Home Cart 0 Sign in  
X

[ CAS No. 1276056-83-7 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 1276056-83-7
Chemical Structure| 1276056-83-7
Chemical Structure| 1276056-83-7
Structure of 1276056-83-7 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 1276056-83-7 ]

Related Doc. of [ 1276056-83-7 ]

Alternatived Products of [ 1276056-83-7 ]

Product Details of [ 1276056-83-7 ]

CAS No. :1276056-83-7 MDL No. :MFCD18793417
Formula : C5H7BrN2O Boiling Point : -
Linear Structure Formula :- InChI Key :YLTQBUUGYXTAHV-UHFFFAOYSA-N
M.W :191.03 Pubchem ID :57415773
Synonyms :

Calculated chemistry of [ 1276056-83-7 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.4
Num. rotatable bonds : 1
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 37.32
TPSA : 38.05 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) : -7.42 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.56
Log Po/w (XLOGP3) : 0.07
Log Po/w (WLOGP) : 0.52
Log Po/w (MLOGP) : 0.29
Log Po/w (SILICOS-IT) : 0.87
Consensus Log Po/w : 0.46

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.41
Solubility : 7.37 mg/ml ; 0.0386 mol/l
Class : Very soluble
Log S (Ali) : -0.42
Solubility : 72.1 mg/ml ; 0.378 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.48
Solubility : 6.3 mg/ml ; 0.033 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.6

Safety of [ 1276056-83-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 1276056-83-7 ]

* 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 [ 1276056-83-7 ]

[ 1276056-83-7 ] Synthesis Path-Downstream   1~50

  • 1
  • [ 84547-84-2 ]
  • [ 1276056-83-7 ]
YieldReaction ConditionsOperation in experiment
92% With borane-THF; In tetrahydrofuran; at 80℃; for 12.0h;Inert atmosphere; A mixture of 4-bromo- 1 -methyl - 1 //-pyrazole-5-carboxylic acid (4.80 g, 23.4 mmol, CAS 84547-84-2) in THF (40.00 mL) was added BH3/THF (93.60 mL, 1 M). The mixture was stirred at 80 C for 12 hours under N2 atmosphere. To the mixture was added EtOAc (200 mL). The mixture was washed with saturated NaHCO, (200 mL x 3). The organic layer was dried over anhydrous Na2S04, filtered and concentrated to give a residue. The residue was purified by column chromatography (petroleum ether : ethyl acetate = 100 : 0 to 100 : 10) to give (4-bromo-l -methyl- li-pyrazol-5-yl)methanol (4.10 g, 92% yield) as a white solid. 1HNMR (400 MHz, DMSO-6): d 7.26 (s, 1H), 4.62 (s, 2H), 3.86 (s, 3H).
77% With borane-THF; In tetrahydrofuran; at 50℃; for 48.0h; A mixture of 4-bromo- 1 -methyl- 1 H-pyrazole-5-carboxylic acid (5.0 g, 24.4 mmol) and BH3.THF (36.6 mL of a 1 M solution in THF, 36.6 mmol) in THF (50 mL) was stirred at 50 C for 2 days; at this point LCMS showed the completion of the reaction. The reaction was cooled to RT and cautiously quenched with aq. 1N HC1 and stirred at RT for 1 h, after which the mixture was extracted with EtOAc (3 X 50 mL). The combined organic extracts were concentrated in vacuo. The residue was chromato graphed (80 g Si02; continuous gradient from 0% to 100% EtOAc in hexanes, 25 min) to give the title compound (3.60 g, 18.9 mmol, 77 % yield) as a white solid. LCMS, [M+H]+ = 193.0.
77% With borane-THF; In tetrahydrofuran; at 50℃; for 48.0h;Inert atmosphere; A mixture of 4-bromo- 1 -methyl- 1 H-pyrazole-5-carboxylic acid (5.0 g, 24.4 mmol) and BH3.THF (36.6 mL of a 1 M solution in THF, 36.6 mmol) in THF (50 mL) was stirred at 50 C for 2 days; at this point LCMS showed the completion of the reaction. The reaction was cooled to RT and cautiously quenched with aq. IN HC1 and stirred at RT for 1 h, after which the mixture was extracted with EtOAc (3 X 50 mL). The combined organic extracts were concentrated in vacuo. The residue was chromatographed (80 g Si02; continuous gradient from 0% to 100% EtOAc in hexanes, 25 min) to give the title compound (3.60 g, 18.9 mmol, 77 % yield) as a white solid. LCMS, [M+H]+ = 193.0.
77% With borane-THF; In tetrahydrofuran; at 50℃; for 48.0h; A mixture of 4-bromo-l-methyl-lH-pyrazole-5-carboxylic acid (5.0 g, 24.4 mmol) and BH3.THF (36.6 mL of a 1 M solution in THF, 36.6 mmol) in THF (50 mL) was stirred at 50 C for 2 days; at this point LCMS showed the completion of the reaction. The reaction was cooled to RT and cautiously quenched with aq. 1N F1C1 and stirred at RT for 1 h, after which the mixture was extracted with EtOAc (3 X 50 mL). The combined organic extracts were concentrated in vacuo. The residue was (0667) chromatographed (80 g S1O2; continuous gradient from 0% to 100% EtOAc in hexanes, 25 min) to give the title compound (3.60 g, 18.9 mmol, 77 % yield) as a white solid. LCMS, [M+H]+ = 193.0.
Example 44 (4-{3-[(1S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-1-methyl-1H-pyrazol-5-yl)methanol To a solution of <strong>[84547-84-2]4-bromo-2-methyl-2H-pyrazole-3-carboxylic acid</strong> (20.0 mg, 0.0976 mmol) in THF (3 mL, 40 mmol) was added 1.0 M of BH3.THF in THF (0.49 mL, 0.49 mmol), and the resulting solution was heated to 60 C. overnight. The material was extracted with EtOAc, and washed with sat. NaHCO3 (3*) to remove carboxylic acid starting material. The organic layer was concentrated in vacuo. 3-[(S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (15.0 mg, 0.0348 mmol), (1,1'bis-(diphenylphosphino)-ferrocene) palladium dichloride (3.57 mg, 0.00488 mmol), K2CO3 (20.2 mg, 0.146 mmol) and 4:1 dioxane:H2O (1 mL, 10 mmol) were added, and the mixture was heated to 95 C. for 30 min. The solution was used directly for HPLC purification, and the fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): delta=1.80 (d, J=7.1 Hz, 3H), 3.67 (br. s., 3H), 3.96 (s, 3H), 4.55 (s, 2H), 5.08-5.17 (m, 1H), 6.90 (dd, J=9.1, 4.3 Hz, 1H), 7.08 (t, J=8.8 Hz, 1H), 7.34 (d, J=1.3 Hz, 1H), 7.46 (s, 1H), 7.53 (s, 1H), 8.15-8.22 (m, 1H). MS (ES+): m/z=415.13/417.13 (100/50) [MH+]. HPLC: tR=1.37 min (polar-3 min, UPLC-ACQUITY).
With borane-THF; In tetrahydrofuran; at 20 - 50℃; for 73.0h; To a RT solution of 4-bromo-l -methyl- lH-pyrazole-5-carboxylic acid (2.0 g, 9.8 mmol) in THF (24.4 ml) was added BH3.THF complex (19.5 mL of a 1M solution in TFIF, 19.5 mmol) and the reaction was stirred at RT for 1 h, then was heated to 50 C and stirred at 50 C for 3 days, then was cooled to RT. The reaction was quenched slowly by dropwise addition of 1M aq. HC1 (10 mL) at RT, then was partitioned between CH2Cl2 (30 mL) and water (30 mL). The aqueous phase was extracted with CFLCh (2 X 30 mL) and the combined organic extracts were dried (MgS04) and filtered through a pad of Si02 to give the crude title compound (1.86 g, 100 % yield) as a white solid. LCMS, [M + H]+ = 191.0, 193.0.

  • 2
  • [ 1350322-64-3 ]
  • [ 1276056-83-7 ]
  • [ 1350323-54-4 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In 1,4-dioxane; water at 95℃; for 0.5h; 44 Example 44 (4-{3-[(1S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-1-methyl-1H-pyrazol-5-yl)methanol To a solution of 4-bromo-2-methyl-2H-pyrazole-3-carboxylic acid (20.0 mg, 0.0976 mmol) in THF (3 mL, 40 mmol) was added 1.0 M of BH3.THF in THF (0.49 mL, 0.49 mmol), and the resulting solution was heated to 60° C. overnight. The material was extracted with EtOAc, and washed with sat. NaHCO3 (3*) to remove carboxylic acid starting material. The organic layer was concentrated in vacuo. 3-[(S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (15.0 mg, 0.0348 mmol), (1,1'bis-(diphenylphosphino)-ferrocene) palladium dichloride (3.57 mg, 0.00488 mmol), K2CO3 (20.2 mg, 0.146 mmol) and 4:1 dioxane:H2O (1 mL, 10 mmol) were added, and the mixture was heated to 95° C. for 30 min. The solution was used directly for HPLC purification, and the fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.80 (d, J=7.1 Hz, 3H), 3.67 (br. s., 3H), 3.96 (s, 3H), 4.55 (s, 2H), 5.08-5.17 (m, 1H), 6.90 (dd, J=9.1, 4.3 Hz, 1H), 7.08 (t, J=8.8 Hz, 1H), 7.34 (d, J=1.3 Hz, 1H), 7.46 (s, 1H), 7.53 (s, 1H), 8.15-8.22 (m, 1H). MS (ES+): m/z=415.13/417.13 (100/50) [MH+]. HPLC: tR=1.37 min (polar-3 min, UPLC-ACQUITY).
  • 3
  • [ 1276056-83-7 ]
  • [ 1454300-91-4 ]
  • [ 76-05-1 ]
  • (1-methyl-4-(6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazol-5-yl)methanol trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
8% Stage #1: (4-bromo-1-methyl-1H-pyrazol-5-yl)methanol; 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium hydrogencarbonate In 1,4-dioxane; water at 140℃; for 0.75h; Microwave irradiation; Stage #2: trifluoroacetic acid In water; acetonitrile for 0.1h; 250 EXAMPLE 250: (l-methyl-4-(6-(trifiuoromethyl)-lH-indazol-4-yl)-lH-pyrazol-5- yl)methanol EXAMPLE 250: (l-methyl-4-(6-(trifiuoromethyl)-lH-indazol-4-yl)-lH-pyrazol-5- yl)methanol [0792] A vial was charged with a mixture of 4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2- yl)-6-(trifluoromethyl)-lH-indazole (0.1 g, 0.320 mmol), (4-bromo-l -methyl- lH-pyrazol-5- yl)methanol (0.086 g, 0.449 mmol) and PdCl2(dppf) (0.012 g, 0.016 mmol) in dioxane (8 mL) and aqueous saturated NaHC03 (2 mL). The resulting light brown suspension was heated at 140°C for 45 minutes in a microwave reactor. The reaction mixture was subsequently concentrated and the crude residue was purified by preparative HPLC, eluting with 30%> ACN (containing 0.035% TFA) in H20 (containing 0.05% TFA) over a period of 6 minutes. The product-containing fractions were combined and volatiles removed in vacuo to give a TFA salt of the title compound as an off white solid (8 mg, 8%). 1H NMR (400 MHz, OMSO-de) δ ppm 3.96 (s, 3 H), 4.56 (d, J=4.80 Hz, 2 H), 5.53 (t, J=4.93 Hz, 1 H), 7.43 (s, 1 H), 7.78-7.92 (m, 2 H), 8.30 (s, 1 H), 13.62 (s, 1 H); ESI-MS m/z [M+H]+ calc'd for Ci3HiiF3N40, 297.1; found 297.14.
  • 4
  • [ 1276056-83-7 ]
  • [ 74-88-4 ]
  • [ 1578484-60-2 ]
YieldReaction ConditionsOperation in experiment
67% Stage #1: (4-bromo-1-methyl-1H-pyrazol-5-yl)methanol With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide for 0.25h; Stage #2: methyl iodide In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 16h; 150 Preparation 150: 4-Bromo-5-(methoxymethyl)-1 -methyl-1 /-/-pyrazole Preparation 150: 4-Bromo-5-(methoxymethyl)-1 -methyl-1 /-/-pyrazole NaH (60%, 58 mg) was added to a solution of (4-bromo-1 -methyl-1 H-pyrazol-5- yl)methanol (Preparation 149, 97 mg, 1 .03 mmol) in THF/DMF (8/4 mL). After stirring for 15 minutes, iodomethane (439 mg, 3.09 mmol) in THF (1 mL) was added. The resulting solution was stirred at room temperature for 16 hours. The reaction mixture was diluted with brine and extracted with EtOAc. The combined organic layers were washed with water, dried over sodium sulphate and concentrated in vacuo to afford the title compound (142 mg, 67%). 1 H NMR (500 MHz, CDCI3): δ 7.42 (s, 1 H), 4.49 (s, 2H), 3.91 (s, 3H), 3.34 (s, 3H). LCMS (ESI) Rt = 2.13 minutes MS m/z 205 [M79Br+H]+
  • 5
  • [ 473528-88-0 ]
  • [ 1276056-83-7 ]
YieldReaction ConditionsOperation in experiment
90% With methanol; sodium tetrahydroborate; at 20℃; for 2h; Preparation 149: (4-Bromo-1 -methyl-1 /-/-pyrazol-5-yl)methanol To a solution of 4-bromo- 1 -methyl- 1 H-pyrazole-5-carbaldehyde (677 mg, 3.58 mmol) in MeOH (8 ml.) at 0C, NaBH4 (136 mg, 0.86 mmol) was added. The solution was stirred at room temperature for 2 hours. The reaction was concentrated in vacuo and diluted with water. The solution was extracted with EtOAc, the organic layer collected, dried over sodium sulphate and concentrated in vacuo to afford the title compound as a white solid (614 mg, 90%). 1 H NMR (500 MHz, CDCI3): delta 7.43 (s, 1 H), 4.72 (s, 2H), 3.97 (s, 3H), 2.09 (s, 1 H). LCMS (ESI) Rt = 1 .29 minutes MS m/z 191 [M79Br+H]+
79% With sodium tetrahydroborate; In methanol; at 0 - 20℃; To a solution of compound 4-bromo-l -methyl- lH-pyrazole-5-carbaldehyde (200 mg, 1.06 mmol) in methanol (20 mL) was added NaBH4 (80 mg, 2.13 mmol) at 0 C. The mixture was stirred for 1 h and allowed to warm to room temperature. After concentrated under reduce pressure, the residue was purified on silica gel (Petroleum ether : ethyl acetate = 8 : 1) to give a white solid (160 mg, 79%). LRMS m/z (M+H) 190.0 found, 190.0 required.
  • 6
  • [ 1269291-90-8 ]
  • [ 1276056-83-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: hydrogenchloride / tetrahydrofuran; water / 48 h / 0 - 20 °C 2: N-Bromosuccinimide / N,N-dimethyl-formamide / 20 °C 3: sodium tetrahydroborate / methanol / 0 - 20 °C
  • 7
  • [ 27258-33-9 ]
  • [ 1276056-83-7 ]
  • 8
  • [ 1276056-83-7 ]
  • [ 126747-14-6 ]
  • 4-[5-(Hydroxymethyl)-1-methylpyrazol-4-yl]benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; potassium carbonate In water; acetonitrile at 100℃; for 0.5h; Microwave irradiation;
  • 9
  • [ 1276056-83-7 ]
  • 4-methyl-2-(1-methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1H- pyrazol-4-yl)pyrimidin-5-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation; Inert atmosphere
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 16 h / 100 °C / Inert atmosphere 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / water; acetonitrile / 1 h / 100 °C / Microwave irradiation

  • 10
  • [ 1276056-83-7 ]
  • isopropyl (1S,3S)-3-((4-methyl-2-(1-methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1H-pyrazol-4-yl)pyrimidin-5-yl)oxy)cyclohexane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation; Inert atmosphere 4.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / toluene / 9 h / 85 °C / Inert atmosphere
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation 4: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 9 h / 85 °C
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: water; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1.5 h / 120 °C / Sealed tube; Inert atmosphere; Microwave irradiation
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / water; acetonitrile / 1 h / 100 °C / Microwave irradiation 4.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / toluene / 9 h / 85 °C

  • 11
  • [ 1276056-83-7 ]
  • isopropyl (1S,3S)-3-((2-(5-(hydroxymethyl)-1-methyl-1H-pyrazol-4-yl)-4-methylpyrimidin-5-yl)oxy)cyclohexane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation; Inert atmosphere 4.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / toluene / 9 h / 85 °C / Inert atmosphere 5.1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere
Multi-step reaction with 5 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation 4: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 9 h / 85 °C 5: pyridinium p-toluenesulfonate; methanol / 2 h / 60 °C
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: water; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1.5 h / 120 °C / Sealed tube; Inert atmosphere; Microwave irradiation 4.1: pyridinium p-toluenesulfonate; methanol / 60 °C
Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / water; acetonitrile / 1 h / 100 °C / Microwave irradiation 4.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / toluene / 9 h / 85 °C 5.1: pyridinium p-toluenesulfonate; methanol / 60 °C

  • 12
  • [ 1276056-83-7 ]
  • isopropyl (1S,3S)-3-((2-(5-(bromomethyl)-1-methyl-1H-pyrazol-4-yl)-4-methylpyrimidin-5-yl)oxy)cyclohexane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation; Inert atmosphere 4.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / toluene / 9 h / 85 °C / Inert atmosphere 5.1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 6.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C / Inert atmosphere
Multi-step reaction with 6 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation 4: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 9 h / 85 °C 5: pyridinium p-toluenesulfonate; methanol / 2 h / 60 °C 6: phosphorus tribromide / dichloromethane / 20 °C
Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: water; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1.5 h / 120 °C / Sealed tube; Inert atmosphere; Microwave irradiation 4.1: pyridinium p-toluenesulfonate; methanol / 60 °C 5.1: phosphorus tribromide / dichloromethane / 0 - 20 °C
Multi-step reaction with 6 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / water; acetonitrile / 1 h / 100 °C / Microwave irradiation 4.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / toluene / 9 h / 85 °C 5.1: pyridinium p-toluenesulfonate; methanol / 60 °C 6.1: phosphorus tribromide / dichloromethane / 0 - 20 °C

  • 13
  • [ 1276056-83-7 ]
  • isopropyl (1S,3S)-3-((2-(5-(azidomethyl)-1-methyl-1H-pyrazol-4-yl)-4-methylpyrimidin-5-yl)oxy)cyclohexane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation; Inert atmosphere 4.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / toluene / 9 h / 85 °C / Inert atmosphere 5.1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 6.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C / Inert atmosphere 7.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation 4: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 9 h / 85 °C 5: pyridinium p-toluenesulfonate; methanol / 2 h / 60 °C 6: phosphorus tribromide / dichloromethane / 20 °C 7: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C
Multi-step reaction with 6 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: water; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1.5 h / 120 °C / Sealed tube; Inert atmosphere; Microwave irradiation 4.1: pyridinium p-toluenesulfonate; methanol / 60 °C 5.1: phosphorus tribromide / dichloromethane / 0 - 20 °C 6.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C
Multi-step reaction with 7 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / water; acetonitrile / 1 h / 100 °C / Microwave irradiation 4.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / toluene / 9 h / 85 °C 5.1: pyridinium p-toluenesulfonate; methanol / 60 °C 6.1: phosphorus tribromide / dichloromethane / 0 - 20 °C 7.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C

  • 14
  • [ 1276056-83-7 ]
  • (1S,3S)-3-((6-(5-(((butoxycarbonyl)amino)methyl)-1-methyl-1H-pyrazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexanecarboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 9 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: tetrahydroxydiboron; XPhos; potassium acetate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) / 1,2-dimethoxyethane; ethanol / 1 h / 80 °C / Inert atmosphere; Sealed tube 2.2: 0.5 h / Inert atmosphere 2.3: 16 h / 80 °C / Inert atmosphere 3.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 1,4-dioxane / 2 h / 70 - 80 °C / Inert atmosphere 4.1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 5.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C / Inert atmosphere 6.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 7.1: water; triphenylphosphine / tetrahydrofuran / 20 °C / Inert atmosphere 8.1: sodium hydrogencarbonate / water; ethyl acetate / 20 °C / Inert atmosphere 9.1: water; lithium hydroxide monohydrate / tetrahydrofuran; methanol / 20 °C / Inert atmosphere
  • 15
  • [ 1276056-83-7 ]
  • 2-methyl-6-(1-methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1H-pyrazol-4-yl)pyridin-3-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: tetrahydroxydiboron; XPhos; potassium acetate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) / 1,2-dimethoxyethane; ethanol / 1 h / 80 °C / Inert atmosphere; Sealed tube 2.2: 0.5 h / Inert atmosphere 2.3: 16 h / 80 °C / Inert atmosphere
  • 16
  • [ 1276056-83-7 ]
  • (1S,3S)-isopropyl 3-((2-methyl-6-(1-methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1H-pyrazol-4-yl)pyridin-3-yl)oxy)cyclohexanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: tetrahydroxydiboron; XPhos; potassium acetate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) / 1,2-dimethoxyethane; ethanol / 1 h / 80 °C / Inert atmosphere; Sealed tube 2.2: 0.5 h / Inert atmosphere 2.3: 16 h / 80 °C / Inert atmosphere 3.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 1,4-dioxane / 2 h / 70 - 80 °C / Inert atmosphere
  • 17
  • [ 1276056-83-7 ]
  • isopropyl trans-3-((6-(5-(bromomethyl)-1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10 h / 85 °C / Inert atmosphere; Sealed tube 3.1: dipotassium hydrogenphosphate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) / 1,4-dioxane; water / 48 h / 20 - 60 °C / Inert atmosphere 4.1: pyridinium p-toluenesulfonate / methanol / 4 h / 60 °C / Inert atmosphere 5.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C / Inert atmosphere
Multi-step reaction with 5 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); dipotassium hydrogenphosphate / 1,4-dioxane; water / 48 h / 20 - 60 °C 4: pyridinium p-toluenesulfonate; methanol / 4 h / 60 °C 5: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C
Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: dipotassium hydrogenphosphate; chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) methyl-t-butyl ether adduct / 1,4-dioxane; water / 24 h / 60 °C / Inert atmosphere 4.1: pyridinium p-toluenesulfonate; methanol / 4 h / 60 °C 5.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C
  • 18
  • [ 1276056-83-7 ]
  • (1S,3S)-isopropyl 3-((6-(5-(hydroxymethyl)-1-methyl-1H-pyrazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: tetrahydroxydiboron; XPhos; potassium acetate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) / 1,2-dimethoxyethane; ethanol / 1 h / 80 °C / Inert atmosphere; Sealed tube 2.2: 0.5 h / Inert atmosphere 2.3: 16 h / 80 °C / Inert atmosphere 3.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 1,4-dioxane / 2 h / 70 - 80 °C / Inert atmosphere 4.1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere
  • 19
  • [ 1276056-83-7 ]
  • (1S,3S)-isopropyl 3-((6-(5-(bromomethyl)-1-methyl-1H-pyrazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: tetrahydroxydiboron; XPhos; potassium acetate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) / 1,2-dimethoxyethane; ethanol / 1 h / 80 °C / Inert atmosphere; Sealed tube 2.2: 0.5 h / Inert atmosphere 2.3: 16 h / 80 °C / Inert atmosphere 3.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 1,4-dioxane / 2 h / 70 - 80 °C / Inert atmosphere 4.1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 5.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C / Inert atmosphere
  • 20
  • [ 1276056-83-7 ]
  • (1S,3S)-isopropyl 3-((6-(5-(azidomethyl)-1-methyl-1H-pyrazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: tetrahydroxydiboron; XPhos; potassium acetate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) / 1,2-dimethoxyethane; ethanol / 1 h / 80 °C / Inert atmosphere; Sealed tube 2.2: 0.5 h / Inert atmosphere 2.3: 16 h / 80 °C / Inert atmosphere 3.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 1,4-dioxane / 2 h / 70 - 80 °C / Inert atmosphere 4.1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 5.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C / Inert atmosphere 6.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere
  • 21
  • [ 1276056-83-7 ]
  • (1S,3S)-isopropyl 3-((6-(5-(aminomethyl)-1-methyl-1H-pyrazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: tetrahydroxydiboron; XPhos; potassium acetate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) / 1,2-dimethoxyethane; ethanol / 1 h / 80 °C / Inert atmosphere; Sealed tube 2.2: 0.5 h / Inert atmosphere 2.3: 16 h / 80 °C / Inert atmosphere 3.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 1,4-dioxane / 2 h / 70 - 80 °C / Inert atmosphere 4.1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 5.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C / Inert atmosphere 6.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 7.1: water; triphenylphosphine / tetrahydrofuran / 20 °C / Inert atmosphere
  • 22
  • [ 1276056-83-7 ]
  • (1S,3S)-isopropyl 3-((6-(5-(((butoxycarbonyl)amino)methyl)-1-methyl-1H-pyrazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: tetrahydroxydiboron; XPhos; potassium acetate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) / 1,2-dimethoxyethane; ethanol / 1 h / 80 °C / Inert atmosphere; Sealed tube 2.2: 0.5 h / Inert atmosphere 2.3: 16 h / 80 °C / Inert atmosphere 3.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 1,4-dioxane / 2 h / 70 - 80 °C / Inert atmosphere 4.1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 5.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C / Inert atmosphere 6.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 7.1: water; triphenylphosphine / tetrahydrofuran / 20 °C / Inert atmosphere 8.1: sodium hydrogencarbonate / water; ethyl acetate / 20 °C / Inert atmosphere
  • 23
  • [ 1276056-83-7 ]
  • (1S,3S)-3-((6-(5-(((butoxycarbonyl)(methyl)amino)methyl)-1-methyl-1H-pyrazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexanecarboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 10 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: tetrahydroxydiboron; XPhos; potassium acetate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) / 1,2-dimethoxyethane; ethanol / 1 h / 80 °C / Inert atmosphere; Sealed tube 2.2: 0.5 h / Inert atmosphere 2.3: 16 h / 80 °C / Inert atmosphere 3.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 1,4-dioxane / 2 h / 70 - 80 °C / Inert atmosphere 4.1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 5.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C / Inert atmosphere 6.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 7.1: water; triphenylphosphine / tetrahydrofuran / 20 °C / Inert atmosphere 8.1: sodium hydrogencarbonate / water; ethyl acetate / 20 °C / Inert atmosphere 9.1: water; lithium hydroxide monohydrate / tetrahydrofuran; methanol / 20 °C / Inert atmosphere 10.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 - 20 °C / Inert atmosphere 10.2: 1 h / 0 - 20 °C / Inert atmosphere 10.3: 20 °C / Inert atmosphere
  • 24
  • [ 1276056-83-7 ]
  • 1-methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10 h / 85 °C / Inert atmosphere; Sealed tube
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 16 h / 100 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube
Multi-step reaction with 2 steps 1: pyridinium p-toluenesulfonate / dichloromethane / 18 h / 20 °C 2: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 18 h / 80 °C / Inert atmosphere

  • 25
  • [ 1276056-83-7 ]
  • C23H33N5O5*C2HF3O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 9 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation; Inert atmosphere 4.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / toluene / 9 h / 85 °C / Inert atmosphere 5.1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 6.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C / Inert atmosphere 7.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 8.1: water; triphenylphosphine / tetrahydrofuran / 20 °C / Inert atmosphere 9.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 4 h / 20 °C / Inert atmosphere 9.2: 20 °C / Inert atmosphere 9.3: 0.4 h / 25 °C / Inert atmosphere
  • 26
  • [ 1276056-83-7 ]
  • isopropyl trans-3-((6-(1-methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)- 1H-pyrazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10 h / 85 °C / Inert atmosphere; Sealed tube 3.1: dipotassium hydrogenphosphate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) / 1,4-dioxane; water / 48 h / 20 - 60 °C / Inert atmosphere
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); dipotassium hydrogenphosphate / 1,4-dioxane; water / 48 h / 20 - 60 °C
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: dipotassium hydrogenphosphate; chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) methyl-t-butyl ether adduct / 1,4-dioxane; water / 24 h / 60 °C / Inert atmosphere
  • 27
  • [ 1276056-83-7 ]
  • C2HF3O2*C25H29N5O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 9 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation; Inert atmosphere 4.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / toluene / 9 h / 85 °C / Inert atmosphere 5.1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 6.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C / Inert atmosphere 7.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 8.1: water; triphenylphosphine / tetrahydrofuran / 20 °C / Inert atmosphere 9.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0.17 h / 20 °C / Inert atmosphere 9.2: 20 °C / Inert atmosphere 9.3: 0.4 h / 25 °C / Inert atmosphere
  • 28
  • [ 1276056-83-7 ]
  • isopropyl trans-3-((6-(5-(hydroxymethyl)-1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10 h / 85 °C / Inert atmosphere; Sealed tube 3.1: dipotassium hydrogenphosphate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II) / 1,4-dioxane; water / 48 h / 20 - 60 °C / Inert atmosphere 4.1: pyridinium p-toluenesulfonate / methanol / 4 h / 60 °C / Inert atmosphere
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); dipotassium hydrogenphosphate / 1,4-dioxane; water / 48 h / 20 - 60 °C 4: pyridinium p-toluenesulfonate; methanol / 4 h / 60 °C
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: dipotassium hydrogenphosphate; chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) methyl-t-butyl ether adduct / 1,4-dioxane; water / 24 h / 60 °C / Inert atmosphere 4.1: pyridinium p-toluenesulfonate; methanol / 4 h / 60 °C
  • 29
  • [ 1276056-83-7 ]
  • isopropyl (1S,3S)-3-((2-(5-(aminomethyl)-1-methyl-1H-pyrazol-4-yl)-4-methylpyrimidin-5-yl)oxy)cyclohexane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C / Inert atmosphere 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation; Inert atmosphere 4.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / toluene / 9 h / 85 °C / Inert atmosphere 5.1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 6.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C / Inert atmosphere 7.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 8.1: water; triphenylphosphine / tetrahydrofuran / 20 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation 4: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 9 h / 85 °C 5: pyridinium p-toluenesulfonate; methanol / 2 h / 60 °C 6: phosphorus tribromide / dichloromethane / 20 °C 7: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C 8: water; triphenylphosphine / tetrahydrofuran / 20 °C
Multi-step reaction with 7 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: water; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1.5 h / 120 °C / Sealed tube; Inert atmosphere; Microwave irradiation 4.1: pyridinium p-toluenesulfonate; methanol / 60 °C 5.1: phosphorus tribromide / dichloromethane / 0 - 20 °C 6.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C 7.1: water; triphenylphosphine / tetrahydrofuran / 20 °C
Multi-step reaction with 8 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / water; acetonitrile / 1 h / 100 °C / Microwave irradiation 4.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / toluene / 9 h / 85 °C 5.1: pyridinium p-toluenesulfonate; methanol / 60 °C 6.1: phosphorus tribromide / dichloromethane / 0 - 20 °C 7.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C 8.1: water; triphenylphosphine / tetrahydrofuran / 20 °C

  • 30
  • [ 110-87-2 ]
  • [ 1276056-83-7 ]
  • 4-bromo-1-methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1H-pyrazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% With toluene-4-sulfonic acid In dichloromethane at 0 - 20℃; 1.1B; 66.B 66B. 4-bromo-1-methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1H-pyrazole p-TsOH.H2O (0.050 g, 0.262 mmol) was added to a RT solution of Intermediate 66A (1.0 g, 5.23 mmol) and 3,4-dihydro-2H-pyran (1.32 g, 15.7 mmol) in DCM (10 mL) at 0 °C. The reaction was allowed to warm to RT and was stirred overnight at RT. The mixture was cooled to 0°C, neutralized with sat’d aq. NaHC03 to pH 7, then was partitioned between DCM (10 mL) and H20 (10 mL). The aqueous layer was extracted with DCM (3 x 10 mL). The combined organic extracts were dried (MgS04) and concentrated in vacuo. The residue was chromatographed (40 g Si02; continuous gradient from 0%-80% EtOAc in hexanes over 14 min) to give the title compound (1.4 g, 5.09 mmol, 97 % yield) as a colorless oil. NMR (500 MHz, CDC13) d 7.41 (s, 1H), 4.72 (d, J= 12.9 Hz, 1H), 4.65 (dd, J= 4.1, 3.0 Hz, 1H), 4.58 (d, J= 12.9 Hz, 1H), 3.93 (s, 3H), 3.88 (ddd, J= 11.6, 8.3, 3.1 Hz, 1H), 3.57 (dddd, j= 11.0, 5.0, 3.9, 1.4 Hz, 1H), 3.49 (d, J= 5.5 Hz, 2H), 1.85 - 1.75 (m, 1H), 1.75 - 1.66 (m, 1H), 1.66 - 1.48 (m, 4H). LCMS, [M+H]+ = 275.1.
97% With toluene-4-sulfonic acid In dichloromethane at 0 - 20℃; Intermediate 1 A. 4-bromo- 1 -methyl-5 -(((tetrahydro-2H-pyran-2-yl)oxy)methyl)- 1 H- pyr azole pTsOH.H20 (0.050 g, 0.262 mmol) was added to a solution of (4-bromo-l- methyl- 1 H-pyrazol- 5 -yl)methanol (1.0 g, 5.2 mmol) and 3 ,4-dihydro-2H-pyran (1.32 g, 15.7 mmol) in DCM (10 mL) at 0 °C. The reaction was allowed to warm to RT and stirred overnight at RT. The reaction was cooled to 0 °C and neutralized with satd aq. NaHC03 to pH 7. The mixture was partitioned between DCM (10 mL) and water (10 mL), and the aqueous layer was extracted with DCM (3 x 10 mL). The combined organic extracts were dried (MgS04) and concentrated in vacuo. The residue was chromato graphed (Si02; EtOAc/hexanes) to provide title compound (1.40 g, 5.09 mmol, 97 % yield) as a colorless oil. NMR (500 MHz, CDC13) d 7.41 (s, 1H), 4.72 (d, J= 12.9 Hz, 1H), 4.65 (dd, j= 4.1, 3.0 Hz, 1H), 4.58 (d, J= 12.9 Hz, 1H), 3.93 (s, 3H), 3.88 (ddd, /= 11.6, 8.3, 3.1 Hz, 1H), 3.57 (dddd, j= 11.0, 5.0, 3.9, 1.4 Hz, 1H), 3.49 (d, J= 5.5 Hz, 2H), 1.85 - 1.75 (m, 1H), 1.75 - 1.66 (m, 1H), 1.66 - 1.48 (m, 4H). [M+H]+ = 275.1.
97% With toluene-4-sulfonic acid In dichloromethane at 0 - 20℃; Inert atmosphere; 1B Intermediate 1 A. 4-bromo-l -methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-lH- pyrazole pTsOH.H20 (0.050 g, 0.262 mmol) was added to a solution of (4-bromo-l- methyl- 1 H-pyrazol-5-yl)methanol (1.0 g, 5.2 mmol) and 3,4-dihydro-2H-pyran (1.32 g, 15.7 mmol) in DCM (10 mL) at 0 °C. The reaction was allowed to warm to RT and stirred overnight at RT. The reaction was cooled to 0 °C and neutralized with satd aq. NaHC03 to pH 7. The mixture was partitioned between DCM (10 mL) and water (10 mL), and the aqueous layer was extracted with DCM (3 10 mL). The combined organic extracts were dried (MgS04) and concentrated in vacuo. The residue was chromatographed (S1O2; EtO Ac/hexanes) to provide title compound (1.40 g, 5.09 mmol, 97 % yield) as a colorless oil. NMR (500 MHz, CDC13) d 7.41 (s, 1H), 4.72 (d, J= 12.9 Hz, 1H), 4.65 (dd, j= 4.1, 3.0 Hz, 1H), 4.58 (d, J= 12.9 Hz, 1H), 3.93 (s, 3H), 3.88 (ddd, J= 11.6, 8.3, 3.1 Hz, 1H), 3.57 (dddd, /= 11.0, 5.0, 3.9, 1.4 Hz, 1H), 3.49 (d, /= 5.5 Hz, 2H), 1.85 - 1.75 (m, 1H), 1.75 - 1.66 (m, 1H), 1.66 - 1.48 (m, 4H). LCMS, [M+H]+ = 275.1.
97% With toluene-4-sulfonic acid In dichloromethane at 0 - 20℃; Intermediate 1 A. 4-bromo- 1 -methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)- 1 H- pyrazole pTsOH.H20 (0.050 g, 0.262 mmol) was added to a solution of (4-bromo-l- methyl- lH-pyrazol- 5 -yl)methanol (1.0 g, 5.2 mmol) and 3,4-dihydro-2H-pyran (1.32 g, 15.7 mmol) in DCM (10 mL) at 0 °C. The reaction was allowed to warm to RT and stirred overnight at RT. The reaction was cooled to 0 °C and neutralized with satd aq. NaHC03 to pH 7. The mixture was partitioned between DCM (10 mL) and water (10 mL), and the aqueous layer was extracted with DCM (3 x 10 mL). The combined organic extracts were dried (MgS04) and concentrated in vacuo. The residue was (0646) chromatographed (Si02; EtO Ac/hexanes) to provide title compound (1.40 g, 5.09 mmol, 97 % yield) as a colorless oil. MHz, CDC13) d 7.41 (s, 1H), 4.72 (d, J= 12.9 Hz, 1H), 4.65 (dd, J= 4.1, 3.0 Hz, 1H), 4.58 (d, J= 12.9 Hz, 1H), 3.93 (s, 3H), 3.88 (ddd, J= 11.6, 8.3, 3.1 Hz, 1H), 3.57 (dddd, J= 11.0, 5.0, 3.9, 1.4 Hz, 1H), 3.49 (d, j= 5.5 Hz, 2H), 1.85 - 1.75 (m, 1H), 1.75 - 1.66 (m, 1H), 1.66 - 1.48 (m, 4H). [M+H]+ = 275.1.
5.90 g With pyridinium p-toluenesulfonate In dichloromethane at 20℃; for 18h; 16 16B. 4-bromo-l-methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-lH-pyrazole A mixture of compound 16A (4.20 g, 22.0 mmol), dihydropyran (4.0 mL, 44.0 mmol), and PPTS (0.55 g, 2.20 mmol) in CH2CI2 (20 mL) was stirred at RT for 18 h, then was concentrated in vacuo. The crude oil was chromatographed (80 g S1O2; continuous gradient from 0% to 40% EtOAc in hexane over 30 min) to give the title compound (5.90 g, 21.44 mmol, 98 % yield) as a clear oil. NMR (400 MHz, CDCh) d 7.41 (s, 1H), 4.76 - 4.54 (m, 3H), 3.93 (s, 3H), 3.88 (ddd, J= 1.4, 8.1, 3.2 Hz, 1H), 3.61 - 3.53 (m, 1H), 1.89 - 1.49 (m, 6H).
1.56 g With pyridinium p-toluenesulfonate In dichloromethane at 20℃; for 16h;

Reference: [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2019/126098, 2019, A1 Location in patent: Page/Page column 84; 85; 110; 111
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2019/126089, 2019, A1 Location in patent: Page/Page column 87; 88; 92
[3]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2019/126085, 2019, A1 Location in patent: Page/Page column 83; 85-86; 89-90; 98
[4]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2019/126103, 2019, A1 Location in patent: Page/Page column 88-89; 92-93
[5]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2020/60915, 2020, A1 Location in patent: Page/Page column 145
[6]Cheng, Peter T. W.; Kaltenbach, Robert F.; Zhang, Hao; Shi, Jun; Tao, Shiwei; Li, Jun; Kennedy, Lawrence J.; Walker, Steven J.; Shi, Yan; Wang, Ying; Dhanusu, Suresh; Reddigunta, Ramesh; Kumaravel, Selvakumar; Jusuf, Sutjano; Smith, Daniel; Krishnananthan, Subramaniam; Li, Jianqing; Wang, Tao; Heiry, Rebekah; Sum, Chi Shing; Kalinowski, Stephen S.; Hung, Chen-Pin; Chu, Ching-Hsuen; Azzara, Anthony V.; Ziegler, Milinda; Burns, Lisa; Zinker, Bradley A.; Boehm, Stephanie; Taylor, Joseph; Sapuppo, Julia; Mosure, Kathy; Everlof, Gerry; Guarino, Victor; Zhang, Lisa; Yang, Yanou; Ruan, Qian; Xu, Carrie; Apedo, Atsu; Traeger, Sarah C.; Cvijic, Mary Ellen; Lentz, Kimberley A.; Tirucherai, Giridhar; Sivaraman, Lakshmi; Robl, Jeffrey; Ellsworth, Bruce A.; Rosen, Glenn; Gordon, David A.; Soars, Matthew G.; Gill, Michael; Murphy, Brian J. [Journal of Medicinal Chemistry, 2021, vol. 64, # 21, p. 15549 - 15581]
  • 31
  • [ 1276056-83-7 ]
  • 6-(1-methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1H-pyrazol-4-yl)pyridin-3-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); tetrahydroxydiboron / 1,2-dimethoxyethane; ethanol / 0.25 h / 80 °C / Inert atmosphere; Sealed tube 2.2: 0.25 h / Inert atmosphere; Sealed tube 2.3: 16 h / 80 °C / Sealed tube; Inert atmosphere
  • 32
  • [ 1276056-83-7 ]
  • C30H34N6O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3.1: chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); dipotassium hydrogenphosphate / 1,4-dioxane; water / 48 h / 20 - 60 °C 4.1: pyridinium p-toluenesulfonate; methanol / 4 h / 60 °C 5.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C 6.1: n-butyllithium / tetrahydrofuran; hexane / 0.08 h / -78 - 20 °C 6.2: 48 h / 20 °C
  • 33
  • [ 1276056-83-7 ]
  • C27H37N7O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 9 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation 4: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 9 h / 85 °C 5: pyridinium p-toluenesulfonate; methanol / 2 h / 60 °C 6: phosphorus tribromide / dichloromethane / 20 °C 7: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C 8: water; triphenylphosphine / tetrahydrofuran / 20 °C 9: N-ethyl-N,N-diisopropylamine / butan-1-ol / 1.33 h / 180 °C
  • 34
  • [ 1276056-83-7 ]
  • C26H35N7O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 9 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation 4: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 9 h / 85 °C 5: pyridinium p-toluenesulfonate; methanol / 2 h / 60 °C 6: phosphorus tribromide / dichloromethane / 20 °C 7: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C 8: water; triphenylphosphine / tetrahydrofuran / 20 °C 9: N-ethyl-N,N-diisopropylamine / butan-1-ol / 3 h / 180 °C / Microwave irradiation
  • 35
  • [ 1276056-83-7 ]
  • C27H37N7O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / 1,4-dioxane; water / 1.5 h / 120 °C / Microwave irradiation 4: pyridinium p-toluenesulfonate; methanol / 60 °C 5: phosphorus tribromide / tetrahydrofuran / 0 - 20 °C 6: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C 7: water; triphenylphosphine / tetrahydrofuran / 20 °C 8: N-ethyl-N,N-diisopropylamine / butan-1-ol / 3 h / 180 °C
  • 36
  • [ 1276056-83-7 ]
  • C32H35N3O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); dipotassium hydrogenphosphate / 1,4-dioxane; water / 48 h / 20 - 60 °C 4: pyridinium p-toluenesulfonate; methanol / 4 h / 60 °C 5: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C 6: silver carbonate / toluene / 72 h / 20 °C
  • 37
  • [ 1276056-83-7 ]
  • isopropyl (1S,3S)-3-((4-ethyl-2-(1-methyl-5-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1H-pyrazol-4-yl)pyrimidin-5-yl)oxy)cyclohexane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / 1,4-dioxane; water / 1.5 h / 120 °C / Microwave irradiation
  • 38
  • [ 1276056-83-7 ]
  • isopropyl (1S,3S)-3-((4-ethyl-2-(5-(hydroxymethyl)-1-methyl-1H-pyrazol-4-yl)pyrimidin-5-yl)oxy)cyclohexane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / 1,4-dioxane; water / 1.5 h / 120 °C / Microwave irradiation 4: pyridinium p-toluenesulfonate; methanol / 60 °C
  • 39
  • [ 1276056-83-7 ]
  • isopropyl (1S,3S)-3-((2-(5-(bromomethyl)-1-methyl-1H-pyrazol-4-yl)-4-ethylpyrimidin-5-yl)oxy)cyclohexane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / 1,4-dioxane; water / 1.5 h / 120 °C / Microwave irradiation 4: pyridinium p-toluenesulfonate; methanol / 60 °C 5: phosphorus tribromide / tetrahydrofuran / 0 - 20 °C
  • 40
  • [ 1276056-83-7 ]
  • isopropyl (1S,3S)-3-((2-(5-(azidomethyl)-1-methyl-1H-pyrazol-4-yl)-4-ethylpyrimidin-5-yl)oxy)cyclohexane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / 1,4-dioxane; water / 1.5 h / 120 °C / Microwave irradiation 4: pyridinium p-toluenesulfonate; methanol / 60 °C 5: phosphorus tribromide / tetrahydrofuran / 0 - 20 °C 6: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C
  • 41
  • [ 1276056-83-7 ]
  • isopropyl (1S,3S)-3-((2-(5-(aminomethyl)-1-methyl-1H-pyrazol-4-yl)-4-ethyl-pyrimidin-5-yl)oxy)cyclohexane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / 1,4-dioxane; water / 1.5 h / 120 °C / Microwave irradiation 4: pyridinium p-toluenesulfonate; methanol / 60 °C 5: phosphorus tribromide / tetrahydrofuran / 0 - 20 °C 6: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C 7: water; triphenylphosphine / tetrahydrofuran / 20 °C
  • 42
  • [ 1276056-83-7 ]
  • trans-3-((6-(1-methyl-5-(((4-phenylpyrimidin-2-yl)amino)methyl)-1H-pyrazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3.1: chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); dipotassium hydrogenphosphate / 1,4-dioxane; water / 48 h / 20 - 60 °C 4.1: pyridinium p-toluenesulfonate; methanol / 4 h / 60 °C 5.1: phosphorus tribromide / 1,2-dimethoxyethane / 0 - 20 °C 6.1: n-butyllithium / tetrahydrofuran; hexane / 0.08 h / -78 - 20 °C 6.2: 48 h / 20 °C 7.1: lithium hydroxide monohydrate / tetrahydrofuran; water; methanol; hexane / 18 h / 20 °C
  • 43
  • [ 1276056-83-7 ]
  • (1S,3S)-3-((2-(5-(((4-isopropoxypyrimidin-2-yl)amino)methyl)-1-methyl-1H-pyrazol-4-yl)-4-methylpyrimidin-5-yl)oxy)cyclohexane-1-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 10 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation 4: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 9 h / 85 °C 5: pyridinium p-toluenesulfonate; methanol / 2 h / 60 °C 6: phosphorus tribromide / dichloromethane / 20 °C 7: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C 8: water; triphenylphosphine / tetrahydrofuran / 20 °C 9: N-ethyl-N,N-diisopropylamine / butan-1-ol / 1.33 h / 180 °C 10: lithium hydroxide monohydrate / tetrahydrofuran; water; methanol; butan-1-ol / 20 °C
  • 44
  • [ 1276056-83-7 ]
  • (1S,3S)-3-((2-(5-(((4-ethoxypyrimidin-2-yl)amino)methyl)-1-methyl-1H-pyrazol-4-yl)-4-methyl-pyrimidin-5-yl)oxy)cyclohexane-1-carboxylic acid bis(trifluoroacetic acid) [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 10 steps 1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 10 h / 85 °C / Sealed tube 3: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1 h / 100 °C / Microwave irradiation 4: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / 9 h / 85 °C 5: pyridinium p-toluenesulfonate; methanol / 2 h / 60 °C 6: phosphorus tribromide / dichloromethane / 20 °C 7: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C 8: water; triphenylphosphine / tetrahydrofuran / 20 °C 9: N-ethyl-N,N-diisopropylamine / butan-1-ol / 3 h / 180 °C / Microwave irradiation 10: lithium hydroxide monohydrate / tetrahydrofuran; water; methanol; butan-1-ol / 20 °C
  • 45
  • [ 1276056-83-7 ]
  • (1S,3S)-3-((2-(5-((4-(cyclopropylmethyl)-1H-1,2,3-triazol-1-yl)methyl)-1-methyl-1H-pyrazol-4-yl)-4-methylpyrimidin-5-yl)oxy)cyclohexane-1-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: water; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1.5 h / 120 °C / Sealed tube; Inert atmosphere; Microwave irradiation 4.1: pyridinium p-toluenesulfonate; methanol / 60 °C 5.1: phosphorus tribromide / dichloromethane / 0 - 20 °C 6.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C 7.1: sodium L-ascorbate; copper(ll) sulfate pentahydrate / water; <i>tert</i>-butyl alcohol / 16 h / 37 °C 7.2: 14 h / 20 °C
Multi-step reaction with 8 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / water; acetonitrile / 1 h / 100 °C / Microwave irradiation 4.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / toluene / 9 h / 85 °C 5.1: pyridinium p-toluenesulfonate; methanol / 60 °C 6.1: phosphorus tribromide / dichloromethane / 0 - 20 °C 7.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C 8.1: sodium L-ascorbate; copper(ll) sulfate pentahydrate / water; <i>tert</i>-butyl alcohol / 16 h / 37 °C 8.2: 14 h / 20 °C
  • 46
  • [ 1276056-83-7 ]
  • (1S,3S)-3-((2-(5-(((3-isopropyl-1,2,4-thiadiazol-5-yl)amino)methyl)-1-methyl-1H-pyrazol-4-yl)-4-methylpyrimidin-5-yl)oxy)cyclohexane-1-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: water; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / acetonitrile / 1.5 h / 120 °C / Sealed tube; Inert atmosphere; Microwave irradiation 4.1: pyridinium p-toluenesulfonate; methanol / 60 °C 5.1: phosphorus tribromide / dichloromethane / 0 - 20 °C 6.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C 7.1: water; triphenylphosphine / tetrahydrofuran / 20 °C 8.1: N-ethyl-N,N-diisopropylamine / butan-1-ol / 2 h / 180 °C / Microwave irradiation 8.2: 20 °C
Multi-step reaction with 9 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 0 - 20 °C 2.1: potassium acetate / 1,4-dioxane / 0.08 h / Inert atmosphere 2.2: 10.08 h / 85 °C / Inert atmosphere; Sealed tube 3.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); sodium carbonate / water; acetonitrile / 1 h / 100 °C / Microwave irradiation 4.1: 1,1'-(Azodicarbonyl)dipiperidin; tributylphosphine / toluene / 9 h / 85 °C 5.1: pyridinium p-toluenesulfonate; methanol / 60 °C 6.1: phosphorus tribromide / dichloromethane / 0 - 20 °C 7.1: sodium azide / N,N-dimethyl-formamide / 1 h / 80 °C 8.1: water; triphenylphosphine / tetrahydrofuran / 20 °C 9.1: N-ethyl-N,N-diisopropylamine / butan-1-ol / 2 h / 180 °C / Microwave irradiation 9.2: 20 °C
  • 47
  • [ 1276056-83-7 ]
  • 4-bromo-5-(bromomethyl)-1-methyl-1H-pyrazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With carbon tetrabromide; triphenylphosphine In dichloromethane at 0℃; b (R)-2-methyl-A-|(4,SVl -methyl-4, 6-dihydro-l //-spiro lcvclopentalc I pyrazole-5,4,-piperidin]-4-yl]propane-2-sulfinamide, Intermediate CP Step b: The compound of (4-bromo-l-methyl-li -pyrazol-5-yl)methanol (3.00 g, 15.7 mmol) and CBr4 (6.23 g, 18.8 mmol) was added in DCM (100 mL). Then PPh3 (4.93 g, 18.8 mmol) in DCM (50 mL) was added dropwise at 0 °C and the mixture was stirred at 0 °C for 0.5 h. The reaction was quenched with brine (100 mL) and the partitioned layers were separated. The aqueous phase was extracted with DCM (100 mL x 2). The combined organic layers were washed with brine (150 mL), dried over anhydrous Na2S0 , filtered and concentrated to give a residue. The residue was purified by flash silica gel chromatography (petroleum ether : ethyl acetate = 100 : 0 to 100 : 10) to afford 4-bromo-5-(bromom ethyl)- 1- methyl- l//-pyrazole (3.20 g, 81% yield) as a colorless oil. LCMS m/z [M+H]+ = 252.8, 254.8, 256.8.
73.8% With carbon tetrabromide; triphenylphosphine In dichloromethane at 0℃; for 0.5h; 8.2 Step 2. To a solution of (4-bromo-2-methyl-pyrazol-3-yl) methanol (7.75 g, 40.6 mmol, 1 eq) in DCM (70 mL) was added CBr4(16.2 g, 48.7 mmol, 1.2 eq) followed by addition of a solution of PPh3 (12.8 g, 48.7 mmol, 1.2 eq) in DCM (2 mL) dropwise at 0 °C. The mixture was stirred at 0 °C for 0.5 h. The mixture was slowly quenched with water and extracted with EtOAc (3*100 mL). The combined organic layers were washed with brine (2*100 mL), dried over Na2SO4, filtered and concentrated in vacuum. The residue was purified by column chromatography on silica gel (PE: EA = 25: 1-3: 1) to give 4-bromo-5-(bromomethyl)-1- methyl-pyrazole (7.60 g, 29.9 mmol, 73.8% yield) as a colorless oil.1H NMR (400 MHz, DMSO-d6) δ (ppm) 7.56 (s, 1H), 4.75 (s, 2H), 3.87 (s, 3H).
73.8% With carbon tetrabromide; triphenylphosphine In dichloromethane at 0℃; for 0.5h; 8.2 Step 2. To a solution of (4-bromo-2-methyl-pyrazol-3-yl) methanol (7.75 g, 40.6 mmol, 1 eq) in DCM (70 mL) was added CBr4(16.2 g, 48.7 mmol, 1.2 eq) followed by addition of a solution of PPh3 (12.8 g, 48.7 mmol, 1.2 eq) in DCM (2 mL) dropwise at 0 °C. The mixture was stirred at 0 °C for 0.5 h. The mixture was slowly quenched with water and extracted with EtOAc (3*100 mL). The combined organic layers were washed with brine (2*100 mL), dried over Na2SO4, filtered and concentrated in vacuum. The residue was purified by column chromatography on silica gel (PE: EA = 25: 1-3: 1) to give 4-bromo-5-(bromomethyl)-1- methyl-pyrazole (7.60 g, 29.9 mmol, 73.8% yield) as a colorless oil.1H NMR (400 MHz, DMSO-d6) δ (ppm) 7.56 (s, 1H), 4.75 (s, 2H), 3.87 (s, 3H).
  • 48
  • [ 1276056-83-7 ]
  • [ 7693-46-1 ]
  • (4-bromo-1-methyl-1H-pyrazol-5-yl)methyl (4-nitrobenzene) carbonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With pyridine In tetrahydrofuran; dichloromethane at 0 - 20℃; for 16h; 16.3 Step (3) 4-bromo-1-methyl-1H-pyrazol-5-yl)methyl (4-nitrobenzene) carbonate Compound 16-5 (3g, 15.71mmol) and pyridine (3.44g, 47.13mmol) were dissolved in dichloromethane (50mL), and phenyl 4-nitrochloroformate (4.76g, 23.56mmol) was added at 0°C Into the reaction solution,Stir at room temperature overnight. Extract with dichloromethane (60 mL×2), and the combined organic phases were washed with saturated brine (40 mL),After concentration, use column chromatography to separate (wet loading,Petroleum ether/ethyl acetate = 5/1) to obtain compound 16-6 as a pale yellow solid (4.2 g, yield 75%).
  • 49
  • [ 1276056-83-7 ]
  • [ 5720-07-0 ]
  • (4-(4-methoxyphenyl)-1-methyl-1H-pyrazol-5-yl)methanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water at 100℃; Inert atmosphere; 2.3; 11.3 Step (3) (4-(4-methoxyphenyl)-1-methyl-1H-pyrazol-5-yl)methanol Compound 2-3 (800mg, 4.19mmol),4-Methoxyphenylboronic acid (760mg, 5.03mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (178mg, 025mmol) added to 1,4-dioxane (16 mL), and then add potassium carbonate (1.45 g, 10.48 mmol) in water (4 mL) under nitrogen protection, and react at 100°C overnight. Filter and spin dry the organic phase,Extract with ethyl acetate (30mL×2),After concentration, it is separated by column chromatography (PE/EA=1/1),Compound 2-5 was obtained as a brown solid (750 mg, yield 82%).
  • 50
  • [ 514816-42-3 ]
  • [ 1276056-83-7 ]
YieldReaction ConditionsOperation in experiment
93.5% With lithium aluminium hydride In tetrahydrofuran at 0℃; for 0.25h; 8.1 Step 1 To a solution of methyl 4-bromo-2-methyl-pyrazole-3-carboxylate (9.5 g, 43.4 mmol, 1 eq) in THF (100 mL) was added LiAlH4(1.65 g, 43.4 mmol, 1 eq). The mixture was stirred at 0 °C for 15 min and then slowly quenched with water (0.086 mL) followed by addition of saturated sodium hydroxide (1.65 mL) and water (4.8 mL). The reaction mixture was filtered and concentrated under reduced pressure to give (4-bromo-2-methyl-pyrazol-3-yl) methanol (7.75 g, 40.6 mmol, 93.5% yield) as a colorless oil. LCMS: 190.9 (M+1)+.
93.5% With lithium aluminium hydride In tetrahydrofuran at 0℃; for 0.25h; 8.1 Step 1 To a solution of methyl 4-bromo-2-methyl-pyrazole-3-carboxylate (9.5 g, 43.4 mmol, 1 eq) in THF (100 mL) was added LiAlH4(1.65 g, 43.4 mmol, 1 eq). The mixture was stirred at 0 °C for 15 min and then slowly quenched with water (0.086 mL) followed by addition of saturated sodium hydroxide (1.65 mL) and water (4.8 mL). The reaction mixture was filtered and concentrated under reduced pressure to give (4-bromo-2-methyl-pyrazol-3-yl) methanol (7.75 g, 40.6 mmol, 93.5% yield) as a colorless oil. LCMS: 190.9 (M+1)+.
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 1276056-83-7 ]

Bromides

Chemical Structure| 1374868-77-5

[ 1374868-77-5 ]

(4-Bromo-1,3-dimethyl-1H-pyrazol-5-yl)methanol

Similarity: 0.97

Chemical Structure| 915707-65-2

[ 915707-65-2 ]

(4-Bromo-1-methyl-1H-pyrazol-3-yl)methanol

Similarity: 0.91

Chemical Structure| 5775-86-0

[ 5775-86-0 ]

4-Bromo-1,5-dimethylpyrazole

Similarity: 0.84

Chemical Structure| 84547-84-2

[ 84547-84-2 ]

4-Bromo-1-methyl-1H-pyrazole-5-carboxylic acid

Similarity: 0.84

Chemical Structure| 1454848-83-9

[ 1454848-83-9 ]

4-Bromo-3-(hydroxymethyl)-1-methyl-1H-pyrazole-5-carbonitrile

Similarity: 0.83

Alcohols

Chemical Structure| 1374868-77-5

[ 1374868-77-5 ]

(4-Bromo-1,3-dimethyl-1H-pyrazol-5-yl)methanol

Similarity: 0.97

Chemical Structure| 915707-65-2

[ 915707-65-2 ]

(4-Bromo-1-methyl-1H-pyrazol-3-yl)methanol

Similarity: 0.91

Chemical Structure| 1454848-83-9

[ 1454848-83-9 ]

4-Bromo-3-(hydroxymethyl)-1-methyl-1H-pyrazole-5-carbonitrile

Similarity: 0.83

Related Parent Nucleus of
[ 1276056-83-7 ]

Pyrazoles

Chemical Structure| 1374868-77-5

[ 1374868-77-5 ]

(4-Bromo-1,3-dimethyl-1H-pyrazol-5-yl)methanol

Similarity: 0.97

Chemical Structure| 915707-65-2

[ 915707-65-2 ]

(4-Bromo-1-methyl-1H-pyrazol-3-yl)methanol

Similarity: 0.91

Chemical Structure| 5775-86-0

[ 5775-86-0 ]

4-Bromo-1,5-dimethylpyrazole

Similarity: 0.84

Chemical Structure| 84547-84-2

[ 84547-84-2 ]

4-Bromo-1-methyl-1H-pyrazole-5-carboxylic acid

Similarity: 0.84

Chemical Structure| 1454848-83-9

[ 1454848-83-9 ]

4-Bromo-3-(hydroxymethyl)-1-methyl-1H-pyrazole-5-carbonitrile

Similarity: 0.83