[ CAS No. 5349-17-7 ] {[proInfo.proName]}

Name: 5349-17-7|2-Bromo-1-(pyridin-4-yl)ethanone hydrobromide|95%
Brand: Ambeed
SKU: A237594
Rating: 97 (28 reviews)

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Cat. No.: {[proInfo.prAm]}

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Quality Control of [ 5349-17-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 5349-17-7 ]

SDS Specification

Alternatived Products of [ 5349-17-7 ]

Product Details of [ 5349-17-7 ]

CAS No. :	5349-17-7	MDL No. :	MFCD02681893
Formula :	C₇H₇Br₂NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	RGALBQILADNMKA-UHFFFAOYSA-N
M.W :	280.94	Pubchem ID :	2776239
Synonyms :

Calculated chemistry of [ 5349-17-7 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	52.34
TPSA :	29.96 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) :	-6.55 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	2.06
Log Po/w (WLOGP) :	2.62
Log Po/w (MLOGP) :	1.08
Log Po/w (SILICOS-IT) :	2.2
Consensus Log Po/w :	1.59

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.15
Solubility :	0.198 mg/ml ; 0.000706 mol/l
Class :	Soluble
Log S (Ali) :	-2.32
Solubility :	1.35 mg/ml ; 0.00481 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.23
Solubility :	0.164 mg/ml ; 0.000582 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	1.63

Safety of [ 5349-17-7 ]

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

Application In Synthesis of [ 5349-17-7 ]

* 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 [ 5349-17-7 ]
Downstream synthetic route of [ 5349-17-7 ]

[ 5349-17-7 ] Synthesis Path-Upstream 1~5

1
[ 5349-17-7 ]
[ 17356-08-0 ]
[ 30235-28-0 ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: at 100℃; for 0.5 h; Biotage microwave Stage #2: With sodium hydrogencarbonate In water	COMPOUND 3a4-(Pyridin-4-yl)thiazol-2-amine. Synthesis of batch 1. A mixture of 4-(bromoacetyl)pyridine hydrobromide (2) (2.21 g, 7.90 mmol), thiourea (0.60 g, 7.90 mmol) in anhydrous EtOH (10 ml) was stirred in a Biotage microwave at 100 °C for 30 min. After colling to room temperature, the solid precipitate was filtered, dried under vacuum.Synthesis of batch 2. A mixture of 4-(bromoacetyl)pyridine hydrobromide (2) (2.54 g, 9.06 mmol), thiourea (0.69 g, 9.06 mmol) in anhydrous EtOH (10 ml) was stirred in a Biotage microwave at 100 °C for 30 min. After colling to room temperature, the solid precipitate was filtered, dried under vacuum.Synthesis of batch 3. A mixture of 4-(bromoacetyl)pyridine hydrobromide (2) (2.16 g, 7.73 mmol), thiourea (0.58 g, 7.73 mmol) in anhydrous EtOH (10 ml) was stirred in a Biotage microwave at 100 °C for 30 min. After colling to room temperature, the solid precipitate was filtered, dried under vacuum.Batches 1, 2, and 3 were combined, suspended in an aqueous sat. solution of NaHC0₃ , filtered, dried under vacuum to provide the title compound as a pale pink solid (5.53 g, 31.27 mmol, 95percent), 1H NMR (400 MHz, CD₃OD) δ 8.49 (d, J= 6.3 Hz, 2H), 7.79 (d, J= 6.3 Hz, 2H), 7.25 (s, 1H).
93%	Stage #1: Reflux Stage #2: With ammonium hydroxide In ethanol; water for 2 h;	A mixture of 2-bromo-l-pyridin-4-yl-ethanone hydrobromide (10 g, 35.59 mmol) and thiourea (2.71 g, 35.59 mmol) in absolute EtOH (100 mL) was re fluxed overnight. After cooling, the reaction mixture was diluted with water (400 mL), the pH was adjusted to 11 with ammonium hydroxide solution, and it was further stirred for 2h. The resulting precipitate was filtered, washed with water, and dried in vacuo to provide 5.85 g of 4-(2-amino- thiazol-4-yl)-pyridine as a pinkish solid (93percent yield): 1H NMR (DMSO-dtf, ppm) δ 7.23 (broad s, 2H), 7.42 (s, 1H), 7.74 (d, 2H), 8.56 (d, 2H); [M+H]⁺ m/z 178

Reference： [1] MedChemComm, 2012, vol. 3, # 6, p. 699 - 709
[2] Patent: WO2011/130740, 2011, A2, . Location in patent: Page/Page column 42
[3] Patent: WO2012/125981, 2012, A2, . Location in patent: Page/Page column 131
[4] Journal of Medicinal Chemistry, 2010, vol. 53, # 2, p. 787 - 797
[5] Patent: WO2009/114552, 2009, A1, . Location in patent: Page/Page column 133

2
[ 1122-54-9 ]
[ 5349-17-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	at 0 - 75℃; for 4 h;	4-Bromoacetyl-pyridine, HBr salt; Dibromine (17.2g, 108 mmol) was added dropwise to a cold (0°C) solution of 4-acetyl- pyridine (12 g, 99 mmol) in acetic acid containing 33percent of HBr (165 mL) under vigourous stirring. The vigorously stirred mixture was warmed to 40°C for 2h and then to 75°C. After 2h at 75°C, the mixture was cooled and diluted with ether (400 mL) to precipitate the product. which was recovered by filtration and washed with ether and acetone to give white crystals (100percent). This material may be recrystallised from methanol and ether.
98.1%	With N-Bromosuccinimide In ethyl acetate at 20 - 75℃; for 8 h;	The reaction bottle was added on the batch mother liquor 558g,Additional ethyl acetate 42g,121.1 g of 4-acetylpyridine was added with stirring,Stir well after 20 ~ 30 ° C batchwise add NBS186.9g;Add temperature slowly warmed to 65 ~ 75 ,TLC monitoring of raw materials reaction is completed, cooled to 0 ~ 10 full crystallization.Filtered, washed with 650g deionized water beating,Filtered again, dried to get white275.6 g of 4- (bromoacetyl) pyridine hydrobromide,The molar yield was 98.1percent,
94%	With bromine In tetrachloromethane for 1 h; Reflux	To a stirred solution of l-(pyridin-4-yl)-ethanone (10 g, 0.08 mol) in CCl₄ (150 mL) was added Br₂ (3.99 mL, 0.02 mol) dropwise at 0⁰C and the mixture was then refluxed for 1 h. The reaction mixture was filtered and dried in vacuo to afford 2-bromo-l -(pyridin-4- yl)-ethanone hydrobromide (22 g, 94percent) as a solid.

90%	With hydrogen bromide; bromine; acetic acid In water at 20℃;	EXAMPLE 1 2-Bromo-1-pyridin-4-ylethanone hydrobromide To a stirred solution of 4-acetylpyridine (10 mL, 90 mmol) in glacial acetic acid (40 mL) and 48percent hydrobromic acid (15 mL), bromine (4.65 mL, 90 mmol) in glacial acetic acid (10 mL) was added dropwise. After addition, the solution was stirred at room temperature overnight. The white precipitate was filtered off and washed with absolute ethanol, thus obtaining the title compound (22.2 g, 90percent) as a white solid containing traces of dibromoderivative, that was used as such in the next step. ¹H NMR (DMSO-d₆/400 MHz) δ ppm 5.05 (s, 2 H) 8.15 (d, 2 H) 9.0 (d, 2 H).
90%	With hydrogen bromide; bromine; acetic acid In water at 20℃;	Example 1; 2-Bromo-1 -pyridin-4-ylethanone hydrobromide; To a stirred solution of 4-acetylpyridine (10 mL, 90 mmo.) in glacial acetic acid (40 mL) and 48percent hydrobromic acid (15 mL), bromine (4.65 mL, 90 rnmoS) in giacial acetic acid (10 mL) was added dropwise. After addition, the solution was stirred at room temperature overnight. The white precipitate was filtered off and washed with absolute ethanol, thus obtaining the title compound (22.2 g, 90percent) as a white solid containing traces of dibromoderivative, that was used as such in the next step.¹H NMR (DMSOd₆ / 400 MHz) δ ppm 5.05 (s, 2 H) 8.15 (d, 2 H) 9.0 (d, 2 H).
87%	at 20 - 70℃; for 1 h;	Step 1. 2-Bromo-1-lvridin-4-yl-ethanone. To a 0° C. solution of 4-acetylpyridine (4.90 g, 41.3 mmol) and 48percent HBr (7.0 mL) in acetic acid (46.0 mL) was added, dropwise over 15 min, a solution of Br₂(2.3 mL, 45 mmol) in acetic acid (8.0 mL). After the addition was complete, the mixture was allowed to warm to rt and then was heated at 70° C. for 1 h. The mixture was cooled to 0° C. and treated with diethyl ether. The resultant white solid was isolated by vacuum filtration to give 9.90 g (87percent) of the ketone as the HBr salt. MS: exact mass calcd for C₇H₆BrNO, 199.0; m/z found, 200.2 [M+H]⁺.
85%	With hydrogen bromide; bromine; acetic acid In water at 70℃; for 3 h;	Preparation of 4-Bromoacetylpyridine, HBr saltHBrBromine (24 g, 150 mmol) in 4 mL of 45percent HBr was added drop wise under vigorous stirring to a solution at 70°C of 4-acetyl-pyridine (18 g, 148 mmol) in acetic acid containing 45percent of HBr (165 mL). The vigorously stirred mixture was kept at 70⁰C for 3h. The mixture was cooled and the precipitate collected by filtration and washed with petroleum ether(40-65°C)/methanol (1/1, 100 mL) to give 35.8 g of a white crystals of (85percent).
234.6 g	With bromine In tetrachloromethane for 1 h; Reflux	Bromine (131.92 g, 825.49 mmol) was added slowly at room temperature to a stirred solution of 3-1 (100 g, 825.491 mmol) in CC1₄ (2.5 L). The reaction mixture was then heated slowly to reflux for lh [reaction is exothermic and may be vigorous once it reaches 72 °C] . The product was precipitated out as light yellow solid. The reaction mixture was then cooled to room temperature and the product was collected by filtration, washed three times with diethyl ether (1.5 L in total) and dried to obtain compound 3-2 (234.6 g).
0.72 g	With hydrogen bromide; bromine; acetic acid In water at 20℃; for 4 h; Cooling with ice	Intermediate C: Preparation of 2-bromo-l-(pyridin-4-yl)ethanone hydrobromide To a solution of l-(pyridin-4-yl)ethanone (1.0 g, 8.25 mmol) in HO Ac (60 mL) under ice bath was added aqueous HBr (1 mL, 48percent) and Br₂ (1.45 g, 9.1 mmol) in HO Ac (20 mL). The mixture was stirred at rt for 4 h during which time a precipitate formed. Filtration of the solid provided 2-bromo-l-(pyridin-4-yl)ethanone hydrobromide (0.72 g, 3.6 mmol) as a yellow solid. LCMS [M+H]⁺ = 200.1.

Reference： [1] Patent: WO2005/73225, 2005, A1, . Location in patent: Page/Page column 49-50
[2] Patent: CN106632001, 2017, A, . Location in patent: Paragraph 0026; 0027; 0028; 0029
[3] Journal of Medicinal Chemistry, 2010, vol. 53, # 2, p. 787 - 797
[4] Patent: WO2009/158393, 2009, A1, . Location in patent: Page/Page column 51
[5] Patent: US2007/142415, 2007, A1, . Location in patent: Page/Page column 17
[6] Patent: WO2007/96334, 2007, A1, . Location in patent: Page/Page column 31
[7] Patent: US2006/293316, 2006, A1, . Location in patent: Page/Page column 34
[8] Patent: WO2006/106437, 2006, A2, . Location in patent: Page/Page column 26
[9] Journal of Medicinal Chemistry, 2017, vol. 60, # 16, p. 6942 - 6990
[10] Australian Journal of Chemistry, 1981, vol. 34, # 6, p. 1295 - 1302
[11] Australian Journal of Chemistry, 1989, vol. 42, # 10, p. 1735 - 1748
[12] Journal of Medicinal Chemistry, 2003, vol. 46, # 22, p. 4702 - 4713
[13] Journal of Heterocyclic Chemistry, 2003, vol. 40, # 5, p. 861 - 868
[14] Journal of Organic Chemistry, 2006, vol. 71, # 2, p. 713 - 723
[15] Patent: WO2013/148228, 2013, A1, . Location in patent: Page/Page column 11; 12
[16] Patent: WO2014/66132, 2014, A1, . Location in patent: Page/Page column 22-23
[17] Journal of Medicinal Chemistry, 2014, vol. 57, # 15, p. 6458 - 6467
[18] Patent: WO2015/88565, 2015, A1, . Location in patent: Paragraph 00209
[19] Patent: WO2015/88564, 2015, A1, . Location in patent: Paragraph 00234
[20] Patent: WO2009/114552, 2009, A1, . Location in patent: Page/Page column 78-79

3
[ 350-03-8 ]
[ 5349-17-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogen bromide; bromine In water; acetic acid at 40 - 75℃; for 2 - 4 h;	Preparation of 2-Bromo-l-pyridin-4-yl-ethanone hydrobromide Dibromine (17.2g, 108 mmol) was added drop wise to a cold (O⁰C) solution of 3- acetyl-pyridine (12 g, 99 mmol) in acetic acid containing 33percent of HBr (165 mL) under vigourous stirring. The vigorously stirred mixture was warmed to 40°C for 2h and then to 75°C. After 2h at 75°C, the mixture was cooled and diluted with ether (400 mL) to precipitate the product, which was recovered by filtration and washed with ether and acetone to give white crystals (100percent). This material may be recrystallized from methanol and ether. EPO <DP n="36"/>¹H NMR (DMSO-/) δ = 5.17 (s, 2H) ; 8.32 (dd, J= 6.1-1.6 Hz, 2H) ; 9.12 (dd, J- 6.1-1.6 Hz, 2H) ; 12.51 (br s, IH).

Reference： [1] Patent: WO2006/64375, 2006, A2, . Location in patent: Page/Page column 34-35

4
[ 1122-54-9 ]
[ 5349-17-7 ]

Reference： [1] Patent: WO2005/13986, 2005, A1, . Location in patent: Page/Page column 43

5
[ 621-40-9 ]
[ 5349-17-7 ]
[ 315702-99-9 ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: for 3 h; Heating; Reflux Stage #2: With ammonia In ethanol; water at 20℃; for 2 h;	7V-(3-Methylphenyl)-4-(4-pyridinyl)-l,3-thiazol-2-amine (5) ("STF- 62247"). A mixture of bromoketone hydrobromide 1 (1.13 g, 4.03 mmol) and 3- methylphenylthiourea 4 (0.67 g, 4.03 mmol) in EtOH (20 mL) was stirred at reflux temperature for 3 h. The mixture was cooled to 20 ⁰C, diluted with water (50 mL), the pH adjusted to ca. 8 with aqueous NH₃ and the mixture stirred at 20 ⁰C for 2 h. The precipitate was filtered, washed with water (5 mL) and dried. The crude solid was purified by column chromatography, eluting with a gradient (50-100percent) of EtO Ac/pet, ether, to give amine 5 (0.94 g, 87percent) as a cream powder: mp(EtOAc/pet. ether) 158-160 ⁰C; ¹H NMR δ 10.27 (br s, 1 H, NH), 8.62 (dd, J = 4.6, 1.6 Hz, 2 H, H-2', H-6'), 7.84 (dd, J= 4.6, 1.6 Hz, 2 H, H-3', H-5'), 7.69 (s, 1 <n="82"/>H, H-5), 7.57 (br d, J= 7.9 Hz, 1 H, H-6"), 7.47 (br s, 1 H, H-2"), 7.24 (dd, J= 7.8, 7.5 Hz, 1 H, H-5"), 6.81 (br d, J= 7.5 Hz, 1 H, H-4"), 2.33 (s, 3 H, CH₃); ¹³C NMR δ 163.5, 150.1 (2), 147.6, 140.9, 140.8, 138.1, 128.8, 122.2, 119.8 (2), 117.5, 114.1, 107.2, 21.2; MS m/z 268.4 (MH⁺, 100percent). Anal, calcd for Ci₅Hi₃N₃S-¹Z₄H₂O: C, 66.27; H, 5.01; N, 15.46. Found: C, 64.48; H, 5.08; N, 15.08percent.

Reference： [1] Journal of Medicinal Chemistry, 2010, vol. 53, # 2, p. 787 - 797
[2] Patent: WO2009/114552, 2009, A1, . Location in patent: Page/Page column 80-81

[ 5349-17-7 ] Synthesis Path-Downstream 1~88

1
[ 16696-83-6 ]
[ 5349-17-7 ]
4-(2'-methylthiothiazol-4'-yl)pyridine hydrobromide [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1980,vol. 33,p. 2291 - 2298

2
[ 1122-54-9 ]
[ 5349-17-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogen bromide; bromine; acetic acid; at 0 - 75℃; for 4h;	4-Bromoacetyl-pyridine, HBr salt; Dibromine (17.2g, 108 mmol) was added dropwise to a cold (0C) solution of 4-acetyl- pyridine (12 g, 99 mmol) in acetic acid containing 33% of HBr (165 mL) under vigourous stirring. The vigorously stirred mixture was warmed to 40C for 2h and then to 75C. After 2h at 75C, the mixture was cooled and diluted with ether (400 mL) to precipitate the product. which was recovered by filtration and washed with ether and acetone to give white crystals (100%). This material may be recrystallised from methanol and ether.
98.1%	With N-Bromosuccinimide; In ethyl acetate; at 20 - 75℃; for 8h;	The reaction bottle was added on the batch mother liquor 558g,Additional ethyl acetate 42g,121.1 g of 4-acetylpyridine was added with stirring,Stir well after 20 ~ 30 C batchwise add NBS186.9g;Add temperature slowly warmed to 65 ~ 75 ,TLC monitoring of raw materials reaction is completed, cooled to 0 ~ 10 full crystallization.Filtered, washed with 650g deionized water beating,Filtered again, dried to get white275.6 g of 4- (bromoacetyl) pyridine hydrobromide,The molar yield was 98.1%,
94%	With bromine; In tetrachloromethane; for 1h;Reflux;	To a stirred solution of l-(pyridin-4-yl)-ethanone (10 g, 0.08 mol) in CCl4 (150 mL) was added Br2 (3.99 mL, 0.02 mol) dropwise at 00C and the mixture was then refluxed for 1 h. The reaction mixture was filtered and dried in vacuo to afford 2-bromo-l -(pyridin-4- yl)-ethanone hydrobromide (22 g, 94%) as a solid.

90%	With hydrogen bromide; bromine; acetic acid; In water; at 20℃;	EXAMPLE 1 2-Bromo-1-pyridin-4-ylethanone hydrobromide To a stirred solution of 4-acetylpyridine (10 mL, 90 mmol) in glacial acetic acid (40 mL) and 48% hydrobromic acid (15 mL), bromine (4.65 mL, 90 mmol) in glacial acetic acid (10 mL) was added dropwise. After addition, the solution was stirred at room temperature overnight. The white precipitate was filtered off and washed with absolute ethanol, thus obtaining the title compound (22.2 g, 90%) as a white solid containing traces of dibromoderivative, that was used as such in the next step. 1H NMR (DMSO-d6/400 MHz) delta ppm 5.05 (s, 2 H) 8.15 (d, 2 H) 9.0 (d, 2 H).
90%	With hydrogen bromide; bromine; acetic acid; In water; at 20℃;	Example 1; 2-Bromo-1 -pyridin-4-ylethanone hydrobromide; To a stirred solution of 4-acetylpyridine (10 mL, 90 mmo.) in glacial acetic acid (40 mL) and 48% hydrobromic acid (15 mL), bromine (4.65 mL, 90 rnmoS) in giacial acetic acid (10 mL) was added dropwise. After addition, the solution was stirred at room temperature overnight. The white precipitate was filtered off and washed with absolute ethanol, thus obtaining the title compound (22.2 g, 90%) as a white solid containing traces of dibromoderivative, that was used as such in the next step.1H NMR (DMSOd6 / 400 MHz) delta ppm 5.05 (s, 2 H) 8.15 (d, 2 H) 9.0 (d, 2 H).
87%	With hydrogen bromide; bromine; acetic acid; at 20 - 70℃; for 1h;	Step 1. 2-Bromo-1-lvridin-4-yl-ethanone. To a 0 C. solution of 4-acetylpyridine (4.90 g, 41.3 mmol) and 48% HBr (7.0 mL) in acetic acid (46.0 mL) was added, dropwise over 15 min, a solution of Br2 (2.3 mL, 45 mmol) in acetic acid (8.0 mL). After the addition was complete, the mixture was allowed to warm to rt and then was heated at 70 C. for 1 h. The mixture was cooled to 0 C. and treated with diethyl ether. The resultant white solid was isolated by vacuum filtration to give 9.90 g (87%) of the ketone as the HBr salt. MS: exact mass calcd for C7H6BrNO, 199.0; m/z found, 200.2 [M+H]+.
85%	With hydrogen bromide; bromine; acetic acid; In water; at 70℃; for 3h;	Preparation of 4-Bromoacetylpyridine, HBr saltHBrBromine (24 g, 150 mmol) in 4 mL of 45% HBr was added drop wise under vigorous stirring to a solution at 70C of 4-acetyl-pyridine (18 g, 148 mmol) in acetic acid containing 45% of HBr (165 mL). The vigorously stirred mixture was kept at 700C for 3h. The mixture was cooled and the precipitate collected by filtration and washed with petroleum ether(40-65C)/methanol (1/1, 100 mL) to give 35.8 g of a white crystals of (85%).
56%	With bromine; In acetic acid; toluene; at 0 - 20℃;	Bromine (0.23 mL, 4.54 mmol) in toluene (4 mL) was added dropwise to a mixture of 4-acetylpyridine (500 mg, 4.13 mmol), AcOH (2 mL) and toluene (8 mL) at 0 C. The mixture was stirred at rt overnight. The solid was collected, washed with Et20 and dried to give the title compound (650 mg, 2.31 mmol, 56 %).
234.6 g	With bromine; In tetrachloromethane; for 1h;Reflux;	Bromine (131.92 g, 825.49 mmol) was added slowly at room temperature to a stirred solution of 3-1 (100 g, 825.491 mmol) in CC14 (2.5 L). The reaction mixture was then heated slowly to reflux for lh [reaction is exothermic and may be vigorous once it reaches 72 C] . The product was precipitated out as light yellow solid. The reaction mixture was then cooled to room temperature and the product was collected by filtration, washed three times with diethyl ether (1.5 L in total) and dried to obtain compound 3-2 (234.6 g).
	With hydrogen bromide; bromine; In water; acetic acid;	To a stirred solution of 4-acetyl pyridine (3.62 g, 29.88 mmol) in acetic acid (30 mL) is added a 48% aqueous solution of hydrogen bromide (5.3 mL, 47.16 mmol). Bromine is added (1.6 mL, 31.14 mmol) drop wise in 4 equal portions. The reaction is stirred for about 2 hours and a solid precipitated. Bromine (1.6 mL, 31.14 mmol) is added and the reaction is stirred overnight. The resulting precipitate is collected, washed with diethyl ether, and dried under vacuum to give the title compound (8.6 g, 102%). 1H NMR (d6-DMSO) delta 9.02 (d, 2H), 8.17 (d, 2H), 5.08 (2H)
0.72 g	With hydrogen bromide; bromine; acetic acid; In water; at 20℃; for 4h;Cooling with ice;	Intermediate C: Preparation of 2-bromo-l-(pyridin-4-yl)ethanone hydrobromide To a solution of l-(pyridin-4-yl)ethanone (1.0 g, 8.25 mmol) in HO Ac (60 mL) under ice bath was added aqueous HBr (1 mL, 48%) and Br2 (1.45 g, 9.1 mmol) in HO Ac (20 mL). The mixture was stirred at rt for 4 h during which time a precipitate formed. Filtration of the solid provided 2-bromo-l-(pyridin-4-yl)ethanone hydrobromide (0.72 g, 3.6 mmol) as a yellow solid. LCMS [M+H]+ = 200.1.
	With hydrogen bromide; bromine; In water; acetic acid; at 20℃; for 4h;Cooling with ice;	[00234] To a solution of l-(pyridin-4-yl)ethanone (1.0 g, 8.25 mmol) in HOAc (60 mL) under ice bath was added aqueous HBr (1 mL, 48%) and Br2 (1.45 g, 9.1 mmol) in HOAc (20 mL). The mixture was stirred at rt for 4 h during which time a precipitate formed. Filtration of the solid provided 2-bromo-l-(pyridin-4-yl)ethanone hydrobromide (0.72 g, 3.6 mmol) as a yellow solid. LC/MS [M+H]+ = 200.1.
	With hydrogen bromide; bromine; acetic acid; at 0 - 75℃;	Example 1-1 7V-Phenyl-4-(4-pyridinyl)-l,3-thiazol-2-amine (3). [0220] 2-Bromo-l-(pyridin-4-yl)ethanone Hydrobromide (1). Br2 (4.45 mL, 86.7 mmol) was added dropwise to a stirred a solution of 4-acetylpyridine (10.0 g, 82.5 mmol) in 30% HBr/HOAc (100 mL) at 0-5 0C. The mixture was stirred at 40 0C for 1 h and then 75 0C for 1 h. The mixture was cooled to 20 0C, diluted with <n="80"/>Et2O (400 niL) and stirred for 30 min. The precipitate was filtered, washed with Et2O (25 rnL) and dried under vacuum to give the hydrobromide salt 1 (22.39 g, 97%) as a cream powder: mp (HOAc/ether) 190-195 0C [lit. (Ogawa, K. J. Chem. Soc Perkin 1. 1985, 2417) mp 197-200 0C]; 1H NMR delta 9.02 (br d, J= 5.5 Hz, 2 H, H-2', H-6'), 8.71 (br s, 1 H, N HBr), 8.15 (br d, J= 5.5 Hz, 2 H, H-3', H-5'), 5.06 (s, 2 H, CH2Br).
2.529 g	With hydrogen bromide; bromine; acetic acid; In water; at 25℃; for 20h;Inert atmosphere;	4-acetylpyridine (1.00 mL, 9.04 mmol) was added to a solution of HBr (47 % in 0, 4.56 mL, 27.12 mmol) in AcOH (20 mL) at 25 C. Bromine (1.59 g, 0.51 mL, 9.94 mmol) was added dropwise to the solution, then a white precipitate appeared slowly. The mixture was stirred for 20 h. Diethyl ether (20 mL) was added, the solid was filtered and washed with diethyl ether (2 x 5 mL). After drying under vacuum, 4-(2-bromoacetyl)pyridin-l-ium bromide was obtained as an off-white solid (2.529 g) which was used without further purification.

Reference： [1]Patent: WO2005/73225,2005,A1 .Location in patent: Page/Page column 49-50
[2]Patent: CN106632001,2017,A .Location in patent: Paragraph 0026; 0027; 0028; 0029
[3]Journal of Medicinal Chemistry,2010,vol. 53,p. 787 - 797
[4]Patent: WO2009/158393,2009,A1 .Location in patent: Page/Page column 51
[5]Patent: US2007/142415,2007,A1 .Location in patent: Page/Page column 17
[6]Patent: WO2007/96334,2007,A1 .Location in patent: Page/Page column 31
[7]Patent: US2006/293316,2006,A1 .Location in patent: Page/Page column 34
[8]Patent: WO2006/106437,2006,A2 .Location in patent: Page/Page column 26
[9]Journal of Medicinal Chemistry,2017,vol. 60,p. 6942 - 6990
[10]Australian Journal of Chemistry,1981,vol. 34,p. 1295 - 1302
[11]Patent: WO2019/53427,2019,A1 .Location in patent: Page/Page column 54-55
[12]Australian Journal of Chemistry,1989,vol. 42,p. 1735 - 1748
[13]Journal of Medicinal Chemistry,2003,vol. 46,p. 4702 - 4713
[14]Journal of Heterocyclic Chemistry,2003,vol. 40,p. 861 - 868
[15]Journal of Organic Chemistry,2006,vol. 71,p. 713 - 723
[16]Patent: WO2013/148228,2013,A1 .Location in patent: Page/Page column 11; 12
[17]Patent: WO2014/66132,2014,A1 .Location in patent: Page/Page column 22-23
[18]Journal of Medicinal Chemistry,2014,vol. 57,p. 6458 - 6467
[19]Patent: WO2015/88565,2015,A1 .Location in patent: Paragraph 00209
[20]Patent: WO2015/88564,2015,A1 .Location in patent: Paragraph 00234
[21]Patent: WO2009/114552,2009,A1 .Location in patent: Page/Page column 78-79
[22]Patent: WO2019/201865,2019,A1 .Location in patent: Page/Page column 14; 55-56

3
[ 14150-95-9 ]
[ 5349-17-7 ]
[ 79690-72-5 ]

Reference： [1]Australian Journal of Chemistry,1981,vol. 34,p. 1295 - 1302

4
[ 5349-17-7 ]
[ 513-74-6 ]
4-(pyridin-4'-yl)thiazole-2⁽³⁾-thione hydrobromide [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1980,vol. 33,p. 2291 - 2298

5
[ 5349-17-7 ]
[ 104484-08-4 ]
[ 104484-15-3 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1985,p. 2417 - 2424

6
[ 5349-17-7 ]
[ 27366-72-9 ]
N,N-dimethyl<4-(pyridin-4'-yl)thiazol-2-yl>methylamine [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1981,vol. 34,p. 2423 - 2429

7
[ 5349-17-7 ]
[ 24812-53-1 ]
N,N-dimethyl-2-<4'-(pyridin-4''-yl)thiazol-2'-yl>amine [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1981,vol. 34,p. 2423 - 2429

8
[ 5349-17-7 ]
[ 80948-02-3 ]
N,N-dimethyl-2-<4'-(pyridin-4''-yl)thiazol-2'-yl>propylamine [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1981,vol. 34,p. 2423 - 2429

9
[ 5349-17-7 ]
[ 141353-03-9 ]
6-(Benzyl-methyl-amino)-2-pyridin-4-yl-imidazo[1,2-b]pyridazin-3-ol [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1992,vol. 45,p. 751 - 757

10
[ 5349-17-7 ]
[ 121041-64-3 ]
6-(2-Methoxy-phenoxy)-2-pyridin-4-yl-imidazo[1,2-b]pyridazin-3-ol [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1989,vol. 42,p. 1735 - 1748

11
[ 5349-17-7 ]
[ 122479-48-5 ]
6-(3-Methoxy-benzylamino)-2-pyridin-4-yl-imidazo[1,2-b]pyridazin-3-ol [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1989,vol. 42,p. 1759 - 1768

12
[ 5349-17-7 ]
[ 144793-03-3 ]
[ 144792-99-4 ]

Reference： [1]Journal of Organic Chemistry,1992,vol. 57,p. 6749 - 6755

13
[ 5349-17-7 ]
[ 121041-65-4 ]
6-(3-Methoxy-benzylsulfanyl)-2-pyridin-4-yl-imidazo[1,2-b]pyridazin-3-ol [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1989,vol. 42,p. 1735 - 1748

14
[ 5349-17-7 ]
[ 78129-66-5 ]
2-<4'-(pyridin-4''-yl)thiazol-2'-ylthio>-acetamide hydrobromide [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1980,vol. 33,p. 2291 - 2298

15
[ 5349-17-7 ]
(4-pyridinyl)glyoxal hydrobromide [ No CAS ]

Reference： [1]Heterocycles,1990,vol. 31,p. 2163 - 2172

16
[ 5349-17-7 ]
[ 62-55-5 ]
4-(2'-methylthiazol-4'-yl)pyridine hydrobromide [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1980,vol. 33,p. 2291 - 2298

17
[ 5349-17-7 ]
[ 65-85-0 ]
[ 875783-84-9 ]

Reference： [1]Journal of Organic Chemistry,2006,vol. 71,p. 713 - 723

18
[ 64-17-5 ]
[ 5349-17-7 ]
[ 156093-78-6 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1202 - 1206

19
[ 5349-17-7 ]
[ 94-02-0 ]
2-phenyl-5-pyridin-4-yl-1H-pyrrole-3-carboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%		Step 1: Formation of pyrrole ring (3); 2-Bromo-l-pyridin-4-ylethanone hydrobromide 1 (1.7 g, 6.2 mmol) was added to a mixture of 3-oxo-3-phenyl-propionic acid ethyl ester 2 (R=H, 1 g, 5.2 mmol) in 100 mL of dry THF and NaH (0.5 g, 13.0 mmol) at 0 0C. The solution was left at 00C for 1 h and then stirred at rt for 3 h. The solvent was removed and the residue was dissolved in 60 mL of EtOH, ammonium acetate (1.4 g, 18.7 mmol) was added and the reaction mixture was left overnight at rt. The crude material was purified by flash chromatography (DCM/MeOH 98:2) affording 920 mg (60%) of 2-phenyl-5-pyridin-4- yl-lH-pyrrole-3-carboxylic acid ethyl ester as a solid.1R NMR (DMSOd6 / 400 MHz) delta ppm 1.20 (t, J=7.08 Hz, 3H), 4.16 (q, J=7.08 Hz, 2H), 7.30 (d, J=2.81 Hz, IH), 7.43 (m, 3H), 7.64 (m, 2H), 7.79 (m, 2H), 8.53 (m, 2H), 12.12 (s, IH); ESI (+) MS: m/z 293 (MH+).

Reference： [1]Patent: WO2007/110344,2007,A1 .Location in patent: Page/Page column 36
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 7296 - 7315

20
[ 5349-17-7 ]
2-cyclohexyl-5-pyridin-4-yl-1H-pyrrole-3-carboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%		Step 1: Formation of pyrrole ring (6); To a solution of S-cyclohexyl-S-oxo-propionic acid ethyl ester 5 (1.6 g, 8.3 mmol) in anhydrous THF (200 mL), cooled at 00C, NaH (900 mg, 21 mmol) was added. After 15 min 2-bromo-l-pyridin-4-yl-ethanone hydrobromide 1 (3 g, 10.8 mmol) was added and the mixture was stirred 5 h at 00C. The solvent was removed and the residue was dissolved in EtOH (120 mL). Ammonium acetate (1.9 g, 25 mmol) was added and the solution was stirred overnight at rt. After solvent removal the residue was dissolved in EtOAc and the organic phase was washed with a saturated aqueous solution OfNa2COs, then with water, dried (Na2SOzO and concentrated. The crude material was purified by silica gel chromatography (eluant: EtOAc) to yield 2-cyclohexyl-5-pyridin-4-yl-lH- pyrrole-3-carboxylic acid ethyl ester as a white solid (1.1 g, 43%). 1H NMR (DMSO-d6/ 400 MHz) delta ppm l.33 (m, IH) 1.30 (t, J=7.13 Hz, 3H) 1.70-1.88 (m, 7H) 3.44-3.56 (m, IH) 4.20 (q, J=7.15 Hz, 2H) 7.06 (d, J=2.68 Hz, IH) 7.71 (d, J=6.22 Hz, 2H) 8.50 (d, J=6.22 Hz, 2H) 11.37 (bs, IH); ESI (+) MS: m/z 299 (MH+).

Reference： [1]Patent: WO2007/110344,2007,A1 .Location in patent: Page/Page column 42

21
[ 5349-17-7 ]
4-(3-ethoxycarbonyl-5-pyridin-4-yl-1H-pyrrol-2-yl)-piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%		Step 1: Formation of pyrrole ring (9); To a solution of 4-(2-ethoxycarbonyl-acetyl)-piperidine-l-carboxylic acid tert -butyl ester 8 (2.5 g, 8.3 mmol) in anhydrous THF (200 mL), cooled at 00C, NaH (900 mg, 21 mmol) was added. After 15 min 2-bromo-l-pyridin-4-yl-ethanone hydrobromide 1 (3 g, 10.8 mmol) was added and the mixture was stirred 5 h at 00C. The solvent was removed under reduced pressure and the residue was dissolved in EtOH (120 mL). Ammonium acetate (1.9 g, 25 mmol) was added and the solution was stirred overnight at rt. After solvent removal the residue was dissolved in EtOAc and the organic phase was washed with a saturated aq solution of Na2CO3, then with water, dried (Na2SOzO and <n="45"/>concentrated. The crude material was purified by silica gel chromatography (eluant: EtOAc) to yield 4-(3-ethoxycarbonyl-5-pyridin-4-yl-lH-pyrrol-2-yl)-piperidine-l- carboxylic acid tert-butyl ester as a pink solid (1.55 g, 47%).1U NMR (DMSOd6/ 400 MHz) delta ppm 1.30 (t, J=7.07 Hz, 3H) 1.45 (s, 9H) 1.71 (bd, 2H) 1.80-1.92 (m, 2H) 2.79 (bs, 2H) 3.64-3.74 (m, IH) 4.15 (bd, J=I 1.46 Hz, 2H) 4.21 (q, J=7.07 Hz, 2H) 7.08 (d, J=2.68 Hz, IH) 7.71 (d, J=6.22 Hz, 2H) 8.50 (d, ./=6.10 Hz, 2H) 11.45 (bs, IH); ESI (+) MS: m/z 400 (MH+).

Reference： [1]Patent: WO2007/110344,2007,A1 .Location in patent: Page/Page column 43-44

22
[ 5349-17-7 ]
sodium salt of ethyl cyanoacetate [ No CAS ]
[ 951784-47-7 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃;	Step 1: Condensation to cyanoester (29); To a suspension of sodium metal (81 mg, 3.5 mmol) in 10 mL anhydrous EtOH, ethylcyanoacetate (0.37 mL, 3.5 mmol) was added at 00C. The solution was stirred until sodium was completely dissolved. The solvent was evaporated to obtain a white solid that was added portionwise to a stirred solution of bromoacetylpyridine 1 (1.0 g, 3.5 mmol) in anhydrous THF (20 mL) and DIEA (0.6 mL, 3.5 mmol). The reaction mixture was stirred overnight at rt. The solvent was removed, the residue was suspended in water and extracted with DCM. The organic extracts were dried over Na2SC^ and concentrated. The crude was purified by flash chromatography (DCM/MeOH 95:5) to give 710 mg (87%) of 2-cyano-4-oxo-4-pyridin-4-yl-butyric acid ethyl ester as a reddish oil.1U NMR (DMSOd6/ 400 MHz) delta ppm 1.23 (t, J=7.07 Hz, 3H), 3.88 (d, J=5.25 Hz, 2H), 4.21 (q, J=7.07 Hz, 2H), 4.64 (t, J=5.25 Hz, IH), 7.89 (d, J=6.00 Hz, 2H), 8.85 (d, J=6.00 Hz, 2H); ESI (+) MS: m/z 233 (MH+).

Reference： [1]Patent: WO2007/110344,2007,A1 .Location in patent: Page/Page column 64

23
[ 1122-54-9 ]
BrH*C₇H₅Br₂NO [ No CAS ]
[ 5349-17-7 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen bromide; bromine; In water; acetic acid; at 20℃;	To a stirred solution of 4-acetylpyridine (10 mL, 90 MMOLS) in glacial acetic acid (40 mL) and 48% HYDROBROMIC acid (15 ML), bromine (4.65 mL, 90 mmols) in glacial acetic acid (10 mL) was added dropwise. After addition, the solution was stirred at room temperature overnight. The white precipitate was filtered off and washed with absolute ethanol, thus obtaining the title compound (22.2 G Y=90%) as a white solid containing traces of dibromoderivative, that was used as such in the next step. 'H NMR (DMSO-D6/300 MHz) S ppm 5.05 (s, 2 H) 8.15 (d, 2 H) 9.0 (d, 2 H).

Reference： [1]Patent: WO2005/13986,2005,A1 .Location in patent: Page/Page column 43

24
5-phenylpiperidine-2,4-dione [ No CAS ]
[ 5349-17-7 ]
7-phenyl-2-pyridin-4-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium acetate; In ethanol; at 20℃; for 1h;	A solution of 5-PHENYLPIPERIDINE-2, 4-dione (556 mg, 2.94 MMOL) and ammonium acetate (603 MG, 7.83 MMOL) in ethanol (20 mL) was treated with 2-BROMO-1-PYRIDIN-4-YLETHANONE hydrobromide (550 mg, 1.96 MMOL) at room temperature for one hour. The mixture was concentrated under reduced pressure, diluted with ethyl acetate and washed with 5% NaHCO3 solution and with water. The organic layer was dried over Na2SO4 and evaporated to dryness. The crude material was chromatographed on silica gel eluted with methylene CHLORIDE/METHANOL 9/1 to give the desired compound as a red foamy free base solid. The free base was dissolved in ethanol, treated with 4 N hydrochloric acid in dioxane and diluted with ethyl acetate until precipitation of the hydrochloride salt that was filtered, thus affording the title compound (220 mg; Y=34%). 'H NMR (DMSO-d6/400 MHz) 5 ppm 3.87 (dd, 2H, J=5. 73, 11.95), 4.41 (t, 1 H), 7.18-7. 38 (m, 6H), 7.66 (s, 1H), 8.18 (d, 2H, J=7.08), 8.70 (d, 2H, J=7. 08), 12.55 (BS, 1H).

Reference： [1]Patent: WO2005/13986,2005,A1 .Location in patent: Page/Page column 45

25
[ 5239-39-4 ]
[ 5349-17-7 ]
6,6-dimethyl-2-pyridin-4-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium acetate; In ethanol; at 20℃;	A suspension OF 6, 6-DIMETHYFPIPERIDINE-2, 4-dione (225 mg, 1.6 MMOL) and 2-bromo-1-pyridin- 4-Y . ETHANONE HYDROBROMIDE (300 mg, 1.06 MMOL) in ethanol (12 mL) was treated with ammonium acetate (329 mg, 4.27 MMOL) and kept at room temperature overnight. The mixture was evaporated under reduced pressure, taken up with water (14 mL) and filtered to give 200 mg of the title compound, as a pink solid free base. The free base was dissolved in methanol (14 mL), treated with 4 N hydrochloric acid in dioxane (0.5 mL) and diluted with ethyl acetate until precipitation of the hydrochloride salt that was filtered, thus affording the title compound (192 mg, Y=64%) as a white solid. H NMR (DMSO-D6/400 MHz) 5 ppm 1.29 (s, 6H), 2.90 (s, 2H), 7. 27 (s, 1H), 7.59 (s, 1H), 8.18 (d, 2H, J=7. 07), 8.70 (d, 2H, J=7. 07), 12.65 (bs, 1H).

Reference： [1]Patent: WO2005/13986,2005,A1 .Location in patent: Page/Page column 46

26
[ 845267-70-1 ]
[ 5349-17-7 ]
7-isopropyl-2-pyridin-4-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58.2%	With ammonium acetate; In ethanol; at 20℃;	A suspension of 5-isopropylpiperidine-2, 4-dione (1.9 g, 12.24 MMOL) and 2-bromo-1-pyridin-4- YLETHANONE hydrobromide (2.6 G, 9. 42 MMOL) in ethanol (120 mL) was treated with ammonium acetate (2. 9 9, 37.7 MMOL) at room temperature The resulting solution was stirred overnight. The mixture was concentrated under reduced pressure, diluted with ethyl acetate and washed with NAOH 0.5 M (pH=9). The aqueous layer was extracted with ethyl acetate (x5). The collected organic layers were dried over NA2S04 and evaporated to dryness. The crude material was chromatographed on silica gel, eluting with METHYLENE CHLORIDE/ETHANOL 10/1, to give the desired compound (1.4 G, 5.48 mmol, 58.2 %). 1 H NMR (400 MHz, DMSO-D6) 5 ppm 0.92 (d, J=6.95 Hz, 3 H) 0.94 (d, J=6.70 Hz, 3 H) 1.95- 2.13 (m, 1 H) 2.69 (m, 1 H) 3.35 (m, 1 H) 3.50 (m, 1 H) 6.97 (d, J=3.61 Hz, 1 H) 7.00 (d, J=2.43 Hz, 1 H) 7.65 (d, J=6.22 Hz, 2 H) 8.50 (d, J=6. 22 Hz, 2 H) 11.74 (s, 1 H) ESI (+) MS: m/z 256 (MH+).

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 293 - 307
[2]Patent: WO2005/13986,2005,A1 .Location in patent: Page/Page column 46

27
[ 59277-89-3 ]
[ 5349-17-7 ]
C₈H₉N₅O₃CHCC₅H₄N [ No CAS ]

Reference： [1]Nucleosides, nucleotides and nucleic acids,2005,vol. 24,p. 571 - 575

28
[ 5349-17-7 ]
[ 50607-30-2 ]
[ 845714-00-3 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2647 - 2654

29
[ 5349-17-7 ]
[ 611-10-9 ]
ethyl 2-oxo-1-[2-oxo-2-(4-pyridyl)ethyl]cyclopentane-1-carboxylate [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2007,p. 3227 - 3238

30
[ 630409-82-4 ]
[ 5349-17-7 ]
[(2-nitrophenyl)methyl](4-(pyridin-4-yl)(1,3-thiazol-2-yl))amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; water; at 45℃; for 1.5h;	[0418] (b) Preparation of [(2-nitrophenyl)methyl](4-(4-pyridyl)(1,3-thiazol-2-yl))amine. To a heated (45 C.) slurry of amino[(2-nitrophenyl)methyl]amino}methane-1-thione (Step a) (841 mg, 4.0 mmol) in 50% aqueous MeOH (50 mL) was added 4-(bromoacetyl)pyridine hydrobromide (Aust. J. Chem. 1989, 42, 1735; 1.16 g, 4.1 mmol) and the reaction was stirred at 45 C. for 1.5 h. The reaction was cooled to RT and the solids were filtered and washed with water. Drying over P2O5 overnight gave a pale yellow powder. MS m/z: 313 (M+1), 311 (M-1). Calc'd for C15H12N4O2S-312.07.

Reference： [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 6574 - 6595
[2]Patent: US2003/229068,2003,A1 .Location in patent: Page 34

31
[ 5349-17-7 ]
[ 118838-55-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tetrahydroborate; In methanol; water; at -10℃; for 1.08333h;	A solution of <strong>[5349-17-7]4-bromoacetylpyridine hydrobromide</strong> (Taurins, A.; Blaga, A. J. [HETEROCYCLIC CHEM.,] 1970,7, [1137-1141)] (14.5 g) in methanol (150 mL) is cooled to [- 10 C] (internal). A solution of sodium borohydride (3.03 g) in water (50 mL) is added drop-wise over 1 h. The reaction mixture is allowed to stir for an additional 5- 10 min after the addition is complete. Hydrobromic acid (48%) is added to pH 3-4. The reaction mixture is concentrated in vacuo to remove methanol and then poured into cold ethyl acetate (100 [ML)/2] N [NAOH] (50 [ML).] The organic layer is removed, dried [(MGS04),] filtered, and concentrated in vacuo to yield 8.406 g of the bromohydrin as a pink solid. The crude bromohydrin (5.00 g) is dissolved in methanol (20 mL), and a 2.0 M solution of methylamine in methanol (125 [ML)] is added. The reaction mixture is stirred at room temperature for 18 h and then concentrated in vacuo. The resulting orange oil is dissolved in water (50 [ML),] adjusted to pH 12 with a 2 N [NAOH] solution, and extracted with ethyl acetate (4 x 100 [ML).] The combined organic layers are dried [(MGS04),] filtered, and concentrated in vacuo. The resulting yellow solid is purified by column chromatography [(CHCL3/METHANOL,] 95/5,90/10 ; [CHCL3/METHANOL/NH4OH,] 90/10/1) to yield 0.986 g of the title compound as a pale orange solid. Physical characteristics. M. p. 90-93 C ; 1H NMR (400 MHz, DMSO-D6) delta 8.49, 7.35, 5.49, 4.66-4. 63,2. 63-2.54, 2.29, 1.67 ; MS (ESI+) m/z 153 (M+H) +.

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 209 - 221
[2]Patent: WO2004/22567,2004,A1 .Location in patent: Page 38-39

32
[ 5349-17-7 ]
ethyl 1-butyl-8-oxo-2-(4-pyridyl)-1,4,5,6,7,8-hexahydroazocine-4-carboxylate [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2007,p. 3227 - 3238

33
[ 5349-17-7 ]
C₂₄H₂₅N₃O₅ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1202 - 1206

34
[ 5349-17-7 ]
[ 71708-14-0 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1202 - 1206

35
[ 5349-17-7 ]
[ 864378-56-3 ]

Reference： [1]Journal of Heterocyclic Chemistry,2005,vol. 42,p. 947 - 954

36
[ 5349-17-7 ]
11-(N-methyl-4'-pyridinium)naphtho[2,1-b]furan iodide [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,2005,vol. 42,p. 947 - 954

37
[ 5349-17-7 ]
[ 639785-75-4 ]

Reference： [1]Journal of Heterocyclic Chemistry,2003,vol. 40,p. 861 - 868

38
[ 5349-17-7 ]
4-(1-oxido-4-pyridyl)-3-phenyl-2(5H)furanone [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,2003,vol. 40,p. 861 - 868

39
[ 5349-17-7 ]
[ 610270-74-1 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 4702 - 4713

40
[ 5349-17-7 ]
7-(4-fluoro-phenyl)-6-pyridin-4-yl-7<i>H</i>-pyrrolo[2,3-<i>d</i>]pyrimidin-4-ylamine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 4702 - 4713

41
[ 5349-17-7 ]
N,N'-dicyano-2-(4-pyridyl)pyrazino[2,3-b]naphthoquinodiimine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 216 - 224

42
[ 5349-17-7 ]
4-(N,N'-dicyanopyrazino[2,3-b]naphthoquinodiimin-2-yl)-1-methylpyridinium triflate [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2001,vol. 66,p. 216 - 224

43
[ 5349-17-7 ]
1-(methoxymethyl)-2-phenyl-4-(4-pyridyl)imidazole [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2180 - 2190

44
[ 5349-17-7 ]
4-(2'-methylthiothiazol-4'-yl)pyridine hydrobromide [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1980,vol. 33,p. 2291 - 2298

45
[ 5349-17-7 ]
2-<4'-(pyridin-4''-yl)thiazol-2'-ylthio>-acetamide [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1980,vol. 33,p. 2291 - 2298

46
[ 5349-17-7 ]
3-methoxy-6-(3'-methoxybenzylamino)-2-(pyridi-4''-yl)imidazo<1,2-b>pyridazine [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1989,vol. 42,p. 1759 - 1768

47
[ 5349-17-7 ]
[ 121041-28-9 ]

Reference： [1]Australian Journal of Chemistry,1989,vol. 42,p. 1735 - 1748

48
[ 5349-17-7 ]
[ 121040-73-1 ]

Reference： [1]Australian Journal of Chemistry,1989,vol. 42,p. 1735 - 1748

49
[ 5349-17-7 ]
[ 79690-73-6 ]

Reference： [1]Australian Journal of Chemistry,1981,vol. 34,p. 1295 - 1302

50
[ 5349-17-7 ]
[ 86626-21-3 ]

Reference： [1]Journal of Heterocyclic Chemistry,1983,vol. 20,p. 419 - 421
[2]Journal of Heterocyclic Chemistry,1983,vol. 20,p. 419 - 421

51
[ 5349-17-7 ]
3-(4-pyridyl)imidazo<2,1-b>thiazole [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,1983,vol. 20,p. 419 - 421

52
[ 5349-17-7 ]
[ 86626-19-9 ]

Reference： [1]Journal of Heterocyclic Chemistry,1983,vol. 20,p. 419 - 421
[2]Journal of Heterocyclic Chemistry,1983,vol. 20,p. 419 - 421

53
[ 5349-17-7 ]
[ 133661-34-4 ]

Reference： [1]Heterocycles,1990,vol. 31,p. 2163 - 2172

54
[ 5349-17-7 ]
[ 133689-99-3 ]

Reference： [1]Heterocycles,1990,vol. 31,p. 2163 - 2172

55
[ 5349-17-7 ]
[ 103-67-3 ]
[ 216970-85-3 ]

Yield	Reaction Conditions	Operation in experiment
43%	In dichloromethane;	Step 1: To a solution of N-benzyl-N-methylamine (3.7 cm3) in dry dichloromethane (40 cm3), cooled to 0 C. was added with stirring, <strong>[5349-17-7]4-bromoacetylpyridine hydrobromide</strong> (4.0 g). The reaction was allowed to warm to room temperature, then stirred for a further 18 hr. The solvent was stripped at reduced pressure, and the residue partitioned between ethyl acetate and dilute aqueous Na2CO3. The organic phase was separated, dried (Na2SO4), evaporated, and the residue subjected to chromatography on silica gel, eluent 5% methanol in dichloromethane, to afford 4-(N-benzyl-N-methylaminoacetyl)pyridine, 1.49 g, 43%, as a yellow gum.
43%	In dichloromethane; at 0 - 20℃; for 18h;	Step 1: To a solution of N-benzyl-N-methylamine (3.7 cm3) in dry dichloromethane (40 cm3), cooled to 0 C. was added with stirring, <strong>[5349-17-7]4-bromoacetylpyridine hydrobromide</strong> (4.0 g). The reaction was allowed to warm to room temperature, then stirred for a further 18 hr. The solvent was stripped at reduced pressure, and the residue partitioned between ethyl acetate and dilute aqueous Na2CO3. The organic phase was separated, dried (Na2SO4), evaporated, and the residue subjected to chromatography on silica gel, eluent 5% methanol in dichloromethane, to afford 4-(N-benzyl-N-methylaminoacetyl)pyridine, 1.49 g, 43%, as a yellow gum.

Reference： [1]Patent: US6200982,2001,B1
[2]Patent: US6352994,2002,B2 .Location in patent: Page column 23

56
[ 16982-21-1 ]
[ 5349-17-7 ]
ethyl 4-(pyridin-4-yl)thiazole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	In ethanol; for 4h;Reflux;	A mixture of <strong>[5349-17-7]4-bromoacetylpyridine hydrobromide</strong> 3 (10 g, 0.0533 mmol) with ethyl thiooxamate 4 (4.4 mL, 0.0355 mmol) in ethanol (40 mL) was refluxed upon stirring for 4 h. The reaction mixture was concentrated under reduced pressure, and water was added to the residue. pH Of the mixture was adjusted to 10 with 8 N NaOH aqueous solution at 0C and extracted with chloroform. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to afford compound 5 as brown solid, yield 75%. 1H NMR spectrum, delta, ppm: 1.48 t (3H), 4.53q (2H), 7.85 d.d (2H, J = 4.4, 1.6 Hz), 7.98 s (1H), 8.71d.d (2H, J = 4.4, 1.6 Hz). MS (ESI): m/z: 235 [M + H]+.

Reference： [1]Russian Journal of General Chemistry,2019,vol. 89,p. 2522 - 2527
[2]Patent: US6359134,2002,B1 .Location in patent: Referential example 18
[3]Journal of Medicinal Chemistry,2017,vol. 60,p. 6942 - 6990

57
[ 593270-19-0 ]
[ 5349-17-7 ]
[ 593270-36-1 ]

Yield	Reaction Conditions	Operation in experiment
		[0505] [CHEMMOL-00037] [0506] The title compound was synthesised from [3-(3-Dimethylaminomethylene-thioureido)-propyl]-carbamic acid tert-butyl ester and <strong>[5349-17-7]2-bromo-1-(4-pyridinyl)-1-ethanone hydrobromide</strong> (commercially available) according to the procedure described for Example H. MS (m/e): 263.2 (MH+, 100%).

Reference： [1]Patent: US2003/225141,2003,A1 .Location in patent: Page 24

58
[ 5349-17-7 ]
[ 17356-08-0 ]
4-pyridin-4-yl-thiazol-2-ylamine dihydrobromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; for 2h;Heating / reflux;	4-PYRIDIN-4-YL-THIAZOL-2-YLAMINE : To 4- (BROMOACETYL)-PYRIDINE hydrobromide (Can. J. Chem. , 1970,7, 1137) (97.5 g, 0.35 mol) and thiourea (26.5 g, 0.35 mol) was added ethanol (900 mL) and the mixture heated to reflux for 2 hours. After cooling to 4 C the product was filtered, washed with ethanol and diethyl ether and dried under suction. The solid 4-pyridin-4-yl-thiazol-2-ylamine dihydrobromide (88.7 g) was dissolved in warm water (500 mL) and the desired 4-PYRIDIN-4-YL-THIAZOL-2-YLAMINE obtained as a light brown solid upon addition of 7% aqueous ammonium hydroxide (800 mL). 43.5 g, 71%. LH NMR (500 MHz, DMSO-d6) 6 8.53 (2H, d), 7.71 (2H, d), 7.38 (1H, s), 7.16 (2H, br).

Reference： [1]Patent: WO2004/41813,2004,A1 .Location in patent: Page 119-120

59
[ 625-53-6 ]
[ 5349-17-7 ]
ethyl-4-pyridin-4-yl-thiazol-2-ylamine dihydrobromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; for 1h;Heating / reflux;	Ethyl- (4-pyridin-4-yl-thiazol-2-yl)-amine : To 4- (bromoacetyl)-pyridine hydrobromide (Can. J. Chem. , 1970,7, 1137) (16.7 g, 59 mmol) and N-ethylthiourea (6.3 g, 61 mmol) was added ethanol (160 mL) and the mixture heated to reflux for 1 hour. A thick solid formed. After cooling to 4 C the product was filtered, washed with ethanol and diethyl ether and dried under suction. The solid ETHYL4-PYRIDIN-4-YL-THIAZOL-2-YLAMINE dihydrobromide (13.7 g) was stirred in IN NaOH (100 mL) for 30 min then filtered, washed with IN NaOH and water, and dried. to afford ETHYL4-PYRIDIN-4-YL-THIAZOL-2-YLAMINE (6.7 g, 56%). [M+H] + = 206.'H NMR (500 MHz, DMSO-d6) 8 8.56 (2H, d), 7.75 (3H, m), 7.40 (1H, s), 3.3 (2H, obscured), 1.20 (3H, t).

Reference： [1]Patent: WO2004/41813,2004,A1 .Location in patent: Page 120

60
[ 92303-09-8 ]
[ 5349-17-7 ]
[ 727383-97-3 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; at 150℃; for 0.0833333h;	To a solution of 3-cyano-6-methyl-2(1H)-pyridinone (Aldrich) (2.0 g, 15 mmol) and Et3N (30 ML, 215 mmol) in 80 ML pyridine was bubbled H2S gas for 5.5 h.The flask was capped and stirred overnight at RT. H2S gas was bubbled for another 18 h and the mixture was filtered.The solid was washed with pyridine and dried in vacuo.A portion of this crude material (166 mg, 1 mmol) and 4-(bromoacetyl)pyridine hydrobromide (prepared by the method described in Aust. J. Chem., 42:1735 (1989); 299 g, 1.1 mmol) in 3 ML EtOH was heated at 150 C. for 5 min in the microwave synthesizer.The resulting solid was filtered, washed with EtOH, and dried in vacuo.The crude material was washed with a minimal amount of DMSO followed by water and dried in vacuo to give an orange amorphous solid. Mp: >300 C. MS m/z: 270 (M+1); 268 (M-1). Calc'd for C14H11N3OS: 269.06.

Reference： [1]Patent: US2004/147561,2004,A1 .Location in patent: Page 71

Yield	Reaction Conditions	Operation in experiment
67%	With hydrogen bromide; bromine; acetic acid; at 70℃; for 3h;	General procedure: Preparation of 2-bromo-1 -pyridin-3-yl-ethanone, HBr salt l-a Bromine (24 g, 150 mmol) in 4 mL of 45% HBr was added dropwise under vigourous stirring to a solution at 70C of 3-acetyl-pyridine (18 g, 148 mmol) in acetic acid containing 45% of HBr (165 mL). The vigorously stirred mixture was kept at 70C for 3h. The mixture was cooled and the precipitate collected by filtration and washed with petroleum ether/methanol (1/1 , 100 mL) to give 35.8 g of a white crystals (85%). H NMR (300 MHz, DMSO-d6) delta 12.77 {br s, 1 H), 9.29 (m, 1 H), 8.79-8.99 (m, 1 H), 8.42-8.70 (m, 1 H), 7.78- 7.96 (m, 1 H), 5.09 (s, 2H).

62
[ 5349-17-7 ]
[ 34064-35-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tetrahydroborate; In ethanol; at 20℃; for 2h;	To a solution of 2-Bromo-l-(4-pyridinyl)-l-ethanone hydrobromide (4.0 g, 14.4 mmol) in anhydrous ethanol (80 ml) is added NaBH4 (2.0 g, 52.8 mmol). The reaction mixture is stirred at RT for 2 h. The mixture is filtered and l-(2-Phenylethyl)piperazine (4.9 ml, 26.0 mmol) is added to the filtrate. The solution is heated to reflux and refiuxed for 5 h. Excessive ethanol is removed by distillation. The resulting pale yellow solid is dissolved in chloroform (80 ml), the insoluble parts are filtered off and the filtrate is concentrated by distillation under reduced pressure. The product is purified by chromatography on silica (MeOH/EtOAc, 5:1) to give a pale yellow solid; yield: 32 % ; chemical formula: Ci9H2SN3O; molecular weight: 311,42.1H NMR (300 MHz, CDCl3) delta 2.83 - 2.84 (m, 14H), 4.73 (dd, IH, J= 10.5 Hz, J = 3.8 Hz),7.20 - 7.30 (m, 5H), 7.31 (dd, 2H, J = 4.7 Hz, J = 1.5 Hz), 8.57 (dd, 2H, J = 4.4 Hz, J = 1.5Hz);FT-IR (KBr) 3420, 1639, 1458, 1409, 1128, 854, 696, 622 cm"1;EI MS mZz SlO [M-H+];HR MS m/z calcd for C19H24N3O [M-H+] C9H24N3O 310.191938, found 310.192050.
	With sodium tetrahydroborate; In ethanol; at 20℃; for 2h;	To 1.01 g (3.6 [MMOL)] of [4-BROMOACETYLPYRIDINE] hydrobromide, prepared as described in Example 1, was added 20 [ML] of absolute ethanol and 0.5 g (13.2 [MMOL)] of sodium boronhydride, and the reaction mixture was stirred at [20C] for 2 hours, then filtered and to the filtrate containing [4-PYRIDYLOXIRANE] was added 1.3 ml 33% [ETHANOLIC] solution of [METHYLAMINE.] The reaction mixture was heated at reflux temperature of the reaction mixture for 3 hours, evaporated to a dry residue and to it was added 20 ml of chloroform, and a solid portion was filtered off. The filtrate was evaporated and an obtained oil residue was purified by column chromatography on silica gel (silica gel 60, mobile phase: [CHCI3] : ethyl acetate = 10: 2). This yields 0.30 g (55%) of a title compound in the form of the oil base (molecular weight: 152.196, gross formula: [C8H12N20).]

Reference： [1]Patent: WO2007/73935,2007,A1 .Location in patent: Page/Page column 19
[2]Patent: WO2004/7456,2004,A1 .Location in patent: Page 20

63
[ 773104-00-0 ]
[ 5349-17-7 ]
4-methyl-3-(4-pyridin-4-yl-thiazol-2-ylamino)-benzoic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydrogencarbonate; In ethanol; at 75℃; for 20h;	4-Methyl-3- (4-pyridin-4-yl-thiazol-2-ylamino)-benzoic acid methyl ester; A mixture of 4-bromoacetyl-pyridine, HBr salt (0.40g, 1.43 mmol), 4-methyl-3- thioureido-benzoic acid methyl ester (0.32g, 1.43 mmol) and KHCO3 (-0. 4g) in ethanol (10 mL) was heated at 75C for 20h. The mixture was cooled, filtered (removal of KHCO3) and evaporated under reduced pressure. The residue was dissolved in CHC13 (40 mL) and washed with saturated aqueous sodium hydrogen carbonate solution and with water. The organic layer was dried over Na2S04 and concentrated. The crude product was triturated in small amount of ethyl acetate and filtered to give the final product as an orange solid.

Reference： [1]Patent: WO2005/73225,2005,A1 .Location in patent: Page/Page column 50-51

64
[ 857654-01-4 ]
[ 5349-17-7 ]
4-(4-pyridin-4-yl-thiazol-2-ylmethoxy)piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 136: 4-(4-Pyridin-4-yl-thiazol-2-ylmethoxy)piperidine-1-carboxylic acid tert-butyl ester A solution of 2-bromo-1-pyridin-4-yl-ethanone hydrobromide (35mg, 124mol) and 4- thiocarbamoylmethoxypiperidine-1-carboxylic acid tert-butyl ester (Preparation 18,34mg, 124Rmol) in methanol (2ml) was heated at 60C for 1. 5h. The reaction mixture was diluted with EtOAc (60ml), washed with saturated aqueous NaHCO3 (15ml) and brine (15ml) then dried (MgSO4). The solvent was removed and the residue purified by flash chromatography (EtOAc) to afford the title compound: RT = 2.95min, mlz (ES+) = 376.1 [M+H] +.

Reference： [1]Patent: WO2005/61489,2005,A1 .Location in patent: Page/Page column 56-57

65
[ 15570-12-4 ]
[ 5349-17-7 ]
[ 374754-27-5 ]

Yield	Reaction Conditions	Operation in experiment
56%	With potassium hydroxide; In ethanol; water;	EXAMPLE 1 Preparation of 4-[6-methoxybenzo[b]thiophen-3-yl]pyridine hydrochloride 3-methoxybenzenethiol (0.60 ml, 4.836 mmol) was added to a solution of potassium hydroxide (0.74 g, 11.21 mmol) in a mixture of water (6 ml) and ethanol (9 ml) under cooling with ice. After the addition of 2-bromo-1-pyridin-4-yl-ethanone hydrobromide (1.70 g, 6.051 mmol; H. Erlenmeyen et al., Helv. Chim. Acta., 31, 1142 (1948)), the mixture was stirred for 3.5 hours at room temperature. After removing ethanol by evaporation under reduced pressure, the residue was extracted with diethyl ether (100 ml). The organic layer was washed with water, and then with saturated brine (sodium chloride solution), dried with anhydrous magnesium sulfate, then the solvent was evaporated under reduced pressure to obtain crude 2-(3-methoxyphenylsulfanyl)-1-pyridin-4-yl ethanone (700 mg, 56%). 1H-NMR(CDCl3) delta: 3.75(s, 3H), 4.19(s, 2H), 6.77(dd, J=1.8, 8.6 Hz, 1H), 6.88(dd, J=1.8, 2.4, 1H), 6.91(d, J=7.9 Hz, 1H), 7.18(t, J=7.9 Hz, 1H), 7.67(d, J=6.1 Hz, 2H), 8.77(d, J=6.1 Hz, 2H).

Reference： [1]Patent: US2003/130340,2003,A1

66
[ 504-29-0 ]
[ 5349-17-7 ]
[ 38922-82-6 ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide; water;	a) 2-(4-Pyridyl)imidazo[1,2-a]pyridine (Formula (C) Compound A stirred suspension of 1.0 g (3.6 mmoles) of 4-(bromoacetyl)pyridine hydrobromide and 1.02 g (10.8 mmoles) of 2-aminopyridine in dry dimethylformamide is treated with 0.76 g (7.2 mmoles) of powdered anhydrous sodium carbonate and heated between 35 and 100 C. under an argon atmosphere until no further product forms. The solvent is removed in vacuo and the residue is dissolved in water. The aqueous mixture is extracted with chloroform and the organic phase washed with water, dried over anhydrous potassium carbonate and stripped in vacuo. The residue is chromatographed on silica to afford the title compound.

Reference： [1]Patent: US5317019,1994,A

67
[ 5349-17-7 ]
4-azidoacetylpyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium azide; In water; at 20℃; for 2h;	Preparation of (4-fluoro-2-methyl-5-nitro-phenyl)-(5-pyridin-4-yl-oxazol-2-yl)-amine IV-b To a stirred solution of <strong>[5349-17-7]4-bromoacetylpyridine hydrobromide</strong> ll-a (1 .2 g, 4.27 mmol) in 20 ml_ of water was added portionwise sodium azide (305 mg, 4.69 mmol). The reaction mixture was stirred at room temperature for 2h and treated with saturated aqueous NaHC03 until pH=7. The resultant mixture was extracted with DCM and the combined organic layers were concentrated under vacuum at room temperature to give 4- azidoacetylpyridine as a brown syrup which was used without further purification.
		Preparation of 2-Methyl-5-nitro-phenyl)-(5-pyridin-4-yl-oxazol-2-yl)-amineTo a solution of <strong>[5349-17-7]4-bromoacetylpyridine hydrobromide</strong> (5 g, 17.8 mmol) in 8O mL of water was added sodium azide (1.16 g, 17.8 mmol) and the contents stirred at room temperature for 30 min. The reaction mixture was cooled to O0C, treated slowly with saturated aqueous NaHCO3 until pH=6-7, extracted with dichloromethane (3x3 OmL) and the combined organic phases were dried over MgSO4, concentrated at room temperature under reduced pressure to a final volume of 25 mL, and diluted with dioxane (30 mL). The resulting solution was concentrated to remove the remaining EPO <DP n="28"/>(lower boiling) dichloromethane. To the final volume (25 mL) was added at O0C, 2- methyl-5-nitrophenyl isocyanate (1.58 g, 8.9 mmol) (commercially available) and portion wise triphenylphosphine (2.62 g, 8.9 mmol). The reaction mixture was then stirred for 1 h at room temperature and heated for an additional 2 h at 100C. After evaporation of the solvent under reduced pressure the residue was crystallized in dichloromethane/ethanol (10mL/5mL), to give the title compound as yellow crystals (0.9 g, 34%). m p > 220 C

Reference： [1]Patent: WO2014/202763,2014,A1 .Location in patent: Page/Page column 51-52
[2]Patent: WO2006/106437,2006,A2 .Location in patent: Page/Page column 26-27

68
[ 350-03-8 ]
[ 5349-17-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogen bromide; bromine; In water; acetic acid; at 40 - 75℃; for 2 - 4h;	Preparation of 2-Bromo-l-pyridin-4-yl-ethanone hydrobromide Dibromine (17.2g, 108 mmol) was added drop wise to a cold (O0C) solution of 3- acetyl-pyridine (12 g, 99 mmol) in acetic acid containing 33% of HBr (165 mL) under vigourous stirring. The vigorously stirred mixture was warmed to 40C for 2h and then to 75C. After 2h at 75C, the mixture was cooled and diluted with ether (400 mL) to precipitate the product, which was recovered by filtration and washed with ether and acetone to give white crystals (100%). This material may be recrystallized from methanol and ether. EPO <DP n="36"/>1H NMR (DMSO-/) delta = 5.17 (s, 2H) ; 8.32 (dd, J= 6.1-1.6 Hz, 2H) ; 9.12 (dd, J- 6.1-1.6 Hz, 2H) ; 12.51 (br s, IH).

Reference： [1]Patent: WO2006/64375,2006,A2 .Location in patent: Page/Page column 34-35

69
N-(2-hydroxyethyl)-2-(4-carbomethoxymethoxyphenyl)-1-methyl-ethylamine [ No CAS ]
[ 5349-17-7 ]
[ 126325-31-3 ]

Yield	Reaction Conditions	Operation in experiment
43%	potassium bicarbonate; In ethyl acetate;	EXAMPLE 10 N-[2-(4-Carbomethoxymethoxyphenyl)-1-methylethyl]-2-hydroxy-2-(pyridin-4-yl)-morpholine Prepared analogously to Example 1 by reacting N-(2-hydroxyethyl)-2-(4-carbomethoxymethoxyphenyl)-1-methyl-ethylamine with 4-bromoacetyl-pyridine-hydrobromide in the presence of potassium hydrogen carbonate. The product is purified over silica gel using ethyl acetate as eluant. Yield: 43% of theory, oil. According to 1 H-NMR spectrum (400 MHz, CDCl3 /CD3 OD) there is an approximately 1:1 mixture of the pairs of diastereoisomers. delta=0.979 ppm (d, 3H). delta=1.000 ppm (d, 3H).

Reference： [1]Patent: US5026702,1991,A

70
[ 5349-17-7 ]
[ 7544-75-4 ]
[ 122454-71-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; In N-methyl-acetamide; methylene chloride acetone; water;	EXAMPLE 19 2-(4-Pyridyl) 6,7 dihydro [5H]-pyrrolo[1,2 a]imidazole A stirred suspension of 10q (35.6 mmoles) of 4-(bromoacetyl) pyridine hydrobromide and 12.9 q (107 mmoles) of 2-imino-pyrrolidine hydrochloride in 100 ml of dry dimethylformamide was treated with 18.9 q (178 mmoles) of anhydrous sodium carbonate. This suspension was heated at 80 C. overnight in an oil bath. The solvent was removed in vacuo, the residue dissolved in water and extracted with chloroform. The organic layer was washed three times with water, dried over anhydrous potassium carbonate and stripped in vacuo. The residue was chromatographed on silica and eluted with 10-15% methanol in methylene chloride acetone (85:15). This fraction was stripped in vacuo and the solid residue recrystallized twice from ethyl acetate to afford the desired titled compound, mp 140-141 C., 1 H-NMR (250 MHz, CDCl3) delta8 62 (2H,d), 7.60(2H,d), 7.34(lH,s), 4.04(2H,t), 2.95 (2H,t), 2.64(2H,q).

Reference： [1]Patent: US5002941,1991,A

71
[ 53542-79-3 ]
[ 5349-17-7 ]
4-hydroxy-3-methyl 5-propyl-2-(isonicotinoyl)-benzofuran [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In acetone;	Step A Preparation of 4-hydroxy-3-methyl 5-propyl-2 -(isonicotinoyl) benzofuran A mixture of 2,6-dihydroxy-5-propylaceto-phenone (5.8 g; 30mmoles), <strong>[5349-17-7]4-bromoacetylpyridine hydrobromide</strong> (16.8 g; 60mmoles), anhydrous potassium carbonate (16.5 g; 120mmoles) and acetone (200 ml) was refluxed for 22 hours. The mixture was filtered, concentrated, and chromatographed to obtain 2 g of the title compound. m.p. 203-205 C. Calcd for C18 H17 NO3: C, 73.20; H, 5.80; N, 4.76. Found: C, 73.04; H, 5.88; N, 4.64.

Reference： [1]Patent: US4863958,1989,A

72
N-(5-chloro-2-{(E)-2-[1-(2-cyanoethyl)-1H-1,2,3,4-tetrazol-5-yl]ethenyl}phenyl)benzenesulfonamide [ No CAS ]
[ 5349-17-7 ]
[6-chloro-3-(1H-1,2,3,4-tetrazol-5-ylmethyl)-1H-indol-2-yl](4-pyridinyl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 13 [6-CHLORO-3-(1H-1,2,3,4-TETRAZOL-5-YLMETHYL)-1H-INDOL-2-YL](4-PYRIDINYL)METHANONE The title compound was prepared according to the procedure described in step 5 of Example 1 from N-(5-chloro-2-{(E)-2-[1-(2-cyanoethyl)-1H-1,2,3,4-tetrazol-5-yl]ethenyl}phenyl)benzenesulfonamide (Example 1, step 4) and <strong>[5349-17-7]4-bromoacetylpyridine hydrobromide</strong> (L. W. Deady, M. S. Stanborough, Aust. J. Chem., 1981, 34 , 1295). MS (EI) m/z: 338 (M+). IR (KBr) nu: 3246, 2870, 1637, 1526, 1439, 1323, 1248, 943, 841. 1H-NMR (DMSO-d6) delta: 11.92 (1H, s), 8.80 (2H, d, J=4.5 Hz), 7.68 (1H, d, J=8.7 Hz), 7.63 (2H, d, J=4.5 Hz), 7.51 (1H, d, J=1.8 Hz), 7.15 (1H, dd, J=1.8, 8.7 Hz), 4.58 (2H, s).

Reference： [1]Patent: EP1065206,2001,A1

73
5-chloro-3-(phenylsulfonyl)-1H-indole-2-carbothioamide [ No CAS ]
[ 5349-17-7 ]
5-chloro-3-(phenylsulfonyl)-2-(5-pyridin-4-yl-1,3-thiazol-2-yl)-1H-indole trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; In acetone; at 100℃; for 0.333333h;Irradiation;	A mixture of 5-chloro-3-(phenylsulfonyl)-lH-indole-2-carbothioamide (35 mg, 0.1 mmol) and 2-bromo-l-pyridin-4-ylethanone (HBr salt, 31 mg, 0.11 mmol)) in acetone was microwaved at 1000C for 20 minutes, after which the mixture was cooled down and concentrated and the residue purified by LCMS to provide the title compoundas a TFA salt (brown solid). Analytical LCMS: single peak (214 nm), 2.709 min, ES MS (M+l) = 452; lH NMR (500 MHz, d6-DMSO) delta 13.23 (s, IH), 9.4 (s, IH), 8.90 (d, J =5.6, Hz, 2H), 8.38 (d, J =5.7, Hz, 2H), 8.10 (d, J =1.9, Hz, IH), 8.00 (d, J =7.5, Hz, 2H), 7.69-7.57 (m, 4H), 7.45 (dd, J =8.8, 2.0 Hz, IH); HRMS, calc'd for C22H15CIN3O2S2 (M+H),452.0289; found 452.0284.

Reference： [1]Patent: WO2007/2458,2007,A2 .Location in patent: Page/Page column 56

74
[ 942297-65-6 ]
[ 5349-17-7 ]
[ 942297-75-8 ]

Yield	Reaction Conditions	Operation in experiment
30%	With ammonium acetate; In ethanol; at 20℃; for 18h;	EXAMPLE 20 DL-6-(3-benzyloxycarbonylamino-propyl)-4-oxo-2-pyridin-4-yl-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester To a suspension of 2-bromo-1-pyridin-4-ylethanone hydrobromide (0.76 g, 2.59 mmol) and DL-2-(3-benzyloxycarbonylamino-propyl)-4,6-dioxo-piperidine-1-carboxylic acid tert-butyl ester (1.05 g, 2.59 mmol) in absolute EtOH (40 mL), ammonium acetate (0.81 g, 10.8 mmol) was added and the deep red solution was stirred at room temperature for 18 h. After solvent removal, the residue was treated with ethyl acetate/abs. Ethanol 15:1 (50 mL), the precipitate was filtered off and the obtained solution was charged on flash silica gel and eluted with ethyl acetate/abs. Ethanol 15:1. In this way the title compound was obtained as a yellowish solid (0.4 g, 30% yield). ESI (+) MS: m/z 505 (MH+)

Reference： [1]Patent: US2007/142415,2007,A1 .Location in patent: Page/Page column 19

75
[ 845267-78-9 ]
[ 5349-17-7 ]
[ 942425-76-5 ]

Yield	Reaction Conditions	Operation in experiment
55%	With ammonium acetate; In ethanol; at 20℃; for 24h;	tert-butyl 2,4-dioxopiperidine-1-carboxylate (4: 1.0 g, 4.69 mmol, 1.0 equivalent)And 2-bromo-1- (pyridin-4-yl) ethan-1-one hydrobromide (5: 1.33 g, 4.69 mmol, 1.0 equivalent)To a solution of ethanol (18.8 mL)Ammonium acetate (1.45 g, 18.9 mmol, 4.0 equiv) was added at room temperature.After stirring for 24 hours, the reaction mixture was quenched with saturated aqueous NaHCO3 and separated into aqueous and organic layers.The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried over Na2SO4,Concentrated under reduced pressure.The crude residue was washed with diethyl ether to obtain a PHA precursor Boc-PHA (1) as a yellow solid (806 mg, 55% yield).The physical property data of the PHA precursor Boc-PHA (1) is described below.

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 487 - 501
[2]Patent: JP2019/210254,2019,A .Location in patent: Paragraph 0053; 0056-0057

76
[ 67706-68-7 ]
[ 5349-17-7 ]
[ 947327-37-9 ]

Yield	Reaction Conditions	Operation in experiment
		Example 8; 2-(te/t-Butoxycarbonylamino-methyl)-beta-pyridin-4-yl-1H-pyrrole-3-carboxylic acid ethyl ester; 4-terf-Butoxycarbony.amino-3-oxo-butyric acid ethy. ester (1 g) and 408 mg of sodium hydride (60% oil dispersion) dissolved in 20 mL of anhydrous THF were stirred 1 hour at room temperature and then cooled down to 0C. A suspension of 1.2 g of 2-bromo-1-pyridin-4- yiethanone hydrobromide in 10 mL of anhydrous THF was added dropwise and the mixture left stirring at O0C for 4 hours. The resulting solution was dried, the residue was dissolved in 30 ml of ethyl alcohol/acetic acid 1 :1 and 1.25 g of ammonium acetate were added. The solution was Seft stirring for 5 hours and then dried. The raw product was dissolved in ethyl acetate, washed (x3) with brine and dried over anh. sodium sulfate. The solvent was removed and the raw product was purified by flash chromatography over silica gel, thus providing 460 mg of the title compound,1H NMR (400 MHz, DMSO-DS) delta ppm 1.30 (t, J=7.07 Hz1 3 H) 1.41 (S1 9 H) 4.22 (d, J=7.07 Hz, 2 H) 4.50 (d, J=5.49 Hz, 2 H) 6.91 (s, 1 H) 7.15 (d, J=2.68 Hz, 1 H) 7.70 (dd, J=4.63, 1.59 Hz, 2 H) 8.52 (dd, ./=4.63, 1.59 Hz, 2 H) 11.94 (s, 1 H).

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 487 - 501
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 7296 - 7315
[3]Patent: WO2007/96334,2007,A1 .Location in patent: Page/Page column 34

77
[ 5349-17-7 ]
[ 74-89-5 ]
[ 50607-30-2 ]
1-Methyl-2-pyridin-4-yl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 487 - 501

78
[ 5349-17-7 ]
1-(2-methyl-5-nitrophenyl)guanidine nitrate [ No CAS ]
[ 892119-40-3 ]

Reference： [1]European Journal of Medicinal Chemistry,2008,vol. 43,p. 1444 - 1453

79
[ 630410-67-2 ]
[ 5349-17-7 ]
[ 630410-68-3 ]

Yield	Reaction Conditions	Operation in experiment
		(d) Preparation of [2-(dimethylamino)ethyl]methyl(4-nitro-3-[(4-(4-pyridyl)(1,3-thiazol-2-yl))amino]-methyl)phenyl)-amine.To a slurry of N-([(5-([2-(dimethylamino)ethyl]-methylamino}-2-nitrophenyl)methyl]-amino}-thioxomethyl)benzamide (Step c) (1.09 g, 2.6 mmol) in 70% aqueous MeOH (31 ML) was added K2CO3 (416 mg, 3.0 mmol) and the reaction was heated to 65 C. After 1.5 h, the reaction was cooled to (45 C.) and 2-bromo-1-(4-pyridyl)ethan-1-one hydrobromide (838 mg, 3.0 mmol) was added.After 1 h, the reaction mixture was cooled to RT and purified by flash chromatography with CH2Cl2:2M NH3 in MeOH (49:1, 19:1) as eluant to afford a yellow amorphous solid. MS m/z: 413 (M+1); 411 (M-1). Calc'd for C20H24N6O2S-412.17.

Reference： [1]Patent: US2003/229068,2003,A1 .Location in patent: Page 46

80
[ 630410-71-8 ]
[ 5349-17-7 ]
[ 630410-72-9 ]

Yield	Reaction Conditions	Operation in experiment
		(d) Preparation of [5-(4-methylpiperazinyl)-2-nitrophenyl]-methyl}(4-(4-pyridyl)(1,3-thiazol-2-yl))amine.To a slurry of N-[(([5-(4-methylpiperazinyl)-2-nitrophenyl]methyl}-amino)-thioxomethyl]-benzamide (Step c) (1.47 g, 3.5 mmol) in 70% aqueous MeOH (50 ML) was added K2CO3 (550 mg, 3.9 mmol) and the reaction was heated at reflux.After 1.5 h, the reaction was cooled to 40 C., and 2-bromo-1-(4-pyridyl)ethan-1-one hydrobromide (990 mg, 3.5 mmol) was added.After 1 h, the reaction mixture was cooled to RT and purified by flash chromatography with CH2Cl2:MeOH (19:1) as eluant to afford a yellow-orange amorphous solid. MS m/z: 411 (M+1); 409 (M-1). Calc'd for C20H22N6O2S-410.15.

Reference： [1]Patent: US2003/229068,2003,A1 .Location in patent: Page 47

81
[ 630410-77-4 ]
[ 5349-17-7 ]
[ 630410-78-5 ]

Yield	Reaction Conditions	Operation in experiment
		(c) Preparation of [5-(2,4-dimethylphenoxy)-2-nitrophenyl]-methyl}(4-(4-pyridyl)(1,3-thiazol-2-yl))amine.To a solution of N-[([5-(2,4-dimethylphenoxy)-2-nitrophenyl]methyl}-amino)thioxomethyl]-benzamide (Step b) (956 mg, 2.2 mmol) in 70% aqueous MeOH (50 ML) was added K2CO3 (367 mg, 2.7 mmol) and the reaction was heated to reflux.After 3 h, the reaction was cooled to 40 C. and 2-bromo-1-(4-pyridyl)ethan-1-one hydrobromide (624 mg, 2.2 mmol) was added.After 1.5 h, the reaction mixture was cooled to RT, concentrated in vacuo and purified by flash chromatography with hexanes:EtOAc (9:1, 3:1, 1:1) as eluant to afford an orange foam. MS m/z: 433 (M+1); 431 (M-1). Calc'd for C23H20N4O3S-b 432.13.

Reference： [1]Patent: US2003/229068,2003,A1 .Location in patent: Page 48

82
[ 630410-83-2 ]
[ 5349-17-7 ]
[ 630410-84-3 ]

Yield	Reaction Conditions	Operation in experiment
		(c) Preparation of [(2-chloro-6-nitrophenyl)methyl](4-(4-pyridyl)(1,3-thiazol-2-yl))amine.To a solution of N-([(2-chloro-6-nitrophenyl)methyl]amino}thioxomethyl)benzamide (Step b) (1.22 g, 3.5 mmol) in 70% aqueous MeOH (50 ML) was added K2CO3 (567 mg, 4.1 mmol) and the reaction was heated to reflux.After 1.5 h, the reaction was cooled (40 C.) and 2-bromo-1-(4-pyridyl)ethan-1-one hydrobromide (992.4 mg, 3.5 mmol) was added.After 1.5 h, the reaction mixture was cooled to RT and purified by flash chromatography with hexanes:EtOAc:CH2Cl2:MeOH (9:1:0:0, 3:1:0:0, 1:1:0:0, 0:0:49:1) as eluant to afford an off-white amorphous solid. MS m/z: 347 (M+1); 345 (M-1). Calc'd for C15H11ClN4O2S-b 346.03.

Reference： [1]Patent: US2003/229068,2003,A1 .Location in patent: Page 49

83
[ 630410-60-5 ]
[ 5349-17-7 ]
[ 630410-61-6 ]

Yield	Reaction Conditions	Operation in experiment
		(b) Preparation of [(2-nitro-5-piperidylphenyl)methyl](4-(4-pyridyl)(1,3-thiazol-2-yl))amine.To a suspension of N-(([(2-nitro-5-piperidylphenyl)methyl]amino)thioxomethyl) benzamide (Step a) (427, 1.1 mmol) mg) in 70% aqueous MeOH was added K2CO3 (203 mg, 1.4 mmol) and the reaction was heated to reflux.After 1.5 h the reaction was cooled to RT and to the reaction mixture was added 2-bromo-1-(4-pyridyl)ethan-1-one hydrobromide (309 mg, 1.1 mmol) and the mixture was heated to 45 C. After 2 h the reaction mixture was cooled to RT and purified by flash chromatography with CH2Cl2:MeOH (99:1, 49:1) as eluant to afford a green-brown solid. MS m/z: 396 (M+1); 394(M-1). Calc'd for C20H21N5O2S-b 395.14.

Reference： [1]Patent: US2003/229068,2003,A1 .Location in patent: Page 45

84
[ 1147940-08-6 ]
[ 5349-17-7 ]
[ 1147940-16-6 ]

Yield	Reaction Conditions	Operation in experiment
74%	With hydrogenchloride; In ethanol; for 0.333333h;Heating / reflux;	2-Methyl-5-[2-(4-pyridin-4-yl-thiazol-2-yl)ethyl]-2,3,4,5-tetrahydro-lH- pyrido[4,3-b]indole (G8-d). A mixture of 7-a (1.Og, 3.7mmol), 2-bromo-l-pyridin-4-yl- ethanone hydrobromide (1.029 g, 3.7 mmol) and 5% HCl in ethanol (44 mL) was heated at reflux for 20 min. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue partitioned between CH2Cl2 and aqueous NaOH solution. The organic layer was washed with water, dried over Na2SO4 and evaporated. The solid residue was washed with acetone. Recrystallization from 2-propanol afforded G8-d (0.42g, 30.6%), mp 158.5-159.5 0C. 1H NMR (DMSO-d6ZCCl4, 1:1): 2.42 (3H,s), 2.67 (4H,s), 3.44 (2H,t), 3.53 (2H,s), 4.52 (2H,t), 6.90-7.09 (2H,m), 7.27-7.40 (2H,m), 7.86 (2H,d), 8.17 (lH,s), 8.58 (2H,d).

Reference： [1]Patent: WO2009/55828,2009,A1 .Location in patent: Page/Page column 366

85
C₁₃H₂₁NO₄ [ No CAS ]
[ 5349-17-7 ]
C₂₀H₂₅N₃O₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 293 - 307

86
[ 5349-17-7 ]
[ 2227-79-4 ]
[ 1188301-88-3 ]

Yield	Reaction Conditions	Operation in experiment
92%	In ethanol; at 80℃; for 1.5h;	A solution of 4-(bromoacetyl)pyridine hydrobrornide (2 g, 7. 12 mmol) andthiobenzamide (976 mg, 7.12 rnmol) in absolute EtOH (20 mL) was stirred at 80 C)C for l.Sh,cooled to room temperature, and concentrated in vacuo. The resulting solid was trinLrated withsaturated aqueous potassium carbonate, filtered, washed with water, and dried in vacuo to give1.57 g of the title product as a light pink solid (92% yield): 1 H Ntv1R (DMSO-d6. ppm) o 7.58(m, 3H), 8.03 (d, 2H), 8.08 (dd, 2H), 8.56 (s, l H), 8.70 (d, 2H); [M+H 'J rn/z 239.
	In N,N-dimethyl-formamide; at 20℃; for 12h;	To the solution of 4-(bromoacetyl)pyridine hydrobromide (500 mg, 1.8 mmol) in dry DMF (5 mL) was added thiobenzamide (242 mg, 1.8 mmol,) and the resulting reaction was stirred at rt for 12 h. Thereafter, the reaction quenched with saturated aqueous NaHCO3 solution (25 mL) and the mixture extracted with EtOAc (3*25 mL). The combined organic extracts were washed with water (25 mL), dried (Na2SO4), and concentrated. The resulting residue was purified by flash chromatography (SiO2, 100:0-0:100 hexanes-EtOAc) furnished 2-phenyl-4-(pyridin-4-yl)thiazole: LCMS (m/z): 239.0 (MH+), tR=0.64 min.
		To the solution of 4- (bromoacetyl)pyridine hydrobromide (500 mg, 1.8 mmol) in dry DMF (5mL) was added thiobenzamide (242mg, 1.8 mmol,) and the resulting reaction was stirred at rt for 12 h. Thereafter, the reaction quenched with saturated aqueous NaHCOs solution (25mL) and the mixture extracted with EtOAc (3 X 25 mL). The combined organic extracts were washed with water (25 mL), dried (Na2SO^, and concentrated. The resulting residue was purified by flash chromatography (SiO2, 100 : 0 - 0 : 100 hexanes-EtOAc) furnished 2-phenyl-4-(pyridin-4-yl)thiazole: LCMS (m/z): 239.0 (MH+), tR = 0.64 min.

Reference： [1]Patent: WO2014/172639,2014,A1 .Location in patent: Paragraph 00198-00199
[2]Patent: US2013/210818,2013,A1 .Location in patent: Paragraph 0371
[3]Patent: WO2009/115572,2009,A2 .Location in patent: Page/Page column 112

87
[ 5349-17-7 ]
[ 618-39-3 ]
[ 234766-97-3 ]

Yield	Reaction Conditions	Operation in experiment
99.3%	In N,N-dimethyl-formamide; at 40℃; for 20h;Cooling with ice;	Intermediate 1: 4-(2-phenyl-lH-imi azol-4-yl)pyridine[00199] 2-Bromo-l-pyridin-4-yl-ethanone hydrobromide (lOg, 35.3 mmol) in DMF(500 mL) was added dropwise over l-2h to a solution of benzamidine (16.8g, 139 mmol) in DMF (200 mL) at ice bath temperature. The mixture was removed from the ice bath after 2 hrs and heated at 40C for 18h. The solvent was removed in vacuo and ethyl acatate was added. The mixture was stirred for 30 minutes in ethylacetate and a dark orange oil formed in the bottom layer. Water was added and the layers were separated. The organic layer was washed with saturated sodium bicarbonate (2X) and was dried over magnesium sulfate. The solution was concentrated to an oil which solidified on sitting to afford 4-(2 -phenyl- 1H- imidazol-4-yl)pyridine (7.8g, 99.3%): [M+H+] m/z 222.
72%		2-Bromo-l-(pyrindin-4- yl)ethanone hydrobromide (6.4 g, 23 mmol) was added portionwise to a solution of benzamidine (11.2 g, 93 mmol) in dry DMF (50 mL) at 0 0C, maintaining an internal temperature of <5 0C. The stirred reaction was allowed to warm to rt over 2 h and then heated to 40 0C for 16 h. The crude reaction was poured into saturated aqueous NaetaCtheta3 solution (600 mL), and partition and extracted with EtOAc (3 X 300 mL). The combined organic layers were dried (Na2SC^) and evaporated. The resulting crude residue was purified by flash chromatography (SiO2, 100 : 0 - 90 : 10 DCM-MeOH) to give 3.68 g (72%) of 4-(2-phenyl-lH-imidazol-4-yl)pyridine: 1H NMR (CDCl3) delta 9.73 (broad s, 1 H), 8.61 (d, J= 6.0, 1.2 Hz, 2 H), 7.91 (d, J = 8.0, 1.6 Hz, 2 H), 7.77 (d, J = 6.0, 1.2 Hz, 2 H), 7.57 (s, 1 H), 7.48 (m, 3H).

Reference： [1]Patent: WO2011/85269,2011,A1 .Location in patent: Page/Page column 71
[2]Patent: WO2009/115572,2009,A2 .Location in patent: Page/Page column 89

88
[ 458-05-9 ]
[ 5349-17-7 ]
[ 1187669-25-5 ]

Yield	Reaction Conditions	Operation in experiment
		[0332] 7V-(3-Fluorophenyl)-4-(4-pyridinyl)-l,3-thiazol-2-amine (121). Reaction of bromoketone hydrobromide 1 (0.65 g, 2.3 mmol) and 3-fluorophenylthiourea (120) (0.39 g, 2.3 mmol) gave amine 121 (0.45 g, 71%) as a white powder: mp (EtOAc/pet. ether) 229-230 0C; 1H NMR delta 10.59 (br s, 1 H, NH), 8.63 (dd, J = 4.5, 1.6 Hz, 2 H, H-2', H-6'), 7.35 (dd, J= 4.5, 1.6 Hz, 2 H, H-3', H-5'), 7.28-7.31 (m, 1 H, H-2"), 7.76 (s, 1 H, H-5), 7.34-7.41 (m, 2 H, H-5", H-6"), 6.77-6.84 (m, 1 H, H-4"); 13C NMR delta 163.0, 162.4 (d, J= 240 Hz), 150.1 (2), 147.6, 142.4 (d, J = 11 Hz), 140.8, 130.5 (d, J= 10 Hz), 119.8 (2), 112.7 (d, J= 2 Hz), 108.0, 107.5 (d, J= 21 Hz), 103.5 (d, J= 26 Hz). Anal, calcd for Ci4Hi0FN3S: C, 61.98; H, 3.72; N, 15.49. Found: C, 61.91; H, 3.79; N, 15.20%.

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 787 - 797
[2]Patent: WO2009/114552,2009,A1 .Location in patent: Page/Page column 144

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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. 5349-17-7 ] {[proInfo.proName]}

Quality Control of [ 5349-17-7 ]

Related Doc. of [ 5349-17-7 ]

Product Details of [ 5349-17-7 ]

Calculated chemistry of [ 5349-17-7 ]

Physicochemical Properties

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Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

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Application In Synthesis of [ 5349-17-7 ]

[ 5349-17-7 ] Synthesis Path-Upstream 1~5

[ 5349-17-7 ] Synthesis Path-Downstream 1~88

Similar Product of [ 5349-17-7 ]

Related Functional Groups of [ 5349-17-7 ]

Bromides

Ketones

Related Parent Nucleus of [ 5349-17-7 ]

Pyridines

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[ 5349-17-7 ]

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[ 5349-17-7 ]

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