenanthroline-N-oxide (39 mg, 0.2 mmol, 20 molpercent) and Cs2CO3 (650 mg, 2.0mmol). The reaction flask was evacuated under argon. p-cyanochlorbenzene (138 mg, 1.0mmol), pyrazole (102 mg, 1.5 mmol) and DMF (2 mL) were added under an atmosphere of argon gas. The reaction was carried out at 120 °C for 72 hours until the starting reaction was complete (the reaction was complete by TLC). After completion of the reaction, a brown oil was obtained which was diluted with ethyl acetate. The inorganic salt was removed by filtration and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography using petroleum ether / ethyl acetate as eluant to give 1-(4-carbonitrilephenyl)pyrazole as a pale yellow oil in a yield of 51percent.
Reference: [1] Advanced Synthesis and Catalysis, 2007, vol. 349, # 17-18, p. 2673 - 2676
[2] Chemistry - A European Journal, 2014, vol. 20, # 18, p. 5231 - 5236
[3] Journal of Organic Chemistry, 2011, vol. 76, # 9, p. 3151 - 3159
[4] RSC Advances, 2016, vol. 6, # 64, p. 59550 - 59564
[5] Patent: CN104356131, 2016, B, . Location in patent: Paragraph 0316-0327
  • 49
  • [ 288-13-1 ]
  • [ 623-00-7 ]
  • [ 25699-83-6 ]
YieldReaction ConditionsOperation in experiment
98% at 90℃; for 30 h; sealed tube Following General Procedure A (90 0C, 30 hours), 1H-pyrazole (205 mg, 3.0 mmol) is coupled with 4-bromobenzonitrile (364 mg, 2.0 mmol). The crude brown oil is purified by flash chromatography on silica gel (eluent: dichloromethane / hexanes = 50/50) to provide 330 mg (98 percent isolated yield) of the desired product as a white solid. identificationMp: 89°C. <n="45"/>1H NMR (400 MHz5 CDCI3): δ 7.92-7.93 (d, 1 H1 H7), 7.75-7.78 (m, 2H, H3l5), 7.65-7.70 (m, 3H, H2,B,9), 6.46-6:47 (dd, 1H1 H8).13C NMR (100 MHz, CDCI3): δ 142.95 (C1), 142.50 (C9), 133.68 (C3,5), 126.94 (C7), 118.93 (C2,6), 118.44 (C10), 109.53 (C4), 109.15 (C8). IR (KBr) : v (cm-1) = 3153, 3136, 3066, 2226(CN), 1610, 1528, 1513, 1392, 1342, 1252, 1199, 1176, 1127, 1030, 934, 834, 813, 749, 650, 572, 545. GC/MS: rt = 18.92 min, M/Z = 169. HRMS: 170.0700 (M+H). Theoretical: 170.0718.
82% With copper(I) oxide; caesium carbonate; N-phenyl-2-pyridincarboxamide-1-oxide In acetonitrile for 20 h; Inert atmosphere; Reflux General procedure: In 50 mL round bottom flask, aryl halide (1.0 mmol), pyrazole (1.2 mmol), ligand (0.04 mmol), Cu2O (0.10 mmol), cesium carbonate (2.0 mmol), and dry solvent (20 mL) were placed under nitrogen atmosphere. The reaction mixture was heated in oil bath up to specified temperature under constant stirring for 20 h and then allowed to cool to room temperature. The reaction mixture was filtered through a plug of Celite in a fritted filter funnel and washed with ethyl acetate. If DMSO is used as solvent, it is extracted by washing the filtrate with 25 mL water for three times. The organic phase was dried over anhydrous MgSO4 and was removed under reduced pressure to provide the crude product which was purified by column chromatography on silica gel, using hexane and ethyl acetate in 3:1 ratio, respectively, as an eluent.
78% With copper(l) iodide; tetrabutylammomium bromide; N-(2-aminoethyl)-N'-{2-[(2-aminoethyl)amino]ethyl}ethane-1,2-diamine In water at 125℃; for 24 h; General procedure: Iodobenzene (1.0 mmol), imidazole (1.5 mmol), TEPA (2.0 mmol), TBAB (0.3 mmol), CuI (0.1 mmol), and 3 mL H2O were added to a 10 mL flask, which was subsequently capped with a rubber balloon. The mixture was stirred in a preheated oil bath at 125 °C for 12 h. After cooling the mixture to the room temperature, 5 mL water was added and the product was extracted by ethyl acetate (10 mL×3). The combined organic layer was washed by brine (15 mL), dried over anhydrous MgSO4, and evaporated under the reduced pressure. Further purification by silica gel column chromatography (6:1 petroleum ether/ethyl acetate) give the 1-phenyl-1H-imidazole.
Reference: [1] Angewandte Chemie - International Edition, 2007, vol. 46, # 6, p. 934 - 936
[2] Patent: WO2008/4088, 2008, A2, . Location in patent: Page/Page column 43-44
[3] Journal of Organic Chemistry, 2005, vol. 70, # 13, p. 5164 - 5173
[4] New Journal of Chemistry, 2017, vol. 41, # 8, p. 3082 - 3088
[5] European Journal of Organic Chemistry, 2004, # 4, p. 695 - 709
[6] ChemCatChem, 2014, vol. 6, # 8, p. 2373 - 2383
[7] Chemistry - A European Journal, 2014, vol. 20, # 18, p. 5231 - 5236
[8] Tetrahedron Letters, 2016, vol. 57, # 20, p. 2197 - 2200
[9] Tetrahedron, 2013, vol. 69, # 30, p. 6230 - 6233
[10] Organic and Biomolecular Chemistry, 2011, vol. 9, # 12, p. 4671 - 4684
[11] Angewandte Chemie - International Edition, 2009, vol. 48, # 2, p. 333 - 336
  • 50
  • [ 288-13-1 ]
  • [ 3058-39-7 ]
  • [ 25699-83-6 ]
Reference: [1] Chemistry - A European Journal, 2014, vol. 20, # 18, p. 5231 - 5236
[2] Catalysis Science and Technology, 2017, vol. 7, # 19, p. 4401 - 4412
  • 51
  • [ 288-13-1 ]
  • [ 873-74-5 ]
  • [ 25699-83-6 ]
Reference: [1] Chemistry - A European Journal, 2014, vol. 20, # 45, p. 14619 - 14623
  • 52
  • [ 288-13-1 ]
  • [ 529-28-2 ]
  • [ 102908-37-2 ]
YieldReaction ConditionsOperation in experiment
82% With (N,N'-bis(salicylidenate)cyclohexane-1,2-diamine)copper(II); sodium hydroxide In dimethyl sulfoxide at 100℃; for 12 h; Sealed tube General procedure: Complex 2 (0.05 mmol) was added to a 5 mL of a sealed tube containing the aryl iodide or bromide (0.5 mmol), 1H-pyrazole (0.75 mmol), NaOH (1 mmol), and DMSO (1 mL). The mixture was stirred at 100 °C for 12 h. After being cooled to room temperature, the mixture was quenched with 10 mL H2O and extracted with EtOAc(3 × 20 mL). The combined EtOAc extracts were dried with anhydrous Na2SO4, filtered and the solvent was removed under reduced pressure.The residue was purified by flash column chromatography on silicagel with PE/EtOAc (from 10:1 to 5:1) as the eluent to afford the pure products. All N-aryl pyrazoles reported here are known products and were characterised by 1H NMR, and GC-MS.
68% With bis(1-dodecylimidazole)cupronium dichlorocuprate; tetrabutylammomium bromide; potassium carbonate In water at 80℃; for 15 h; Green chemistry General procedure: At first [Cu(Im12)2]CuCl2 (0.5 mmol, 0.305 g) was added to a 25 mL round bottom flask containing water (4 mL), indole (0.117 g, 1 mmol) and iodobenzene (0.203 g, 1 mmol).K2CO3 (0.276 g, 2 mmol) and TBAB (0.322 g, 1 mmol) was added and the reaction stirred at 80 °C for 12 h. The reaction progress was monitored by TLC(EtOAc/n-hexane; 1:3 v/v) and after completion, the organic phase was extracted from the ionic liquid with EtOAc (2 8 mL) and concentrated in vacuo. The promoter was used directly for the next run. The product was purified by silica gel column chromatography (EtOAc/n-hexane; 1:3 v/v). The isolated product was dried under vacuum overnight to give a yield of 92percent. All products are known in the literature and were identified by comparison of their FT-IR, 1H, and 13C NMR spectra with the literature data.
54% With copper diacetate; sodium hydroxide; 3-(diphenylphosphino)propionic acid In 1,4-dioxane at 100℃; for 24 h; Sealed tube General procedure: Cu(OAc)2 (0.03mmol), L2 (0.06mmol), aryl idione or bromide (0.5mmol), 1H-pyrazole (0.75mmol), NaOH (1mmol), and 1,4-dioxane (1mL) was added into a 5mL tube, then sealed. The mixture was stirred at 100°C for certain time. After cooling to room temperature, the mixture was quenched with 10mL H2O and extracted with EtOAc (3×20mL). The combined EtOAc extracts were dried with anhydrous Na2SO4 and filtrated and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel with PE/EtOAc, as the eluent, to afford the desired products.
30% With copper(l) iodide; manganese(II) fluoride; (1R,2R)-1,2-diaminocyclohexane; potassium hydroxide In water at 60℃; for 24 h; General procedure: The N-nucleophile (1.47 mmol), CuI (Sigma-Aldrich, 99.999percent purity, 0.147 mmol), MnF2 (Sigma-Aldrich, 98percent purity, 0.441 mmol), KOH (2.94 mmol), the aryl halide (2.21 mmol), trans-1,2-diaminocyclohexane (0.294 mmol) and water (0.75 mL) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 60C for 24 h. After cooling to room temperature, the mixture was diluted with dichloromethane and filtered through a pad of Celite. The combined organic extracts were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of known products was confirmed by 1H and 13C NMR spectroscopic analysis.

Reference: [1] Advanced Synthesis and Catalysis, 2007, vol. 349, # 17-18, p. 2673 - 2676
[2] Journal of Chemical Research, 2013, vol. 37, # 10, p. 636 - 637
[3] Tetrahedron Letters, 2015, vol. 56, # 46, p. 6360 - 6363
[4] Chinese Chemical Letters, 2014, vol. 25, # 5, p. 775 - 778
[5] Advanced Synthesis and Catalysis, 2009, vol. 351, # 5, p. 720 - 724
[6] Advanced Synthesis and Catalysis, 2010, vol. 352, # 18, p. 3241 - 3245
[7] Angewandte Chemie - International Edition, 2007, vol. 46, # 46, p. 8862 - 8865
[8] Journal of Organic Chemistry, 2009, vol. 74, # 19, p. 7514 - 7517
[9] Chemistry - A European Journal, 2009, vol. 15, # 13, p. 3072 - 3075
[10] Tetrahedron Letters, 2011, vol. 52, # 52, p. 7171 - 7174
[11] Chemical Communications, 2009, # 41, p. 6258 - 6260
  • 53
  • [ 288-13-1 ]
  • [ 578-57-4 ]
  • [ 102908-37-2 ]
YieldReaction ConditionsOperation in experiment
51% With copper diacetate; sodium hydroxide; 3-(diphenylphosphino)propionic acid In 1,4-dioxane at 120℃; for 36 h; Sealed tube General procedure: Cu(OAc)2 (0.03mmol), L2 (0.06mmol), aryl idione or bromide (0.5mmol), 1H-pyrazole (0.75mmol), NaOH (1mmol), and 1,4-dioxane (1mL) was added into a 5mL tube, then sealed. The mixture was stirred at 100°C for certain time. After cooling to room temperature, the mixture was quenched with 10mL H2O and extracted with EtOAc (3×20mL). The combined EtOAc extracts were dried with anhydrous Na2SO4 and filtrated and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel with PE/EtOAc, as the eluent, to afford the desired products.
Reference: [1] Advanced Synthesis and Catalysis, 2007, vol. 349, # 17-18, p. 2673 - 2676
[2] Chinese Chemical Letters, 2014, vol. 25, # 5, p. 775 - 778
  • 54
  • [ 288-13-1 ]
  • [ 100-66-3 ]
  • [ 102908-37-2 ]
  • [ 35715-67-4 ]
Reference: [1] Science, 2015, vol. 349, # 6254, p. 1326 - 1330
[2] Patent: WO2016/196816, 2016, A1, . Location in patent: Paragraph 00324; 00370
[3] Chemistry - A European Journal, 2017, vol. 23, # 72, p. 18161 - 18165
  • 55
  • [ 288-13-1 ]
  • [ 5720-06-9 ]
  • [ 102908-37-2 ]
Reference: [1] Helvetica Chimica Acta, 2010, vol. 93, # 5, p. 974 - 979
  • 56
  • [ 288-13-1 ]
  • [ 14521-80-3 ]
YieldReaction ConditionsOperation in experiment
12.20 g at 5 - 15℃; (1) 6.81 g (0.1 mol) of pyrazole was dissolved in 50.0percent of hydrobromic acid (161.80 g, containing 1.0 mol of hydrogen bromide).Under stirring, the temperature is controlled at 5-15° C., and a 25.0percent solution of potassium dichromate 47.07 g is added dropwise.After completion of the dropwise addition, the reaction temperature was controlled at 5-15° C. to allow the reaction system to undergo a bromination reaction. During the reaction, samples were taken at regular intervals and detected by high performance liquid chromatography.When it was detected that the mass of 3-bromopyrazole in the reaction system accounted for 93.0percent of the total mass of organic matter in the reaction system, 4.31 g (0.06 mol) of ferrous oxide was added to terminate the reaction to obtain a feed liquid containing 3-bromopyrazole; (2) Add 73.5 g of chlorobenzene to the feed solution, stir and extract for 2 hours, let stand for 1 hour, take the organic phase and allow it to cool down to -15°C to -5°C,The solids were analyzed by elution from the organic phase. The resulting 12.20 g of solid was 3-bromopyrazole. The yield was calculated to be 83percent. After the determination, the main content was 98.5percent.
Reference: [1] Patent: CN107954913, 2018, A, . Location in patent: Paragraph 0017
  • 57
  • [ 288-13-1 ]
  • [ 507-20-0 ]
  • [ 15754-60-6 ]
Reference: [1] Bulletin de la Societe Chimique de France, 1986, # 1, p. 129 - 132
  • 58
  • [ 288-13-1 ]
  • [ 75-26-3 ]
  • [ 18952-87-9 ]
YieldReaction ConditionsOperation in experiment
57% Neat (no solvent) Example 55:; N-[6-(2-Isopropyl-2H-pyrazol-3-yl)-2,4-dioxo-7-trifluoromethyl-l,4-dihydro-2H- quinazolin-3-yl]-methanesulfonamide; 1 -Isopropy 1- 1 H-pyrazole; A mixture of pyrazole (5 g, 73.44 mmol), NaHCO3 (12.2 g, 2 eq) and 2-bromopropane (15 mL, 2eq) was stirred at 1200C for 90 h. Over this period, 2-bromopropane was added when necessary to keep an adequate volume. The solids were removed by filtration and the resulting solution was distillated. From the distillation, a colorless syrup (4.6 g, bp 1480C, 57percent) was collected..
53% With sodium hydroxide In water for 144 - 168 h; Heating / reflux 1-isopropyl-1H-pyrazole :
To a solution of pyrazole (50.0 g, 735.3 mmol) in aqueous sodium hydroxide (123.5 g NaOH/200 ml of water), was added isopropyl bromide (180.0 g, 1470.1 mmol) and the mixture was then heated to reflux for 6-7 days.
The reaction mixture was cooled and extracted with ethyl acetate (3 x 300 ml).
The combined organic layers were dried over MgS04Removal of the volatiles in vacuo provided a light yellow oil, which was distilled via Kugelrohr at 140°C and 10 Torr, to provide 1-isopropyl-1H-pyrazole as a colorless oil (43 g, 53percent). LCMS mlz (percent) =111 M+H+ , (100).
1H NMR (400 MHz, DMSO-d&6) δ: 7.72 (d, J= 2.3 Hz, 1H), 7.41 (t, 1H), 6.21 (t, 1H), 4.5 (q, 1H), 1.41-1.37 (d, J= 11.1 Hz).
46.4%
Stage #1: With sodium hydride In N,N-dimethyl-formamide at 20℃; for 1 h;
Stage #2: at 20℃; for 2 h;
Step 1
1-Isopropyl-1H-pyrazole
To a suspension of NaH (14 g, 0.35 mol 60percent in mineral oil) in DMF (120 mL) was added dropwise of a solution of pyrazole (20 g, 0.29 mol) in DMF (30 mL) at ° C. After addition, the suspension was stirred for 1 hour at room temperature.
Isopropyl bromide (53.4 g, 0.44 mol) was added dropwise, and the reaction mixture was stirred at room temperature for 2 hours.
Water was added to quench the reaction and the mixture was extracted with diethyl ether.
The combined ether layers were washed with water, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure.
The residue was distilled under vacuum to afford 1-isopropyl-1H-pyrazole as a colorless liquid (15.0 g, 46.4percent).
Reference: [1] Patent: WO2006/108591, 2006, A1, . Location in patent: Page/Page column 112
[2] Journal of Medicinal Chemistry, 2010, vol. 53, # 5, p. 1923 - 1936
[3] Patent: WO2005/12254, 2005, A1, . Location in patent: Page/Page column 129
[4] Patent: US2009/170873, 2009, A1, . Location in patent: Page/Page column 48
  • 59
  • [ 288-13-1 ]
  • [ 75-30-9 ]
  • [ 18952-87-9 ]
Reference: [1] Russian Chemical Bulletin, 2014, vol. 63, # 2, p. 443 - 456[2] Izv. Akad. Nauk, Ser. Khim., 2014, # 2, p. 443 - 456,14
  • 60
  • [ 288-13-1 ]
  • [ 74-96-4 ]
  • [ 2817-71-2 ]
Reference: [1] Russian Journal of Organic Chemistry, 2006, vol. 42, # 4, p. 550 - 554
[2] Bulletin de la Societe Chimique de France, 1986, # 1, p. 129 - 132
[3] Patent: WO2015/97123, 2015, A1, . Location in patent: Page/Page column 132; 164
[4] Journal of Materials Chemistry C, 2016, vol. 4, # 35, p. 8235 - 8244
  • 61
  • [ 288-13-1 ]
  • [ 540-51-2 ]
  • [ 2817-71-2 ]
Reference: [1] Patent: CN107501181, 2017, A, . Location in patent: Paragraph 0016; 0018
  • 62
  • [ 288-13-1 ]
  • [ 75-03-6 ]
  • [ 2817-71-2 ]
Reference: [1] Synthetic Communications, 1990, vol. 20, # 18, p. 2849 - 2853
[2] Journal of Chemical Thermodynamics, 1999, vol. 31, # 1, p. 129 - 138
[3] Patent: WO2013/19690, 2013, A1, . Location in patent: Paragraph 00702; 00932
  • 63
  • [ 288-13-1 ]
  • [ 109-65-9 ]
  • [ 52096-24-9 ]
Reference: [1] Synthetic Communications, 1990, vol. 20, # 18, p. 2849 - 2853
[2] Bulletin de la Societe Chimique de France, 1986, # 1, p. 129 - 132
[3] Ultrasonics Sonochemistry, 2016, vol. 32, p. 432 - 439
  • 64
  • [ 288-13-1 ]
  • [ 33036-62-3 ]
  • [ 52096-24-9 ]
Reference: [1] Patent: CN107501181, 2017, A, . Location in patent: Paragraph 0026; 0028
  • 65
  • [ 288-13-1 ]
  • [ 630-17-1 ]
  • [ 1643-19-2 ]
  • [ 725746-83-8 ]
  • [ 52096-24-9 ]
Reference: [1] Patent: EP1580189, 2005, A1, . Location in patent: Page/Page column 32
  • 66
  • [ 288-13-1 ]
  • [ 542-69-8 ]
  • [ 52096-24-9 ]
Reference: [1] Patent: WO2013/19690, 2013, A1, . Location in patent: Paragraph 00932
  • 67
  • [ 288-13-1 ]
  • [ 2075-46-9 ]
  • [ 26621-44-3 ]
Reference: [1] Catalysis Communications, 2012, vol. 19, p. 37 - 41
  • 68
  • [ 288-13-1 ]
  • [ 26621-44-3 ]
Reference: [1] Journal of Heterocyclic Chemistry, 2013, vol. 50, # 6, p. 1322 - 1327
  • 69
  • [ 288-13-1 ]
  • [ 556-52-5 ]
  • [ 98484-49-2 ]
Reference: [1] Heterocycles, 1998, vol. 48, # 4, p. 617 - 620
  • 70
  • [ 288-13-1 ]
  • [ 61706-54-5 ]
  • [ 67129-08-2 ]
Reference: [1] Patent: WO2013/104478, 2013, A1, . Location in patent: Page/Page column 18
  • 71
  • [ 288-13-1 ]
  • [ 108-24-7 ]
  • [ 37687-18-6 ]
Reference: [1] Journal of Organic Chemistry, 2016, vol. 81, # 2, p. 689 - 698
  • 72
  • [ 67129-08-2 ]
  • [ 288-13-1 ]
  • [ 1131-01-7 ]
Reference: [1] Bulletin des Societes Chimiques Belges, 1989, vol. 98, # 5, p. 319 - 326
  • 73
  • [ 67129-08-2 ]
  • [ 288-13-1 ]
  • [ 4073-98-7 ]
  • [ 1131-01-7 ]
Reference: [1] Bulletin des Societes Chimiques Belges, 1989, vol. 98, # 5, p. 319 - 326
  • 74
  • [ 288-13-1 ]
  • [ 2314-97-8 ]
  • [ 20154-03-4 ]
Reference: [1] Journal of Fluorine Chemistry, 2010, vol. 131, # 1, p. 98 - 105
  • 75
  • [ 103582-19-0 ]
  • [ 288-13-1 ]
  • [ 33689-29-1 ]
  • [ 15366-34-4 ]
Reference: [1] Heterocycles, 1985, vol. 23, # 10, p. 2619 - 2628
  • 76
  • [ 67129-08-2 ]
  • [ 288-13-1 ]
  • [ 4073-98-7 ]
Reference: [1] Bulletin des Societes Chimiques Belges, 1989, vol. 98, # 5, p. 319 - 326
  • 77
  • [ 288-13-1 ]
  • [ 50-00-0 ]
  • [ 87-62-7 ]
  • [ 4073-98-7 ]
  • [ 125709-82-2 ]
Reference: [1] Bulletin des Societes Chimiques Belges, 1989, vol. 98, # 5, p. 319 - 326
  • 78
  • [ 67129-08-2 ]
  • [ 288-13-1 ]
  • [ 4073-98-7 ]
  • [ 1131-01-7 ]
Reference: [1] Bulletin des Societes Chimiques Belges, 1989, vol. 98, # 5, p. 319 - 326
  • 79
  • [ 288-13-1 ]
  • [ 3994-46-5 ]
Reference: [1] Liebigs Annalen der Chemie, 1985, # 9, p. 1732 - 1751
[2] Heterocycles, 1983, vol. 20, # 7, p. 1271 - 1274
[3] Tetrahedron Letters, 1985, vol. 26, # 44, p. 5485 - 5488
[4] Archiv der Pharmazie, 1987, vol. 320, # 2, p. 115 - 120
[5] Journal of Organic Chemistry, 1985, vol. 50, # 26, p. 5520 - 5523
[6] Journal of Medicinal Chemistry, 1996, vol. 39, # 2, p. 570 - 581
[7] Organic Letters, 2011, vol. 13, # 9, p. 2492 - 2494
[8] Journal of the American Chemical Society, 2011, vol. 133, # 31, p. 12285 - 12292
  • 80
  • [ 288-13-1 ]
  • [ 81945-73-5 ]
YieldReaction ConditionsOperation in experiment
38%
Stage #1: With 3-chloro-benzenecarboperoxoic acid In ethyl acetate at 20℃; for 240 h;
Stage #2: With sodium hydroxide; sodium phosphate In water
Example 56:; N-[6-(2-Hydroxy-2H-pyrazol-3-yl)-2,4-dioxo-7-trifluoromethyl-l,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide; Pyrazol-1-ol; OHHVi N O.A mixture of pyrazole (10 g, 147 mmol) and mCPBA (36.2 g, 147 mmol) in AcOEt (500 mL) was stirred at r.t. for 1O d. The solution was concentrated in vacuo to afford a yellow paste which was extracted with water (6 x 100 mL) and coned HCl (100 mL). The aqueous phase was washed with DCM (2 x 100 mL). The organic layers were combined, concentrated in vacuo and extracted with coned HCl (50 mL). The aqueous phases were combined and 115 g of trisodium phosphate dodecahydrate were added followed by NaOH until pH 10. The aqueous phase was concentrated in vacuo to a volume of 400 mL and was then extracted in continue with OCMfEt2O (2/3) for 40 h. The organic phase was concentrated in vacuo and the residue dissolved in CHCl3. The insoluble material was removed by filtration and washed with EPO <DP n="115"/>chloroform. The aqueous phase was acidified with 200 mL of coned HCl and then extracted continuously with DCMTEt2O (2/3) for 70 h. The organic phases were combined and concentrated in vacuo to afford pyrazol-1-ol (4.7 g, 38percent) as a yellow syrup.
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1995, # 3, p. 243 - 248
[2] Liebigs Annalen, 1995, # 8, p. 1563 - 1566
[3] Patent: WO2006/108591, 2006, A1, . Location in patent: Page/Page column 113-114
  • 81
  • [ 288-13-1 ]
  • [ 100-11-8 ]
  • [ 110525-57-0 ]
YieldReaction ConditionsOperation in experiment
76% With potassium carbonate In acetonitrile at 20℃; A mixture of 4-nitrobenzyl bromide (0.500 g, 2.31 mmol), lH-pyrazole (0.362 g, 5.23 mmol), and potassium carbonate (0.704 g, 5.09 mmol) in acetonitrile (30 mL) was stirred at rt overnight. After this time, the mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by column chromatography (silica, hexanes/ethyl acetate) to afford the title compound (0.380 g, 76percent) as a white solid. MW = 203.20. ]H NMR (CDC13, 500 MHz) δ 8.21-8.19 (m, 1H), 8.19-8.16 (m, 1H),7.61- 7.57 (m, 1H), 7.48-7.44 (m, 1H), 7.32-7.28 (m, 2H), 6.35 (t, / = 2.1 Hz, 1H), 5.44 (s, 2H); APCI MS m/z 204 [M + H]+.
Reference: [1] Organic Preparations and Procedures International, 2000, vol. 32, # 4, p. 385 - 390
[2] Patent: WO2014/66659, 2014, A1, . Location in patent: Paragraph 0824
  • 82
  • [ 288-13-1 ]
  • [ 100-14-1 ]
  • [ 110525-57-0 ]
Reference: [1] Tetrahedron Letters, 1986, vol. 27, # 51, p. 6209 - 6212
[2] Farmaco, 1992, vol. 47, # 3, p. 335 - 344
  • 83
  • [ 288-13-1 ]
  • [ 446-52-6 ]
  • [ 138479-47-7 ]
Reference: [1] Australian Journal of Chemistry, 1991, vol. 44, # 8, p. 1097 - 1114
[2] Journal of the American Chemical Society, 2011, vol. 133, # 39, p. 15244 - 15247
[3] Angewandte Chemie - International Edition, 2012, vol. 51, # 11, p. 2690 - 2694
  • 84
  • [ 288-13-1 ]
  • [ 13360-57-1 ]
  • [ 133228-21-4 ]
YieldReaction ConditionsOperation in experiment
91% With 1,4-diaza-bicyclo[2.2.2]octane In acetonitrile at 20℃; for 18 h; EXAMPLE 802- Amino- 1 -(4-chloro-phenyD- 1 - [4-(3 -ethyl- 1 H-pyrazol-4-y D-phenyl] -ethanol8OA. Pyrazole-1-sulphonic acid dimethylamide; 1,4-Diazabicyclo[2.2.2]octane (DABCO, 10. Ig, 90.3mmol) and dimethylsulphamoylchloride (8.8ml, 82.9mmol) were added sequentially to a solution of pyrazole (4.8g, 81.9mmol) in EPO <DP n="192"/>acetonitrile (125ml) whilst stirring at room temperature. After 18 hours, the reaction was concentrated in vacuo and wet with water and ethyl acetate. The organic layer was removed and washed with hydrochloric acid (2N) and then brine before drying (MgSO^ and concentrating in vacuo to furnish the title compound as a colourless oil (13. Ig, 91percent). LC/MS (PS-A2) Rt 2.16 [M+H]+176
91% With 1,4-diaza-bicyclo[2.2.2]octane In acetonitrile at 20℃; for 18 h; Jl. Pyrazole-1-sulphonic acid dimethylamide1,4-Diazabicyclo[2.2.2]octane (DABCO, lO.lg, 90.3 mmol) and dimethylsulphamoylchloride (8.8 ml, 82.9 mmol) were added sequentially to a solution of pyrazole (4.8g, 81.9 mmol) in acetonitrile (125 ml) whilst stirring at room temperature. After 18 hours, the reaction mixture was concentrated in vacuo and partitioned between water and ethyl acetate. The organic layer was removed and washed with hydrochloric acid (2N) and then brine before drying (MgSO^ and concentrating in vacuo to furnish the title compound as a colourless oil (13. Ig, 91percent).
82%
Stage #1: With sodium hydride In tetrahydrofuran at 0℃; for 0.333333 h;
Stage #2: at 0 - 20℃; for 2 h;
To a stirred solution of pyrazole (12 g, 176 mmol) in THF (200 mL) was added portionwise sodium hydride (50percent, 8.46 g, 212 mmol) at 00C. After 20 min, dimethylsulfamoyl chloride (17 mL, 157 mmol) was added dropwise, and the stirring was continued for 1 h at the same temperature. Then, the mixture was allowed to room temperature for 1 h. The mixture was poured into saturated aqueous NaHCO3 (400 mL) and extracted with EtOAc (400 mL) , and the extract was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Purif, silica gel, hexane to 50:50 hexane/EtOAc) to afford the title compound (25.3 g, 82percent) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 2.95 (6H, s) , 6.40 (IH, m) , 7.75 (IH, m) , 7.99 (IH, d, J = 2.7 Hz).
75%
Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 1 h;
Stage #2: at 0 - 20℃; for 2 h;
A solution of lH-pyrazole (30 g, 440 mmol) in tetrahydrofuran (500 mL) was treated with sodium hydride (26 g, 648 mmol, 60percent) at 0 °C, and then stirred for 1 h at 0 °C. N,N-Dimethylsulfamoyl chloride (95 g, 661 mmol) was added dropwise at 0 °C. The resulting solution was stirred for additional 2 h at room temperature and then quenched by water. The resulting solution was extracted with dichloromethane and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate/petroleum ether (1/6) to afford to N,N-dimethyl-lH-pyrazole-l -sulfonamide ( 58 g, 75percent) as colorless oil. LCMS (ESI): M+H+ = 175.0.
6.24 g With triethylamine In toluene at 10 - 35℃; for 18 h; To a solution of 1H-pyrazole (5.00 g) in toluene (67.0 mL) were added dimethylsulfamoyl chloride (7.89 mL) and triethylamine (13.3 mL) at room temperature, and the reaction mixture was stirred at room temperature for 18 hr. The resulting solid was removed by filtration, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (6.24 g). 1H NMR (400 MHz, CDCl3) δ 2.91 (6H, s), 6.38 (1H, dd, J = 2.6, 1.8 Hz), 7.72 (1H, d, J = 1.2 Hz), 7.96 (1H, d, J = 2.4 Hz)

Reference: [1] Synthesis, 2006, # 5, p. 793 - 798
[2] Chemistry - An Asian Journal, 2015, vol. 10, # 8, p. 1626 - 1630
[3] Advanced Synthesis and Catalysis, 2014, vol. 356, # 7, p. 1555 - 1561
[4] Patent: WO2006/136830, 2006, A1, . Location in patent: Page/Page column 190-191
[5] Patent: WO2006/136829, 2006, A2, . Location in patent: Page/Page column 129
[6] Patent: WO2010/101302, 2010, A1, . Location in patent: Page/Page column 209-210
[7] Patent: WO2015/52226, 2015, A1, . Location in patent: Paragraph 0498
[8] Chemische Berichte, 1991, vol. 124, p. 1639 - 1650
[9] Patent: WO2007/43677, 2007, A1, . Location in patent: Page/Page column 487
[10] Patent: WO2008/91594, 2008, A2, . Location in patent: Page/Page column 87
[11] Patent: WO2010/132999, 2010, A1, . Location in patent: Page/Page column 183-184
[12] Patent: EP2540728, 2013, A1, . Location in patent: Page/Page column 53
[13] Patent: EP2818473, 2014, A1, . Location in patent: Paragraph 0581
[14] Patent: WO2008/130021, 2008, A2, . Location in patent: Page/Page column 389-390
[15] Patent: WO2007/14290, 2007, A2, . Location in patent: Page/Page column 70
  • 85
  • [ 288-13-1 ]
  • [ 459-57-4 ]
  • [ 99662-34-7 ]
YieldReaction ConditionsOperation in experiment
29% With potassium carbonate In N,N-dimethyl-formamide at 100℃; To a solution of Compound 1 (10 g, 80.6 mmol) in dry DMF (100 mL) were added pyrazole (5.5 g, 80.6 mmol) and K2C03 (12.2 g, 88.7 mmol). The resulting solution was stirred at 100 °C for overnight. After cooling to RT, the residue was treated with water and extracted with EA. The organic extracts were washed with water, brine, dried over anhydrous Na2SO4, filtered and concentrated to give a crude oil. The crude product was purified by recrystallization to afford Compound 2 (4 g, 29 percent).1HNMR (CDC13, 300 MHz) ö: 6.5-6.6 (s, 1 H), 7.7-7.8 (s, 1 H), 7.9-8.0 (d, 2 H), 8.0-8.1 (d, 2 H), 8.1-8.2 (s, 1 H), 10.0-10.1 (s, 1 H).
Reference: [1] New Journal of Chemistry, 2018, vol. 42, # 17, p. 14630 - 14641
[2] Journal of Medicinal Chemistry, 1998, vol. 41, # 13, p. 2390 - 2410
[3] ChemMedChem, 2013, vol. 8, # 6, p. 967 - 975
[4] Journal of Medicinal Chemistry, 2013, vol. 56, # 12, p. 5213 - 5217
[5] Patent: WO2016/77232, 2016, A2, . Location in patent: Page/Page column 42; 43
[6] Journal of Organic Chemistry, 2013, vol. 78, # 7, p. 3222 - 3234
[7] Patent: CN106966981, 2017, A, . Location in patent: Paragraph 0055-0057
  • 86
  • [ 288-13-1 ]
  • [ 1122-91-4 ]
  • [ 99662-34-7 ]
YieldReaction ConditionsOperation in experiment
89% With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 12 h; To a solution of Compound 1 (30 g, 162.1 mmol) in dry DMF (200 mL) were added 1H- pyrazole (11 g, 162.1 mmol) and K2C03 (24.8 g, 178.3 mmol). The resulting solution was stirred at 80 °C for 12 hours. After cooling to RT, the residue was treated with water and extracted with EA. The organic extracts were washed with water, brine, dried over anhydrous Na2SO4, filtered and concentrated to give a crude oil. The crude product was purified by recrystallization to afford Compound 2 (25 g, 89 percent).
1 g With copper(l) iodide; caesium carbonate; <i>L</i>-proline In N,N-dimethyl-formamide at 120℃; for 20 h; Inert atmosphere To a solution of 4-bromobenzaldehyde (2.0 g, 0.010 mole) in DMF 20 mL under N2 at 25 °C, was added lH-pyrazole (0.668 g, 0.0098 mole), copper iodide (0.185 g, 0.0009 mole), L-proline (0.224 g, 0.0019 mole) and cesium carbonate (6.4 g, 0.0196 mole). The reaction mixture was heated at 120 °C for 20 hours, cooled to RT, filtered through celite and washed with ethyl acetate (50 mL). The filtrate was concentrated under vacuum to obtain the crude compound which was further purified by flash chromatography using ethyl acetate: n-hexane (40:60) to obtain 4-(pyrazol- l- yl)benzaldehyde. Yield: 1.0 g; - NMR (DMSO-d6, 400 MHz) δ ppm: 6.62 (s, 1H), 7.84 (s, 1H),8.01 - 8.03 (d, J = 8.4 Hz, 2H), 8.07 (d, J = 8.4 Hz, 2H), 8.67 (s, 1H), 10.00 (s, 1H); Mass (m/z): 173.1 (M+H)+.
Reference: [1] ChemCatChem, 2014, vol. 6, # 8, p. 2373 - 2383
[2] Patent: WO2016/77232, 2016, A2, . Location in patent: Page/Page column 51
[3] Tetrahedron, 2008, vol. 64, # 10, p. 2471 - 2479
[4] Bulletin of the Chemical Society of Japan, 2008, vol. 81, # 4, p. 515 - 517
[5] Inorganic Chemistry, 2010, vol. 49, # 1, p. 331 - 338
[6] Patent: WO2018/42362, 2018, A1, . Location in patent: Page/Page column 47-48
  • 87
  • [ 288-13-1 ]
  • [ 104-88-1 ]
  • [ 99662-34-7 ]
Reference: [1] Tetrahedron, 2008, vol. 64, # 10, p. 2471 - 2479
  • 88
  • [ 288-13-1 ]
  • [ 87199-17-5 ]
  • [ 99662-34-7 ]
Reference: [1] Helvetica Chimica Acta, 2010, vol. 93, # 5, p. 974 - 979
  • 89
  • [ 288-13-1 ]
  • [ 420-04-2 ]
  • [ 4023-02-3 ]
YieldReaction ConditionsOperation in experiment
43% With hydrogenchloride In 1,4-dioxane for 1 h; Reflux Pyrazole (1.634 g, 24 mmol) and cyanamide (1 g, 24 mmol) were dissolved in 1,4-dioxane (24 mL), and 4M-HCl (6 mL) dissolved in 1,4- dioxane then stirred under reflux for 1 hour. After completion of the reaction, the reaction product was recrystallized in an ice water bath under the condition of diethyl ether. Yield 43percent
Reference: [1] Journal of Organic Chemistry, 1992, vol. 57, # 8, p. 2497 - 2502
[2] Organic Letters, 2004, vol. 6, # 26, p. 4925 - 4927
[3] Patent: KR101808950, 2017, B1, . Location in patent: Paragraph 0233-0236
[4] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 24, p. 2771 - 2774
[5] Journal of Medicinal Chemistry, 2005, vol. 48, # 3, p. 812 - 820
  • 90
  • [ 288-13-1 ]
  • [ 170570-77-1 ]
  • [ 169590-41-4 ]
Reference: [1] Patent: US5521207, 1996, A,
  • 91
  • [ 288-13-1 ]
  • [ 24424-99-5 ]
  • [ 219580-32-2 ]
YieldReaction ConditionsOperation in experiment
59% With triethylamine In dichloromethane at 20℃; General procedure: To a solution of pyrazole 1-5 (1 equiv.) and triethylamine (1.5 equiv.) in dichloromethane (for 0.05mol of pyrazole – 50 mL of dichloromethane were user) Di-tert-butyl dicarbonate (1.2 equiv) wereadded at room temperature and left to stir overnight. Dichloromethane was washed with saturatedNaHCO3 solution (1×25 mL – for 50 mL of dichloromethane) then with deionized H2O (1 × 25mL). Organic layer was dried with anhydrous Na2SO4, and evaporated under reduced pressure.
Reference: [1] Tetrahedron Letters, 2006, vol. 47, # 43, p. 7551 - 7556
[2] Chemistry - A European Journal, 2016, vol. 22, # 28, p. 9687 - 9692
[3] Arkivoc, 2014, vol. 2014, # 6, p. 54 - 71
  • 92
  • [ 110-87-2 ]
  • [ 288-13-1 ]
  • [ 449758-17-2 ]
YieldReaction ConditionsOperation in experiment
100% at 100℃; for 12 h; Inert atmosphere Scheme 2. Synthesis of 5-bromopyrazoles 22a and 22b. Reagents and conditions: a) DHP (xs), TFA (0.1 equiv), 100 °C, 12 h (quant for 20a and 20b);
99% at 95℃; for 5 h; 7H-Pyrazole (14.3g, 0.21mol) is dissolved in 3,4-dihydro-2η-pyran (26.74g, 0.32mol) in the presence of a catalytic amount of TFA (O.lmL, 1.3mmol). The reaction mixture is stirred at 950C for 5 hours, cooled and then quenched using NaH (0.2g, 5mmol). The solvent is removed to give the title compound as a brown oil (33.3g, 99percent), which is used in the next step without further purification.
96%
Stage #1: for 5 h; Reflux
Stage #2: for 0.166667 h;
Reference example 1 [1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl] boronic acid 1-(tetrahydropyran-2-yl)-1H-pyrazole
A mixture of pyrazole (14.3 g, 0.21 mmol), 3,4-dihydro- 2H-pyrane (29 mL, 0.32 mmol) and trifluoroacetic acid (0.1 mL, 0.0013 mmol) was heated under reflux for 5 hours.
After the mixture was cooled to room temperature, sodium hydride (60percent, 0.2 g, 0.008 mmol) was added thereto, and the mixture was stirred for 10 minutes.
The reaction mixture was subjected to distillation under reduced pressure (60-65°C, 0.5-1 mmHg), whereby 1-(tetrahydropyran-2-yl)-1H-pyrazole (30.8 g, 96percent) was obtained.
49%
Stage #1: for 5 h; Reflux
Stage #2: With sodium hydride In mineral oil
A mixture of 1H-pyrazole (6.00 g, 88.1 mmol), 3,4-dihydro-2H-pyran (9.00 g, 107 mmol), and TFA (cat. 2.00 mL) was heated to reflux for 5 hr. At the end of reaction, NaH (100 mg, 4.17 mmol) was added to quench the reaction. The resulting mixture was extracted with ethyl acetate, washed with brine, dried over MgSO4, filtered, and evaporated. The residue was purified by silica gel chromatography eluting with EtOAc/petroleum ether (1:100) to afford 1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole (6.6 g, 49percent yield) as pale yellow sold. LCMS (ESI) m/z: 153.1 [M+H+].

Reference: [1] Tetrahedron Letters, 2006, vol. 47, # 27, p. 4665 - 4669
[2] Tetrahedron Letters, 2007, vol. 48, # 23, p. 4123 - 4126
[3] Journal of Organic Chemistry, 2016, vol. 81, # 4, p. 1718 - 1722
[4] Patent: WO2017/66606, 2017, A1, . Location in patent: Page/Page column 49
[5] Patent: WO2007/138072, 2007, A2, . Location in patent: Page/Page column 54
[6] Chemistry - A European Journal, 2016, vol. 22, # 28, p. 9687 - 9692
[7] Journal of Medicinal Chemistry, 2004, vol. 47, # 12, p. 2995 - 3008
[8] Patent: EP2210880, 2010, A1, . Location in patent: Page/Page column 73
[9] Journal of the American Chemical Society, 2018, vol. 140, # 31, p. 9788 - 9792
[10] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 12, p. 4547 - 4559
[11] Patent: US2012/245144, 2012, A1, . Location in patent: Page/Page column 150
[12] Journal of Organic Chemistry, 2008, vol. 73, # 11, p. 4309 - 4312
[13] Organic Process Research and Development, 2007, vol. 11, # 5, p. 870 - 876
[14] RSC Advances, 2015, vol. 5, # 31, p. 24081 - 24093
[15] Patent: WO2017/120429, 2017, A1, . Location in patent: Page/Page column 306
  • 93
  • [ 110-87-2 ]
  • [ 288-13-1 ]
  • [ 449758-17-2 ]
Reference: [1] ChemMedChem, 2015, vol. 10, # 12, p. 1974 - 1979
  • 94
  • [ 288-13-1 ]
  • [ 25015-63-8 ]
  • [ 269410-08-4 ]
Reference: [1] Angewandte Chemie - International Edition, 2013, vol. 52, # 49, p. 12915 - 12919[2] Angew. Chem., 2013, vol. 125, # 49, p. 13153 - 13157,5
  • 95
  • [ 288-13-1 ]
  • [ 73183-34-3 ]
  • [ 269410-08-4 ]
Reference: [1] Journal of the American Chemical Society, 2014, vol. 136, # 11, p. 4287 - 4299
  • 96
  • [ 288-13-1 ]
  • [ 73781-91-6 ]
  • [ 321533-62-4 ]
YieldReaction ConditionsOperation in experiment
93%
Stage #1: With sodium hydride In dimethyl sulfoxide at 0 - 20℃; for 1 h;
Stage #2: at 20℃; for 6 h;
Example 7. Preparation of 0-(6-pyrazol-l-yl-pyridin-3-almethel)-hadroxylamine (Compound of formula (Xl)); Step 7a. Preparation of 6-Pyrazol-1-vl-nicotinic acid methyl ester (Compound of formula (XI-a)); To a solution of pyrazole (19.4g, 0. 28mol) in 100 mL anhydrous DMSO, which was at a temperature of 0°C, was added NaH (7. 5g, 0. 3mol) gradually over a period of 30 min. The resulting reaction mixture was allowed to warm to room temperature, at which the mixture continued to agitate for an additional 30 min. Methyl 6- chloronicotinate (35g, 0. 2mol) was added to the stirring reaction mixture and agitated vigorously for a period of 6 hr. The reaction mixture was subsequently cooled to a temperature of about 0°C and poured into a saturated aqueous, 0°C NH4C1 solution. The resulting precipitate was filtered, washed with water, and dried to give a compound of formula (XI-a) (38.3g, 93percent yield) as an off-white solid.
40%
Stage #1: With sodium hydride In N,N-dimethyl acetamide for 0.166667 h;
Stage #2: at 95℃;
Stage #3: With sodium hydroxide In water
Pyrazole (2.4 g, 35.4 mmol) was added to DMA (100 ml) and to this was slowly added NaH (1.85 g, 38.6 mmol). The reaction mixture was stirred for 10 mins under a nitrogen atmosphere. To the resulting anion was added methyl 6-chloropyridine-3-carboxylate (5.5 g, 32.2 mmol) and the reaction was heated at 95° C. overnight. The reaction mixture was evaporated to dryness, quenched with 2.0 N NaOH (100 ml), extracted with DCM (3.x.100 ml), dried (MgSO4) and the solvent removed in vacuo to yield a brown solid. This solid was purified via silica column chromatography, eluting with 0-40percent diethyl ether in iso-hexane. A white solid was obtained, which was dissolved in hot iso-hexane. On cooling a white solid was obtained which was filtered and dried (2.6 g, 40percent); 1H NMR (400.132 MHz, CDCl3) δ 3.96 (s, 3H), 6.50 (s, 1H), 7.77 (s, 1H), 8.05 (d, 1H), 8.40 (dd, 1H), 8.62 (d, 1H), 9.02 (d, 1H); MH+203.
Reference: [1] Patent: WO2005/70918, 2005, A1, . Location in patent: Page/Page column 40
[2] Patent: US2008/153812, 2008, A1, . Location in patent: Page/Page column 102
  • 97
  • [ 288-13-1 ]
  • [ 883230-69-1 ]
  • [ 883230-94-2 ]
YieldReaction ConditionsOperation in experiment
62% With caesium carbonate; copper(II) nitrate In N,N-dimethyl-formamide at 130℃; for 24 h; Schlenk technique General procedure: The 2-substituted 5-halopyridine or 5-halopyrimidine substrate (0.5 mmol), an N-heterocyclic amine (1.0 mmol), Cu(NO3)2 (0.1 mmol) and Cs2CO3 (1.0 mmol) were added to a 25-mL Schlenk tube, followed by addition of DMF (2 mL). This mixture was stirred at 130 °C or 140 °C (see schemes and tables) under air atmosphere for 24 h. Then, the reaction mixture was added to brine (15 mL) and this mixture was extracted with CH2Cl2 (3 × 15 mL). The combined extracts were concentrated under reduced pressure and the product was isolated by flash chromatography on a silica gel (200–300 mesh) column.
Reference: [1] Synthesis (Germany), 2017, vol. 49, # 23, p. 5120 - 5130
  • 98
  • [ 288-13-1 ]
  • [ 883230-68-0 ]
  • [ 883230-94-2 ]
YieldReaction ConditionsOperation in experiment
53% With caesium carbonate; copper(II) nitrate In N,N-dimethyl-formamide at 130℃; for 24 h; Schlenk technique General procedure: The 2-substituted 5-halopyridine or 5-halopyrimidine substrate (0.5 mmol), an N-heterocyclic amine (1.0 mmol), Cu(NO3)2 (0.1 mmol) and Cs2CO3 (1.0 mmol) were added to a 25-mL Schlenk tube, followed by addition of DMF (2 mL). This mixture was stirred at 130 °C or 140 °C (see schemes and tables) under air atmosphere for 24 h. Then, the reaction mixture was added to brine (15 mL) and this mixture was extracted with CH2Cl2 (3 × 15 mL). The combined extracts were concentrated under reduced pressure and the product was isolated by flash chromatography on a silica gel (200–300 mesh) column.
Reference: [1] Synthesis (Germany), 2017, vol. 49, # 23, p. 5120 - 5130
  • 99
  • [ 288-13-1 ]
  • [ 883230-94-2 ]
YieldReaction ConditionsOperation in experiment
49% With caesium carbonate; copper(II) nitrate In N,N-dimethyl-formamide at 130℃; for 24 h; Schlenk technique General procedure: The 2-substituted 5-halopyridine or 5-halopyrimidine substrate (0.5 mmol), an N-heterocyclic amine (1.0 mmol), Cu(NO3)2 (0.1 mmol) and Cs2CO3 (1.0 mmol) were added to a 25-mL Schlenk tube, followed by addition of DMF (2 mL). This mixture was stirred at 130 °C or 140 °C (see schemes and tables) under air atmosphere for 24 h. Then, the reaction mixture was added to brine (15 mL) and this mixture was extracted with CH2Cl2 (3 × 15 mL). The combined extracts were concentrated under reduced pressure and the product was isolated by flash chromatography on a silica gel (200–300 mesh) column.
Reference: [1] Synthesis (Germany), 2017, vol. 49, # 23, p. 5120 - 5130
  • 100
  • [ 288-13-1 ]
  • [ 478258-70-7 ]
  • [ 883230-94-2 ]
YieldReaction ConditionsOperation in experiment
46% With caesium carbonate; copper(II) nitrate In N,N-dimethyl-formamide at 130℃; for 24 h; Schlenk technique General procedure: The 2-substituted 5-halopyridine or 5-halopyrimidine substrate (0.5 mmol), an N-heterocyclic amine (1.0 mmol), Cu(NO3)2 (0.1 mmol) and Cs2CO3 (1.0 mmol) were added to a 25-mL Schlenk tube, followed by addition of DMF (2 mL). This mixture was stirred at 130 °C or 140 °C (see schemes and tables) under air atmosphere for 24 h. Then, the reaction mixture was added to brine (15 mL) and this mixture was extracted with CH2Cl2 (3 × 15 mL). The combined extracts were concentrated under reduced pressure and the product was isolated by flash chromatography on a silica gel (200–300 mesh) column.
Reference: [1] Synthesis (Germany), 2017, vol. 49, # 23, p. 5120 - 5130
  • 101
  • [ 288-13-1 ]
  • [ 32779-36-5 ]
  • [ 883230-94-2 ]
YieldReaction ConditionsOperation in experiment
440 mg With caesium carbonate In N,N-dimethyl acetamide at 120℃; for 0.5 h; 1st Step
Pyrazole (130 mg) and cesium carbonate (610 mg) were added to a DMAc (10 ml) solution containing 5-bromo-2-chloropyrimidine (300 mg), followed by stirring at 120° C. for 0.5 hours.
The reaction mixture was adjusted to room temperature and water was added to the mixture.
Next, the organic layers were collected, washed with saturated saline, and dried over anhydrous sodium sulfate.
The solvent was distilled away under reduced pressure and a yellow solid of 5-bromo-2-(pyrazol-1-yl)pyrimidine (440 mg) was thus obtained.
MS (ESI m/z): 226 (M+H)
Reference: [1] RSC Advances, 2015, vol. 5, # 100, p. 82097 - 82111
[2] Patent: WO2006/38100, 2006, A1, . Location in patent: Page/Page column 84
[3] Patent: US2014/309225, 2014, A1, . Location in patent: Paragraph 0901; 0902; 0903; 0904
  • 102
  • [ 288-13-1 ]
  • [ 411235-57-9 ]
  • [ 1151814-36-6 ]
Reference: [1] Patent: JP5668756, 2015, B2, . Location in patent: Paragraph 0147
  • 103
  • [ 288-13-1 ]
  • [ 591-18-4 ]
  • [ 294877-33-1 ]
YieldReaction ConditionsOperation in experiment
78% With potassium phosphate monohydrate; manganese(II) chloride tetrahydrate; (S,S)-1,2-diaminocyclohexane In water for 24 h; Reflux In a 500 ml round-bottomed flask, 10.0 g (147 mmol) pyrazole,2.91 g (14.7 mmol) of MnCl 2 .4H 2 O, 67.7 g (294 mmol) of K 3 PO 4 .H 2 O,62.3 g (220 mmol) of 1-bromo-3-iodobenzene, 3.35 g (29.4 mmol) of trans-1,2-diaminocyclohexane and 70 ml of water were added and refluxed for 24 hours.After completion of the reaction, the temperature was lowered to room temperature, and methylene chloride was added thereto, followed by filtration using Celite.The filtrate was concentrated under reduced pressure and then subjected to column purification using ethyl acetate and n-hexane as eluent. (25.6 g, yield 78percent).
51% With copper(l) iodide; (S,S)-1,2-diaminocyclohexane; potassium carbonate In 1,4-dioxane for 19 h; Reflux 1-bromo-3-iodobenzene (18.20 g, 64.3 mmol), 1H-pyrazole (4.38 g, 64.3 mmol), and (1S,2S)-cyclohexane-1,2-diamine (1.5 g, 12.9 mmol) in dioxane (400 mL) were placed into a 1 L round-bottomed flask. Copper(I) iodide (0.613 g, 3.22 mmol) and potassium carbonate (17.78 g, 129 mmol) were added, and the reaction mixture was stirred at reflux for 19 h.
The crude mixture was then filtered through a pad of celite.
The filtrate was diluted with 400 mL of dichloromethane, and was washed with water.
The organic layer was concentrated and chromatographed on silica gel with 5percent ethyl acetate in hexane to give 7.3 g (51percent) of 1-(3-bromophenyl)-1H-pyrazole as a white solid.
Synthesis of N-(3-(1N-pyrazol-1-yl)phenyl)-3-(1-(2,6-dimethylphenyl)-1H-imidazol-4-yl)-N-phenylaniline.
Reference: [1] Patent: KR101897044, 2018, B1, . Location in patent: Paragraph 0444-0445; 0448-0450
[2] Patent: EP2574613, 2013, A1, . Location in patent: Paragraph 0144
  • 104
  • [ 288-13-1 ]
  • [ 1073-06-9 ]
  • [ 294877-33-1 ]
YieldReaction ConditionsOperation in experiment
4.7 g
Stage #1: With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.5 h;
Stage #2: at 130℃; for 2 h;
To a suspension of sodium hydride (3.52 g, 88 mmol) in DMF (40 ml), was added pyrazole (3.0 g, 44 mmol) in portions. After stirring at room temperature for 30 minutes, 1 -bromo-3- fluorobenzene (9.3 g, 53 mmol) in DMF (20 ml) was added dropwise and the resulting mixture was stirred for 2 hours at 130 °C. The mixture was cooled and quenched by the addition of a saturated aqueous NH4CI solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2S04 and concentrated under reduced pressure. The residue was purified using normal phase chromatography, eluting with petroleum ether containing 10percent ethyl acetate to give 1 -(3-bromophenyl)-1 H-pyrazole (4.7 g) as yellow solid.
Reference: [1] Patent: WO2013/41457, 2013, A1, . Location in patent: Page/Page column 23
  • 105
  • [ 288-13-1 ]
  • [ 591-19-5 ]
  • [ 294877-33-1 ]
Reference: [1] Chemistry - A European Journal, 2014, vol. 20, # 45, p. 14619 - 14623
  • 106
  • [ 288-13-1 ]
  • [ 1337962-43-2 ]
  • [ 1337962-47-6 ]
YieldReaction ConditionsOperation in experiment
77% With caesium carbonate In N,N-dimethyl-formamide at 85℃; for 24 h; To a solution of 0.15 g (0.55 mmol) of 5-bromo-6-chloro-2-(lH-pyrazol-l-yl)pyrimidine-4-amine (Intermediate 5) in 3 ml of DMF were added 0.1 1 g (1.64 mmol) of lH-pyrazole and 0.18 g (0.55 mmol) of cesium carbonate. The mixture was stirred at 85 °C for 24 hours. The solvent DMF was concentrated under reduced pressure. The crude residue was washed with water and dried to give 0.13 g (77 percent) of Example 1.1H-RM (300 MHz, DMSO-d6): δ = 6.57 (dd, 1H), 6.60 (dd, 1H), 7.52 (s, 1H), 7.81 (d, 1H), 7.87 (d, 1H), 8.41 (s, 1H), 8.51 (d, 1H), 8.60 (d, 1H).
Reference: [1] Patent: WO2011/121418, 2011, A1, . Location in patent: Page/Page column 26-27
Same Skeleton Products
Historical Records

Pharmaceutical Intermediates of
[ 288-13-1 ]

Crizotinib Related Intermediates

Chemical Structure| 141699-59-4

[ 141699-59-4 ]

tert-Butyl 4-((methylsulfonyl)oxy)piperidine-1-carboxylate

Chemical Structure| 7379-35-3

[ 7379-35-3 ]

4-Chloropyridine hydrochloride

Chemical Structure| 877397-70-1

[ 877397-70-1 ]

(R)-3-(1-(2,6-Dichloro-3-fluorophenyl)ethoxy)-2-nitropyridine

Chemical Structure| 877399-50-3

[ 877399-50-3 ]

tert-Butyl 4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylate

Chemical Structure| 73183-34-3

[ 73183-34-3 ]

4,4,4',4',5,5,5',5'-Octamethyl-2,2'-bi(1,3,2-dioxaborolane)

Related Parent Nucleus of
[ 288-13-1 ]

Pyrazoles

Chemical Structure| 1453-58-3

[ 1453-58-3 ]

3-Methylpyrazole

Similarity: 0.79

Chemical Structure| 1820-80-0

[ 1820-80-0 ]

1H-Pyrazol-3-amine

Similarity: 0.79

Chemical Structure| 930-36-9

[ 930-36-9 ]

1-Methylpyrazole

Similarity: 0.79

Chemical Structure| 916420-28-5

[ 916420-28-5 ]

1H-Pyrazole-5-amine

Similarity: 0.79

Chemical Structure| 28466-26-4

[ 28466-26-4 ]

4-Aminopyrazole

Similarity: 0.74