Structure of 1009033-87-7
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CAS No. : | 1009033-87-7 |
Formula : | C17H20BNO2 |
M.W : | 281.16 |
SMILES Code : | CC1(C)OB(OC1(C)C)C1=CC=C(C=C1)C1=CC=NC=C1 |
MDL No. : | MFCD12828171 |
InChI Key : | PTNMCYWJKRZCDE-UHFFFAOYSA-N |
Pubchem ID : | 58526497 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 21 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.35 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 86.15 |
TPSA ? Topological Polar Surface Area: Calculated from |
31.35 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.46 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.05 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.89 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.9 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.26 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.05 |
Solubility | 0.0248 mg/ml ; 0.0000883 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.8 |
Solubility | 0.0446 mg/ml ; 0.000158 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.14 |
Solubility | 0.000205 mg/ml ; 0.000000728 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
Yes |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
Yes |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.56 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.87 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | A 100 mL sealed tube was charged with 4-(4-bromophenyl)pyridine (0.9 g, 3.8mmol), bis(pinacolato)diboron (1.17 g, 4.61 mmol), potassium acetate (0.745 g, 7.6mmol) and 1-4 dioxane (10 mL). The reaction mixture was purged with argon for 30mm. Then, Pd(dppf)C12 (0.75 g, 0.05 eq) was added and heated at 100 00 over night.After cooing, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous Na2SO4. The organic layer was concentrated under vacuo to yield crude product, which was purified by combif lash to yield title compound (1.0 g, 100.0percent). LCMS: (M+H) = 282.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With caesium carbonate;palladium diacetate; XPhos; In tetrahydrofuran; for 22h;Inert atmosphere; Reflux; | In a stream of argon, 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxabororan-2-yl)phenyl]pyridine (420 mg), 2,4-bis(5-chlrobiphenyl-3-yl)-6-phenyl-1,3,5-triazine (263 mg), cesium carbonate (485 mg), palladium acetate (5.6 mg) and 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (23.7 mg) were suspended in tetrahydrofuran (15 mL), and the suspension was refluxed for 22 hours. The reaction mixture was left to stand at room temperature, and then low-boiling ingredients were distilled away under a reduced pressure. Methanol was added to the obtained solid. The solid precipitate was recovered by filtration, and the obtained crude product was purified by silica gel chromatography using a methanol/chloroform (1:100 - 1:50) mixed liquid as a developing solvent to give 232 mg of the target 6-phenyl-2,4-bis[4-(4-pyridyl)-1,1':3',1'-terphenyl-5'-yl]-1,3,5-triazine as a white powder (yield: 61%). 1H-NMR (CDCl3) :delta7.49(brt,J=7.1Hz,2H) 7.57(d,J=7.5Hz, 4H), 7.61-7.66(m,7H),7.82-7.86(m,8H),7.94(d,J=8.5Hz,4H),8.10(t,J= 1.7Hz,2H),8.73(dd,J=4.5,1.6Hz,4H),8.84(brdd,J=7.7,1.7Hz,2H), 9.04(d,J=1.7Hz,4H). 13C-NMR(CDCl3) :delta121.5(CH*4),126.5(CH*2) ,127.1(CH*2) ,127.4 (CH*4),127.6(CH*4),127.9(CH*2),128.1(CH*4),128.7(CH*2),129.0 (CH*4),129.1(CH*2),130.0(CH*2),132.8(CH),136.1(quart.),137.5 (quart.*2),137.6(quart.*2),140.7(quart.*2),141.4(quart.*2), 141.6(quart.*2),142.6(quart.*2),147.8(quart.*2),150.4(CH*4), 171.8(quart.*2),171.9(quart.). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With caesium carbonate; XPhos;palladium diacetate; In tetrahydrofuran; for 87h;Inert atmosphere; Reflux; | In a stream of argon, 0.40 g (0.81 mmol) of 2-(3,5-dibromophenyl)-4,6-di-p-tolylpyrimidine, 0.48 g (1.70 mmol) of 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxabororan-2-yl)phenyl]-pyridine, 0.55 g (1.70 mmol) of cesium carbonate, 7 mg (0.032 mmol) of palladium acetate and 31 mg (0.065 mmol) of 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl were suspended in 20 mL of tetrahydrofuran, and the obtained suspension was heated under reflux for 87 hours. The reaction mixture was cooled to room temperature, and was then distilled under a reduced pressure to remove all volatile materials. Methanol was added to the concentrate and the thus-deposited solid was collected by filtration. The thus-obtained crude product was purified by silica gel chromatography using a chloroform/methanol (100:1) mixed solvent as an eluent to give 0.30 g of the target 2-[4,4"-di(4-pyridyl)-1,1' :3',1"-terphenyl- 5'-yl]-4,6-di-p-tolylpyrimidine as a white solid (yield: 58%). 1H-NMR(CDCl3):delta2.50(s,6H),7.41(d,J=8.0Hz,4H),7.63(dd,J=4.5, 1.5Hz,4H),7.84(d,J=8.3Hz,4H),7.95(d,J=8.3Hz,4H),8.03(t,J=1.8Hz, 1H),8.05(s,1H),8.24(d,J=8.0Hz,4H),8.73(dd,J=4.5,1.5Hz,4H),9.02(d, J=1.8Hz,2H). 13C-NMR(CDCl3):delta21.6(CH3),31.0(CH3),110.1(CH),121.5(CH×4), 126.7(CH×2),127.3(CH×4),127.5(CH×4),128.2(CH×4),129.7(CH×4),134.7 (quart.×2),137.3(quart.×2),139.9(quart.),141.2(quart.×2),141.3 (quart.×2),142.0(quart.×2),147.9(quart.×2),150.4(CH×4), 164.0(quart.),164.7(quart.×2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 90℃; for 12h; | 15.0 g (32.2 mmol) of the intermediate product (N), 10.9 g (38.6 mmol) of <strong>[1009033-87-7]4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyridine</strong>, and 1.1 g (1.0 mmol) of tetrakis(triphenylphosphine)palladium [Pd(PPh3)4] were dissolved in 300 mL of a tetrahydrofuran (THF) solvent. A solution in which 8.9 g (64.4 mmol) of potassium carbonate (K2CO3) was dissolved in 100 ml of water was added thereto, and they were reacted at 90 C. for 12 hours. The solvent was removed under a reduced pressure, and the reaction product was rinsed with water and methanol. The residues were recrystallized with toluene, precipitated crystals were separated by a filter, rinsed with toluene, and dried to provide a white solid of a compound in 17.0 g (yield: 90%). (calculation value: 584.71, measurement value: MS[M+1] 585.01) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 90℃; for 12h; | 20.0 g (23.6 mmol) of the intermediate product (N), 18.1 g (64.4 mmol) of <strong>[1009033-87-7]4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyridine</strong>, and 1.5 g (1.3 mmol) of tetrakis(triphenylphosphine)palladium [Pd(PPh3)4] were dissolved in 400 ml of a tetrahydrofuran (THF) solvent. A solution in which 11.9 g (85.8 mmol) of potassium carbonate (K2CO3) was dissolved in 200 ml of water was added thereto, and then they were reacted at 90 C. for 12 hours. The solvent was removed under a reduced pressure, and the reaction product was rinsed with water and methanol. The residues were recrystallized with toluene, precipitated crystals were separated by a filter, rinsed with toluene, and dried to provide a white solid of a compound in 16.0 g (yield: 64%). (calculation value: 584.71, measurement value: MS[M+1] 585.01) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: Step-ii: 1-(2-fluorobenzyl)-4-( 4,4,5 ,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H-pyrazole1-(2-fluorobenzyl)-4-iodo-1H-pyrazole (2.25 g, 7.4 mmol) and bispinocalatodiboron (2.07 g,8.2 mmol) were added to a solution of DMSO (20 ml) previously purged with argon (10min). The reaction mixture was purged with argon for a further 15mins, followed by the10 addition of potassium acetate (2.19 g, 22.3 mmol) andbis(triphenylphosphine)palladium(II)dichloride (261 mg, 0.3725 mmol). The resultingmixture was heated to reflux at 80 oc overnight. The reaction was monitored by TLC (40%ethyl acetate in hexane). The reaction mixture was cooled and diluted with ethyl acetate (100ml) and filtered over celite bed and the filtrate was washed with cold water (2x100 ml). The15 organic layer was dried over NazS04, and concentrated under reduced pressure to afford 2.3 gof the crude product which was taken as such for next reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70.5% | Using similar reaction conditions as described in step-ii of example-1, 5-bromo-3-(1-(3-5 fluorobenzyl)-3,5-dimethyl-1 H-pyrazol-4-yl)-l-tosyl-1H-pyrrolo[2,3-b] pyridine (step-i ofexample-14) (150mg, 0.27mmol) was coupled with <strong>[1009033-87-7]4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyridine</strong> (intermediate 45) (91.44mh, 0.32mmol) in sodiumcarbonate (85.86, 0.81mmol), toluene/ethanol/water (5/5/2ml). This afforded 120mg (70.5%yield) of the titled compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18.1% | A 100 mL sealed tube charged with intermediate 37 (1 .0 g, 3.5 mmol), intermediate 3(0.86 g, 3.1 mmol), potassium phosphate tribasic (2.0 g, 10.5 mmol), 1, 4-dioxane (10mL) and water (3 mL) was degassed with nitrogen for 15 mm. To the above solutionPd(PPh3)4 (0.2 g, 0.05 eq) was added and heated at 100 00 over night. After cooling,the reaction mixture was diluted with water and extracted by using ethyl acetate. The combined organic layer was dried and concentrated. The product was purified by combi-flash to yield title compound (0.2 g, 18.1%) as a brown solid. LOMS: (M+H) = 321.0;1H NMR: (DMSO-d6, 300MHz) 610.61(s, 1H), 8.66- 8.67(d, 2H), 7.88-7.91(d,2H), 7.77- 7.78 (d, 2H), 7.53-7.56 (d, 2H), 7.30 (5, 1 H), 6.97 (5, 1 H), 3.54 (5, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | A microwave vial was charged with intermediate 1(0.2 g, 0.9 mmol), intermediate 37(0.24 g, 0.9 mmol) and DMF: 1 ,4-Dioxane: water (2 mL: 0.5 mL: 0.5 mL) mixture. To the above solution potassium phosphate (tribasic) (0.55 g, 1 .8 mmol) was added and the vial was degasified for 15 mm after which Pd(PPh3)4 (0.05 g, 0.03 eq) was added and heated at 150 00 for 30 mm. After cooling, the reaction mixture diluted with water and extracted by using ethyl acetate. The combined organic layer was dried andconcentrated. The product was purified by chromatography to yield title compound (0.075 g, 27.0%) as a brown solid. LCMS: (M+H) = 305.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | <a> Synthesis of Intermediate (44- 1) A flask was charged with 4,6-dichloropyridine (596 mg, 4.0 mmol), followed by being purged with argon gas. To the flask, thereafter, dioxane (60 mL), which had been deaerated with argon gas, 4-(4-pyridyl)phenyl boronic acid pinacol ester (4.0 mmol, 2.26 g), bis(triphenylphosphine) palladium(II) dichloride (0.3 mmol, 210 mg) were added. After bubbling the solution with argon gas, 2M K2CO3 (20 mL) was added, and the resultant was heated and stirred at 50C for 4 hours. Subsequently, 4-(4,4, 5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)pyridine (4 mmol, 820 mg) was added, and the resulting mixture was heated and stirred at 100C for 4 hours. The resultant was filtered with Celite, and water and chloroform were added to the filtrate to separate an organic layer. Thereafter, a water layer was extracted 5 times with chloroform. The combined organic layer was washed with saturated salt water, followed by drying with sodium sulfate to condensate the filtrate, to thereby obtain a crude product. The crude product was purified by silica-gel column chromatography (eluenf- chloroform/methanol = 93/7), and the obtained solids were dispersed and washed in chloroform/hexane. The solids were collected by filtration, and the obtained solids were vacuum dried to thereby obtain an intermediate (44- 1) as pale yellow solids (the yielded amount: 892 mg, the yield: 72%). NMR (500 MHz, CDCI3, delta) : 9.42 (d, J = 1.7 Hz, 1H), 8.85(dd, Ji = 5.8 Hz, J2 = 1.8 Hz, 2H), 8.73(dd, Ji = 6.3 Hz, J2 = 1.7 Hz, 2H), 8.31 (d, J =8.6 Hz, 2H), 8.2l(d, J = 1.7 Hz, 1H), 8.04 (dd, Ji = 6.3 Hz, J2 = 1.7 Hz, 2H), 7.84 (d, J =6.9 Hz, 2H), 7.59 (d, Ji = 5.8 Hz, J2 = 1.8 Hz, 2H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | <a> Synthesis of Intermediate (80- 1) Intermediate (80" l) A flask was charged with 2,4,6-trichloropyridine (732 mg, 4.0 mmol), followed by being purged with argon gas. To the flask, thereafter, dioxane (60 niL), which had been deaerated with argon gas, 4-(4-pyridyl)phenyl boronic acid pinacol ester (8.0 mmol, 2.26 g), and bis(triphenylphosphine)palladium(II) dichloride (0.3 mmol, 210 mg) were added. After bubbling the solution with argon gas, 2M K2CO3 (20 mL) was added, and the resultant was heated and stirred at 50C for 4 hours. Next, 4-4,4, 5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)pyridine (4 mmol, 820 mg) was added and the resultant was heated and stirred at 100C for 4 hours. Subsequently, the resultant was filtered with Celite, and water and chloroform were added to the filtrate to separate an organic layer. Thereafter, a water layer was extracted 5 times with chloroform. The combined organic layer was washed with saturated salt water, followed by drying with sodium sulfate to condensate the filtrate, to thereby obtain a crude product. The crude product was purified by silica-gel column chromatography (eluent: chloroform/methanol = 93/7), and the obtained solids were dispersed and washed in chloroform/hexane. The solids were collected by filtration, and the obtained solids were vacuum dried to thereby obtain an intermediate (80- 1) as pale yellow solids (the yielded amount: 1.19 g, the yield: 64% H NMR (500 MHz, CDCI3, delta) : 8.87 (dd, Ji = 4.7 Hz, J2 = 1.7 Hz, 2H), 8.75 (dd, Ji = 4.0 Hz, J2 = 1.7 Hz, 4H), 8.58 (dd, Ji = 4.7 Hz, J2 = 1.7 Hz, 2H), 8.45 (dt Ji = 8.0 Hz, J2 = 1.7 Hz, 4H), 8.21 (s, 1H), 7.88 (dd, Ji = 8.6 Hz, J2 = 1.7 Hz, 4H), 7.61 (dd, Ji = 4.7 Hz, J2 = 1.7 Hz, 4H) | |
61% | 2, 4, 6-trichloropyrimidine (732 mg, 4.0 mmol) was placed in a flask,After substitution with argon gas,Dioxane (60 mL) degassed with argon gas,4- (4-pyridyl) phenylboronic acid pinacol ester (8.0 mmol, 2.26 g) represented by the following structural formula (28)Bis (triphenylphosphine) palladium (II) dichloride (0.3 mmol, 210 mg) was added.After bubbling the solution with argon gas,2 M K 2 CO 3 (20 mL) was added,And the mixture was heated and stirred at 50 C. for 4 hours.Then 4- (4,4,5,5-tetramethyl-1,3,2-dioxeSabololan-2-yl) pyridine(4 mmol, 820 mg) was added,And the mixture was heated and stirred at 100 C. for 4 hours.Subsequently, the contents were filtered through celite, water and chloroform were added to the filtrate to separate the organic layer,The aqueous layer was extracted with chloroform.The combined organic layer was dried over sodium sulfate and the filtrate was concentrated to give a crude product.This was purified by silica gel chromatography (developing solvent: chloroform / methanol)The solid obtained after the concentration was dried under vacuum,The target compound was obtained as a pale yellow solid (yield 1.13 g, yield 61%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; water; at 20 - 50℃; for 30h;Inert atmosphere; | <a> Synthesis of Intermediate (9- 1) Intermediate (9- 1) A flask was charged with 3.0 g of 2,4,6-trichloro- l,3, 5-triazine, and was purged with argon gas. To the flask, thereafter, dioxane (100 mL), phenylpyridine boronic acid pinacol ester (18.5 g), and PdCl2(PPh3)2 (600 mg) were added. To the mixture, 2M K2CO3 (17 mL) was added, and the resulting mixture was stirred for 14 hours at 50C, followed by stirring for 16 hours at room temperature. The resultant was filtered with Celite, and water and chloroform were added to the filtrate to separate an organic layer. Thereafter, a water layer was extracted 3 times with chloroform. The combined organic layer was washed with saturated salt water, followed by drying with sodium sulfate to condensate the filtrate, to thereby obtain a crude product (the yielded amount: 7.5 g) . The crude product was purified by silica-gel column chromatography (eluent^ CHC methanol = 93/7), and the obtained solids were dispersed and washed in chloroform/hexane. The solids were collected by filtration, and the obtained solids were vacuum dried to thereby obtain a target (the yielded amount: 6.9 g, the yield'- 78%) as white solids. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 90℃; for 12h; | 20.0 g (44.3 mmol) of the intermediate product (F), 29.9 g (106.4 mmol) of <strong>[1009033-87-7]4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyridine</strong> and 2.6 g (2.2 mmol) of tetrakis(triphenylphosphine)palladium [Pd(PPh3)4] were dissolvedin 400 ml of tetrahydrofuran (THF) as a solvent, a solution obtained by dissolving 24.5 g (177.3 mmol) of potassiumcarbonate (K2CO3) in 200 ml of water was added thereto, and the mixture was reacted at 90 C for 12 hours. A crystalformed therein was separated with a filter and washed with water and methanol. The residue was recrystallized withchloroform, and the precipitated crystal was separated with a filter, washed with methanol and dried, obtaining 20.0 gof a yellow solid compound (a yield: 66 %). (calculation value: 688.82, measurement value: MS[M+1] 689.12) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 90℃; for 12h; | 10.0 g (50.2 mmol) of 2,4-dichloroquinazoline, 31.1 g (110.5 mmol) of <strong>[1009033-87-7]4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyridine</strong> and 2.9 g (2.5 mmol) of tetrakis(triphenylphosphine)palladium [Pd(PPh3)4] were dissolvedin 200 ml of tetrahydrofuran (THF) as a solvent, a solution obtained by dissolving 27.8 g (200.9 mmol) of potassiumcarbonate (K2CO3) in 100 ml of water was added thereto, and the mixture was reacted at 90 C for 12 hours. Afterremoving the solvent under a reduced pressure, the obtained reactant was washed with water and methanol. The residuewas recrystallized with toluene, and the precipitated crystal was separated with a filter, washed with methanol and dried,obtaining 15.0 g of a white solid compound (a yield: 68 %). (calculation value: 436.51, measurement value: MS[M+1]436.86) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; at 100℃; for 8h;Inert atmosphere; | 4,6-Dichloropyrimidine (1.49 g, 10 mmol) was placed in a flask, and after substitution with argon gas, dioxane (120 mL) degassed with argon gas,4- (4-pyridyl) phenylboronic acid pinacol ester (20 mmol, 5.6 g),Bis (triphenylphosphine) palladium (II) dichloride (0.2 mmol, 140 mg) was added.After bubbling the solution with argon gas, 2 M aqueous potassium carbonate solution (40 mL) was added,And the mixture was heated and stirred at 100 C. for 8 hours.The contents were filtered through celite, water and chloroform were added to the filtrate to separate the organic layer, and the aqueous layer was extracted with chloroform.The combined organic layer was dried over sodium sulfate and the filtrate was concentrated to give a crude product.This was purified by silica gel chromatography (developing solvent: chloroform / methanol), the obtained solid was washed with chloroform / hexane, and the solid collected by filtration was vacuum-dried to obtain the desired product as a pale yellow solid (yield 1 .58 g, yield 41%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In toluene; at 50℃; for 5h;Inert atmosphere; | In a flask, 1.83 g of 2,4,6-trichloropyrimidine, 5.65 g of the boronic acid ester shown in the above scheme (1), and 0.35 g of dichlorobis (triphenylphosphine) palladium were placed and purged with argon.100 ml of toluene and 20 ml of 2 M potassium carbonate aqueous solution were added and stirred at 50 C. for 5 hours.The reaction solution was washed with an aqueous sodium chloride solution and then purified by column chromatography to obtain a colorless solid.Yield 40%.Further, the obtained solid was stirred with triple molar amount of bromooctylphosphonic acid in the presence of DMF solvent at 90 C. for 4 hours to obtain (actual -1) as a colorless solid.Yield 60%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.6 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; toluene; for 18h;Inert atmosphere; Reflux; | The specific operation process is: in a 100mL three-necked flask,Compound D02 (2.06 g, 0.004 mol) was added.Compound E08 (2.24 g, 0.008 mol),Potassium carbonate (1.1 g, 0.008 mol), toluene (46 g), deionized water (25 g),Under the protection of nitrogen, the catalyst Pd(PPh3)4 (0.18g) was added.The temperature is raised to reflux, the reaction is kept for 18 hours, the temperature is lowered to 40 C, and the liquid is separated.The aqueous phase was extracted once with 50 mL of tetrahydrofuran, and the organic phases were combined.The solvent is removed, and the obtained crude product is purified by silica gel column chromatography.The eluent is dichloromethane: petroleum ether = 1:1 (volume ratio),Obtained the target product C15 crude 1.9g,Further sublimation purification using a chemical vapor deposition system, sublimation temperature 365 C,Obtained 1.6g target C15, |
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