Structure of 38696-20-7
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CAS No. : | 38696-20-7 |
Formula : | C10H7BrN2 |
M.W : | 235.08 |
SMILES Code : | BrC1=CN=C(N=C1)C2=CC=CC=C2 |
MDL No. : | MFCD09999220 |
InChI Key : | ZZKCBZDJCZZPSM-UHFFFAOYSA-N |
Pubchem ID : | 14387745 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 55.17 |
TPSA ? Topological Polar Surface Area: Calculated from |
25.78 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.39 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.89 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.91 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.29 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.73 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.74 |
Solubility | 0.0432 mg/ml ; 0.000184 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.09 |
Solubility | 0.19 mg/ml ; 0.00081 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.03 |
Solubility | 0.0022 mg/ml ; 0.00000938 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) |
No |
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) |
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 |
-5.68 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 |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.64 |
* 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 |
---|---|---|
38% | With potassium phosphate; copper(l) iodide; N,N-diethylsalicylamide; In N,N-dimethyl-formamide; at 90℃; for 24h; | Step 2: 4-(Pyrimidin-5-ylamino)-piperidine-1-carboxylic acid tert-butyl ester A mixture of <strong>[38696-20-7]5-bromo-2-phenyl-pyrimidine</strong> (3.50 g, 14.89 mmol, 1.0 equiv), 4-amino-piperidine-1-carboxylic acid tert-butyl ester (4.48 g, 22.33 mmol, 1.5 equiv), copper(I) iodide (0.28 g, 1.49 mmol, 0.1 equiv), N,N-diethylsalicylamide (0.58 g, 2.98 mmol, 0.2 equiv) and K3PO4 (3.16 g, 14.89 mmol, 1.0 equiv) in degassed DMF (30 mL) was heated under Ar to 90° C. for 24 h. The solvent was removed under reduced pressure and the crude reaction product extracted from water (300 mL) and 25percent NH4OH (30 mL) with ethyl acetate (3*300 mL). The combined organic phases were dried over Na2SO4, concentrated by evaporation under reduced pressure and the crude material purified by silica column chromatography eluding with a gradient of heptane/ethyl acetate (4:1-->1:1) to provide 1.98 g (38percent) of the title compound. MS (ESI): 377.1 [M+Na]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
178 mg (56%) | tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; | Step A (2E)-3-(2-Phenyl-5-pyrimidinyl)-2-propenoic Acid Methyl Ester Dioxane (1.3 mL) was added to a mixture of <strong>[38696-20-7]5-bromo-2-phenylpyrimidine</strong> (310 mg, 1.32 mmol, prepared as described in Org. Lett. 2002, 4, 513), tri-t-butylphosphonium tetrafluoroborate (11 mg, 0.038 mmol), and tris(dibenzylideneacetone)dipalladium(0) (18 mg, 0.020 mmol). N-Methyldicyclohexylamine (0.31 mL, 1.45 mmol) and methyl acrylate (0.24 mL, 2.67 mmol) were added and the mixture was stirred for 72 h at room temperature. The mixture was diluted with ethyl acetate, filtered through a small plug of silica gel which was washed with additional ethyl acetate, and the combined filtrates were concentrated. The residue was triturated with 5:1 hexane/ethyl acetate and the solid was filtered and dried in vacuo to provide 178 mg (56percent) of the title compound as an off-white solid. MS 241 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
226 mg (34%) | With n-butyllithium; In tetrahydrofuran; diethyl ether; | REFERENCE EXAMPLE 71 2-Phenyl-5-pyrimidinecarboxyaldehyde To a solution of <strong>[38696-20-7]5-bromo-2-phenylpyrimidine</strong> (850 mg, 3.65 mmol, prepared as described in Org. Lett. 2002, 4, 513) in THF (15 mL) at -100° C. was added dropwise n-BuLi (1.60 mL, 4.00 mmol, 2.5 M solution in hexanes). The reaction mixture was stirred at -100° C. for 15 min, and methyl formate (0.26 mL, 4.20 mmol) was added dropwise. The reaction mixture was stirred for an additional 15 min at -100° C., carefully quenched with a 1 M HCl solution in diethyl ether (4.50 mL, 4.50 mmol), warmed to room temperature, and concentrated in vacuo. The crude reaction mixture was partitioned between dichloromethane and sat. aq. NaHCO3, the organic layer dried with Na2SO4, and concentrated in vacuo. Purification by medium pressure liquid chromatography (SiO2, 4:1 hexanes/ethyl acetate) gave 226 mg (34percent) of the title compound. MS 185 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With copper(I) oxide; copper; potassium carbonate; In 1,2-dimethoxyethane; at 130℃; | Example 1; 5-cyclopropyl-2-(2-phenylpyrimidin-5-ylamino)benzoic acidIn a schlenck tube, a mixture of Intermediate 8 (0.2Og, 1.15mmol), Intermediate 21 (0.30, 1.15mmol), potassium carbonate (1.72 mmol, 0.238 g), Cu2O (0.06 mmol, 0.008 g) and Cu (0.11 mmol, 0.007 g) in DME (5 ml) was heated at 13O0C overnight, under argon atmosphere. The solvent was evaporated and the crude mixture was purified over SiO2 <n="77"/>eluting with CH2CI2/ MeOH mixtures affording 0.12O g (57percent of yield) of the expected compound.1H NMR (400 MHz, DMSO-d6) delta ppm 0.6 (s, 2 H) 0.9 (m, 2 H) 1.9 (m, 1 H) 7.2 (d,J=8.6 Hz, 1 H) 7.3 (d, J=8.2 Hz, 1 H) 7.5 (m, 2 H) 7.7 (m, 1 H) 8.3 (d, J=7.0 Hz, 2H) 8.5 (m, 1 H) 8.8 (s, 2 H) 9.4 (s, 1 H) 13.3 (m, 1 H).ESI/MS (m/e, percent): 332 [(M+1)+, 100] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6% | Oxazole (124 mg, 1.8 mmol) was dissolved in stirring tetrahydrofuran (20 mL) under nitrogen at -78° C. and treated with n-butyllithium (2.0 M in cyclohexane, 1.1 mL, 2.2 mmol) maintaining internal temperature below -60° C. After stirring ten minutes, ZnCl2 (0.48 g, 3.5 mmol) was added portionwise. The cooling bath was removed and the solution was allowed to reach room temperature. Tetrakis(triphenylphosphine)palladium(0) (30 mg, 5 mole percent) and <strong>[38696-20-7]5-bromo-2-phenylpyrimidine</strong> (309 mg, 1.30 mmol) were added and the mixture heated at 60° C. for four hours. Solvent was removed under reduced pressure and the mixture partitioned between saturated aqueous ammonium chloride and ethyl acetate. The organic phase was retained and additional ethyl acetate extractions of the aqueous phase performed. The combined extracts were dried with anhydrous sodium sulfate, the solution filtered, and solvent removed under reduced pressure. Purification by silica gel flash chromatography (9:1 to 7:3 v/v hexane-ethyl acetate) through a 12-g Silicycle.(R). flash silica cartridge afforded the title compound as an off-white solid (17 mg, 6percent yield); Rf 0.66 with 3:1 v/v hexane-ethyl acetate; melting point 175-177° C.; 1H-NMR (300 MHz; DMSO-d6) delta 9.42 (s, 2H), 8.48 (dd, 2H), 8.41 (s, 1H), 7.56-7.62 (m, 3H), 7.54 (s, 1H); MS (ESI+) m/z 224 (M+1), (ESI-) m/z 222 (M-1); H-PGDS FPBA IC50: 7.8 muM. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | To a solution of 4-Iodo-1-trityl-1H-imidazole (Synthonix, 2.0 g, 4.58 mmol) in THF (50 mL) at room temperature was added ethylmagnesium bromide (Aldrich, 1.0 M solution in THF, 5.5 mL, 5.50 mmol) under dry conditions. After stirring for 90 minutes, zinc chloride (Aldrich, 0.749. g, 5.50 mmol) was added to the reaction mixture. After stirring for an additional 90 minutes, tetrakis(triphenyl)phosphine)palladium (Strem, 0.529 g, 0.46 mmol) and <strong>[38696-20-7]5-bromo-2-phenylpyrimidine</strong> (as prepared in Example 1, step A, 1.29 g, 5.50 mmol) were added to the reaction mixture. The reaction mixture was heated in a 70° C. oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with 0.5 M EDTA buffer (at pH ~9) (2*250 mL) followed by brine (150 mL). The organics were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash silica column chromatography using an 80 g Silicycle.(R). column (elution with 10-30percent ethyl acetate in hexane) which afforded the desired intermediate, 2-phenyl-5-(1-trityl-1H-imidazol-4-yl)pyrimidine, as a white solid (1.38 g, 65percent). Rf 0.87 with 95:5 v/v dichloromethane-methanol; 1H-NMR (400 MHz; DMSO-d6) delta 9.29 (s, 2H), 8.42 (m, 2H), 7.92 (d, 1H), 7.62 (d, 1H), 7.56-7.43 (m, 13H), 7.24-7.22 (m, 6H); MS (ESI-) m/z 463.0 (M-1); H-PGDS FPBA IC50: >20 muM. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | A stirring mixture consisting of palladium(II) acetate (215 mg, 0.32 mmol) and triphenylphosphine (335 mg, 1.28 mmol) in 1,4-dioxane (25 mL) was heated at 80° C. for 30 minutes. The dark reaction mixture was cooled to room temperature, and to this reaction mixture was added a solution consisting of <strong>[38696-20-7]5-bromo-2-phenylpyrimidine</strong> (Example 1A, 3.0 g, 13 mmol) and tributyl(1-ethoxyvinyl)tin (4.74 mL, 14.0 mmol) in 1,4-dioxane (63 mL). The reaction mixture was stirred and heated at 75° C. overnight and was subsequently cooled to room temperature. The reaction progress was monitored by thin layer chromatography (95:5 v/v hexanes-ethyl acetate) until completion. The reaction mixture was treated with 1 N hydrochloric acid (19 mL) for one hour at room temperature and poured into a saturated aqueous sodium bicarbonate solution. The organic material was extracted two times with a mixture of ethyl acetate and hexanes, and the combined organic phase was washed sequentially with water and brine, and was dried over anhydrous magnesium sulfate, filtered through a well packed pad of magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in dichloromethane (30 mL) and diluted with hexanes (30 mL). The resulting precipitate was filtered to give the title intermediate (872 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With potassium carbonate;trifuran-2-yl-phosphane; palladium diacetate; In N,N-dimethyl-formamide; at 140℃; for 16h;Inert atmosphere; | To a mixture consisting of <strong>[38696-20-7]5-bromo-2-phenylpyrimidine</strong> (1.2 g, 5.1 mmol), palladium (II) acetate (Strem, 0.048 g, 0.21 mmol), tris(2-furyl)phosphine (TCI America, 0.098 g, 0.43 mmol) and potassium carbonate (1.17 g, 8.52 mmol) was added a solution consisting of 1-benzyl-2-phenyl-1H-imidazole (1.0 g, 4.3 mmol) in N,N-dimethylformamide (10 mL). The reaction mixture was brought to reflux at 140° C. (degrees Celsius) while under a N2 atmosphere. After stirring for 16 hours at reflux the solution was cooled to room temperature. The reaction mixture was partitioned between ethyl acetate (250 mL) and saturated aqueous ammonium chloride (100 mL). The phases were separated and the organic layer was washed with brine (150 mL), and was subsequently dried over anhydrous magnesium sulfate. Concentration under reduced pressure affords the crude product as an orange oil (0.658 g). The product was purified by flash silica column chromatography. Elution through a 80-g Silicycle.(R). flash silica cartridge with gradient of 5percent to 30percent ethyl acetate in hexanes afforded the title intermediate (0.495 g, 30percent yield); Rf 0.38 with 1:1 v/v ethyl acetate-hexane; 1H-NMR (400 MHz; CDCl3) delta 8.7 (s, 2H), 8.4 (m, 2H), 7.6 (m, 2H), 7.5-7.25 (m, 10H), 6.9 (m, 2H), 5.32 (s, 2H); MS (ESI+) m/z 389.2 (M+1); H-PGDS FPBA IC50: 15 muM. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | With silver carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triphenylphosphine; In water; at 60℃; for 18h;Inert atmosphere; | Silver carbonate (317 mg, 1.15 mmol), triphenylphosphine (16 mg, 0.06 mmol) and Pd(dppf)Cl2.CH2Cl2 (24 mg, 5 mole percent) were stirred together at room temperature under nitrogen. 5-Bromo-2-phenylpyrimidine (163 mg, 0.69 mmol) was added followed by 2-phenyl-oxazole (84 mg, 0.58 mmol; prepared according to Ohnmacht, S. A. et al., Chemical Communications, 2008, 1241-1243). Finally water (6 mL) was added and the mixture heated for 18 hours at 60° C. The mixture was cooled to room temperature and filtered through Celite washing with DCM and acetone. Purification by silica gel flash chromatography (100percent DCM) through a 12-g Silicycle.(R). flash silica cartridge gave title compound as light yellow solid (19 mg, 11percent yield); Rf 0.68 with DCM; melting point 228-231° C.; 1H-NMR (300 MHz; DMSO-d6) delta 9.39 (s, 2H), 8.45 (dd, 2H), 8.17 (dd, 2H), 8.11 (s, 1H), 7.54-7.65 (m, 6H); MS (ESI+) m/z 300 (M+1), (ESI-) m/z 298 (M-1); H-PGDS FPBA IC50: 125 muM. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | With potassium phosphate; potassium carbonate;4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; water; at 100℃; for 18h; | Diisopropyl 1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-ylboronate (595 mg, 1.46 mmol) prepared according to the procedure described in the Journal of Organic Chemistry, 2008, 73, 1241-1243) was combined with Pd2(dba)3 (13 mg, 0.013 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (19 mg, 0.033 mmol). 1,4-Dioxane (10 mL) and <strong>[38696-20-7]5-bromo-2-phenylpyrimidine</strong> (343 mg, 1.46 mmol) were added followed by 1.27 M aqueous K3PO4 (958 mg dissolved in 3.5 mL of water) and the mixture heated at 100° C. for 18 hours with stirring. The mixture was cooled to room temperature and filtered through Celite washing with ethyl acetate. The solvent was removed under reduced pressure and the concentrate partitioned between water and ethyl acetate. The organic phase was retained and dried with anhydrous sodium sulfate. The solution was filtered and the solvent removed under reduced pressure. Purification by silica gel flash chromatography (9:1 to 3:2 v/v hexane-ethyl acetate gradient) through a 12-g Silicycle.(R). flash silica cartridge gave title intermediate as a white solid (51 mg, 11percent yield); Rf 0.70 with 40percent ethyl acetate in hexane; MS (ESI+) m/z 307 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With caesium carbonate;palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In N,N-dimethyl-formamide; at 110℃; for 18h;Sealed tube; | In a sealed tube, cesium carbonate (1.95 g, 6.00 mmol), tert-butyl-4-thiazolecarboxylate (556 mg, 3.00 mmol; prepared according to the procedure described in Organic Letters, 2008, 10(13), 2909), palladium(II) acetate (47 mg, 0.21 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (240 mg, 0.42 mmol) were combined with <strong>[38696-20-7]5-bromo-2-phenylpyrimidine</strong> (705 mg, 3.00 mmol) in dry DMF (11 mL) and the mixture heated at 110° C. for 18 hours with stirring. The mixture was cooled to room temperature and filtered through Celite washing with hot ethyl acetate. Solvent was removed under reduced pressure and the residue purified by silica gel flash chromatography (9:1 to 3:2 v/v hexane-ethyl acetate gradient) through a 40-g Silicycle.(R). flash silica cartridge. The title compound was obtained as a white solid (646 mg, 63percent yield); Rf 0.75 with 1:1 v/v hexane-ethyl acetate; 1H-NMR (300 MHz; CDCl3) delta 9.37 (s, 2H), 8.52 (dd, 2H), 8.15 (s, 1H), 7.54 (m, 3H), 1.64 (s, 9H); MS (ESI+) m/z 340 (M+1); H-PGDS FPBA IC50: 5.9 muM. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84.2% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; for 12h;Heating; | Synthesis of Intermediate A-3 [0110] 10 g (1 eq, 0.048 mol) of A-1 and 14.06 g (1.1 eq, 0.049 mol) of A-2 were added to a flask and dissolved in 700 m? of toluene. 0.08 g (0.03 eq, 0.000144 mmol) of Pd2(dba)3, 4.27 g (1.2 eq, 0.057 mol) of Na(t-bu)O, and 0.07 g (0.06 eq, 0.00288 mmol) of P(t-Bu)3 were added to the flask and dissolved in 150 ml of additional toluene to prepare a mixture, and the mixture was thermally agitated for 12 hours to prepare a reaction solution. The reaction solution was filtered through Celite and then subjected to a column chromatography to obtain 14.7 g (yield rate = 84.2percent) of Compound 1. [0111] Elemental Analysis for C24H16N4: calcd C, 79.98; H, 4.47; N, 15-55. [0112] HRMS for C24H16N4 [M]+: calcd 360.14, found 360. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | With palladium diacetate; N-ethyl-N,N-diisopropylamine; tris-(o-tolyl)phosphine; In N,N-dimethyl-formamide; at 20 - 140℃; for 16h;Inert atmosphere; | [000297] Synthesis of (E)-3-(2-phenylpyrimidin-5-yl) acrylamide (364): To a stirred solution of compound 363 (300 mg, 1.28 mmol) in DMF (20 mL) under inert atmosphere was added acrylamide 356 (109 mg, 1.53 mmol) at RT and purged under argon for 10 mm. To this were added o-tolyl phosphine (42 mg, 0.07 mmol), palladium acetate (15.7 mg, 0.07 mmol), and diisopropyl ethyl amine (0.28 mL, 1.53 mmol) at RT; heated to 140°C and stirred for 16 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted water (100 mL) and extracted with 10percent MeOH/ CH2C12 (2 x 50 mL). The combined organic extracts were dried over sodium sulphate, filtered and concentrated in vacuo to obtain the crude. The crude compound was triturated with 50percent EtOAc/ hexanes (10 mL) and dried in vacuo to afford compound 364 (50 mg, 17percent) as an off-white solid. TLC: 70percent EtOAc/ hexanes (Rj: 0.2); 1H-NMR (DMSO-d6, 400 MHz): oe 9.10 (s, 2H), 8.43-8.4 1 (m, 2H), 7.64 (br s, 1H), 7.55-7.54 (m, 3H), 7.47 (d, J 16.0 Hz, 1H), 7.22 (br s, 1H), 6.85 (d, J= 16.0 Hz,1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In water; N,N-dimethyl-formamide; for 2h;Inert atmosphere; Reflux; | 2-ethoxycarbonyl phenyl BornicAcid 20.0 g (103.1 mmol), 2- phenyl-5-bromopyrimidine 20.2g (85.9 mmol), potassium acetate and 25.3 g (257.7 mmol), dichloro diphenylphosphinoferrocene palladium (II) 4.9 g (6.01 mmol) and 170 mL of dimethylformamide, was dissolved in 30 mL of distilled water was stirred at reflux for 2 hours in a nitrogen stream.After completion of the reaction diluting the reaction solution in water, 3 L, and extracted with 1L ethyl acetate.Collect the organic layer was washed twice with 1L of water, back washed once with 1L saturated brine and dried over anhydrous magnesium sulfate and filtered and concentrated.The concentrated residue was purified by a dichloromethane: ethyl acetate = 5: 1 (v / v) and purified by silica gel column in a solvent the intermediate product (D) 24.1 g (Yield: 92percent) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
208.64 g | 101.06 g benzonitrile, 241.56g of the above-mentioned self-made N, N, N ', N' -tetramethyl-2-bromo-malondialdehydediimine hydrochlorideand methanol was added to the reaction container. The temperature was controlled to 20 °C, and 5.40 g sodium methanolatewas added to the reaction system. The reaction was continued for 2 hours. 160.47 g ammonium chloride was then added, and the reaction was continued for 4 hours at 40 °C. 64.82 g sodium methanolate was then added, and the reaction was continued at reflux for 5 hours. The solution was cooled down to room temperature. After filtering, washing, and drying, 208.64g of 2-phenyl-5-bromo-pyrimidine was obtained. The yield is 90.6percent, and HPLC purity is of 98.8percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In water; acetonitrile; for 6.5h;Inert atmosphere; Microwave irradiation; | Subsequently, 0.96 g of <strong>[38696-20-7]5-bromo-2-phenylpyrimidine</strong> obtained in the above step 1, 1.21 g of 2,6-dimethylphenylboronic acid, 0.87 g of sodium carbonate, 0.76 g of bis (triphenylphosphine) palladium (II) dichloride (Abbreviation: Pd (PPh 3) 2 Cl 2), 15 mL of water and 15 mL of acetonitrile were placed in a recovery flask equipped with a reflux tube and argon bubbling was carried out for 15 minutes. The reaction vessel was heated by irradiating microwave (2.45 GHz 100 W) for 3 hours. Here, 1.21 g of 2,6-dimethylphenylboronic acid, 0.87 g of sodium carbonate and 0.035 g of Pd (PP 3) 2 Cl 2 were placed in a flask and argon bubbling was carried out for 15 minutes. This reaction vessel was heated again by irradiating microwave (2.45 GHz 100 W) for 3 hours. Thereafter, the obtained mixture was suction filtered with water. The obtained solid was purified by flash column chromatography using toluene as a developing solvent to obtain the desired pyrimidine derivative Hppm 2-dmp (white powder, yield 64percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65.6% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; for 24h;Reflux; Inert atmosphere; | 250ml of four bottles, in the atmosphere of nitrogen,0.01 mol of <strong>[38696-20-7]5-bromo-2-phenylpyrimidine</strong> was added,0.015 mol of intermediate G1, 0.03 mol of sodium tert-butoxide,1 x 10-4 mol Pd2 (dba) 3,1 x 10-4 mol tri-tert-butylphosphine,150 ml of toluene, heated to reflux for 24 hours,Sampling point plate, the reaction is complete;Natural cooling, filtration, the filtrate steamed, through the silica gel column, the target product,Purity 98.8percent, yield 65.6percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.1% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; for 24h;Inert atmosphere; Reflux; | 250ml four-necked flask, in a nitrogen-purged atmosphere,0.01 mol of <strong>[38696-20-7]5-bromo-2-phenylpyrimidine</strong>, 0.015 mol of intermediate J1, 0.03 mol of sodium tert-butoxide, 1 x 10-4 mol of Pd2 (dba) 3,1 X 10-4 mol tri-tert-butylphosphine,150ml of toluene, heated to reflux for 24 hours, sampling point plate, the reaction was complete; natural cooling, filtration, the filtrate was swirled through a silica gel column to obtain the target product, purity 98.7percent, yield 67.1percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 50 - 150℃;Inert atmosphere; | (1) In a 500mL three-necked bottle,(9H-carbazol-3-yl)boronic acid (25.32 g, 150 mmol),<strong>[38696-20-7]5-bromo-2-phenylpyrimidine</strong> (28.21 g, 120 mmol),Sodium tert-butoxide (23.04 g, 240 mmol),Tri-tert-butylphosphine tetrafluoroborate (0.21 g, 0.72 mmol), added 250 mL of toluene,Tris(dibenzylideneacetone)dipalladium (0.33 g, 0.36 mmol) was added under a nitrogen atmosphere.The temperature is raised to 50-150 ° C for 4 to 48 hours, the liquid phase monitoring reaction is completed, and cooled to room temperature.Washed, filtered, separated by column chromatography,40.31g of (9-(2-phenylpyrimidin-5-yl)-9H-indazol-3-yl)boronic acid was obtained in a yield of 92percent |
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