Structure of 56022-07-2
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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. : | 56022-07-2 |
Formula : | C7H5Cl2NO2 |
M.W : | 206.03 |
SMILES Code : | CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 |
MDL No. : | MFCD03086007 |
InChI Key : | CIVCELMLGDGMKZ-UHFFFAOYSA-N |
Pubchem ID : | 820405 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
66% | 2,4-dichloro-6-methylnicotinic acid A solution of commercially available (Maybridge) ethyl 2,4-dichloro-6-methylpyridine-3-carboxylate (1.0 g, 4.3 mmol) and NaOH (342 mg, 8.6 mmol) in water (1.7 mL) and MeOH (1.5 mL) was heated to 80 C. for 4 h. The mixture was acidified using 50% H2SO4 and filtered. The solid was washed with cold water and dried to give of 2,4-dichloro-6-methylpyridine-3-carboxylic acid (582 mg, 66%): LCMS RT: 0.70 min, MH+: 206.2. | |
With water; lithium hydroxide; In tetrahydrofuran; at 85℃; for 72h; | (0728) [00272] Into a 250-mL round-bottom flask was added ethyl 2,4-dichloro-6-methylpyridine-3- carboxylate (3.00 g, 12,8 mmol ), THF (30 mL), and water (30 mL) followed by the portion-wise addition of LiOH (1.23 g, 51.3 mmol). The resulting solution was stirred for 3 days at 85 C and then concentrated in vacuo. The pH was adjusted to 3 with 4 N HC1 (aq) and the resulting (0729) 107 (0730) 144628010 vl precipitate was collected by filtration and dried in vacuo to afford 2,4-dichloro-6-methylnicotinic acid as a white solid (3.0 g), The material was used without further purification. LCMS (ESI, m/z): 206 | |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; at 80℃; for 2h; | [00497] 2,4-Dichloro-6-methylnicotinic acid (8.7 g, 43.0 mmol) was mixed with SOCl2 (31 mL). The resulting mixture was heated to 80 C. for 2 h and concentrated in vacuo to give the acid chloride as yellow oil. The oil was then dissolved in CH2Cl2 (10 mL) and the solution was added to a cooled suspension of AlCl3 (21.3 g, 160.0 mmol) in CH2Cl2 (50 mL) at 0 C. After 2 h at 0 C., vinylidene chloride (2.16 mL, 80.0 mmol) was added to the above suspension. The resulting mixture was then left to warm to room temperature and stirred overnight. The reaction mixture was poured into crushed ice and the resulting mixture was extracted with CH2Cl2. The combined organic layers were cooled to 0 C. and TEA (14.9 mL) was added. After 1 h of stirring, the organic layer was washed with 10% aqueous HCl (100 mL), water (200 mL), brine (100 mL), and dried over Na2SO4. Solvents were removed in vacuo and the residue was purified by passing it through a pad of silica gel with 15% EtOAc in Hex as the eluent to provide 3,3-dichloro-1-(2,4-dichloro-6-methyl-3-pyridinyl)-2-propen-1-one (5.2 g, 46%): LCMS RT: 3.13 min, MH+: 284.6. Alternatively, the acid chloride could be prepared by using oxalyl chloride with a catalytic amount of DMF. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 1; Preparation of 2-chloro-N [ (4-fluorophenyl) methyl]-6-methyl-4-propoxy- 3-pyridinecarboxamide (Compound 29); Step A: Preparation of 2-chloro-6-methyl-4-propoxy-3-pyridinecarboxylic acid; To <strong>[56022-07-2]2,4-dichloro-6-methyl-3-pyridinecarboxylic acid</strong> (1 g) in N, N-dimethylformamide (DMF) (10 mL) was added sodium hydride (0.43 g). After gas evolution ceased, 1-propanol (0.4 mL) was added, and the mixture heated at 80 C overnight. The mixture was cooled and water added. The mixture was extracted with ether to remove any residual oil. The aqueous phase was adjusted to pH 2 using 1 N hydrochloric acid and then extracted with ethyl acetate (3x). The combined ethyl acetate extracts were washed with water (3x) then brine and dried (MgS04). The solvent evaporated in vacuo to leave a solid, which was triturated with 1-chlorobutane-hexanes to provide the title compound as a yellow solid (0.55 g), melting 195-200 C. 1H NMR (DMSO-d6, 300 MHz) 8 13.05 (br s, 1H) 7.10 (s, 1H), 4.09 (t, 2H), 2.42 (s, 3H), 1.60-1. 80 (m, 2H), 0.94 (t, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 3; Preparation of 2-chloro-N- [ (4-fluorophenyl) methyl]-6-methyl-4- (l-methylethoxy)- 3-pyridinecarboxamide (Compound 64); Step A: Preparation of 2, 4-dichloro-N- [ (4-fluorophenyl) methyl]-6-methyl-3-pyridine- carboxamide; To <strong>[56022-07-2]2,4-dichloro-6-methyl-3-pyridinecarboxylic acid</strong> (3.0 g) was added thionyl chloride (25 mL), and the reaction mixture was heated at reflux for 1.5 h. The excess thionyl chloride was evaporated in vacuo, and dichloromethane was added and evaporated in vacuo. The residual brown oil was dissolved in dichloromethane (approximately 5 mL) and added to a solution of 4-fluorobenzenemethanamine (406 mg) and triethylamine (2.6 mL) in dichloromethane (10 mL) cooled to 0 C. The reaction mixture was stirred at room temperature overnight. The reaction mixture was then poured into water and extracted with dichloromethane (2x) with addition of ethyl acetate to keep solids in solution. The combined organic extracts were dried (MgSO4), filtered and evaporated in vacuo. The resulting yellow solid was triturated with 1-chlorobutane-hexanes to provide the title compound as a tan solid (3.99 g). A sample purified by silica gel chromatography using ethyl acetate-hexanes (1: 1) as eluant, followed by trituration with 1-chlorobutane-hexanes had a melting point of 150- 151 C. H NMR (CDC13, 300 MHz) 8 7.30-7. 40 (m, 2H), 7.17 (s, 1H), 7.05 (t, 2H), 6.03 (br t, 1H), 4.64 (d, 2H), 2.53 (s, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(0732) [00273] Into a 250-mL round-bottom flask was added <strong>[56022-07-2]2,4-dichloro-6-methylnicotinic acid</strong> (2,00 g, 9.71 mmol) and dichloromethane (50-mL) followed by the portion-wise addition of oxaiyl chloride (6.35 g, 4.29 mL, 50.0 mmol). To this mixture was added DMF (50 mg, 0.053 mL) dropwise and with stirring. The resulting solution was stirred for 2 h at RT and then concentrated in vacuo to afford a crude product that was dissolved in dichloromethane (50-mL). To this solution was added NL Cl (2.12 g, 11.5 mmol) and triethylamine (10 g, 13.8 mL, 99.0 mmol) dropwise and with stirring. After stirring for 2 h at RT the reaction was quenched with 10 mL of water/ice and the resulting mixture was extracted with dichloromethane (3 x 30 mL). The organic layers were combined, washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to afford 2,4-dichloro-6-methylnicotinamide as a white solid (2.1 g). The material was used without further purification. LCMS (ESI, m/z): 205 [M+H]+. |
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