(5-METHYLPYRIDIN-3-YL)METHANOL

General Procedure for the Synthesis of Intermediate Benzylbromo bromides; [0116] Typical romides[0117] Step 1. Methyl 5-methylnicotinate (10 mmol, 1.52g) was dissolved in 50 Ml dried THF, then cooled to 0 deg with ice-bath. LiAlH4 (16 mmol, 0.61g) was added in small portions during about 20 minutes. The mixture stirred for another 20 minutes until the reaction was completed, which monitored by TLC. 1.5 mL water was dropwised into the mixture to quench the reaction, then filtered, solution was concentrated to get the (5-methylpyridin-3-yl)methanol, Yield was high to 85percentExample-2S2, Preparation of 5-methyl-3-pyridinemethanol:According to the molar portion of 2 parts of magnesium chloride, 2 parts of potassium borohydride, Tetrahydrofuran mixture, The temperature was raised to 67 ° C, Reflux 2h, Cooled to room temperature to obtain a solution B;Methyl 5-methyl nicotinate obtained in S1 was added to tetrahydrofuran for dissolution, Adjust the temperature to 40 , Solution B was added dropwise, Solution B was added dropwise within 1.3h, Insulation 1h, Dropping and insulation kept stirring process, Cooled to room temperature to obtain a solution C;The reaction was quenched by adding methanol, Warmed to 40 ° C, Rotary evaporation to remove tetrahydrofuran and methanol to give a concentrate D;After adding water to concentrate D, Add ethyl acetate extract, Co-extraction three times, The combined ethyl acetate phase, Add anhydrous sodium sulfate until the moisture content of 0.3wtpercentFiltering, taking ethyl acetate phase rotary evaporation 5-methyl-3-pyridine methanol;Typical procedures: 6-bromonicotinaldehyde (930 mg, 5.0 mmol), NaOAc (820 mg, 10.0 mmol), MeOH (30 mL), and PdClUnder nitrogen, the trichloromethyl chloroformate (1.98g, 10.00mmol) was dissolved in dry dichloromethane (10 mL), cooled to 0 deg C After stirring for 5 minutes, a solution of The mesylate of In a 100mL single-mouth bottle, Add the last step product, Hydrobromide (5 mL, 40%, 0.036 mol) was added dropwise under ice bath conditions.After the addition is completed, the solvent is removed by rotary evaporation.Obtaining a brown solid and adding an appropriate amount of tetrahydrofuran solution (the purpose of adding the tetrahydrofuran solution is to prevent the product from adhering to the container wall), Stir for half an hour, filter, Obtained a white solid (5.7g, 84.4%, above step yield)Example-3Synthesis of Rupatadine base (Formula-4) from Typical procedures: 6-bromonicotinaldehyde (930 mg, 5.0 mmol), NaOAc (820 mg, 10.0 mmol), MeOH (30 mL), and PdCl2 (45 mg) were mixed in a glass bottle capped with a balloon filled with hydrogen. After stirred at 35 C for 4 h, the mixture was filtered and washed with MeOH. The solvent was removed and the residue was dissolved in water, neutralized with solid NaHCO3, and extracted with ethyl acetate. The organic phase was dried over anhyd Na2SO4, and then filtered. The solvent was removed and the residue was subjected to chromatography to yield pyridin-3-ylmethanol (428 mg, 78%).Step 2.; Alcohol (10 mmol) were refluxed in 10ml HBr (40% aq) for more than 5 hours, and monitored through TLC or LC-MS. After completed, mixture were heated in order to evaporator solvents (water and excess HBr) until the mixture became sticky. Cool the mixture, add acetone to the mixture, precipitated solid and filtered followed by drying. Yield was high to80%.General Procedure for the Synthesis of Intermediate Benzylbromo bromides; [0116] Typical romides[0117] Step 1. Methyl 5-methylnicotinate (10 mmol, 1.52g) was dissolved in 50 Ml dried THF, then cooled to 0 deg with ice-bath. LiAlH4 (16 mmol, 0.61g) was added in small portions during about 20 minutes. The mixture stirred for another 20 minutes until the reaction was completed, which monitored by TLC. 1.5 mL water was dropwised into the mixture to quench the reaction, then filtered, solution was concentrated to get the Example-2Synthesis of S2, Preparation of Step 1: NaBH4 (3.31 g, 87.5 mmol) was added at rt to a solution of methyl 5-methylnicotinate (2.37 g, 15.7 mmol) in MeOH (50 mL). The mixture was stirred at rt for 6 h then heated overnight at reflux. The reaction was allowed to cool to rt then it was quenched by cautious addition of Na2504 10H20. The suspension was stirred for 2 h at rt, thenvolatiles were removed under reduced pressure. The residue was taken up in CH2C12, filtered and concentrated under reduced pressure to yield 1.85 g (97%) of crude (5-methylpyridin-3- yl)methanol which was used in next step without further purification. MS (m/z) 124 (M+H).In a 100mL three-neck bottle, Add the above product (3) methyl 5-methylnicotinate (5.0 g, 0.033 mol)And 50mL of methanol, Heated to 55 C, Sodium borohydride (4, 4 g, 0.12 mol) was added in small portions, and the solution changed from colorless to yellow.And a lot of bubbles are generated.Reaction at 55 C for 1 h, TLC showed the reaction was complete.An appropriate amount of water was added, and methanol was evaporated under reduced pressure. The residue was purified with ethyl acetate.The organic phase was dried over anhydrous sodium sulfate and the solvent was evaporated.A yellow liquid (4.2 g) was obtained without further purification.Used directly in the next step of the reaction.

Molecular Weight:123.15
XLogP3:0.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:123.068413911
Monoisotopic Mass:123.068413911
Topological Polar Surface Area:33.1
Heavy Atom Count:9
Complexity:85
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes