Structure of 365564-07-4
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CAS No. : | 365564-07-4 |
Formula : | C14H21BO4 |
M.W : | 264.13 |
SMILES Code : | COC1=CC(=CC(OC)=C1)B1OC(C)(C)C(C)(C)O1 |
MDL No. : | MFCD05865191 |
InChI Key : | CZYHRTIJLUONKY-UHFFFAOYSA-N |
Pubchem ID : | 16217660 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 19 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.57 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 75.9 |
TPSA ? Topological Polar Surface Area: Calculated from |
36.92 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 |
2.85 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.08 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.9 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.57 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.31 |
Solubility | 0.13 mg/ml ; 0.000491 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.28 |
Solubility | 0.137 mg/ml ; 0.00052 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.25 |
Solubility | 0.0147 mg/ml ; 0.0000557 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
No |
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) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.89 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) |
3.13 |
* 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 |
---|---|---|
99% | With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 1,1'-di(pyridin-2-yl)-1,1',3,3'-tetrahydro-2,2'-bibenzo[d][1,3,2]diazaborole; at 100℃; for 16h;Inert atmosphere; | The Examples milligrams Preparation of 3,5-dimethoxybenzene boronic acid pinacol ester, specifically including the steps of: nitrogenEnvironment, the reaction flask was added 1,3-dimethoxybenzene (69.1mg, 0.5mmol),CoupletBoronic acid pinacol ester(126.9mg, 0.5mmol, of formula (5)),Methoxy-1,5-cyclooctadiene iridium dimer(3.4mg, 0.005mmol, 1%, formula (6)),Borane pyridine ligands ago(4.0mg, 0.01mmol, 2%, of Formula (1))And cyclopentyl methyl ether(1mL, 1,3-dimethoxybenzene reaction concentration is 0.5mol / L),The reaction at 100 16h; the reaction was completed by rotary evaporation (20 ~ 40 ) removing the solvent (cyclopentyl methyl ether), was purified by columnChromatography (using 200-300 mesh size silica gel, substance to be purified by silica gel ratio of 50 to 100: 1, eluent stoneOleyl ether and ethyl acetate, the volume ratio 20 ~ 50: 1) to afford the product to give a colorless 3,5-dimethoxybenzene boronic acid pinacol ester solid(125mg, 99%), |
90% | With bis(1,5-cyclooctadiene)diiridium(I) dichloride; 1-(4,4'-di-tert-butyl-[2,2'-bipyridin]-6-yl)-2-(dimethyl(phenyl)silyl)-2,3-dihydro-1H-benzo[d][1,3,2]diazaborole; at 100℃; for 3h;Schlenk technique; Inert atmosphere; Sealed tube; | General procedure: B2pin2, [IrCl(COD)]2 (1.0 mol%), preligand 1 (2.0 mol%), and (hetero)arene (0.2 mmol, ifsolid) were placed in a dried Schlenk flask (15 mL in volume) equipped with a stirring bar. Afterevacuating and refilling the flask with dry nitrogen three times, (hetero)arene (0.2 mmol, if liquid)and methoxycyclopentane (CAPE, 0.5 mL) were added with syringes under a stream of nitrogen.The resulting mixture was stirred at the corresponding temperature for the assigned time. After cooling to room temperature, the reaction mixture was concentrated and then purified by columnchromatography on silica gel to give the target product (The spectra data for the borylated compoundscan be seen in the Supplementary Material). |
68.4% | With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine; In cyclohexane; at 20℃;Inert atmosphere; | 1523.6 mg (6 mmol) of pinacol diboronate (B2pin2), 132.6 mg of [Ir (0 Torr) (COD)] and 107.4 mg (0.30 mmol) of 4,4-di-tert-butyl linkage Into 15 mL of cyclohexane, add dtbpy, protect with N2, stir at room temperature, and add 1.22 mL of 1,3-dimethoxybenzene while stirring. Stir the reaction for 10 h. Evaporate the solvent and purify by column chromatography. Petroleum ether: Elution with ethyl acetate (V:V=5:1), dried to give 1083.4 mg of compound 3 with a yield of 68.4%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 160℃; for 0.166667h;Microwave irradiation; | to a solution of LG2-101 (32 mg, 0.119 mmol), 2-(3,5- dimethoxyphenyl)-(4,4,5,5-tetramethyl-l,3,2-dioxaborolane (47 mg, 0.178 mmol, 1.5 equiv.) and Tetrakis(triphenylphosphine)-palladium(0) (16 mg, 0.013 mmol) in THF (1.0 ml) was added 0.5 ml of aqueous 1 N K2CO3 solution. The resultant mixture was heated at 160 0C under microwave irradiation for 10 min. The mixture was diluted with EtOAc, and the organic phase was separated out. After removal of solvent, the residue was subjected to flash column chromatography on silica gel (elution with hexane-EtOAc) to yield LG2-102 as a white gel (16 mg, 41%). ESI-MS: m/z 325 (M+l); IH NMR (600 MHz, CDC13): delta 7.60 (IH, d, J= 4.8 Hz), 7.55 (IH, s), 7.36 (IH, d, J= 4.8 Hz), 6.673 (IH, s), 6.670 (IH, s), 6.53 (IH, s), 6.14 (IH, t, J= 5.4 Hz, NH), 3.85 (6H, s), 3.46 (2H, dd, J= 5.4, 12.0 Hz), 1.18 (IH, m), 0.59 (2H, m), 0.32 (2H, m); 13C NMR (150.9 MHz, CDC13): delta 161.41, 149.54, 133.76, 130.59, 130.47, 129.07, 128.25, 107.78, 106.16, 100.37, 55.54, 45.84, 10.71, 3.62. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.9% | EXAMPLE 21 4-amino-8-(3,5-dimethoxyphenyl)-N-propyl-cinnoline-3-carboxamide Using method A, 4-amino-8-bromo-N-propyl-cinnoline-3-carboxamide (100 mg, 0.33 mmol) and 2-(3,5-dimethoxyphenyl)-4,4,5,5-tetramethyl-(1,3,2)-dioxaborolane (256 mg, 0.97 mmol) were reacted to afford the title compound (110 mg, 93.9% yield) as an off-white solid. 1H NMR (300 MHz, CDCl3) delta 8.57 (br, 1H), 7.87 (d, J=8.2 Hz, 1H), 7.79 (dd, J=7.2 Hz, J'=1.3 Hz, 1H), 7.71 (t, J=7.7 Hz, 1H), 6.79 (d, 3H), 3.83 (s, 6H), 3.47 (q, J=6.7 Hz, 2H), 1.67 (m, J=7.3 Hz, 2H), 1.01 (t, J=7.4 Hz, 3H) MS APCI, m/z=367 (M+H) HPLC 1.98 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate;dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; at 125℃; for 1h; | A mixture of ethyl 4-chloro-5-(4-fluorophenyl)-6-methyl-3-pyridinecarboxylate (i.e. the product of Step C) (1.5 g, 5.7 mmol), 2-(3,5-dimethoxyphenyl)-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (2.42 g 9.17 mmol), potassium phosphate (2.43 g, 11.5 mmol), palladium acetate (0.047 g, 0.21 mmol) and 2-dicyclohexylphosphino-2',6'- dimethoxybiphenyl was heated at 125 0C for 1 h. The reaction mixture was cooled, dichloromethane was added and the layers were separated. The organic layer was washed with water and concentrated under reduced pressure. The resulting residue was purified by medium pressure liquid chromatography (10 to 40% ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a white solid (1.0 g).1H NMR (CDCl3): delta 8.91 (s, IH), 6.96 (m, 4H), 6.26 (t, IH), 6.07 (d, 2H), 4.10 (q, 2H), 3.63 (s, 6H), 2.40, (s, 3H), 1.02 (t, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With potassium phosphate; tris-(o-tolyl)phosphine;tris-(dibenzylideneacetone)dipalladium(0); In tetrahydrofuran; at 20℃; for 16h;Sealed; Inert atmosphere; | A sealed degassed mixture of 3,5-dimefhoxyphenylboronic acid pinacol ester (50 mg, 0.177 mmol), teri-butyl-bromoacetate (22 mu, 0.148 mmol), P(o-tol)3 (4.1 mg, 0.0133 mmol),Pd2(dba)3 (4.1 mg, 0.0044 mmol), K3PO4 (157 mg, 0.739 mmol) in THF (3 mL) under argon was stirred at room temperature for 16 h. The reaction mixture was diluted with 20 mL of Et20 and then washed with brine. The reaction mixture was dried with MgSC , dried under reduced pressure and purified by flash chromatography to give tert-butyl 2-(3,5-dimethoxyphenyl)acetate as a yellow liquid (18 mg, 48%). NMR (400 MHz, CDCh) delta 6.43 (d, J = 2.0 Hz, 2 H), 6.36 (t, J = 2.3 Hz, 1 H), 3.78 (s, 6 H), 3.45 (s, 2 H), 1.44 (s, 9 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water; potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; N,N-dimethyl-formamide; at 110℃; for 0.5h;microwave irradiation; | A mixture of 1 ,1 -dimethylethyl 4-(3-bromo-4-[(3-chlorophenyl)sulfonyl]amino}-6- methylthieno[2,3-6]pyridin-2-yl)-1 /-/-pyrazole-1 -carboxylate (Description 75) (100 mg, 0.171 mmol), <strong>[365564-07-4]3,5-dimethoxyphenylboronic acid pinacol ester</strong> (90 mg, 0.343 mmol), potassium carbonate (95 mg, 0.685 mmol) and tetrakis(triphenylphosphine)palladium(0) (3.96 mg, 3.43 muetaetaomicronIota) were weighed into a microwave vial. 1 ,4-Dioxane (1.5 mL), DMF (0.75 mL) and water (0.38 mL) were added and the mixture heated in a microwave at 1 10C for 30 min. At this point, both reaction mixtures were combined and concentrated. The residue was passed through an SCX cartridge, eluting with MeOH (75 mL) and then with 2M NH3 in MeOH (100 mL). The basic methanolic solution was concentrated and purified by MDAP (acidic conditions), to give the title compound (45 mg). LCMS (A) m/z: 541 [M+1]+, Rt 1 .26 min (acidic). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
254 mg | In a reaction flask charged with Pd(OAc)2 (4.5 mg, 0.02 mmol), potassium iodide (83 mg, 0.5 mmol), and XPhos (28 mg, 0.06 mmol) under argon atmosphere was added, in this following order: anhydrous solvent (2 mL), Et3N (0.4 mL, 3 mmol), l-chloro-3,5- dimethoxybenzene (0.17 mL, 1 mmol) and diisopropylammoborane (0.3 mL, 2 mmol). The reaction was then heated at 50 C. After total consumption of either starting material, the reaction was cooled at -5 C, quenched with anhydrous MeOH (2 mL) and stirred for 1 h at room temperature. All volatiles were removed under vacuum before adding pinacol (153 mg, 1.3 mmol) in Et20 (2 mL), and the mixture was stirred for 4 h at room temperature. The reaction mixture was diluted with Et20 (10 mL), and the organic phase was washed first with a solution of HC1 (0.1 N, 2x10 mL), followed by an aqueous solution of CuCl2 (50g/L, 3x10 mL), dried over anhydrous Na2S04, filtered and concentrated under vacuum. The crude oil was passed through a pad of silica gel, eluting with Et20. The resulting filtrate was concentrated under vacuum to afford 2-(3,5- dimethoxyphenyl)-4,4,5,5-tetramethyl-l ,3,2-dioxaborolane (254 mg, 95%). 1H NMR (300 MHz, CDC13) delta 7.35 (dd, IH, J 7.4, 0.9 Hz), 7.17 (t, IH, J 7.8 Hz), 6.96 (dd, IH, J 7.5, 1.0 Hz), 3.82 (s, 3H), 2.44 (s, 3H), 1.36 (s, 12H); 13C NMR (100 MHz, CDC13) delta 160.50, 1 1 1.72, 104.59, 83.96, 55.47, 24.94; nB NMR (96 MHz, CDC13) delta +30.29; MS (EI) tR = 10.527 min; m/z: 264 (M+, 100%). | |
254 mg | at 20℃; for 4h;Inert atmosphere; | In a reaction flask charged with Pd(OAc)2 (4.5 mg, 0.02 mmol), potassium iodide (83 mg, 0.5 mmol), and XPhos (28 mg, 0.06 mmol) under argon atmosphere was added, in this following order: anhydrous solvent (2 mL), Et3N (0.4 mL, 3 mmol), 1-chloro-3,5-dimethoxybenzene (0.17 mL, 1 mmol) and diisopropylaminoborane (0.3 mL, 2 mmol). The reaction was then heated at 50 C. After total consumption of either starting material, the reaction was cooled at -5 C, quenched with anhydrous MeOH (2 mL) and stirred for 1 h at room temperature. All volatiles were removed under vacuum before adding pinacol (153 mg, 1.3 mmol) in Et2O (2 mL), and the mixture was stirred for 4 h at room temperature. The reaction mixture was diluted with Et2O (10 mL), and the organic phase was washed first with a solution of HCl (0.1 N, 2x10 mL), followed by an aqueous solution of CuCl2 (50g/L, 3x10 mL), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude oil was passed through a pad of silica gel, eluting with Et2O. The resulting filtrate was concentrated under vacuum to afford 2-(3,5-dimethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (254 mg, 95%). 1H NMR (300 MHz, CDCl3) delta 7.35 (dd, 1H, J 7.4, 0.9 Hz), 7.17 (t, 1H, J 7.8 Hz), 6.96 (dd, 1H, J 7.5, 1.0 Hz), 3.82 (s, 3H), 2.44 (s, 3H), 1.36 (s, 12H); 13C NMR (100 MHz, CDCl3) delta 160.50, 111.72, 104.59, 83.96, 55.47, 24.94; 11B NMR (96 MHz, CDCl3) delta +30.29; MS (EI) tR = 10.527 min; m/z: 264 (M+, 100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With Pd(OTf)2(CH3CN)4; sodium hydrogencarbonate; N-acetyl-D-tert-leucine; silver carbonate; p-benzoquinone; In tert-Amyl alcohol; water; dimethyl sulfoxide; at 100℃; for 18h;Inert atmosphere; Schlenk technique; | General procedure: In a 50 ml Schlenk tube, starting material 1 (49.8 mg, 0.2 mmol), 4-methoxycarbonylphenylboronic acid pinacol ester (2) (104.8 mg, 0.4 mmol),Pd(OTf)2(MeCN)4 (11.4 mg, 0.02 mmol), Ac-D-tLeu-OH (3) (6.9 mg, 0.04 mmol),NaHCO3 (100.8 mg, 1.2 mmol), Ag2CO3 (110.3 mg, 0.4 mmol) and 1,4-benzoquinone (10.8 mg, 0.1 mmol) were combined. The flask was evacuated and backfilled with N2 three times, before a solution of dimethylsulfoxide (DMSO,6.0 mg, 0.076 mmol), water (20 mg, 1.1 mmol) and t-amyl-OH (1 ml, 0.2 M) was added. The reaction mixture was then stirred at 100 8C for 18 hours. After being allowed to cool to room temperature, the mixture was diluted with a 1:1 mixture of hexanes:ethyl acetate, and filtered through a pad of celite. The filtrate was concentrated in vacuo, and the resulting residue purified by column chromatography using an eluent of hexanes:ethyl acetate. The product, 1b, was obtained as a light-yellow liquid (62.9 mg, 82%).The above procedure to prepare 1b is generally representative for all the products shown in Tables 3 and 4. Any deviations from this protocol are specified in the footnotes of the tables. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80 mg | With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 90℃; for 2h;Sealed tube; | A mixture of 6-chloro-3-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[4,3-c]pyridine (0.06 g, 0.2 mmol), <strong>[365564-07-4]2-(3,5-dimethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (0.060 g, 0.23 mmol), [1,1'-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) complex with dichloromethane (1:1) (10 mg, 0.02 mmol), and potassium phosphate (80. mg, 0.38 mmol) in 1,4-dioxane (0.5 mL) and water (0.07 mL) in a reaction vial was degassed and sealed. The mixture was stirred at 90 C. for 2 h. After cooling it was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-50%) to afford the desired product (80 mg). LCMS (M+H)+=420.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl-formamide; at 80℃; for 60h;Inert atmosphere; | A 200-mL two-neck round-bottom flask was charged with anitrogen atmosphere, and to the flask, 1-bromo-3,5-dimethoxybenzene (2.92 g, 13.82 mmol), bis(pinacolato)diboron (5.26 g, 20.73 mmol), Pd(dppf)Cl2?CH2Cl2 (1.56 g, 1.91 mmol) and KOAc (2.10 g, 20.73 mmol) were added into 80 mL of dry DMF. The mixture was stirred at 80C for 60 h under nitrogen. Then, DMF was removed by vacuum distillation, and the residue was extracted with CH2Cl2 (3 20 mL). The CH2Cl2 layer was washed with H2O (2 x 20 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give a brown crude. The crude product was purified by column chromatography on silica gel (eluent: EtOAc: hexane, 2/3 v/v) to give white compound as a first band. (1.16 g, 88%). 1H-NMR (500 MHz, DMSO) delta(ppm)= 6.95(2H, d, J= 2.6 Hz), 6.57 (1H, t, J= 2.5 Hz), 3.81 (6H, s), and 1.34 (12H, s). |
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl-formamide; at 90℃; for 39h;Inert atmosphere; | To a solution of 30 ml of anhydrous DMF, 1.29 g, 5 lf of dicarboxylidene diboron (1-bromo-3,5-dimethoxybenzene with frequency The molar ratio of the Ershou Er shed was 1: 1 ? 1, 0.69 g, 6.99 mmol of KOAc, 0.59 g, and 0. 69 mmol of PdCl2 (dppf) CH2C12 was added and stirred at 90 C for 39 hours. The resulting solution was distilled off under reduced pressure except that CH2C12 extracted the organic phase and Na2S04 was removed Water and distilled under reduced pressure to give the crude product. The crude product was purified by column chromatography. The stationary phase uses a sphere of 63 ~ 210mupi The mobile phase consisted of 40/6 (^ (012) 03013), and the column size was 7.511. The purified product was purified to give a white product. MS (MALDI-T0F, CH2C12): pi / zeta = 265.09, [M] Calculated value 265.1641, M = Ci4H2iB4.500MHz, DMSO): delta (ppm) = 6 ? 95 (2H, d, J = 2.6Hz), 6 ? 57 (1H, t, J = 2.5 Hz), 3.81 (6H, s), 1.34 (12H, s) | |
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl-formamide; at 80℃; for 39h;Inert atmosphere; | Under a nitrogen atmosphere,2.92 g, 13.82 mmol of 1-bromo-3,5-dimethoxybenzene was dissolved in 80 ml of dry DMF,Continuous addition of 3.86g,15.20 mmol of pinacol diboron,2.10 g, 20.73 mmol KOAc,1.56 g, 1.91 mmol PdCl2 (dppf) · CH2Cl2,The mixture was stirred at 80 C for 39 hours,The resulting solution was distilled under reduced pressure to remove DMF,CH2Cl2 extraction of organic phase,Na2SO4 dehydration,After distillation under reduced pressure by column chromatography.The stationary phase was a spherical silica gel of 63 to 210 m,The EtOAc / CH3 (CH2) 4CH3 solution with a fixed phase diameter of 7.5 cm in height of 8 cm and a mobile phase of 40/60,The purified white material was purified by column chromatography with 2.18 g of 5.22 mmol of 4-bromo-2,6-bis [2- (1-methyl) benzimidazolyl] pyridine in 60 ml of anhydrous DMF,2.79 g, 28.46 mmol KOAc,0.87 g, 1.06 mmol PdCl2 (dppf) · CH2Cl2,The mixture was stirred at 80 C for 60 hours,The resulting solution was distilled under reduced pressure to remove DMF,CH2Cl2 extraction of organic phase,Dehydration of Na2SO4, distillation under reduced pressure by column chromatography,The stationary phase was a spherical silica gel of 63 to 210 m,Fixed phase diameter of 7.5cm height of 8cm,The mobile phase consisted of 60/40 EtOAc / CH3 (CH2) 4CH3 solution,The white intermediate 1 purified by column chromatography was dissolved in 50 ml of anhydrous CH2Cl2,In the ice bath slowly drip 1.0M, 15ml, 15mmol of BBr3 (dropping time 30min)After completion of the dropwise addition, the temperature was gradually raised to room temperature for 12 hours,The resulting solution was quenched by the dropwise addition of 20 ml of water in an ice-water bath,The aqueous phase was adjusted to pH to neutral and the organic phase was extracted with EtOAc.After washing with water, Na2SO4 was dehydrated, distilled under reduced pressure and washed with Hex. After filtration, the white intermediate 2 was recrystallized from DMSO / H2O and dissolved with 1.50 g of 4.45 mmol of 1- (4-bromobutyl) -pyrene 60 ml of DMF solution,1.52 g, 11.05 mmol of K2CO3 was added and stirred at 80 C for 90 h. The organic phase was extracted by distillation under reduced pressure. The organic phase was extracted with CH2Cl2 and dehydrated with Na2SO4. After distillation under reduced pressure, the column was purified by column chromatography using a spherical silica gel of 63 to 210 m A mixed solution of 30/70 EtOAc / CH2Cl2 with a diameter of 7.5 cm and a mobile phase of 30 cm and a mobile phase was purified by column chromatography to give the product Py2G1MeBip as a white product. |
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