Structure of 775304-79-5
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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. : | 775304-79-5 |
Formula : | C9H10N2O3 |
M.W : | 194.19 |
SMILES Code : | O=C(OC)C1=CC=CC(C(NO)=N)=C1 |
MDL No. : | MFCD22413692 |
* 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 hydroxylamine; In methanol; at 70℃; for 1.5h; | Into a 1000-mL round-bottom flask, was placed <strong>[13531-48-1]methyl 3-cyanobenzoate</strong> (20 g, 124.10 mmol, 1.00 equiv), methanol (200 mL), and 50percent NH2OH (10 mL). The resulting solution was stirred for 1.5 h at 70 oC in an oil bath. The resulting mixture was concentrated under vacuum. This resulted in 24 g (100percent) of methyl (Z)-3-(N'- hydroxycarbamimidoyl)benzoate as a tan solid. |
95% | With hydroxylamine; In ethanol; water;Reflux; | General procedure: To a solution of cyanide (8.0 mmol) in 20 mL ethanol was added hydroxylamine (solution 50percent in water) (4.0 mL) at room temperature. Thereaction mixture was stirred atreflux for 3 to 4 hours until the nitriles were completed converted(monitored by TLC). The mixture solution was evaporated and extracted withdichloromethane (10 mL×3). The combined organic layers were washed with brine(10 mL), dried over anhydrous Na2SO4, filtered andconcentrated to give the crude product, which was further purified by columnchromatography to afford compounds 4and 8. |
With hydroxylamine; In water; tert-butyl alcohol; at 40 - 45℃; for 6.75 - 7.66667h;Product distribution / selectivity; | Methyl 3-[5-(2-fluorophenvn-[l,2,41oxadiazol-3-yll-benzoate [0153] Batch 1[0154] Methyl 3-cyanobenzoate (105 kg) and molten terf-butanol were charged to a dry reactor. 50percent aqueous hydroxylamine (43L, 47.4 kg) was added to the clear solution of <strong>[13531-48-1]methyl 3-cyanobenzoate</strong> in molten ter/-butanol in an inert atmosphere over about 2 hours and 48 minutes. The maximum batch temperature during the addition of 50percent aqueous hydroxylamine was about 430C. The addition rate of 50percent aqueous hydroxylamine varied from about 9L per hour at the onset of addition to about 30L per hour. The batch temperature was maintained by alteration of the jacket set point on the reactor. In particular, the set point was changed from about 40.50C at the beginning of the addition to <n="18"/>about 29.6°C as the addition rate increased. The reaction was deemed complete (i.e., less than about 0.5percent ester) after stirring for about 4 hours at about 40-450C. [0155] The batch was transferred to a dry reactor and chased through with about 1 OL of molten /erf-butanol. The jacket set point was decreased from about 33°C when the batch was received by the dry reactor to about 27°C after transfer was complete. Partial crystallization of the batch was observed which did not adversely affect stirring. The batch was cooled to about 34.4°C and triethylamine (72.6 kg, 100L) was charged to the reactor. The jacket temperature set point was raised from about 20.40C to about 31.00C to maintain the batch temperature with the range of about 30-350C. Following a line rinse with molten /er/-butanol (1 OL), the batch was charged with 2-fluorobenzoyl chloride (113.7 kg, 86.0L). The addition rate over the first third of the charge was about 25L per hour. The jacket inlet temperature was lowered to about 15°C during this period and the batch temperature remained at about 34.6°C. The addition was complete after about 5.5 hours. The maximum batch temperature during the addition was about 38.8°C. The addition rate was slowed towards the end of the addition with the final 27 liters of 2-fluorobenzoyl being added at about 1 IL per hour. The reaction was deemed complete (i.e., less than about 0.5percent methyl 3-amidinobenzoate) after stirring for about 2 hours at 30-350C. [0156] The batch was then heated to reflux temperature (about 82°C) over about 1 hour and 42 minutes and stirred for about an additional 18 hours. During stirring, some product partially crystallized to form a slurry. The slurry was cooled to bout 400C to allow for sampling, during which full crystallization occurred. The batch was reheated to reflux temperature and stirred for about 1 hour and 50 minutes. The batch was then cooled over about 2 hours to about 69°C and 630L of purified water was slowly added over about 4 hours and 15 minutes while the batch temperature was maintained at between about 66- 69°C. The slurry was cooled to about 22.4°C over about 3 hours and 14 minutes and transferred to 2X200L ceramic filters fitted with 25-30mu mesh polypropylene filter cloths. Transfer of the material from the vessel onto the filters was complete after about 55 minutes. The filter cakes were washed with 50percent aqueous toer/-butanol (210L), allowing about 10 minutes for the wash to soak into each cake. The cakes were then dried in vacuo over about 5-10 minutes. Purified water was applied to the filter cakes as a secondary wash (158L per cake) to remove residual terr-butanol and triethylammonium chloride salt. <n="19"/>Liquors were removed after drying in vacuo for about 5 minutes. The cakes were dried in vacuo for about an additional 2 hours and then sampled using liquid chromatography. The purity of the cakes was determined to be about 99.6percent by liquid chromatography. [0157] After drying the cakes in vacuo for about 8 hours and 25 minutes, the wet cake (207.4kg) was transferred to an air oven. Drying in the air oven was performed at about 50-550C for about 52 hours. The overall yield of isolated product was about 89.9 percent (174.65kg), which can be adjusted to about 90.7percent after accounting for material consumed by sampling. [0158] Batch 2[0159] Methyl 3-cyanobenzoate (105 kg) and molten rerf-butanol were charged to a dry reactor. 50percent aqueous hydroxylamine (47.85 kg) was charged to the reactor in an inert atmosphere over about 3 hours and 29 minutes. The temperature was maintained at about 40-450C during addition. The reaction was deemed complete (i.e., less than about 0.5percent ester) after stirring for about 3 hours and 16 minutes at about 40-450C. [0160] The batch was transferred to a dry reactor as described for Batch 1. The batch was cooled to about 34.4°C and charged with triethylamine (72.6kg, 100L). The addition was performed over a period of about 45 minutes while maintaining the batch temperature at about 30-350C. The jacket inlet temperature was raised from about 31.40C to about 32.6°C during the addition. After line rinse with molten ter/-butanol, the batch wa... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 0 - 100℃; for 6.0h; | To a 25 mL pear shaped flask were added <strong>[828-52-4]4-(hydroxymethyl)bicyclo[2.2.2]octane-1-carboxylic acid</strong> (160 mg, 0.85 mmol) (Kiesman W. F. et. al. WO 2001/034610) and BOP (38 mg, 0.85 mmol) in DMF (1 mL) followed by methyl (Z)-3-(N'-hydroxycarbamimidoyl)benzoate (Tung, R. D. WO 2016/073545) (150 mg, 0.77 mmol). To this mixture was added Et3N (0.32 mL, 2.3 mmol) at 0 C. The reaction mixture was stirred for 2 h at rt, and 4 h at 100 C. The reaction was cooled, the solvent was concentrated and the residue was dissolved in EtOAc (50 mL). The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash column chromatography (24 g silica gel column; A=Hex, B=EtOAc; 15 min grad.; 0-30% B; flow rate=24 mL/min). The pure fractions were combined, concentrated and dried in vacuo to afford the title compound (120 mg, 45% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) delta=8.54 (t, J=1.5 Hz, 1H), 8.26 (dt, J=7.8, 1.5 Hz, 1H), 8.16 (dt, J=7.9, 1.6 Hz, 1H), 7.74 (t, J=7.7 Hz, 1H), 5.76 (s, 1H), 4.46 (t, J=5.5 Hz, 1H), 3.99-3.85 (m, 3H), 3.11 (d, J=5.4 Hz, 2H), 1.99 (d, J=7.8 Hz, 6H), 1.55-1.39 (m, 6H). MS (ESI) 343 (M+H). |
Tags: 775304-79-5 synthesis path| 775304-79-5 SDS| 775304-79-5 COA| 775304-79-5 purity| 775304-79-5 application| 775304-79-5 NMR| 775304-79-5 COA| 775304-79-5 structure
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