CAS No. :	19798-81-3
Formula :	C₅H₅BrN₂
M.W :	173.01
SMILES Code :	BrC1=CC=CC(N)=N1
MDL No. :	MFCD00137843
InChI Key :	BKLJUYPLUWUEOQ-UHFFFAOYSA-N
Pubchem ID :	300809

Safety of 2-Amino-6-bromopyridine

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302+H312+H332-H315-H319-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Application In Synthesis of 2-Amino-6-bromopyridine

* 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 [ 19798-81-3 ]
Downstream synthetic route of [ 19798-81-3 ]

[ 19798-81-3 ] Synthesis Path-Upstream 1~2

1
[ 19798-81-3 ]
[ 882521-96-2 ]
[ 178039-84-4 ]
[ 120-07-0 ]

References: [1] Synthesis, 2010, # 1, p. 85 - 90.

2
[ 19798-81-3 ]
[ 921-03-9 ]
[ 878197-68-3 ]

Yield	Reaction Conditions	Operation in experiment
72%	at 25 - 65℃; for 2 - 4 h;	The reactor is charged with 2-amino-6-bromopyridine (3.0 Kg, 17.3 mol) and dimethoxyethane ( 12 Liters) and stirred under nitrogen. 1,1,3-Trichloroacetone (5.6 Kg, 30.3 mol) is added to the 25° C solution in a single portion and the reaction solution is warmed to 65 ⁰C jacket temperature and maintained for approximately 2 to 4 hours until judged complete. The reaction is cooled to 10° C and held for approximately one hour and filtered. The solids are rinsed with dimethoxyethane (6 Liters). The solid is placed back in the reactor and treated with dimethoxyethane (12 Liters) and 2N HCI (12 Liters) and warmed to aproximately 75 degrees for 16 to 20 hours or until judged complete. The reaction is cooled to approximately 1O⁰C and pH is adjusted to approximately 8 with 3 N NaOH. The resulting solids are filtered and washed with water. The solid is dried at 50⁰C for 16 hours to yield 5- bromoimidazo[1 ,2-a]pyridine-2-carbaldehyde, (2.81 Kg, 72percent yield) 1H NMR (400 MHz, DMSO-D6) δ ppm 10.05 (s, 1 H) 8.66 (s, 1 H) 7.72 (s, 1 H) 7.42 (s, 1 H) 7.35 (S, 1 H)
50%	Stage #1: at 70℃; for 15 h; Stage #2: for 7 h; Heating / reflux Stage #3: With calcium carbonate In water for 1.5 h; Heating / reflux	To a solution of 2-amino-6-bromopyridine (10 g, 58 mmol) in ethylene glycol dimethyl ether (66 mL) was added trichloroacetone (18 mL, 173 mmol). The mixture was stirred at 7O⁰C for 15 hours and the resulting precipitate was collected by filtration and refluxed in ethyl alcohol (50 mL) for 7 hours. The reaction mixture was cooled to room temperature, concentrated, dissolved in dichloromethane, and washed with saturated aqueous sodium bicarbonate. The organic layer was isolated, dried with magnesium sulfate, and concentrated. The resulting solid was refluxed in aqueous calcium carbonate for 1.5 hours, cooled to room temperature, and extracted with dichloromethane. The organic layer was dried with magnesium sulfate and concentrated to give 6.6 g (50percent yield) 5-bromoimidazo[1 ,2-a]pyridine-2- carbaldehyde as an orange solid. ¹H-NMR (CDCI₃): δ 10.16 (s, 1H), 8.37 (s, 1 H), 7.69 (d, 1H)₁ 7.22 (m, 1H), 7.16 (m, 1 H); TLC (10percent ammonium hydroxide- acetonitrile) R_f = 0.44.

References: [1] Organic Process Research and Development, 2009, vol. 13, # 4, p. 781 - 785.
[2] Patent: WO2007/87549, 2007, A2, . Location in patent: Page/Page column 49.
[3] Patent: WO2007/87549, 2007, A2, . Location in patent: Page/Page column 39-40.

[ 19798-81-3 ] Synthesis Path-Downstream 1~10

1
[ 19798-81-3 ]
[ 885069-14-7 ]
[ 1112982-65-6 ]

Yield	Reaction Conditions	Operation in experiment
28%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 95℃;	Example 73; (Method E) N-(6-(6-(2-Fluorophenylsulfonamido)pyridin-2-yl)benzo[d]thiazol-2-yl)acetamide; Step 1. N-(6-(6-aminopyridin-2-yl)benzo[d]thiazol-2-yl)acetamide; 6-Bromopyridin-2-amine (0.5 g, 3 mmol) was dissolved in 1,4-dioxane (6 mL). Then N-(6-(4,4,5,5- tetramethyl-1,3-dioxolan-2-yl)benzo[d]thiazol-2-yl)acetamide (1.0 g, 3.1 mmol), 2M Na2CO3 (3 mL, 6 mmol), and tetrakis(triphenylphosphine)palladium (0) (0.4 g, 0.4 mmol) were added to the mixture. The flask was fitted with a reflux condenser, placed into a pre-heated (95 C) bath, and allowed to stir under an inert atmosphere overnight. The flask was removed from the heat bath and allowed to cool to ambient temperature. The mixture was diluted with 5: 1 DCM / MeOH and saturated NaHCO3. The aqueous layer was extracted with 5:1 DCM/MeOH three times, and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by silica gel chromatography (1-5% MeOH/DCM ) to give N-(6-(6-aminopyridin-2-yl)benzo[d]thiazol-2-yl)acetamide (0.23 g, 28% yield) as a light yellow solid. MS (ESI pos. ion) m/z: 285 (MH+). Calculated exact mass for C14Hi2N4OS: 284.

References: [1]Patent: WO2009/17822,2009,A2 .Location in patent: Page/Page column 48; 62.

2
[ 19798-81-3 ]
[ 1010120-55-4 ]

References: [1]CrystEngComm,2018,vol. 20,p. 3006 - 3010.
[2]Patent: WO2012/970,2012,A1 .
[3]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 5014 - 5021.
[4]Patent: WO2013/189771,2013,A1 .
[5]Drugs of the Future,2014,vol. 39,p. 547 - 551.
[6]Journal of Medicinal Chemistry,2014,vol. 57,p. 9323 - 9342.
[7]Patent: US2015/224199,2015,A1 .
[8]Patent: US2015/225398,2015,A1 .
[9]Patent: WO2016/165952,2016,A1 .
[10]Journal of Medicinal Chemistry,2017,vol. 60,p. 5663 - 5672.
[11]Patent: WO2009/155565,2009,A1 .
[12]Patent: EP3492469,2019,A1 .

3
[ 334769-80-1 ]
[ 19798-81-3 ]
tert-butyl (2S,5S)-2-((6-bromopyridin-2-yl)carbamoyl)-5-methylpyrrolidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
737 mg	With pyridine; trichlorophosphate; In dichloromethane; at 0℃; for 4h;	In a pre-dried flask, (2 S, 5 S)-1-(tert-butoxycarbonyl)-4-methylpyrrolidine-2-carboxylic acid (purchased from Aldrich) (522 mg, 2.28 mmol), 6-bromopyridin-2-amine (394 mg, 2.28 mmol) are placed, and then anhydrous DCM (15 mL) was added. The flask was placed in an ice bath. To the solution, dry pyridine (0.37 mL, 4.56 mmol) was added in one portion, followed by addition of POCl3(220 muL, 2.28 mmol). After completion of addition, the mixture was stirred for 4 hours at 0° C., and then the reaction was quenched with water (15 mL). The DCM layer was collected and the aqueous phase was extracted with DCM (15 mL×2). The combined DCM solution was washed with brine, and dried over MgSO4. The solution was filtered and concentrated; the resulting residue was purified to give 737 mg of pure product.

References: [1]Patent: WO2017/35353,2017,A1 .Location in patent: Paragraph 1116.

4
[ 19798-81-3 ]
[ 931-53-3 ]
[ 33985-71-6 ]
5-bromo-N-cyclohexyl-2-(2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)imidazo[1,2-a]pyridin-3-amine [ No CAS ]