[ CAS No. 10201-73-7 ] {[proInfo.proName]}

Name: 10201-73-7|2-Amino-4-methoxypyridine|98%
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Quality Control of [ 10201-73-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 10201-73-7 ]

Product Details of [ 10201-73-7 ]

CAS No. :	10201-73-7	MDL No. :	MFCD07437849
Formula :	C₆H₈N₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QPHBCOSULYSASF-UHFFFAOYSA-N
M.W :	124.14	Pubchem ID :	10898715
Synonyms :

Calculated chemistry of [ 10201-73-7 ] Expand+

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.17
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	35.13
TPSA :	48.14 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.72 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.25
Log Po/w (XLOGP3) :	0.48
Log Po/w (WLOGP) :	0.68
Log Po/w (MLOGP) :	-0.07
Log Po/w (SILICOS-IT) :	0.64
Consensus Log Po/w :	0.6

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.34
Solubility :	5.68 mg/ml ; 0.0458 mol/l
Class :	Very soluble
Log S (Ali) :	-1.06
Solubility :	10.8 mg/ml ; 0.087 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.75
Solubility :	2.21 mg/ml ; 0.0178 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.6

Safety of [ 10201-73-7 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P264-P270-P301+P312-P302+P352-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 10201-73-7 ]

* 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 [ 10201-73-7 ]
Downstream synthetic route of [ 10201-73-7 ]

[ 10201-73-7 ] Synthesis Path-Upstream 1~14

1
[ 19798-80-2 ]
[ 124-41-4 ]
[ 10201-73-7 ]

Yield	Reaction Conditions	Operation in experiment
79%	at 145℃; for 6 h; Sealed tube	j00604j A solution of 4-chloropyridin-2-amine (10 g, 78.1 mmol) in sodium methoxide solution (50 mL, 1M solution) in a sealed tube was heated at 145 °C for 6 h. The solvent was concentrated in vacuo resulting in residue which was purified by chromatography on silica gel,eluting with 10percent methanol in DCM to give 7.7 g, 79percent yield of the title compound as an off white solid. MS (ESj: m/z = 125.04 [M+H], 281.75 [M/2+H] LCMS: tR = 0.17 mm.
16%	at 150℃; for 3 h;	Step 1 : To a solution of 4-chloropyridin-2-amine (3 g, 23.2 mmol) in DMSO (60 mL) was added sodium methoxide (12.6 g, 232 mmol) and the mixture was then stirred at 150 °C for 3 hours then poured into ice- water. The product was extracted with EtOAc (2x100 mL), and the combined organic layers were washed with water (50 mL) and brine (50 mL), dried (Na₂S0₄) and concentrated. The residue was purified by silica gel chromatography using a solvent system of 50percent petroleum ether/EtOAc to give 4-methoxypyridin-2 -amine (460 mg, 16percent) as a yellow solid MS ESI calcd for C₆H₈N₂0 [M + H]⁺ 125, found 125.
16%	at 150℃; for 3 h;	To a solution of 4-chloropyridin-2-amine (3 g, 23.2 mmol) in DMSO (60 mL) was added sodium methoxide (12.6 g, 232 mmol) and the mixture was then stirred at 150 °C for 3 hours then poured into ice-water. The product was extracted with EtOAc (2x100 mL), and the combined organic layers were washed with water (50 mL) and brine (50 mL), dried (Na₂S0₄) and concentrated. The residue was purified by silica gel chromatography using a solvent system of 50percent petroleum ether/EtOAc to give 4-methoxypyridin-2-amine (460 mg, 16percent) as a yellow solid MS ESI calc'd for C₆H₈N₂0 [M + H]⁺ 125, found 125.

Reference： [1] Patent: WO2015/106292, 2015, A1, . Location in patent: Paragraph 00592; 00603; 00604
[2] Journal of Organometallic Chemistry, 1996, vol. 523, # 2, p. 145 - 151
[3] Australian Journal of Chemistry, 1982, vol. 35, # 9, p. 1841 - 1849
[4] Australian Journal of Chemistry, 1982, vol. 35, # 10, p. 2025 - 2034
[5] Patent: WO2012/151137, 2012, A1, . Location in patent: Page/Page column 50-51
[6] Patent: WO2014/74422, 2014, A1, . Location in patent: Paragraph 00165

2
[ 29681-43-4 ]
[ 10201-73-7 ]

Reference： [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 8, p. 3076 - 3080
[2] Journal of the Chemical Society. Perkin Transactions 1, 2001, # 17, p. 2012 - 2021
[3] Organic Preparations and Procedures International, 1997, vol. 29, # 1, p. 117 - 122
[4] Patent: EP2314588, 2011, A1,

3
[ 19798-80-2 ]
[ 67-56-1 ]
[ 10201-73-7 ]

Yield	Reaction Conditions	Operation in experiment
57.4%	for 48 h; Reflux	2-Amino-4-chloropyridine (970mg, 7.18mmol) was dissolved in 50mL methanol. Sodium methoxide was prepared in situ, by adding sodium (450mg, 19.6mmol) to the stirred solution. The reaction mixture was then stirred under reflux for 48 hours. TLC control indicated complete conversion. The reaction mixture was then cooled to room temperature. The pH value was adjusted to pH 8 by adding 10percent aqueous hydrochloric acid. The solvent was removed in vacuum, the remaining residue was resuspended in diethyl ether and the insoluble components were removed by filtration. The solvent was removed in vacuum. Yield 511mg, 57.4percent. 1H NMR (DMSO-d6) δ 3.72 (s, 3H), 5.86 (bs, 2H, NH2), 5.98 (d, J=2.2Hz, 1H), 6.14 (dd, J1=2.3Hz, J2=5.9Hz, 1H), 7.72 (d, J=5.9Hz, 1H). 13C NMR (DMSO-d6) δ 54.60, 91.14, 100.89, 148.37, 161.34, 166.30.

Reference： [1] Tetrahedron Letters, 2015, vol. 56, # 47, p. 6606 - 6609

4
[ 89488-29-9 ]
[ 10201-73-7 ]

Reference： [1] Advanced Synthesis and Catalysis, 2013, vol. 355, # 4, p. 627 - 631

5
[ 1122-96-9 ]
[ 10201-73-7 ]

Reference： [1] Journal of Organic Chemistry, 2007, vol. 72, # 12, p. 4554 - 4557
[2] Chemical and Pharmaceutical Bulletin, 1980, vol. 28, # 2, p. 465 - 472
[3] Organic Letters, 2013, vol. 15, # 11, p. 2616 - 2619
[4] Chemistry - A European Journal, 2013, vol. 19, # 28, p. 9137 - 9141

6
[ 90151-10-3 ]
[ 10201-73-7 ]

Reference： [1] Journal of the Chemical Society. Perkin Transactions 1, 2001, # 17, p. 2012 - 2021

7
[ 551950-46-0 ]
[ 10201-73-7 ]

Reference： [1] Organic Preparations and Procedures International, 1997, vol. 29, # 1, p. 117 - 122

8
[ 98-98-6 ]
[ 10201-73-7 ]

Reference： [1] Patent: EP2314588, 2011, A1,
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 8, p. 3076 - 3080

9
[ 74404-98-1 ]
[ 10201-73-7 ]

Reference： [1] Chemical and Pharmaceutical Bulletin, 1980, vol. 28, # 2, p. 465 - 472

10
[ 19798-80-2 ]
[ 10201-73-7 ]

Reference： [1] Patent: US5972975, 1999, A,

11
[ 187973-18-8 ]
[ 10201-73-7 ]

Reference： [1] Organic Preparations and Procedures International, 1997, vol. 29, # 1, p. 117 - 122
[2] Patent: EP2314588, 2011, A1,

12
[ 130721-78-7 ]
[ 10201-73-7 ]

Reference： [1] Australian Journal of Chemistry, 1982, vol. 35, # 10, p. 2025 - 2034
[2] Australian Journal of Chemistry, 1982, vol. 35, # 9, p. 1841 - 1849

13
[ 53750-66-6 ]
[ 10201-73-7 ]

Reference： [1] Patent: EP2314588, 2011, A1,

14
[ 10201-73-7 ]
[ 1232431-11-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With N-Bromosuccinimide In acetonitrile at 0 - 20℃; for 1 h;	Step 3: 5-bromo-4-methoxyl-2-aminopyridine To a solution of 4-methoxyl-2-aminopyridine (12.4 g, 100 mmol) in acetonitrile (500 mL), N-bromobutanimide (17.8 g, 100 mmol) was added in portions at 0°C under stirring. Upon completion of the addition, the mixture was stirred at room temperature for 1 hour. The solvent was evaporated and CH₂Cl₂ was added. The solution was washed with saturated sodium bicarbonate, dried, and concentrated to give 5-bromo-4-methoxyl-2-aminopyridine (20.3 g, 100percent yield), which was directly used in the next step. MS m/z [ESI]: 203.0 [M+1].
81%	With dihydrogen peroxide; 1-butylpyridinium bromide; toluene-4-sulfonic acid In 1,2-dimethoxyethane at 80℃; for 24 h; Schlenk technique; Inert atmosphere; Green chemistry	General procedure: To a mixture of 2-aminopyridine (0.5 mmol, 1 equiv), p-TSA (0.4 mmol,0.8 equiv), 1-butylpyridinium bromide (1.5 mmol, 3 equiv) in a 50 mL Schlenk tube were added 1,2-dimethoxyethane (2 mL) under air. Then H₂O₂(1.2 mmol, 2.4 equiv) was added. The mixture was stirred at 80°C for 24 h. And then the mixture was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to give the products.
79%	at 23℃; for 1 h;	Step 1: [0430] To a solution of 4-methoxy-pyridin-2-ylamine (10.0 g, 80.64 mmol) in acetic acid (320 mL) was added Br₂(3.75 mL, 72.58 mmol) in acetic acid (80 mL) dropwise at RT and the resulting RM was stirred at RT for 1 h. The solid precipitate was separated by filtration, washed with hexane and dried to yield 5-bromo-4-methoxy-pyridin-2-ylamine (13.0 g, 79percent). [0431] LC-MS (Method 4): m/z [M+1]⁺=203.1 & 204.8 (MW calc. 203.04); R_t=2.43 min.

73%	With bromine In acetic acid at 0 - 30℃; for 4 h;	2-Amino-4-methoxypyridine (1.24 g, 10 mmol) was dissolved in 100 mL of acetic acid, After cooling to 0 degrees, A solution of bromine (1.92 g, 12 mmol) in acetic acid (30 mL) was added dropwise. Dropping is completed, The solution is reacted at 30 degrees. 4h, TLC monitoring raw material has been completely reacted, To the reaction solution was added 40 mL of saturated aqueous sodium sulfite solution, 25 degrees stirring reaction 0.5h, Concentrated under reduced pressure, The residue was extracted with ethyl acetate (150 mL × 3) Dried over anhydrous sodium sulfate, filter, The filtrate was concentrated under reduced pressure, Column chromatography (V (methylene chloride) / V (methanol) = 20/1), Obtained as a light yellow solid (1.45 g, 73percent).
69%	With bromine In acetic acid at 20℃; for 1 h;	A solution of Br₂ (1 M in AcOH, 10 mL, 10 mmol) was slowly added into a solution commercially available compound 12-1 (1.24 g, 10 mmol) in AcOH (35 mL) at rt. After stirring at rt for 1 hr, the reaction mixture was filtered and the solid was dried in vacuo to give compound 12-2 (1.41 g, 69percent yield). NMR (300 MHz, CD₃OD): δ 7.84 (s, 1 H), 6.29 (s, 1 H), 3.87 (s, 3H) ppm.
47%	With N-Bromosuccinimide; acetic acid In acetonitrile at 20℃; for 1 h; Inert atmosphere	(41c). A mixture of 2-amino-4-methoxypyridine (2.4 g, 19 mol)and N-bromosuccinimide (3.1 g, 17 mmol) was dissolved in aceticacid (6 mL) and stirred at room temperature for 1 h. The reactionmixture was concentrated under vacuum, basified with saturatedaqueous K2CO3 and extracted with EtOAc. The combined organicswere dried, concentrated under vacuum, and purified by silicagel column chromatography, eluting with 50:1 CH2Cl2:MeOH, togive 41c (1.85 g, 47percent). LCMS 203 [M+H]+.
15.1 g	at 20℃; for 1.5 h;	To a stirred solution of 4-methoxypyridin-2-ylamine (15 g, 121 mmol) in acetic acid (490 mL), at room temperature, is slowly added bromine as a 1M solution in acetic acid (120 mL, 120 mmol). After 1.5 h, the reaction mixture is filtered and the collected solid is dissolved in EtOAc. The mixture is washed with saturated NaHCO₃followed by water and then brine. The organic layer is dried over anhydrous Na₂SO₄, filtered, and the filtrate is concentrated under reduced pressure to provide 15.1 g of 5-bromo-4-methoxypyridin-2-ylamine (I-24-1).

Reference： [1] Patent: EP2952510, 2015, A1, . Location in patent: Paragraph 0143
[2] Tetrahedron Letters, 2014, vol. 55, # 36, p. 5058 - 5061
[3] Patent: US2015/166505, 2015, A1, . Location in patent: Paragraph 0428; 0429; 0450
[4] Patent: CN104513257, 2017, B, . Location in patent: Paragraph 0411; 0412; 0413
[5] Patent: WO2012/58125, 2012, A1, . Location in patent: Page/Page column 139; 140
[6] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 15, p. 3947 - 3963
[7] Patent: EP3235816, 2017, A1, . Location in patent: Paragraph 0102-0103
[8] Patent: US2018/72717, 2018, A1, . Location in patent: Paragraph 0283; 0334; 0468

[ 10201-73-7 ] Synthesis Path-Downstream 1~22

1
[ 90151-10-3 ]
[ 10201-73-7 ]

Reference： [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2001,p. 2012 - 2021

2
[ 10201-73-7 ]
[ 329794-40-3 ]
(4-methoxy-pyridin-2-yl)-(5-phenyl-thiazol-2-yl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride In tetrahydrofuran Heating;

Reference： [1]Bilodeau, Mark T.; Rodman, Leonard D.; McGaughey, Georgia B.; Coll, Kathleen E.; Koester, Timothy J.; Hoffman, William F.; Hungate, Randall W.; Kendall, Richard L.; McFall, Rosemary C.; Rickert, Keith W.; Rutledge, Ruth Z.; Thomas, Kenneth A. [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 11, p. 2941 - 2945]

3
[ 29681-43-4 ]
[ 10201-73-7 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 3076 - 3080
[2]Journal of the Chemical Society. Perkin Transactions 1 (2001),2001,p. 2012 - 2021
[3]Organic Preparations and Procedures International,1997,vol. 29,p. 117 - 122
[4]Patent: EP2314588,2011,A1

4
[ 10201-73-7 ]
[ 84487-08-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: concd. H₂SO₄, fuming HNO₃ / 0.33 h / 0 °C 2: 93 percent / concd. H₂SO₄ / 0 - 20 °C

Reference： [1]Deady, Leslie W.; Korytsky, Olga L.; Rowe, Jeffrey E. [Australian Journal of Chemistry, 1982, vol. 35, # 10, p. 2025 - 2034]

5
[ 10201-73-7 ]
[ 78-95-5 ]
[ 1204527-87-6 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-amino-4-methoxypyridine With sodium carbonate In ethanol at 20℃; Stage #2: chloroacetone In ethanol at 80℃; for 16h;	77 To a stirred solution of Int-1 (3.0 g, 24 mmol) in EtOH (150 mL) was added Na2CO3 (3.8 g, 35 mmol) at room temperature and stirred for 15 minutes, then Int-2 (3.4 g, 36 mmol) was added and the reaction mixture was stirred at 80° C. for 16 hours. The volatiles were concentrated under reduced pressure and the residue was diluted with water (200 mL). The aqueous layer was extracted with EtOAc (3×200 mL) and the combined organic extracts were washed with water (50 mL), brine (2×75 mL), dried over anhydrous Na2SO4 and concentrated under vacuum to afford Int-3 (2.5 g) as crude oil. This crude compound was taken to the next stage without any further purification. 1H NMR (200 MHz, dmso-d6): δ 7.83 (d, J=12 Hz, 1H), 7.18 (brs, 1H), 6.8 (s, 1H), 6.45 (d, J=12 Hz, 1H), 3.85 (s, 3H), 2.4 (s, 3H). To a stirred solution of Int-3 (2.5 g, 15 mmol) in acetonitrile (60 mL) was added NIS (4.1 g, 18 mmol) portion wise at room temperature and stirred for 2 hours. After the reaction completion, the reaction mass was diluted with excess water and the stirring was continued for another 30 minutes. The precipitated solid was filtered off and dried under vacuum to afford Int-4 (3.5 g, 79%) as solid. Mass (m/z): 389 [M++1]. 1H NMR (200 MHz, CDCl3): δ 7.85 (d, J=12 Hz, 1H), 6.85 (brs, 1H), 6.6 (d, J=12 Hz, 1H), 3.9 (s, 3H), 2.45 (s, 3H). Int-4 (3.5 g, 12 mmol) was dissolved in DME-H2O (200 mL, 3:1) and purged with N2 for 15 minutes. Then PdCl2(dppf)-DCM (1.9 g, 2.4 mmol) and Int-5 (1.5 g, 9.6 mmol) were added and stirred for 10 minutes, finally Na2CO3 (1.9 g, 18 mmol) was added and the reaction mixture was stirred at 100° C. for 6 hours. After the completion of reaction, the volatiles were concentrated under vacuum. The residue was diluted with ice water (20 mL) and extracted with EtOAc (3×100 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain crude material, which was purified by column chromatography using 2% MeOH/DCM to afford Int-6 (0.7 g, 21%). Mass (m/z): 274.1 [M++1]. 1H NMR (200 MHz, CDCl3): δ 8.5 (d, J=6.8 Hz, 1H), 8.1 (d, J=6.8 Hz, 1H), 7.4 (s, 1H), 7.3 (m, 1H), 6.85 (m, 1H), 6.6 (d, J=12 Hz, 1H), 3.9 (s, 3H), 2.5 (s, 3H). To a stirred solution of Int-6 (0.7 g, 2.5 mmol) in acetonitrile (10 mL) were added tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3) (0.07 g, 0.076 mmol), Xanthpos (0.106 g, 0.2 mmol), Cs2CO3 (1.49 g, 4.6 mmol) and Int-7 (0.38 g, 2.5 mmol) at room temperature under argon purging, then stirred for 1 hour. The reaction mixture was heated to 100° C. for 16 hours. After the reaction completion, the volatiles were concentrated under reduced pressure. The residue was washed with ether, diluted with water and stirred for 15 minutes. The precipitated solid was filtered and dried under vacuum to afford Int-8 (0.240 g, 24%). Mass (m/z): 390 [M++1]. 1H NMR (200 MHz, dmso-d6): δ 10.2 (brs, 1H), 8.8 (brs, 1H), 8.35-8.45 (m, 2H), 8.25-8.18 (m, 1H), 7.82-7.95 (m, 1H), 7.15 (d, J=6.6 Hz, 1H), 7.0 (s, 1H), 7.0 (s, 1H), 6.65-6.76 (m, 1H), 3.85 (s, 3H), 2.45 (s, 3H). To a stirred solution of Int-8 (0.24 g, 0.61 mmol) in MeOH-DCM (25 mL, 3:1) was added 50% NH2OH (6 mL) at 0° C. After being stirred for 10 minutes at 0° C., a solution of NaOH (0.2 g) in water (2 mL) was added and stirred for additional 30 minutes at 0° C. The reaction mixture was then warmed to room temperature and stirred for 2 hours. The volatiles were concentrated under reduced pressure after the reaction completion. The residue was diluted with water (15 mL) at 0° C., acidified to about pH 7 using 2 N HCl and stirred for 10 minutes. The precipitated solid was filtered and dried under vacuum to afford the title compound (0.15 g, 62%) as a solid. Mass (m/z): 391 [M++1]. 1H NMR (200 MHz, dmso-d6): δ 10.2 (brs, 1H), 9.0 (brs, 1H), 8.6 (s, 1H), 8.35-8.45 (m, 2H), 7.85-8.05 (m, 2H), 7.78 (d, J=12.5 Hz, 1H), 7.08 (d, J=6.6 Hz, 1H), 7.0 (s, 1H), 6.65-6.75 (m, 1H), 6.41 (brs, 1H), 3.85 (s, 3H), 2.45 (s, 3H).

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - US2010/29638, 2010, A1 Location in patent: Page/Page column 126

6
[ 886502-58-5 ]
[ 10201-73-7 ]
[ 1204526-99-7 ]

Yield	Reaction Conditions	Operation in experiment
12%	In 1,2-dimethoxyethane at 20℃; Reflux;	48; 49 To a stirred solution of 1,1,1-trifluoro-2,4-pentane-dione (7 g, 45.4 mmol) in benzene (7 mL) was added sulfuryl chloride (3.6 mL, 45.4 mmol) slowly over a period of 2 hours at room temperature and then stirred for 2 hours at the same temperature. The reaction mixture was quenched with 7 mL water, followed by addition of ethyl acetate (20 mL) slowly. The organic phase was separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure at 25° C. to afford crude Int-1 (11 g, contains trace amount of EtOAc) as liquid. The crude compound was used in the next step without purification. Mass (m/z): 189 [M++1]. To a stirred solution of 4-methoxypyridin-2-amine (2.0 g, 16.1 mmol) in DME (20 ml) was added Int-1 (6.0 g, 32.2 mmol) at room temperature and the reaction mixture was stirred at reflux temperature for 3 hours. The volatiles were concentrated under reduced pressure. The crude material was purified by silica gel column chromatography eluting with EtOAc/hexane (15:85) to afford Int-2 (0.5 g, 12%). Mass (m/z): 259 [M++1]. 1H NMR (200 MHz, dmso-d6): δ 9.23 (d, J=6.2 Hz, 1H), 6.78 (t, J=7.4 Hz, 1H), 6.61 (d, J=7.8 Hz, 1H), 4.01 (s, 3H), 2.77 (s, 3H). A solution of Int-2 (0.4 g, 1.56 mmol) in DMF-DMA (10 mL) was stirred at reflux temperature for 16 hours. After the reaction, the volatiles were concentrated under reduced pressure. The crude material was washed with hexane (2×15 mL) to afford Int-3 (0.4 g, 81%) as brown color solid. Mass (m/z): 314 [M++1]. 1H NMR (200 MHz, dmso-d6): δ 9.22 (d, J=8 Hz, 1H), 7.80 (d, J=12.2 Hz, 1H), 6.95 (s, 1H), 6.71-6.78 (dd, J=2.4, 2.6 Hz, 1H), 5.68 (d, J=12 Hz, 1H), 3.87 (s, 3H), 3.18 (s, 3H), 2.93 (s, 3H). To a solution of Int-3 (0.88 g, 2.81 mmol) in DMF (10 mL) was added Int-4 (1.3 g, 7.0 mmol) followed by K2CO3 (1.16 g, 8.4 mmol) at room temperature and the reaction mixture was stirred at 100° C. for 16 hours. The reaction mixture was cooled to room temperature, diluted with ice-water (80 mL) and further stirred for 20 minutes. The precipitated solid was filtered off, washed with water (2×10 mL) and dried under vacuum to afford Int-5 (0.8 g, 66%) as brown solid. Mass (m/z): 444 [M++1]. 1H NMR (200 MHz, dmso-d6): δ 10.27 (brs, 1H), 9.03 (d, J=7.6 Hz, 1H), 8.72 (d, J=5.2 Hz, 1H), 7.93-7.89 (m, 4H), 7.22-7.13 (m, 2H), 6.84 (d, J=7 Hz, 1H), 3.91 (s, 3H), 3.82 (s, 3H). A mixture of Int-5 (0.9 g) and 4 N HCl (20 mL) was stirred at reflux temperature for 3 hours. The reaction mixture was cooled to room temperature to 0° C. and then stirred for 20 minutes. The precipitated solid was filtered off, washed with water (2×10 mL) and dried under vacuum to afford Int-6 (0.7 g, 90%) as solid. Mass (m/z): 432 [M++1]. 1H NMR (200 MHz, dmso-d6): δ 10.27 (brs, 1H), 9.03 (d, J=7.6 Hz, 1H), 8.72 (d, J=5.2 Hz, 1H), 7.93-7.89 (m, 4H), 7.22-7.13 (m, 2H), 6.84 (d, J=7 Hz, 1H), 3.82 (s, 3H).

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - US2010/29638, 2010, A1 Location in patent: Page/Page column 101

7
[ 107-20-0 ]
[ 10201-73-7 ]
[ 342613-71-2 ]

Yield	Reaction Conditions	Operation in experiment
87%	With sodium hydrogencarbonate In ethanol at 78℃; for 4h;	1.1 Step 1: Preparation of 7-methoxyimidazo[1,2-a]pyridine (1a) Add 4-methoxypyridin-2-amine (7.37g, 59.4mol) and 2-chloroacetaldehyde (11.64g, 148.6mol) into a clean flask and dissolve it with 25mL of ethanol.Add sodium bicarbonate (9.98 g, 118.9 mol). After stirring for 4 hours at room temperature of 78°C,Extract and separate with ethyl acetate and water, combine the organic phases, and dry with anhydrous sodium sulfate,After spin-drying the solvent and column chromatography (dichloromethane/methanol=30:1, V/V), a brown oily pure product was obtained, and the desired product (9.95 g, 87.0%) was obtained.
75%	With sodium hydrogencarbonate In ethanol for 6h; Reflux;	j00601j 7-Methoxyimidazo jl,2-aj pyridine (3) j00602j A solution of 4-methoxypyridin-2-amine (10 g, 80 mmol) in ethanol (150 mL)was charged with sodium hydrogen carbonate (13.4 g, 160 mmol) and chloroacetaldehyde (20 mL, 120 mmol, 45% wt solution in water) and heated at reflux for 6 h. The solvent was concentrated in vacuo resulting in residue which was purified by chromatography on silica gel, eluting with 20% ethyl acetate in n-hexane to give 8.70 g, 75% yield of the title compound as yellow oil. MS (ESj: m/z = 149.02 [M+H] LCMS: tR = 0.17 mm.
57%	With sodium hydrogencarbonate In ethanol; water for 3h; Reflux; Inert atmosphere;

Reference： [1]Current Patent Assignee: SUN YAT-SEN UNIVERSITY (CHINA) - CN113620943, 2021, A Location in patent: Paragraph 0064-0069
[2]Current Patent Assignee: COFERON, INC. - WO2015/106292, 2015, A1 Location in patent: Paragraph 00592; 00601; 00602
[3]Tung, Yen-Shih; Coumar, Mohane Selvaraj; Wu, Yu-Shan; Shiao, Hui-Yi; Chang, Jang-Yang; Liou, Jing-Ping; Shukla, Paritosh; Chang, Chun-Wei; Chang, Chi-Yen; Kuo, Ching-Chuan; Yeh, Teng-Kuang; Lin, Chin-Yu; Wu, Jian-Sung; Wu, Su-Ying; Liao, Chun-Chen; Hsieh, Hsing-Pang [Journal of Medicinal Chemistry, 2011, vol. 54, # 8, p. 3076 - 3080]

8
[ 10201-73-7 ]
[ 1232431-11-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With N-Bromosuccinimide; In acetonitrile; at 0 - 20℃; for 1h;	Step 3: 5-bromo-4-methoxyl-2-aminopyridine To a solution of 4-methoxyl-2-aminopyridine (12.4 g, 100 mmol) in acetonitrile (500 mL), N-bromobutanimide (17.8 g, 100 mmol) was added in portions at 0C under stirring. Upon completion of the addition, the mixture was stirred at room temperature for 1 hour. The solvent was evaporated and CH2Cl2 was added. The solution was washed with saturated sodium bicarbonate, dried, and concentrated to give 5-bromo-4-methoxyl-2-aminopyridine (20.3 g, 100% yield), which was directly used in the next step. MS m/z [ESI]: 203.0 [M+1].
81%	With dihydrogen peroxide; 1-butylpyridinium bromide; toluene-4-sulfonic acid; In 1,2-dimethoxyethane; at 80℃; for 24h;Schlenk technique; Inert atmosphere; Green chemistry;	General procedure: To a mixture of 2-aminopyridine (0.5 mmol, 1 equiv), p-TSA (0.4 mmol,0.8 equiv), 1-butylpyridinium bromide (1.5 mmol, 3 equiv) in a 50 mL Schlenk tube were added 1,2-dimethoxyethane (2 mL) under air. Then H2O2 (1.2 mmol, 2.4 equiv) was added. The mixture was stirred at 80C for 24 h. And then the mixture was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to give the products.
79%	With bromine; acetic acid; at 23℃; for 1h;	Step 1: [0430] To a solution of 4-methoxy-pyridin-2-ylamine (10.0 g, 80.64 mmol) in acetic acid (320 mL) was added Br2 (3.75 mL, 72.58 mmol) in acetic acid (80 mL) dropwise at RT and the resulting RM was stirred at RT for 1 h. The solid precipitate was separated by filtration, washed with hexane and dried to yield 5-bromo-4-methoxy-pyridin-2-ylamine (13.0 g, 79%). [0431] LC-MS (Method 4): m/z [M+1]+=203.1 & 204.8 (MW calc. 203.04); Rt=2.43 min.

73%	With bromine; In acetic acid; at 0 - 30℃; for 4h;	2-Amino-4-methoxypyridine (1.24 g, 10 mmol) was dissolved in 100 mL of acetic acid, After cooling to 0 degrees, A solution of bromine (1.92 g, 12 mmol) in acetic acid (30 mL) was added dropwise. Dropping is completed, The solution is reacted at 30 degrees. 4h, TLC monitoring raw material has been completely reacted, To the reaction solution was added 40 mL of saturated aqueous sodium sulfite solution, 25 degrees stirring reaction 0.5h, Concentrated under reduced pressure, The residue was extracted with ethyl acetate (150 mL × 3) Dried over anhydrous sodium sulfate, filter, The filtrate was concentrated under reduced pressure, Column chromatography (V (methylene chloride) / V (methanol) = 20/1), Obtained as a light yellow solid (1.45 g, 73%).
69%	With bromine; In acetic acid; at 20℃; for 1h;	A solution of Br2 (1 M in AcOH, 10 mL, 10 mmol) was slowly added into a solution commercially available compound 12-1 (1.24 g, 10 mmol) in AcOH (35 mL) at rt. After stirring at rt for 1 hr, the reaction mixture was filtered and the solid was dried in vacuo to give compound 12-2 (1.41 g, 69% yield). NMR (300 MHz, CD3OD): delta 7.84 (s, 1 H), 6.29 (s, 1 H), 3.87 (s, 3H) ppm.
47%	With N-Bromosuccinimide; acetic acid; In acetonitrile; at 20℃; for 1h;Inert atmosphere;	(41c). A mixture of 2-amino-4-methoxypyridine (2.4 g, 19 mol)and N-bromosuccinimide (3.1 g, 17 mmol) was dissolved in aceticacid (6 mL) and stirred at room temperature for 1 h. The reactionmixture was concentrated under vacuum, basified with saturatedaqueous K2CO3 and extracted with EtOAc. The combined organicswere dried, concentrated under vacuum, and purified by silicagel column chromatography, eluting with 50:1 CH2Cl2:MeOH, togive 41c (1.85 g, 47%). LCMS 203 [M+H]+.
41%	With bromine;	5-bromo-4-methoxypyridin-2-amine was prepared from 4-methoxypyridin-2-amine and bromine using Method 25. The product was purified by flash chromatography eluting with EtOAc in hexane (30 % to 70 % gradient) to yield 5-bromo-4-methoxypyridin-2-amine as a white solid (3.15 g, 41 %). MS: m/z = 203.0 [M+H]+.
	With bromine; acetic acid; at 20℃; for 1h;	A solution of compound 7a-1 (500 mg, 4 mmol) in 10 ml of acetic acid was added to a solution of bromine (4 ml, 1 M in acetic acid) and stirred at room temperature for 1 hour. The reaction was complete and the mixture was filtered and extracted with ethyl acetate and saturated sodium bicarbonate. The organic phase was dried over anhydrous sodium sulfate, separated and concentrated under reduced pressure to give the crude product which was purified by Combi-flash column chromatography to give the compound 7a-2 (340 mg). Purity: 78%, yield: 41%. spectrum data: MS m/z(ESI): 203[M+H]+.
15.1 g	With bromine; acetic acid; at 20℃; for 1.5h;	To a stirred solution of 4-methoxypyridin-2-ylamine (15 g, 121 mmol) in acetic acid (490 mL), at room temperature, is slowly added bromine as a 1M solution in acetic acid (120 mL, 120 mmol). After 1.5 h, the reaction mixture is filtered and the collected solid is dissolved in EtOAc. The mixture is washed with saturated NaHCO3 followed by water and then brine. The organic layer is dried over anhydrous Na2SO4, filtered, and the filtrate is concentrated under reduced pressure to provide 15.1 g of 5-bromo-4-methoxypyridin-2-ylamine (I-24-1).

Reference： [1]Patent: EP2952510,2015,A1 .Location in patent: Paragraph 0143
[2]Tetrahedron Letters,2014,vol. 55,p. 5058 - 5061
[3]Patent: US2015/166505,2015,A1 .Location in patent: Paragraph 0428; 0429; 0450
[4]Patent: CN104513257,2017,B .Location in patent: Paragraph 0411; 0412; 0413
[5]Patent: WO2012/58125,2012,A1 .Location in patent: Page/Page column 139; 140
[6]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 3947 - 3963
[7]Patent: WO2019/79373,2019,A1 .Location in patent: Paragraph 00262
[8]Patent: EP3235816,2017,A1 .Location in patent: Paragraph 0102-0103
[9]Patent: US2018/72717,2018,A1 .Location in patent: Paragraph 0283; 0334; 0468

9
[ 73112-16-0 ]
[ 10201-73-7 ]
[ 1407500-69-9 ]

Yield	Reaction Conditions	Operation in experiment
50%	With sodium t-butanolate;dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); In 1,4-dioxane; at 80℃; for 1.5h;Microwave irradiation;	Step 2: To a solution of 4-methoxypyridin-2-amine (620 mg, 5 mmol) and 2,6- dibromo-4-methylpyridine (1123 mg, 5.25 mmol) in dioxane (18 mL) was added l,l'-bis(di- tertbutylphosphino) ferrocene palladium dichloride (280 mg, 0.5 mmol) and sodium tert- butoxide (437 mg, 5.25 mmol). Then the mixture stirred under microwave irradiation for 1.5 hours at 80C. Then the mixture was poured into water (50 mL), and extracted with EtOAc (100 mL). The organic layer was washed with water (50 mL) and brine (50 mL), dried and concentrated. The residue purified by silica gel chromatography using a solvent system of 75% petroleum ether/EtOAc. The product containing fractions were collected and concentrated to give 6-bromo-N-(4-methoxypyridin-2-yl)-4-methylpyridin-2-amine (627 mg, 50 %). MS ESI calcd for CI2H12BrN30 [M + H]+ 294, found 294.
50%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium t-butanolate; In 1,4-dioxane; at 80℃; for 1.5h;Microwave irradiation;	To a solution of 4-methoxypyridin-2-amine (620 mg, 5 mmol) and 2,6- dibromo-4-methylpyridine (1 123 mg, 5.25 mmol) in dioxane (18 mL) was added l, l'-bis(di- tertbutylphosphino) ferrocene palladium dichloride (280 mg, 0.5 mmol) and sodium tert- butoxide (437 mg, 5.25 mmol). Then the mixture stirred under microwave irradiation for 1.5 hours at 80C. Then the mixture was poured into water (50 mL), and extracted with EtOAc (100 mL). The organic layer was washed with water (50 mL) and brine (50 mL), dried and concentrated. The residue purified by silica gel chromatography using a solvent system of 75% petroleum ether/EtOAc. The product containing fractions were collected and concentrated to give 6-bromo-N-(4-methoxypyridin-2-yl)-4-methylpyridin-2-amine (627 mg, 50 %). MS ESI calc'd for C12H12BrN30 [M + H]+ 294, found 294.

Reference： [1]Patent: WO2012/151137,2012,A1 .Location in patent: Page/Page column 51
[2]Patent: WO2014/74422,2014,A1 .Location in patent: Paragraph 00166

10
[ 89488-29-9 ]
[ 10201-73-7 ]

Reference： [1]Advanced Synthesis and Catalysis,2013,vol. 355,p. 627 - 631

11
[ 10201-73-7 ]
[ 1226879-32-8 ]

Yield	Reaction Conditions	Operation in experiment
46%	With N-iodo-succinimide In N,N-dimethyl-formamide at 25℃; for 1h;	1 To a three-necked flask was added 2-amino-4-methoxypyridine (7.8 g, 62.9 mmol), N,N-dimethylformamide (150 mL); N-iodosuccinimide (14.1 g, 62.7 mmol) was added at 25°C. The reaction solution was stirred at 25 °C for 60 minutes. The reaction solution was diluted with water (400 mL), filtration gave a solid crude product, the residue was purified by silica gel column chromatography (dichloromethane: methanol = 20: 1), to give a brown solid, the target product 5-iodo-4-methoxy-2-aminopyridine (7.24 g, 28.9 mmol, 46%).
44%	With iodine; silver trifluoromethanesulfonate In methanol at 18 - 80℃; for 10h; Inert atmosphere; Microwave irradiation;

Reference： [1]Current Patent Assignee: PEPTECH CORP - CN107011256, 2017, A Location in patent: Paragraph 0016-0017
[2]Sharp, Phillip P.; Banwell, Martin G.; Renner, Jens; Lohmann, Klaas; Willis, Anthony C. [Organic Letters, 2013, vol. 15, # 11, p. 2616 - 2619]

12
[ 10201-73-7 ]
[ 32111-21-0 ]
C₁₀H₁₀N₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 4h;Inert atmosphere;	A solution of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (1) (1.34g, 6.Slmmol), 4-methoxypyridin-2-amine (2)(0.85g, 6.83mmol), Cs2003 (4.24g, 13.01 mmol) and Xantphos (0.17g, 0.29mmol) indioxane (22mL) was purged with N2(g) for 10mm then Pd2(dba)3 (0.12g, 0.l3mmol) was added, re-purged for -5mm and reaction was heated to 90C for 4h. Once cooled down to rt, the mixture was partitioned between H20 (l5OmL) and EtOAc (3 x l2OmL). Combined organics were dried over Na2504, filtered and concentrated invacuo. The residue was purified by flash column chromatography withCH2CI2/EtOAc (9:1-0:1) to yield (3) (809mg, 61%) as a yellow solid.1H NMR (500 MHz, Chloroform-d), OH ppm: 8.70 (d, J=1.3 Hz, 1H), 8.11-8.22 (m,3H), 8.08 (d, J=2.7 Hz, 1H), 7.43 (d, J=2.2 Hz, 1H), 6.52 (dd, J=5.8, 2.3 Hz, 1H),3.88 (5, 3H).LCMS (ES): Found 203.2 [M+H].
61%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; for 4h;Inert atmosphere;	A solution of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (1 ) (1 .34g, 6.51 mmol), 4-methoxypyridin-2-amine (2) (0.85g, 6.83mmol), Cs2C03 (4.24g, 13.01 mmol) and Xantphos (0.17g, 0.29mmol) in dioxane (22mL) was purged with N2(g) for 10min then Pd2(dba)3 (0.12g, 0.13mmol) was added, re-purged for ~5min and reaction was heated to 90C for 4h. Once cooled down to rt, the mixture was partitioned between H20 (150ml_) and EtOAc (3 x 120ml_). Combined organics were dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by flash column chromatography with CH2CI2/EtOAc (9: 1 -0: 1 ) to yield (3) (809mg, 61 %) as a yellow solid. 1 H NMR (500 MHz, Chloroform-d), deltaEta ppm: 8.70 (d, J=1 .3 Hz, 1 H), 8.1 1 -8.22 (m, 3H), 8.08 (d, J=2.7 Hz, 1 H), 7.43 (d, J=2.2 Hz, 1 H), 6.52 (dd, J=5.8, 2.3 Hz, 1 H), 3.88 (s, 3H). LCMS (ES): Found 203.2 [M+H]+.
61%		Example PP (0552) (0553) PP (0554) A solution of <strong>[32111-21-0]2-<strong>[32111-21-0]iodopyrazine</strong></strong> (1 ) (1.34g, 6.51 mmol), 4-methoxypyridin-2-amine (2) (0.85g, 6.83mmol), Cs2C03 (4.24g, 13.01 mmol) and Xantphos (0.17g, 0.29mmol) in dioxane (22ml_) was purged with N2(g) for 10min then Pd2(dba)3 (0.12g, 0.13mmol) was added, re-purged for ~5min and reaction was heated to 90C for 4h. Once cooled down to rt, the mixture was partitioned between H20 (150ml_) and EtOAc (3 x 120ml_). Combined organics were dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by flash column chromatography with CH2CI2/EtOAc (9: 1-0:1) to yield (3) (809mg, 61 %) as a yellow solid. (0555) 1 H NMR (500 MHz, Chloroform-d), deltaEta ppm: 8.70 (d, J=1.3 Hz, 1 H), 8.1 1-8.22 (m, 3H), 8.08 (d, J=2.7 Hz, 1 H), 7.43 (d, J=2.2 Hz, 1 H), 6.52 (dd, J=5.8, 2.3 Hz, 1 H), 3.88 (s, 3H). (0556) LCMS (ES): Found 203.2 [M+H]+.

Reference： [1]Patent: WO2014/181137,2014,A1 .Location in patent: Page/Page column 74
[2]Patent: WO2017/29514,2017,A1 .Location in patent: Page/Page column 106; 107
[3]Patent: WO2017/208032,2017,A1 .Location in patent: Page/Page column 82

13
[ 71838-16-9 ]
[ 10201-73-7 ]
7-methoxy-2-methyl-pyrido[2,1-b]quinazolin-11-one [ No CAS ]

Reference： [1]Organic Letters,2015,vol. 17,p. 1569 - 1572

14
[ 71838-16-9 ]
[ 10201-73-7 ]
(2-bromo-4-methyl-phenyl)-(4-methoxy-pyridin-2-yl)-amine [ No CAS ]

Reference： [1]Organic Letters,2015,vol. 17,p. 1569 - 1572

15
[ 10201-73-7 ]
[ 1211520-71-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: N-Bromosuccinimide / acetonitrile / 1 h / 0 - 20 °C 2.1: sodium nitrite; hydrogen bromide / water / 0.5 h / -10 °C 2.2: 2 h

Reference： [1]Current Patent Assignee: SHOUYAO HOLDINGS BEIJING CO LTD; SINO BIOPHARMACEUTICAL LIMITED - EP2952510, 2015, A1

16
[ 10201-73-7 ]
[ 2430-99-1 ]
7-methoxy-2-phenyl-3-p-tolylimidazo[1,2-a]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With potassium hydrogencarbonate In acetonitrile at 80℃; for 4h;

Reference： [1]Roslan, Irwan Iskandar; Ng, Kian-Hong; Wu, Ji'-En; Chuah, Gaik-Khuan; Jaenicke, Stephan [Journal of Organic Chemistry, 2016, vol. 81, # 19, p. 9167 - 9174]

17
[ 2926-30-9 ]
[ 10201-73-7 ]
4-methoxy-3-(trifluoromethyl)pyridin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With H₂O₈S₂*2H₃N; [4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridine-N¹,N¹]bis-{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C}iridium(III) hexafluorophosphate In dimethyl sulfoxide at 40℃; for 0.5h; Flow reactor; UV-irradiation;	Trifluoromethylation; General Procedure: General procedure: In an oven-dried vial equipped with a magnetic stirrer and a PTFE septum, [Ir{dF(CF3)ppy}2](dtbpy)]PF6 (5.6 mg, 1 mol%) was added to a mixture of the substrate (0.5 mmol, 1 equiv), CF3SO2Na (1.5 mmol, 3 equiv), and (NH4)2S2O8 (0.5 mmol, 1 equiv) in DMSO (5 mL). The solution was pumped into the Vapourtec photoreactor (fluoropolymer tube, 1.3 mm i.d., 10 mL) and the liquid flowrate was set at 0.33 mL/min (30 min residence time). The reactor was irradiated with 54 blue LEDs (450 nm, total power 24 W). The reaction mixture collected from the outlet was diluted with H2O and extracted with Et2O (3×). The combined organic layers were washed with brine, dried over MgSO4, and concentrated in vacuo. The crude was then pre-adsorbed onto silica, dried in vacuo, and purified by flash chromatography to yield the trifluoromethylated product.

Reference： [1]Abdiaj, Irini; Bottecchia, Cecilia; Alcazar, Jesus; Noël, Timothy [Synthesis, 2017, vol. 49, # 22, p. 4978 - 4985]

18
[ 10201-73-7 ]
[ 1211520-39-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-chloro-succinimide / acetonitrile / 1.5 h / 0 °C 2: hydrogen bromide; bromine; sodium nitrite / water / 1 h / 0 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2017/197555, 2017, A1

19
[ 2314-97-8 ]
[ 10201-73-7 ]
[ 1227581-92-1 ]
[ 1227571-99-4 ]

Yield	Reaction Conditions	Operation in experiment
1: 18% 2: 12%	With N,N,N,N,-tetramethylethylenediamine; 5,5'-bis((2-(trifluoromethyl)phenyl)ethynyl)-2,2'-bithiophene In N,N-dimethyl-formamide at 20℃; for 0.333333h; Irradiation; Overall yield = 30 %;

Reference： [1]Bottecchia, Cecilia; Martín, Raúl; Abdiaj, Irini; Crovini, Ettore; Alcazar, Jesús; Orduna, Jesús; Blesa, María Jesús; Carrillo, José R.; Prieto, Pilar; Noël, Timothy [Advanced Synthesis and Catalysis, 2019, vol. 361, # 5, p. 945 - 950]

20
[ 10201-73-7 ]
[ 33631-05-9 ]

Yield	Reaction Conditions	Operation in experiment
88%	With L-Selectride; In tetrahydrofuran; for 72h;Reflux; Inert atmosphere;	General procedure: Toa solution of 1 (1.00 mmol) in THF (7.0 mL) was added L-selectride(1 M in THF, 3.0 mL, 3.00 mmol, 3 equiv) under an argonatmosphere. After being refluxed and monitored by TLC, thereaction mixture was quenched with MeOH and evaporated invacuo. The residue was purified by silica gel column chromatographyto give the desired compound 2.

Reference： [1]Synlett,2019,vol. 30,p. 951 - 954

21
[ 10201-73-7 ]
[ 1033810-70-6 ]

Reference： [1]Patent: WO2019/214634,2019,A1

22
[ 10201-73-7 ]
[ 937263-71-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: ethanol / 10 h / Reflux 2: hydroxylamine-O-sulfonic acid; pyridine / methanol / 10 h / Reflux 3: pyridine hydrochloride / 4 h / 160 °C 4: caesium carbonate / N,N-dimethyl-formamide / 2 h / 100 °C 5: palladium 10% on activated carbon; hydrogen / methanol / 3 h / 45 °C / 2068.65 Torr

Reference： [1]Current Patent Assignee: DIZAL (JIANGSU) PHARMACEUTICAL CO., LTD. - WO2019/214634, 2019, A1

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Technical Information

• 1,4-Addition of an Amine to a Conjugated Enone • 1,4-Addition of an Amine to a Conjugated Enone • Acetal Formation • Amides Can Be Converted into Aldehydes • Amine Synthesis from Nitriles • Amine Synthesis from Nitriles • Amines Convert Acyl Chlorides into Amides • Amines Convert Esters into Amides • Azide Reduction by LiAlH4 • Azide Reduction by LiAlH4 • Basicity of Amines • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Chan-Lam Coupling Reaction • Chichibabin Reaction • Diazotization Reaction • DIBAL Attack Nitriles to Give Ketones • Enamine Formation • Esters Are Reduced by LiAlH4 to Give Alcohols • Esters Hydrolyze to Carboxylic Acids and Alcohols • Ether Synthesis by Oxymercuration-Demercuration • Ethers Synthesis from Alcohols with Strong Acids • Formation of an Amide from an Amine and a Carboxylic Acid • Formation of an Amide from an Amine and a Carboxylic Acid • Grignard Reagents Transform Esters into Alcohols • Hantzsch Pyridine Synthesis • Hemiaminal Formation from Amines and Aldehydes or Ketones • Hemiaminal Formation from Amines and Aldehydes or Ketones • Hofmann Elimination • Hofmann Rearrangement • Hydride Reductions • Hydrolysis of Imines to Aldehydes and Ketones • Imine Formation from Amines and Aldehydes or Ketones • Leuckart-Wallach Reaction • Mannich Reaction • Methylation of Ammonia • Methylation of Ammonia • Nitrosation of Amines • Nomenclature of Ethers • Peptide Bond Formation with DCC • Petasis Reaction • Preparation of Amines • Preparation of Ethers • Preparation of LDA • Primary Ether Cleavage with Strong Nucleophilic Acids • Pyridines React with Grignard or Organolithium Reagents • Reactions of Amines • Reactions of Ethers • Reduction of an Amide to an Amine • Reduction of an Amide to an Amine • Reductive Amination • Reductive Amination • Ring Opening of Azacyclopropanes • Ring Opening of Azacyclopropanes • Ring Opening of Oxacyclobutanes • Ring Opening of Oxacyclopropane • Specialized Acylation Reagents-Vilsmeier Reagent • Strecker Synthesis • Synthesis of 2-Amino Nitriles • Synthesis of Alcohols from Tertiary Ethers • The Nucleophilic Opening of Oxacyclopropanes • Ugi Reaction

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Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 10201-73-7 ] {[proInfo.proName]}

Quality Control of [ 10201-73-7 ]

Related Doc. of [ 10201-73-7 ]

Product Details of [ 10201-73-7 ]

Calculated chemistry of [ 10201-73-7 ] Expand+

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 10201-73-7 ]

Application In Synthesis of [ 10201-73-7 ]

[ 10201-73-7 ] Synthesis Path-Upstream 1~14

[ 10201-73-7 ] Synthesis Path-Downstream 1~22

Technical Information

Related Functional Groups of [ 10201-73-7 ]

Ethers

Amines

Related Parent Nucleus of [ 10201-73-7 ]

Pyridines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 10201-73-7 ]

Related Parent Nucleus of
[ 10201-73-7 ]