Home Cart 0 Sign in  

[ CAS No. 886373-28-0 ]

{[proInfo.proName]} ,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 886373-28-0
Chemical Structure| 886373-28-0
Structure of 886373-28-0 * Storage: {[proInfo.prStorage]}

Quality Control of [ 886373-28-0 ]

Related Doc. of [ 886373-28-0 ]

SDS
Alternatived Products of [ 886373-28-0 ]
Alternatived Products of [ 886373-28-0 ]

Product Details of [ 886373-28-0 ]

CAS No. :886373-28-0 MDL No. :MFCD07375030
Formula : C6H2BrFN2 Boiling Point : 238°C at 760 mmHg
Linear Structure Formula :- InChI Key :N/A
M.W :201.00 g/mol Pubchem ID :44196680
Synonyms :

Safety of [ 886373-28-0 ]

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

Application In Synthesis of [ 886373-28-0 ]

  • Upstream synthesis route of [ 886373-28-0 ]
  • Downstream synthetic route of [ 886373-28-0 ]

[ 886373-28-0 ] Synthesis Path-Upstream   1~9

  • 1
  • [ 886373-28-0 ]
  • [ 124-41-4 ]
  • [ 36057-46-2 ]
YieldReaction ConditionsOperation in experiment
95% at 70℃; for 3 h; Inert atmosphere 5-bromo-3-methoxypicolinonitrile
To a solution of 5-bromo-3-fluoropyridine-2-carbonitrile (2.00 g, 9.93 mmol) in THF (80 mL) was added sodium methoxide (2.68 g, 49.59 mmol) at room temperature.
The resulting solution was then stirred for 3 h at 70° C.
When the reaction was done, the pH value of the reaction mixture was adjusted to 7 with hydrogen chloride solution (3 M).
The resulting mixture was extracted with ethyl acetate (100 mL*3).
The organic phases were combined, washed with brine and dried over sodium sulfate.
The solvent was removed under reduced pressure to yield 5-bromo-3-methoxypyridine-2-carbonitrile as a brown solid (2.00 g, 95percent). MS: m/z=213.0 [M+H]+.
75% at 20℃; for 2 h; Sodium methoxide (9.7 g, 0.18 mol) in methanol (50 ml) was added dropwise to a suspension of 5-bromo-3-fluoropyridine-2-carbonitrile (30 g, 0.15 mol) in methanol (150 ml) at room temperature.
After completion of the dropwise addition, the mixture was reacted for 2 hours while the reaction solution became clear.
A small amount of glacial acetic acid was added to the solution to adjust the pH to between 7 and 8, and ice water (300 ml) was added.
The reaction solution was concentrated until a solid precipitated, and allowed to stand and cool for 2 hours so that the solid precipitated more thoroughly.
The precipitated solid was filtered off and the filter cake was washed with water, collected and air dried at room temperature to obtain 5-bromo-3-methoxypyridine-2-carbonitrile as a white solid (24 g, 75percent yield).
69% for 18 h; Heating / reflux 5-Bromo-2-cyano-3-methoxy-pyridine: Mix sodium methoxide (141 mg, 2.61 mmol) and 5-bromo-2- cyano-3-fluoro-pyridine (105 mg, 0.52 mmol) in THF (5 mL) and reflux for 18 h. Add pH 7 phosphate buffer solution and extract with EtOAc. Dry the EtOAc extracts over MgSO4. Remove the drying agent and evaporate the filtrate. Purify the crude product using a silica gel chromatography and elute with EtOAc/hexane (0 to 30 percent) to give 77 mg (69percent yield) of S-bromo^-cyano-S-methoxy-pyridine.
Reference: [1] Patent: US2016/376283, 2016, A1, . Location in patent: Paragraph 1219; 1220
[2] Patent: EP3275864, 2018, A1, . Location in patent: Paragraph 0032; 0038; 0044; 0050; 0056; 0062
[3] Patent: WO2007/87488, 2007, A2, . Location in patent: Page/Page column 24
  • 2
  • [ 886373-28-0 ]
  • [ 669066-91-5 ]
YieldReaction ConditionsOperation in experiment
18.3 g at 140℃; for 4 h; A mixture of 5-bromo-3-fluoro-pyridine-2-carbonitrile (21.0 g, 100 mmol) in concentrated HCI (200 ml)was refluxed at 140°C for 4 hours. After cooling to room temperature, the reaction mixture was pouredinto ice-water. The precipitated solid was filtered under vaccum and dried to give the desired compound(18.3 g). 1H NMR (d6-DMSO, 400MHz): 13.76 (s, 1H), 8.64 (s, 1H), 8.33-8.36 (dd, 1H). 19F NMR (d6-DMSO, 300MHz): -113.70 (d, iF).
Reference: [1] Patent: WO2009/36996, 2009, A2, . Location in patent: Page/Page column 105
[2] Patent: WO2017/174449, 2017, A1, . Location in patent: Page/Page column 89; 90
  • 3
  • [ 886373-28-0 ]
  • [ 669066-93-7 ]
YieldReaction ConditionsOperation in experiment
848 mg
Stage #1: With diisobutylaluminium hydride In dichloromethane; toluene at -78 - 0℃;
Stage #2: With hydrogenchloride In dichloromethane; water; toluene at -78℃;
(1)
Synthesis of 5-bromo-3-fluoropyridine-2-carbaldehyde [172-1] (hereinafter referred to as a compound [172-1])
5-Bromo-3-fluoropyridin-2-carbonitrile obtained by the method described in the document () (4. 5 g) was dissolved in dichloromethane (140 mL) and cooled to -78°C. 1.0M toluene solution (33 mL) of diisobutylaluminum hydride was added at -78°C, and then the reaction mixture was warmed to 0°C and stirred for 5 minutes.
The reaction mixture was cooled again to -78°C, and added 3N-hydrochloric acid, and extracted with chloroform.
The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure.
The obtained residue was purified by silica gel column chromatography to give the titled compound (848 mg) as a yellow solid.
1H-NMR (400 MHz, CDCl3) δ: 10.17 (1H, s), 8.69 (1H, s), 7.80 (1H, dd, J = 9.1, 1.3 Hz).
848 mg With diisobutylaluminium hydride In dichloromethane; toluene at -78 - 0℃; for 0.0833333 h; (1) Synthesis of 5-bromo-3-fluoropyridine-2-carboaldehyde [47-1] (hereinafter referred to as a compound [47-1]) 5-Bromo-3-fluoropyridine-2-carbonitrile (4.5 g), which was obtained by the method described in the document (Journal of Organic Chemistry, 2009, Vol. 74, 4547), was dissolved in dichloromethane (140 mL), and the solution was cooled to -78°C. 1.0M toluene solution of diisobutylaluminum hydride (33 mL) was added to the mixture at -78°C, and the solution was warmed to 0°C and the solution was stirred for 5 minutes. The reaction mixture was cooled again to -78°C, 3N-hydrochloric acid was added to the reaction mixture, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (848 mg) as a yellow solid. 1H-NMR (400 MHz, CDCl3) δ: 10.17 (1H, s), 8.69 (1H, s), 7.80 (1H, dd, J = 9.1, 1.3 Hz).
Reference: [1] Patent: EP2669270, 2013, A1, . Location in patent: Paragraph 0950-0951
[2] Patent: EP2878594, 2015, A1, . Location in patent: Paragraph 0582-0584
  • 4
  • [ 573675-25-9 ]
  • [ 886373-28-0 ]
YieldReaction ConditionsOperation in experiment
59%
Stage #1: With sulfuric acid; tetrabutyl ammonium fluoride In N,N-dimethyl-formamide at -40℃; for 1 h;
Stage #2: With hydrogenchloride In water; N,N-dimethyl-formamide at -40℃;
Step C: 5-Bromo-3-fluoro-pyridine-2-carbonitrile To a mixture of H2SO4 (0.2 ml) and TBAF solution (131 ml, 131 mmol, 1M in THF) was added DMF (40 ml) dropwise at -40° C. Then a solution of 5-bromo-3-nitro-pyridine-2-carbonitrile (10 g, 43 mmol) in DMF (130 ml) was added at -40° C. and the reaction mixture was stirred for 1 h. The reaction was then quenched by addition of 2M HCl solution at -40° C. adjusting the pH to 3. The resulting mixture was extracted twice with EtOAc and the combined organic extracts were washed twice with water, with brine, dried with Na2SO4 and evaporated in vacuo. The remaining residue was purified by chromatography (silica gel; hexane/EtOAc 90:10-80:20) to obtain the title compound as yellow solid (5.2 g, 59percent).
59%
Stage #1: With sulfuric acid; tetrabutyl ammonium fluoride In tetrahydrofuran; N,N-dimethyl-formamide at -40℃; for 1 h;
Stage #2: With hydrogenchloride In tetrahydrofuran; water; N,N-dimethyl-formamide at -40℃;
Step C: 5-Bromo-3-fluoro-pyridine-2-carbonitrileTo a mixture of H2S04 (0.2 ml) and TBAF solution (131 ml, 131 mmol, 1M in THF) was added DMF (40 ml) dropwise at -40°C. Then a solution of 5-bromo-3-nitro-pyridine-2- carbonitrile (10 g, 43 mmol) in DMF (130 ml) was added at -40°C and the reaction mixture was stirred for 1 h. The reaction was then quenched by addition of 2M HC1 solution at -40°C adjusting the pH to 3. The resulting mixture was extracted twice with EtOAc and the combined organic extracts were washed twice with water, with brine, dried with Na2S04 and evaporated in vacuo. The remaining residue was purified bychromatography (silica gel; hexane / EtOAc 90: 10-80:20) to obtain the title compound as yellow solid (5.2 g, 59percent).
42% With sulfuric acid; tetrabutyl ammonium fluoride In tetrahydrofuran; N,N-dimethyl-formamide at -40 - 20℃; for 2.5 h; Tetrabutylammonium fluoride (26.3 ml, 26.3 mmol, 1M in THF) was charged to a round bottom flask and cooled to -40°C. This was treated with sulfuric acid (0.04 ml, 0.074 g, 0.750 mmol). It was then treated with DMF (18 ml) until the suspension became homogenous. To this mixture was added slowly a solution of 5-bromo-3- nitropicolinonitrile (2.0 g, 8.77 mmol) dissolved in DMF (32 ml). Once the addition was complete the reaction was allowed to stir at -40°C for 90 minutes and at roomtemperature for another 1 hour. The reaction was then quenched with 2 N HC1 (20 ml), then diluted with H20 (100 ml) and extracted with EtOAc (3 x 100 ml). The extracts were washed with H20 (4 x 100 ml) followed by brine (1 x 100 ml). The organic layer was dried (Na2S04), filtered, and concentrated in vacuo to give 2.15 g of crude material. The material was purified using the ISCO system (40 g of silica gel column. Eluted using 10 EtOAc / 90 heptane to 50 EtOAc 50 Heptane over 20 min). The pure fractions were combined and concentrated to yield 0.7458 g (42percent) of pure desired product. 1H NMR (300 MHz, METHANOL-i/4) δ ppm 8.27 (dd, J=8.20, 1.76 Hz, 1 H) 8.70 (s, 1 H).
Reference: [1] Patent: US2012/165338, 2012, A1, . Location in patent: Page/Page column 22
[2] Patent: WO2012/89601, 2012, A1, . Location in patent: Page/Page column 54
[3] Patent: WO2012/66070, 2012, A1, . Location in patent: Page/Page column 96-97
[4] Patent: WO2005/63690, 2005, A1, . Location in patent: Page/Page column 29
[5] Patent: WO2009/36996, 2009, A2, . Location in patent: Page/Page column 105
[6] Patent: WO2006/52514, 2006, A1, . Location in patent: Page/Page column 8
[7] Patent: EP2471792, 2012, A1, . Location in patent: Page/Page column 76
[8] Patent: US2012/190681, 2012, A1, . Location in patent: Page/Page column 28
[9] Patent: WO2006/132837, 2006, A1, . Location in patent: Page/Page column 19-20
  • 5
  • [ 669066-90-4 ]
  • [ 886373-28-0 ]
YieldReaction ConditionsOperation in experiment
73%
Stage #1: With sodium chloride; trichlorophosphate In dichloromethaneHeating / reflux
Stage #2: With sodium hydrogencarbonate In dichloromethane; water at 20℃;
Stir amixture of S-bromo-S-fluoro-pyridine^-carboxylic acid amide (0.375 mg, 1.71 mmol) and NaCl (0.120 g, 2.05 mmol) in CH2Cl2 (20 ml). After 15 minutes, addPOCl3 (0.795 ml, 8.55 mmol) and reflux the mixture overnight. Cool the mixture to room temperature, and dilute with CH2Cl2; wash with saturated NaHCO3 solution, dry over (MgSO^. Purify the crude product using silica chromatography (0-50percent EtOAc/Hexane) to produce 0.25 g (73percent yield) of 5-bromo-2-cyano-3- fluoro-pyridine.
Reference: [1] Patent: WO2007/87488, 2007, A2, . Location in patent: Page/Page column 23
  • 6
  • [ 573675-25-9 ]
  • [ 886373-28-0 ]
  • [ 1160936-51-5 ]
Reference: [1] Journal of Organic Chemistry, 2009, vol. 74, # 12, p. 4547 - 4553
  • 7
  • [ 15862-34-7 ]
  • [ 886373-28-0 ]
Reference: [1] Patent: US2012/165338, 2012, A1,
[2] Patent: WO2012/89601, 2012, A1,
[3] Patent: WO2006/132837, 2006, A1,
  • 8
  • [ 15862-37-0 ]
  • [ 886373-28-0 ]
Reference: [1] Patent: US2012/165338, 2012, A1,
[2] Patent: WO2012/89601, 2012, A1,
[3] Patent: WO2006/132837, 2006, A1,
  • 9
  • [ 886373-28-0 ]
  • [ 1150617-54-1 ]
Reference: [1] Patent: EP2669270, 2013, A1,
[2] Patent: EP2878594, 2015, A1,
Historical Records

Related Functional Groups of
[ 886373-28-0 ]

Fluorinated Building Blocks

Chemical Structure| 1162674-74-9

[ 1162674-74-9 ]

5-Bromo-3-fluoro-2-methylpyridine

Similarity: 0.90

Chemical Structure| 97509-75-6

[ 97509-75-6 ]

3-Fluoropicolinonitrile

Similarity: 0.84

Chemical Structure| 831203-14-6

[ 831203-14-6 ]

2-(5-Bromo-3-fluoropyridin-2-yl)acetonitrile

Similarity: 0.83

Chemical Structure| 1206968-92-4

[ 1206968-92-4 ]

(5-Bromo-3-fluoropyridin-2-yl)methanol

Similarity: 0.79

Chemical Structure| 669066-93-7

[ 669066-93-7 ]

5-Bromo-3-fluoropyridine-2-carboxaldehyde

Similarity: 0.79

Nitriles

Chemical Structure| 97509-75-6

[ 97509-75-6 ]

3-Fluoropicolinonitrile

Similarity: 0.84

Chemical Structure| 831203-14-6

[ 831203-14-6 ]

2-(5-Bromo-3-fluoropyridin-2-yl)acetonitrile

Similarity: 0.83

Chemical Structure| 298709-29-2

[ 298709-29-2 ]

3,5-Difluoropicolinonitrile

Similarity: 0.75

Chemical Structure| 1353636-66-4

[ 1353636-66-4 ]

3-Bromo-5-fluoroisonicotinonitrile

Similarity: 0.71

Chemical Structure| 886364-86-9

[ 886364-86-9 ]

5-Bromo-4-methylpicolinonitrile

Similarity: 0.70

Bromides

Chemical Structure| 1162674-74-9

[ 1162674-74-9 ]

5-Bromo-3-fluoro-2-methylpyridine

Similarity: 0.90

Chemical Structure| 831203-14-6

[ 831203-14-6 ]

2-(5-Bromo-3-fluoropyridin-2-yl)acetonitrile

Similarity: 0.83

Chemical Structure| 1206968-92-4

[ 1206968-92-4 ]

(5-Bromo-3-fluoropyridin-2-yl)methanol

Similarity: 0.79

Chemical Structure| 669066-93-7

[ 669066-93-7 ]

5-Bromo-3-fluoropyridine-2-carboxaldehyde

Similarity: 0.79

Chemical Structure| 407-20-5

[ 407-20-5 ]

3-Bromo-5-fluoropyridine

Similarity: 0.76

Related Parent Nucleus of
[ 886373-28-0 ]

Pyridines

Chemical Structure| 1162674-74-9

[ 1162674-74-9 ]

5-Bromo-3-fluoro-2-methylpyridine

Similarity: 0.90

Chemical Structure| 97509-75-6

[ 97509-75-6 ]

3-Fluoropicolinonitrile

Similarity: 0.84

Chemical Structure| 831203-14-6

[ 831203-14-6 ]

2-(5-Bromo-3-fluoropyridin-2-yl)acetonitrile

Similarity: 0.83

Chemical Structure| 1206968-92-4

[ 1206968-92-4 ]

(5-Bromo-3-fluoropyridin-2-yl)methanol

Similarity: 0.79

Chemical Structure| 669066-93-7

[ 669066-93-7 ]

5-Bromo-3-fluoropyridine-2-carboxaldehyde

Similarity: 0.79