[ CAS No. 152684-26-9 ] {[proInfo.proName]}

Name: 152684-26-9|5-Bromo-3-methoxy-2-nitropyridine|98%
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Quality Control of [ 152684-26-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 152684-26-9 ]

Product Details of [ 152684-26-9 ]

CAS No. :	152684-26-9	MDL No. :	MFCD00834963
Formula :	C₆H₅BrN₂O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	OLWFTDPHNVYMMN-UHFFFAOYSA-N
M.W :	233.02	Pubchem ID :	817774
Synonyms :

Calculated chemistry of [ 152684-26-9 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.17
Num. rotatable bonds :	2
Num. H-bond acceptors :	4.0
Num. H-bond donors :	0.0
Molar Refractivity :	47.25
TPSA :	67.94 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.53 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.5
Log Po/w (XLOGP3) :	1.68
Log Po/w (WLOGP) :	1.76
Log Po/w (MLOGP) :	1.45
Log Po/w (SILICOS-IT) :	-0.09
Consensus Log Po/w :	1.26

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.58
Solubility :	0.611 mg/ml ; 0.00262 mol/l
Class :	Soluble
Log S (Ali) :	-2.72
Solubility :	0.443 mg/ml ; 0.0019 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.39
Solubility :	0.943 mg/ml ; 0.00405 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.43

Safety of [ 152684-26-9 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 152684-26-9 ]

* 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 [ 152684-26-9 ]
Downstream synthetic route of [ 152684-26-9 ]

[ 152684-26-9 ] Synthesis Path-Upstream 1~3

1
[ 152684-26-9 ]
[ 42409-58-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	Stage #1: for 2.5 h; Stage #2: With sodium carbonate In water; ethyl acetate	A 3-neck I -L flask was fitted with a heating mantle, temperature controller, and an overhead stirrer. To the reaction flask was added 2-nitro-3_'"iethoxy-5-bromopyridine 2 (37.5 g 0.16 mol), acetic acid (600 ml), and iron powder ( 18.9 g, 0.34 mol), and the resulting mixture was stirred and heated at 80 ⁰C for 2.5 h. The reaction was deemed complete by LCMS and allowed to cool to rt. The reaction mixture was filtered through Celite and the filter cake was washed with acetic acid, and the combined filtrate and washings were concentrated. The resulting residue was partitioned between saturated aqueous Na₂CO₃ solution (400 mi) and EtOAc (400 ml) and the layers separated. The organic phase was washed with brine (200 mL), dried (Na>=SC^), filtered, and concentrated to afford 32.5 g (0.16 mol, 99 percent yield) of a tan solid as 2-amino-3-methoxy-5- bromopyridine:¹H NMR (300 MHz, DMSO^fe) δ pom 7.56 (d, ./= 2.1 Hz, 1 H), 7.17 (d, ./ = 2.1 Hz, 1 H), 5.93 (br s, 2 H), 3.79 (s, 3 H); LCMS m/s (MH⁺) 203.0, /_R - 0.34 min.

Reference： [1] Patent: WO2010/100127, 2010, A1, . Location in patent: Page/Page column 69-70

2
[ 50720-12-2 ]
[ 152684-26-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sulfuric acid; nitric acid In water at 0℃; for 20 h;	The compound (20.91 g, 0.11 mol) obtained in Step 1 was dissolved in concentrated sulfuric acid (63 ml), nitric acid (5.2 ml, 0.12 mol) was added under ice-cooling, and the mixture was stirred for 20 hr. The reaction mixture was gently poured into ice water and the mixture was stirred. The precipitated solid was filtered and washed with water. The obtained solid was dissolved in ethyl acetate, and the solution was washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to give the object product as a pale-yellow solid (21.97 g, yield 85percent). ¹H NMR(CDCl₃400 MHz) (δ) ppm: 4.01 (3H, s), 7.68 (1H, d, J=1.6 Hz), 8.16 (1H, d, J=1.9 Hz)
76%	Stage #1: at 20℃; Stage #2: at 0 - 20℃; Stage #3: With sodium carbonate In water; ethyl acetate	To a cooled flask containing 3-methoxy-5-bromopyridine I (39,8 g, 0.21 mol) was slowly added concentrated H₂SO4 (120 ml) with the reaction mixture temperature maintained below 20 °C. The resulting mixture was stirred unitl homogeneity. The reaction mixture was cooled to 0-5 f^tC and 90percent I INO3 (16>;5 g, 0.24 moi) was added dropwise while maintaining constant temperature. The resulting reaction mixture was stirred for 24 h, at ambient temperature. The reaction was deemed complete (<;5percent of 1 by HPLC) and the reaction mixture was poured onto ice (400 g), then partitioned with EtOAc (400 ml). The layers were separated and (he organic phase was sequentially washed with saturated aqueous Na₂CO₃ solution (400 ml), water (400 ml) and brine (400 ml), dried overNa₂SO-i) Tillered, and concentrated under reduced pressure to furnish a pale yellow solid (45.8 g) as crude product. The material was recrystallized from MTBE (175 mL) and the crystals were harvested, washed with cold MTBK (80 mL-), and dried under high vacuum to give 22.7 g of yellow soiM as product. The mother liquor and filtraie were combined, concentrated, and recrystoellized from MTBE (35 mL) gave 6.3 g of pure product, The remaining mother liquor and filtrates were combined and concentrated. The resulting residue was purified by silica gel chromatography, eluting with a slow gradient of hexanes-EtOAc (hexanes, 4:1 hexancs-EtOAc) to give 8.5 g of product, Λ combined total of 37.5 g (0.16 mol, 76percent yield) of a yellow crystalline solid was obtained as 2-nitro-3 -methoxy-5 -bromopyridine:¹H NMR (30Q MHz, CDCl₃) 6 8.16 (d, J.(TM). 1.9 Hz, 1 H), 7.68 (d, J = 1.6 Hz, 1 H), 4.01 (s, 3 H); IXMS m/z (MH') 232.9, /_R 0.73 min.

Reference： [1] Patent: US2006/84665, 2006, A1, . Location in patent: Page/Page column 70
[2] Patent: WO2010/100127, 2010, A1, . Location in patent: Page/Page column 69-70
[3] Acta Chemica Scandinavica, 1993, vol. 47, # 8, p. 805 - 812
[4] Recueil des Travaux Chimiques des Pays-Bas, 1955, vol. 74, p. 1171,1174

3
[ 625-92-3 ]
[ 152684-26-9 ]

Reference： [1] Acta Chemica Scandinavica, 1993, vol. 47, # 8, p. 805 - 812
[2] Recueil des Travaux Chimiques des Pays-Bas, 1955, vol. 74, p. 1171,1174

[ 152684-26-9 ] Synthesis Path-Downstream 1~42

1
[ 50720-12-2 ]
[ 152684-26-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sulfuric acid; nitric acid; In water; at 0℃; for 20.0h;	The compound (20.91 g, 0.11 mol) obtained in Step 1 was dissolved in concentrated sulfuric acid (63 ml), nitric acid (5.2 ml, 0.12 mol) was added under ice-cooling, and the mixture was stirred for 20 hr. The reaction mixture was gently poured into ice water and the mixture was stirred. The precipitated solid was filtered and washed with water. The obtained solid was dissolved in ethyl acetate, and the solution was washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to give the object product as a pale-yellow solid (21.97 g, yield 85%). 1H NMR(CDCl3 400 MHz) (delta) ppm: 4.01 (3H, s), 7.68 (1H, d, J=1.6 Hz), 8.16 (1H, d, J=1.9 Hz)
76%		To a cooled flask containing 3-methoxy-5-bromopyridine I (39,8 g, 0.21 mol) was slowly added concentrated H2SO4 (120 ml) with the reaction mixture temperature maintained below 20 C. The resulting mixture was stirred unitl homogeneity. The reaction mixture was cooled to 0-5 ftC and 90% I INO3 (16>;5 g, 0.24 moi) was added dropwise while maintaining constant temperature. The resulting reaction mixture was stirred for 24 h, at ambient temperature. The reaction was deemed complete (<;5% of 1 by HPLC) and the reaction mixture was poured onto ice (400 g), then partitioned with EtOAc (400 ml). The layers were separated and (he organic phase was sequentially washed with saturated aqueous Na2CO3 solution (400 ml), water (400 ml) and brine (400 ml), dried overNa2SO-i) Tillered, and concentrated under reduced pressure to furnish a pale yellow solid (45.8 g) as crude product. The material was recrystallized from MTBE (175 mL) and the crystals were harvested, washed with cold MTBK (80 mL-), and dried under high vacuum to give 22.7 g of yellow soiM as product. The mother liquor and filtraie were combined, concentrated, and recryst°llized from MTBE (35 mL) gave 6.3 g of pure product, The remaining mother liquor and filtrates were combined and concentrated. The resulting residue was purified by silica gel chromatography, eluting with a slow gradient of hexanes-EtOAc (hexanes, 4:1 hexancs-EtOAc) to give 8.5 g of product, Lambda combined total of 37.5 g (0.16 mol, 76% yield) of a yellow crystalline solid was obtained as 2-nitro-3 -methoxy-5 -bromopyridine:1H NMR (30Q MHz, CDCl3) 6 8.16 (d, J 1.9 Hz, 1 H), 7.68 (d, J = 1.6 Hz, 1 H), 4.01 (s, 3 H); IXMS m/z (MH') 232.9, /R» 0.73 min.

Reference： [1]Patent: US2006/84665,2006,A1 .Location in patent: Page/Page column 70
[2]Patent: WO2010/100127,2010,A1 .Location in patent: Page/Page column 69-70
[3]Acta Chemica Scandinavica,1993,vol. 47,p. 805 - 812
[4]Recueil des Travaux Chimiques des Pays-Bas,1955,vol. 74,p. 1171,1174

2
[ 152684-26-9 ]
[ 5720-05-8 ]
[ 152684-18-9 ]

Reference： [1]Acta Chemica Scandinavica,1993,vol. 47,p. 805 - 812

3
[ 152684-26-9 ]
[ 13331-27-6 ]
[ 152684-19-0 ]

Reference： [1]Acta Chemica Scandinavica,1993,vol. 47,p. 805 - 812

4
[ 152684-26-9 ]
[ 98-80-6 ]
[ 152684-17-8 ]

Reference： [1]Acta Chemica Scandinavica,1993,vol. 47,p. 805 - 812

5
[ 152684-26-9 ]
[ 140-88-5 ]
[ 870837-73-3 ]

Yield	Reaction Conditions	Operation in experiment
69%	With triethylamine; johnphos;palladium diacetate; In N,N-dimethyl-formamide; at 80℃; for 3.0h;	To a DMF (20 mL) solution of <strong>[152684-26-9]5-bromo-3-methoxy-2-nitropyridine</strong> (726 mg) synthesized according to the method described in Acta Chemica Scandinavica vol.47, p. 805, 1993, ethyl acrylate (0.44 mL), palladium acetate (35 mg), 2-(di-tert-butylphosphino) biphenyl (93 mg) and TEA (0.87 mL) were added, and the reaction solution was agitated at 80 C. for 3 hours. After the reaction solution was allowed to be cooled to room temperature, ethyl acetate and a saturated ammonium chloride solution were added to the reaction solution to separate an organic layer. After the obtained organic layer was dried over anhydrous magnesium sulfate, solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent:heptane-ethyl acetate 2:1), and 787 mg (69%) of (E)-3-(5-methoxy-6-nitropyridin-3-yl)acrylic acid ethyl ester was obtained. The physical properties of the compound are as follows. 1H-NMR (CDCl3) delta (ppm): 1.35 (t, J=7.6 Hz, 3H), 4.01 (s, 3H), 4.28 (q, J=7.6 Hz, 2H), 6.58 (d, J=16.4 Hz, 1H), 7.56 (d, J=1.6 Hz, 1H), 7.67 (d, J=16.4 Hz, 1H), 8.20 (d, J=1.6 Hz, 1H).

Reference： [1]Patent: US2006/4013,2006,A1 .Location in patent: Page/Page column 60

6
[ 625-92-3 ]
[ 152684-26-9 ]

Reference： [1]Acta Chemica Scandinavica,1993,vol. 47,p. 805 - 812
[2]Recueil des Travaux Chimiques des Pays-Bas,1955,vol. 74,p. 1171,1174

7
[ 152684-26-9 ]
[ 105650-23-5 ]

Reference： [1]Acta Chemica Scandinavica,1993,vol. 47,p. 805 - 812

8
[ 152684-26-9 ]
[ 152684-14-5 ]

Reference： [1]Acta Chemica Scandinavica,1993,vol. 47,p. 805 - 812

9
[ 152684-26-9 ]
3-methylamino-5-(4-methylphenyl)-2-nitropyridine [ No CAS ]

Reference： [1]Acta Chemica Scandinavica,1993,vol. 47,p. 805 - 812

10
[ 152684-26-9 ]
3-methoxy-2-methylamino-5-(3-nitrophenyl)pyridine [ No CAS ]

Reference： [1]Acta Chemica Scandinavica,1993,vol. 47,p. 805 - 812

11
[ 152684-26-9 ]
3-methylamino-2-nitro-5-(3-nitrophenyl)pyridine [ No CAS ]

Reference： [1]Acta Chemica Scandinavica,1993,vol. 47,p. 805 - 812

12
[ 152684-26-9 ]
[ 880870-66-6 ]

Yield	Reaction Conditions	Operation in experiment
63%	With tetrabutyl ammonium fluoride; In tetrahydrofuran; N,N-dimethyl-formamide; at 70℃; for 15.0h;	The compound (21.97 g, 94.28 mmol) obtained in Step 2 was dissolved in dimethylformamide (190 ml), 1 M tetrabutylammonium fluoride tetrahydrofuran solution (190 ml, 0.19 mol) was added, and the mixture was stirred with heating at 70 C. for 15 hr. The reaction mixture was added to water, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography (hexane:ethyl acetate=10:1) to give the object product as a white solid (12.21 g, yield 63%). 1H NMR(CDCl3 400 MHz) (delta) ppm: 3.92 (3H, s), 7.40 (1H, dd, J=8.6, 2.1 Hz), 7.81 (1H, dd, J=2.0, 1.0 Hz)
		Example 327Synthesis of (1R,2S)-2-[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(6-fluoro-5-methoxypyridin-3-yl)-2-phenylcyclopropanecarboxamide (327)(1) Synthesis of 3-bromo-6-fluoro-5-methoxypyridine (327-1)Tetrabutyl ammonium fluoride (1.0 M THF solution: 3.9 ml) was added to a DMF (5 ml) solution of <strong>[152684-26-9]5-bromo-3-methoxy-2-nitropyridine</strong> (CAS No. 152684-26-9) (450 mg), and the obtained mixture was stirred at 70 C. for 72 hours. The reaction solution was cooled to room temperature. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (n-heptane:ethyl acetate=10:1 to 2:1), so as to obtain the title compound (258 mg).1H-NMR (400 MHz, CDCl3) 5 (ppm): 3.91 (s, 3H), 7.39 (dd, J=8.8, 2.4 Hz, 1H), 7.80 (t, J=2.4 Hz, 1H).

Reference： [1]Patent: US2006/84665,2006,A1 .Location in patent: Page/Page column 70
[2]Patent: US2012/95031,2012,A1 .Location in patent: Page/Page column 162

13
[ 152684-26-9 ]
[ 1123195-03-8 ]

Yield	Reaction Conditions	Operation in experiment
	With formic acid; ammonium chloride; acetic anhydride; iron; In tetrahydrofuran; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethanol; water;	Synthesis of N-(5-bromo-3-methoxypyridin-2-yl)formamide Iron (67.3 g) and ammonium chloride (129 g) were added to a solution of <strong>[152684-26-9]5-bromo-3-methoxy-2-nitropyridine</strong> (56.0 g, CAS: 152684-26-9) in ethanol (500 mL) and water (200 mL). The reaction solution was stirred at 80 to 90C for one hour and then left to cool to room temperature. The reaction solution was filtered through celite and washed with ethanol. Then, the filtrate was concentrated under reduced pressure. The residue was diluted with ethyl acetate and water, and the organic layer was separated. The resulting organic layer was washed with brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was diluted with THF (84 mL). The THF solution was added dropwise to a mixed solution of formic acid (78.1 mL) and acetic anhydride (78.3 mL) at room temperature. Then, the reaction solution was stirred for one hour. Ice water (500 mL) was added to the reaction solution, and the precipitated crystals were collected by filtration. The crystals were washed with water and then air-dried. The crystals were recrystallized from toluene to obtain 34.1 g of the title compound. The property value of the compound is as follows. ESI-MS; m/z 231 [M++H].

Reference： [1]Patent: EP2181992,2010,A1

14
[ 64-18-6 ]
[ 152684-26-9 ]
[ 1123195-03-8 ]

Yield	Reaction Conditions	Operation in experiment
		Preparation Example 1-3Synthesis of 3-methoxy-2-(4-methyl-1H-imidazol-1-yl)-5-tributylstannylpyridine [0545][0546]Synthesis of N-(5 -bromo-3 -methoxypyridin-2- vDformamideIron (67.3 g) and ammonium chloride (129 g) were added to a solution of 5- bromo-3-methoxy-2-nitropyridine (56.0 g, CAS No.152684-26-9) in ethanol (500 mL) and water (200 mL). The reaction solution was stirred at 80 to 90C for one hour and then left to cool to room temperature. The reaction solution was filtered through celite and washed with ethanol.Then, the filtrate was concentrated under reduced pressure. The residue was diluted with ethyl acetate and water, and the organic layer was separated. The resulting organic layer was washed with brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was diluted with THF (84 mL). The THF solution was added dropwise to a mixed solution of formic acid (78.1 mL) and acetic anhydride (78.3 mL) at room temperature.Then, the reaction solution was stirred for one hour. Ice water (500 mL) was added to the reaction solution, and the precipitated crystals were collected by filtration. The crystals were washed with water and then air-dried. The crystals were recrystallized from toluene to obtain 34.1 g of the title compound. The property values of the compound are as follows. ESI-MS; 111/7231 [M+ +H]. [0547] Synthesis of N-fS-bromo-3-methoxypyridin-2-ylVN-(2-oxopropyl)formarnideCesium carbonate (96 g), potassium iodide (2.45 g) and chloroacetone (23.5 mL) were added to a solution of N-(5-chloro-3-methoxypyridin-2-yl)formamide (34.1 g) in DMF (200 mL), and the mixture was stirred at 80C for 45 minutes. Ice water and ethyl acetate were added to the reaction solution, and the organic layer was separated. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 52.8 g of the crude title compound. The property values of the compound are as follows. ESI-MS; m/z 287 [M+ +H]. [0548] Synthesis of S-bromo-S-methoxy^-^-methyl-1H-imidazol-1-y?pyridineA mixture of the crude N-(5-bromo-3-methoxypyridin-2-yl)-N-(2- oxopropyl)formamide (26.4 g), acetic acid (52.8 mL) and ammonium acetate (35.5 g) was stirred at 130C for one hour. The reaction solution was left to cool to room temperature and concentrated under reduced pressure. The residue diluted with ice water, ethyl acetate and aqueous ammonia, and the organic layer was separated. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain 5.69 g of the title compound. The property values of the compound are as follows. ESI-MS; m/z 268 [M+ +H] .1 H-NMR (CDCl3 ) delta (ppm): 2.29 (s, 3H), 3.97 (s, 3H), 7.48 (brs, 1H), 7.49 (d, J = 2.0 Hz, 1H),8.12 (d, J = 2.0 Hz, 1H), 8.30 (brs, 1H).[0549]Synthesis of 3 -methoxy-2-(4-methyl- 1 H-imidazol- 1 -ylV 5-tributylstannylpyridine Hexa-n-butylditin (2.07 mL) and tetrakis(triphenylphosphine)palladium (0) (319 mg) were added to a suspension of 5-bromo-3-methoxy-2-(4-methyl-1H-imidazol-1-yl)pyridine (740 mg) in xylene (11 mL), and the mixture was stirred at 155C for two hours and 30 minutes. The reaction solution was purified by silica gel column chromatography (carrier: Wakogel C- 200; elution solvent: heptane:ethyl acetate = 3:1) to obtain 325 mg of the title compound. The property values of the compound are as follows.1 H-NMR (CDCl3 ) delta (ppralpha): 0.90 (t, J = 7.2 Hz, 9H), 1.13 (t, J = 7.2 Hz5 6H), 1.30-1.40 (m, 6H), 1.50-1.60 (m, 6H), 2.30 (d, J = 1.2 Hz, 3H), 3.95 (s, 3H), 7.38 (d, J - 1.2 Hz, 1H), 7.52 (t, J = 1.2 Hz, 1H), 8.03 (d, J = 1.2 Hz, 1H), 8.33 (d, J = 1.2 Hz, 1H).

Reference： [1]Patent: WO2010/98487,2010,A1 .Location in patent: Page/Page column 163-165

15
[ 152684-26-9 ]
[ 42409-58-5 ]

Yield	Reaction Conditions	Operation in experiment
99%		A 3-neck I -L flask was fitted with a heating mantle, temperature controller, and an overhead stirrer. To the reaction flask was added 2-nitro-3'«iethoxy-5-bromopyridine 2 (37.5 g» 0.16 mol), acetic acid (600 ml), and iron powder ( 18.9 g, 0.34 mol), and the resulting mixture was stirred and heated at 80 0C for 2.5 h. The reaction was deemed complete by LCMS and allowed to cool to rt. The reaction mixture was filtered through Celite and the filter cake was washed with acetic acid, and the combined filtrate and washings were concentrated. The resulting residue was partitioned between saturated aqueous Na2CO3 solution (400 mi) and EtOAc (400 ml) and the layers separated. The organic phase was washed with brine (200 mL), dried (Na?SC^), filtered, and concentrated to afford 32.5 g (0.16 mol, 99 % yield) of a tan solid as 2-amino-3-methoxy-5- bromopyridine:1H NMR (300 MHz, DMSO^fe) delta pom 7.56 (d, ./= 2.1 Hz, 1 H), 7.17 (d, ./ = 2.1 Hz, 1 H), 5.93 (br s, 2 H), 3.79 (s, 3 H); LCMS m/s (MH+) 203.0, /R - 0.34 min.

Reference： [1]Patent: WO2010/100127,2010,A1 .Location in patent: Page/Page column 69-70

16
[ 152684-26-9 ]
[ 1369766-55-1 ]

Reference： [1]Patent: US2012/95031,2012,A1

17
[ 152684-26-9 ]
[ 73183-34-3 ]
[ 1374110-13-0 ]

Yield	Reaction Conditions	Operation in experiment
70%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 100℃; for 16.0h;Inert atmosphere;	Synthesis of 347 A mixture of 346 (1.40 g, 6 mol), 314 (1.53 g, 6 mol), potassium acetate (2.36 g, 24 mol), PdCl2(dppf)·CH2Cl2 (245 mg, 0.3 mmol) and 1,4-dioxane (25 ml) was stirred under an argon atmosphere at 100C for 16 hours. The reaction solution was allowed to return to room temperature and insolubles were removed by filtration, and the solvent of the filtrate was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate = 2/1) and then washed with n-hexane to obtain 347 (1.17 g, 70%) as a colorless solid. mp 130-131C APCI-MS m/z 281[M+H]+

Reference： [1]Patent: EP2634177,2013,A1 .Location in patent: Paragraph 0522; 0523

18
[ 152684-26-9 ]
[ 1374110-14-1 ]

Reference： [1]Patent: EP2634177,2013,A1

19
[ 152684-26-9 ]
[ 1374110-15-2 ]

Reference： [1]Patent: EP2634177,2013,A1

20
[ 152684-26-9 ]
[ 1374110-16-3 ]

Reference： [1]Patent: EP2634177,2013,A1

21
[ 152684-26-9 ]
[ 1374110-17-4 ]

Reference： [1]Patent: EP2634177,2013,A1

22
[ 152684-26-9 ]
3-methoxy-5-(methylsulfanyl)pyridin-2-amine [ No CAS ]