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Chemical Structure| 1153949-38-2
Chemical Structure| 1153949-38-2
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Product Details of [ 1153949-38-2 ]

CAS No. :1153949-38-2 MDL No. :MFCD18206946
Formula : C17H26BN3O2 Boiling Point : -
Linear Structure Formula :- InChI Key :-
M.W : 315.22 Pubchem ID :-
Synonyms :

Safety of [ 1153949-38-2 ]

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

Application In Synthesis of [ 1153949-38-2 ]

* 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 [ 1153949-38-2 ]

[ 1153949-38-2 ] Synthesis Path-Downstream   1~24

  • 1
  • [ 3934-20-1 ]
  • [ 1153949-38-2 ]
  • [ 1153949-40-6 ]
YieldReaction ConditionsOperation in experiment
67% With potassium phosphate In 1,4-dioxane; water at 100℃; 33.2 A mixture of 2,4-dichloropyrimidine (0.28 g, 1.9 mmol), 3-cyclopentyl-3-(4-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)-lH-pyrazol-l-yl)propanenitrile (0.500 g, 1.59 mmol), tetrakis(triphenylphosphine)palladium (100 mg, 0.1 mmol), and potassium phosphate (1.0 g, 4.8 mmol) in 1,4-dioxane (5 mL) and water (0.5 mL) was heated at 100 0C overnight. After cooling to room temperature, the mixture was diluted with EtOAc, washed with water, brine, dried over MgSO4, i concentrated. The residue was purified on silica gel, eluting with 0 to 80% EtOAc in hexanes, to give the desired product (323 mg, 67%). LCMS (M+H) 302.0.
  • 2
  • [ 269410-08-4 ]
  • [ 591769-05-0 ]
  • [ 1153949-38-2 ]
YieldReaction ConditionsOperation in experiment
81% With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 20℃;Inert atmosphere; Reflux; Racemic 3-Cyclopentyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrile (23).; To a 500 mL round bottom flask equipped with a stir bar, condenser and nitrogen inlet was charged <strong>[591769-05-0]3-cyclopentylacrylonitrile</strong> (8, a mixture of E and Z isomers, 8.46 g, 0.067 mol, 1.3 equiv), acetonitrile (242 mL, 4.64 mol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (4, 10.0 g, 0.0515 mol), and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 16.2 ml, 0.108 mol, 2.1 equiv) at room temperature. The resulting solution was then warmed to reflux, and the reaction mixture was stirred at reflux for 18 hours. When the reaction was deemed complete, the reaction mixture was allowed to cool to room temperature followed by concentration under reduced pressure. The residue was purified directly by flash column chromatography (SiO2, 0percent to 30percent ethyl acetate/hexane gradient elution) to afford 3-cyclopentyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propanenitrile (23, 13.1 g, 16.2 g theoretical, 81percent) as off-white solids. This racemic mixture was directly used for subsequent chiral column separation with out further purification. For 23: 1H NMR (DMSO-d6, 400 MHz) delta ppm 8.07 (d, 1H, J=0.53 Hz), 7.65 (s, 1H), 4.42 (td, 1H, J=19.2, 4.5 Hz), 3.14 (dd, 1H, J=9.39, 17.2 Hz), 3.08 (dd, 1H, J=4.58, 17.2 Hz), 2.31 (m, 1H), 1.75 (m, 1H), 1.62-1.32 (m, 4H), 1.29-1.01 (m, 15H); C17H26BN3O2 (MW, 315.22) LCMS (EI) m/e 316 [M++H].
73% With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 60℃; To a solution of 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (2.00 g, 0.0103 mol) in acetonitrile (30 mL) was added <strong>[591769-05-0]3-cyclopentylacrylonitrile</strong> (1.25 g, 0.0103 mol), followed by 1,8- diazabicyclo[5.4.0]undec-7-ene (1.54 mL, 0.0103 mol). The resulting mixture was stirred at 60 0C <n="54"/>overnight, then evaporated to dryness. The residue was purified on silica gel, eluting with 0 to 50percent EtOAc in hexanes, to give the desired product (2.36 g, 73percent). LCMS (M+H) 316.1.
27.5% With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 60℃; for 18h; To a solution of compound 3-b (1 g, 8.26 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.4 g, 12.39 mmol) in acetonitril (10 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (2.5 g, 16.52 mmol). The mixture was stirred at 60° C. for 18 hours. The mixture was concentrated in vacuum. To the residue was added water (50 mL), then the mixture was extracted with ethyl acetate (100 mL×3). The organic layers were combined, washed with water (60 mL×3) and saturated brine (60 mL) in sequence, dried over anhydrous sodium sulfate. The mixture was filtrated, the filtrate was concentrated in vacuum, the residue was purified by silica column chromatography (petroleum ether:ethyl acetate=3:1) to give yellow oil 3-a (715 mg, yield: 27.5percent). LC-MS (ESI): m/z=316 [M+H]+.
  • 3
  • [ 1153949-38-2 ]
  • [ 19646-07-2 ]
  • [ 1153949-49-5 ]
YieldReaction ConditionsOperation in experiment
82% With potassium phosphate In 1,4-dioxane; water at 100℃; 101.1 A mixture of 2,4-dichloro-5-methoxypyrimidine (0.68 g, 3.8 mmol), 3-cyclopentyl-3-(4-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazol-l-yl)propanenitrile (1.0 g, 3.17 mmol), tetrakis(triphenylphosphine)palladium (200 mg, 0.2 mmol), and potassium phosphate (2.0 g, 9.6 mmol) in 1,4-dioxane (9 mL) and water (0.9 mL) was heated at 100 0C overnight. After cooling to room temperature, the mixture was diluted with EtOAc, washed with water, brine, dried over MgSO/t, concentrated. The residue was purified on silica gel, eluting with 0 to 60% EtOAc-hexanes, to give the desired product (860 mg, 82%). LCMS (M+H) 331.9.
  • 4
  • [ 1780-31-0 ]
  • [ 1153949-38-2 ]
  • [ 1153949-46-2 ]
YieldReaction ConditionsOperation in experiment
78% With potassium phosphate In 1,4-dioxane; water at 100℃; 70.1 A mixture of 2,4-dichloro-5-methylpyrimidine (0.62 g, 3.8 mmol), 3-cyclopentyl-3-(4-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazol-l-yl)propanenitrile (1.0 g, 3.17 mmol), tetrakis(triphenylphosphine)palladium (200 mg, 0.2 mmol), and potassium phosphate (2.0 g, 9.6 mmol) in 1,4-dioxane (9 mL) and water (0.9 mL) was heated at 100 0C overnight. After cooling to room temperature, the mixture was diluted with EtOAc, washed with water, brine, dried over MgSO4, concentrated. The residue was purified on silica gel, eluting with 0 to 80% EtOAc-hexanes, to give the desired product (780 mg, 78%). LCMS (M+H) 316.0.
  • 5
  • [ 941685-26-3 ]
  • [ 1153949-38-2 ]
  • [ 941685-39-8 ]
YieldReaction ConditionsOperation in experiment
83.6% With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 20 - 90℃;Inert atmosphere; Racemic 3-cyclopentyl-3-{4-[7-(2-trimethylsilanylethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]pyrazol-1-yl}propionitrile (9, racemic SEM-protected compound).; Method C.; Into a 25 ml round bottom flask equipped with a stir bar, condenser, thermocouple and 3-way valve was charged 3-cyclopentyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propanenitrile (23, 0.697 g, 2.21 mmol, 1.3 equiv), <strong>[941685-26-3]4-chloro-7-[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine</strong> (3a, 0.506 g, 1.69 mmol), 1,4-dioxane (4.44 mL), water (4.44 mL), and sodium bicarbonate (NaHCO3, 0.666 g, 7.93 mmol, 4.7 equiv) at room temperature. The resulting mixture was degassed four times backfilling with nitrogen each time before tetrakis(triphenylphosphine)palladium(0) (91.6 mg, 0.079 mmol, 0.047 equiv) was added. The resulting reaction mixture was degassed four times backfilling with nitrogen each time. The reaction was then warmed to 90 C. for 2-6 h. When TLC and HPLC showed that the coupling reaction was deemed complete, the reaction mixture was allowed to cool to room temperature followed by dilution with water (5 mL) and ethyl acetate (10 mL). The two layers were separated, and the aqueous layer was back extracted with ethyl acetate (10 mL). The combined organic fractions were washed with water (10 mL) and saturated aqueous NaCl solution (10 mL), dried over magnesium sulfate (MgSO4), and concentrated under reduced pressure to give the crude product (9) as an amber oil. The crude product was purified by flash column chromatography (SiO2, 0% to 40% ethyl acetate/hexane gradient elution) to afford racemic 3-cyclopentyl-3-{4-[7-(2-trimethylsilanylethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]pyrazol-1-yl}propionitrile (9, racemic SEM-protected compound, 617 mg, 737.9 mg theoretical, 83.6% yield) as a yellow oil. For 9: 1H NMR (DMSO-d6, 400 MHz) delta ppm 8.83 (s, 1H), 8.75 (s, 1H), 8.39 (s, 1H), 7.77 (d, 1H, J=3.7 Hz), 7.09 (d, 1H, J=3.7 Hz), 5.63 (s, 2H), 4.53 (td, 1H, J=19.4, 4.0 Hz), 3.51 (t, 2H, J=8.1 Hz), 3.23 (dq, 2H, J=9.3, 4.3 Hz), 2.41 (m, 1H), 1.79 (m, 1H), 1.66-1.13 (m, 7H), 0.81 (t, 2H, J=8.2 Hz), 0.124 (s, 9H); C23H32N6OSi (MW, 436.63), LCMS (EI) m/e 437 (M++H) and m/e 459 (M++Na).
  • 6
  • [ 1153949-38-2 ]
  • [ 1146629-84-6 ]
  • [ 1236033-24-1 ]
YieldReaction ConditionsOperation in experiment
1: 99.6 % ee 2: 99.2 % ee With Chiralpak IA In hexanes; ethanol at 20℃; (R)-3-cyclopentyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrile ((R)-24) and (S)-3-cyclopentyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrile ((S)-24).; A solution of racemic 3-cyclopentyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propanenitrile (23, 13.1 g, 41.56 mmol) in a mixture of ethanol and hexanes (8:2 by volume) was injected into preparative HPLC system equipped with a chiral column (20×250 mm) packed with amylose tri(3,5-dimethylphenyl)carbamate immobilized on silicagel (Chiralpak IA) from Chiral Technologies Inc. The chiral column was eluted with mobile phase made by a mixture of ethanol (EtOH) and hexanes in a 1 to 9 volume ratio at a flow rate of 18 mL/min at room temperature. The column elution was monitored by UV at wavelength 220 nm. Under these conditions, a baseline separation of the two enantiomers was achieved and the retention times were 7.0 minutes (Peak 1, the undesired (S)-enantiomer (S)-24) and 8.3 minutes (Peak 2, the desired (R)-enantiomer (R)-24), respectively. Each injection was 0.8 mL of feed solution at a concentration of 100 mg/mL and each run cycle was 14 minutes by using stack injections. Total 164 injections were taken for this separation process. Fractions for Peak 1 (the undesired (S)-enantiomer, (S)-24) and Peak 2 (the desired (R)-enantiomer, (R)-24) were collected separately from each injection, and fractions collected for each peak were concentrated under reduced pressure. The residue from each evaporator was further dried under high vacuum to constant weight to afford (R)-3-cyclopentyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrile ((R)-24, 6.19 g, 6.55 g theoretical, 94.5% yield) from Peak 2 as off-white solids and (5)-3-cyclopentyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrile ((S)-24, 6.08 g, 6.55 g theoretical, 92.8% yield) from Peak 1 as off-white solids.A chiral HPLC method was developed for chiral purity evaluation of both enantiomers of compound 24 ((R)-24 and (S)-24) by using a Chiralpak IA column (4.6×50 mm, 5 μm) purchased from Chiral Technologies, Inc. Two enantiomers ((R)-24 and (S)-24) are separated with a resolution greater than 3.0 by using a mobile phase made from 15% ethanol and 85% hexanes at room temperature with a flow rate of 1 mL/min. The UV detection wavelength is 220 nm. The retention times are 6.4 minutes for (S)-24 and 7.6 minutes for (R)-24, respectively.The quality of each enantiomer separated by preparative chiral HPLC including chemical purity (HPLC area %) and chiral purity (chiral HPLC area %) was analyzed and their structures are confirmed by NMRs and LC/MS. For (R)-24: achiral purity (98.8 area % by HPLC detected at 220 nm); chiral purity (99.8 area % by chiral HPLC; 99.6% ee); 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.07 (d, 1H, J=0.53 Hz), 7.65 (s, 1H), 4.42 (td, 1H, J=19.2, 4.5 Hz), 3.14 (dd, 1H, J=9.39, 17.2 Hz), 3.08 (dd, 1H, J=4.58, 17.2 Hz), 2.31 (m, 1H), 1.75 (m, 1H), 1.62-1.32 (m, 4H), 1.29-1.01 (m, 15H); C17H26BN3O2 (MW, 315.22) LCMS (EI) m/e 316 (M++H). For (S)-24: achiral purity (98.6 area % by HPLC detected at 220 nm); chiral purity (99.6 area % by chiral HPLC; 99.2% ee); 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.07 (d, 1H, J=0.53 Hz), 7.65 (s, 1H), 4.42 (td, 1H, J=19.2, 4.5 Hz), 3.14 (dd, 1H, J=9.39, 17.2 Hz), 3.08 (dd, 1H, J=4.58, 17.2 Hz), 2.31 (m, 1H), 1.75 (m, 1H), 1.62-1.32 (m, 4H), 1.29-1.01 (m, 15H); C17H26BN2O2 (MW, 315.22) LCMS (EI) m/e 316 [M++H].
  • 7
  • [ 1153949-38-2 ]
  • [ 1146629-75-5 ]
  • [ 1236033-05-8 ]
YieldReaction ConditionsOperation in experiment
88.6% With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 20 - 82℃;Inert atmosphere; Racemic (4-(1-(2-Cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate (20).; Method B.; Into a 50 ml round bottom flask equipped with a stir bar, condenser and 3-way valve connected to nitrogen and vacuum was charged <strong>[1146629-75-5](4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate</strong> (3f, 700 mg, 2.61 mmol), 3-cyclopentyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propanenitrile (23, 935 mg, 2.97 mmol, 1.13 equiv), 1,2-dimethoxyethane (DME, 10 mL, 96 mmol), water (5 mL, 0.28 mol) and potassium carbonate (K2CO3, 1.82 g, 7.84 mmol, 3.0 equiv) at room temperature. The resulting reaction mixture was degassed three times back filling with nitrogen each time before being charged tetrakis(triphenylphosphine)palladium(0) (30 mg, 0.026 mmol, 0.010 equiv). The resulting reaction mixture was degassed four times back filling with nitrogen each time and then warmed to 82 C. The reaction mixture was stirred at 82 C. for 6 hours. When the reaction was deemed complete, the reaction mixture was cooled to room temperature before being diluted with ethyl acetate (45 mL) and water (10 mL). The resulting mixture was stirred until the majority of solids had gone into solution. The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×25 mL). The combined organic fractions were washed with aqueous brine (2×25 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (SiO2, 0-50% ethyl acetate/hexane gradient elution) to afford racemic 4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate (20, 0.97 g, 1.1 g theoretical, 88.6% yield) as colorless oil, which solidified upon standing at room temperature in vacuo. For 20: 1H NMR (CDCl3, 300 MHz) delta 8.85 (s, 1H), 8.29 (s, 1H), 8.27 (s, 1H), 7.45 (d, 1H, J=3.8 Hz), 6.73 (d, 1H, J=3.8 Hz), 6.22 (s, 2H), 4.23 (ddd, 1H, J=10.0, 8.6, 4.0 Hz), 3.10 (dd, 1H, J=17.0, 8.6 Hz), 2.92 (dd, 1H, J=17.0, 4.0 Hz), 2.56 (m, 1H), 2.0-1.25 (m, 8H), 1.12 (s, 9H); C23H28N6O2 (MW, 420.51), LCMS (EI) m/e 421 (M++H).
  • 8
  • [ 1269823-10-0 ]
  • [ 73183-34-3 ]
  • [ 1153949-38-2 ]
YieldReaction ConditionsOperation in experiment
With potassium acetate In 1,4-dioxane at 120℃; for 3h; microwave; To a degassed solution of 3 -cyclopentyl-3 -(4-iodo- 1 H-pyrazol- 1 -yl)propanenitrile 34f(0.43 g, 1.35 mmol) in anhydrous 1,4-dioxane (4.0 mL, 51 mmol) was added 4,4,4',4',5,5,5,,5'- octamethyl-2,2'-bi(l,3,2-dioxaborolane) 34g (0.366 g, 1.43mmol),tetrakis(triphenylphosphine)palladium(0) (47 mg, 0.041 mmol) and potassium acetate (0.41 g, 4.06 mmol) and heated at 120 °C via microwave for 3 hour. The reaction mixture was concentrated in vacuum and the residue obtained was purified by flash column chromatography (silica gel 24 g, eluting with 0-50% ethyl acetate in hexane) to furnish 3-cyclopentyl-3-(4- (4,4,5, 5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazol-l-yl)propanenitrile 34h (0.32 g) which was contaminated with 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(l,3,2-dioxaborolane) 34g. The reaction mixture was used as such for next step assuming 50% purity.
  • 9
  • [ 872-53-7 ]
  • [ 1153949-38-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium <i>tert</i>-butylate / tetrahydrofuran / 49 h / 0 - 20 °C 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 20 °C 3: potassium acetate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane / 3 h / 120 °C / microwave
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 0.5 h / 0 °C / Inert atmosphere 1.2: 1 h / 0 - 20 °C / Inert atmosphere 2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 18 h / 60 °C
  • 10
  • [ 591769-05-0 ]
  • [ 1153949-38-2 ]
  • 11
  • [ 1153949-38-2 ]
  • [ 1269823-06-4 ]
  • [ 1269823-09-7 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In 1,4-dioxane at 100℃; for 48h; Inert atmosphere; To a solution of (4-chloro-7H-pyrrolo[2,3-c]pyridazin-7-yl)methyl pivalate 32a (0.21 g, 0.77 mmol) in 1,4-dioxane (5 mL), was added 3-cyclopentyl-3-(4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)-lH-pyrazol-l-yl)propanenitrile 34h (0.32 g , from above step)tetrakis(triphenylphosphine)palladium(0) (0.035 g, 0.031 mmol) and solid potassium carbonate (0.4 g, 3 mmol, 3.0 equiv) at room temperature. The resulting reaction mixture was degassed and heated at 100 °C for 48 h. The reaction mixture was neutralized with glacial acetic acid, diluted with water (10 ml) and ethyl acetate (10 ml). The reaction mixture was filtered to remove insoluble residues. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2 x 25 mL). The combined organic layers were washed with brine (25 mL), dried, filtered and concentrated in vacuum. The residue obtained was purified by flash column chromatography(silica gel 25 g, eluting with 0 - 100% ethyl acetate/methanol (9:1) in hexane) to furnish (4-(l-(2-cyano-l-cyclopentylethyl)-lH-pyrazol-4-yl)-7H-pyrrolo[2,3-c]pyridazin-7- yl)methyl pivalate 34i (0.025 g, 6%) as a colorless oil; 1H NMR (300 MHz, CDC13) δ 9.16 (s, 1H), 8.12 (s, 1H), 8.09 (s, 1H), 7.74 (d, J= 3.7, 1H), 6.73 (d, J= 3.7, 1H), 6.44 (s, 2H), 4.35 - 4.22 (m, 1H), 3.14 (dd, J= 8.5, 17.0, 1H), 2.96 (dd, J= 3.9, 17.0, 1H), 2.61 (dd, J= 7.4, 17.0, 1H), 1.96 (m, 1H), 1.82 - 1.48 (m, 6H), 1.33 (m, 1H), 1.15 (s, 9H); MS (ES+) 421.05 (M+l), 443.03 (M+23), 863.11 (2M+23), (ES-) 455.07 (M+35).
  • 12
  • [ 1153949-38-2 ]
  • [ 1269823-06-4 ]
  • [ 1269823-08-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane / 48 h / 100 °C / Inert atmosphere 2: sodium hydroxide / water; methanol / 3 h / 20 °C
  • 13
  • [ 16234-14-3 ]
  • [ 1153949-38-2 ]
  • C17H16ClN5S [ No CAS ]
YieldReaction ConditionsOperation in experiment
40.7% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,4-dioxane; water at 80℃; for 16h; Inert atmosphere; 3 Preparation of Compound 3 Under nitrogen, to a suspension of compound 3-a (715 mg, 2.27 mmol), 2,4-dichlorotheino[3,2-d]pyrimidine (465 mg, 2.27 mmol) and sodium carbonate (72 mg, 6.80 mmol) in 1,4-dioxane (4 mL) and water (4 mL) was added Pd(dppf)Cl2 (233 mg, 0.28 mmol). The mixture was stirred at 80° C. for 16 hours. The mixture was concentrated, and to the residue was added water (20 mL). Then the mixture was extracted with methylene chloride (20 mL×3), the organic layers were combined, washed with water (60 mL×3) and saturated brine (60 mL) in sequence, and then dried over anhydrous sodium sulfate, filtrated. The filtrate was concentrated in vacuum, and the residue was purified by silica column chromatography (petroleum ether:ethyl acetate=2:1) to give light yellow solid 3 (330 mg, yield: 40.7%). LC-MS (ESI): m/z=358 [M+H]+.
  • 14
  • [ 1153949-38-2 ]
  • 3-cyclopentyl-3-(4-(2-(phenylamino)thieno[3,2-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / 16 h / 80 °C / Inert atmosphere 2: toluene-4-sulfonic acid / 2-methyl-propan-1-ol / 16 h / 110 °C
  • 15
  • [ 1153949-38-2 ]
  • 3-cyclopentyl-3-(4-(2-(pyrimidin-5-ylamino)thieno[3,2-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / 16 h / 80 °C / Inert atmosphere 2: toluene-4-sulfonic acid / 2-methyl-propan-1-ol / 16 h / 110 °C
  • 16
  • [ 885500-55-0 ]
  • [ 1153949-38-2 ]
  • ethyl 4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
23% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,2-dimethoxyethane; water; at 82℃; for 12h;Inert atmosphere; A mixture of <strong>[885500-55-0]ethyl 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carboxylate</strong> (0.075 g, 0.33 mmol), 3-cyclopentyl-3-(4-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)-1H-pyrazol-1-yl) propanenitrile (0.12 g, 0.38 mmol,) and potassium carbonate (0.14 g, 1.0 mmol) in 1,2-dimethoxyethane:water (7:3 mL) was degassed with argon for about 15 minutes. Then tetrakis(triphenylphosphine)palladium(0) (10 mg, 0.004 mmol) was added and the resulting mixture was heated to 82 C. for 12 hours. After cooling to ambient temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The crude material was purified using flash chromatography (50% ethyl acetate/hexane) to provide ethyl 4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate as an off-white solid (0.03 g, 23% yield): 1H NMR (400 MHz, DMSO-d6) delta 11.98 (s, 1H), 8.53 (s, 1H), 8.23 (s, 1H), 7.70 (s, 1H), 7.56 (t, J=2.8 Hz, 1H), 6.52 (t, J=1.6 Hz, 1H), 4.49-4.67 (m, 1H), 4.17-4.25 (m, 2H), 3.03-3.22 (m, 2H), 2.34-2.39 (m, 1H), 1.76-1.89 (m, 1H), 1.43-1.55 (m, 4H), 1.22-1.45 (m, 3H), 1.14-1.22 (m, 3H); MS (ES) m/z 378.1 (M+H).
  • 17
  • [ 1153949-38-2 ]
  • ethyl 4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate [ No CAS ]
  • ethyl 4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / 1,2-dimethoxyethane; water / 12 h / 82 °C / Inert atmosphere 2: Resolution of racemate
  • 18
  • [ 1153949-38-2 ]
  • isopropyl 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carboxylate [ No CAS ]
  • isopropyl 4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
35% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,2-dimethoxyethane; water at 82℃; for 16h; Inert atmosphere; Sealed tube; 2.2 Step 2:
Preparation of Isopropyl 4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate To a stirred mixture of ethyl 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (0.3 g, 1.25 mmol), racemic-3-cyclopentyl-3-(4-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)-1H-pyrazol-1-yl) propanenitrile (0.39 g, 1.25 mmol) and potassium carbonate (0.520 g, 3.77 mmol) in 1,2-dimethoxyethane:water (3 mL:1.5 mL) was added tetrakis(triphenylphosphine)palladium(0) (14 mg, 0.012 mmol) under an argon atmosphere and the mixture heated to 82° C. for 16 hours in a sealed tube. After cooling to ambient temperature, the reaction mixture was diluted with water and extracted in to ethyl acetate. The organic layer was washed with water, saturated sodium bicarbonate and brine. The organic layer was dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The crude material was purified directly by using flash chromatography (32% ethyl acetate/hexane) to provide isopropyl 4-(1-(2-cyano-1-cyclopentylethyl)-H-pyrazol-4-yl)-H-pyrrolo[2,3-b]pyridine-5-carboxylate as an off-white solid (0.170 g, 35% yield): MS (ES) m/z 392.3 (M+H).
  • 19
  • [ 1153949-38-2 ]
  • isopropyl 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carboxylate [ No CAS ]
  • isopropyl 4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate [ No CAS ]
  • isopropyl 4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / 1,2-dimethoxyethane; water / 16 h / 82 °C / Inert atmosphere; Sealed tube 2: Resolution of racemate
  • 20
  • (2E)-3-cyclopentylprop-2-enenitrile [ No CAS ]
  • [ 269410-08-4 ]
  • [ 1153949-38-2 ]
YieldReaction ConditionsOperation in experiment
33% With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile for 18h; Reflux; 1.1 Step 1:
Preparation of racemic-3-cyclopentyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrile A solution of (E)-3-cyclopentylacrylonitrile (0.81 g, 6.70 mmol), 4-(4,4,5,5-tetra-methyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.0 g, 5.14 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (1.6 mL, 10.81 mmol) in acetonitrile (15 mL) was heated to reflux for 18 hours. After cooling to ambient temperature, the reaction mixture was concentrated in vacuo and the crude material was purified by flash chromatography (30% ethyl acetate/hexane) to provide 3-cyclopentyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrile as a viscous oil (0.54 g, 33% yield): MS (ES) m/z 316.2 (M+H).
  • 21
  • [ 1153949-38-2 ]
  • 4-bromo-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]
  • [ 941688-05-7 ]
YieldReaction ConditionsOperation in experiment
73% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 120℃; for 12h; Inert atmosphere; Sealed tube;
  • 22
  • [ 479633-63-1 ]
  • [ 1153949-38-2 ]
  • 3-cyclopentyl-3-(4-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 80℃; for 4h; Inert atmosphere; 1.1 1.3-cyclopentyl-3-(4-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1- yl)propanenitrile(Compound 4)Preparation Mix compound 2 (10g, 32.5mmol, 1eq) and compound 3 (12.3g, 39.0mmol, 1.2eq), add 100ml of dioxane, 50ml of water, potassium carbonate (17.9g, 0.13mol, 4eq), and replace with nitrogen. ; Add tetrakis (triphenylphosphine) palladium (0.2g, 2%wt), replace with nitrogen, and heat to 80°C for 4h. TLC detected that compound 2 was almost completely consumed, and the temperature was cooled down. The reaction solution was poured into 100 ml ethyl acetate and 100 ml water for quenching, stirred for 1 h, allowed to stand for separation, and the organic layer was washed with saturated sodium chloride (100 ml), dried over anhydrous sodium sulfate, and concentrated. The remaining ethyl acetate and n-hexane were refined to obtain about 12 g of off-white solid 4 (yield 81.0%).
  • 23
  • [ 1153949-38-2 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 4 h / 80 °C / Inert atmosphere 2.1: acetonitrile / 60 °C 3.1: sodium hydroxide / water; methanol / 2 h / 20 °C 3.2: 1 h
  • 24
  • [ 1153949-38-2 ]
  • (R)-3-cyclopentyl-3-(4-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile dibenzoyltartaric acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 4 h / 80 °C / Inert atmosphere 2: acetonitrile / 60 °C
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