Home Cart 0 Sign in  

[ CAS No. 6298-19-7 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 6298-19-7
Chemical Structure| 6298-19-7
Structure of 6298-19-7 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 6298-19-7 ]

Related Doc. of [ 6298-19-7 ]

Alternatived Products of [ 6298-19-7 ]

Product Details of [ 6298-19-7 ]

CAS No. :6298-19-7 MDL No. :MFCD00006238
Formula : C5H5ClN2 Boiling Point : -
Linear Structure Formula :- InChI Key :MEQBJJUWDCYIAB-UHFFFAOYSA-N
M.W :128.56 Pubchem ID :80528
Synonyms :

Calculated chemistry of [ 6298-19-7 ]

Physicochemical Properties

Num. heavy atoms : 8
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 1.0
Num. H-bond donors : 1.0
Molar Refractivity : 33.65
TPSA : 38.91 Ų

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) : -6.52 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.2
Log Po/w (XLOGP3) : 0.8
Log Po/w (WLOGP) : 1.33
Log Po/w (MLOGP) : 0.4
Log Po/w (SILICOS-IT) : 1.37
Consensus Log Po/w : 1.02

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.7
Solubility : 2.59 mg/ml ; 0.0201 mol/l
Class : Very soluble
Log S (Ali) : -1.2
Solubility : 8.14 mg/ml ; 0.0633 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.24
Solubility : 0.735 mg/ml ; 0.00571 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.49

Safety of [ 6298-19-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362-P403+P233-P501 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 6298-19-7 ]

* 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 [ 6298-19-7 ]
  • Downstream synthetic route of [ 6298-19-7 ]

[ 6298-19-7 ] Synthesis Path-Upstream   1~45

  • 1
  • [ 6298-19-7 ]
  • [ 6636-78-8 ]
Reference: [1] Chemische Berichte, 1936, vol. 69, p. 2593,2604
  • 2
  • [ 6298-19-7 ]
  • [ 39620-04-7 ]
Reference: [1] Recueil des Travaux Chimiques des Pays-Bas, 1950, vol. 69, p. 673,690
  • 3
  • [ 6298-19-7 ]
  • [ 5028-20-6 ]
YieldReaction ConditionsOperation in experiment
70% With copper(ll) sulfate pentahydrate In water at 160℃; for 1 h; Microwave irradiation 3-Amino-2-chloropyridine (400 mg, 3.1 mmol) and copper sulfate pentahydrate (78 mg, 0.31 mmol, 0.10 eq.) were added to a microwave pressure vessel with 40percent methylamine in water (2.33 ml) and heated at 160 °C for 1 h. The crude product was cooled to RT and filtered through Celite. The crude mixture was treated with aqueous sodium carbonate, extracted with EtOAc (2x), dried over anhydrous NaSO4 , filtered, and dried under vacuum. After purification by column chromatography, using a solvent gradient from hexane to EtOAc, the desired compound 22 was isolated as orange solid (70percent)
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 5, p. 1117 - 1123
[2] Journal of Heterocyclic Chemistry, 2008, vol. 45, # 6, p. 1641 - 1649
[3] Chemische Berichte, 1936, vol. 69, p. 2593,2604
  • 4
  • [ 6298-19-7 ]
  • [ 13061-96-6 ]
  • [ 3430-10-2 ]
Reference: [1] Tetrahedron, 1998, vol. 54, # 23, p. 6311 - 6318
  • 5
  • [ 6298-19-7 ]
  • [ 52200-48-3 ]
YieldReaction ConditionsOperation in experiment
80.1% With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; hydrogen bromide; sodium nitrite In water at 10 - 20℃; for 2 h; Example 3
3-Bromo-2-chloropyridine (7)
Water (45 ml) and 48percent hydrobromic acid (27 ml) were added to 3-amino-2-chloropyridine (6) (2.57 g, 20 mmol) at room temperature.
To the mixed solution, 2,2,6,6-tetramethylpiperidine 1-oxyl (0.31 g, 2 mmol) was added at room temperature, and the mixture was cooled to 10° C. or lower.
Then, sodium nitrite (4.14 g) dissolved in water (30 ml) was added thereto.
After stirring at room temperature for approximately 2 hours, a 10 mol/L aqueous sodium hydroxide solution (40 ml) was added thereto, followed by extraction twice with toluene (300 ml).
The toluene layers were combined and washed with water (50 ml).
The solvent was distilled off by the concentration of the toluene layer under reduced pressure to obtain 3-bromo-2-chloropyridine (7) (3.08 g, 80.1percent).
Reference: [1] Patent: US2013/144061, 2013, A1, . Location in patent: Paragraph 0229; 0230
[2] Journal of Organic Chemistry, 1995, vol. 60, # 5, p. 1408 - 1412
  • 6
  • [ 6298-19-7 ]
  • [ 38240-21-0 ]
Reference: [1] Journal of Heterocyclic Chemistry, 1980, vol. 17, # 1, p. 149 - 153
  • 7
  • [ 6298-19-7 ]
  • [ 57-55-6 ]
  • [ 38240-21-0 ]
Reference: [1] Patent: US5814651, 1998, A,
  • 8
  • [ 6298-19-7 ]
  • [ 74-88-4 ]
  • [ 40932-43-2 ]
YieldReaction ConditionsOperation in experiment
89%
Stage #1: With lithium diisopropyl amide In tetrahydrofuran at -78 - 0℃; for 1 h;
Stage #2: at -78 - 20℃; for 16 h;
To a solution of 2-chloro-3-pyridinamine (0.0465 mol) in THF (45ml) at-78°C under N2 flow, LDA 2. 0M (0.0513 mol) was added dropwise. The mixture was allowed to warm to 0°C and was stirred for 1 hour and then cooled TO-78°C. Then CH3I (0.0582 mol) was added and the reaction mixture was allowed to warm to room temperature and was stirred for 16 hours. A saturated NH4CL-SOLUTION was added and the mixture was extracted with AcOEt. The separated organic layer was dried (NA2S04), filtered and the solvent was evaporated. The residue was purified by short open column chromatography over silica gel (eluent: hexane/AcOEt 80/20). The product fractions were collected and the solvent was evaporated. Yield: 5. 91g of intermediate compound 1 (89percent).
Reference: [1] Patent: WO2004/106298, 2004, A1, . Location in patent: Page 19-20
[2] Synthesis, 1999, # 11, p. 1893 - 1902
[3] Advanced Functional Materials, 2018, vol. 28, # 44,
[4] Patent: US2004/19051, 2004, A1, . Location in patent: Page 11
  • 9
  • [ 6298-19-7 ]
  • [ 40932-43-2 ]
Reference: [1] Journal of the Chemical Society, 1957, p. 442,443
[2] Patent: EP3299371, 2018, A1,
[3] Patent: US2018/148451, 2018, A1,
  • 10
  • [ 6298-19-7 ]
  • [ 557-21-1 ]
  • [ 42242-11-5 ]
Reference: [1] Patent: WO2008/130021, 2008, A2, . Location in patent: Page/Page column 455-456
  • 11
  • [ 6298-19-7 ]
  • [ 42242-11-5 ]
Reference: [1] Patent: US5212310, 1993, A,
[2] Patent: US5326868, 1994, A,
[3] Patent: US5625063, 1997, A,
[4] Patent: US6013650, 2000, A,
  • 12
  • [ 6298-19-7 ]
  • [ 42242-11-5 ]
Reference: [1] Zeitschrift fuer Chemie (Stuttgart, Germany), 1990, vol. 30, # 1, p. 20 - 21
  • 13
  • [ 6298-19-7 ]
  • [ 20265-38-7 ]
Reference: [1] Chemische Berichte, 1936, vol. 69, p. 2593,2604
  • 14
  • [ 6298-19-7 ]
  • [ 7689-62-5 ]
Reference: [1] Patent: EP2727920, 2014, A1,
[2] Patent: US2015/322063, 2015, A1,
  • 15
  • [ 6298-19-7 ]
  • [ 141-32-2 ]
  • [ 10261-82-2 ]
YieldReaction ConditionsOperation in experiment
2.51 g With bis(tri-t-butylphosphine)palladium(0); triethylamine In cyclohexyl acetate at 150℃; for 40 h; Inert atmosphere Triethylamine (13 mL), butyl acrylate (10 mL), and bis(tritert-butylphosphine)palladium (0) (350 mg) were added to a solution of 2-chloro-3-aminopyridine (6.00 g) in cyclohexyl acetate (60 mL), and the mixture was stirred at 150°C for 40 hours under a nitrogen atmosphere. The resulting mixture was left to be cooled at room temperature. When the mixture was cooled to 70°C, water (30 mL) was added thereto, and the resulting mixture was left to be cooled at room temperature under stirring. After subjecting the resulting mixture to sonication for 30 minutes, the mixture was filtered and the residue was washed with water (3 mL). The obtained residue was suspended in ethyl acetate (3 mL)/2-propanol (4 mL) and then subjected to sonication. Further, the suspension was filtered, and the residue was washed with ethyl acetate (3 mL) and hexane, and thereafter is dried to obtain a compound 0001-1 (2.51 g) as a pale yellow solid. 1H-NMR (DMSO-d6) δ: 11.90 (1H, s), 8.47 (1H, dd), 7.93 (1H, d), 7.68 (1H, ddd), 7.51 (1H, dd), 6.75 (1H, dd). MS m/z (M+H): 147.
Reference: [1] Patent: EP2727920, 2014, A1, . Location in patent: Paragraph 0263-0264
  • 16
  • [ 462-08-8 ]
  • [ 6298-19-7 ]
  • [ 62476-56-6 ]
YieldReaction ConditionsOperation in experiment
76%
Stage #1: With hydrogenchloride In water at 30 - 35℃;
Stage #2: With dihydrogen peroxide In water at 10 - 19℃; for 8.33333 h;
Stage #3: With sodium hydroxide In water; toluene at 25 - 35℃;
EXAMPLE 2; Preparation of 3-amino-2-chloropyridine 2 using hydrogen peroxide; 3-Aminopyridine 3 (30.0 g, 0.32 mole) was add to 300 mL of 37percent aqueous HC1 in a 1-L Morton flask with overhead stirring at about 30-35 °C. After the mixture was cooled to about 10 °C, 23 g (0.34 mol) of 50 percent hydrogen peroxide was added over 20 minutes at about 10-12 °C. The mixture was held at about 10 °C for 2 hours and then was allowed to warm to about 19 °C over 2 hours and held at that temperature for additional 4 hours. HPLC analysis showed approximately 90 percent conversion of 3-aminopyridine 3. After cooling the reaction mixture to 10 °C, a solution of 6 g of sodium sulfite in 50 mL of water was added. To the mixture were added 50 mL of toluene and 200 g (2.5 mol) of 50 percent aqueous sodium hydroxide at about 25-35 °C. Then water was added to dissolve precipitated NaCl, and the layers were separated. The organic phase was back-extracted with 45 g of 10 percent aqueous HC1 to recover some 3-amino-2-chloropyridine 2 in the toluene extract, and this was added back to the original aqueous phase. The combined aqueous phases were neutralized to pH 3 with 50 percent aqueous NaOH and extracted with toluene for 3 times. The toluene extracts were combined, washed with 30 mL of saturated aqueous NaCl, and concentrated to dryness to afford 33 g of crude 3-amino-2-chloropyridine 2 (76 percent yield) with 94 percent purity. The product contained about 3 wt percent 3-amino-2, 6-dichloropyridine by HPLC assay.
74%
Stage #1: With hydrogenchloride In water at 30 - 35℃;
Stage #2: With chlorine In water at 15 - 20℃; for 1.5 h;
Stage #3: With sodium hydroxide In toku; water at 25 - 40℃;
EXAMPLE 3; Preparation of 3-amino-2-chloropyridine 2 using chlorine; 3-Aminopyridine 3 (21.0 g, 0.223 mol) was added to 90 mL (ca. 108 g, 1. 08 mol) of concentrated aqueous HC1 (ca. 37percent) in a 300-mL sidearm flask with magnetic stirring at 30-35 °C. The mixture was cooled to 15 °C (thick slurry) and chlorine gas was sparged just above the surface over about 1.5 hours at 15-20 °C. HPLC analysis showed approximately 93 percent conversion of 3-aminopyridine 3. The mixture was cooled to 10 °C and a solution of 6 g of sodium sulfite in 50 mL of water was added. To the mixture was added 30 mL of toluene and 80 g (1.0 mol) of 50 percent aqueous sodium hydroxide at about 25-40 °C. Then water was added to dissolve precipitated NaCI, and the layers were separated. The aqueous phase was extracted once more with 30 mL of toluene. To the aqueous phase was added 10 g of 50 percent NaOH, and extracted with another 50 mL of toluene to remove 3-amino-2, 6- dichloropyridine. The combined organic phase was back-extracted with 40 mL of 0.2 N aqueous HC1 to recover some 3-amino-2-chloropyridine 2 in the toluene extracts, and this was added back to the original aqueous phase. The combined aqueous phases were diluted with 100 mL of toluene and neutralized to pH 3 with about 20 g of 50percent aqueous NaOH at about 35 °C. The aqueous phase was extracted with two 50-mL portions of toluene. The toluene layers were combined and washed with 20 mL of saturated aqueous NaCI. The solution was concentrated to dryness to afford 21.4 g of crude 3-amino-2-chloropyridine 2 (74 percent yield) with 98.6 percent purity, which contained about 1.4 wt percent 3-amino-2,6- dichloropyridine.
Reference: [1] Patent: WO2005/70888, 2005, A2, . Location in patent: Page/Page column 15
[2] Patent: WO2005/70888, 2005, A2, . Location in patent: Page/Page column 16
[3] Chemische Berichte, 1936, vol. 69, p. 2593,2604
  • 17
  • [ 462-08-8 ]
  • [ 7647-01-0 ]
  • [ 7732-18-5 ]
  • [ 7722-84-1 ]
  • [ 6298-19-7 ]
  • [ 62476-56-6 ]
Reference: [1] Chemische Berichte, 1936, vol. 69, p. 2593,2604
  • 18
  • [ 462-08-8 ]
  • [ 7647-01-0 ]
  • [ 7732-18-5 ]
  • [ 7722-84-1 ]
  • [ 6298-19-7 ]
  • [ 62476-56-6 ]
Reference: [1] Chemische Berichte, 1936, vol. 69, p. 2593,2604
  • 19
  • [ 6298-19-7 ]
  • [ 104830-06-0 ]
Reference: [1] Chemical & Pharmaceutical Bulletin, 1985, vol. 33, # 11, p. 4764 - 4768
  • 20
  • [ 6298-19-7 ]
  • [ 98-80-6 ]
  • [ 101601-80-3 ]
YieldReaction ConditionsOperation in experiment
90% With sodium hydroxide; sodium carbonate; benzaldehyde In water; toluene To 2-chloro-3-aminopyridine (1.06 g, 8.24 mmol) in toluene (25 mL) was added benzaldehyde (0.878 g, 8.27 mmol).
The reaction mixture was stirred at reflux in a Dean-Stark apparatus until GC/MS analysis of the reaction mixture no longer showed starting material.
The reaction mixture was cooled to room temperature and the toluene solution containing benzylidene-(2-chloro-pyridin-3-yl)-amine was added to a mixture of phenylboronic acid (1.30 g, 10.7 mmol), sodium carbonate (2.66 g, 25.1 mmol), and tetrakis(triphenylphosphine)palladium(0) (47 mg, 0.38mol percent) in water (10 mL).
The reaction mixture was heated to 100° C. for 30 minutes, cooled to room temperature and poured into 1N aqueous sodium hydroxide (10 mL).
The aqueous layer was removed and the toluene layer was extracted with 1N aqueous hydrochloric acid (twice with 15 mL).
The aqueous layer was neutralized to pH 12 with 6N aqueous sodium hydroxide and extracted with MTBE (twice with 20 mL).
The MTBE extracts were dried over magnesium sulfate, filtered and concentrated to afford 2-phenyl-3-aminopyridine as a solid which crystallized from diisopropyl ether (1.26 g, 90percent yield). M. p.=87-68° C. 1H NMR (300 MHz, CDCl3) δ3.88 (bs, 2), 7.02-7.11 (m, 2), 7.28-7.53 (m, 3), 7.6714 7.71 (m, 2), 8.13-8.16 (m, 1).
13C NMR (100 MHz, CDCl3) δ122.57, 122.96, 128.14, 128.38, 128.72, 138.54, 139.86, 139.93, 144.93.
Reference: [1] Patent: US6316632, 2001, B1,
  • 21
  • [ 6298-19-7 ]
  • [ 98-80-6 ]
  • [ 101601-80-3 ]
YieldReaction ConditionsOperation in experiment
97% With sodium carbonate; benzaldehyde; triphenylphosphine In water; toluene A solution of palladium acetate (224.5 mg, 1.00 mmol) and triphenylphosphine (1.05 g, 4.00 mmol) in toluene (1000 mL) was stirred at room temperature for 15 minutes.
Phenylboronic acid (114 g, 935 mmol), 2-chloro-3-aminopyridine (100 g, 778 mmol), benzaldehyde (83.4 g, 786 mmol), and toluene (500 mL) were then added followed by a solution of sodium carbonate (200 g, 1.89 mol) in water (1500 mL).
The mixture was heated to reflux for 18 hours, cooled to room temperature, and the layers were separated.
The organic layer was washed with water (500 mL) and 2.5M aqueous hydrochloric acid was added (630 mL).
The aqueous layer was separated and washed with toluene (300 mL).
The pH was adjusted to 12-13 using 50percent aqueous sodium hydroxide and the mixture was extracted with methyl-tert-butyl ether (500 mL).
The organic layer was concentrated and the product was crystallized from diisopropyl ether to afford 2-phenyl-3-aminopyridine (128 g, 97percent yield). M. p.=67-68° C. 1H NMR (300 MHz, CDCl3) δ3.88 (bs, 2), 7.02-7.11 (m, 2).
7.28-7.53 (m, 3), 7.67-7.71 (m, 2), 8.,13-8.16 (m, 1).
13C NMR (100 MHz, CDCl3) δ122.57, 122.96, 128.14, 128.38, 128.72, 138.54, 139.86, 139.93, 144.93.
88% With potassium phosphate; tetrabutylammomium bromide In water at 90℃; for 6 h; Green chemistry General procedure: To a 10-mL reaction vial, heteroaryl halide (1.0 mmol), boronic acid (1.2 mmol), K3PO4 (2.0 mmol), tetra-butylammonium bromide (TBAB) (0.5 mmol), and 4 (0.1 mol percent) in water (3.5 mL) were added. The reaction mixture was stirred at 85 °C and the reaction progress was monitored by GC–MS analysis. After completion of the reaction, it was diluted with H2O and CH2Cl2. The organic layer was separated from mixture, the dried organic layer over MgSO4, and evaporated under reduced pressure. The crude reaction product was purified using column chromatography on silica-gel to afford the corresponding product with isolated yield up to 98percent.
71%
Stage #1: With bis-triphenylphosphine-palladium(II) chloride In 1,4-dioxane at 20℃; for 0.5 h; Inert atmosphere
Stage #2: With sodium carbonate In 1,4-dioxane; water at 80℃; for 8 h; Inert atmosphere
General procedure: 3-Amino-2-chloropyridine (0.5g, 3.9mmol), phenylboronic acid (0.47 g, 3.9 mmol), and bis(triphenylphosphine)palladium dichloride (0.137 g, 0.195 mmol) were added to 1,4-dioxane (20ml). Under nitrogen atmosphere the mixture was stirred at room temperature for 30 minutes. 1M aqueous sodium carbonate (8 ml) was poured in, and the temperature was raised to 80°C. After the reaction at 80°C for 8 hours, the mixture was distilled off under reduced pressure. The residue was extracted with addition of ethyl acetate and water. The impurities were filtered off from the organic layer, and the solvent was distilled off under reduced pressure. The purification by column chromatography gave the title compound (0.47 g, 71.0percent yield).
Reference: [1] Journal of Organic Chemistry, 2003, vol. 68, # 24, p. 9412 - 9415
[2] Patent: US6316632, 2001, B1,
[3] European Journal of Organic Chemistry, 2012, # 31, p. 6248 - 6259,12
[4] European Journal of Organic Chemistry, 2012, # 31, p. 6248 - 6259
[5] Tetrahedron Letters, 2005, vol. 46, # 20, p. 3573 - 3577
[6] Advanced Synthesis and Catalysis, 2009, vol. 351, # 17, p. 2912 - 2920
[7] Bulletin of the Korean Chemical Society, 2016, vol. 37, # 9, p. 1478 - 1485
[8] Journal of Organic Chemistry, 2005, vol. 70, # 1, p. 388 - 390
[9] Green Chemistry, 2010, vol. 12, # 11, p. 2024 - 2029
[10] Bulletin of the Korean Chemical Society, 2010, vol. 31, # 10, p. 3010 - 3012
[11] Patent: EP2599771, 2013, A1, . Location in patent: Paragraph 0350
[12] Advanced Synthesis and Catalysis, 2013, vol. 355, # 11-12, p. 2274 - 2284
[13] New Journal of Chemistry, 2017, vol. 41, # 24, p. 15420 - 15432
  • 22
  • [ 3262-89-3 ]
  • [ 6298-19-7 ]
  • [ 101601-80-3 ]
Reference: [1] Patent: US2004/171836, 2004, A1, . Location in patent: Page 2; 4
  • 23
  • [ 6298-19-7 ]
  • [ 28557-00-8 ]
  • [ 101601-80-3 ]
Reference: [1] Chemistry - A European Journal, 2015, vol. 21, # 21, p. 7690 - 7694
[2] Tetrahedron Letters, 1998, vol. 39, # 36, p. 6441 - 6444
  • 24
  • [ 6298-19-7 ]
  • [ 101601-80-3 ]
Reference: [1] Organic Process Research and Development, 2001, vol. 5, # 3, p. 254 - 256
  • 25
  • [ 6298-19-7 ]
  • [ 30458-68-5 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 5, p. 1117 - 1123
  • 26
  • [ 6298-19-7 ]
  • [ 21991-39-9 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 5, p. 1117 - 1123
  • 27
  • [ 6298-19-7 ]
  • [ 134-20-3 ]
  • [ 885-70-1 ]
YieldReaction ConditionsOperation in experiment
95%
Stage #1: With potassium <i>tert</i>-butylate In toluene at 50℃; for 1 h;
Stage #2: With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 110℃; for 24 h;
(1) 300 ml of toluene was added to the reaction vessel,257 g of 2-chloro-3-aminopyridine was dissolved in toluene,Stir with a mechanical stirrer.Slowly 292 grams of potassium t-butoxide were added thereto,Add a rate of 5percent / min,Stir evenly.Then 393 g of methyl anthranilate was added dropwise to the reaction solvent,Dropping speed is 3percent Dosage / min.The reaction was carried out at 50 ° C for 1 hour,After the reaction,Add 400 ml of toluene,4.49 grams of palladium acetate and12.5 grams of binaphthalene diphenylphosphine,The reaction temperature was raised to 110 ° C for 24 hours.After completion of the reaction, the solvent was distilled off under reduced pressure, and the white solid was collected by suction filtration. The mixture was recrystallized from 600 ml of a mixed solvent of 50percent acetone and water. The mixture was filtered and washed with petroleum ether to obtain a cyclized intermediate benzodiazepine 66 g of the compound, the product yield was 95percent and the purity was 99percent.
Reference: [1] Patent: CN106432227, 2017, A, . Location in patent: Paragraph 0017; 0018
[2] Journal of Heterocyclic Chemistry, 1998, vol. 35, # 3, p. 675 - 686
  • 28
  • [ 6298-19-7 ]
  • [ 87-25-2 ]
  • [ 885-70-1 ]
Reference: [1] Journal of Medicinal Chemistry, 1989, vol. 32, # 8, p. 1718 - 1724
  • 29
  • [ 109-01-3 ]
  • [ 6298-19-7 ]
  • [ 5028-17-1 ]
Reference: [1] Organic Preparations and Procedures International, 1998, vol. 30, # 6, p. 709 - 713
  • 30
  • [ 6298-19-7 ]
  • [ 25797-03-9 ]
Reference: [1] Tetrahedron, 2003, vol. 59, # 9, p. 1571 - 1587
  • 31
  • [ 6298-19-7 ]
  • [ 17288-35-6 ]
Reference: [1] European Journal of Medicinal Chemistry, 2012, vol. 54, p. 660 - 668
  • 32
  • [ 617-35-6 ]
  • [ 6298-19-7 ]
  • [ 17288-32-3 ]
YieldReaction ConditionsOperation in experiment
190 mg
Stage #1: at 20℃; for 24 h;
Stage #2: at 160℃; for 0.333333 h; Microwave irradiation
3-Amino-2-chloro-pyridine 4f (150 mg, 1.17 mmol), ethyl pyruvate 8 (0.25 ml, 2.00 mmol), pyridinium p-toluenesulfonate, (73 mg, 0.29 mmol) and tetraethoxy-silane (0.26 ml, 1.18 mmol) were suspended in 0.4 ml pyridine and stirred for 24 h at 20 °C. Afterwards Pd[P(C6H6)3]4 (70 mg, 0.06 mmol) and N,N-dicyclohexylmethylamine (0.35 ml, 2.06 mmol) were added and the reaction mixture was heated in a microwave oven to 160 °C for 20 min. The reaction mixture is diluted with 100 ml dichloromethan and extracted two times with 50 ml of a half saturated aqueous sodium hydrogencarbonat solution. The organic layer was dried with sodium sulfate, the solvent was evaporated under reduced pressure and the crude product was purified using chromatography method P3, yielding 190 mg (1.00 mmol) of 1H-Pyrrolo[3,2-b]pyridine-2-carboxylic acid ethyl ester. The ester was dissolved in 17 ml ethanol and 5 ml water. To this solution lithium hydroxide (120 mg, 5.00 mmol) was added. After 16 h the pH value of the reaction mixture was adjusted to pH 4 and the solvent is evaporated in vacuum. The crude product was purified using an acid ion exchanger (Strata-X-C, Phenomenex), yielding of 155 mg (82percent) of the title compound. Purity by method A1: >95percent; MS (ESI) m/z 163 (M + H)+; 1H NMR (DMSO) δ (ppm) 13.34 (br, 1H), 8.77 (d, J = 5.3 Hz, 1H), 8.53 (d, J = 8.3 Hz, 1H), 7.73 (dd, J = 5.4 Hz, J = 8.3 Hz, 1H), 7.33 (br, 1H); 13C NMR (500 MHz, DMSO) δ (ppm) 161.4 (s), 138.0 (s), 136.1 (s), 135.8 (s), 132.7 (s), 128.6 (s), 119.6 (s), 101.2 (s).
Reference: [1] Angewandte Chemie - International Edition, 2016, vol. 55, # 39, p. 11859 - 11862[2] Angew. Chem., 2016, vol. 128, p. 12038 - 12041,4
[3] European Journal of Medicinal Chemistry, 2012, vol. 54, p. 660 - 668
  • 33
  • [ 6298-19-7 ]
  • [ 17288-32-3 ]
Reference: [1] Synthesis, 2005, # 15, p. 2571 - 2577
  • 34
  • [ 6298-19-7 ]
  • [ 1513-66-2 ]
Reference: [1] Patent: EP1382603, 2004, A1, . Location in patent: Page 133
  • 35
  • [ 6298-19-7 ]
  • [ 17282-04-1 ]
Reference: [1] Tetrahedron, 1996, vol. 52, # 1, p. 23 - 36
[2] Synthetic Communications, 2004, vol. 34, # 5, p. 759 - 766
[3] Journal of Fluorine Chemistry, 1981, vol. 18, p. 497 - 506
[4] Tetrahedron, 1993, vol. 49, # 16, p. 3325 - 3342
[5] Tetrahedron Letters, 1985, vol. 26, # 40, p. 4903 - 4906
  • 36
  • [ 6298-19-7 ]
  • [ 78607-36-0 ]
Reference: [1] Journal of Organic Chemistry, 2004, vol. 69, # 22, p. 7752 - 7754
[2] Synthesis, 2007, # 1, p. 81 - 84
[3] Tetrahedron Letters, 2009, vol. 50, # 52, p. 7263 - 7267
[4] Chemical & Pharmaceutical Bulletin, 1985, vol. 33, # 11, p. 4764 - 4768
  • 37
  • [ 6298-19-7 ]
  • [ 143621-35-6 ]
Reference: [1] Tetrahedron, 1998, vol. 54, # 23, p. 6311 - 6318
[2] Tetrahedron, 1998, vol. 54, # 23, p. 6311 - 6318
  • 38
  • [ 6298-19-7 ]
  • [ 148639-07-0 ]
Reference: [1] Tetrahedron, 1993, vol. 49, # 16, p. 3325 - 3342
  • 39
  • [ 6298-19-7 ]
  • [ 116026-99-4 ]
Reference: [1] Tetrahedron, 1998, vol. 54, # 23, p. 6311 - 6318
  • 40
  • [ 6298-19-7 ]
  • [ 169833-70-9 ]
Reference: [1] Organic Letters, 2005, vol. 7, # 17, p. 3817 - 3820
[2] Journal of Medicinal Chemistry, 1995, vol. 38, # 24, p. 4830 - 4838
[3] Patent: WO2016/71214, 2016, A1, . Location in patent: Page/Page column 87-88
  • 41
  • [ 6298-19-7 ]
  • [ 185961-99-3 ]
Reference: [1] Patent: US2011/59954, 2011, A1,
[2] Patent: US2011/195954, 2011, A1,
[3] Patent: US2012/88755, 2012, A1,
[4] Organic Process Research and Development, 2012, vol. 16, # 2, p. 244 - 249
  • 42
  • [ 6298-19-7 ]
  • [ 1073182-86-1 ]
Reference: [1] Patent: WO2008/130021, 2008, A2,
  • 43
  • [ 6298-19-7 ]
  • [ 1309774-03-5 ]
Reference: [1] Patent: EP2727920, 2014, A1,
[2] Patent: US2015/322063, 2015, A1,
  • 44
  • [ 6298-19-7 ]
  • [ 58483-94-6 ]
Reference: [1] Tetrahedron Letters, 2011, vol. 52, # 24, p. 3131 - 3132
[2] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 21, p. 5923 - 5930
  • 45
  • [ 6298-19-7 ]
  • [ 84341-13-9 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 21, p. 5923 - 5930
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 6298-19-7 ]

Chlorides

Chemical Structure| 40932-43-2

[ 40932-43-2 ]

2-Chloro-N-methylpyridin-3-amine

Similarity: 0.88

Chemical Structure| 39217-08-8

[ 39217-08-8 ]

2-Chloropyridine-3,4-diamine

Similarity: 0.88

Chemical Structure| 5632-81-5

[ 5632-81-5 ]

2-Chloropyridine-3,5-diamine

Similarity: 0.88

Chemical Structure| 78607-32-6

[ 78607-32-6 ]

3-Amino-2,5-dichloropyridine

Similarity: 0.88

Chemical Structure| 34552-13-1

[ 34552-13-1 ]

2-Chloro-5-methylpyridin-3-amine

Similarity: 0.86

Amines

Chemical Structure| 40932-43-2

[ 40932-43-2 ]

2-Chloro-N-methylpyridin-3-amine

Similarity: 0.88

Chemical Structure| 39217-08-8

[ 39217-08-8 ]

2-Chloropyridine-3,4-diamine

Similarity: 0.88

Chemical Structure| 5632-81-5

[ 5632-81-5 ]

2-Chloropyridine-3,5-diamine

Similarity: 0.88

Chemical Structure| 78607-32-6

[ 78607-32-6 ]

3-Amino-2,5-dichloropyridine

Similarity: 0.88

Chemical Structure| 34552-13-1

[ 34552-13-1 ]

2-Chloro-5-methylpyridin-3-amine

Similarity: 0.86

Related Parent Nucleus of
[ 6298-19-7 ]

Pyridines

Chemical Structure| 40932-43-2

[ 40932-43-2 ]

2-Chloro-N-methylpyridin-3-amine

Similarity: 0.88

Chemical Structure| 39217-08-8

[ 39217-08-8 ]

2-Chloropyridine-3,4-diamine

Similarity: 0.88

Chemical Structure| 5632-81-5

[ 5632-81-5 ]

2-Chloropyridine-3,5-diamine

Similarity: 0.88

Chemical Structure| 78607-32-6

[ 78607-32-6 ]

3-Amino-2,5-dichloropyridine

Similarity: 0.88

Chemical Structure| 34552-13-1

[ 34552-13-1 ]

2-Chloro-5-methylpyridin-3-amine

Similarity: 0.86