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Chemical Structure| 38696-20-7

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5-Bromo-2-phenylpyrimidine

CAS No.: 38696-20-7

4.5 *For Research Use Only !

Cat. No.: A299474 Purity: 95%

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Product Details of [ 38696-20-7 ]

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

Safety of [ 38696-20-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Calculated chemistry of [ 38696-20-7 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

25.78 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

2.39
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.89
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.91
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

2.29
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

3.17
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.73

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.74
Solubility 0.0432 mg/ml ; 0.000184 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-3.09
Solubility 0.19 mg/ml ; 0.00081 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-5.03
Solubility 0.0022 mg/ml ; 0.00000938 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.68 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.64

Application In Synthesis [ 38696-20-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 38696-20-7 ]

[ 38696-20-7 ] Synthesis Path-Downstream   1~26

  • 1
  • [ 179260-95-8 ]
  • [ 38696-20-7 ]
  • [ 15719-64-9 ]
  • 2
  • [ 38696-20-7 ]
  • 5-bromo-2-o-nitrophenylpyrimidine [ No CAS ]
  • 5-bromo-2-(3-nitrophenyl)pyrimidine [ No CAS ]
  • 4
  • sodium salt of 5-bromo-2-phenylpyrimidine-4-hydroxamic acid [ No CAS ]
  • [ 38696-20-7 ]
  • [ 26789-00-4 ]
  • 5
  • sodium salt of 5-bromo-2-phenylpyrimidine-4-hydroxamic acid [ No CAS ]
  • [ 38696-20-7 ]
  • [ 26789-00-4 ]
  • [ 166537-29-7 ]
  • 6
  • [ 38696-20-7 ]
  • [ 87120-72-7 ]
  • [ 1187635-09-1 ]
YieldReaction ConditionsOperation 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]+.
  • 7
  • [ 38696-20-7 ]
  • [ 7560-83-0 ]
  • [ 292638-85-8 ]
  • [ 131274-22-1 ]
  • [ 545426-64-0 ]
YieldReaction ConditionsOperation 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)+.
  • 8
  • [ 38696-20-7 ]
  • [ 107-31-3 ]
  • [ 130161-46-5 ]
YieldReaction ConditionsOperation 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)+.
  • 9
  • [ 38696-20-7 ]
  • [ 68701-47-3 ]
  • [ 1119084-96-6 ]
YieldReaction ConditionsOperation 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]
  • 10
  • [ 288-42-6 ]
  • [ 38696-20-7 ]
  • [ 1217902-01-6 ]
YieldReaction ConditionsOperation 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.
  • 11
  • [ 38696-20-7 ]
  • [ 96797-15-8 ]
  • [ 1217902-45-8 ]
YieldReaction ConditionsOperation 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.
  • 12
  • [ 38696-20-7 ]
  • [ 97674-02-7 ]
  • [ 1071323-12-0 ]
YieldReaction ConditionsOperation 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).
  • 13
  • [ 38696-20-7 ]
  • [ 37734-89-7 ]
  • [ 1217902-36-7 ]
YieldReaction ConditionsOperation 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.
  • 14
  • [ 20662-88-8 ]
  • [ 38696-20-7 ]
  • [ 1217902-05-0 ]
YieldReaction ConditionsOperation 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.
  • 15
  • [ 38696-20-7 ]
  • [ 1217902-60-7 ]
  • [ 1217902-51-6 ]
YieldReaction ConditionsOperation 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).
  • 16
  • [ 38696-20-7 ]
  • [ 1037746-91-0 ]
  • [ 1217902-22-1 ]
YieldReaction ConditionsOperation 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.
  • 17
  • [ 38696-20-7 ]
  • C14H10N2 [ No CAS ]
  • C24H16N4 [ No CAS ]
YieldReaction ConditionsOperation 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.
  • 18
  • [ 38696-20-7 ]
  • C16H27BrMgSSi [ No CAS ]
  • C17H14N2S [ No CAS ]
  • 19
  • [ 38696-20-7 ]
  • C16H27BrMgSSi [ No CAS ]
  • C26H34N2SSi [ No CAS ]
  • 20
  • [ 38696-20-7 ]
  • [ 79-06-1 ]
  • (E)-3-(2-phenylpyrimidin-5-yl)acrylamide [ No CAS ]
YieldReaction ConditionsOperation 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).
  • 21
  • [ 38696-20-7 ]
  • 3-(2-phenylpyrimidin-5-yl)propanamide [ No CAS ]
  • 22
  • [ 38696-20-7 ]
  • tert-butyl (2-(2-phenylpyrimidin-5-yl)ethyl)carbamate [ No CAS ]
  • 23
  • [ 38696-20-7 ]
  • 2-(2-phenylpyrimidin-5-yl)ethan-1-amine hydrochloride [ No CAS ]
  • 24
  • [ 38696-20-7 ]
  • 5-bromo-2-(3-nitrophenyl)pyrimidine [ No CAS ]
  • 25
  • [ 38696-20-7 ]
  • 2-phenylindeno[2,1-d]pyrimidine-9-one [ No CAS ]
  • 26
  • [ 38696-20-7 ]
  • C24H18N2O [ No CAS ]
 

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Technical Information

Categories

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