Structure of 102368-13-8
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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. : | 102368-13-8 |
Formula : | C11H8N2O2S |
M.W : | 232.26 |
SMILES Code : | S=C(N1C=CC=CC1=O)N2C=CC=CC2=O |
MDL No. : | MFCD00075238 |
InChI Key : | KXMMNJQMGILZDB-UHFFFAOYSA-N |
Pubchem ID : | 853162 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P264-P271-P280-P302+P352-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 64.8 |
TPSA ? Topological Polar Surface Area: Calculated from |
76.09 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.49 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.23 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.69 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.4 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.95 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.35 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.48 |
Solubility | 0.773 mg/ml ; 0.00333 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.43 |
Solubility | 0.872 mg/ml ; 0.00375 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.49 |
Solubility | 0.746 mg/ml ; 0.00321 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.84 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.15 |
* 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 |
---|---|---|
93% | In dichloromethane; at 20℃; for 2h; | Isoquinolin-3-amine (3.23 g, 22.4 mmol) was added to a solution of 1,1'-thiocarbonyldipyridin-2(1H)-one (5.20 g, 22.4 mmol) in dichloromethane (50 mL) at room temperature. The reaction was stirred for 2 h, then purified by flash chromatography on silica gel (0-10percent ethyl acetate in hexanes). Product fractions were combined and concentrated in vacuo to give 3-isothiocyanatoisoquinoline(3.9 g, 93 percent) as a white solid. 1H NMR (400 MHz, CDCl3) delta ppm 9.12 (1 H, s), 8.00 (1 H, d, J=8.06 Hz), 7.69 - 7.85 (2 H, m), 7.58 - 7.68 (1 H, m), 7.50 (1 H, s). LCMS (method F) tR, 2.47 min, MH+ = 187.23 |
85% | In dichloromethane; at 20℃; for 18h; | Step A: 3-Isothiocyanatoisoquinoline To a solution of 1,1'-thiocarbonyldipyridin-2(1H)-one (0.805 g, 3.47 mmol) in dichloromethane at room temperature was added <strong>[25475-67-6]isoquinolin-3-amine</strong> (0.5 g, 3.47 mmol). The reaction was stirred at room temperature for 18 hours. The LC/MS showed the desired product peak a major peak. The deep orange solution was concentrated and filtered. The filtrate was purified by silica gel chromatography (0-40percent ethyl acetate-hexanes) to afford 4-isothiocyanato-6-(3-methoxyphenyl)pyrimidine (0.55 g, 2.96 mmol, 85percent yield) a white solid. LCMS R.T.=2.47; [M+H]+=187.23. |
85% | In dichloromethane; at 20℃; for 18h; | EXAMPLE 4; (5S*,5'R*)-N-(isoquinolin~3-yl)-4^1-azaspiro[bicyclo[3.2 ]oamine; Step A: 3-Isothiocyanatoisoquinoline; To a solution of 1 , 1 '-thiocarbonyldipyridm-2(l H)-one (0.805 g, 3.47 mmol) in dichloromethane at room temperature was added <strong>[25475-67-6]isoquinolin-3-amine</strong> (0.5 g, 3.47 mmol). The reaction was stirred at room temperature for 18 hours. The LC/MS showed the desired product peak a major peak. The deep orange solution was concentrated and filtered. The filtrate was purified by silica gel cliromatography (0- 40percent ethyl acetate-hexanes) to afford 4-isothiocyanato-6-(3- methoxyphenyl)pyrimidine (0.55 g, 2.96 mmol, 85 percent yield) a white solid. LCMS R.T. - 2.47; [M+H]+ = 187.23. |
85% | In dichloromethane; at 20℃; for 18h; | Step A: 3-IsothiocyanatoisoquinolineTo a solution of l, l'-thiocarbonyldipyridin-2(lH)-one (0.805 g, 3.47 mmol) in dichloromethane at room temperature was added isoquinolin-3 -amine (0.5 g, 3.47 mmol). The reaction was stirred at room temperature for 18 hours. The LC/MS showed the desired product peak a major peak. The deep orange solution was concentrated and filtered. The filtrate was purified by silica gel chromatography (0- 40percent ethyl acetate-hexanes) to afford 4-isothiocyanato-6-(3- methoxyphenyl)pyrimidine (0.55 g, 2.96 mmol, 85 percent yield) a white solid. LCMS R.T. = 2.47; [M+H]+ = 187.23. |
85% | In dichloromethane; at 20℃; for 18h; | To a solution of 1,1'-thiocarbonyldipyridin-2(lH)one(0.805 g, 3.47 mmol) in dichloromethane at room temperature was added <strong>[25475-67-6]isoquinolin-3-amine</strong> (0.5 g, 3.47 mmol).The reaction was stirred at room temperature for 18 hours.The LC/MS showed the desired product peak a major peak.The deep orange solution was concentrated and filtered. Thefiltrate was purified by silica gel chromatography (0-40percentethyl acetate-hexanes) to afford 4-isothiocyanato-6-(3-methoxyphenyl)pyrimidine (0.55 g, 2.96 mmol, 85percent yield) a white solid. |
In dichloromethane; at 20℃; for 18h; | EXAMPLES 7, 7a, 7b; (3R*,4R*)-N-(Isoquinolin-3-yl)-4'H-l-azaspiro[bicyclo[2.2.1]heptane-3,5'-oxazol]-2' -amine; Step A: 3-Isothiocyanatoisoquinoli; To a solution of l,l'-thiocarbonyldipyridin-2(lH)-one (0.805 g, 3.47 mmol) in dichloromethane at room temperature was added isoquinolin-3 -amine (0.5 g, 3.47 mmol). The reaction was stirred at room temperature for 18 hours. The LC/MS showed the desired product peak a major peak. The deep orange solution was concentrated and filtered. The filtrate was purified by silica gel chromatography (0- 40percent ethyl acetate-hexanes) to afford 4-isothiocyanato-6-(3- methoxyphenyl)pyrimidine (0.55 g, 2.96 mmol, 85 percent yield) a white solid. LCMS R.T. = 2.47; [M+H]+ = 187.23. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In dichloromethane; for 4h; | To a solution of IV-e (600 mg, 3.53 mmol) in DCM (40 ml_) was added 1 ,1 '-Thiocarbonyldi- 2(1 H)-pyridone (232 mg, 3.88 mmol) and the reaction mixture was stirred for 4h. After evaporation of solvent the resulting crude product was purified by silica gel chromatography using 25% AcOEt in cyclohexane as eluent to give 1 -fluoro-4- isothiocyanato-5-methyl-2-nitro-benzene IV-a as a yellow syrup (740 mg, 99%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | In dichloromethane; at 20℃; for 16.6667h; | [015581 3-isothiocyanato-2,4-dimethoxypyridine, Example 771.1. A 2L round bottom flask was charged with 1,1”-thiocarbonyldi-2(1H)-pyridone (47.0 g, 202 mmol) and dissolved in dry DCM (405 mL). To that solution was added 2,6- dimethoxyaniline (31 g, 202 mmol) dissolved in DCM (405 mL) via an addition funnel at RT over 40 minutes. After 16 hours, the reaction was concentrated in vacuo and purified on silica gel (0-20% EtOAc in heptanes) to give 2-isothiocyanato-1,3-dimethoxybenzene (32 g, 164 mmol, 81 % yield). LCMS-ESI (POS.) mlz: 197.1 (M+H)t |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; at 20℃; for 2h; | General procedure: Isoquinolin-3-amine (3.23 g, 22.4 mmol) was added to a solution of 1,1'-thiocarbonyldipyridin-2(1H)-one (5.20 g, 22.4 mmol) in dichloromethane (50 mL) at room temperature. The reaction was stirred for 2 h, then purified by flash chromatography on silica gel (0-10% ethyl acetate in hexanes). Product fractions were combined and concentrated in vacuo to give 3-isothiocyanatoisoquinoline(3.9 g, 93 %) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | In dichloromethane; at 20℃; | Into a 250-mL round-bottom flask, was placed tert-butyl 5-amino-1H-indazole-1- carboxylate (2 g, 8.57 mmol, 1.00 equiv), 1-[(2-oxo-1,2-dihydropyridin-1-yl)carbothioyl]-1,2- dihydropyridin-2-one (2 g, 8.61 mmol, 1.00 equiv), and dichloromethane (75 mL). The resulting solution was stirred overnight at room temperature. The resulting mixture was washed with 2x50 mL of sat. sodium bicarbonate and 1x50 mL of brine. The organic mixture was dried over anhydrous sodium sulfate. The solids were removed by filtration. The resulting mixture was concentrated under vacuum. This resulted in 1.5 g (64percent) of tert-butyl 5-isothiocyanato- 1H-indazole-1-carboxylate as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | In dichloromethane; at 40℃; for 3h; | To <strong>[1192814-45-1]5,6-dichloropyridin-2-amine</strong> (0.47 g, 2.88mmol) in dichloromethane (25 mL) was added 1,1'-thiocarbonyldipyridin-2(1H)-one (0.68 g, 2.94 mmol). The reaction was stirred at 40 C. for 3 hours, then cooled to room temperature.The crude material was purified by chromatography(Biotage: 25-100% ethyl acetate/hexane) 2,3-dichloro-6isothiocyanatopyridine(0.48 g, 2.34 mmol, 81% yield) as awhite powder. |
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