33742-70-0|6-Chloro-N-methyl-3-nitropyridin-2-amine| Ambeed

Structure of 33742-70-0

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

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

Quality Control of [ 33742-70-0 ] Purity: 95% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 33742-70-0 ]

CAS No. :	33742-70-0
Formula :	C₆H₆ClN₃O₂
M.W :	187.58
SMILES Code :	O=[N+](C1=CC=C(Cl)N=C1NC)[O-]
MDL No. :	MFCD08460164
InChI Key :	XBUWSEJQFZDJAZ-UHFFFAOYSA-N
Pubchem ID :	10750094

Safety of [ 33742-70-0 ]

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

Computational Chemistry of [ 33742-70-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	6
Fraction Csp3	0.17
Num. rotatable bonds	2
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	47.37
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	70.74 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.4
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	2.51
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.49
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.	0.87
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	-0.45
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.17

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.82
Solubility	0.282 mg/ml ; 0.00151 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.	-3.64
Solubility	0.0428 mg/ml ; 0.000228 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	-2.46
Solubility	0.647 mg/ml ; 0.00345 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.	-5.66 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	3.0 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)	2.37

Application In Synthesis of [ 33742-70-0 ]

* 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 [ 33742-70-0 ]
Downstream synthetic route of [ 33742-70-0 ]

[ 33742-70-0 ] Synthesis Path-Upstream 1~1

1
[ 5470-18-8 ]
[ 4093-88-3 ]
[ 33742-70-0 ]

References: [1] Patent: US5624935, 1997, A, .

[ 33742-70-0 ] Synthesis Path-Downstream 1~42

1
[ 33742-70-0 ]
[ 89660-14-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With hydrogenchloride; tin(II) chloride dihdyrate; In water; for 18.0h;Reflux;	6-Chloro-N-methyl-3-nitropyridin-2-amine(9) (10.5 g, 56 mmol) and tin(II) chloride dihydrate (50.5 g,224 mmol) were suspended in concentrated HCl (80 mL) and refluxed for 18h. The solution was cooled to 0 C and5M aqueous NaOH was cautiously added until the solution had a pH of 8. The mixture was subsequently partitioned with300 mL ethyl acetate and the layers were separated. The organics were washed with brine (200 mL),dried over sodium sulfate, filtered and concentrated in vacuo to give 6-chloro-N2-methylpyridine-2,3-diamine(10) as an off-white solid(7.5 g, 85%). HRMS m/z(M+H): calculated = 158.0480; observed = 158.0471.
63%	With iron; acetic acid; at 80℃; for 3.0h;	To a mixture of D5 (15.8 g, 84.2 mmol) in acetic acid (100 mL) was added iron powder (15.4 g, 276 mmol). The reaction mixture was stirred at 80 C. for 3 hours, whereupon it was cooled to room temperature and filtered. The filter cake was washed with ethyl acetate (2×100). The combined organic layers were concentrated under reduced pressure and the crude material was purified by silica gel chromatography (Eluent: 1:1 ethyl acetate/petroleum ether) to afford D6 (8.40 g, 63% yield) as a brown solid. 1H NMR (400 MHz, chloroform-d) delta 6.79 (d, J=7.7 Hz, 1H), 6.49 (d, J=7.7 Hz, 1H), 3.00 (s, 3H)
63%	With iron; acetic acid; at 80℃; for 3.0h;	To a mixture of C59 (15.8 g, 84.2 mmol) in acetic acid (100 ml_) was added iron powder (15.4 g, 276 mmol). The yellow mixture was stirred at 80 C for 3 hours. The reaction was cooled to room temperature and filtered. The filter cake was washed with EtOAc (2 x 100). The combined organic layers were concentrated under reduced pressure and the crude product was purified by flash chromatography (120 g silica gel, 50% EtOAc / petroleum ether) to afford C60 (8.40 g, 63% yield) as a brown solid. 1H NMR (CDCI3) d 6.80 (d, 1 H), 6.50 (d, 1 H), 3.39 (br s, 2H), 3.01 (s, 3H).

59.7%	With iron; ammonium chloride; In methanol; water; at 20℃; for 3.0h;Reflux;	To a solution of <strong>[33742-70-0]6-chloro-N-methyl-3-nitropyridin-2-amine</strong> (630 mg, 3.36 mmol) in MeOH (10 ml) and water (10 ml) was added Fe (940.8 mg, 16.8 mmol) and NH4C1 (898.8 mg, 168 mmol) at 20C. The mixture was stirred for 3 hours under reflux temperature until TLC (PE: EA =3: 1) showed that the reaction was complete. The mixture was filtered, the filtrate concentrated and residue treated with water (10 ml) and extracted with ethyl acetate (2x20 ml). The combined organic layers were washed with brine (30 ml), dried over Na2S04 and concentrated to give the desired product (316 mg, 59.7%) as a yellow solid which was used in next step without further purification. LCMS (m/z): 158.1 [M+H]+.
	With hydrogenchloride; stannous chloride dihydrate; In water;Reflux;	6-Chloro-N-methyl-3-nitropyridin-2-amine (28-1, 10.5 g, 56 mmol) and tin(II) chloride dihydrate (50.5 g, 224 mmol) were suspended in concentrated HCl (80 mL) and refluxed overnight. The solution was cooled to room temperature and then added very slowly to a NaOH/ethyl acetate solution at -78 C, until the solution had a slightly basic pH. The suspension was washed with sodium bicarbonate, brine, dried over sodium sulfate, filtered, and concentrated to produce 6-chloro-N2-methylpyridine-2,3-diamine (28-2) as a black solid. HRMS (M+H)+: observed =158.0471, calculated =158.0480.
		6-chloro-N2-methylpYridine-2,3-diamine (1-2) <strong>[33742-70-0]6-chloro-N-methyl-3-nitropyridin-2-amine</strong> (l-l)(10.5g, 56 mmol) and Tin(II) chloride dihydrate(50 g, 220 mmol) were suspended in concentrated HC1 (80 mL) and refluxed overnight. The solution was cooled to room temperature and then added very slowly to a NaOH/Ethyl acetate solution at -78C, until the solution had a slightly basic pH. The suspension was washed with sodium bicarbonate, brine, dried over sodium sulfate, filtered, and concentrated to produce the black solid 6-chloro-N2-methylpyridine-2,3-diamine(l~2). MS (M+H)+: observed = 158.0, calculated = 158.6.
		6-Chloro-N-methyl-3-nitropyridin-2-amine (1-1, 10.5 g, 56 mmol) and tin(II) chloride dehydrate (50.5 g, 224 mmol) were suspended in concentrated HC1 (80 mL) and refiuxed overnight. The solution was cooled to room temperature and then added very slowly to a NaOH/ethyl acetate solution at -78 C, until the solution had a slightly basic pH. The suspension was washed with sodium bicarbonate, brine, dried over sodium sulfate, filtered, and concentrated to produce 6-chloro-N2-methylpyridine-2,3-diamine (1-2) as a black solid.
	With hydrogenchloride; tin(II) chloride dihdyrate; In water;Reflux;	6-Chloro-N2-methylpyridine-2,3-diamine (1-2)6-Chloro-N-methyl-3-nitropyridin-2-amine (1-1, 10.5 g, 56 mmol) and tin(II) chloride dehydrate (50.5 g, 224 mmol) were suspended in concentrated HCI (80 mL) and refluxed overnight. The solution was cooled to room temperature and then added very slowly to a NaOH/ethyl acetate solution at -78C, until the solution had a slightly basic pH. The suspension was washed with sodium bicarbonate, brine, dried over sodium sulfate, filtered, and concentrated to produce 6-chloro-N2-methylpyridine-2,3-diamine (1-2) as a black solid. HRMS (M+H)+: observed = 158.0487, calculated = 158.0480.
	With hydrogen; In tetrahydrofuran; methanol; at 20℃; for 23.0h;	Step 102.2: 6-chloro-N2-methylpyridine-2,3-diamine The title compound was prepared in analogy to the procedure described in Step 85.2 using <strong>[33742-70-0]6-chloro-N-methyl-3-nitropyridin-2-amine</strong> (Step 102.1) at RT for 23 hr. The crude material was purified by silica gel column chromatography (25% EtOAc/hexane) to afford a purple solid. tR: 0.64 min (LC-MS 2); ESI-MS: 158 [M+H]+ (LC-MS 2); Rf=0.12 (25% EtOAc/Hexane).
	With hydrogen; In tetrahydrofuran; at 20℃; for 23.0h;	To a solution of 5-bromo-N,3-dimethyl-2-nitroaniline (Step 85.1) (2.7 g, 11.02 mmol) in THF(100 mL) and MeOH (100 mL) was added Raney Nickel (189 mg, 2.203 mmol) and the resultingmixture was stirred under hydrogen atmosphere at RT for 16 hr. The reaction was filtered through a pad of Celite and the resulting filtrate was concentrated under reduced pressure to afford the title product (2.5 g, 10.56 mmol, 96% yield) as off-white solid. tR: 0.94 mm (LC-MS 2); ESl-MS: 214 [M+H] (LC-MS 2). The title compound was prepared in analogy to the procedure described in Step 85.2 using <strong>[33742-70-0]6-chloro-N-methyl-3-nitropyridin-2-amine</strong> (Step 102.1) at RT for 23 hr. The crude material waspurified by silica gel column chromatography (25% EtOAc/hexane) to afford a purple solid. tR:0.64 mm (LC-MS 2); ESl-MS: 158 [M+H] (LC-MS 2); R = 0.12 (25% EtOAc/Hexane).
	With iron; acetic acid; In ethanol; water;	3.0 g <strong>[33742-70-0]6-chloro-N-methyl-3-nitro-pyridin-2-amine</strong> (16 mmol) was dissolved in the mixture of 30 ml ethanol and 15 ml water then 4.47 g iron powder (80 mmol, 5 eq.) was added. To this mixture 1.2 ml glacial acetic acid was added dropwise then the reaction mixture was refluxed until no further conversion was observed. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure and the residue was purified via flash chromatography using DCM as eluent to give 6-chloro-2-methylamino-3-aminopyridine. MS(M+H) = 158.2
	With iron; acetic acid; at 80℃; for 3.0h;	To a mixture of <strong>[33742-70-0]6-chloro-N-methyl-3-nitropyridin-2-amine</strong> (15.8 g, 84.2 mmol) in AcOH (100 mL) was added iron powder (15.4 g, 276 mmol). The yellow mixture was stirred at 80 C. for 3 h. The reaction was cooled to RT and filtered. The filtercake was washed with EtOAc (2*100). The combined organic layers were concentrated under reduced pressure and the crude product was purified by flash chromatography (120 g silica gel, 50% EtOAc/PE) to afford 3-amino-6-chloro-2-methylaminopyridine (8.40 g, 63% yield) as a brown solid. 1H NMR (CDCl3) delta 6.80 (d, 1H), 6.50 (d, 1H), 3.39 (br s, 2H), 3.01 (s, 3H).

References: [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 1260 - 1264.
[2]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 312 - 317.
[3]Patent: US2019/382384,2019,A1 .Location in patent: Paragraph 0493; 0495.
[4]Patent: WO2019/239371,2019,A1 .Location in patent: Page/Page column 86.
[5]Patent: WO2014/100695,2014,A1 .Location in patent: Paragraph 00395.
[6]European Journal of Medicinal Chemistry,1983,vol. 18,p. 501 - 506.
[7]Patent: WO2011/109277,2011,A1 .Location in patent: Page/Page column 76.
[8]Patent: WO2011/156245,2011,A2 .Location in patent: Page/Page column 25-26.
[9]Patent: WO2011/34741,2011,A1 .Location in patent: Page/Page column 23-24.
[10]Patent: WO2012/174199,2012,A1 .Location in patent: Page/Page column 22-23.
[11]Patent: US2014/349990,2014,A1 .Location in patent: Paragraph 0952; 0953; 1015; 1016.
[12]Patent: WO2014/191896,2014,A1 .Location in patent: Page/Page column 193; 194; 209.
[13]Patent: WO2017/55530,2017,A1 .Location in patent: Page/Page column 31.
[14]Patent: US2018/170908,2018,A1 .Location in patent: Paragraph 0443.

2
[ 882856-58-8 ]
[ 33742-70-0 ]
[ 882856-88-4 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In toluene; for 24.0h;Heating / reflux;	To a solution of 300 mg (0.9 mmol) of Intermediate 2 and 206 mg (1.1 mmol) 6- chloro-N-methyl-3-nitropyridin-2-amine in 5 mL toluene was added 0.33 mL (1.4 mmol) of N,N- diisopropylethylamine and the solution was stirred under nitrogen at reflux for 24 h. The reaction mixture was then cooled to ambient temperature, diluted with 25 mL ethyl acetate, and washed sequentially with saturated aqueous sodium bicarbonate solution and saturated aqueous brine (25 mL each). The organic phase was then dried over magnesium sulfate, filtered, and evaporated in vacuo to yield a yellow solid which was purified by reverse phase HPLC (YMC Pro-C18 column, gradient elution, 10-90% acetonitrile/water with 0.1% trifluoroacetic acid) to afford the title compound as a yellow crystalline solid.

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 4579 - 4583.
[2]Patent: WO2006/39325,2006,A2 .Location in patent: Page/Page column 35; 51.

3
[ 33742-70-0 ]
[ 882856-89-5 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 4579 - 4583.

4
[ 33742-70-0 ]
C₂₆H₃₂F₃N₅O₃ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 4579 - 4583.

5
[ 33742-70-0 ]
C₂₆H₃₀F₃N₅O₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 4579 - 4583.

6
[ 33742-70-0 ]
C₂₁H₂₂F₃N₅*C₂HF₃O₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 4579 - 4583.

7
[ 33742-70-0 ]
[ 90817-34-8 ]