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[ CAS No. 1073354-70-7 ] {[proInfo.proName]}

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Chemical Structure| 1073354-70-7
Chemical Structure| 1073354-70-7
Structure of 1073354-70-7 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1073354-70-7 ]

CAS No. :1073354-70-7 MDL No. :MFCD09027070
Formula : C16H27BN2O4 Boiling Point : -
Linear Structure Formula :- InChI Key :GNLNGVZPEKSDAR-UHFFFAOYSA-N
M.W : 322.21 Pubchem ID :16218387
Synonyms :

Calculated chemistry of [ 1073354-70-7 ]

Physicochemical Properties

Num. heavy atoms : 23
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.75
Num. rotatable bonds : 4
Num. H-bond acceptors : 5.0
Num. H-bond donors : 0.0
Molar Refractivity : 90.84
TPSA : 62.58 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.93 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 3.29
Log Po/w (WLOGP) : 2.58
Log Po/w (MLOGP) : 1.66
Log Po/w (SILICOS-IT) : 1.56
Consensus Log Po/w : 1.82

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.81
Solubility : 0.0502 mg/ml ; 0.000156 mol/l
Class : Soluble
Log S (Ali) : -4.28
Solubility : 0.0169 mg/ml ; 0.0000526 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -3.66
Solubility : 0.0703 mg/ml ; 0.000218 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 3.74

Safety of [ 1073354-70-7 ]

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

Application In Synthesis of [ 1073354-70-7 ]

* 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 [ 1073354-70-7 ]

[ 1073354-70-7 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 857530-80-4 ]
  • [ 24424-99-5 ]
  • [ 1073354-70-7 ]
YieldReaction ConditionsOperation in experiment
62% With sodium carbonate; In 1,4-dioxane; at 20℃; for 48h; To a stirred solution of 3, 5-dimethyl-4-(4,4, 5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1 Hpyrazole (0.5 g, 2.25 mmol) in 1,4-dioxane (10.0 mL) and 2M Na2CO3 solution (2.5 mL) was added Boc-anhydride (0.62 mL, 2.70 mmol) and stirred at RT for 48 h. After completion of the reaction, the reaction mixture was diluted with EtOAc (200 mL), washed with water (100 mL), brine (50 mL), dried over sodium sulphate and concentrated. The residue was purified on silicagel (100-200 mesh) to isolate the title compound as off-white solid (0.45 g, 62%). 1H NMR (400 MHz, DMSO-d6) oe 3.31 (s, 3H), 2.21 (s, 3H), 1.55 (s, 9H), 1.26 (s, 12H); LC-MS: m/z 323.2(M+1).
62% With sodium carbonate; In 1,4-dioxane; water; at 20℃; for 48h; Intermediate-72 RRN 213Synthesis of tert-butyl 3, 5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (0203) (0204) To a stirred solution of <strong>[857530-80-4]3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong> (0.5 g, 2.25 mmol) in 1,4-dioxane (10.0 mL) and 2M Na2CO3 solution (2.5 mL) was added Boc-anhydride (0.62 mL, 2.70 mmol) and stirred at RT for 48 h. After completion of the reaction, the reaction mixture was diluted with EtOAc (200 mL), washed with water (100 mL), brine (50 mL), dried over sodium sulphate and concentrated. The residue was purified on silica gel (100-200 mesh) to isolate the title compound as off-white solid (0.45 g, 62%). 1H NMR (400 MHz, DMSO-d6) delta 3.31 (s, 3H), 2.21 (s, 3H), 1.55 (s, 9H), 1.26 (s, 12H); LC-MS: m/z 323.2 (M+1)+.
With dmap; In acetonitrile; at 10 - 35℃; for 3h; Reference Example 1; tert-butyl <strong>[857530-80-4]3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong>-1-carboxylate 3,5-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (3.05 g) was dissolved in acetonitrile (80 mL), and N,N-dimethylaminopyridine (1.09 g) and di-tert-butyl bicarbonate (4.1 mL) were added. The reaction mixture was stirred at room temperature for 3 hr. Saturated brine was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The obtained residue was washed with hexane-diisopropyl ether to give the title compound (3.40 g) as colorless crystals.1H-NMR (DMSO-d6) delta: 1.27 (12H, s), 1.55 (9H, s), 2.21 (3H, s), 2.59 (3H, s).
With sodium carbonate; In 1,4-dioxane; water; Example 167[5-(4-Dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2-yl]-[2-(3,5- dimethyl-1 H-pyrazol-4-yl)-pyridin-4-yl]-methanoneSynthetic scheme Step 13,5-Dimethyl-4-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl esterThe mixture of 3,5-dimethyl-4-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)- pyrazole 91 g, 4.5 mmole), di-tert-butyl dicarbonate (1.18 g, 5.40 mmole), 2 mole of Na2CO3 aqueous (4.5 ml, 9.01 mmole) and dioxane (30 ml) was stirred overnight. Reaction solution was diluted with water and extracted with EtOAc. EtOAc layer was concentrated. Residue was purified by using chromatograph eluting with 20% to 50% EtOAc in heptane to afford 3.5-dimethyl-4-(4,4.5,5- tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-pyrazole-1 -carboxylic acid tert-butyl ester. 1 H NMR (400MHz, CD2CI2) delta 1.33 (s, 9H), 1.52 (s, 6H), 1.66 (s, 6H), 2.34 (s, 3H), 2.67 (s, 3H). HR-MS m/z 323.2132 (M+1 ).

  • 2
  • [ 1073354-70-7 ]
  • [ 623-00-7 ]
  • [ 1126779-19-8 ]
  • [ 51463-73-1 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃; for 4.0h;Inert atmosphere; (Synthesis method 2) <strong>[1073354-70-7]tert-butyl 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate</strong> (14.4 g) synthesized in Reference Example 1, 4-bromobenzonitrile (8.13 g) and sodium carbonate (11.8 g) were dissolved in dimethoxyethane-water (6:1), and tetrakis(triphenylphosphine)palladium(0) (5.16 g) was added under a nitrogen atmosphere. The reaction mixture was stirred at 90 C. for 4 hr, poured into water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The obtained residue was applied to column chromatography to remove the impurities, whereby a mixture of tert-butyl 4-(4-cyanophenyl)-3,5-dimethyl-1H-pyrazole-1-carboxylate and the title compound was obtained. TFA (50 mL) was added to the obtained mixture, and the mixture was stirred at room temperature for 15 min. The reaction mixture was concentrated, and azeotroped with toluene. The obtained residue was purified by column chromatography (hexane-ethyl acetate), and recrystallized from diethyl ether-hexane to give the title compound (2.00 g) as colorless crystals. 1H-NMR (CDCl3) delta: 2.33 (6H, s), 7.39 (2H, d), 7.71 (2H, d).
  • 3
  • [ 1073354-70-7 ]
  • [ 154607-01-9 ]
  • [ 1126779-15-4 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃; for 4.0h; Reference Example 42-chloro-4-(3,5-dimethyl-1H-pyrazol-4-yl)benzonitrile (Synthesis method 1) A mixture of <strong>[1073354-70-7]tert-butyl 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate</strong> (1.70 g) synthesized in Reference Example 1, 4-bromo-2-chlorobenzonitrile (1.14 g), tetrakis(triphenylphosphine)palladium(0) (0.58 g), sodium carbonate (1.4 g), 1,2-dimethoxyethane (40 mL) and water (7 mL) was stirred at 90 C. for 4 hr. Water and ethyl acetate were added to the reaction mixture, and the organic layer was separated. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by column chromatography (hexane-ethyl acetate), and each fraction was suspended in diisopropyl ether and collected by filtration to give the title compound (193 mg) and tert-butyl 4-(3-chloro-4-cyanophenyl)-3,5-dimethyl-1H-pyrazole-1-carboxylate (620 mg) as a solid. A mixture of tert-butyl 4-(3-chloro-4-cyanophenyl)-3,5-dimethyl-1H-pyrazole-1-carboxylate (600 mg) and TFA was stirred at room temperature for 3 hr, neutralized with saturated aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The obtained residue was washed with diisopropyl ether to give the title compound (328 mg) as colorless crystals
  • 4
  • [ 1073354-70-7 ]
  • [ 1254163-37-5 ]
  • [ 1254163-51-3 ]
YieldReaction ConditionsOperation in experiment
31.5% With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 120℃; for 0.666667h;Microwave irradiation; Step 24-{4-[5-(4-Dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2- carbonyl]pyridi-2-yl}-3,5-dimethyl-pyrazole-1 -carboxylic acid tert-butyl ester The mixture of [5-(4-dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl]- [2-bromo-pyridin-4-yl]-methanone (Example 162) (50 mg, 0.12 mmole), 3,5- dimethyl-4-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-pyrazole-1 -carboxylic acid tert-butyl ester. (37.5 mg, 0.12 mmole), Pd(Ph3)4 (27 mg, 0.023 mmole), 2 molar of K3PO4 aqueous (0.1 ml, 0.23 mmole), and dioxane (3.0 ml) was degassed and heated to 1200C for 40 minutes in microwave. Reaction solution was diluted with water and extracted with EtOAc. EtOAc layer was concentrated. Residue was purified by using HPLC (20% to 40% of acetonitrile in water with 0.1% NH4OH) to afford 4-{4-[5-(4-dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridine-2- carbonyl]pyridi-2-yl}-3,5-dimethyl-pyrazole-1 -carboxylic acid tert-butyl ester (20 mg, 31.5 %). 1 H NMR (400MHz, CD2CI2) delta 1.68 (s, 9H), 1.90 (m, 2H), 2.05 (m, 2H), 2.44 (s, 6H), 2.74 (m, 1 H), 2.77 (s, 6H), 4.16 (m, 2H), 4.56 (m, 2H), 6.90 (d, J=9.54 Hz, 1 H), 7.96 (d, J=9.03 Hz, 1 H), 8.25 (dd, J=5.02 Hz, 1 H), 8.51 (s, 1 H), 8.93 (d, J= 5.02 Hz, 1 H). MS (ESI) m/z 545 [M+1].
  • 5
  • [ 1073354-70-7 ]
  • [ 1254163-44-4 ]
  • [ 1254163-54-6 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 120℃; for 0.666667h;Microwave irradiation; Example 170(5-[1 ,4]Diazepan-1 -yl-3H-imidazo[4,5-b]-pyridin-2-yl)-[2-(3,5-dimethyl-1 H-pyrazol- 4-yl)-pyridin-4-yl]-methanoneSynthetic schemeThe mixture of [4-[2-(2-bromo-pyridine-4-carbonyl)-3H-imidazo[4,5-b]pyridine-5-yl]- diazepane-1-carboxylic acid tert-butyl ester (Example 163) (58 mg, 0.1 16 mmole), 3,5-dimethyl-4-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (Example 167) (37 mg, 0.116 mmole), Pd(Ph3)4 (13.4 mg, 0.012 mmole), 2 molar of K3PO4 aqueous (0.12 ml, 0.23 mmole), and dioxane (3.0 ml) was degassed and heated to 1200C for 40 minutes in microwave. Reaction solution was diluted with water and extracted with EtOAc. EtOAc layer was concentrated to afford 40mg of crude 4-{2-[2-(1-tert-butoxycarbonyl-3,5-dimethyl- 1 H-pyrazol-4-yl)-pyridine-4-carbonyl]-3H-imidazo[4,5-b]pyridin-5-yl}- [1 ,4]diazepane-1-carboxylic acid tert-butyl ester, which was dissolved in 2 ml of 2 molar HCI ether solution. The acidic solution was stirred for 2 hours, then solvent was removed. Residue was washed with CH2Cb and was purified by using HPLC, eluting with 10 to 20 % of acetonitrile in water (0.1% of NH4OH) to yield (5- [1 ,4]diazepan-1 -yl-3H-imidazo[4,5-b]-pyridin-2-yl)-[2-(3,5-dimethyl-1 H-pyrazol-4- yl)-pyridin-4-yl]-methanon (7 mg, 42%) as a yellow solid. 1 H NMR (400MHz, CD3OD) delta 1.98 (m, 1 H), 2.04 (m, 1 H), 2.40 (m, 1 H), 2.79 (m, 1 H), 3.01 (m, 1 H), 3.64 (m, 1 H), 3.84 (m, 5H), 6.78 (m, 1 H), 7.83 (d, J=9.03 Hz, 1 H), 7.95 (m, 1 H), 8.19 (d, J=17.07 Hz, 1 H), 8.76 (m, 1 H). HR-MS m/z 417.2144 (M+1 ).
  • 6
  • [ 1073354-70-7 ]
  • [ 1254163-50-2 ]
  • [ 1254163-53-5 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 120℃; for 0.666667h;Microwave irradiation; Example 169[2-(3,5-Dimethyl-1 H-pyrazol-4-yl)-pyridin-4-yl]-(5-piperazin-1-yl-3H-imidazo[4,5- b]pyridine-2-yl)-methanoneSynthetic scheme4-{2-[2-(1-tert-Butoxycarbonyl-3,5-dimethyl-1 H-pyrazol-4-yl)-pyridine-4-carbonyl]- 3H-imidazo[4,5-b]pyridin-5-yl}-piperazine-1-carboxylic acid tert-butyl esterThe mixture of [4-[2-(2-bromo-pyridine-4-carbonyl)-3H-imidazo[4,5-b]pyridine-5-yl]- piperazine-1-carboxylic acid tert-butyl ester (Example 164) (100 mg, 0.205 mmole), 3,5-dimethyl-4-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (Example 167) (66 mg, 0.205 mmole), Pd(Ph3)4 (23 mg, 0.021 mmole), 2 molar of K3PO4 aqueous (0.21 ml, 0.41 mmole), and dioxane (3.0 ml) was degassed and heated to 1200C for 40 minutes in microwave. Reaction solution was diluted with water and extracted with EtOAc. EtOAc layer was concentrated to afford 120mg of crude 4-{2-[2-(1-tert-butoxycarbonyl-3,5-dimethyl- I H-pyrazol^-yO-pyridine^-carbonyO-SH-imidazo^^-blpyridin-delta-ylJ-piperazine-i- carboxylic acid tert-butyl ester, which was dissolved in 3 ml of 2 molar HCI ether solution. The acidic solution was stirred for 2 hours, then solvent was removed. Residue was washed with EtOAc and was purified by using HPLC, eluting with 10 to 20 % of acetonitrile in water (0.1% of NH4OH) to yield [2-(3,5-Dimethyl-1 H- pyrazol-4-yl)-pyridin-4-yl]-(5-piperazin-1-yl-3H-imidazo[4,5-b]pyridine-2-yl)- methanon (20 mg, 24%) as a yellow solid. 1 H NMR (400MHz, CD3OD) delta 2.41 (s, 6H), 2.94 (m, 4H), 3.61 (m, 4H), 6.88 (d, J=9.03 Hz, 1 H), 7.87 (d, J=9.03 Hz, 1 H), 7.94 (d, J=5.02 Hz, 1 H), 8.17 (s, 1 H), 8.76 (d, J= 5.02 Hz, 1 H). HR-MS m/z 403.1981 (M+1 ).
  • 7
  • [ 1073354-70-7 ]
  • [ 1354288-75-7 ]
  • [ 1354287-81-2 ]
YieldReaction ConditionsOperation in experiment
With potassium fluoride;tris-(dibenzylideneacetone)dipalladium(0); bis(tri-t-butylphosphine)palladium(0); In N,N-dimethyl-formamide; at 100℃; for 19.0h;Inert atmosphere; 5,7-Difluoro-N-(5-iodo-2-morpholinopyridin-4-yl)-3-methyl-2-(pyridin-2-yl)- quinolin-4-amine (97 mg, 0.17 mmol), tert-butyl 3,5-dimethyl-4-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole-l-carboxylate (113 mg, 0.35 mmol), tris(dibenzylideneacetone)dipalladium (0) (16 mg, 0.018 mmol), bis(tri- tert-butylphosphine)palladium (0) (19 mg, 0.037 mmol), and potassium fluoride (26 mg, 0.45 mmol) were added to a vial then degassed and backfilled with argon. To the flask, anhydrous DMF (1.5 mL) was added by syringe. The resulting reaction was heated to 100 C and monitored with TLC and LC-MS. After 19 h, the reaction was cooled to rt then poured into water. After extracting twice with EtOAc and twice with DCM, the combined organic extractions were dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on silica gel (0-55% of a premixed solution of 89:9: 1 DCM: MeOH: ammonium hydroxide in DCM) to afford a purple film that was further purified with HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution). The desired fractions were concentrated then diluted with EtOAc.After washing twice with saturated aq. sodium bicarbonate solution and once with brine, the solvent was removed under reduced pressure to yield a yellowish film that was purified using SFC to afford a faint yellow solid as N-(5-(3,5-dimethyl- lH-pyrazol-4-yl)-2-morpholinopyridin-4-yl)-5,7-difluoro-3-methyl-2-(pyridin-2- yl)quinolin-4-amine. .H NMR (500 MHz, MeOH) delta ppm 8.73 (1 H, d, J=4.6 Hz), 8.10 (1 H, td, J=7.7, 1.5 Hz), 7.90 (1 H, d, J=7.8 Hz), 7.70 (3 H, m), 7.31 (1 H, ddd, J=12.4, 9.4, 2.4 Hz), 5.66 (1 H, s), 3.75 (4 H, t, J=4.9 Hz), 3.46 (4 H, m), 2.32 (3 H, s), 2.30 (3 H, s), 2.22 (3 H, s). Mass Spectrum (pos.) m/e: 528.1 (M+H)+.
  • 8
  • [ 69249-61-2 ]
  • [ 1073354-70-7 ]
  • 1-Boc-3,5-dimethyl-4-[2-(3-hexylthienyl)]-1H-pyrazole [ No CAS ]
  • 9
  • [ 1073354-70-7 ]
  • 4-[2-(3-hexylthienyl)]-3,5-dimethyl-1H-pyrazole [ No CAS ]
  • 10
  • [ 1073354-70-7 ]
  • tris-(μ-N,N'-(4-[2-(3-hexylthienyl)]3,5-dimethylpyrazolato)trigold(I)) [ No CAS ]
  • 11
  • [ 1073354-70-7 ]
  • [ 154717-20-1 ]
  • 1-Boc-4-[5-(3,3'-dihexyl-2,2'-bithienyl)]-3,5-dimethyl-1H-pyrazole [ No CAS ]
  • 12
  • [ 1073354-70-7 ]
  • [ 154717-20-1 ]
  • 4-[5-(3,3'-dihexyl-2,2'-bithienyl)]-3,5-dimethyl-1H-pyrazole [ No CAS ]
  • 13
  • [ 1073354-70-7 ]
  • 6-bromo-1-[(4,4-difluorocyclohexyl)methyl]-3-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]pyrrolo[3,2-b]pyridine [ No CAS ]
  • 1-[(4,4-difluorocyclohexyl)methyl]-6-(3,5-dimethyl-1H-pyrazol-4-yl)-3-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]pyrrolo[3,2-b]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
44.9% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In water; acetonitrile; at 140℃; for 0.666667h;Microwave irradiation; To 6-bromo-l-[(4,4- difluorocyclohexyl)methyl]-3-[l-(2,2,2-trifluoroethyl)pyrazol-4-yl]pyrrolo[3,2-b]pyridine (42, 0.06 g, 0.12 mmol) in acetonitrile (3 ml) was added tert-butyl 3,5-dimethyl-4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)pyrazole- 1 -carboxylate (0.08 g, 0.25 mmol), [1, 1'- bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.02 g, 0.13 mmol), and 1M aqueous potassium carbonate (1.2 ml). The reaction was heated under at 140 C for 40 minutes in a microwave reactor. The reaction was poured into water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and filtered. The filtrate was concentrated, and purified by silica gel flash chromatography eluting with 20- 100% ethyl acetate in hexane, and then further purified with RP- HPLC to give product (P-0440, 25.5 mg, 44.9%) MS (ESI) [M+H+]+ = 493.3.
  • 14
  • [ 1073354-70-7 ]
  • 5-bromo-N-cyclopentyl-N-(2,4-dimethoxybenzyl)-2-methoxybenzenesulfonamide [ No CAS ]
  • N-cyclopentyl-N-(2,4-dimethoxybenzyl)-5-(3,5-dimethyl-1H-pyrazol-4-yl)-2-methoxybenzenesulfonamide [ No CAS ]
  • 15
  • [ 1073354-70-7 ]
  • 1-((5-bromopyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one [ No CAS ]
  • 1-((5-(3,5-dimethyl-1H-pyrazol-4-yl)pyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-7-methoxyquinolin-2(1H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 90℃; for 16.0h;Inert atmosphere; Example-Vu: Synthesis of 7-(3 .5 -dimethylisoxazol-4-yl?)-6-methoxy-4-(pyridin-4-ylmethyl?)- 2H-benzo [N [1 ,4loxazin-3(4H)-one (Compound-i 7) To a stirred solution of intermediate-28 (0.10 g, 0.29 mmol) in 1,2-DME (4.0 mL) andH20 (1.0 mL) were added 3,5-dimethylisoxazoleboronic acid (0.123 g, 0.87 mmol), sodiumcarbonate (0.077 g, 0.73 mmol) and degassed with nitrogen purging for 20 mm. Then tetrakis triphenylphosphine palladium (0.017 g, 0.015 mmol) was added and heated at 90C for 16 h. After completion of reaction, the reaction mixture was diluted with EtOAc (50 mL), washed with water (50 mL), brine (50 mL), dried over sodium sulphate and concentrated. The residue waspurified by prep. TLC to afford the title compound as a brown solid (0.04 g, 38%). 1H NMR (400 MHz, DMSO-d6) oe 8.55 (d, J=4.9 Hz, 2H), 7.36 (d, J=4.9 Hz, 2H), 6.96 (s, 1H), 6.66 (s, 1H), 5.27 (s, 2H), 4.80 (s, 2H), 3.58 (s, 3H), 2.22 (s, 3H), 2.04 (s, 3H); LC-MS: m/z 366.1 (M+i).:_Example-XX: Synthesis of 1 -((5-(3 ,5 -dimethyl- 1 H-pyrazol-4-yl)pyridin-2-yl)methyl)-6-(3 , 5- dimethylisoxazol-4-yl)-7-methoxyquinolin-2( 1 H)-one (Compound-99) The process of this was adopted from compound- 17 (Example-Vu). 1H NMR (400 MHz,DMSO-d6): oe 12.39 (bs, 1H), 8.47 (d, J=i.4 Hz, 1H), 7.91 (d, J=9.3 Hz, 1H), 7.14 (dd, J1=2.4Hz, J2=8.3 Hz, 1H), 7.63 (s, 1H), 7.37 (d, J=8.3 Hz, 1H), 7.23 (s, 1H), 6.59 (d, J=9.3 Hz, 1H), 5.66 (s, 2H), 3.78 (s, 3H), 2.25 (s, 9H), 2.06 (s, 3H); LC-MS: m/z 456.2 (M+i).
  • 16
  • [ 1073354-70-7 ]
  • 5-chloro-3-(naphthalen-2-yl)furo[3,2-b]pyridine [ No CAS ]
  • 5-(3,5-dimethyl-1H-pyrazol-4-yl)-3-(naphthalen-2-yl)furo[3,2-b]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
29% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,2-dimethoxyethane; water; for 48.0h;Inert atmosphere; Reflux; Tert-butyl 3 ,5 -dimethyl-4-(4,4,5,5-tetramethyl- 1 ,3 ,2-dioxaborolan-2-yl)- 1 H-pyrazole- 1 - carboxylate (55 mg, 0.17 mmol), the product from Preparative Example 5A (40 mg, 0.14 mmol), K3P04 (91 mg, 0.43 mmol), 1 ,2-dimethoxyethane (2 mL), H20 (0.5 mL) and PdCl2(dppf) (3.1 mg, 4.3 mupiomicron) were added into a 25 mL round bottom flask and the mixture was refluxed under N2 for 24 h. Then, additional tert-butyl 3,5-dimethyl-4- (4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yI)-lH-pyrazole-l-carboxylate (30 mg, 0.09 mmol) and PdCl2(dppf) (4 mg, 5.4 muiotaetaomicron) were added and the mixture was refluxed under N2 for additional 24 h. The solvent was evaporated and the residue was loaded on silica gel and purified by column chromatography (EtOAc MeOH; 30:1) and then re- chromatographed (EtOAc/hexane; 1 :1). So obtained material was purified by preparative TLC (EtOAc/hexane; 1 :1) and then by another preparative TLC (CH2Cl2/MeOH; 15:1). The product was obtained as a colorless wax (7.2 mg, 29 % yield). 1H NMR (300 MHz, CDC13) S 8.99 (s, 1H), 8.28 (s, 1H), 8.06 (dd, J = 8.6, 1.6 Hz, 1H), 7.99 - 7.79 (m, 4H), 7.57 - 7.43 (m, 2H), 7.39 (d, J= 8.6 Hz, 1H), 2.62 (s, 6H). I3C NMR (126 MHz, CDC13) S 150.4, 147.0, 145.8, 145.3, 144.7, 143.4, 133.8, 132.9, 128.4, 128.3, 128.2, 127.8, 126.4, 126.3, 126.0, 124.7, 121.6, 1 18.9, 118.8, 118.1, 12.9, 12.3. HRMS (APCI): calcd. for C22Hi7N30 [M+H]+ = 340.1444; found [M+H]+ = 340.1441.
  • 17
  • [ 1073354-70-7 ]
  • 8-bromo-N-tert-butyl-1-(3,5-dichlorophenyl)-7-methoxy-N-methyl-1,4-dihydrochromeno[4,3-c]pyrazole-3-carboxamide [ No CAS ]
  • tert-butyl 4-(3-(tert-butyl(methyl)carbamoyl)-1-(3,5-dichlorophenyl)-7-methoxy-1,4-dihydrochromeno[4,3-c]pyrazol-8-yl)-3,5-dimethyl-1H-pyrazole-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 1.0h;Inert atmosphere; Microwave irradiation; To a solution of 8-bromo-N-tert-butyl-1- (3, 5-dichlorophenyl) -7-methoxy-N-methyl-1, 4-dihydrochromeno [4, 3-c] pyrazole-3-carboxamide (330 mg, 0.61 mmol) in dioxane/H2O (5/1, 6 mL) was added tert-butyl 3, 5-dimethyl-4- (4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) -1H-pyrazole-1-carboxylate (297 mg, 0.92 mmol) , PdCl2(dppf) (89 mg, 0.12 mmol) and Cs2CO3 (398 mg, 1.22 mmol) at RT under nitrogen. The reaction mixture was stirred at 90 for 1h under MW conditions. The reaction mixture was filtered through celite and washed with DCM (50 mL) . The filtrate was concentrated in vacuum and the crude product was purified by column chromatograph using pet ether: ethyl acetate as eluent to afford the desired compound (230 mg, 56 ) as an off-white solid.
  • 18
  • [ 1073354-70-7 ]
  • [ 1616289-36-1 ]
  • 5,8-dichloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-(3,5-dimethyl-1H-pyrazol-4-yl)-3,4-dihydroisoquinolin-1(2H)-one [ No CAS ]
  • 19
  • [ 1073354-70-7 ]
  • [ 1616289-36-1 ]
  • tert-butyl 4-(2-((2-(benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)-5,8-dichloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-3,5-dimethyl-1H-pyrazole-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
47.5% With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In water; toluene; at 120℃;Inert atmosphere; A solution of 2-((2-(benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)-7-bromo-5, 8- dichloro-3,4-dihydroisoquinolin-1(2H)-one (Cpd L, 500 mg, 0.961 mmol), 1-Boc-3,5- dimethylpyrazole-4-boronic acid pinacol ester (460 mg, 1.43 mmol), tripotassium phosphate (408 mg, 1.92 mmol), palladium(II) acetate (32.4 mg, 0.144 mmol), and 2-dicyclohexylphosphino-2?,6?-dimethoxybiphenyl (S-phos, 118 mg, 0.288 mmol) in toluene (15 mL) and water (1.5 mL) was degassed with nitrogen and stirred at 120 C overnight. After cooling to room temperature, the mixture was diluted with water (20 mL) and extracted with ethyl acetate (2 x 20 mL). The combined organic layers were washed with brine (20 mL), dried over sodium sulfate, concentrated, and purified bysilica gel chromatography (petroleum ether/EtOAc =3/1 Rf-0.3) to give tert-butyl 4-(2- ((2-(benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)-5,8-dichloro-1 -oxo-1 2,3,4-tetrahydroisoquinolin-7-yl)-3,5-dimethyl-1 H-pyrazole-1 -carboxylate (I a, 290 mg, 47.5%) as a yellow gum. MS: 635 [M+H].
  • 20
  • [ 1073354-70-7 ]
  • C12H15BrN2O [ No CAS ]
  • C22H30N4O3 [ No CAS ]
  • 21
  • [ 195817-69-7 ]
  • [ 1073354-70-7 ]
  • 4-(2,6-dimethyl-3,6-dihydro-2H-pyran-4-yl)-3,5-dimethyl-1H-pyrazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
854 mg With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; water; at 100℃; for 18.0h;Inert atmosphere; 2,6-dimethyl-3,6-dihydro-2H-pyran-4-yl) trifluoromethanesulfonate (1075mg, 4.13mmol) and tert- butyl 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyrazole-1 -carboxylate (1464.15mg, 4.54mmol) were dissolved in 1 ,4-dioxane (9ml_) before adding potassium phosphate tribasic (1315mg, 6.2mmol) in Water (2ml_) and degassing by bubbling N2 through the mixture for 10 mins. Tricyclohexylphosphine (58mg, 0.21 mmol) and tris(dibenzylideneacetone)dipalladium (0) (95mg, 0.1 Ommol) were added, degassing continued for a further 2 mins prior to heating thermally 100C (external probe) for 18hrs. The reaction was cooled and then the dioxane was removed in vacuo. The mixture was then partitioned between water and EtOAc. The organic layer was washed with water several times, then dried over sodium sulphate filtered and concentrated. The resulting residue was then loaded onto a methanol primed SCX cartridge. The column was eluted with methanol (3CV) and 1 M ammonia in methanol (3CV). The ammonia flush was concentrated to give 4-(2,6-dimethyl-3,6-dihydro-2H-pyran-4-yl)-3,5-dimethyl-1 H-pyrazole (854mg, 4.14mmol, 100.% yield) as a mixture of stereoisomers. MS Method 2: RT: 1 .66min, ES+ m/z 391 .3 [M+H]+ H NMR (400MHz, CDCb) delta/ppm: 5.46-5.48 (m, 1 H), 4.35-4.43 (m, 1 H), 3.76-3.85 (m, 1 H), 2.25 (s, 6H), 2.05-2.22 (m, 2H), 1 .28-1 .32 (m, 6H).
  • 22
  • [ 1073354-70-7 ]
  • 5,8-dichloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-(3,5-dimethyl-1H-pyrazol-4-yl)-3,4-dihydroisoquinolin-1(2H)-one [ No CAS ]
  • 23
  • [ 1073354-70-7 ]
  • 5,8-dichloro-2-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)-methyl)-7-(1,3,5-trimethyl-1H-pyrazol-4-yl)-3,4-dihydroisoquinolin-1(2H)-one [ No CAS ]
  • 24
  • [ 1073354-70-7 ]
  • 2-(3-amino-3-oxopropyl)-3’-hydroxy-[1,1‘-biphenyl]-4-yl trifluoromethansulfonate [ No CAS ]
  • 3-[4-(3,5-dimethyl-1H-pyrazol-4-yl)-3'-hydroxybiphenyl-2-yl]propanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
7% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 80℃; for 96.0h;Microwave irradiation; Inert atmosphere; Sealed tube; A 20 niL microwave th?* was charged wth h.ydroxybheny4y triPuoromethanesuWonate(0.50 g 120 mmo). tobutyi (4borodc acid :pthacd ester)3<5dimethyf I (050 g. 1.54 mmd) and caesium carbonate (083 g,256 mmci) in a 5oution of water (10 mL) and 1 .4icxane (1 mL).Nitmgen was bubded through the mixture for 5 minbefore iti bis(diphenytphosphino)ferrocene,dichicropallathum(fl), complex with dichioromethane(O) (10 moi%. 0.105 g, 0.128 mmol}was added, the reaction vial sealed and placed in a microwave reactor for D0hat 80 C. On coolingwaler (60 mL) was added, and the mixture washed with ethyl acetate (50 mi.). The org amo phase was separated and washed with 2M hydrochloric add (2.0 ml). Aqueous phases were combined, further acidified topH I and washed with ethyl acetate (3 x 50 mU.. Combined organic phases were dried over anhy?drous magnesium su?phate. filtered, concentrated and the crude residue purified by flash chromatography (methanoltdicthioromethane) 1. give a.n off white sohd. This material was further purified by trituration from dichloromethane? chloroform to give P42 (DM30 g. 7%) as an offwhife sclid2H NMR(400 MHz, DMW?d.k) 59.47(5. 1 H), 8..19(s, ?1 H), 725 J.19(m. 3 H). 7.15 (d, Js 1.2 Hz. 2 H). 6.78 6fl(m.2 H). 6.73 .70 (m, 2 H), 2.76 (1, J t7, Hz H), 2.30 2.25 (m. 2H1. 2.23 (5,6 H); .HPLC(waterj?ACt +0,1% ThA gradient) 96.21 % at 220 nm;LCMS[M+H}t 336.20.
  • 25
  • [ 1073354-70-7 ]
  • 6-bromo-N-(3-chlorobenzyl)-2-(4-(2-(dimethylamino)ethyl)piperazin-1-yl)quinazolin-4-amine [ No CAS ]
  • N-(3-chlorobenzyl)-6-(3,5-dimethyl-1H-pyrazol-4-yl)-2-(4-(2-(dimethylamino)ethyl)piperazin-1-yl)quinazolin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
8.03% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 95℃;Inert atmosphere; In a 2-neck flask was placed 6-bromo-N-(3-chlorobenzyl)-2-(4-(2-(dimethylamino)ethyl)piperazin-1-yl)quinazolin-4-amine (25.2 mg, 0.05 mmol), tert-butyl 3,5- dimethyl-4-(4,4, 5, 5-tetramethyl- 1, 3,2-dioxaborolan-2-yl)- 1 H-pyrazole- 1 -carboxylate (32.2 mg, 0.10 mmol), PdCI2(dppf)-CH2CI2 adduct (4.08 mg, 5.0 pmol), and K2003 (41.5 mg, 0.30 mmol). The air was removed and re-filled with N2 (2-3 times). Then added a mixture of 1 ,4-dioxane (1ml) and water (0.5 ml) was added and stirred at 95 00 (pre-heated) for overnight. The organic layer was separated and the aqueous layer was extracted with EtOAc (5 mL x 2). The compined organic was dried (Na2SO4) and filtered. After removal of solvent, the product was filtered through a PL-Thio-resin, eluted with EtOAc, dried. Then added TFA (0.5 mL) and stirred for 10 mm to help complete deprotection. Then the mixture was concentrated to remove most of TFA,dissolved in DMF, and substmitted for purification using basic condition to give N-(3-chlorobenzyl)-6-(3,5-dimethyl- 1 H-pyrazol-4-yl)-2-(4-(2-(dimethylam ino)ethyl) piperazin- 1-yl)quinazolin-4-amine, 2TFA (3 mg, 4.02 pmol, 8.03 % yield) . H NMR (400 MHz, DMSO-d6) O11.83 (5, 1H), 10.01 (5, 1H), 8.13 (5, 1H), 7.75 (d, J= 8.7 Hz, 1H), 7.68 (d, J= 8.5 Hz, 1H), 7.46(d, J= 2.0 Hz, 1H), 7.40-7.27 (m, 3H), 4.79 (d, J= 5.7 Hz, 2H), 3.81 (brs, 4H), 3.22 (t, J= 6.1Hz, 2H), 2.79 (5, 6H), 2.69 - 2.60 (m, 2H), 2.55 (br s, 4H), 2.20 (5, 6H); MS (M+H)= 519.
  • 26
  • [ 943750-38-7 ]
  • [ 1073354-70-7 ]
  • tert-butyl 4-(4-(1-(tert-butoxycarbonyl) pyrrolidin-2-yl)phenyl)-3,5-dimethyl-1H-pyrazole-1-carboxylate [ No CAS ]
  • 27
  • [ 1073354-70-7 ]
  • 6-chloro-4-(3,5-dimethyl-1H-pyrazol-4-yl)-1-(4-fluoro-3,5-dimethylbenzyl)-2-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-benzo-[d]imidazole [ No CAS ]
  • 28
  • [ 1073354-70-7 ]
  • 6-chloro-4-(3,5-dimethyl-1H-pyrazol-4-yl)-1-(4-fluoro-3,5-dimethylbenzyl)-2-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-benzo-[d]imidazole trifluoroacetate [ No CAS ]
  • 29
  • [ 1073354-70-7 ]
  • 4-bromo-6-chloro-1-(4-fluoro-3,5-dimethylbenzyl)-2-(piperazin-1-yl)-1H-benzo[d]imidazole [ No CAS ]
  • C25H28ClFN6*C2HF3O2 [ No CAS ]
  • 30
  • [ 1073354-70-7 ]
  • 4-bromo-6-chloro-1-(4-fluoro-3,5-dimethylbenzyl)-2-(piperazin-1-yl)-1H-benzo[d]imidazole [ No CAS ]
  • C30H36ClFN6O2 [ No CAS ]
  • 31
  • [ 1073354-70-7 ]
  • tert-butyl-6-(4-bromo-6-chloro-1-(4-fluoro-3,5-dimethylbenzyl)-1H-benzo[d]imidazol-2-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate [ No CAS ]
  • C36H44ClFN6O4 [ No CAS ]
  • 32
  • [ 1073354-70-7 ]
  • C24H20BrNO3 [ No CAS ]
  • C34H35N3O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
90 mg With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 95℃; Compound 31d (100 mg, 0.22 mmol) under nitrogenCompound 46a (107 mg, 0.33 mmol),K2CO3 (60mg, 0.44mmol)And PdCl2(dppf).CH2Cl2 (9mg, 0.011mmol) was placed in the reaction flask,Dioxane (5 mL) and water (0.5 mL) were added and heated to 95 C overnight.After completion of the reaction, the mixture was cooled to room temperature and purified by silica gel column chromatography to yield Compound 46b (90mg).
  • 33
  • 5-[3-(benzyloxy)-7-bromo-1-fluoronaphthalen-2-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione [ No CAS ]
  • [ 1073354-70-7 ]
  • 5-[3-(benzyloxy)-7-(3,5-dimethyl-1H-pyrazol-4-yl)-1-fluoronaphthalen-2-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In N,N-dimethyl acetamide; water; at 85℃; for 14.0h;Inert atmosphere; Sealed tube; To a microwave vial were added the product of Example 1G (0.200 g, 0.430 mmol), [l,T-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (0.053 g, 0.064 mmol), teri-butyl 3,5-dimethyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)- 1 //-pyrazolc- 1 -carboxylatc (0.277 g, 0.860 mmol), and potassium carbonate (0.178 g, 1.29 mmol). The vial was sealed, evacuated, and refilled with nitrogen. The evacuation/refill cycle was repeated three additional times. Next, a mixture of dimethylacetamide (1.9 mL) and water (0.24 mL)- which had been degassed using the same evacuation/refill process described above- was added. The vial was then heated to 85 C for 14 hours. The mixture was cooled to ambient temperature and partitioned between ethyl acetate (15 mL) and 0.1 M hydrochloric acid (25 mL). The layers were separated and the aqueous phase was extracted with ethyl acetate (2 x 10 mL). The organic phases were combined, washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was loaded onto diatomaceous earth and purified using silica gel chromatography (24 g column, 0 to 30% methanol in dichloromethane) to give the title compound (0.077 g, 0.16 mmol, 37% yield). 1 H NMR (400 MHz, D SO-uV,) d ppm 7.92 (d, 7 = 8.5 Hz, 1H), 7.80 (d, 7 = 1.6 Hz, 1H), 7.61 - 7.51 (m, 3H), 7.47 (s, 1H), 7.39 (t,
  • 34
  • [ 1073354-70-7 ]
  • [ 103697-17-2 ]
  • C20H29N2O5P [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; at 100℃; for 6.0h;Inert atmosphere; According to the Suzuki-Miyaura cross-coupling reaction[41], 1.0 g (0.003 mol) of diethyl 4-iodophenylphosphonate,1.1 g (0.004mol) of 3,5-dimethylpyrazole-4-boronicacid pinacol ester, and 3.9 g (0.012 mol) of Cs2CO3 wereplaced in a two necked 250mL flask under nitrogen andsuspended in 100 mL of 1,4-dioxane. Finally, 0.122mg(0.15mmol) of Pd(dppt)Cl2 was added under constant stirring.The suspension was heated to 100C for 6h. Afterthe reaction was completed as monitored by TLC, thecooled dark beige suspension was filtered and subjectedto column chromatography (silica gel, 97: 3% ethyl acetate-methanol) to yield 0.76 g (76%) of pure oily product.- 1H NMR (600MHz, CDCl3): delta(ppm)=1.35 (t, 6H), 1.66(m, 9H), 2.26 (s, 3H), 2.46 (s, 3H), 4.19 (q, 4H), 7.32 (d,2H), 7.84 (d, 2H) (Fig. S4). - 13C NMR (600MHz, CDCl3): delta(ppm)=16.75 (CH3), 28.42 (CH3), 62.59 (CH3), 85.74 (CH2)136.83 (s, C-N), 140.70 (C-O), 148.89-150.69 (aromaticC atoms) (Fig. S5). - 31P{H} NMR (600 MHz, CDCl3): delta(ppm)=18.61 (Fig. S6).
  • 35
  • [ 1073354-70-7 ]
  • 3-chloro-6-({1-[4-(difluoromethyl)phenyl]-4-methyl-1H-1,2,3-triazol-5-yl}methoxy)pyridazine [ No CAS ]
  • 3-({1-[4-(difluoromethyl)phenyl]-4-methyl-1H-1,2,3-triazol-5-yl}methoxy)-6-(3,5-dimethyl-1H-pyrazol-4-yl)pyridazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
29.8 mg With methanol; [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3chloro-pyridyl)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 120℃; for 0.5h;Inert atmosphere; To <strong>[1073354-70-7]tert-butyl 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate</strong> (48 mg, 0.150 mmol) is added a solution of Example III.1 (35 mg, 0.10 mmol) in 0.5 mL methanol, 1 mL 1,4 dioxane, 2 M aq sodium carbonate solution (0.10 mL, 0.20 mmol) and Pd-PEPPSI (0.84 mg 0.001 mmol) under argon and the reaction mixture is stirred for 30 min at 120 C. The reaction mixture is evaporated. The residue is diluted with 2 mL TFA and is stirred for 1 h at RT. The mixture is purified by preparative HPLC to give 29.8 mg of the product. ESI-MS: 412 [M+H]+
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tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate

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Chemical Structure| 1402174-61-1

[ 1402174-61-1 ]

tert-Butyl 5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate

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Related Parent Nucleus of
[ 1073354-70-7 ]

Pyrazoles

Chemical Structure| 1009071-34-4

[ 1009071-34-4 ]

tert-Butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate

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Chemical Structure| 2377607-37-7

[ 2377607-37-7 ]

tert-Butyl 3-cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate

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Chemical Structure| 947533-31-5

[ 947533-31-5 ]

(1-(tert-Butoxycarbonyl)-3,5-dimethyl-1H-pyrazol-4-yl)boronic acid

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Chemical Structure| 552846-17-0

[ 552846-17-0 ]

tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate

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Chemical Structure| 1402174-61-1

[ 1402174-61-1 ]

tert-Butyl 5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate

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