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Structure of 1722-12-9

Chemical Structure| 1722-12-9

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Product Details of [ 1722-12-9 ]

CAS No. :1722-12-9
Formula : C4H3ClN2
M.W : 114.53
SMILES Code : ClC1=NC=CC=N1
MDL No. :MFCD00006060
InChI Key :UNCQVRBWJWWJBF-UHFFFAOYSA-N
Pubchem ID :74404

Safety of [ 1722-12-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319
Precautionary Statements:P261-P270-P271-P264-P280-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330-P302+P352+P312-P304+P340+P312-P501

Computational Chemistry of [ 1722-12-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 27.04
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.

1.41
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

0.36
Log Po/w (WLOGP)?

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

1.13
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.

0.16
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

1.74
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.96

Water Solubility

Log S (ESOL):?

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

-1.41
Solubility 4.44 mg/ml ; 0.0388 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.

-0.47
Solubility 39.2 mg/ml ; 0.342 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

-2.21
Solubility 0.705 mg/ml ; 0.00615 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

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.

-6.74 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

2.0
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)

1.19

Application In Synthesis of [ 1722-12-9 ]

* 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.

  • Upstream synthesis route of [ 1722-12-9 ]
  • Downstream synthetic route of [ 1722-12-9 ]

[ 1722-12-9 ] Synthesis Path-Upstream   1~9

  • 1
  • [ 1722-12-9 ]
  • [ 2949-92-0 ]
  • [ 49844-93-1 ]
References: [1] Angewandte Chemie - International Edition, 2006, vol. 45, # 18, p. 2958 - 2961.
  • 2
  • [ 110-91-8 ]
  • [ 1722-12-9 ]
  • [ 57356-66-8 ]
YieldReaction ConditionsOperation in experiment
79% With 1-methyl-3-(2-pyridinyl)-3,4,5,6-tetrahydropyrimidin-3-ium hexafluorophosphate; potassium <i>tert</i>-butylate; palladium diacetate In 1,2-dimethoxyethane at 100℃; for 0.666667 h; Microwave irradiation General procedure: The Buchwald–Hartwig amination reaction under microwave irradiation was conducted in a CEM Discover apparatus. A 10-mL Teflon vessel was charged with 1.0 mmol of hetero-aryl halide, 3.0 mmol of amine, 2.0 of mmol base, 0.05 mmol of Pd(OAc)2 , 0.10 mmol of LHX, and 2.0 mL of solvent. The mixture was irradiated at 150 W at 100 °C for the specified time and then allowed to cool. The reaction mixture was extracted 3 times with diethyl ether, and the combined organic extracts were washed with water, dried (MgSO4) , and evaporated to dryness. Purification of the residue by flash chromatography on silica gel afforded the pure products.
79% With potassium carbonate In N,N-dimethyl-formamide for 24 h; To a solution of morpholine 5a (3.63 mL, 42 mmol) in DMF (50 mL), K2CO3 (5.8 g, 42 mmol) was added; after 20 min stirring, 2-chloropyrimidine (4.0 g,35 mmol) was added. The reaction mixture was stirred for 24 h, the solvent was removed in vacuo, the residue was purified by column chromatography (elution with ethyl acetate—hexane, 1 : 1).
12% With (2-mesityl-1H-inden-3-yl)dicyclohexyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate In 1,2-dimethoxyethane at 120℃; for 24 h; Inert atmosphere General procedure: Pd(dba)2/1-catalyzed amination of aryl halides: An oven-dried Schlenk tube equipped with a magnetic stirring bar was charged with Pd(dba)2 (5.8 mg, 0.010 mmol), ligand 1 (8.6 mg, 0.020 mmol) and tBuONa (134 mg, 1.4 mmol). The flask was capped with a rubber septum, evacuated, and then flushed with argon. This cycle was repeated three times. Amine (1.2 mmol), aryl halide (1.0 mmol) and DME (4 mL) were then successively added by syringe. The tube was stirred at room temperature for several minutes and then placed into a preheated oil bath (120 °C) for the time period as indicated in tables. After completion of reaction as judged by GC analysis, the reaction tube was allowed to cool to room temperature and the reaction mixture was adsorbed onto silica gel, and then purified by column chromatography (hexane/ethyl acetate as eluent) to afford the desired product.
References: [1] European Journal of Organic Chemistry, 2016, vol. 2016, # 36, p. 5957 - 5963.
[2] ChemSusChem, 2013, vol. 6, # 8, p. 1455 - 1460.
[3] Journal of Organic Chemistry, 2017, vol. 82, # 7, p. 3741 - 3750.
[4] Turkish Journal of Chemistry, 2015, vol. 39, # 1, p. 121 - 129.
[5] Russian Chemical Bulletin, 2014, vol. 63, # 6, p. 1350 - 1358[6] Izv. Akad. Nauk, Ser. Khim., 2014, # 6, p. 1350 - 1358.
[7] Journal of Organometallic Chemistry, 2012, vol. 706-707, p. 99 - 105.
[8] Journal of the Chemical Society, 1954, p. 1190,1192.
[9] European Journal of Medicinal Chemistry, 2017, vol. 136, p. 270 - 282.
  • 3
  • [ 110-91-8 ]
  • [ 1722-12-9 ]
  • [ 64-17-5 ]
  • [ 57356-66-8 ]
References: [1] Journal of the Chemical Society, 1954, p. 1190,1192.
  • 4
  • [ 1722-12-9 ]
  • [ 105-53-3 ]
  • [ 63155-11-3 ]
YieldReaction ConditionsOperation in experiment
92%
Stage #1: With sodium hydride In N,N-dimethyl-formamide; mineral oil at -78℃; for 0.166667 h;
Stage #2: at 20 - 120℃; for 90 h;
To a solution of diethylmalonate (6.65 mL, 43.65 mmol) in DMF (30 mL) at -78 °C,was added NaH (1.76 g, 52.38 mmol, 60percent dispersion in mineral oil). The reaction was stirredfor 10 min at -78 °C, warmed to room temperature and 2-chloropyrimidine (1.0 g, 8.73 mmol)in DMF (3 mL) was added. The reaction mixture was heated to 80 °C for 72 hours, then to120 °C for 18 hours, and upon completion was cooled to room temperature. The solution was15 quenched by addition of IN HCl, neutralized with saturated aqueous NaHC03 and extractedwith EtOAc (3X). The combined organics were dried over Na2S04, filtered, concentrated andpurified by flash chromatography on silica gel (0-1 00percent EtOAc in hexanes) to give the titlecompound as a yellow-orange oil (1.34 g, 92percent). MS 167 (MH+).
References: [1] Patent: WO2014/25706, 2014, A1, . Location in patent: Page/Page column 87.
  • 5
  • [ 1722-12-9 ]
  • [ 57260-73-8 ]
  • [ 584-08-7 ]
  • [ 137583-05-2 ]
References: [1] Patent: US6159964, 2000, A, .
  • 6
  • [ 1722-12-9 ]
  • [ 107-15-3 ]
  • [ 137583-05-2 ]
References: [1] Journal of Medicinal Chemistry, 2018, vol. 61, # 1, p. 360 - 371.
[2] Journal of Medicinal Chemistry, 1992, vol. 35, # 4, p. 705 - 716.
  • 7
  • [ 1722-12-9 ]
  • [ 1126-09-6 ]
  • [ 111247-60-0 ]
YieldReaction ConditionsOperation in experiment
81% for 18 h; Reflux; Inert atmosphere Method ACompound 1: l-Pyrimidin-2-yl-piperidine-4-carboxylic acid ethyl esterA mixture of 2-chloropyrimidine (2.28g, 20mmol) and ethyl isonipecotate (4.72g, 30mmol) in toluene (10ml) was heated at reflux for 18 h. then cooled to RT. The mixture was diluted with EtOAc and washed with saturated aqueous NaHCO3. The organics were separated, dried, and the solvents removed in vacuo. The residue was purified by flash chromatography on silica (eluant: EtOAc/pet. ether 40/60 v/v) to yield the title compound as a colourless oil.Yield = 4.0Og, 81percent. (ESI+): [M+H]+ = 236.0
References: [1] Farmaco, 1993, vol. 48, # 10, p. 1439 - 1445.
[2] Patent: WO2010/97576, 2010, A1, . Location in patent: Page/Page column 39.
[3] Journal of Medicinal Chemistry, 2013, vol. 56, # 21, p. 8696 - 8711.
  • 8
  • [ 1722-12-9 ]
  • [ 395082-55-0 ]
YieldReaction ConditionsOperation in experiment
18%
Stage #1: With N,N,N,N,-tetramethylethylenediamine; zinc(II) chloride In tetrahydrofuran at 0℃; for 2 h; Inert atmosphere
Stage #2: With iodine In tetrahydrofuranInert atmosphere
To a stirred, cooled (0 °C) solution of 2,2,6,6-tetramethylpiperidine (0.50 mL, 3.0 mmol) in THF (6 mL) were successively added BuLi(about 1.6 M hexanes solution, 3.0 mmol) and, 5 min later, ZnCl2·TMEDA7 (0.26 g, 1.0mmol). The mixture was stirred for 15 min at 0 °C before introduction of 2-chloropyrimidine(2, 0.11 g, 1.0 mmol). After 2 h at this temperature, a solution of I2 (0.76 g, 3.0 mmol) in THF(10 mL) was added. The mixture was stirred overnight before addition of an aqueoussaturated solution of Na2S2O3 (10 mL) and extraction with AcOEt (3 x 20 mL). The combinedorganic layers were dried over MgSO4, filtered and concentrated under reduced pressure.Purification was performed by chromatography on silica gel (eluent: heptane/AcOEt 95/5) toafford 4a in 18percent yield as a beige powder
References: [1] Chemistry - A European Journal, 2009, vol. 15, # 6, p. 1468 - 1477.
[2] Synlett, 2015, vol. 26, # 20, p. 2811 - 2816.
  • 9
  • [ 1722-12-9 ]
  • [ 541-41-3 ]
  • [ 1196152-00-7 ]
References: [1] Patent: US9953768, 2018, B2, . Location in patent: Page/Page column 79-80.
 

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