Home Cart Sign in  
Chemical Structure| 4331-28-6 Chemical Structure| 4331-28-6

Structure of 4331-28-6

Chemical Structure| 4331-28-6

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

,{[proInfo.pro_purity]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size Price VIP Price

US Stock

Global Stock

In Stock
{[ item.pr_size ]} Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

  • {[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Alternative Products

Product Details of [ 4331-28-6 ]

CAS No. :4331-28-6
Formula : C3H6ClN3
M.W : 119.55
SMILES Code : NC1=CNN=C1.[H]Cl
MDL No. :MFCD01693708
InChI Key :KZDSLIPVDTVHLL-UHFFFAOYSA-N
Pubchem ID :78034

Safety of [ 4331-28-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 4331-28-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 2.0
Molar Refractivity 29.96
TPSA ?

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

54.7 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

-0.29
Log Po/w (WLOGP)?

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

0.8
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.

-0.68
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

0.56
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.08

Water Solubility

Log S (ESOL):?

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

-0.93
Solubility 14.1 mg/ml ; 0.118 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.

-0.4
Solubility 47.7 mg/ml ; 0.399 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

-0.76
Solubility 20.6 mg/ml ; 0.173 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.

-7.24 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)

1.3

Application In Synthesis of [ 4331-28-6 ]

* 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 [ 4331-28-6 ]

[ 4331-28-6 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 1426921-32-5 ]
  • [ 4331-28-6 ]
  • 2-cyclopropylmethoxy-5-[2-(1H-pyrazol-4-ylamino)pyridin-4-yl]-benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
26.6 mg With tris-(dibenzylideneacetone)dipalladium(0); lithium hexamethyldisilazane; In tetrahydrofuran; tert-butyl alcohol; at 140.0℃; for 2h;Inert atmosphere; A solution of 5-(2-chloropyridin-4-yl)-2-cyclopropylmethoxybenzonitrile (0.25 g, 0.0878 mmol) in t-butanol (5 ml) is degassed with nitrogen for 5 min. 1H-Pyrazol-4-ylamine hydrochloride (0.12 g, 1.08 mmol), Josiphos (24.3 mg, 0.00439 mmol) and tris(dibenzylideneacetone)dipalladium(0) (40.0 mg, 0.00439 mmol) is then added. A solution of 1.6M lithium bis(trimethylsilyl)amide in THF (0.35 g, 2.1 mmol) is added dropwise. The mixture is irradiated in the microwave at 140 C. for 2 h. 30 ml of water are then added, and the mixture is filtered. The crude product is purified by chromatography, giving 26.6 mg of the desired product as brown solid; [0540] 1H NMR (400 MHz, DMSO-d6): delta [ppm] 12.47 (bs, 1H), 8.80 (s, 1H), 8.13 (d, J=5.36 Hz, 1H), 8.04 (d, J=2.16 Hz, 1H), 7.92 (dd, J=2.24, 8.82 Hz, 2H), 7.54 (bs, 1H), 7.34 (d, J=8.92 Hz, 1H), 6.92 (d, J=5.28 Hz, 1H), 6.86 (s, 1H), 4.06 (d, J=7.00 Hz, 2H), 1.23-1.30 (m, 1H), 0.59-0.63 (m, 2H), 0.31-0.39 (m, 2H); [0541] LCMS: (method A) 332 (M+H), RT. 3.25 min; [0542] HPLC: (method A) RT. 3.23 min.
  • 2
  • [ 2075-46-9 ]
  • [ 63680-90-0 ]
  • [ 4331-28-6 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; triethylsilane; Pd/Al2O3; In ethanol; water; at 15.0℃; for 73h;Inert atmosphere; A 1000-mL, multi-neck cylindrical jacketed reactor, fitted with a mechanical stirrer, temperature probe and nitrogen inlet, was charged with 4-nitropyrazole (50.0 g, 429 mmol) and palladium on alumina (5 wt %, 2.5 g). Ethanol (150 mL) was added, followed by a slow addition of concentrated hydrochloric acid (37 wt %, 180 mL). The reaction was cooled to 15 C., and triethylsilane (171 mL, 1072 mmol) was added slowly via addition funnel over 1 hour, while maintaining the internal temperature at 15 C. The reaction was stirred at 15 C. for 72 hours, after which the reaction mixture was filtered through a Celite pad and the pad was rinsed with warm ethanol (40 C., 2×100 mL). The combined filtrates were separated and the aqueous layer (bottom layer) was concentrated to 100 mL. Acetonitrile (200 mL) was added and the resulting suspension was stirred at 20 C. for 1 hour and filtered. The filter cake was rinsed with acetonitrile (2×100 mL) and dried under vacuum at 20 C. to afford a white solid (10:1 mixture of 1a and 1H-pyrazol-4-amine, 65.5 g, 99%): 1H NMR (400 MHz, DMSO-d6) delta 10.52 (bs, 3H), 8.03 (s, 1H); EIMS m/z 117 ([M]+).
  • 3
  • [ 944709-42-6 ]
  • [ 4331-28-6 ]
  • 6-bromo-N-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With triethylamine; In N,N-dimethyl-formamide; at 95℃; for 18h; 6,8-dibromo-[1,2,4]triazolo[1,5-a]pyrazine (22.1 g, 80 mmol) and 1H-pyrazol-4-aminehydrochloride (10.0 g, 84 mmol) were combined in DMF (398 mL). Triethylamine (33.3 mL, 239mmol) was added and the mixture was heated to 95 °C for 18 h. The reaction mixture was thencooled to ambient temperature and concentrated under reduced pressure. The residue was suspendedin water (300 mL) and sonicated and filtered. Trituration in ether provided 6-bromo-N-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine (19.3 g, 68.9 mmol, 87percent); 1H NMR (400MHz, DMSO-d6) delta 12.67 (s, 1H), 10.65 (s, 1H), 8.54 (s, 1H), 8.10 (s, 1H), 7.82 (s, 1H).
  • 4
  • [ 4331-28-6 ]
  • (R)-2-(methylcarbamoyl)-6-(1-phenylethyl)isonicotinic acid [ No CAS ]
  • (R)-N<SUP>2</SUP>-methyl-6-(1-phenylethyl)-N<SUP>4</SUP>-(1H-pyrazol-4-yl)pyridine-2,4-dicarboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With N-ethyl-N,N-diisopropylamine; O-(benzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate; In N,N-dimethyl-formamide; at 20.0℃; for 2.75h; To a mixture of (R)-2-(methylcarbamoyl)-6-(1-phenylethyl)isonicotinic acid (53.7 mg, 0.19 mmol),HATU (86.7 mg, 0.23 mmol) and 1H-pyrazol-4-amine, hydrochloride (28.9 mg, 0.24 mmol) in DMF (1mL) was added DIPEA (0.132 mL, 0.76 mmol). The resulting dark grey solution was stirred at rt for2.75 h. The reaction mixture was diluted with DMSO (2 mL) and directly purified by MDAP (3 mLinjection, high pH). The required fractions (fractions 1 and 2) were combined and evaporated in vacuoto give the desired product as a light yellow solid - (R)-N2-methyl-6-(1-phenylethyl)-N4-(1H-pyrazol-4-yl)pyridine-2,4-dicarboxamide (39.9 mg, 0.11 mmol, 61 % yield)LCMS (2 mm High pH): Rt = 0.92 mi [MH]+ = 350.3.
  • 5
  • [ 4331-28-6 ]
  • (±)-2-(methoxy(phenyl)methyl)-6-(methylcarbamoyl)isonicotinic acid [ No CAS ]
  • (+/-)-6-(methoxy(phenyl)methyl)-N<SUP>2</SUP>-methyl-N<SUP>4</SUP>-(1H-pyrazol-4-yl)pyridine-2,4-dicarboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% 2-(Methoxy(phenyl)methyl)-6-(methylcarbamoyl)isonicotinic acid (150 mg, 0.50 mmol) was added to a dry flask. DMF (2 mL) was added, followed by HATU (228 mg, 0.60 mmol) and 1H-pyrazol-4-amine, hydrochloride (59.7 mg, 0.50 mmol). The reaction was stirred for 2 mm and then DIPEA (0.262 mL,1.498 mmol) was added. The reaction was stirred at rt for 30 mm. The reaction mixture was added directly to 3 x LCMS vials, diluting with DMS0/Me0H and purified by 3 x MDAP (High pH). Theappropriate fractions were concentrated in vacuoto afford the desired product as a yellow solid - (+1- )-6-(methoxy(phenyl)methyl)-N2-methyl-N4-( 1 H-pyrazol-4-yl)pyridine-2,4-dicarboxamide (100 mg, 0.27 mmol, 55 % yield)LCMS (2 mm Formic): Rt = 0.82 mi [MH]+ = 366.3.1H NMR (400 MHz, DMS0-d6) O ppm 12.69 (br. s., 1 H) 10.92 (5, 1 H), 8.67 (q, J=4.8 Hz, 1H), 8.45 (d, J=1.7 Hz, 1 H), 8.17 (d, J=1.5 Hz, 1 H), 8.04 (br. 5., 1 H), 7.72 (br. 5., 1 H), 7.51 (d, J=7.1 Hz, 2 H), 7.36 (t, J=7.5 Hz, 2 H), 7.24 - 7.31 (m, 1 H), 5.52 (5, 1 H), 3.39 (5, 3 H), 2.88 (d, J=4.9 Hz, 3 H)
  • 6
  • [ 4331-28-6 ]
  • 2-benzyl-6-(methylcarbamoyl)isonicotinic acid [ No CAS ]
  • 6-benzyl-N<SUP>2</SUP>-methyl-N<SUP>4</SUP>-(1H-pyrazol-4-yl)pyridine-2,4-dicarboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% With N-ethyl-N,N-diisopropylamine; O-(benzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate; In N,N-dimethyl-formamide; at 20.0℃; for 3.5h; To a mixture of 2-benzyl-6-(methylcarbamoyl)isonicotinic acid (251.8 mg, 0.93 mmol) and HATU(565.5 mg, 1.49 mmol) was added <strong>[4331-28-6]1H-pyrazol-4-amine hydrochloride</strong> (166.0 mg, 1.39 mmol) andDMF (4 mL). DIPEA (0.570 mL, 3.26 mmol) was added and the mixture was stirred at rt for 3.5 h.The mixture was concentrated under a stream of nitrogen and then diluted with acetonitrile to a totalvolume of 5 mL and directly purified by MDAP (5 x 1 mL injection; high pH) and the required fractions(fraction 1 from each run) were evaporated under a stream of nitrogen. The residues were eachredissolved in methanol ( 5 mL), combined into a tarred vial and the solvent evaporated under a stream of nitrogen to give a pale yellow solid - 6-benzyl-N2-methyl-N4-(1H-pyrazol-4-yl)pyridine-2,4- dicarboxamide (198.9 mg, 0.59 mmol, 64 % yield)LCMS (2 mm High pH): Rt = 0.85 mi [MH]+ = 336.1.1H NMR (400 MHz, DMSO-d6) O ppm 12.71 (br. 5., 1 H), 10.88 (s, 1 H), 8.78 (q, J=4.5 Hz, 1H), 8.40 (d, J=1.5 Hz, 1 H), 8.02 (br. 5., 1 H), 7.90 (d, J=1.5 Hz, 1 H), 7.70 (br. 5., 1 H), 7.36 - 7.41 (m, 2 H), 7.29 - 7.36 (m, 2 H), 7.19 - 7.26 (m, 1 H), 4.25 (s, 2 H), 2.88 (d, J=4.9 Hz, 3 H)
  • 7
  • [ 4331-28-6 ]
  • (S)-2-(methylcarbamoyl)-6-(1-phenylethyl)isonicotinic acid [ No CAS ]
  • (S)-N<SUP>2</SUP>-methyl-6-(1-phenylethyl)-N<SUP>4</SUP>-(1H-pyrazol-4-yl)pyridine-2,4-dicarboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With N-ethyl-N,N-diisopropylamine; O-(benzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate; In N,N-dimethyl-formamide; at 20.0℃; for 2h; To a mixture of (S)-2-(methylcarbamoyl)-6-(1-phenylethyl)isonicotinic acid (80.5 mg, 0.28 mmol) and HATU (172.0 mg, 0.45 mmol) was added <strong>[4331-28-6]1H-pyrazol-4-amine hydrochloride</strong> (51.6 mg, 0.43 mmol) and DMF (1.8 mL). DIPEA (0.173 mL, 0.99 mmol) was added and the mixture was stirred at rt for 2 h. The mixture was concentrated under a stream of nitrogen and diluted with acetonitrile to a total volume of 2 mL and directly purified by MDAP (2 x 1 mL injection; formic) and the required fractions (fraction 1 from both runs) were combined and evaporated in vacuo. The residue was redissolved inmethanol ( 6 mL) and transferred to a tarred vial, the solvent evaporated under a stream of nitrogen and the residue dried in vacuo to give the desired product as a yellow solid, (S)-N2-methyl-6-(1- phenylethyl)-N4-( 1 H-pyrazol-4-yl)pyridine-2,4-d icarboxamide (87.5 mg, 0.25 mmol, 88 % yield)LCMS (2 mm Formic): Rt = 0.91 mi [MH]+ = 350.3.1H NMR (400 MHz, DMSO-d6) O ppm 10.87 (5, 1 H) 8.80 (d, J=4.2 Hz, 1 H), 8.38 (5, 1 H) 7.80 - 7.96(m, 3 H), 7.43 (d, J=7.6 Hz, 2 H), 7.31 (t, J=7.2 Hz, 2 H), 7.13 - 7.25 (m, 1 H), 4.45 (q, J=6.6 Hz, 2 H), 2.91 (d, J=3.9 Hz, 3 H), 1.74 (d, J=6.8 Hz, 3 H)
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 4331-28-6 ]

Amines

Chemical Structure| 28466-26-4

A159049 [28466-26-4]

4-Aminopyrazole

Similarity: 0.97

Chemical Structure| 1063734-49-5

A114149 [1063734-49-5]

1-Methyl-1H-pyrazol-4-amine dihydrochloride

Similarity: 0.84

Chemical Structure| 127107-23-7

A247043 [127107-23-7]

1-Methyl-1H-pyrazol-4-amine hydrochloride

Similarity: 0.84

Chemical Structure| 69843-13-6

A152410 [69843-13-6]

1-Methyl-1H-pyrazol-4-amine

Similarity: 0.82

Chemical Structure| 1896159-87-7

A759680 [1896159-87-7]

N,1-Dimethyl-1H-pyrazol-4-amine dihydrochloride

Similarity: 0.80

Related Parent Nucleus of
[ 4331-28-6 ]

Pyrazoles

Chemical Structure| 28466-26-4

A159049 [28466-26-4]

4-Aminopyrazole

Similarity: 0.97

Chemical Structure| 1063734-49-5

A114149 [1063734-49-5]

1-Methyl-1H-pyrazol-4-amine dihydrochloride

Similarity: 0.84

Chemical Structure| 127107-23-7

A247043 [127107-23-7]

1-Methyl-1H-pyrazol-4-amine hydrochloride

Similarity: 0.84

Chemical Structure| 69843-13-6

A152410 [69843-13-6]

1-Methyl-1H-pyrazol-4-amine

Similarity: 0.82

Chemical Structure| 1896159-87-7

A759680 [1896159-87-7]

N,1-Dimethyl-1H-pyrazol-4-amine dihydrochloride

Similarity: 0.80