Structure of 543740-89-2
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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. : | 543740-89-2 |
Formula : | C6H5IN2O2 |
M.W : | 264.02 |
SMILES Code : | O=C(O)C1=CN=C(N)C(I)=C1 |
MDL No. : | MFCD12827873 |
InChI Key : | FKCUPIYQJSBUPO-UHFFFAOYSA-N |
Pubchem ID : | 11425541 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H312-H332 |
Precautionary Statements: | P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P330-P363-P501 |
* 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 |
---|---|---|
71% | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20 - 60℃; for 5.16667h; | Step 3 (S)-6-amino-5-iodo-N-[methyl(oxo)phenyl-λ6-sulfanylidene]nicotinamideTo a solution of <strong>[543740-89-2]6-amino-5-iodonicotinic acid</strong> (330 mg, 1.3 mmol), N, N- diisopropylethylamine (0.44 mL, 2.5 mmol), and (S)-(+)-S-methyl-S-phenylsulfoximine (291 mg, 1.9 mmol) in 7.0 mL DMF at room temperature was added BOP (608 mg, 1.4 mmol). The solution was stirred 10 minutes and then heated at 60 0C for 5 hours. The mixture was dissolved in EtOAc, washed with Na2CO3 solution, H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The brown oil was purified by chromatography (silica gel, hexane/acetone). The product containing fractions were purified by chromatography one additional time (silica gel, EtOAc/MeOH). To give the title compound as a white foam (354 mg, 71%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Step 26-amino-5-iodonicotinic acidA solution of methyl 6-amino-5-iodonicotinate (723 mg, 2.6 mmol) and potassium hydroxide (729 mg, 13.0 mmol) in 40 mL methanol/H2O (3: 1 ratio) was heated at 50 0C. After 4 hours 10 mL THF was added and the reaction continued until 22 hours. The reaction was cooled to room temperature and concentrated HCl added until the solution was pH 4. The solution was concentrated to a volume of 15mL and the resulting precipitate filtered, rinsed with H2O and 40% EtOAc/hexane to give the title compound as a white solid (443mg, 65%). | |
1.77 g | With water; potassium hydroxide; In tetrahydrofuran; at 50℃; for 48h; | Preparation 4 6-Amino-5-iodonicotinic acid A mixture of methyl 6-amino-5-iodonicotinate, (2.78 g, 10 mmol, 1 eq) and potassium hydroxide (2.8 g, 5 eq) in THF/H2O (120 mL, 3:1) was heated at 50 C. for 48 hours. The reaction was then cooled to room temperature and concentrated HCl was drop wise added until a pH around 3-4 was achieved. The solution was concentrated and the resulting precipitate was collected by filtration to give the title compound as a slightly brown solid (1.77 g.) 1H NMR (DMSO-d6) δ: 12.64 (br. s., 1H), 8.47 (d, J=2.1 Hz, 1H), 8.25 (d, J=1.8 Hz, 1H), 6.88 (br. s., 2H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.65 g | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 70℃; for 1h; | A solution of methyl 5-(S-methylsulfonimidoyl)pentanoate (2.32 g) was dissolved in anhydrous DMF (30 mL) and to this solution was added 5-iodo-6-amino-nicotinic acid (3.17 g, 1 eq), diisopropylethylamine (4.2 mL, 2 eq), and BOP (5.85 g, 1.1 eq). The reaction mixture was heated at 70 C. for 1 hour and then partitioned between EtOAc and aq NH4Cl. The organic layer was separated, washed sequentially with aq NH4Cl (1×), saturated aq NaHCO3 (1×), brine (1×), and dried with anhydrous Na2SO4 overnight. The upper solution layer was decanted, concentrated, and the brown oily reside was subject to column chromatography ( acetone-CHCl3 1:100 to MeOH-acetone-CHCl3 1:2:50). Concentration of the product eluting fractions provided the title compound as a slight yellow colored foam (2.65 g). 1H NMR (DMSO-d6) δ: 8.52 (d, J=2.1 Hz, 1H), 8.31 (d, J=1.9 Hz, 1H), 6.72 (br. s., 2H), 3.52-3.63 (m, 5H), 3.38 (s, 3H), 2.39 (t, J=7.2 Hz, 2H), 1.61-1.86 (m, 4H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; diisopropylamine; In N,N-dimethyl-formamide; at 70℃; for 1.5h;Inert atmosphere; | To a 250 mL round bottom flask containing 5-iodo-6-amino-nicotinic acid (5 g, 18.9 mmol) and dimethylsulfoximine (1.94 g, 1.1 eq) in anhydrous DMF (50 mL) was added diisopropylamine (6.6 mL, 2 eq) and BOP (9.21 g, 1.1 eq) under nitrogen atmosphere. The reaction mixture was heated at 70 C. for 1.5 hours and then partitioned between aq NH4Cl and EtOAc. The aqueous layer was separated and extracted once with EtOAc. The two organic layers were combined, and washed with saturated aq NaHCO3/brine (1:1, 1×), brine (1×), and dried with anhydrous Na2SO4. The solution layer was decanted, concentrated, and the brown solid residue was treated with EtOAc with stirring at RT for 30 minutes. The solid which formed was colleded by filtration and dried to give the title compound as an offwhite solid (5.31 g, 83%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24 mg | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; diisopropylamine; In N,N-dimethyl-formamide; at 70℃; for 6h; | A solution of ethyl(S-methylsulfonimidoyl)acetate was dissolved in anhydrous DMF (1 mL) and treated with 5-iodo-6-amino-nicotinic acid (82 mg, 1.05 eq), diisopropylamine (0.1 mL, 2 eq), and BOP (149 mg, 1.1 eq) with stirring. The reaction mixture was heated to 70 C. for 6 hours and then partitioned between EtOAc and aq NH4Cl. The organic layer was separated, washed with saturated aq NaHCO3 (1×) and brine (1×), and dried over Na2SO4. The organic phase was filtered and concentrated. The residue as purified by gradient column chromatography (EtOAc-Hexane 1:9 to 2:3). Concentration of the product containing fractions provided the title compound as a brown oil (24 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 60℃; for 20h; | Preparation 5 6-amino-5-iodo-N-(4-oxido-1,4λ4-oxathian-4-ylidene)nicotinamide To a solution of 1,4-oxathiane (510 mg, 3.21 mmol, 1.05 eq) in anhydrous DMF (8 mL) was added <strong>[543740-89-2]6-amino-5-iodonicotinic acid</strong> (806 mg, 1.0 eq), diisopropylethylamine (1.1 mL, 2 eq), and BOP (1.484 g, 1.1 eq). The reaction mixture was heated at 60 C. for 20 hours and then partitioned between EtOAc and aq NH4Cl. The organic layer was separated, washed further with saturated aq NaHCO3 (1*), brine (1*), and dried with anhydrous Na2SO4 overnight. The upper solution layer was decanted, concentrated, and the brown oily reside was subject to column chromatography (EtOAc-Hex 1:5 to 3:1). Concentration of the product eluting fractions gave the title compound as white solid (889 mg, 77%). 1H NMR (DMSO-d6) δ: 8.57 (d, J=2.1 Hz, 1H), 8.35 (d, J=2.1 Hz, 1H), 6.78 (br. s., 2H), 4.10-4.15 (m, 2H), 3.91 (ddd, J=12.6, 8.5, 2.1 Hz, 2H), 3.79-3.84 (m, 2H), 3.55-3.60 (m, 2H) |
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