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Chemical Structure| 50840-23-8 Chemical Structure| 50840-23-8
Chemical Structure| 50840-23-8

5-Methylpyrimidin-2-amine

CAS No.: 50840-23-8

4.5 *For Research Use Only !

Cat. No.: A154541 Purity: 98%

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Product Details of [ 50840-23-8 ]

CAS No. :50840-23-8
Formula : C5H7N3
M.W : 109.13
SMILES Code : NC1=NC=C(C)C=N1
MDL No. :MFCD00463477
InChI Key :MHZNCOBCMWBPPM-UHFFFAOYSA-N
Pubchem ID :12999933

Safety of [ 50840-23-8 ]

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

Calculated chemistry of [ 50840-23-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 6
Fraction Csp3 0.2
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 31.4
TPSA ?

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

51.8 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.16
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

0.22
Log Po/w (WLOGP)?

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

0.38
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.

-0.31
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

0.69
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.43

Water Solubility

Log S (ESOL):?

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

-1.21
Solubility 6.73 mg/ml ; 0.0616 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-0.87
Solubility 14.8 mg/ml ; 0.136 mol/l
Class?

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

Very 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

-1.62
Solubility 2.64 mg/ml ; 0.0242 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

No
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

No
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.

-6.81 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)

1.23

Application In Synthesis of [ 50840-23-8 ]

* 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 [ 50840-23-8 ]

[ 50840-23-8 ] Synthesis Path-Downstream   1~29

  • 1
  • [ 7153-13-1 ]
  • [ 50840-23-8 ]
  • 2
  • [ 50-01-1 ]
  • [ 42588-57-8 ]
  • [ 50840-23-8 ]
  • 3
  • [ 50840-23-8 ]
  • [ 6541-19-1 ]
  • 8-methyl-1,6b,10,11-tetraazabenzo[a]fluorene-5,6-dione [ No CAS ]
  • 4
  • [ 50840-23-8 ]
  • [ 599-88-2 ]
  • 5
  • [ 1780-36-5 ]
  • [ 50840-23-8 ]
  • 6
  • [ 50840-23-8 ]
  • [ 929568-22-9 ]
  • S-6-methoxy-4-(5-methylpyrimidin-2-ylamino)-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
32% With caesium carbonate;palladium diacetate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 150℃; for 1h;Irradiation; 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (87mg, 0.15mmol) and palladium (II) acetate (21mg, 0.09mmol) were added under nitrogen to a deoxygenated suspension of S- 4-chloro-6-methoxy-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-l-yl}pyrimidine (358mg, lmmol), <strong>[50840-23-8]2-amino-5-methylpyrimidine</strong> (131mg, 1.2mmol) and cesium carbonate (489mg, 1.5mmol) in anhydrous 1,4-dioxane (5ml). The mixture was heated at 1500C in a sealed vessel under microwave irradiation for 1 hour. The mixture was allowed to cool, insoluble material was removed by filtration and the volatiles removed from the filtrate by evaporation. The residue was purified by column chromatography on silica gel eluting with EtOAc / isohexane (20:80 increasing in polarity to 50:50) to give the title compound (136mg, 32%); NMR (500.13 MHz, 373K) 2.10 (IH, s), 2.15 (2H, d), 2.21 (3H, s), 3.77-3.78 (2H, m), 3.76- 3.80 (3H, m), 5.46-5.48 (IH, m), 6.79 (IH, s), 6.95 (IH, s), 7.44-7.47 (IH, m), 7.91-7.93 (IH, m), 7.96 (IH, t), 8.42 (2H, s), 8.62 (IH, s), 8.66-8.68 (IH, m); m/z 431 [MH]+.
  • 7
  • [ 50840-23-8 ]
  • N-{trans-3-[(5-cyano-6-methylpyridin-2-yl)oxy]-2,2,4,4-tetramethylcyclobutyl}-6-methylimidazo[1,2-a]pyrimidine-3-carboxamide [ No CAS ]
  • 8
  • [ 209959-33-1 ]
  • [ 544-97-8 ]
  • [ 50840-23-8 ]
YieldReaction ConditionsOperation in experiment
80% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 110℃; for 16h;Inert atmosphere; Step B: A mixture of 2-[bis(tert-butoxycarbonyl)amino]-5-bromopyrimidine (3.0 g, 8.0 mmol), dimethylzinc (1.2 M x 8.0 mL, 9.6 mmol) and [Iota , - bis(diphenylphosphino)ferrocene]dichloropalladium(II) (130 mg, 0.16 mmol) in 1 ,4-dioxane (30 mL) was stirred at 1 10 C for 16 h under Argon. The mixture was cooled to room temperature, diluted with ethyl acetate and washed with saturated NH4C1, water and brine. The organic layer was dried over NaS04, concentrated and purified by silica gel column chromatography (0-35% EtOAc in hexanes) to give a white solid, which was dissolved in trifluoroacetic acid (5.0 mL). After 5 min, the solvent was removed and the residue was partitioned between ethyl acetate and an aqueous saturated NaHC03 solution. The organic layer was dried over NaS04, filtered and concentrated to give the title compound (0.7 g, 80%>) as a white solid. MS m/z 110.1 [M+H]+.
80% Step B: A mixture of 2-[bis(tert-butoxycarbonyl)amino]-5-bromopyrimidine (3.0 g, 8.0 mmol), dimethylzinc (1.2 M×8.0 mL, 9.6 mmol) and [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (130 mg, 0.16 mmol) in 1,4-dioxane (30 mL) was stirred at 110 C. for 16 h under Argon. The mixture was cooled to room temperature, diluted with ethyl acetate and washed with saturated NH4Cl, water and brine. The organic layer was dried over NaSO4, concentrated and purified by silica gel column chromatography (0-35% EtOAc in hexanes) to give a white solid, which was dissolved in trifluoroacetic acid (5.0 mL). After 5 min, the solvent was removed and the residue was partitioned between ethyl acetate and an aqueous saturated NaHCO3 solution. The organic layer was dried over NaSO4, filtered and concentrated to give the title compound (0.7 g, 80%) as a white solid. MS m/z 110.1 [M+H]+.
  • 9
  • [ 50840-23-8 ]
  • 3-bromo-2-(chloromethyl)-6-methylimidazo[1,2-a]pyrimidine [ No CAS ]
  • 10
  • [ 50840-23-8 ]
  • 1-(3-bromo-6-methylimidazo[1,2-a]pyrimidin-2-yl)-N-methylmethanamine [ No CAS ]
  • 11
  • [ 50840-23-8 ]
  • tert-butyl((3-bromo-6-methylimidazo[1,2-a]pyrimidin-2-yl)methyl)(methyl)carbamate [ No CAS ]
  • 12
  • [ 50840-23-8 ]
  • methyl 2-[(1R)-1-({3-[bis(tert-butoxycarbonyl)-amino]-6-(2-[(tert-butoxycarbonyl)methylamino]methyl}-6-cyanoimidazo[1,2-a]pyridin-3-yl)pyrazin-2-yl}oxy)ethyl]-4-fluorobenzoate [ No CAS ]
  • 14
  • [ 50840-23-8 ]
  • (5R)-8-amino-3-fluoro-5,14,19-trimethyl-18,19-dihydro-7,11-(metheno)pyrimido[2′,1′:2,3]imidazo[4,5-h][2,5,11]benzoxadiazacyclotetradecin-20(5H)-one [ No CAS ]
  • 15
  • [ 50840-23-8 ]
  • N-methyl-1-(6-methylimidazo[1,2-a]pyrimidin-2-yl)methanamine [ No CAS ]
  • 16
  • [ 50840-23-8 ]
  • [ 534-07-6 ]
  • 2-(chloromethyl)-6-methylimidazo[1,2-a]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
24% In tetrahydrofuran; at 90℃; for 72h;Molecular sieve; Step 2: The reaction was done in two batches using 1 g and 9.36 g of compound 185 and the crude material obtained from both batches was combined for purification. To a slurry of compound 185 (9.36 g, 85.82 mmol) in dry THF (250 mL) was added dichloroacetone (21 .80 g, 171.64 mmol) and 4A molecular sieves (25 g). The reaction mixture was heated at 90 C for 3 days, then the reaction mixture was concentrated and the resulting residue dissolved in water (200 mL). The solution was treated with solid K2C03 (10 g) and stirred for 10 min before extraction with ethyl acetate (3 x 400 mL). The combined ethyl acetate extracts were washed with brine (100 mL) and concentrated to give the crude product as thick brown oil. The aqueous phase was subjected to liquid-liquid extraction with DCM (500 mL) and the resulting product obtained was combined with the crude oil obtained from the ethyl acetate extractions for purification. Purification by silica gel column chromatography using 0.5% - 1 % MeOH in DCM furnished compound 186 as off-white solid (4.2 g, 24% yield).1 H NMR (400 MHz, Chloroform-d) delta 8.44 (d, J = 2.4 Hz, 1 H), 8.23 (dd, J = 2.4, 1 .2 Hz, 1 H), 7.56 (d, J = 0.8 Hz, 1 H), 4.79 (d, J = 0.8 Hz, 2H), 2.37 (d, J = 1.1 Hz, 3H). LCMS m/z 182 [M+H]+.
  • 20
  • [ 50840-23-8 ]
  • [ 84911-18-2 ]
  • [ 1335054-73-3 ]
YieldReaction ConditionsOperation in experiment
23% With sodium hydrogencarbonate; In 1,2-dimethoxyethane; for 36h;Inert atmosphere; Reflux; 2-Amino-5-methylpyrimidine (1.0 g, 8.9 mmol), ethyl-2-bromoacetoacetate(2.3 g, 10.7 mmol) and sodium bicarbonate (1.1 g, 13.3 mmol) were dissolved in 25 mL of 1,2-dimethoxyethane (DME) and heated for 36 h at reflux. The reaction mixture was filtered; solids were collected and washed with CH2Cl2. The filtrate was concentrated in vacuo and the residue was dissolved in CH2Cl2 and washed with 5% acetic acid solution (2x) and brine. The organic phase was collected, dried over Na2SO4, filtered and then concentrated in vacuo. Crude material obtained was purified by silica gel column chromatography with a 25% ethyl acetate : CH2Cl2 solvent system to give 0.457 g (23%) of ethyl 2,6-dimethylimidazo[1,2-a]pyrimidine-3-carboxylate as a light solid. 1H NMR (300 MHz, CDCl3) delta 9.37 (dd, J = 2.4, 1.1 Hz, 1H), 8.53 (d, J = 2.4 Hz, 1H), 2.75 (s, 3H), 4.41 (q, J = 7.1, 7.1, 7.1 Hz, 2H), 2.40 (s, 3H) 1.44 (t, J = 7.1, 7.1 Hz, 3H).
  • 21
  • [ 50840-23-8 ]
  • C38H47FN6O9 [ No CAS ]
  • 22
  • [ 50840-23-8 ]
  • C18H17N3O2 [ No CAS ]
  • 5-methyl-N-(5-methylpyrimidin-2-yl)-4-[4-(1H-pyrazol-1-yl)benzyl]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
3. Compound C24 was converted to its methyl ester via treatment with hydrogen chloride in methanol at 60 C. 5-Methylpyrimidin-2-amine and trimethylaluminum were combined in toluene and tetrahydrofuran, and heated at 30 C for 16 hours. The methyl ester was then added, and the reaction mixture was heated at 80 o to provide the product.
  • 23
  • [ 50840-23-8 ]
  • [ 1476847-52-5 ]
  • 2-(4-(benzyloxy)-6-methoxybenzofuran-2-yl)-6-methylimidazo[1,2-a]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
61.4% In isopropyl alcohol; at 20 - 80℃; for 40h; In an 80 mE high pressure vessel under nitrogen,mixture of <strong>[50840-23-8]5-methylpyrimidin-2-amine</strong> (0.245 g, 2.245 mmol) and 1 -(4-(benzyloxy)-6-methoxybenzothran-2-yl)-2- bromoethanone (0.599 g, 1.596 mmol) in 2-propanol (16 mE) was stirred at room temperature for 16 h and a further 24 h at 80 C. The cooled mixture was diluted with dichloromethane and the organic solution was washed once with saturated aqueous sodium bicarbonate, once with brine and finally it was dried over anhydrous sodium sulfate andconcentrated in vacuo. The residue was purified on the ISCO using a 40 g Innoflash column (Hexane/EtOAc) and the solid obtained was triturated with methanol to give2-(4-(benzyloxy)-6-methoxybenzofuran-2-yl)-6-methylimi- dazo[1,2-a]pyrimidine (0.378 mg, 61.4%) as a beige solid. EC (Analytical Method A): 2.117 mm; (Analytical Method B): 2.3 14 mi HRMS (ESI): calcd for C23H2QN303 [M+H] mlz 386.1499; found 386.1488. ?H NMR (400 MHz,DMSO-d5) oe 8.79 (dd, J=1.2, 2.3 Hz, 1H), 8.46 (d, J=2.3 Hz,1H), 8.19 (s, 1H), 7.56-7.50 (m, 2H), 7.46-7.39 (m, 2H),7.38- 7.32 (m, 1H), 7.24 (d, J=0.8 Hz, 1H), 6.90-6.87 (m,1H), 6.55 (d, J=2.0 Hz, 1H), 5.28 (s, 2H), 3.81 (s, 3H), 2.323H).
  • 24
  • [ 50840-23-8 ]
  • 6-methoxy-2-(6-methylimidazo[1,2-a]pyrimidin-2-yl)benzofuran-4-ol [ No CAS ]
  • 25
  • [ 50840-23-8 ]
  • 4-(((6-methoxy-2-(6-methylimidazo[1,2-a]pyrimidin-2-yl)benzofuran-4-yl)oxy)methyl)-2-phenylthiazole [ No CAS ]
  • 26
  • [ 50840-23-8 ]
  • 4-(4-(((6-methoxy-2-(6-methylimidazo[1,2-a]pyrimidin-2-yl)benzofuran-4-yl)oxy)methyl)thiazol-2-yl)-N,N-dimethylbenzamide [ No CAS ]
  • 27
  • [ 50840-23-8 ]
  • 4-(4-(((6-methoxy-2-(6-methylimidazo[1,2-a]pyrimidin-2-yl)benzofuran-4-yl)oxy)methyl)-5-methyl-thiazol-2-yl)morpholine [ No CAS ]
  • 28
  • [ 50840-23-8 ]
  • [ 1446333-79-4 ]
  • 7-fluoro-3-(6-methylimidazo[1,2-a]pyrimidin-2-yl)-2H-chromen-2-one hydrobromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% In ethanol; at 95℃; for 16h; Step A: Following the procedure in Example 36, Part 3, 3-(2-bromoacetyl)-7-fluoro-2H-chromen-2-one (0.855 g, 3.0 mmol) and <strong>[50840-23-8]5-methylpyrimidin-2-amine</strong> (0.327 g, 3.0 mmol) in EtOH (6.0 mL) gave 7-fluoro-3-(6-methylimidazo[1,2-a]pyrimidin-2-yl)-2H-chromen-2-one hydrobromide (0.37 g, 42%) as a pale yellow solid. MS m/z 296.2 [M+H]+.
 

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Technical Information

Categories

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[ 50840-23-8 ]

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