Structure of 1421227-97-5
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 1421227-97-5 |
Formula : | C22H20N2O4S |
M.W : | 408.47 |
SMILES Code : | O=S(CC(C1=CC=C(C)N=C1)=O)(C2=CC=C(CC(C3=CC=C(C)N=C3)=O)C=C2)=O |
* 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 |
---|---|---|
In an anhydrified 4-neck flask there were introduced at 20-25C 5.0 g of (4-methylsulfonyl)phenyl acetic acid of formula (IV) and 100 mL of anhydrous THF and stirring is carried out at 20-25C. 1.0 g of sodium hydride dispersion in mineral oil (60% w/w, MW: 24.00; 1.1 molar equivalents) is added in portions in about 5 minutes, ensuring that the temperature does not exceed 45-50C. After completing the addition the mixture is heated to 65-70C for 1 hr. Maintaining at T=65-70C there are rapidly added 21 g (1.0 equiv.) of t-BuMgCl 1.0 M solution in THF (PM116.87) (23 mL). The mixture is left under stirring for 1 hr at 65-70C then is rapidly added, still at 65-70C, a solution of 1.78 g (0.5 equiv.) of methyl ester of the 6-methylpyridine-3-carboxylic acid of formula (III - R=Me) in 5 ml of Anhydrous THF. After completing the addition the mixture is maintained at 65-70C for 1 hr. Maintaining at T=65-70C there are rapidly added 10.5 g (0.5 equiv.) of t-BuMgCl 1.0 M solution in THF (PM 116.87) (11.5 mL). The mixture is left under stirring for 1 hr at 65-70C then there is rapidly added, still at 65-70C, a solution of 260 mg (0.075 equiv.) of methyl ester of 6-methylpyridine-3-carboxylic acid of formula (III - R=Me) in 1 mL of anhydrous THF. After completing addition the mixture is maintained at 65-70 C for 1 hr. Maintaining at T=65-70 C there are rapidly added 10.5 g (0.5 equiv.) of t-BuMgCl 1.0 M solution in THF (PM 116.87) (11.5 mL). The mixture is left under stirring for 1 hr at 65-70 C then there is rapidly added, still at 65-70 C, a solution of 260 mg (0.075 equiv.) of methyl ester of the 6-methylpyridine-3-carboxylic acid of formula (III - R=Me) in 1 mL of Anhydrous THF. After completing addition the mixture is maintained at 65-70 C for 1 hr. Cooling is carried out to 20-25C. The yield is calculated in solution through titration: 80%. The product is isolated according to the preceding example. It is obtained a molar yield equivalent to 73% and with 94.4% HPLC purity (A%) and amount of impurity '408' = 2.02% (A%) (see figure 4). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With tert-butylmagnesium chloride; In tetrahydrofuran; at 65 - 70℃; for 1.5h; | In a 4-neck anhydrous flask there are introduced at 20-25C, 10.2 g of Lithium (4-methylsulfonyl)phenyl acetate of formula (II- M=Li) (1.0 mol. equiv), 200 mL of Anhydrous THF and the mixture is heated to 65-70C (up to reflux). Maintaining at T=65-70 C there are simultaneously dosed in the mixture in about 1 hour: a) 66.0 g of t-BuMgCl 1.0 M solution in THF (about 74.2 mL) (1.6 mol. equiv.) andb) a solution of 4.64 g of the methyl ester of the 6-methylpyridine-3-carboxylic acid of formula (III - R=Me) (0.65 mol. equiv.) in 15 mL of Anhydrous THF. After completing the addition, the mixture is stirred at 65-70 C for 30 minutes. The reaction is controlled through HPLC then it is cooled to 20-25C and the reaction mixture is diluted under vigorous stirring with 100 mL of water. Maintaining the temperature comprised in the range between 20C and 25C the mixture is brought to pH comprised between 1 and 0 by adding about 15 mL of 32% hydrochloric acid. Stirring is carried out at 20-25C for 30 minutes controlling the pH. The phases are separated by putting aside the organic phase useful for recovering the lithium (4-methylsulfonyl)phenyl acetate. The aqueous phase is washed using 2x50 mL of MTBE and the organic phases are recombined and used for recovering the (4-methylsulfonyl)phenyl acetate lithium. The aqueous phase is distilled at low pressure for removing the residue organic solvent. The product is precipitated under heat (40-45C) by adding 7.5 mL of 30% aqueous NaOH followed by cooling to room temperature. The product is filtered and dried in an oven under vacuum at 50C for 8 hours. There are obtained 6.9 g of product as a white solid corresponding to a 78% molar yield. HPLC purity 96.9% (A%). Impurity '408' = 0.21% (HPLC %) (Figure 3). The organic phases obtained as described above are recombined to bring to a pH comprised between 11 and 12 by adding about 1 g of LiOH monohydrate solid. The mixture is concentrated to residue at low pressure at a maximum temperature of 40C. The residue is suspended at room temperature in 2 volumes of Methanol. Stirring is carried out at room temperature for at least 3 hours. The suspension is filtered and the solid is washed using cold methanol then dried at low pressure at 90C for 8 hours, to obtain 2.5 g of (4-methylsulfonyl)phenyl acetate lithium. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63.8% | With potassium tert-butylate; In tetrahydrofuran; for 3h;Reflux; | 1.74 g (6·0 mmol) of compound C, 1.36 g (9·0 mmol) of methyl 6-methylnicotinate, 1.01 g (9.0 mmol) of potassium t-butoxide were mixed with 21 mL of tetrahydrofuran, and heated to reflux. After the reaction was completed by 3h. TLC, 30 mL of water, 40 mL of dichloromethane was slowly added, and the liquid phase was separated, and the aqueous phase was extracted with dichloromethane (40 mL of X 2 ), dichloromethane was combined, washed twice with saturated brine, and the organic phase was separated. Drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and purified by column chromatography to yield 1.56 g of pale yellow solid, Compound D, yield 63.8% |
Tags: 1421227-97-5 synthesis path| 1421227-97-5 SDS| 1421227-97-5 COA| 1421227-97-5 purity| 1421227-97-5 application| 1421227-97-5 NMR| 1421227-97-5 COA| 1421227-97-5 structure
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