852227-86-2|5-(Chloromethyl)-1,3-dimethyl-1H-pyrazole| Ambeed

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Quality Control of [ 852227-86-2 ] Purity: 98% SDS Specification

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Product Details of [ 852227-86-2 ]

CAS No. :	852227-86-2
Formula :	C₆H₉ClN₂
M.W :	144.60
SMILES Code :	CC1=NN(C)C(CCl)=C1
MDL No. :	MFCD07368502
InChI Key :	SGEZKPNUNBVVLB-UHFFFAOYSA-N
Pubchem ID :	4961270

Safety of [ 852227-86-2 ]

GHS Pictogram:
Signal Word:	Danger
Hazard Statements:	H302-H314
Precautionary Statements:	P260-P264-P270-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P405-P501
Class:	8
UN#:	3261
Packing Group:	Ⅲ

Computational Chemistry of [ 852227-86-2 ] Show Less

Physicochemical Properties

Num. heavy atoms	9
Num. arom. heavy atoms	5
Fraction Csp3	0.5
Num. rotatable bonds	1
Num. H-bond acceptors	1.0
Num. H-bond donors	0.0
Molar Refractivity	38.22
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	17.82 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.73
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	1.06
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.32
Log P_o/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.	1.08
Log P_o/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	1.71
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.38

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.75
Solubility	2.57 mg/ml ; 0.0178 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.	-1.03
Solubility	13.6 mg/ml ; 0.0943 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	-2.18
Solubility	0.951 mg/ml ; 0.00658 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.	-6.43 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	1.0 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)	1.55

Application In Synthesis of [ 852227-86-2 ]

* 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 [ 852227-86-2 ]
Downstream synthetic route of [ 852227-86-2 ]

[ 852227-86-2 ] Synthesis Path-Upstream 1~1

1
[ 57012-20-1 ]
[ 852227-86-2 ]

References: [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 23, p. 8013 - 8029.

[ 852227-86-2 ] Synthesis Path-Downstream 1~39

1
[ 914079-49-5 ]
[ 852227-86-2 ]
3-bromo-5-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-2-(2,5-dimethyl-2H-pyrazol-3-ylmethoxy)-N,N-dimethyl-benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 3h;	Example 42 3-Bromo-5-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-2-(2,5-dimethyl-2H-pyrazol-3-ylmethoxy)-N,N-dimethyl-benzenesulfonamide A mixture of the compound described in example 41a (153 mg), potassium carbonate (125 mg), and <strong>[852227-86-2]5-chloromethyl-1,3-dimethyl-1H-pyrazole</strong> (55 mg) in DMF (1.4 ml) was heated at 60 C. for 3 h. The mixture was diluted with 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by preparative HPLC (Method B), then purified by chromatography on aluminum oxide using ethyl acetate as eluent.Yield: 51 mg. MS-ESI: [M+H]+=616.2/618.2; anal. HPLC: Rt=18.40 min. (method 2)
	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 3h;	Example 423-Bromo-5-(3-cvano-2-methyl-5-oxo-7-propyl-l,4,5,6,7,8-hexahvdro-quinolin-4-yl)-2- (2,5-dimethyl-2H-pyrazol-3-vhtauiethoxy)-iV,iV-dimethyl-benzenesulfonamideA mixture of the compound described in example 41a (153 mg), potassium carbonate (125 mg), and 5-chloromethyl-l,3-dimethyl-lH-pyrazole (55 mg) in DMF (1.4 ml) was heated at 60 0C for 3 h. The mixture was diluted with IN hydrochloric acid and extracted with ethyl acetate. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by preparative EtaPLC (Method B), then purified by chromatography on aluminum oxide using ethyl acetate as eluent.Yield: 51 mg. MS-ESI: [M+Eta]+ = 616.2/618.2; anal. HPLC: Rt = 18.40 min. (method2)

References: [1]Patent: US2008/300270,2008,A1 .Location in patent: Page/Page column 33.
[2]Patent: WO2006/117370,2006,A1 .Location in patent: Page/Page column 65.

3
[ 852227-86-2 ]
[ 100200-99-5 ]
[ 935289-74-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In ISOPROPYLAMIDE; at 140℃; for 18h;	A mixture of nitroguaiacol potassium salt hydrate (1.00 g, 4.83 mmol), <strong>[852227-86-2]5-(chloromethyl)-1,3-dimethyl-1H-pyrazole</strong> (1.0 g. 6.91 mmol) and K2CO3 (14.47 g, 1.99 mmol) in dimethylacetamide (35 mL) was stirred at 140 C. for 18 hours. The mixture was diluted with a solution of sat. NaHCO3, extracted with EtOAc, dried over Na2SO4 and concentrated. The crude product was subjected to ISCO flash chromatography (silica gel/hexane-EtOAc 100:0 to 0:100 gradient) to give the title compound (860 mg) as an off-white solid. Following dissolution in MeOH (150 mL) and addition of 10% Pd/C (150 mg), this nitro aryl ether was reduced by stirring under 50 psi H2 for 3 hours. Filtration and concentration of the filtrate yielded the title compound (660 mg, 58% yield) as an off-white solid. 1H NMR (400 MHz, CHLOROFORM-D) delta ppm 2.18-2.26 (m, 3 H), 3.76-3.84 (m, 3 H), 3.85-3.91 (m, 3 H), 4.87-4.94 (m, 2 H), 5.98-6.04 (m, 1 H), 6.17 (d, 1 H), 6.29 (d, 1 H), 6.73 (d, 1 H). HPLC (Method No.1): 1.69 min. LCMS m/z: 248 (M+H).

References: [1]Patent: US2007/93508,2007,A1 .Location in patent: Page/Page column 10.

4
[ 852227-86-2 ]
[ 1184870-03-8 ]
[ 1184870-05-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; acetonitrile; at 80℃; for 3h;	Example 11: Preparation of (S)-2-(benzofuran-5-sulfonamido)-3-(4-((l,3- dimethyl-lH-pyrazol-5-yl)methoxy)phenyl)-N,N-diisobutyIpropanamide (159); Compound 235 was prepared following the procedure for Scheme 1 except that instead of Boc-L-3-pyridylalanine N-Boc-L-tyrosine was used as the starting material. To a solution of compound 235 (205 mg, 0.52 mmol) in DMF/acetonitrile (1:1, 8 ml) were added potassium carbonate (359 mg, 2.6 mmol) and 5-chloromethyl-l,3-dimethylpyrazole (90 mg, 0.62 mmol). The mixture was stirred at 80 0C. After 3 hrs, water (7 ml) was added to quench the reaction. The aqueous phase was extracted with EtOAc (10 ml) and the organic layer was washed with brine (10 ml), dried over anhydrous MgSO4 and then concentrated in vacuo. The crude material was purified by flash column chromatography (50% EtOAc in hexanes) to provide compound 236 (200 mg, 77%) as a colorless oil. [M+H]+ 501.2, HPLC purity: >99%.To a solution of compound 236 (200 mg, 0.40 mmol) in dichloromethane (4 ml) was added 4N HCl in dioxane (4 ml). The mixture was stirred for 1 hr at room temperature and concentrated in vacuo. To a solution of the resulting material in dichloromethane (4 ml) was added triethylamine (63 mul, 0.45 mmol) and benzofuran-5- sulfonyl chloride (39 mg, 0.18 mmol). After 30 min, water (5 ml) was added to quench the reaction. The aqueous phase was extracted with dichloromethane (5 ml) and the organic layer was washed with brine (5 ml), dried over anhydrous MgSO4 and then concentrated in <n="79"/>vacuo. The crude material was purified by preparative TLC (EtOAc) to provide compound 159 (71 mg, 80%) as a white solid. [M+H]+ 581.3, HPLC purity: >99%.

References: [1]Patent: WO2009/105774,2009,A2 .Location in patent: Page/Page column 77-78.

5
[ 852227-86-2 ]
[ 1215177-08-4 ]
[ 1215177-25-5 ]

Yield	Reaction Conditions	Operation in experiment
50%		Example 155-(3-(Cvclopentyloxy)-4-methoxyphenyl)-1-((1.3-dimethylpyrazol-5-yl)methyl)pyrimidin-2- oneKl (1.2 g, 7.2 mmol) was added to a solution of 5-chloromethyl-1 ,3-dimethylpyrazole (415 mg, 2.9 mmol) in DMF (10 mL) and the mixture was stirred at rt for 30 min. IntermediateA (822 mg, 2.9 mmol) followed by NaH (60 % suspention in oil, 287 mg, 7.2 mmol) were added and the mixture was stirred at rt for 1 h. The mixture was quenched with icecold water (20 mL) and extracted with DCM (3x20 mL). The combined extracts were washed with brine (20 mL), dried over Na2SO4 and concentrated. Crystallization from MeCN gave the title compound. Yield and spectroscopic data are listed in Table 1

References: [1]Patent: WO2010/29299,2010,A1 .Location in patent: Page/Page column 60; 67.

6
[ 936351-54-1 ]
[ 852227-86-2 ]
C₃₂H₄₀BrN₃O₃S [ No CAS ]