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Chemical Structure| 865156-68-9 Chemical Structure| 865156-68-9

Structure of 865156-68-9

Chemical Structure| 865156-68-9

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Product Details of [ 865156-68-9 ]

CAS No. :865156-68-9
Formula : C6H4BrN3
M.W : 198.02
SMILES Code : BrC1=CN2C(N=C1)=NC=C2
MDL No. :MFCD09261434
InChI Key :BQMWMOQCMFLRQQ-UHFFFAOYSA-N
Pubchem ID :26967622

Safety of [ 865156-68-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 865156-68-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 9
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 40.69
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

30.19 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.43
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

1.8
Log Po/w (WLOGP)?

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

1.49
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.

0.95
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

1.2
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.37

Water Solubility

Log S (ESOL):?

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

-2.87
Solubility 0.269 mg/ml ; 0.00136 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.

-2.05
Solubility 1.75 mg/ml ; 0.00885 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

-2.57
Solubility 0.533 mg/ml ; 0.00269 mol/l
Class?

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

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.

-6.23 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

1.0
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)

1.69

Application In Synthesis of [ 865156-68-9 ]

* 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 [ 865156-68-9 ]

[ 865156-68-9 ] Synthesis Path-Downstream   1~18

  • 1
  • [ 1072-97-5 ]
  • [ 2032-35-1 ]
  • [ 865156-68-9 ]
YieldReaction ConditionsOperation in experiment
62% A suspension of 2-amino-5-bromopyrimidine (3.0 g, 17.2 mmol), bromoacetaldehyde diethyl acetal (3.2 mL, 20.7 mmol) and 48% HBr (1.7 mL) in EtOH was heated was heated to 80 0C in a sealed tube for 16 h. After cooling to rt, the reaction was adjusted to pH ~12 with 6N NaOH and the resultant precipitate was collected by filtration, rinsed with water followed by hexanes and dried to a constant weight to give 2.12 g (62%) of 6-bromoimidazo[l,2-alpha]pyrimidine as a white solid. MS(ES)+ m/e 199.7 [M+H]+.
  • 2
  • [ 107-20-0 ]
  • [ 7752-82-1 ]
  • [ 865156-68-9 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In water; at 25℃; for 24h; c) 6-Bromo-imidazo[1,2-a]pyrimidine; 50 mmol of 5-bromo-pyrimidin-2-ylamine are dissolved in 200 mi of saturated aqueous sodium hydrogencarbonate solution. 55 mmol of chloroacetaldehyde are added to the reaction mixture and the mixture is stirred for 24 hours at 25C. The mixture is extracted with ethyl acetate (3x300 mi) and the combined extracts are dried over sodium sulphate and evaporated under reduced pressure. Flash chromatography (Si02 60F) of the residue provides the title compound which is identified on the basis of its Rf-value.
In ethanol; water; at 20℃; for 16h;Heating / reflux; Example 9; 211 212 213Part A:To compound 211 (1.00 g, 5.74 mmol) in ethanol (100 ml_) was added chloroacetaldehyde (50 wt% solution in water, 7.34 ml_, 57.5 mmol) at room temperature. The reaction mixture was heated at reflux for 16 hours at which time LC- MS analysis indicated that the reaction was complete. The reaction mixture was concentrated under vacuum. The residue was taken back up in ethyl acetate and saturated sodium bicarbonate. The organic and aqueous layers were separated. The organic layer was washed with brine, dried over anh. sodium sulfate and concentrated to afford compound 212 as a beige solid. 1H NMR (400 MHz, DMSO-d6) delta 9.32 (d, 1 H), 8.56 (d, 1 H), 7.85 (d, 1 H), 7.74 (d, 1 H).
With sodium hydrogencarbonate; In water; at 25℃; for 24h; c) 6-Bromo-imidazof1w2-alPyrimidine; 50 mmol of 5-bromo-pyrimidin-2-ylamine are dissolved in 200 mi of saturated aqueous sodium hydrogencarbonate solution. 55 mmol of chloroacetaldehyde are added to the reaction mixture and the mixture is stirred for 24 hours at 25C. The mixture is extracted with ethyl acetate (3x300 ml) and the combined extracts are dried over sodium sulphate and evaporated under reduced pressure. Flash chromatography (SiO2 60F) of the residue provides the title compound which is identified on the basis of its Rf-value
  • 3
  • [ 915278-11-4 ]
  • [ 865156-68-9 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In water; Step 1: 6-Bromoimidazo[l,2-alpha]pyrimidinium hydrobromide. A suspension of 5-bromo-2- aminopyrimidine (6.00 g, 34.5 mmol), bromoacetaldehyde diethylacetal (10.4 mL, 69.0 mmol), 4.0 mL 48% aqueous HBr and 40 mL ethanol was stirred at reflux overnight. Then, the suspension was cooled to room temperature, filtered and dried in vacuo to afford the title compound as an off-white solid. The HBr salt generated above was treated with aqueous NaHCC>3 and the aqueous mixture was extracted with CH2Cl2 to afford after concentration in vacuo pale yellow crystals. 1H NMR (600 MHz, DMSOd6) delta 9.74 (d, IH, J = 2.4 Hz); 9.12 (d, IH, J = 2.4 Hz); 8.28 (d, IH, J = 1.8 Hz); 8.20 (d, IH, J = 1.8 Hz); 6.0 (br s, IH). LCMS (APCI) exact mass calc'd for [M + H]+ (C6H5N3Br) requires mlz 198.0, 200.0 found 197.7, 199.7. EPO <DP n="43"/>
  • 4
  • [ 865156-68-9 ]
  • [ 1067902-23-1 ]
  • [ 1067895-51-5 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; methanol; water; at 100℃; A mixture of 3-cyclobutyl-9-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-3,9-diazaspiro[5.5]undecane (60 mg, 0.15 mmol), <strong>[865156-68-9]6-bromoimidazo[1,2-a]pyrimidine</strong> (35 mg, 0.18 mmol), Pd(PPh)4 (18 mg, 0.015) and K2CO3 (138 mg) in dioxane (4 mL) and water (0.5 mL) is heated overnight at 100 C. Water is added and the mixture is extracted with EA (2×10 mL). The combined organic layers are placed directly on an SCX (ion-exchange) column. The column is first washed with EA (discarded to waste) and second with EA/MeOH/TEA (90:10:10) which is collected. The solvent is removed and the crude product is purified by PTLC (5% TEA in EA/MeOH [95:5]) to give the title compound. 1H NMR (300 MHz, CDCl3) delta 8.79 (1H, d), 8.50 (1H, d), 7.82 (1H, d), 7.56 (1H, d), 7.46 (2H, d), 7.03 (2H, d), 3.74-3.24 (4H, m), 2.93 (1H, m), 2.56-2.45 (4H, m), 2.12-2.09 (2H, m), 1.8-1.67 (12H, m). LC-MS (Method 1): 402.13; RT=1.2 min.
  • 5
  • [ 865156-68-9 ]
  • [ 100-46-9 ]
  • [ 1205125-49-0 ]
YieldReaction ConditionsOperation in experiment
In acetonitrile; at 120℃; for 0.5h;sealed tube; Microwave irradiation; 670 mul of benzylamine, 2 ml of acetonitrile and 400 mg of <strong>[865156-68-9]6-bromoimidazo[1,2-a]pyrimidine</strong> are charged to a glass tube. The tube is sealed and heated at 120 C. for 30 minutes using microwave radiation. After returning to a temperature in the vicinity of 20 C., the reaction medium is evaporated to dryness by evaporation under reduced pressure and the solid isolated is chromatographed, under argon pressure, on silica gel (eluent dichloromethane/methanol 95/5). 112 mg of N-benzylimidazo[1,2-a]pyrimidin-6-amine are thus obtained in the form of an orange lacquer. MS: method A; [M+H]+ m/z=225; Tr=0.38 min.
  • 6
  • [ 108-85-0 ]
  • [ 865156-68-9 ]
  • [ 1205125-43-4 ]
YieldReaction ConditionsOperation in experiment
12 ml of ethanol, 920 mg of potassium hydroxide pellets and 1 g of <strong>[865156-68-9]6-bromoimidazo[1,2-a]pyrimidine</strong> are charged to a glass tube. The tube is sealed and heated at 135 C. for 12 minutes using microwave radiation. After returning to a temperature in the vicinity of 20 C., 1.5 ml of bromocyclohexane are added. The tube is again sealed and the combined mixture is heated at 140 C. for 15 minutes using microwave radiation. After returning to a temperature in the vicinity of 20 C., the reaction medium is evaporated to dryness under reduced pressure and the solid isolated is chromatographed, under argon pressure, on silica gel (eluent dichloromethane/methanol 97/3). 75 mg of 6-(cyclohexyloxy)imidazo[1,2-a]pyrimidine are thus obtained in the form of a beige solid. MS: method B; [M+H]+ m/z=218; Tr=2.54 min.
  • 7
  • [ 865156-68-9 ]
  • [ 1205125-38-7 ]
  • 8
  • [ 865156-68-9 ]
  • [ 1205125-39-8 ]
  • 9
  • [ 865156-68-9 ]
  • [ 108-91-8 ]
  • [ 1205125-46-7 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In acetonitrile; at 120℃; for 0.5h;sealed tube; Microwave irradiation; EXAMPLE 25c N-cyclohexylimidazo[1,2-a]pyrimidin-6-amine The product can be prepared in the following way: 3.2 g of <strong>[865156-68-9]6-bromoimidazo[1,2-a]pyrimidine</strong>, 5.5 ml of cyclohexylamine and 32 ml of acetonitrile are charged to a glass tube. The tube is sealed and heated at 120 C. for 30 minutes using microwave radiation. After returning to a temperature in the vicinity of 20 C., 100 ml of an aqueous potassium carbonate solution are added and the resulting aqueous phase is extracted with 3 times 150 ml of ethyl acetate and 1 times 150 ml of dichloromethane. The organic phases are combined, washed with 2 times 200 ml of an aqueous sodium chloride solution, dried over sodium sulphate, filtered and concentrated by evaporation under reduced pressure. The residue obtained is chromatographed on silica gel (eluent dichloromethane/methanol 95/5). 720 mg of N-cyclohexylimidazo[1,2-a]pyrimidin-6-amine are thus obtained in the form of a brown oil. MS: method A; [M+H]+ m/z=217; Tr=0.45 min.
  • 10
  • [ 865156-68-9 ]
  • [ 768-35-4 ]
  • [ 1205125-40-1 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 150℃; for 0.333333h;sealed tube; Microwave irradiation; EXAMPLE 23c 6-(3-fluorophenyl)imidazo[1,2-a]pyrimidine The compound can be prepared in the following way: 400 mg of <strong>[865156-68-9]6-bromoimidazo[1,2-a]pyrimidine</strong> (commercially available product), 345 mg of 3-fluorophenylboronic acid, 69 mg of tetrakis(triphenylphosphine)palladium, 2 ml of a 2M aqueous sodium carbonate solution and 8 ml of dimethylformamide are charged to a sealed glass tube. The medium is heated at 150 C. for 20 minutes using microwave radiation. After returning to a temperature in the vicinity of 20 C., the medium is filtered through a bed of Clarcel Flo M and rinsing is carried out with 2 times 2 ml of dimethylformamide and then 2 times 5 ml of methanol. The filtrate is concentrated to dryness by evaporation under reduced pressure. The solid isolated is suspended in 80 ml of distilled water, stirred, filtered off, washed with distilled water, superficially freed from the washing medium and dried under reduced pressure. 430 mg of 6-(3-fluorophenyl)imidazo[1,2-a]pyrimidine are thus obtained in the form of a light brown solid. MS: method A; [M+H]+ m/z=214; Tr=0.38 min. 1H NMR (400 MHz, d6-DMSO) delta ppm 7.28 (td, J=8.5, 2.6 Hz, 1H) 7.51-7.66 (m, 2H) 7.69 (dt, J=10.5, 2.0 Hz, 1H) 7.78 (d, J=1.5 Hz, 1H) 7.92 (d, J=1.5 Hz, 1H) 8.93 (d, J=2.7 Hz, 1H) 9.38 (d, J=2.7 Hz, 1H).
  • 11
  • [ 865156-68-9 ]
  • [ 1083326-28-6 ]
  • [ 1351597-75-5 ]
  • 15
  • [ 7752-82-1 ]
  • [ 2032-35-1 ]
  • [ 865156-68-9 ]
YieldReaction ConditionsOperation in experiment
20 g Under ice cooling, water (20 mL), hydrobromic acid (content 48%, 20 mL) and bromoacetaldehyde diethyl acetal (45 mL) was added to, and stirred for 1 hour 30 minutes at room temperature. After stirring the reaction solution with ice-cold vigorously was added sodium hydrogen carbonate (31 g), the reaction solution was filtered. To the filtrate, ethanol (122 ml) and 2-amino-5-bromopyrimidine (21 g) was added and stirred for 35 min at 85 C. To the reaction solution was ice-cooled, water (244 mL) was added, was neutralized with sodium hydroxide solution of 4M, and stirred for 30 minutes. Collected by filtration resulting suspension, water (60 mL), followed by n- washed with hexane (60 mL), to give after drying the title compound (20 g) as a solid.
  • 16
  • [ 865156-68-9 ]
  • C7H5FN2O2S [ No CAS ]
  • 17
  • [ 865156-68-9 ]
  • [ 151169-75-4 ]
  • 6-(3,4-dichlorophenyl)imidazo[1,2-a]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
520 mg With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In tetrahydrofuran; water; at 100℃; for 1h;Inert atmosphere; Microwave irradiation; The compound of Reference Example 4 (600 mg), 3,4-dichlorophenylboronic acid (635 mg), tetrakis (triphenylphosphine) palladium (175 mg) and sodium carbonate(803 mg) in tetrahydrofuran / water mixed solution (10.1 mL / 5 mL)Were stirred at 100 C. for 1 hour under a nitrogen atmosphere using a microwave reactor. After cooling to room temperature, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane / ethyl acetate) to give the title compound (520 mg) as a solid.
  • 18
  • [ 865156-68-9 ]
  • N-(2-(3-bromophenyl)propan-2-yl)-2-(trifluoromethyl)benzenesulfonamide [ No CAS ]
  • N-(2-(3-(imidazo[1,2-a]pyrimidin-6-yl)phenyl)propan-2-yl)-2-(trifluoromethyl)benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
EtOH (1.8 mL) was added into a mixture of 4-bromo-3-ethylpyridinehydrobromide (49 mg, 0.18 mmol), B2(OH)4 (49 mg, 0.55 mmol), XPhos-Pd-G2 (14 mg, 0.018 mmol), XPhos (17 mg, 0.037 mmol), and KOAc (54 mg, 0.55 mmol). The reaction was degassed via N2 and stirred at 80C overnight. After cooling to room temperature, solutions of N-(2-(3-bromophenyl)propan-2-yl)-2-(trifluoromethyl)benzenesulfonamide (Intermediate 1J) (100 mg, 0.24 mmol) in EtOH/THF (0.3 mL/0.3 mL) and K2C03 (1.8 M, 0.31 mL, 0.55 mmol) were added respectively into the reaction. The mixture was degassed via N2 again and stirred at 85C overnight. The reaction was cooled to room temperature, filtered through celite, washed with EtOAc (3X), and concentrated in vacuo to give a residue which was dissolved into EtOAc. This solution was washed with brine (IX), dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by MS-HPLC to afford the title compound (16 mg, 20%). LCMS (method A): m/z 449.3 (M+H)+. NMR (CDC13) delta 8.54 (s, 1H), 8.46 (d, 1H), 7.83 (d, 1H), 7.79 (d, 1H), 7.59 (t, 1H), 7.47 (t, 1H), 7.31 (m, 2H), 7.21 (t, 1H), 7.11 (dt, 1H), 7.03 (d, 1H), 5.28 (s, 1H), 2.63 (q, 2H), 1.69 (s, 6H), 1.13 (t, 3H).
 

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