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Structure of 52426-66-1
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CAS No. : | 52426-66-1 |
Formula : | C7H8ClN |
M.W : | 141.60 |
SMILES Code : | CC1=NC=C(CCl)C=C1 |
MDL No. : | MFCD10697567 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H314 |
Precautionary Statements: | P264-P270-P271-P280-P303+P361+P353-P304+P340-P305+P351+P338-P310-P330-P331-P363-P403+P233-P501 |
Class: | 8 |
UN#: | 3265 |
Packing Group: | Ⅱ |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With thionyl chloride; In dichloromethane; for 0.5h; | To a stirred solution of (6-methyl-3-pyridinyl)methanol (166 mg, 1.35 mmol) in dichloromethane (10 ml) was added thionyl chloride (108 mul, 1.48 mmol) giving a colourless solution. After 30 minutes the mixture was concentrated giving a brown solid (240 mg, quant, yield) that was used directly in the next step without purification. 1H NMR (500 MHz, CDCl3) delta 8.79 (1 H, br. s.), 8.55 (1 H, dd, J=8.3, 1.6 Hz), 7.93 (1 H, d, J=8.4 Hz), 4.89 (2 H, s), 2.77 (3 H, s). |
With thionyl chloride; In water; toluene; at 35℃; | Example 4; Synthesis of. 4-(6-Methyl-pyridin-3-ylmethvD-morpholine from 5-chloromethyl-2-methyl- pyridine; To a solution of (6-methyl-3-pyridyl)-methanol (5Og, 0.506mol) in toluene (500ml) and water (9ml) at 35C under nitrogen was added thionyl chloride (66.9 ml, 1.06mol) dropwise After stirring at 35C overnight 300ml was distilled off under vacuum and rediluted with toluene (250ml) and water (10ml) to give a solution of 5-chloromethyl-2- methyl- pyridine_(J.Med.Chem, 2004, 47(11), 4787). The mixture was then heated to 400C <n="29"/>and morpholine (112.2ml, 1.29mol) added and the slurry heated to 800C for 3 hrs. After cooling to room temperature saturated sodium carbonate solution (150ml) was added and the aqueous phase separated and extracted with toluene (200ml). The combined organic layer was washed with brine and concentrated. The oil was dissolved in iso-octane (300ml) at 400C then cooled to -5C overnight. Two crops were obtained which gave 53.65g, 72% yield of 4-[(6-methylpyridin-3-yl)methyl]morpholine as a beige solid. 1H NMR (400MHz;CDCl3): delta 8.4 (d, J=I .72Hz, IH), 7.54 (dd, Z=2A,1.91Hz, IH), 7.1 (d, J=7.92Hz, IH), 3.68 (apparent t, J=4.6, 9.28Hz, 4H), 3.4 (s, 2H), 2.5 (s, 3H), 2.4 (apparent t, J=4.5,8.93Hz, 4H); 13C NMR: (100MHz, CDCl3): delta 157.3, 149.8, 137.2, 129.9, 122.9, 66.9, 60.3, 53.5, 24.1 ppm; MS (ESI) m/z 193 [M+l]+; Melting point: 51-52C. | |
With methanesulfonyl chloride; triethylamine; In dichloromethane; at 0 - 20℃; for 10.3333h; | Triethylamine (96 ml, 0.69 mol) was added to a solution of (6-methyl-3-pyridyl)methanol (28.4 g, 0.23 mol) in methylene chloride (230 ml) while cooling on ice. Mesyl chloride (26.8 ml, 0.35 mol) was then slowly added dropwise over a period of 20 minutes at the same temperature and the mixture was stirred for 10 hours while gradually raising the temperature to room temperature. After confirming completion of the reaction by thin layer chromatography, the mixture was diluted with ethyl acetate and poured into saturated aqueous NaHCO3. After separating the aqueous layer, extraction was performed with ethyl acetate, and the collected organic layer was washed with saturated aqueous NaCl and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to yield the title compound (12.2 g). This was used without further purification for the following reaction.1H-NMR(CDCl3)delta(ppm) 2.56(3H.s), 4.56(2H.s), 7.16(1H.d.J=8.0Hz), 7.62(1H.dd.J=8.0and2.4Hz), 8.49(1H.d.J=2.4Hz) |
In a 250ml round-bottomed flask at room temperature under nitrogen, (6-methyl-3- pyridinyl)methanol (4.32 g, 35.1 mmol, D8) was dissolved in dry dichloromethane (45 ml) to give a yellow solution, which was cooled down to 00C. Thionyl chloride (3 ml, 41.1 mmol) was then added. The resulting pale-orange mixture was stirred at 00C for 15 minutes and at room temperature for 2 hours. The mixture was concentrated in vacuum and the brown residue was partitioned between DCM (150 ml) and saturated NaHCO3 (100 ml). Phases were separated and the organic was washed with saturated NaHCO3 (2 x 100 ml), dried over Na2SO4, filtered and concentrated to give the desired compound as brown oil (4.26 g), that was used without further purification in the next step.UPLC/MS: Found 141.97,143.85 (ES+), retention time 0.29 mins. (chlorine pattern) C7H8CIN requires 141 for 35CI. | ||
With thionyl chloride; In dichloromethane; at 20℃; for 1h;Inert atmosphere; | To a stirred solution of (6-methylpyridin-3-yl)methanol (13 g) in DCM (260 mL), thionyl chloride (13 mL) was added slowly under nitrogen at RT. The mixture was stirred at RT for lh, the reaction was monitored by TLC and LCMS. After completion of reaction, the mixture was concentrated under reduced pressure, the residue was suspended in saturated aq. NaHCC"3 (pH 8) and extracted with DCM (2x100 mL). The organic layer was separated, dried over sodium sulfate and concentrated under vacuum to obtain 12.5 g of product as a yellow oil. | |
0.81 g | With thionyl chloride; In tetrahydrofuran; at 35℃;Cooling with ice; | A) 5- (chloromethyl) -2-methylpyridine To a solution of ( 6-methylpyridin-3-yl ) methanol (1.08 g) in THF (15.0 mL) was added thionyl chloride (1.57 g) under ice- cooling, and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with water and ethyl acetate, saturated aqueous sodium bicarbonate was added thereto, and the mixture was partitioned. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (0.81 g) . XH NMR (300 MHz, CDC13) delta 2.57 (3H, s) , 4.57 (2H, s) , 7.17 (1H, d, J = 7.9 Hz), 7.63 (1H, dd, J = 7.9, 2.3 Hz), 8.50 (1H, d, J = 2.3 Hz) . |
With methanesulfonyl chloride; triethylamine; In dichloromethane; at 20℃;Cooling with ice; | Example 2. N-((l-Aminoisoquinolin-6-yl)methyi)-3-(methoxymethyl)-1-((S-((4-methyl-1H-pyrazol-1- yl)methyl)pyridin-2-yl)methyl)-1H-pyrazoie-4-carboxamide 5-(Chloromethyl)-2-rnethylpyridine A solution of (6-methyipyridin-3-yl)methanol (5.04 g, 40.9 mmol) and triethylamine (7.99 mi, 57.3 mmol) in anhydrous DCM (85 mL) was cooled in an ice-bath before the addition of methanesutfonyl chloride (4.12 ml, 53.2 mmol) dropwise. On completion of the addition the ice-bath was removed and the mixture stirred at rt overnight. The reaction mixture was partitioned between DCM (100 mL) and sat. aq. NaHC03 (150 mL). The aqueous layer was extracted with further DCM (2 x 50 mL) and the combined organics dried (Na2SO4), filtered and concentrated in vacuo to afford 5-(chioromethyl)-2-methylpyridine (5.12 g, 87 % yield) which was used without further purification. MH+ = 141.9 | |
With thionyl chloride; In water; toluene; at 35℃; | a^ 4-rC6-methylpyridin-3-yDmethyl1morpholine; To a solution of (6-methyl-3-pyridyl)-methanol (5Og, 0.506mol) in toluene (500ml) and water (9ml) heated to 35C was added thionyl chloride (66.9 ml, 1.06mol) dropwise. After stirring at 35C over night 300ml was distilled off under vacuum and rediluted with toluene (250ml) and water (lthetaml)to give a solution of 5 '-chloromethyl-2-methyl- pyridine (J.MedChem, 2004, 47(11), 4787). The mixture was then heated to 40C and morpholine (112.2ml, 1.29mol) added and the slurry heated to 80C for 3 hrs. After cooling to room <n="23"/>temperature saturated sodium carbonate solution (150ml) was added and the aqueous phase separated and extracted with toluene (200ml). The combined organic layer was washed with brine and concentrated to give an oil. The oil was dissolved in iso-octane (300ml) at 40C then cooled to -5C overnight. Two crops were obtained which gave 4-[(6- methylpyridin-3-yl)methyl]morpholine as a solid (53.65g, yield: 72%). H NMR(400MHz;CDCl3): delta 8.4 (d, J=1.72Hz, IH), 7.54 (dd, 1=2.1, 1.9 IHz, IH), 7.1 (d, J=7.92etaz, IH), 3.68 (apparent t, J=4.6, 9.28Hz, 4H), 3.4 (s, 2H), 2.5 (s, 3H), 2.4 (apparent t, J=4.5,8.93Hz, 4H); MS (ESI) m/z 193 (M+l)+; Melting point: 51-52C. |
Tags: 52426-66-1 synthesis path| 52426-66-1 SDS| 52426-66-1 COA| 52426-66-1 purity| 52426-66-1 application| 52426-66-1 NMR| 52426-66-1 COA| 52426-66-1 structure
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