2604-39-9|2-Chloro-5-nitropyridin-4-amine| Ambeed

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Quality Control of [ 2604-39-9 ] Purity: 97% SDS Specification

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Product Details of [ 2604-39-9 ]

CAS No. :	2604-39-9
Formula :	C₅H₄ClN₃O₂
M.W :	173.56
SMILES Code :	NC1=CC(Cl)=NC=C1[N+]([O-])=O
MDL No. :	MFCD09033797
InChI Key :	YKWBEPUOVBMENG-UHFFFAOYSA-N
Pubchem ID :	10910058

Safety of [ 2604-39-9 ]

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

Computational Chemistry of [ 2604-39-9 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	1
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	42.47
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	84.73 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.91
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	1.51
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.23
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.	-0.7
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	-0.77
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.44

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.2
Solubility	1.08 mg/ml ; 0.00624 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.	-2.9
Solubility	0.22 mg/ml ; 0.00127 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	-1.66
Solubility	3.81 mg/ml ; 0.0219 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.	-6.29 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)	2.15

Application In Synthesis of [ 2604-39-9 ]

* 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.

Downstream synthetic route of [ 2604-39-9 ]

[ 2604-39-9 ] Synthesis Path-Downstream 1~35

1
[ 2604-39-9 ]
[ 2586-99-4 ]

Yield	Reaction Conditions	Operation in experiment
77%	In ammonium hydroxide;	2,4-Diamino-5-nitropyridine (5): A solution of <strong>[2604-39-9]4-amino-2-chloro-5-nitropyridine</strong> (4) (1.0 g, 5.76 mmol) in 50 ml 28percent NH4OH was heated in a sealed tube at 120° C. for overnight. After cooling the reaction mixture to room temperature afforded orange red solid 5 (0.770 g, 77percent). 1H NMR (DMSO-d6, 500 MHz): delta 8.66 (1H, s), 7.35 (1H, br s), 6.73 (1H, brs), 5.67 (1H, s); EIMS m/z: 155.2 (M+1), 153.2 (M-1)

References: [1]Patent: US2004/116466,2004,A1 .
[2]Roczniki Chemii,1956,vol. 30,p. 1139,1145.
Chem.Abstr., <1957> 12089,.

2
[ 14432-13-4 ]
[ 2604-39-9 ]
[ 2789-25-5 ]

Yield	Reaction Conditions	Operation in experiment
25%; 70%		2-ChloiO-4-nitroaminopyridine (10.0 g, mol) was carefully dissolved in 100 mL of concentrated sulfuric acid at room temperature and heated 100 0C for Ih. After the solution was cooled to room temperature, it was poured onto 250 g of crushed ice and treated with concentrated ammonium hydroxide until pH was reached at 3 while the temperature was kept below 200C with ice bath. The yellow solid was separated and extracted with ethyl acetate (200 ml x 3) from aqueous layer. The collected organic layer was concentrated and the residue was purified with silica gel column chromatography (hexane: EtOAc = 4: 1 to EtOAc v/v) to give 6.0 g of 4-Amino-2-chloro-3-nitropyridine in 70 percent yield and 2.0 g of 4-amino-2- Chloro-5-nitropyridine in 25 percent yield. 4-Amino-2-chloro-3-nitropyridine: mp 179-181 °C; UV (H2O) lambdamax 238.0 (epsilon 13586, pH 11), 1H-NMR (DMSO, 500 MHz) delta 7.91 (d, J= 6.0, IH), 7.37 (s, 2H), 6.83 (d, J = 6.0, IH); 13C-NMR (DMSO, 125 MHz) delta 149.54, 149.24, 142.69, 142.33, 122.45; 4-amino-2-chloro-5-nitropyridine: 1H-NMR (DMSO, 500 MHz) delta 8.85 (s, IH), 7.37 (s, 2H), 6.96 (s, IH).

References: [1]Patent: WO2007/47793,2007,A2 .Location in patent: Page/Page column 87.
[2]Roczniki Chemii,1956,vol. 30,p. 1139,1144.
Chem.Abstr.,1957,p. 12089.
[3]Nucleosides, nucleotides and nucleic acids,2004,vol. 23,p. 67 - 76.
[4]Organic and Biomolecular Chemistry,2013,vol. 11,p. 6526 - 6545.

3
[ 4548-45-2 ]
[ 4214-76-0 ]
[ 2604-39-9 ]
[ 5418-51-9 ]
[ 27048-04-0 ]

References: [1]Journal of Organic Chemistry,1985,vol. 50,p. 484 - 487.
[2]Journal of Organic Chemistry,1985,vol. 50,p. 484 - 487.

5
[ 67-56-1 ]
[ 2604-39-9 ]
[ 127356-38-1 ]

References: [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2231 - 2239.

6
[ 2604-39-9 ]
[ 83277-30-9 ]
[ 194732-40-6 ]

References: [1]Journal of Chemical Research, Miniprint,1997,p. 1359 - 1376.

7
[ 4548-45-2 ]
[ 2604-39-9 ]
[ 27048-04-0 ]

References: [1]Chemical Communications,1998,p. 1519 - 1520.

Yield	Reaction Conditions	Operation in experiment
9%		The mother liquor was purified on SiO2 gel column (30 g) by elution with (Tolune-EtOAc, (85:15) affording the desired minor isomer 4 (11.0 g, 9percent). 1H NMR (DMSO-d6; 500 MHz): delta 8.83 (1H, s), 8.10 (1H, brs), 6.95 (1H, s); EIMS m/z: 174.8 (M+1), 172.8 (M-1).

9
[ 14432-13-4 ]
[ 7664-93-9 ]
[ 2604-39-9 ]
[ 2789-25-5 ]

References: [1]Roczniki Chemii,1956,vol. 30,p. 1139,1144.
Chem.Abstr.,1957,p. 12089.

10
[ 14432-12-3 ]
[ 2604-39-9 ]

Yield	Reaction Conditions	Operation in experiment
8.89%	With sulfuric acid; nitric acid; at 0 - 100℃; for 2.5h;	To a solution of 2-chloropyridin-4-amine (10 g, 78 mmol) in conc. sulfuric acid (60 mL) at 0° C. was slowly added fuming nitric acid (30 mL). Then reaction mixture was stirred for 30 min. The reaction mixture was slowly poured into ice; the pH was adjusted to ?3 with using ammonia solution. The resultant white solid was isolated via filtration. The solid was dissolved in conc. sulfuric acid, then heated to 100° C. for 2 h. The reaction mixture was cooled to room temperature and poured into ice. The aqueous solution was adjusted to pH ?3 using ammonia solution; then was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resultant residue was purified by silica gel chromatography using 30percent ethyl acetate in Pet-ether to afford 2-chloro-5-nitropyridin-4-amine (1.2 g, 6.91 mmol, 8.89percent yield) and 2-chloro-3-nitropyridin-4-amine (6 g, 34.6 mmol, 44.4percent yield) as yellow solids. 1H NMR (400 MHz, DMSO-d6): delta ppm 7.90 (d, J=5.77 Hz, 1H) 7.34 (br. s., 2H) 6.83 (s, 1H). MS: MS m/z 172.2 (M+-1).
	With ammonia; nitric acid; In sulfuric acid;	Step 1: Synthesis of 2-chloro-5-nitropyridin-4-amine To a solution of 2-chloropyridin-4-amine (10 g, 78 mmol) in conc. sulfuric acid (60 mL) at 0° C. was slowly added fuming nitric acid (30 mL). Then reaction mixture was stirred for 30 min. The reaction mixture was slowly poured into ice; the pH was adjusted to ?3 with using ammonia solution. The resultant white solid was isolated via filtration. The solid was dissolved in conc. sulfuric acid, then heated to 100° C. for 2 h. The reaction mixture was cooled to room temperature and poured into ice. The aqueous solution was adjusted to pH ?3 using ammonia solution; then was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resultant residue was purified by silica gel chromatography using 30percent ethyl acetate in Pet-ether to afford 2-chloro-5-nitropyridin-4-amine (1.2 g, 6.91 mmol, 8.89percent yield) and 2-chloro-3-nitropyridin-4-amine (6 g, 34.6 mmol, 44.4percent yield) as yellow solids. 1H NMR (400 MHz, DMSO-d6): delta ppm 7.90 (d, J=5.77 Hz, 1H) 7.34 (br. s., 2H) 6.83 (s, 1H). MS: MS m/z 172.2 (M+-1).

References: [1]Patent: US9643999,2017,B2 .Location in patent: Page/Page column 80; 81.
[2]Nucleosides, nucleotides and nucleic acids,2004,vol. 23,p. 67 - 76.
[3]Roczniki Chemii,1956,vol. 30,p. 1139,1144.
Chem.Abstr.,1957,p. 12089.
[4]Patent: US2014/127156,2014,A1 .Location in patent: Page/Page column.

11
[ 2604-39-9 ]
[ 127356-26-7 ]

References: [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2231 - 2239.
[2]Patent: US2014/127156,2014,A1 .
[3]Patent: US9643999,2017,B2 .

12
[ 2604-39-9 ]
[ 127356-30-3 ]

References: [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2231 - 2239.

13
[ 2604-39-9 ]
[ 127356-08-5 ]

References: [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2231 - 2239.

14
[ 14432-12-3 ]
[ 2604-39-9 ]
[ 2789-25-5 ]

Yield	Reaction Conditions	Operation in experiment
		Example 136: ((2R,3S,4JR/5K)-5-{4-[(lS)-2,3-dihydro-lH-inden-l-ylamino]-lH-imidazo[4,5- c]pyridin-l-yl}-3,4-dihydroxytetrahydrofuran-2-yl)memyl sulfamate (1-149)Step a: 4-amino-2-chloro-3-nitropyridine; [0929] To a solution of 4-amino-2-chloropyridine (10.0 g, 77.8 mmol) in concentratedH2SO4 (6OmL) at 00C was added 90% nitric acid (30 mL) dropwise. The solution was stirred at 0-5 0C for 30 min then poured onto ice (carefully). The pH was brought to ~3 with concentrated aq ammonium hydroxide (~150mL) to obtain a white precipitate which was isolated and dried by filtration. The white solid was dissolved in sulfuric acid (100 mL), heated at 80 C for 5h, stirred at r.t. overnight, then poured on crushed ice. At 0 0C the pH was adjusted to ~3 with concentrated aq ammonium hydroxide (~250 mL) to obtain a yellow precipitate which was isolated by filtration. The solid was dried under vacuum overnight to obtain ~13 g of a mixture of 3- and 5-nitro isomers. A sample (4.0 g) was purified by flash chromatography (0 to 20% DCM/EtOAc) to obtain 1.77 g of the product as a fluffy yellow solid.[0930] LCMS: R.t = 1.15 min, ES+ 174 (formic acid) .
	With sulfuric acid; nitric acid; at 0 - 80℃;pH 1.5 - 3;	(1) at 0 C, 200 g of 2-chloro-4-aminopyridine was dissolved in 1200 mL of concentrated sulfuric acid, and 1000 mL of 65% nitric acid was added dropwise. After completion of the dropwise addition, the reaction was carried out at 15 C for 2 hours and then poured into ice water and stirred at 0 C, The NH3 was adjusted to pH 3, Precipitate a white powdery solid I, filtered. (2) The white powdery solid I was dissolved in 2000 mL of concentrated sulfuric acid, Heated to 80 C reaction 3h, stirring at room temperature overnight, and then into the ice water, 0 C into the NH3 first tune the pH to 1.5, the formation of orange precipitation, filtration, Discard the precipitate, the filtrate and then continue to NH3 to pH 3, filtration, To give a yellow powdery solid II, i.e., isomer 4-amino-2-chloro-3-nitropyridine and 4-amino-2-chloro-5-nitropyridine, the yield of the isomer was 98% Purity of 98%, among them, The yield of 4-amino-2-chloro-3-nitropyridine was 75%. Among them, the reaction at room temperature after stirring overnight there are two purposes: the first is fully responsive; the second is fully cooled; Because the reaction system concentrated sulfuric acid temperature is very high, a short period of time may not cool the internal temperature, concentrated sulfuric acid itself will be added to the water will be exothermic, if the cooling is not completely added to the ice water will be exothermic, prone to danger, so To stirred enough to cool down overnight. (3) The yellow powdery solid II was recrystallized (wherein: the recrystallization reagent was ethyl acetate and petroleum ether, the total amount was 3 times the volume of the yellow powdery solid II, the volume ratio of ethyl acetate to petroleum ether was 1:5), heated to reflux, and then reduced to 30 C to precipitate a yellow powdery solid III. The filtrate was decompressed under reduced pressure to remove the solvent. The residue was recrystallized from 95% ethanol to give the pale yellow powder The solid IV is pure 4-amino-2-chloro-5-nitropyridine in a yield of 22% and a purity of 98%.

References: [1]Patent: WO2006/84281,2006,A1 .Location in patent: Page/Page column 187.
[2]Organic and Biomolecular Chemistry,2013,vol. 11,p. 6526 - 6545.
[3]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 5941 - 5952.
[4]Patent: CN103819398,2016,B .Location in patent: Paragraph 0030-0038.
[5]European Journal of Medicinal Chemistry,2018,vol. 156,p. 240 - 251.
[6]European Journal of Medicinal Chemistry,2019,vol. 176,p. 393 - 409.

15
[ 2604-39-9 ]
[ 506-59-2 ]
[ 886435-69-4 ]

Yield	Reaction Conditions	Operation in experiment
100%		Compound 8; In a microwave tube, a solution of <strong>[2604-39-9]4-amino-2-chloro-5-nitropyridine</strong> (prepared, as described for compound 9) (200 mg; 1.16 mmol) in ethanol (2 ml) was treated sequentially with dimethylamine hydrochloride (471 mg; 5.78 mmol) and triethylamine (781 mu\\; 6.96 mmol). The tube was quickly sealed and irradiated in the microwave (CEM Discover, 150 W, 85 0C, 10 min). The ethanol was evaporated, dichloromethane (15 ml) was added to dissolve the products, and the solution washed with IM sodium hydroxide solution (2 x 10 ml). The organic layer was dried (sodium sulphate), the mixture filtered and the filtrate evaporated to dryness to afford N2,N2-dimethyl-5-nitro-pyridine-2,4-diamine (240 mg, 114percent).

References: [1]Patent: WO2006/50506,2006,A1 .Location in patent: Page/Page column 115.

16
[ 14432-13-4 ]
[ 2604-39-9 ]

Yield	Reaction Conditions	Operation in experiment
		Compound 9; To stirred concentrated sulphuric acid (100 ml) at 4 0C was added 2-chloro-4- aminopyridine (35.0 g; 0.273 mol) in portions. White fuming nitric acid (26 ml) was added drop wise over 20 minutes and the mixture stirred at 4 0C for 1 hour before being poured onto ice (1 L). The resultant mixture was taken to pH 2 with 6 M NaOH at which point a thick precipitate formed. This was filtered, washed with water and dried in air to afford the nitramine intermediate which was used in the next step without further purification.A solution of the nitramine (42 g) in concentrated sulphuric acid (100 ml) was heated at 85 0C for 2 hours, then at 110 0C for a further 1 hour. The mixture was cooled, poured into ice (IL) and basified with concentrated ammonia solution to pH 9. The resultant suspension was filtered and the solid washed with water. The solid was then extracted with hot toluene (3 x 250 ml), and the combined extracts evaporated and chromatographed (heptane: ethyl acetate 9:2) to afford 2-chloro-4- amino-5-nitropyridine as a white solid (4.57g, 10percent);
		316.2 g of this intermediate compound are treated with 2.35 I concentrated sulfuric acid and stirred for 30 minutes at 88-94 °C. The mixture is cooled to room temperature and poured into 2 I of water containing 5 kg ice. 6.5 125percent (w/v) aqueous NH3 solution is slowly added. The resulting precipitate is filtered and pre-dried under reduced pressure. Finally the residue is dried by azeotropic distillation with benzene. After crystallization from benzene the title compound is obtained. 1H NMR (200 MHz, D6-DMSO): delta = 6.96 (s, 1 H), 8.07 (bs, 2H), 8.84 (s, 1 H).

References: [1]Patent: WO2006/50506,2006,A1 .Location in patent: Page/Page column 116.
[2]Patent: EP2017277,2009,A1 .Location in patent: Page/Page column 31.

17
[ 2604-39-9 ]
[ 124-41-4 ]
[ 127356-38-1 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; for 12h;Heating / reflux;	2-Methoxy-5-nitropyridin-4-amine To a suspension of 36.9 g of <strong>[2604-39-9]2-chloro-5-nitropyridin-4-amine</strong> (example E6) in 500 ml methanol is added 250 ml of a freshly prepared solution of sodium methoxide in methanol (5.7 g sodium) and the reaction mixture is refluxed for 12 h. About 500 ml methanol are distilled off and 500 ml of water are added. The resulting precipitate is filtered, washed with ice water and dried under vacuum to the title compound. 1H NMR (400 MHz, D6-DMSO): delta = 8.82 (s, 1 H), 7.65 (bs, 2H), 6.15 (s, 1 H), 3.85 (s, 3H).

References: [1]Patent: EP2017277,2009,A1 .Location in patent: Page/Page column 31.

18
[ 2604-39-9 ]
[ 89182-17-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogen; In ethyl acetate; at 20℃; for 2h;	step 1 : To a solution of <strong>[2604-39-9]2-chloro-5-nitropyridin-4-amine</strong> (4.50 g, 25.93 mmol) in EtOAc (100 mL) was added Raney nickel (0.45 g) followed by stirring under hydrogen at RT for 2 h. The reaction mixture was filtered and the filtrate concentrated under reduced pressure to afford 4.00 g (ca. 100percent) of crude 6- chloropyridine-3,4-diamine as yellow oil. MS (ESI): m/z = 144.3 [M+l]+.
	With hydrogen;palladium 10% on activated carbon; In ethanol; for 12h;	A suspension of 1.04 g of <strong>[2604-39-9]2-chloro-5-nitropyridin-4-amine</strong> (example E6) in 100 ml ethanol is treated with 50 mg Pd/C (10percent Pd) and hydrogenated for 12 h under atmospheric pressure. The reaction mixture is filtered through a plug of celite and the filtrate is concentrated under vacuum. The resulting oil is treated with 4 ml diethoxymethyl acetate and stirred for 2 h at room temperature and for one hour at 90 °C. The reaction mixture is allowed to cool down to room temperature, 20 ml dichloromethane is added and the organic layer is extracted with water (4 x 20 ml). The combined aqueous layers are concentrated to a volume of 10 ml and purified by preparative HPLC to yield the title compound. 1H NMR (200 MHz, D6-DMSO): delta = 7.69 (d, J = 0.8 Hz, 1 H), 8.46 (s, 1 H), 8.75 (d, J = 0.8 Hz, 1 H), 13.0 (bs, 1 H). MS (MH+ found) = 154.1

References: [1]Patent: WO2013/92940,2013,A1 .Location in patent: Page/Page column 54.
[2]Patent: EP2017277,2009,A1 .Location in patent: Page/Page column 29.

19
[ 2604-39-9 ]
[ 24424-99-5 ]
[ 240815-74-1 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; In dichloromethane; for 1h;	A mixture of 169A (995 mg, 5.75 mmol), di-tert-butyl dicarbonate (1.50 g, 6.90 mmol) and DMAP (140 mg, 1.15 mmol) in 60 mL of CH2Cl2 was stirred for 1 hr. The reaction mixture was diluted with CH2Cl2 and washed with 1 N HCl (2X), sat'd NaCl and dried over Na2SO4. Concentration in vacuo gave 1.54 g of 169B.

References: [1]Patent: EP1066286,2009,B1 .Location in patent: Page/Page column 58.

20
[ 64-18-6 ]
[ 2604-39-9 ]
[ 2589-11-9 ]

References: [1]Synlett,2010,p. 2759 - 2764.

21
[ 461-98-3 ]
[ 2604-39-9 ]
[ 1258298-08-6 ]