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[ CAS No. 151733-96-9 ] {[proInfo.proName]}

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Quality Control of [ 151733-96-9 ]

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Product Details of [ 151733-96-9 ]

CAS No. :151733-96-9 MDL No. :MFCD17480455
Formula : C7H8F2N2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :XTHPZTBDQIWSFA-UHFFFAOYSA-N
M.W : 190.15 Pubchem ID :16726262
Synonyms :

Calculated chemistry of [ 151733-96-9 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.43
Num. rotatable bonds : 4
Num. H-bond acceptors : 5.0
Num. H-bond donors : 1.0
Molar Refractivity : 39.74
TPSA : 54.98 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.69 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.95
Log Po/w (XLOGP3) : 1.09
Log Po/w (WLOGP) : 2.04
Log Po/w (MLOGP) : 0.93
Log Po/w (SILICOS-IT) : 2.0
Consensus Log Po/w : 1.4

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.73
Solubility : 3.57 mg/ml ; 0.0188 mol/l
Class : Very soluble
Log S (Ali) : -1.84
Solubility : 2.77 mg/ml ; 0.0146 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.33
Solubility : 0.898 mg/ml ; 0.00472 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.96

Safety of [ 151733-96-9 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 151733-96-9 ]

* 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.

  • Downstream synthetic route of [ 151733-96-9 ]

[ 151733-96-9 ] Synthesis Path-Downstream   1~67

  • 1
  • [ 512-56-1 ]
  • [ 151733-96-9 ]
  • [ 141573-95-7 ]
YieldReaction ConditionsOperation in experiment
64% at 180℃; for 18h; Example P1 : Preparation of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester:A mixture of 5.7 g of 3-difluoromethyl~1 H-pyrazole-4-carboxylic acid ethyl ester (30 mmol) and 25 ml of trimethyl phosphate (214 mmol) is stirred at a temperature of 18O0C for18 hours. 250 ml of an ice-water mixture are then added. The resulting reaction product is filtered, washed with water and dissolved in 50 ml of ethyl acetate. The organic phase is washed with 50 ml of saturated sodium chloride solution and dried over sodium sulfate and concentrated by evaporation. 3.9 g (64 % of theory) of 3-difluoromethyl-1-methyl-1H- pyrazole-4-carboxylic acid ethyl ester are obtained in the form of crystals (m.p. 59-6O0C).
With polyphosphoric acid; at 170℃; for 5h; Example 9:To 8.2 g of ethyl S-difluoromethylpyrazole^-carboxylate (NHDFPE) was added 24.6 g of trimethyl phosphate and 0.60 g of polyphosphoric acid. The mixture was heated to 1700C and stirred for 5 hours. Samples were taken periodically for GC analysis. The results are shown in Figure 5
  • 2
  • [ 151733-96-9 ]
  • [ 62802-42-0 ]
  • [ 1104275-08-2 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In 1-methyl-pyrrolidin-2-one at 150℃; for 1h; Microwave irradiation; 1.C.2 Step 2. Ethyl 3-(difluoromethyl)-l-(5-fluoropyrimidin-2-yl)-lH-pyrazole-4-carboxylate; A solution of ethyl 3-(difluoromethyl)-lH-pyrazole-4-carboxylic acid (190 mg, 1.0 mmol), 2-chloro-5-fluoro-pyrimidine (132 mg, 1.0 mmol) and K2CO3 (276 mg, 2.0 mmol) in NMP (2.0 mL) is heated in a microwave reactor at 150 °C for 1 h. The mixture is poured into H2O, extracted with EtOAc (3 x 25 mL) and dried over anhydrous MgSO4. The crude product is purified by silica gel column chromatography using 15-25 % EtOAc / hexane to afford the title compound as a white solid.
  • 3
  • [ 1086400-66-9 ]
  • [ 151733-96-9 ]
YieldReaction ConditionsOperation in experiment
With hydrazine In ethanol at 0 - 20℃; 1.C.1 C. 3-(DLFLUOROMETHYL)-L-(5-FLUORO-PYRIMIDIN-2-YL)-LH-PYRAZOLE-4-CARBOXYLIC ACID (ADAMANTAN-I -YLMETHYL)-AMIDE (COMPOUND 3); Step 1. Ethyl 3-(difluoromethyl)-lH-pyrazole-4-carboxylate; A mixture of ethyl 4,4-difluoro-3-oxobutanoate (4.65 g, 0.028 moles), acetic anhydride (8.0 g, 0.078 moles) and triethylorthoformate (7.3 g, 0.049 moles) is heated at 110 °C for 4 h. The mixture is concentrated under vacuum to afford (Z)-ethyl 2-(ethoxymethylene)-4,4-difluoro-3-oxobutanoate as yellow oil. The oil is dissolved in EtOH(25 mL) and cooled in an ice bath. To this cooled stirred mixture is added anhydrous hydrazine (0.7 mL, 0. 022 mole) and the mixture is allowed to warm gradually to RT overnight. The mixture is concentrated under vacuum and the crude product is purified by silica gel column chromatography using 1-2 % MeOH / CH2Cl2 to afford the title compound as a yellow solid.
With hydrazine hydrate In methanol at 70℃; for 3h; 74.B Step B: Ethyl 3-(difluoromethyl)-1H-pyrazole-4-carboxylate To a solution of ethyl (Z)-2-(ethoxymethylene)-4,4-difluoro-3-oxobutanoate (11 g, 49.5 mmol) in MeOH (100 mL) at 0 C was added N2H4.H2O (7.6 g, 149 mmol) dropwise and the mixture was stirred at 70 C for 3 h. After this time the mixture was concentrated in vacuo to give the title compound (10 g, crude) as yellow gum. MS (ESI): 190.9 [M + H]+.
  • 4
  • [ 151733-96-9 ]
  • [ 77-78-1 ]
  • ethyl 5-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate [ No CAS ]
  • [ 141573-95-7 ]
YieldReaction ConditionsOperation in experiment
99.9% With tetramethlyammonium chloride; sodium hydroxide; In water; toluene; at 15℃;pH 10.8 - 11;Product distribution / selectivity; Example 1 : Preparation of ethyl 3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxylate(DFPE) using a biphasic solvent system Example 1a19 g (0.10 mol) of ethyl S-difluoromethylpyrazole^-carboxylate, toluene (60 ml), water (70 ml), and tetramethylammonium chloride (0.2 g) were mixed. 4.6 g of 25% aqueous sodium hydroxide (0.03 mol) was added while stirring. The mixture was cooled to 150C. Then, over the course of 2 hours, 15.1 g of dimethyl sulphate (0.12 mol) and 1 1.2 g of additional sodium hydroxide (0.07 mol) were fed simultaneously while maintaining the pH at 10.8 to 1 1.0 and pot temperature at 150C. The reaction mixture was allowed to stir at the same temperature while maintaining the pH at 10.8-1 1.0 by feeding additional sodium hydroxide solution. The bottom aqueous phase was separated off. The organic phase was concentrated in vacuo to give 20.0 g of crude product as a 70:30 mixture of DFPE and ethyl 5-(difluoromethyl)-1 -methyl- 1 H-pyrazole-4- carboxylate (iso-DFPE).The desired DFPE product was purified by vacuum distillation at 95C/5 mbar to remove undesired iso-DFPE, followed by recrystallization in methanol-water. 1 1.8 g (99.9%, 0.06 mol) of DFPE was obtained. DFPE can also be isolated and purified by vacuum distillation at 1 10C/1 mbar.
  • 5
  • [ 151733-96-9 ]
  • [ 121-45-9 ]
  • ethyl 5-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate [ No CAS ]
  • [ 141573-95-7 ]
YieldReaction ConditionsOperation in experiment
30.8%Chromat.; 63.7%Chromat. With methanesulfonic acid; at 160℃; for 7h;Autoclave; Example 1 1 :To 21.66 g of 3-difluoromethylpyrazole-4-carboxylate (NHDFPE) was added 25.3 g of trimethyl phosphite and 0.48 g of methanesulfonic acid. The mixture was heated to 20 160C in a Parr reactor and stirred for 7 hours. A sample was taken at the end of the 7 hour period and analysed by GC. GC analysis indicated 63.7% DFPE and 30.8% iso- DFPE.
  • 6
  • [ 151733-96-9 ]
  • [ 756-79-6 ]
  • ethyl 5-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate [ No CAS ]
  • [ 141573-95-7 ]
YieldReaction ConditionsOperation in experiment
> 10% With methanesulfonic acid; at 160℃; for 7h; Example 10:To 23.2 g of ethyl 3-difluoromethylpyrazole-4-carboxylate (NHDFPE) was added 19.2 g of dimethyl methyl phosphonate and 0.48 g of methanesulfonic acid. The mixture was heated to 1600C and stirred for 7 hours. Samples were taken periodically for GC15 analysis. The results are shown in Figure 6.
  • 8
  • [ 151733-96-9 ]
  • [ 77-78-1 ]
  • [ 141573-95-7 ]
YieldReaction ConditionsOperation in experiment
With N,N-dimethyl-formamide; at 160℃; for 7h; To 1.9 g of ethyl 3-difluoromethylpyrazole-4-carboxylate (NHDFPE) was added 2.5 g of N, N-dimethylformamide /dimethylsulfate salt. The mixture was heated to 160C and stirred for 7 hours. The isomer ratio of ethyl 3-(difluoromethyl)-1-methyl-1 H-pyrazole-4- carboxylate (DFPE): ethyl 5-(difluoromethyl)-1 -methyl- 1 H-pyrazole-4-carboxylate (iso- DFPE) at end of reaction time based on GC analysis was 98:2.
  • 9
  • (E/Z)-ethyl 2-(ethoxymethylene)-4,4-difluoro-3-oxobutanoate [ No CAS ]
  • [ 151733-96-9 ]
YieldReaction ConditionsOperation in experiment
With hydrazine In water at 0℃; for 2.16667h; 1 Weigh 15g (0.28mol) 60% hydrazine hydrate into 1L of three-neck flask with stirrer, 300mL of distilled water, stirrer is started, to 300r / min speed stirring 10min; After stirring, the flask was moved to an ice bath for three means for controlling the temperature at 0 , 3 times in total added thereto 45g2- ethoxy-4,4-difluoro-ethyl acetoacetate, continue shaker reaction 2h; to a three-necked flask after the reaction 50mL of toluene, mixed evenly poured into a separatory funnel, and extracted hierarchical standing, separated extract phase, into the distillation apparatus was heated to 120 deg.] C, the toluene was removed by distillation to give a brown oily liquid -1H- pyrazol-methyl-3-difluoromethyl 4-carboxylate; Weigh 35g of the above prepared 3-difluoromethyl--1H- pyrazole-4-carboxylate 20g and dimethyl carbonate was poured into 1L three-necked flask provided with a stirrer in 250mL toluene was added, the agitator started to 200r / min stirring speed 5min; after mixing evenly transferred to an oil bath pot three-necked flask, heated to 85 reaction incubated 4h, followed by concentration of 5% by mass sodium hydroxide solution was adjusted to pH 7; to adjust the pH of the liquid was allowed to stand 12h after making a good stratification, take the upper oil phase into the distillation apparatus, heated to 115 after the toluene was removed by distillation to give 3-difluoro 1-methyl -1H- pyrazole-4-carboxylate.
  • 10
  • [ 151733-96-9 ]
  • [ 616-38-6 ]
  • [ 141573-95-7 ]
YieldReaction ConditionsOperation in experiment
In toluene; at 85℃; for 4h; Weigh 15g (0.28mol) 60% hydrazine hydrate into 1L of three-neck flask with stirrer, 300mL of distilled water, stirrer is started, to 300r / min speed stirring 10min; After stirring, the flask was moved to an ice bath for three means for controlling the temperature at 0 , 3 times in total added thereto 45g2- ethoxy-4,4-difluoro-ethyl acetoacetate, continue shaker reaction 2h; to a three-necked flask after the reaction 50mL of toluene, mixed evenly poured into a separatory funnel, and extracted hierarchical standing, separated extract phase, into the distillation apparatus was heated to 120 deg.] C, the toluene was removed by distillation to give a brown oily liquid -1H- pyrazol-methyl-3-difluoromethyl 4-carboxylate; Weigh 35g of the above prepared 3-difluoromethyl--1H- pyrazole-4-carboxylate 20g and dimethyl carbonate was poured into 1L three-necked flask provided with a stirrer in 250mL toluene was added, the agitator started to 200r / min stirring speed 5min; after mixing evenly transferred to an oil bath pot three-necked flask, heated to 85 reaction incubated 4h, followed by concentration of 5% by mass sodium hydroxide solution was adjusted to pH 7; to adjust the pH of the liquid was allowed to stand 12h after making a good stratification, take the upper oil phase into the distillation apparatus, heated to 115 after the toluene was removed by distillation to give 3-difluoro 1-methyl -1H- pyrazole-4-carboxylate.
  • 11
  • [ 110-87-2 ]
  • [ 151733-96-9 ]
  • ethyl 3-(difluoromethyl )-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With toluene-4-sulfonic acid In tetrahydrofuran at 20℃; 38.1 Step 1 - Ethyl 3-(difluoromethyl)-l-(tetrahvdro-2H-pyran-2-yl)-lH-pyrazole-4-carboxylate Step 1 - Ethyl 3-(difluoromethyl)-l-(tetrahvdro-2H-pyran-2-yl)-lH-pyrazole-4-carboxylate 3,4-Dihydro-2H-pyran (1.3 g, 15.45 mmol) and 4-methylbenzenesulfonic acid (400 mg, 2.33 mmol) was added to a solution of ethyl 3-(difluoromethyl)-lH-pyrazole-4-carboxylate (2.3 g, 12.10 mmol) in THF (50 mL) and the reaction mixture was stirred overnight at rt. The reaction mixture was concentrated under vacuum and the residue was diluted with NaHC03 (aq, 50 mL) and then extracted with EtOAc. The organic phase was washed with brine, dried over Na2S04 and concentrated under vacuum. The residue was purified by silica gel column chromatography (1.5→5% EtOAc in petroleum ether) to give the subtitle compound (5 g, crude) as a brown oil.
  • 12
  • [ 110-87-2 ]
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / tetrahydrofuran / 20 °C 2: water; sodium hydroxide / ethanol / 5 h / 60 °C
  • 13
  • ethyl β-nitroacrylate [ No CAS ]
  • 2,2-difluoromethyl diazomethane [ No CAS ]
  • [ 151733-96-9 ]
YieldReaction ConditionsOperation in experiment
75% With sodium phosphate; silver(l) oxide In tetrahydrofuran at 20℃; for 12h; Schlenk technique; Inert atmosphere; 6 Example 13- trifluoromethyl-1H-pyrazole-4-carboxylic acid ethyl ester In a dried reaction flask was weighed into 100mLSchlenk Ag 2 O (0.17g, 0.75mmol), Na 3 PO 4 (0.12g, 0.75mmol), 3- nitro-ethyl acrylate (0.73g, 0.5mmol), argon replacement three times, the System CF 3 CHN THF was added a solution of 2 (0.2M, 25mL), stirred at room temperature 3h. TLC monitoring Measuring the reaction is complete, the system was removed by filtration and the metal salts, residue was washed with ethyl acetate, the organic phase Combined, the solvent was evaporated under reduced pressure, the residue was dissolved in dichloromethane, washed with saturated ammonium chloride solution, dried over anhydrous sulfur Sodium sulfate, and column chromatography (eluent: petroleum ether / ethyl acetate = 10 / 1-5 / 1) to give the desired product 3- Trifluoromethyl -1H- pyrazole-4-carboxylic acid ethyl ester 0.65 g, 72% yield, high performance liquid chromatography (HPLC) Purity of 99%.
  • 14
  • C10H16F2N2O2Si [ No CAS ]
  • [ 151733-96-9 ]
YieldReaction ConditionsOperation in experiment
96% With tetrabutyl ammonium fluoride; acetic acid In tetrahydrofuran at 70℃; for 0.5h; Flow reactor;
90% With tetrabutyl ammonium fluoride; acetic acid In tetrahydrofuran at 70℃; for 0.5h;
  • 15
  • [ 151733-96-9 ]
  • [ 1373886-86-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane; N,N-dimethyl-formamide / 0.17 h / 120 °C / Flow reactor 2: lithium hexamethyldisilazane / N,N-dimethyl-formamide / 0.02 h / 40 °C / Flow reactor
  • 17
  • [ 16205-84-8 ]
  • [ 151733-96-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: acetic acid; tert.-butylnitrite / dichloromethane / 0.08 h / 60 °C / Flow reactor 1.2: 0.17 h / 90 °C / Flow reactor 2.1: acetic acid; tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 70 °C / Flow reactor
Multi-step reaction with 2 steps 1.1: tert.-butylnitrite; acetic acid / chloroform / 0.08 h / 60 °C 1.2: 0.17 h / 90 °C / 10343.2 Torr 2.1: acetic acid; tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 70 °C / 6723.1 Torr
  • 18
  • [ 151733-96-9 ]
  • 1-allyl-3-(difluoromethyl)-N-(3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: potassium carbonate / acetone / 4 h / 20 °C / Inert atmosphere 2: sodium hydroxide / water; ethanol / 2 h / 20 °C 3: phosphorus pentachloride / diethyl ether / 1 h / 20 °C / Inert atmosphere 4: pyridine / tetrahydrofuran / 1.5 h / 20 °C / Inert atmosphere
  • 19
  • [ 151733-96-9 ]
  • C22H16F5N3O3 [ No CAS ]
  • C22H16F5N3O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: potassium carbonate / acetone / 4 h / 20 °C / Inert atmosphere 2: sodium hydroxide / water; ethanol / 2 h / 20 °C 3: phosphorus pentachloride / diethyl ether / 1 h / 20 °C / Inert atmosphere 4: pyridine / tetrahydrofuran / 1.5 h / 20 °C / Inert atmosphere 5: tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride; copper(l) iodide / diethyl ether / 6 h / 60 °C / Inert atmosphere; Microwave irradiation
  • 20
  • [ 151733-96-9 ]
  • 1-allyl-3-(difluoromethyl)-1H-pyrazole-4-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate / acetone / 4 h / 20 °C / Inert atmosphere 2: sodium hydroxide / water; ethanol / 2 h / 20 °C
  • 21
  • [ 151733-96-9 ]
  • C8H7ClF2N2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium carbonate / acetone / 4 h / 20 °C / Inert atmosphere 2: sodium hydroxide / water; ethanol / 2 h / 20 °C 3: phosphorus pentachloride / diethyl ether / 1 h / 20 °C / Inert atmosphere
  • 22
  • [ 151733-96-9 ]
  • [ 106-95-6 ]
  • ethyl 1-allyl-3-(difluoromethyl)-1H-pyrazole-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With potassium carbonate In acetone at 20℃; for 4h; Inert atmosphere;
  • 23
  • [ 151733-96-9 ]
  • [ 907204-31-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene / N,N-dimethyl-formamide / 0.17 h / 120 °C / 10343.2 Torr 2: lithium hexamethyldisilazane / N,N-dimethyl-formamide; tetrahydrofuran / 0.02 h / 40 °C
  • 24
  • [ 151733-96-9 ]
  • [ 581809-46-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene / N,N-dimethyl-formamide / 0.17 h / 120 °C / 10343.2 Torr 2: lithium hexamethyldisilazane / N,N-dimethyl-formamide; tetrahydrofuran / 0.02 h / 40 °C
  • 25
  • [ 151733-96-9 ]
  • 5-(difluoromethyl)-1-methyl-N-(3′,4′,5′-trifluoro-[1,1′-biphenyl]-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene / N,N-dimethyl-formamide / 0.17 h / 120 °C / 10343.2 Torr 2: lithium hexamethyldisilazane / N,N-dimethyl-formamide; tetrahydrofuran / 0.02 h / 40 °C
  • 26
  • [ 151733-96-9 ]
  • iso-bixafen [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene / N,N-dimethyl-formamide / 0.17 h / 120 °C / 10343.2 Torr 2: lithium hexamethyldisilazane / N,N-dimethyl-formamide; tetrahydrofuran / 0.02 h / 40 °C
  • 27
  • [ 151733-96-9 ]
  • [ 74-88-4 ]
  • ethyl 5-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate [ No CAS ]
  • [ 141573-95-7 ]
  • 28
  • [ 151733-96-9 ]
  • [3-(difluoromethyl)-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: copper(l) iodide; <i>L</i>-proline / N,N-dimethyl-formamide / 12 h / 90 °C / Inert atmosphere 2: diisobutylaluminium hydride / hexane; dichloromethane / 1 h / -70 °C / Inert atmosphere
  • 29
  • [ 151733-96-9 ]
  • 2-[[3-(difluoromethyl)-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methyl]-2,3-dihydro-1H-isoindole-1,3-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: copper(l) iodide; <i>L</i>-proline / N,N-dimethyl-formamide / 12 h / 90 °C / Inert atmosphere 2: diisobutylaluminium hydride / hexane; dichloromethane / 1 h / -70 °C / Inert atmosphere 3: di-isopropyl azodicarboxylate; triphenylphosphine / tetrahydrofuran / 3 h / 0 - 20 °C / Inert atmosphere
  • 30
  • [ 151733-96-9 ]
  • [3-(difluoromethyl)-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methanamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: copper(l) iodide; <i>L</i>-proline / N,N-dimethyl-formamide / 12 h / 90 °C / Inert atmosphere 2: diisobutylaluminium hydride / hexane; dichloromethane / 1 h / -70 °C / Inert atmosphere 3: di-isopropyl azodicarboxylate; triphenylphosphine / tetrahydrofuran / 3 h / 0 - 20 °C / Inert atmosphere 4: hydrazine hydrate / methanol / 12 h / 60 °C / Inert atmosphere
  • 31
  • [ 151733-96-9 ]
  • N-[[3-(difluoromethyl)-1-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl]methyl]-2-[(4-fluorophenyl)sulfanyl]cyclobutane-1-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: copper(l) iodide; <i>L</i>-proline / N,N-dimethyl-formamide / 12 h / 90 °C / Inert atmosphere 2: diisobutylaluminium hydride / hexane; dichloromethane / 1 h / -70 °C / Inert atmosphere 3: di-isopropyl azodicarboxylate; triphenylphosphine / tetrahydrofuran / 3 h / 0 - 20 °C / Inert atmosphere 4: hydrazine hydrate / methanol / 12 h / 60 °C / Inert atmosphere 5: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 12 h / 20 °C / Inert atmosphere
  • 32
  • [ 151733-96-9 ]
  • C23H19F6N3O3S [ No CAS ]
  • C23H19F6N3O3S [ No CAS ]
  • C23H19F6N3O3S [ No CAS ]
  • (1S,2S)-N-((3-(difluoromethyl)-1-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)methyl)-2-(4-fluorophenylsulfonyl)cyclobutanecarboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: copper(l) iodide; <i>L</i>-proline / N,N-dimethyl-formamide / 12 h / 90 °C / Inert atmosphere 2: diisobutylaluminium hydride / hexane; dichloromethane / 1 h / -70 °C / Inert atmosphere 3: di-isopropyl azodicarboxylate; triphenylphosphine / tetrahydrofuran / 3 h / 0 - 20 °C / Inert atmosphere 4: hydrazine hydrate / methanol / 12 h / 60 °C / Inert atmosphere 5: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 12 h / 20 °C / Inert atmosphere 6: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 0 - 20 °C / Inert atmosphere
  • 33
  • [ 151733-96-9 ]
  • [ 455-13-0 ]
  • ethyl 3-(difluoromethyl)-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With copper(l) iodide; <i>L</i>-proline In N,N-dimethyl-formamide at 90℃; for 12h; Inert atmosphere; 1.4 Example 1, Step 4: Preparation of ethyl 3-(difluoromethyl)-l -[4-(trifluoromethyl)phenyl]-lH- pyrazole-4-carboxylate A mixture of ethyl 3-(difluoromethyl)-lH-pyrazole-4-carboxylate (1.23 g, 6.47 mmol, 1.00 equiv), l-iodo-4-(trifluoromethyl)benzene (2.51 g, 9.21 mmol, 1.42 equiv), Cul (123 mg, 0.65 mmol, 0.10 equiv), L-proline (149 mg, 1.29 mmol, 0.20 equiv), Cs2C03 (5.276 g, 16.19 mmol, 2.50 equiv), and N,N-dimethylformamide (50 mL) was stirred for 12 h at 90°C under nitrogen. The resulting solution was diluted with brine, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by a silica gel column eluting with ethyl acetate/hexane (1/50) to afford the title compound (1.322 g, 61%) as a light yellow solid. LC-MS (ESI): [M+H]+ = 335.1
  • 34
  • [ 151733-96-9 ]
  • (3-(difluoromethyl)-1H-pyrazol-4-yl)methanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
71.9% With diisobutylaluminium hydride In toluene at -78℃; for 1h; intermediate 88A: 3cyc1opropy14WpyrazoI4yI)methanoi To a stirred solution of ethyl 3-(difluoromethyl)-1H-pyrazole-4-carboxylate (2.50 g, 13.15 mmoi) in toluene (75 mnL) was added I)[I3AL-H (39.40 mL, 3940 mmoi) at -78 °C and stirring was continued for I h at -78 °C. The reaction mixture was quenched with MeOH (5 mL) at 78 °C and the precipitated solid was filtered. The resulting filtrate was concentrated underreduced pressure to obtain Intermediate 88A (140 g, 7190%). ‘H NMR (400 MHz, DMOd6)ppm 448 (d, J 502 Hz, 2 H), 4.96 (t, .1 5.27 Hz, I H), 6.77 7.15 (m, 1 H), 7.72 (s, I H),13.06 (br. 5., 1 H. LCMS (ZVIethod4D): retention time 0.394 mm, [M-f-H] 149.2.
71.9% With diisobutylaluminium hydride In toluene at -78℃; for 2h; Intermediate 67A: (6-chloro-4-(trifluoromethyl)pyridin-3-yl)methanol General procedure: To a stirred solution of 6-chloro-4-(trifluoromethyl)nicotinate (2.00 g, 8.35 mmol) in toluene (25 mL) at -78°C was added 1M DIBAL-H in toulene (12.52 mL, 12.52 mmol) and the reaction mixture was stirred at -78°C for 2 h. The resulting reaction mixture was diluted with saturated NH4Cl (40 mL) and extracted with ethyl acetate (2 x 75 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate and evaporated under reduced pressure to obtain Intermediate 67A (2.20 g, 87.00%).1H NMR (400 MHz, DMSO-d6) G^ppm 4.70 (s, 2 H), 5.65 - 5.77 (m, 1 H), 7.88 (s, 1 H), 8.76 (s, 1 H). LCMS: The compound did not ionize well
  • 35
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-1H-pyrazole-4-carbaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: diisobutylaluminium hydride / toluene / 1 h / -78 °C 2: manganese(IV) oxide / acetone / 12 h / 0 - 60 °C
  • 36
  • [ 151733-96-9 ]
  • [ 7051-34-5 ]
  • ethyl 1-(cyclopropylmethyl)-3-(difluoromethyl)-1H-pyrazole-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
47% With caesium carbonate In dimethylsulfoxide-d6 at 120℃; for 3h; 50.A Step A: Ethyl 1-(cyclopropylmethyl)-3-(difluoromethyl)-1H-pyrazole-4- carboxylate To a solution of ethyl 3-(difluoromethyl)-1H-pyrazole-4-carboxylate (2 g, 10.5 mmol) in DMSO (30 mL) was added (bromomethyl)cyclopropane (5.68 g, 42.0 mmol) and Cs2CO3 (6.85 g, 21.0 mmol) and the mixture was heated at 120 C for 3 h. After this time the mixture was concentrated in vacuo and purified by HPLC (using a Phenomenex Synergi Max-RP 10µm, 150x50mm column and using water (containing 0.225%HCOOH) and MeCN from 25% to 55% as the mobile phase at a flow rate of 120 mL/min) to give the title compound as a white solid (1.1 g, 47%). 1H NMR (400 MHz, DMSO-d6) d ppm 8.48 (s, 1H), 7.35 - 7.03 (m, 1H), 4.32 - 4.19 (m, 2H), 4.05 (d, J = 7.0 Hz, 2H), 1.34 - 1.24 (m, 4H), 0.57 - 0.50 (m, 2H), 0.43 - 0.36 (m, 2H). MS (ESI): 245.1 [M + H]+.
  • 37
  • [ 407-20-5 ]
  • [ 151733-96-9 ]
  • 1-(5-bromopyridin-3-yl)-3-(difluoromethyl)-1H-pyrazole-4-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
4.4 g With caesium carbonate In dimethyl sulfoxide at 120℃; for 12h; 74.C Step C: 1-(5-Bromopyridin-3-yl)-3-(difluoromethyl)-1H-pyrazole-4-carboxylic acid A mixture of ethyl 3-(difluoromethyl)-1H-pyrazole-4-carboxylate (5.00 g, 26.3 mmol) and 3-bromo-5-fluoropyridine (4.63 g, 26.3 mmmol) and Cs2CO3 (34.27 g, 105 mmol) in DMSO (100 mL) was stirred at 120 C for 12 h. After this time the mixture was poured into water (100 mL) and washed with EtOAc (100 mL). The aqueous phase was adjusted to pH 3 ~ 4 with 3M HCl. The solid was filtered and dried under vacuum to give the title compound (4.4 g, 81%) as a white solid. MS (ESI): 317.9 [(M + H) (79Br)]+.
  • 38
  • [ 352-24-9 ]
  • [ 151733-96-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: acetic anhydride / 8.5 h / 100 °C 2: hydrazine hydrate / methanol / 3 h / 70 °C
  • 39
  • [ 151733-96-9 ]
  • 1-(cyclopropylmethyl)-3-(difluoromethyl)-1H-pyrazole-4-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: caesium carbonate / dimethylsulfoxide-d6 / 3 h / 120 °C 2: water; sodium hydroxide / methanol / 3 h / 30 °C
  • 40
  • [ 151733-96-9 ]
  • 1-(cyclopropylmethyl)-3-(difluoromethyl)-1H-pyrazole-4-carbonyl chloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: caesium carbonate / dimethylsulfoxide-d6 / 3 h / 120 °C 2: water; sodium hydroxide / methanol / 3 h / 30 °C 3: thionyl chloride / 15 h / 60 °C
  • 41
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-1-(2-methoxyethyl)-1H-pyrazole-4-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 3 h / 80 °C 2: methanol; sodium hydroxide / tetrahydrofuran / 1 h / 60 °C
  • 42
  • [ 151733-96-9 ]
  • (S)-3-(difluoromethyl)-1-(2-methoxyethyl)-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide / 3 h / 80 °C 2: methanol; sodium hydroxide / tetrahydrofuran / 1 h / 60 °C 3: triethylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / ethyl acetate / 3 h / 80 °C
  • 43
  • [ 151733-96-9 ]
  • 1-(5-bromopyridin-3-yl)-3-(difluoromethyl)-1H-pyrazole-4-carbonyl chloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C
  • 44
  • [ 151733-96-9 ]
  • 1-(5-bromopyridin-3-yl)-3-(difluoromethyl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: dmap / dichloromethane / 3 h / 28 °C
  • 45
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1-(5-methylpyridin-3-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: dmap / dichloromethane / 3 h / 28 °C 4: potassium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 48 h / 100 °C / Inert atmosphere
  • 46
  • [ 151733-96-9 ]
  • 1-(5-cyanopyridin-3-yl)-3-(difluoromethyl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: dmap / dichloromethane / 3 h / 28 °C 4: tris-(dibenzylideneacetone)dipalladium(0); zinc; 1,1'-bis-(diphenylphosphino)ferrocene / N,N-dimethyl acetamide / 20 h / 30 - 120 °C / Inert atmosphere
  • 47
  • [ 151733-96-9 ]
  • 1-(5-cyclopropylpyridin-3-yl)-3-(difluoromethyl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: dmap / dichloromethane / 3 h / 28 °C 4: palladium diacetate; tricyclohexylphosphine; caesium carbonate / water; toluene / 12 h / 110 °C
  • 48
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1-(5-methoxypyridin-3-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: dmap / dichloromethane / 3 h / 28 °C 4: sodium methylate / 1-methyl-pyrrolidin-2-one / 0.5 h / 90 °C
  • 49
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-1-(5-(dimethylamino)pyridin-3-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: dmap / dichloromethane / 3 h / 28 °C 4: tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; ruphos / N,N-dimethyl-formamide / 12 h / 100 °C
  • 50
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: dmap / dichloromethane / 3 h / 28 °C 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 2 h / 110 °C / Inert atmosphere
  • 51
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-1-(5-hydroxypyridin-3-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: dmap / dichloromethane / 3 h / 28 °C 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 2 h / 110 °C / Inert atmosphere 5: dihydrogen peroxide; acetic acid / tetrahydrofuran / 1 h / 50 °C / Inert atmosphere
  • 52
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-1-(5-isopropoxypyridin-3-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: dmap / dichloromethane / 3 h / 28 °C 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 2 h / 110 °C / Inert atmosphere 5: dihydrogen peroxide; acetic acid / tetrahydrofuran / 1 h / 50 °C / Inert atmosphere 6: potassium carbonate; potassium iodide / N,N-dimethyl-formamide / 2 h / 80 °C / Inert atmosphere
  • 53
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1-(pyridin-3-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: dmap / dichloromethane / 3 h / 28 °C 4: hydrogen; palladium on activated charcoal / methanol / 4 h / 28 °C / 775.74 Torr
  • 54
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-1-(pyrazin-2-yl)-1H-pyrazole-4-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / N,N-dimethyl-formamide / 100 °C / Inert atmosphere 2: methanol; sodium hydroxide / tetrahydrofuran / 1 h / 60 °C
  • 55
  • [ 151733-96-9 ]
  • (S)-3-(difluoromethyl)-1-(pyrazin-2-yl)-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: copper(l) iodide; potassium carbonate; <i>L</i>-proline / N,N-dimethyl-formamide / 100 °C / Inert atmosphere 2: methanol; sodium hydroxide / tetrahydrofuran / 1 h / 60 °C 3: triethylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / ethyl acetate / 3 h / 80 °C
  • 56
  • [ 151733-96-9 ]
  • 1-(5-bromopyridin-3-yl)-3-(difluoromethyl)-N-(6-(1-isopropyl-1H-imidazol-5-yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: pyridine; dmap / dichloromethane / 1 h / 24 °C
  • 57
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-N-(6-(1-isopropyl-1H-imidazol-5-yl)pyridin-2-yl)-1-(5-methylpyridin-3-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: pyridine; dmap / dichloromethane / 1 h / 24 °C 4: potassium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 17 h / 90 °C
  • 58
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-N-(6-(1-isopropyl-1H-imidazol-5-yl)pyridin-2-yl)-1-(pyridin-3-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: pyridine; dmap / dichloromethane / 1 h / 24 °C 4: hydrogen; palladium on activated charcoal / methanol / 3 h / 20 °C / 775.74 Torr
  • 59
  • [ 151733-96-9 ]
  • 1-(5-cyanopyridin-3-yl)-3-(difluoromethyl)-N-(6-(1-isopropyl-1H-imidazol-5-yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: pyridine; dmap / dichloromethane / 1 h / 24 °C 4: tris-(dibenzylideneacetone)dipalladium(0); zinc; 1,1'-bis-(diphenylphosphino)ferrocene / N,N-dimethyl acetamide / 20 h / 30 - 120 °C / Inert atmosphere
  • 60
  • [ 151733-96-9 ]
  • 1-(5-cyclopropylpyridin-3-yl)-3-(difluoromethyl)-N-(6-(1-isopropyl-1H-imidazol-5-yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: pyridine; dmap / dichloromethane / 1 h / 24 °C 4: palladium diacetate; tricyclohexylphosphine; caesium carbonate / water; toluene / 2 h / 110 °C / Inert atmosphere
  • 61
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-N-(6-(1-isopropyl-1H-imidazol-5-yl)pyridin-2-yl)-1-(5-methoxypyridin-3-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: pyridine; dmap / dichloromethane / 1 h / 24 °C 4: sodium methylate / 1-methyl-pyrrolidin-2-one / 0.5 h / 90 °C
  • 62
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-1-(5-(dimethylamino)pyridin-3-yl)-N-(6-(1-isopropyl-1H-imidazol-5-yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: pyridine; dmap / dichloromethane / 1 h / 24 °C 4: tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; ruphos / N,N-dimethyl-formamide / 3 h / 100 °C / Inert atmosphere
  • 63
  • [ 151733-96-9 ]
  • (5-(3-(difluoromethyl)-4-((6-(1-isopropyl-1H-imidazol-5-yl)pyridin-2-yl)carbamoyl)-1H-pyrazol-1-yl)pyridin-3-yl)boronic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: pyridine; dmap / dichloromethane / 1 h / 24 °C 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 17 h / 100 °C / Inert atmosphere
  • 64
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-1-(5-hydroxypyridin-3-yl)-N-(6-(1-isopropyl-1H-imidazol-5-yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: pyridine; dmap / dichloromethane / 1 h / 24 °C 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 17 h / 100 °C / Inert atmosphere 5: dihydrogen peroxide; acetic acid / tetrahydrofuran / 2 h / 50 °C
  • 65
  • [ 151733-96-9 ]
  • 3-(difluoromethyl)-1-(5-isopropoxypyridin-3-yl)-N-(6-(1-isopropyl-1H-imidazol-5-yl)pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: caesium carbonate / dimethyl sulfoxide / 12 h / 120 °C 2: thionyl chloride / 12 h / 60 °C 3: pyridine; dmap / dichloromethane / 1 h / 24 °C 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 17 h / 100 °C / Inert atmosphere 5: dihydrogen peroxide; acetic acid / tetrahydrofuran / 2 h / 50 °C 6: potassium carbonate; potassium iodide / N,N-dimethyl-formamide / 2 h / 80 °C
  • 66
  • [ 14508-49-7 ]
  • [ 151733-96-9 ]
  • ethyl 3-(difluoromethyl)-1-(pyrazin-2-yl)-1H-pyrazole-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With copper(l) iodide; potassium carbonate; <i>L</i>-proline In N,N-dimethyl-formamide at 100℃; Inert atmosphere; 89.A Step A: Ethyl 3-(difluoromethyl)-1-(pyrazin-2-yl)-1H-pyrazole-4-carboxylate A mixture of ethyl 3-(difluoromethyl)-1H-pyrazole-4-carboxylate (350 mg, 1.8 mmol), 2-chloropyrazine (253 mg, 2.2 mmol), CuI (35 mg, 0.18 mmol), L-proline (42 mg, 0.37 mmol) and potassium carbonate (559 mg, 4 mmol) were dissolved in DMF (12 mL) and heated to 100 °C overnight under a N2 atmosphere. After this time, the reaction was cooled to rt, filtered and the solvent was evaporated in vacuo. The crude material was purified by column chromatography using CH2Cl2 as eluent to give the title compound (350 mg, 71%). 1H NMR (400 MHz, CDCl3) d ppm 9.42 (d, J=1.3 Hz, 1H), 9.03 (s, 1H), 8.64 (d, J=2.5 Hz, 1H), 8.44 (dd, J=2.3, 1.5 Hz, 1H), 7.16 - 7.28 (m, 1H), 4.38 (q, J=7.0 Hz, 2H), 1.40 (t, J=7.2 Hz, 3H). MS (ESI): 269.0 [M + H]+.
  • 67
  • [ 151733-96-9 ]
  • [ 6482-24-2 ]
  • ethyl 3-(difluoromethyl)-1-(2-methoxyethyl)-1H-pyrazole-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% In N,N-dimethyl-formamide at 80℃; for 3h; 51.A Step A: Ethyl 3-(difluoromethyl)-1-(2-methoxyethyl)-1H-pyrazole-4-carboxylate Ethyl 3-(difluoromethyl)-1H-pyrazole-4-carboxylate (250 mg, 1.3 mmol) and 1- bromo-2-methoxy-ethane (237 mg, 1.7 mmol, 160 µL) were dissolved in DMF (2.0 mL) and the mixture was heated at 80 °C for 3 h. After this time the reaction was cooled to rt, diluted with EtOAc, and washed with water (x2). The separated organic layer was dried over MgSO4, filtered and concentrated in vacuo. Purification by silica gel chromatography (50-100% EtOAc in heptane) gave the title compound (325 mg, 61%).1H NMR (400 MHz, CDCl3) d ppm 8.00 (t, J=1.1 Hz, 1H), 6.96 - 7.26 (m, 1H), 4.27 - 4.37 (m, 4H), 3.69 - 3.80 (m, 2H), 3.34 (s, 3H), 1.36 (t, J=7.2 Hz, 3H). MS (ESI): 249.1 [M + H]+.
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