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Type | HazMat fee for 500 gram (Estimated) |
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Structure of 74650-73-0
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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. : | 74650-73-0 |
Formula : | C7H5ClN2O |
M.W : | 168.58 |
SMILES Code : | N#CC1=C(Cl)N=CC(OC)=C1 |
MDL No. : | MFCD18255084 |
InChI Key : | MAXCZWUUQRMEGU-UHFFFAOYSA-N |
Pubchem ID : | 12852019 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H301 |
Precautionary Statements: | P301+P310 |
Class: | 6.1 |
UN#: | 2811 |
Packing Group: | Ⅲ |
* 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 |
---|---|---|
0.53 g (71%) | With potassium tert-butylate; In tetrahydrofuran; ammonium chloride; N,N-dimethyl-formamide; | EXAMPLE 55A Methyl 2-amino-5-methoxy-thieno[2,3-b]pyridine-2-carboxylate To <strong>[74650-73-0]2-chloro-3-cyano-5-methoxypyridine</strong> (0.53 g) and methyl thioglycolate (280 muL) in DMF (10 mL) at 5 C. was added a 1.0M solution of KOtBu/THF (3.8 mL). The reaction was stirred 20 min at 5, then 2 h at RT, quenched in sat'd NH4 Cl, the solid precipitate was collected, washed with water and dried to give 0.53 g (71%) of the title compound. |
0.53 g (71%) | With potassium tert-butylate; In tetrahydrofuran; ammonium chloride; N,N-dimethyl-formamide; | EXAMPLE 55A Methyl 2-amino-5-methoxy-thieno[2,3-b]pyridine-2-carboxylate To <strong>[74650-73-0]2chloro-3-cyano-5-methoxypyridine</strong> (0.53 g) and methyl thioglycolate (280 muL) ini DMF (10 mL) at 5 C. was added a 1 0M solution of KOtBu/THF (3.8 mL). The reaction was stirred 20 min at 5 then 2 h at RT, quenched in sat'd NH4 Cl, the solid precipitate was collected, washed with water and dried to give 0.53 g (71%) of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6.2 g (86%) | With trifluoromethylsulfonic anhydride; In dichloromethane; | (E) Preparation of 2-chloro-5-methoxynicotinonitrile Into a flame dried flask under N2 was placed triphenylphosphine oxide (12.0 g, 0.04 mol) and CH2 Cl2 (50 mL) and the mixture cooled to 0-4 C. A solution of triflic anhydride (6.75 ml, 0.04 mol) in CH2 Cl2 (80 mL) was added dropwise. After the addition, the solution was stirred for 15 min. and 2-chloro-5-methoxynicotinamide (8.0 g, 0.04 mol) was added portionwise over 15 minutes. The mixture was allowed to warm to room temperature with stirring overnight, poured into saturated Na2 CO3 solution and extracted with CHCl3 (2*). After concentration, the residue was chromatographed on silica gel and the product eluted with CHCl3 to yield 6.2 g (86%) of 2-chloro-5-methoxynicotinonitrile 1 H NMR (CDCl3) delta3.9 (3H, s), 7.5 (1H, d, J=3) and 8.3 (1H, d, J=3); (nujol) 2250 cm- 1. |
6.2 g (86%) | With trifluoromethylsulfonic anhydride; In dichloromethane; | (E) Preparation of 2-chloro-5-methoxynicotinonitrile Into a flame dried flask under N2 was placed triphenylphosphine oxide (12.0 g, 0.04 mol) and CH2 Cl2 (50 mL) and the mixture cooled to 0-4 C. A solution of triflic anhydride (6.75 ml, 0.04 mol) in CH2 Cl2 (80 mL) was added dropwise. After the addition, the solution was stirred for 15 min. and 2-chloro-5-methoxynicotinamide (8.0 g, 0.04 mol) was added portionwise over 15 minutes. The mixture was allowed to warm to room temperature with stirring overnight, poured into saturated Na2 CO3 solution and extracted with CHCl3 (2X). After concentration, the residue was chromatographed on silica gel and the product eluted with CHCl3 to yield 6.2 g (86%) of 2-chloro-5-methoxynicotinonitrile 1 H NMR (CDCl3) delta 3.9 (3H, s), 7.5 (1H, d, J=3) and 8.3 (1H, d, J=3); (nujol) 2250 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.55 g (47%) | In N-methyl-acetamide; hydrogenchloride; mineral oil; | EXAMPLE 2 Preparation of (S) 2-(tert-Butylamino-2-hydroxypropoxy)-5-methoxynicotinonitrile A stirred suspension of 50% sodium hydride in mineral oil (0.22 g., 0.045 mole) in dimethylformamide (35 ml.) was treated under nitrogen with (S) 2-phenyl-3-tert-butyl-5-hydroxymethyloxazolidine (1.06 g., 0.0045 mole) and heated on a steam bath for 20 minutes until hydrogen evolution ceased. After cooling to room temperature a solution of <strong>[74650-73-0]2-chloro-5-methoxynicotinonitrile</strong> (0.70 g., 0.0042 mole) in dimethylformamide (20 ml.) was added dropwise and the mixture stirred at room temperature for 21 hours. The mixture was poured into water (200 ml.) and extracted with ether (3*200 ml.). The combined extracts were washed with water, dried over sodium sulfate and concentrated under reduced pressure. The residue was heated on a steam bath in 1 N HCl (65 ml.) for 30 minutes. After cooling, the mixture was extracted with ether (2*50 ml.), the aqueous layer was carefully poured into saturated sodium carbonate solution (40 ml.) and extracted with CHCl3 (3*75 ml.). The solvent was concentrated under reduced pressure and the residue crystallized from hexane to yield 0.55 g (47%) of (S) 2-(3-tert-butylamino-2-hydroxypropoxy)-5-methoxynicotinonitrile melting at 97-98.5 C. Compounds of Formula II where R4 is STR8 are prepared from the corresponding compounds where R4 is OH by conventional acylation with an appropriate alkanoyl halide or alkanoic acid anhydride. This Formula II intermediate is then converted to the corresponding Formula I compound by substituting this intermediate for <strong>[74650-73-0]2-chloro-5-methoxynicotinonitrile</strong> in substantially the same procedure as Example 2. |