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[ CAS No. 70258-18-3 ] {[proInfo.proName]}

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Product Details of [ 70258-18-3 ]

CAS No. :70258-18-3 MDL No. :MFCD00125366
Formula : C6H5Cl2N Boiling Point : -
Linear Structure Formula :- InChI Key :SKCNYHLTRZIINA-UHFFFAOYSA-N
M.W :162.02 Pubchem ID :155479
Synonyms :

Calculated chemistry of [ 70258-18-3 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.17
Num. rotatable bonds : 1
Num. H-bond acceptors : 1.0
Num. H-bond donors : 0.0
Molar Refractivity : 39.01
TPSA : 12.89 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.73 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.83
Log Po/w (XLOGP3) : 2.2
Log Po/w (WLOGP) : 2.32
Log Po/w (MLOGP) : 1.75
Log Po/w (SILICOS-IT) : 2.97
Consensus Log Po/w : 2.21

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.66
Solubility : 0.356 mg/ml ; 0.0022 mol/l
Class : Soluble
Log S (Ali) : -2.1
Solubility : 1.27 mg/ml ; 0.00786 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.65
Solubility : 0.0362 mg/ml ; 0.000223 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.6

Safety of [ 70258-18-3 ]

Signal Word:Danger Class:8
Precautionary Statements:P260-P264-P270-P280-P301+P312+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P363-P405-P501 UN#:3261
Hazard Statements:H302-H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 70258-18-3 ]

* 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 [ 70258-18-3 ]
  • Downstream synthetic route of [ 70258-18-3 ]

[ 70258-18-3 ] Synthesis Path-Upstream   1~38

  • 1
  • [ 70258-18-3 ]
  • [ 108-59-8 ]
  • [ 55676-22-7 ]
YieldReaction ConditionsOperation in experiment
68%
Stage #1: With triethylamine; magnesium chloride In toluene at 25℃; for 1 h;
Stage #2: for 1 h;
Stage #3: With water In dimethyl sulfoxide at 165℃; for 2 h;
EXAMPLE 1
5-Acetyl-2-chloropyridine
Triethylamine (19 mL, 0.14 mol) and dimethyl malonate (7.8 mL, 59 mmol) were added to a round bottom flask containing magnesium chloride (3.8 g, 40 mmol) in anhydrous toluene (46 mL).
The mixture was stirred at 25°C for 1 h.
A solution of 6-chloronicotinyl chloride (10 g, 57 mmol) in anhydrous toluene (50 mL) was slowly added to the mixture.
The reaction was stirred for 1 h, then concentrated HCl (16 mL) was slowly added to the reaction.
Diethyl ether (300 mL) was added and the organic layer was washed with water (2 x 100 mL).
The organic layer was dried (MgSO4), filtered, and concentrated to afford an oil.
The product was stirred in hexanes (200 mL), eventually forming an off-white powder (12.7 g).
The powder was treated with dimethyl sulfoxide (31 mL) and water (1 mL).
The reaction was stirred and heated to 165°C for 2 h.
The reaction was cooled to room temperature, diluted with diethyl ether (250 mL), and washed with water (4 x 200 mL).
The organic layer was dried (MgSO4), filtered, and concentrated to afford a white solid.
The product was passed through a pad of silica (5percent diethyl ether/hexane) to yield a white solid (6.0 g, 68percent). Rf = 0.2 (CH2Cl2); mp 100-102°C; 1H NMR (300 MHz, CDCl3) δ 8.94 (s, 1 H), 8.20 (dd, J = 6, 9 Hz, 1 H), 7.44 (d, J = 8 Hz, 1 H), 2.63 (s, 3 H); MS (EI) mlz 155 (M+).
Reference: [1] Patent: EP1054881, 2008, B1, . Location in patent: Page/Page column 25
  • 2
  • [ 773837-37-9 ]
  • [ 70258-18-3 ]
  • [ 39891-09-3 ]
YieldReaction ConditionsOperation in experiment
85% at 20℃; for 20 h; Reflux Example 46 (1 R)-1-(6-amιno-Pyrιdιn-3-yl-acetyl amιno)-2-(2-hvdroxy-3-carboxyphenyl)ethyl-1- boronic acid formateStep 1. Synthesis of (6-chloropyridin-3-yl) acetonitrite. To a solution of 2-chloro-5-(chloromethyl)pyrιdιne (25 g, 0 154 mol) in ethanol (40 mL) stirring at 0 °C was added a solution of sodium cyanide (8 17 g 0 167 mol) in water (18 mL) The reaction mixture was refluxed for 2 hours then stirred at ambient temperature for a further 18 hours The solvent was evaporated in vacuo and the residue extracted from water into DCM (500 mL), washed with brine dned over sodium sulfate, filtered and evaporated in vacuo The crude material was purified by column chromatography over silica gel eluting with 70/30 DCM/hexanes to afford 20 g (85percent) of product as brown oil which solidified on standing ESI-MS m/z 153 (MH)*
63% at 0 - 100℃; for 3 h; To a stirred solution of 2-chloro-5-(chloromethyl)pyridine (1 g, 6.17 mmol, 1.0 equiv.) in ethanol (10 ml_) was added the solution of NaCN (325 mg, 6.79 mmol, 1.1eq) in H20 (10 mL) dropwise at 0°C and stirred for 3h at 100 °C. The reaction mixture was diluted with water (50ml), extracted with ethyl acetate (70ml_x2) washed with brine (20mL), dried over anhydrous Na2S04 and evaporated under vacuum. The crude was purified by using silica gel chromatography (100-200 mesh) using ethyl acetate /petrol ether (3:7) to get 2-(6- chloropyridin-3-yl)acetonitrile (400 mg, 63 percent) as a yellow solid.
63% at 0 - 100℃; for 3 h; To a stirred solution of 2-chloro-5-(chloromethyl)pyridine (1 g, 6.17 mmol, 1.0 eq) in ethanol (10 mL) was added the solution of NaCN (325 mg, 6.79 mmol, 1.1 eq) in water (10 mL) dropwise at 0 °C and then stirred for 3 h at 100 °C. The reaction mixture was diluted with water (50 mL), extracted with ethyl acetate (2 x 70 mL) washed with brine (20 mL). The organic layer was dried over anhydrous sodium sulphate and evaporated under vacuum. The crude was purified by using silica gel chromatography (100-200 mesh) using ethyl acetate /petrol ether (3:7) to get 2-(6-chloropyridin-3-yl)acetonitrile (400 mg, 63 percent) as a yellow solid.
63% at 0 - 100℃; for 3 h; Step 1:
To a stirred solution of 2-chloro-5-(chloromethyl)pyridine (1 g, 6.17 mmol, 1.0 equiv.) in ethanol (10 mL) was added the solution of NaCN (325 mg, 6.79 mmol, 1.1 eq) in H2O (10 mL) dropwise at 0° C. and stirred for 3 h at 100° C.
The reaction mixture was diluted with water (50 ml), extracted with ethyl acetate (70 mL*2) washed with brine (20 mL), dried over anhydrous Na2SO4 and evaporated under vacuum.
The crude was purified by using silica gel chromatography (100-200 mesh) using ethyl acetate/petrol ether (3:7) to get 2-(6-chloropyridin-3-yl)acetonitrile (400 mg, 63percent) as a yellow solid.
63% at 0 - 100℃; for 3 h; Step 1
To a stirred solution of 2-chloro-5-(chloromethyl)pyridine (1 g, 6.17 mmol, 1.0 eq) in ethanol (10 mL) was added the solution of NaCN (325 mg, 6.79 mmol, 1.1 eq) in water (10 mL) dropwise at 0° C. and then stirred for 3 h at 100° C.
The reaction mixture was diluted with water (50 mL), extracted with ethyl acetate (2*70 mL) washed with brine (20 mL).
The organic layer was dried over anhydrous sodium sulfate and evaporated under vacuum.
The crude was purified by using silica gel chromatography (100-200 mesh) using ethyl acetate/petrol ether (3:7) to get 2-(6-chloropyridin-3-yl)acetonitrile (400 mg, 63percent) as a yellow solid.
21 g With sodium carbonate In ethanol for 4 h; Reflux 16.2 g 2-chloropyridine benzyl chlorine, 5.1 g of sodium cyanide are added to a 250 ml four-mouthed flask. Add 150 ml ethanol, 11 g sodium carbonate. Heat to reflux. Reflux reaction for 4 hours. After the reaction, prolapsed ethanol, add 100 g water and stirred, filtered to obtain 21 g 2-chloropyridine acetonitrile.

Reference: [1] Patent: WO2010/130708, 2010, A1, . Location in patent: Page/Page column 105
[2] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 7, p. 2168 - 2173
[3] Patent: WO2013/13817, 2013, A1, . Location in patent: Page/Page column 111
[4] Patent: WO2013/13815, 2013, A1, . Location in patent: Page/Page column 221
[5] Patent: US2013/29961, 2013, A1, . Location in patent: Paragraph 0705
[6] Patent: US2013/29962, 2013, A1, . Location in patent: Paragraph 1077; 1085
[7] Journal of the American Chemical Society, 2013, vol. 135, # 16, p. 6289 - 6299
[8] Journal of Medicinal Chemistry, 2014, vol. 57, # 3, p. 1079 - 1089
[9] Patent: CN105669584, 2016, A, . Location in patent: Paragraph 0079; 0080; 0081
  • 3
  • [ 70258-18-3 ]
  • [ 143-33-9 ]
  • [ 39891-09-3 ]
YieldReaction ConditionsOperation in experiment
96% at 0 - 100℃; for 20 h; To a solution of 2-chloro-5-(chlofomethyl)pyridine (75g, 0.46mol) in ethanol (120ml) stirring at O0C, was added a solution of sodium cyanide (24.5Og, 0.50mol) in water (40ml). The reaction mixture heated at 10O0C for 2 hours then stirred at room temperature for a further 18 hours. The solvent was evaporated in vacuo and the residue extracted from water into dichloromethane (500ml), washed with brine, dried over sodium sulphate, filtered and evaporated in vacuo. The crude material was purified by column chromatography over silica gel eluting with dichloromethane. The title compound was obtained as a brown oil which solidified on standing (67g, 0.44mol, 96percent). 1H-NMR (CDCl3, 400MHz); δ 3.7 (s, 2H), 7.4 (d, 1H), 7.65 (d, 1H), 8.4 (s, 1H).
45.6% With potassium iodide In ethanol; water at 85℃; for 5 h; 1.17.a
(6-chloro-pyridin-3-yl)-acetonitrile
A solution of 7.5 g (41.66 mmol) of 2-chloro-5-chloromethyl-pyridine, dissolved in 100 ml of ethanol, is added dropwise to a solution of 6.91 g (41.66 mmol) of potassium iodide and 2.24 g (49.01 mmol) of sodium cyanide in 400 ml of an ethanol/water mixture (9:1).
Then the reaction mixture is heated to 85° C. for five hours.
The solvent is substantially distilled off in vacuo and the residue is extracted with water and ethyl acetate.
The organic phase is washed with water three times and dried over sodium sulphate.
The purification is carried out by column chromatography on silica gel (eluant: dichloromethane/ethanol).
Yield: 2.9 g (45.6percent of theory);
C7H5ClN2 (M=152.58);
calc.: molar peak (M+H)+: 151/153 fnd.: molar peak (M+H)+: 151/153.
Reference: [1] Patent: WO2007/45989, 2007, A1, . Location in patent: Page/Page column 9; 24
[2] Patent: US2004/242572, 2004, A1, . Location in patent: Page/Page column 44
[3] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 4, p. 864 - 868
  • 4
  • [ 70258-18-3 ]
  • [ 151-50-8 ]
  • [ 39891-09-3 ]
YieldReaction ConditionsOperation in experiment
89% at 20 - 50℃; To a solution of 2-chloro-5-(chloromethyl)pyridine (5.0 g, 0.031 mol) in ethanol (38 mL) and water (19 mL) was added potassium cyanide (2.41 g, 0.0370 mol) at RT under nitrogen atmosphere.
The reaction mixture was stirred at 50° C. overnight.
The reaction was diluted with water and extracted with DCM.
The organic layer was washed with brine and dried over sodium sulfate.
The solution was filtered and the filtrate was concentrated to afford the desired compound (4.2 g, 89percent).
Analytical LCMS: (M+H)+=153.1.
Reference: [1] Patent: US2008/39457, 2008, A1, . Location in patent: Page/Page column 39
  • 5
  • [ 70258-18-3 ]
  • [ 39891-09-3 ]
YieldReaction ConditionsOperation in experiment
92% at 50℃; for 20 h; A solution of 5.2 g (32 MMOL) of 2-chloro-5-chloromethylpyridine dissolved in 40 mL of ethanol was treated with 20 mL of water and 2.4 g (37 MMOL) of potassium cyanide. The mixture was stirred and heated at 50 °C for 20 hours. The dark mixture was then partitioned between DICHLOROMETHANE and water and the organic layer was washed with brine and dried over sodium sulfate. The solvent was removed under reduced pressure to yield 4.54 g (92percent) of Preparatory Compound E, (6-chloro-3- pyridinyl) acetonitrile, as a dark brown liquid :'H NMR (CDCI3) 8 8.38 (d, J = 3.0 Hz, 1H), 7.71 (dd, J = 3.0 and 7.6 Hz, 1H), 7.42 (d, J = 7.6 Hz, 1H), 3.80 (s, 2H) ppm. GCMS: (EI) m/z 152 (M+).
Reference: [1] Patent: WO2004/57960, 2004, A2, . Location in patent: Page 16
  • 6
  • [ 70258-18-3 ]
  • [ 39891-09-3 ]
Reference: [1] Patent: US4966902, 1990, A,
  • 7
  • [ 70258-18-3 ]
  • [ 124-38-9 ]
  • [ 39891-13-9 ]
YieldReaction ConditionsOperation in experiment
74.3% at 40℃; for 15 h; Autoclave S1: taking 8.72 mmol of 2-chloro-5-chloromethylpyridine catalyst and solvent DMF into the reaction kettle;S2: Carbon dioxide was introduced to make the pressure in the autoclave 3 MPa, and the reaction was adjusted at 40 ° C for 15 hours.S3: acidification was carried out by adding dilute hydrochloric acid to the reaction vessel, ethyl acetate was extracted, the organic phase was combined, and the liquid was removed by rotary evaporation.Further drying in vacuo to give 6-chloro-3-pyridine acetic acidThe catalyst comprises zinc powder and lithium chloride, a chloromethyl heterocyclic compound and zinc powder, and a molar ratio of lithium chloride to the reaction vessel is 1:3:3.2.8 to 2.9 ml of solvent DMF was added per mmol of 2-chloro-5-chloromethylpyridine.
Reference: [1] Patent: CN108218768, 2018, A, . Location in patent: Paragraph 0015-0020; 0024
  • 8
  • [ 70258-18-3 ]
  • [ 39891-13-9 ]
Reference: [1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 4, p. 864 - 868
  • 9
  • [ 70258-18-3 ]
  • [ 23100-12-1 ]
YieldReaction ConditionsOperation in experiment
81% With sodium dihydrogenphosphate; potassium bromide In dimethyl sulfoxide; toluene at 90 - 100℃; Inert atmosphere Take 50g of raw material 2-chloro-5-chloromethyl pyridine,Soluble in 100g DMSO and 200g tolueneAdd 48g of sodium dihydrogen phosphate,3g of potassium bromide. Stirring,Nitrogen was bubbled under the liquid surface.Warm up to 90100°C reaction.After the reaction was completed, it was briefly distilled under reduced pressure and purified by distillation. The distillate was added with 50 g of water and 100 g of methyl tert-butyl ether (MTBE). The mixture was washed and separated, and the MTBE was recovered from the organic phase to obtain 2-chloro-5-aldehyde pyridine, which was weighed 35.6 g and the molar yield was about 81percent.
Reference: [1] Patent: CN107698497, 2018, A, . Location in patent: Paragraph 0072; 0073; 0074; 0077; 0080; 0083
  • 10
  • [ 70258-18-3 ]
  • [ 21543-49-7 ]
Reference: [1] Synthetic Communications, 2011, vol. 41, # 19, p. 2859 - 2869
[2] Patent: US5225423, 1993, A,
  • 11
  • [ 150807-86-6 ]
  • [ 70258-18-3 ]
YieldReaction ConditionsOperation in experiment
97% With phosgene In toluene at 50℃; for 6 h; 18 g (0.1 mol) of 2-chloro-2-chloromethyl-4-cyanobutanal were addedDissolved in 50 ml of toluene,A solution of 33 g (1.1 eqiv)Solid phosgene toluene solution,The reaction was incubated at 50 ° C for 5 hours. Cooling crystallization,Acetamiprid intermediate 2-chloro-5-chloromethylpyridine, yield 97percent.Then methylated, esterified to synthesize acetamiprid original drug,Yield 95percent.
79.5% at 105 - 110℃; for 0.283333 h; Mix 9000g (about 50mol) of 2-chloro-2-chloromethyl-4-cyanobutyraldehyde and 32000ml of chlorobenzene,Dissolve 2870 g (about 9.66 mol) (CCl3)2CO3 with 14000 ml of chlorobenzene.Proportional to the use of the pump to drive the two materials simultaneously into the heating device,0.1m2 continuous reactor equipped with reflux condenser and thermometer at the outletThe reactor outlet material temperature was controlled at 105°C.One-stage reactor outlet sampling, GC analysis, solvent peak deducted,Unreacted 2-chloro-2-chloromethyl-4-cyanobutyraldehyde 1.8percent,2-chloro-5-chloromethylpyridine 87.5percent, (CCl3)2CO 31.6percent.After the material passes through the primary reactor, it is heated toA 0.15m2 secondary reactor equipped with a reflux condenser and thermometer at the outletControl and control the temperature between 105 ~ 110 °C.Secondary reactor outlet sampling, GC analysis, solvent peak deducted,Unreacted 2-chloro-2-chloromethyl-4-cyanobutanal 0.08percent,2-chloro-5-chloromethylpyridine 92.1percent, (CCl3)2CO 31.1percent. Hydrogen chloride tail gas is absorbed by lye.After about 17 minutes, the material enters with mechanical stirring, reflux condenser,Thermometer 20000ml hydrolysis neutralizer with overflowA 10percent Na2CO3 solution was added to the bottle in proportion to control the pH to 7.5-8.Then divide the neutralized material into water,The aqueous layer was extracted twice with chlorobenzene, and the organic layer and the extract were combined and distilled after desolvation under reduced pressure.Collect fractions at 100 to 105 °C (750 mmHg vacuum),This gave 6763 g of 2-chloro-5-chloromethylpyridine. GC analysis, content 95.2percent, yield 79.5percent.
Reference: [1] Patent: CN106699646, 2017, A, . Location in patent: Paragraph 0012; 0013; 0014; 0015; 0016; 0017; 0018-0020
[2] Patent: CN107746386, 2018, A, . Location in patent: Paragraph 0022; 0023; 0024
  • 12
  • [ 18368-64-4 ]
  • [ 70258-18-3 ]
YieldReaction ConditionsOperation in experiment
93.5% at 115 - 120℃; for 5.5 h; Chloro-5-methylpyridine 350g, was added to a 500ml four-necked flask under stirring and heating 115-120 conditions,Into the chlorine reaction 5.5 hours,Control analysis of 2-chloro-5-dichloropyridine <3wtpercentAfter stopping the reaction cooling down,Analysis of feed solution 2-chloro-5-methyl pyridine,2-Chloro-5-chloromethylpyridineAnd 2-chloro-5-dichloromethyl pyridine content,Chloro-5-chloromethylpyridine (calculated as 2-chloro-5-methylpyridine)The yield was 93.5percent.
105.6 kg at 50 - 60℃; UV-irradiation the above-obtained oil layer is mixed with 2-chloro-5-chloromethylpyridine of equal quality, 350 g of azobisisobutyronitrile, and chlorine, and the temperature of the mixture is maintained at 50-60° C., flowing through the ultraviolet light. In the tube reactor, the reaction was completed, 200 kg of water was washed, and the mixture was allowed to stand for delamination to obtain 105.6 kg of 2-chloro-5-chloromethylpyridine liquid having a purity of 99.6percent. The yield was 96.7percent (based on the conversion of 3-methylpyridine. ).
Reference: [1] Patent: CN106243019, 2016, A, . Location in patent: Paragraph 0010; 0011; 0012; 0013; 0014
[2] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 14, p. 4163 - 4167
[3] Patent: CN105801472, 2016, A, . Location in patent: Paragraph 0004; 0007
[4] Patent: CN107739331, 2018, A, . Location in patent: Paragraph 0019; 0020; 0021; 0023; 0024; 0025
  • 13
  • [ 108-77-0 ]
  • [ 150807-86-6 ]
  • [ 70258-18-3 ]
YieldReaction ConditionsOperation in experiment
85.8% With N,N-dimethyl-formamide In toluene at 90 - 100℃; for 2.5 h; Take the compound CCC 0.1mol,Dissolved in 20 ml of toluene,The oil bath was heated to 90 ° C,6.6 g of catalyst N, N-dimethylformamide,A 40 ml portion of toluene solution containing 14.74 g (0.08 mol) of cyanuric chloride was added dropwise,Keep the temperature between 90-100 ° C,Dropping 2h,100 for 30 minutes,Then cooled to 50 ° C,Add 10 ml of water,Then 10.7 g of an aqueous solution of 30percent NaOH was added dropwise at 20-50 ° C,The pH of the aqueous phase is about 8.0-10.0,Start filtering,The filter cake was rinsed with 10 ml of toluene,The separated filtrate was allowed to stand,The upper layer is toluene,De-dissolving,18.4 g of a brown solid,GC internal standard detection containing CCMP 75.4percentYield 85.8percent.
Reference: [1] Patent: CN106699647, 2017, A, . Location in patent: Paragraph 0076-0096
  • 14
  • [ 109205-68-7 ]
  • [ 70258-18-3 ]
YieldReaction ConditionsOperation in experiment
95% With phosphorus pentachloride In chloroform; water; trichlorophosphate EXAMPLE 4
Production of 2-chloro-5-chloromethyl-pyridine
A solution of 2.5 g (20 mmol) of 2-hydroxy-5-hydroxymethylpyridine and 4.16 g of phosphorus pentachloride in 10 ml of phosphoryl chloride was stirred for 6 hours at 105° C.
After cooling, 50 ml of chloroform was added, the excess chlorination reagent being hydrolyzed by careful addition of water.
The organic phase was washed with NaHCO3 solution, dried on NaSO4 and concentrated by evaporation.
The distillation of the oily residue at 16 mm and 120° C. yielded 3.08 g of 2-chloro-5-chloromethyl-pyridine as a colorless oil that solidified during the cooling.
The latter corresponds to a yield of 95 percent relative to the 2-hydroxy-5-hydroxymethyl-pyridine.
Further data concerning the product was:
1 H-NMR: (CDCl3, 300 MHz) δ in ppm: 8.28 (d, J=2.3 Hz, 1H, H-6); 7.72 (dd, J=8.2 Hz, J=2.3 Hz, H-4); 7.34 (d, J=8.2 Hz, 1H, H-3); 4.58 (s, CH2 Cl, 2H).
Reference: [1] Patent: US6022974, 2000, A,
  • 15
  • [ 21543-49-7 ]
  • [ 70258-18-3 ]
Reference: [1] Journal of Medicinal Chemistry, 2000, vol. 43, # 18, p. 3386 - 3399
[2] Patent: US5225423, 1993, A,
[3] Patent: US4966902, 1990, A,
[4] Journal of the American Chemical Society, 2013, vol. 135, # 16, p. 6289 - 6299
[5] Patent: WO2013/82661, 2013, A1, . Location in patent: Page/Page column 28
[6] Chemistry - A European Journal, 2013, vol. 19, # 48, p. 16342 - 16356
[7] Journal of the American Chemical Society, 2013, vol. 135, # 43, p. 16120 - 16132
[8] Journal of Medicinal Chemistry, 2014, vol. 57, # 3, p. 1079 - 1089
  • 16
  • [ 108-99-6 ]
  • [ 70258-18-3 ]
YieldReaction ConditionsOperation in experiment
51% at 250 - 282℃; for 0.25 h; Inert atmosphere General procedure: Chlorination reaction:Take 20g of the above-prepared PdCl2/Al2O3 catalyst,It is added to a quartz tube tube reactor with a length of 20cm and a diameter of 2.4cm.Catalyst bed height 8cm,The resistance wire is turned on until the temperature of the catalyst layer is stable at 250°C.Feed nitrogen (flow rate 200mL/min),3-methylpyridine (flow rate 10 g/h, temperature 200 °C),After mixing with chlorine gas (flow rate 200mL/min), it enters the catalyst layer for chlorination reaction.Stay time 5s,The reaction temperature automatically rises to 280°C±2°C and remains stable. About 15min reaction system reaches steady state,Collect samplesThe yield of 2-chloro-5-chloromethylpyridine was analyzed by gas chromatography.51percent (based on 3-methylpyridine).
Reference: [1] Patent: CN107628989, 2018, A, . Location in patent: Paragraph 0023; 0027; 0029; 0031; 0036; 0041; 0043
[2] Patent: CN105801472, 2016, A,
  • 17
  • [ 109205-68-7 ]
  • [ 70258-18-3 ]
Reference: [1] Patent: US4958025, 1990, A,
  • 18
  • [ 5326-23-8 ]
  • [ 70258-18-3 ]
Reference: [1] Patent: US5225423, 1993, A,
[2] Patent: WO2013/82661, 2013, A1,
[3] Journal of the American Chemical Society, 2013, vol. 135, # 43, p. 16120 - 16132
  • 19
  • [ 150807-86-6 ]
  • [ 10026-13-8 ]
  • [ 70258-18-3 ]
Reference: [1] Patent: US5229519, 1993, A,
  • 20
  • [ 58584-63-7 ]
  • [ 761-65-9 ]
  • [ 70258-18-3 ]
Reference: [1] Patent: US4990622, 1991, A,
  • 21
  • [ 21543-49-7 ]
  • [ 107-06-2 ]
  • [ 70258-18-3 ]
Reference: [1] Patent: US5084459, 1992, A,
  • 22
  • [ 73781-91-6 ]
  • [ 70258-18-3 ]
Reference: [1] Journal of Medicinal Chemistry, 2000, vol. 43, # 18, p. 3386 - 3399
[2] Journal of the American Chemical Society, 2013, vol. 135, # 16, p. 6289 - 6299
[3] Journal of Medicinal Chemistry, 2014, vol. 57, # 3, p. 1079 - 1089
  • 23
  • [ 150807-87-7 ]
  • [ 70258-18-3 ]
Reference: [1] Patent: US5229519, 1993, A,
  • 24
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Reference: [1] Patent: US5116993, 1992, A,
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YieldReaction ConditionsOperation in experiment
144.9 g With hydrogen bromide; acetic acid In toluene at 90 - 100℃; for 10 h; Sealed tube Take 100g raw material 2-chloro-5-chloromethyl pyridine and 200g of toluene was added to the reaction flask, 25percent hydrobromic acidSolution 400g. Heating to 90 ~ 100 . The reaction for 10 hours, desolventizing. The residue was taken up in 200 g of DCM and adjusted to pH = 6-8 with 10percent NaOH solution. The solution was separated and the organic phase was obtained. The DCM was removed by desolvation. The residue is 2-bromo-5-bromomethylpyridine, mass 144.9g, content of 93percent.
Reference: [1] Patent: CN107253930, 2017, A, . Location in patent: Paragraph 0077; 0080; 0083; 0086; 0089
  • 31
  • [ 70258-18-3 ]
  • [ 69045-83-6 ]
YieldReaction ConditionsOperation in experiment
562 g at 275℃; for 60 h; 500 g (3.08 mol) of 2-chloro-5-chloromethylpyridine (molecular weight: 162 g / mol) and 50 g (10percent by weight) of copper oxide were charged into a 1 L four-necked flask equipped with a thermometer, a condenser and a mechanical stir And heated to 275 ° C, and then chlorinated by passing Cl 2 into the above solution, and the reaction was carried out for 60 hours to obtain 562 g (2.12 mol) of 2,3-dichloro-5-trichloromethylpyridine. A solution of 562 g (2.12 mol) of 2,3-dichloro-5-trichloromethylpyridine was heated to 70 ° C and added with 5 g of catalyst antimony pentachloride followed by 210 g (10.5 mol) of hydrogen fluoride at 200 ° C, 8.5 MPa pressure for 30 hours to give 421 g (1.95 mol) of 2,3-dichloro-5-trifluoromethylpyridine in a yield of 63.2percent from 2-chloro-5-chloromethylpyridine,
Reference: [1] Patent: CN104557683, 2016, B, . Location in patent: Paragraph 0021; 0022
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  • [ 149806-06-4 ]
Reference: [1] Patent: CN107698497, 2018, A,
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Reference: [1] Patent: WO2010/130708, 2010, A1,
  • 34
  • [ 70258-18-3 ]
  • [ 124-40-3 ]
  • [ 54864-83-4 ]
YieldReaction ConditionsOperation in experiment
97% at 0 - 20℃; A tetrahydrofuran solution (14.2 ml, 28.4 mmol) of 2M-N,N-dimethylamine was added to a methylene chloride solution (17 ml) of 6-chloronicotinyl chloride (1.00 g, 5.68 mmol), at 0°C, and stirring was carried out at room temperature overnight. The reaction solution was concentrated and the resulting residue was diluted with methylene chloride, followed by sequential washing with water and saline, and the resulting organic layer was dried over anhydrous sodium sulfate. The organic layer was concentrated and the resulting residue was purified by silica gel column chromatography to afford 6-chloro-N,N-dimethylnicotinamide (1.02 g, yield 97percent) as a pale red oil. 1H-NMR (CDCl3, 400 MHz) δ: 8.47 (1H, d, J=2.4 Hz), 7.75 (1H, dd, J=8.2 Hz, 2.4 Hz), 7.40 (1H, d, J=8.2 Hz), 3.13 (3H, s), 3.03 (3H, s). MS (ESI, m/z): 185 (M+H)+.
Reference: [1] Patent: EP2258697, 2010, A1, . Location in patent: Page/Page column 72
  • 35
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  • [ 97004-04-1 ]
Reference: [1] Patent: US5084459, 1992, A,
[2] Patent: CN103242225, 2016, B,
[3] Patent: , 2016, , . Location in patent: Paragraph 0004; 0007
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Reference: [1] Patent: CN104788378, 2017, B, . Location in patent: Paragraph 0057; 0058; 0060
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  • [ 717106-69-9 ]
Reference: [1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 4, p. 864 - 868
  • 38
  • [ 5308-25-8 ]
  • [ 70258-18-3 ]
  • [ 1180132-17-5 ]
YieldReaction ConditionsOperation in experiment
94% at 60 - 70℃; for 2 h; Green chemistry 2-Chloro-5-chloromethylpyridine (162 g, 1.0 mol), tap water 300 mL, and N-ethylpiperazine (171 g, 1.5 mol) were added to a 1 L reaction flask.Raise to 60-70 ° C, stir for 2 h, cool to room temperature,Potassium carbonate (138 g, 1.0 mol) was added and stirred for 10 minutes, the aqueous phase was separated, and dried to give 225 g of product, yield 94percent.
Reference: [1] Patent: CN108440401, 2018, A, . Location in patent: Paragraph 0014; 0032-0040; 0047; 0048
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