847818-74-0

Basic information

• Product Name: 1-Methyl-1H-pyrazole-5-boronic acid pinacol ester
• Synonyms: 1-METHYL-5-(4,4,5,5-TETRAMETHYL-[1,3,2]DIOXABOROLAN-2-YL)-1H-PYRAZOLE;1-METHYL-1H-PYRAZOLE-5-BORONIC ACID PINACOL ESTER;CBI-BB ZERO/005567;1-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole;1H-Pyrazole,1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-;1-Methyl-1H-pyrazole-5-boronic acid pinacol ester ,97%;1H-pyrazole, 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxabo;1-Methyl-pyrazole-5-boronic acid pinacol ester
• CAS NO: 847818-74-0
• Molecular Formula: C₁₀H₁₇BN₂O₂
• Molecular Weight: 208.07
• Product Categories: Boronic ester;Organoborons;Pyrazole
• Mol File: 847818-74-0.mol
• Article Data: 16

Chemical Properties

• Melting Point: 58-61°C
• Boiling Point: 355 °C at 760 mmHg
• Flash Point: 168.5 °C
• Appearance: /
• Density: 1.06 g/cm³
• Vapor Pressure: 0.00125mmHg at 25°C
• Refractive Index: 1.505
• Storage Temp.: Inert atmosphere,Store in freezer, under -20°C
• PKA: 1.94±0.10(Predicted)
• Water Solubility: Slightly soluble in water.
• CAS DataBase Reference: 1-Methyl-1H-pyrazole-5-boronic acid pinacol ester(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Methyl-1H-pyrazole-5-boronic acid pinacol ester(847818-74-0)
• EPA Substance Registry System: 1-Methyl-1H-pyrazole-5-boronic acid pinacol ester(847818-74-0)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 26
• WGK Germany: 3
• TSCA: No
• HazardClass: IRRITANT
• Hazardous Substances Data: 847818-74-0(Hazardous Substances Data)

Usage

Chemical Properties

White to light brown solid

Uses

1-Methyl-1H-pyrazole-5-boronic acid pinacol ester is used as a pharmaceutical intermediate, agrochemical intermediate.

InChI:InChI=1/C10H17BN2O2/c1-9(2)10(3,4)15-11(14-9)8-6-7-12-13(8)5/h6-7H,1-5H3

Synthetic route

1-methyl-1H-pyrazole (930-36-9) + 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane (25015-63-8) → 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0)

Conditions	Yield
Stage #1: 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane With C26H50CoN4O2 at 20℃; for 0.0833333h; Inert atmosphere; Glovebox; Stage #2: 1-methyl-1H-pyrazole at 80℃; for 48h; Inert atmosphere; Sealed tube;	90%

2,3-dimethyl-2,3-butane diol (76-09-5) + (1-methyl-1H-pyrazol-5-yl)boronic acid (720702-41-0) → 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0)

Conditions	Yield
With 4 A molecular sieve In tetrahydrofuran at 20℃; for 2h;	84%
In tetrahydrofuran at 20℃; for 48h; Molecular sieve;	67%

1-methyl-1H-pyrazole (930-36-9) + 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (61676-62-8) → 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0)

Conditions	Yield
Stage #1: 1-methyl-1H-pyrazole With n-butyllithium In tetrahydrofuran at 0 - 20℃; for 1h; Stage #2: 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane In tetrahydrofuran at -78 - 0℃; for 1.25h; Stage #3: With ammonium chloride In tetrahydrofuran	77%
Stage #1: 1-methyl-1H-pyrazole With n-butyllithium In tetrahydrofuran at 0 - 20℃; Stage #2: 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane In tetrahydrofuran at -78℃;	77%
Stage #1: 1-methyl-1H-pyrazole With n-butyllithium In tetrahydrofuran at 0 - 20℃; for 1h; Stage #2: 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane In tetrahydrofuran at -78 - 0℃; for 1.25h;	77%

Triisopropyl borate (5419-55-6) → 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0)

Conditions	Yield
Stage #1: 1-methyl-1H-pyrazole With n-butyllithium In tetrahydrofuran; hexanes at -78 - 20℃; for 1h; Stage #2: Triisopropyl borate In tetrahydrofuran; hexanes for 1h; Stage #3: With hydrogenchloride; water In tetrahydrofuran; hexanes	51%

3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (844501-71-9, 1086111-17-2) + methyl iodide (74-88-4) → 1-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (1020174-04-2) + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0)

Conditions	Yield
With caesium carbonate In acetonitrile at 20℃; for 70h;

1-methyl-1H-pyrazole (930-36-9) + 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane (25015-63-8) → 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) + 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (761446-44-0)

Conditions

Yield

Stage #1: 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer In hexane at 20℃; Glovebox; Inert atmosphere; Stage #2: With 4,4'-di-tert-butyl-2,2'-bipyridine In hexane at 20℃; Glovebox; Inert atmosphere; Stage #3: 1-methyl-1H-pyrazole In hexane at 20℃; for 5h; Reagent/catalyst; Solvent; Glovebox; Inert atmosphere; Overall yield = 67 percent; regioselective reaction;

methyl 4-bromo-5-ethyl-2-thiophenecarboxylate (1047645-89-5) + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → methyl 5-ethyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate (1047645-90-8)

Conditions	Yield
With potassium carbonate; bis(tri-t-butylphosphine)palladium(0) at 80℃; for 1h;	100%

1,1-dimethylethyl (2-{[(5-bromo-3-thienyl)carbonyl]amino}-2-phenylethyl)carbamate (1044851-72-0) + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → 1,1-dimethylethyl [2-({[5-(1-methyl-1H-pyrazol-5-yl)-3-thienyl]carbonyl}amino)-2-phenylethyl]carbamate (1044851-74-2)

Conditions	Yield
With potassium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane; water at 80℃; for 17h; Suzuki Coupling;	100%

2-bromothiophene-4-carboxylic acid (100523-84-0) + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → 5-(2-methyl-2H-pyrazol-3-yl)-thiophene-3-carboxylic acid (1044851-90-2)

Conditions	Yield
With potassium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane; water at 80℃; for 12 - 17h; Suzuki Coupling;	100%

N-(2-bromo-4-(trifluoromethyl)phenyl)acetamide (175135-49-6) + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → N-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)acetamide

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water for 1h; Suzuki Coupling; Reflux;	100%
With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water for 1h; Reflux;	100%

2-[(3R)-3-methylmorpholin-4-yl]-8-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]-1,7-naphthyridin-4-yl trifluoromethanesulfonate + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → (3R)-3-methyl-4-(4-(1-methyl-1H-pyrazol-5-yl)-8-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-1,7-naphthyridin-2-yl)morpholine

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In water at 110℃; for 3h; Inert atmosphere;	100%
With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,2-dimethoxyethane; water at 130℃; for 0.333333h; Suzuki Coupling; Microwave irradiation;

methyl 4-bromo-5-propyl-2-thiophenecarboxylate (1047628-66-9) + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → methyl 4-(1-methyl-1H-pyrazol-5-yl)-5-propyl-2-thiophenecarboxylate (1047628-67-0)

Conditions	Yield
With potassium carbonate; bis(tri-t-butylphosphine)palladium(0) at 80℃; for 1h;	99%

1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → 4-chloro-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)-1H-pyrazole (1430057-83-2)

Conditions	Yield
With N-chloro-succinimide; 2,4,6-trimethylaniline In dichloromethane at 20℃; for 24h; Inert atmosphere;	99%
With 2-chloro-1,3-bis(methoxycarbonyl)guanidine In acetonitrile at 20℃; for 12h; Reagent/catalyst; regioselective reaction;	98%
With N-chloro-succinimide; 2,2,6,6-tetramethylpiperidin-1-oxoammonium trifluoromethanesulfonate In chloroform at 25℃; for 12h; Reagent/catalyst; Schlenk technique;	96%

tert-butyl (2-(4-chloro-1H-pyrrolo[2,3-b]pyridin-2-yl)ethyl)carbamate + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → tert-butyl (2-(4-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)ethyl)carbamate

Conditions	Yield
With methanesulfonic acid(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) In tetrahydrofuran; ethanol; water at 50℃; for 12h; Inert atmosphere;	99%

tert-butyl 1-(4-(2-chloro-7-phenylfuro[2,3-b]pyrazin-6-yl)phenyl)cyclobutylcarbamate (1301612-83-8) + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → tert-butyl 1-(4-(2-(1-methyl-1H-pyrazol-5-yl)-7-phenylfuro[2,3-b]pyrazin-6-yl)phenyl)cyclobutylcarbamate (1301612-87-2)

Conditions	Yield
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0) In water; N,N-dimethyl-formamide at 120℃; for 0.333333h; Microwave irradiation; Inert atmosphere; Sealed tube;	98%

2,4-dichloro-5-fluoropyrimidine (2927-71-1) + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → 2-chloro-5-fluoro-4-(1-methyl-1H-pyrazol-5-yl)pyrimidine

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In tetrahydrofuran; water Reflux;	98%

PU-DZ13 + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → 2-fluoro-9-(2-(isobutylamino)ethyl)-8-((6-(1-methyl-1H-pyrazol-5-yl)benzo[d][1,3]dioxol-5-yl)methyl)-9H-purin-6-amine (1289544-05-3)

Conditions	Yield
With sodium hydrogencarbonate; bis-triphenylphosphine-palladium(II) chloride In water; N,N-dimethyl-formamide at 90℃; for 2h; Suzuki Coupling; Inert atmosphere;	97%

4-Bromo-3-methylbenzoic acid methyl ester (148547-19-7) + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → methyl 3-methyl-4-(1-methyl-1H-pyrazol-5-yl)benzoate

Conditions	Yield
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl-formamide at 100℃; for 10h; Inert atmosphere;	97%

1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → 4-bromo-1-phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (942070-88-4)

Conditions	Yield
With N-Bromosuccinimide; 2,4,6-trimethylaniline In dichloromethane at -40 - 0℃; for 24h; Inert atmosphere; regioselective reaction;	96%

2,6-Dichloropyrimidine (3934-20-1) + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → 2-chloro-4-(1-methyl-1H-pyrazol-5-yl)pyrimidine

Conditions	Yield
With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; potassium carbonate In 1,4-dioxane; water at 120℃; for 2h;	96%

5-bromo-1-(4-fluorophenyl)-3-(1-methylpiperidin-4-yl)-1H-indole (1415089-66-5) + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → C24H25FN4 (1415089-44-9)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In water; toluene at 100℃; Suzuki-Miyaura Coupling; Inert atmosphere;	95%

4-methoxycarbonylphenyl bromide (619-42-1) + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → methyl 4-(1-methyl-1H-pyrazol-5-yl)benzoate (179057-12-6)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium phosphate tribasic trihydrate In N,N-dimethyl-formamide at 0 - 120℃; Suzuki Coupling; Inert atmosphere;	95%
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl-formamide at 100℃; for 10h; Inert atmosphere;	89%
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl-formamide at 0 - 100℃; for 10h; Inert atmosphere;	89%
With tetrakis(triphenylphosphine) palladium(0); potassium phosphate tribasic trihydrate In N,N-dimethyl-formamide at 90℃; Suzuki Coupling; Inert atmosphere;	85%

4-fluoro-3-iodo-naphthalene-1-carbonitrile + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → 4-fluoro-3-(2-methylpyrazol-3-yl)naphthalene-1-carbonitrile

Conditions	Yield
With potassium phosphate; dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) In 1,4-dioxane; water at 80℃; for 18h; Inert atmosphere;	95%

4-bromo-2-fluoro-1-(methylsulfonyl)benzene (648904-84-1) + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → 5-(3-fluoro-4-methanesulfonylphenyl)-1-methyl-1H-pyrazole

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane; water at 100℃; Inert atmosphere;	94%

5-bromo-3-methylpyridine-2-carboxylic acid methyl ester (213771-32-5) + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → methyl 3-methyl-5-(1-methyl-1H-pyrazol-5-yl)picolinate

Conditions	Yield
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl-formamide at 100℃; for 10h; Inert atmosphere;	94%

methyl 2-bromo-[1,2,4]triazolo[1,5-a]pyridine-6-carboxylate + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → methyl 2-(1-methyl-1H-pyrazol-5-yl)[1,2,4]triazolo[1,5-a]pyridine-6-carboxylate

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In 1,4-dioxane; water at 60℃; for 2h;	94%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In 1,4-dioxane; dichloromethane; water at 60℃; for 2h; Suzuki Coupling;	94%

N-[1-(4-chloro-phthalazin-1-yl)-piperidin-4-yl]-4-fluoro-N-methyl-2-trifluoromethyl-benzamide + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → 4-fluoro-N-methyl-N-{1-[4-(1-methyl-1H-pyrazole-5-yl)phthalazin-1-yl]piperidin-4-yl}-2-(trifluoromethyl)benzamide (1258861-20-9)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; water; toluene at 74℃; for 12h; Suzuki Coupling; Inert atmosphere;	92%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; water; toluene at 74℃; for 12h; Suzuki Coupling; Inert atmosphere;	92%

C6H4BrFO3S + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → C10H9FN2O3S

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium phosphate tribasic trihydrate In N,N-dimethyl-formamide at 90℃; Inert atmosphere;	92%

(6-cyano-7-quinolyl)trifluoromethanesulfonate + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → 7-(2-methylpyrazol-3-yl)quinoline-6-carbonitrile

Conditions	Yield
With dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); sodium hydrogencarbonate In 1,4-dioxane; water at 80℃; for 1h; Inert atmosphere;	92%

5-bromo-N-cyclopentyl-N-(2,4-dimethoxybenzyl)-2-methoxybenzenesulfonamide + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → N-cyclopentyl-N-(2,4-dimethoxybenzyl)-2-methoxy-5-(1-methyl-1H-pyrazol-5-yl)benzenesulfonamide

Conditions	Yield
With dichloro-[1,3-bis(2,6-diisopropylpenyl)-2-imidazolidinyliden]-(3-chloropyridyl)palladium(II); caesium carbonate In 1,4-dioxane; water; N,N-dimethyl-formamide at 90℃; for 12h; Suzuki-Miyaura Coupling; Inert atmosphere; Microwave irradiation;	91%

2-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-[3,3‘-bipyridine]-5-carboxamide + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → N-(4-(chlorodifluoromethoxy)phenyl)-2-(1-methyl-1H-pyrazol-5-yl)-[3,3‘-bipyridine]-5-carboxamide

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; water at 100℃; Concentration; Inert atmosphere;	91%

tert-butyl 4-((7-(3-bromophenyl)-6-chloro-4-oxo-4, 7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3-yl)methyl)-4-hydroxypiperidine-1-carboxylate + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → tert-butyl 4-((6-chloro-7-(3-(1-methyl-1H-pyrazol-5-yl)phenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3-yl)methyl)-4-hydroxypiperidine-1-carboxylate

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 140℃; for 0.5h; Suzuki Coupling; Inert atmosphere; Microwave irradiation; Sealed tube;	91%

N-(1-(6-chloro-4,5-dimethyl-3-pyridazinyl)-4-piperidinyl)-4-fluoro-N-methyl-2-(trifluoromethyl)benzamide + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → N-(1-(4,5-dimethyl-6-(1-methyl-1H-pyrazol-5-yl)pyridazin-3-yl)piperidin-4-yl)-4-fluoro-N-methyl-2-(trifluoromethyl)benzamide

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In methanol; water; toluene at 74℃; for 12h; Inert atmosphere;	89%

tert-butyl (R)-4-((S)-10-((4-chloro-2-oxopyridin-1(2H)-yl)methyl)-10-hydroxy-7-azaspiro[4.5]decane-7-carbonyl)-3-phenylpiperazine-1-carboxylate + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → tert-butyl (R)-4-((S)-10-hydroxy-10-((4-(1-methyl-1H-pyrazol-5-yl)-2-oxopyridin-1(2H)-yl)methyl)-7-azaspiro[4.5]decane-7-carbonyl)-3-phenylpiperazine-1-carboxylate

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water at 120℃; for 0.5h; Suzuki Coupling; Inert atmosphere; Sealed tube; Microwave irradiation;	89%

6-bromo-3-cyclopropoxypicolinonitrile + 1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (847818-74-0) → 3-cyclopropoxy-6-(1-methyl-1H-pyrazol-5-yl)picolinonitrile

Conditions	Yield
With dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); sodium carbonate In 1,4-dioxane; water at 25 - 80℃; for 2h;	89%

Upstream product

• 930-36-9 1-methyl-1H-pyrazole 
• 61676-62-8 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 
• 25015-63-8 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane 
• 844501-71-9 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole 
• 74-88-4 methyl iodide 
• 5419-55-6 Triisopropyl borate 
• 76-09-5 2,3-dimethyl-2,3-butane diol 
• 720702-41-0 (1-methyl-1H-pyrazol-5-yl)boronic acid 

Downstream Products

• 1047645-40-8 1,1-dimethylethyl [2-(hydroxy{[4-(1-methyl-1H-pyrazol-5-yl)-2-thienyl]carbonyl}amino)-3-phenylpropyl]carbamate 
• 1047630-52-3 methyl 5-chloro-4-(1-methylpyrazol-5-yl)-2-thiophenecarboxylate 
• 1044851-74-2 1,1-dimethylethyl [2-({[5-(1-methyl-1H-pyrazol-5-yl)-3-thienyl]carbonyl}amino)-2-phenylethyl]carbamate 
• 1044852-16-5 N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-(1-methyl-1H-pyrazol-5-yl)-3-furancarboxamide 
• 1044851-90-2 5-(2-methyl-2H-pyrazol-3-yl)-thiophene-3-carboxylic acid 
• 1332447-95-6 C₂₃H₂₄N₄ 
• 1332448-62-0 2,8-dimethyl-5-(3-(1-methyl-1H-pyrazol-5-yl)phenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 
• 1386394-15-5 5-(1-(cyclohex-1-en-1-yl)ethyl)-1-methyl-1H-pyrazole 
• 1400287-42-4 2-chloro-4-(1-methyl-1H-pyrazol-5-yl)aniline 
• 179057-12-6 methyl 4-(1-methyl-1H-pyrazol-5-yl)benzoate 
• 1427033-90-6 5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(1-methyl-1H-pyrazol-5-yl)benzofuran-3-carboxamide 

Relevant articles and documents

Organolithium Process Under Continuous Flow Conditions

The invention relates to methods for CC bond formation using organolithium compounds under continuous flow conditions in a micro or mesoreactor system, wherein an organic substrate is reacted with an alkyl lithium compound in the presence of a donor solvent to form a Li intermediate, which can be reacted in situ or subsequently in a second reaction step with an electrophile to form an organic secondary product, the organolithium compound RLi being used as a solution in a hydrocarbon or hydrocarbon mixture and the RLi concentration being at least 3 M, preferably at least 4 M.

C-H Borylation Catalysts that Distinguish between Similarly Sized Substituents like Fluorine and Hydrogen

By modifying ligand steric and electronic profiles it is possible to C-H borylate ortho or meta to substituents in aromatic and heteroaromatic compounds, where steric differences between accessible C-H sites are small. Dramatic effects on selectivities between reactions using B2pin2 or 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (HBpin) are described for the first time. Judicious ligand and borane combinations give highly regioselective C-H borylations on substrates where typical borylation protocols afford poor selectivities.

AFURESERTIB: Protein kinase B (PKB) inhibitor Oncolytic

The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays key roles in cellular proliferation and survival. Mutations and alterations in this signal transduction pathway have been described in a variety of solid and hematopoietic malignancies, which may contribute to perpetuation of the disease in a number of ways. Increasing interest in targeting particular facets of this signaling cascade has led to the development of a number of novel anticancer agents, including afuresertib (GSK-2110183), an orally bioavailable pan-inhibitor of the RAC-alpha serine/threonine protein kinase, also referred to as protein kinase B or proto-oncogene c-Akt. The present review summarizes the preclinical and pharmacological aspects of afuresertib and early clinical experience.