Structure of 2620-50-0
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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. : | 2620-50-0 |
Formula : | C8H9NO2 |
M.W : | 151.16 |
SMILES Code : | NCC1=CC=C(OCO2)C2=C1 |
MDL No. : | MFCD00005840 |
InChI Key : | ZILSBZLQGRBMOR-UHFFFAOYSA-N |
Pubchem ID : | 75799 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 40.18 |
TPSA ? Topological Polar Surface Area: Calculated from |
44.48 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.71 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.79 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.72 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.61 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.51 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.61 |
Solubility | 3.69 mg/ml ; 0.0244 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.31 |
Solubility | 7.49 mg/ml ; 0.0495 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.18 |
Solubility | 1.0 mg/ml ; 0.00664 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 |
Yes |
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) |
No |
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 |
-6.66 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 |
1.0 |
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 |
0.0 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) |
1.84 |
* 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 |
---|---|---|
With triethylamine; | Example 65 4-(3,4-Methylenedioxybenzyl)amino-6-cyanoquinazoline STR126 15 ml of isopropyl alcohol, 75 mg of triethylamine and 125 mg of piperonylamine were added to 140 mg of <strong>[150449-97-1]4-chloro-6-cyanoquinazoline</strong>. The obtained mixture was heated under reflux for 5 hours and filtered to recover a precipitate. This precipitate was introduced to a silica gel column, followed by eluding with ethyl acetate to give 200 mg of the title compound. molecular formula; C17 H12 N4 O2 yield (%); 89 m.p. (C.); 243~244 Mass; 305 (M+1)+ NMR delta (DMSO-d6); 4.67 (2H, d, J=5.6Hz), 5.96 (2H, s), 6.84 (2H, s), 6.95 (1H, s), 7.77 (1H, d, J=8.4Hz), 8.56 (1H, s), 8.89 (1H, s), 9.04 (1H, br) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; | EXAMPLE 1 3.02 g of 3,4-methylenedioxybenzylamine ("A") are added to a solution of 3.29 g of <strong>[76872-23-6]2,4-dichloro-6-methylthieno[2,3-d]pyrimidine</strong> in 80 ml of dichloro-methane, and, after 1.52 g of triethylamine have been added, the mixture is stirred for 12 hours at room temperature. The solvent is removed and worked up as customary. This gives 3.38 g of 2-chloro-6-methyl-4-(3,4-methylenedioxybenzylamino)thieno[2,3-d]pyrimidine, m.p. 162. | |
With triethylamine; In dichloromethane; | EXAMPLE 1 3.02 g of 3,4-methylenedioxybenzylamine ("A") are added to a solution of 3.29 g of 2,4-dichloro-6-methylthieno-[2,3-d]-pyrimidine in 80 ml of methylene chloride and, after addition of 1.52 g of triethylamine, the mixture is stirred at room temperature for 12 hours. The solvent is removed and the residue is worked up in the customary manner. 3.38 g of 2-chloro-6-methyl-4-(3,4-methylenedioxybenzylamino)-thieno-[2,3-d]-pyrimidine are obtained, m.p. 162. | |
With triethylamine; In dichloromethane; | EXAMPLE 1 2-Chloro-6-Methyl-4-(3,4-Methylenedioxybenzylamino)-Thieno-[2,3-d]-Pyrimidine A solution of 2,4-dichloro-6-methyl-thieno-[2,3-d]-pyrimidine (3.29 g) in dichloromethane (30 ml) is charged with 3,4-methylenedioxybenzylamine ("A") (3.02 g). Triethylamine (1.52 g) is added, and the mixture is stirred at room temperature. The solvent is removed, and the usual workup yields 2-chloro-6-methyl-4-(3,4-methylenedioxybenzylamino)-thieno-[2,3-d]-pyrimidine (3.38 g) Mp. 162 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 2 2-Chloro-5-Methyl-4-(3,4-Methylenedioxybenzylamino)-Thieno-[2,3-d]-Pyrimidine Following the procedure of Example 1, the reaction of 3,4-methylenedioxybenzylamine with <strong>[56844-38-3]2,4-dichloro-5-methyl-thieno-[2,3-d]-pyrimidine</strong> gives 2-chloro-5-methyl-4-(3,4-methylenedioxybenzylamino)-thieno-[2,3-d]-pyrimidine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; | EXAMPLE 65 4-(3,4-Methylenedioxylbenzyl)amino-6-cyanoquinazoline STR99 15 ml of isopropyl alcohol, 75 mg of triethylamine and 125 mg of piperonylamine were added to 140 mg of <strong>[150449-97-1]4-chloro-6-cyanoquinazoline</strong>. The obtained mixture was heated under reflux for 5 hours and filtered to recover a precipitate. This precipitate was introduced to a silica gel column, followed by eluding with ethyl acetate to give 200 mg of the title compound. molecular formula; C17 H12 N4 O2; yield(%); 89; m.p.( C.); 243~244; Mass; 305 (M+1)+; NMR delta (DMSO-d6); 4.67 (2H, d, J=5.6 Hz), 5.96 (2H, s), 6.84 (2H, s), 6.95 (1H, s), 7.77 (1H, d, J=8.4 Hz), 8.56 (1H, s), 8.89 (1H, s), 9.04 (1H, br). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | To a solution of 3, [4-METHYLENEDIOXYDIHYDROCINNAMIC] acid (0.4 g) in dry [CH2CK] (25 [ML)] under nitrogen, was added oxalyl chloride (0.5 [ML)] with three drops of dry DMF and the mixture was stirred for 1 hour. Solvents were removed in vacuo giving the acid chloride as a yellow solid. To a solution of the acid chloride in dry [CH2CL2] (50 [ML)] under nitrogen, cooled to [0C,] was added dropwise, a solution of 3, 4-(methylenedioxy)benzylamine (0.35 [G)] and pyridine (0.2 [ML)] in [CH2C12] (5 ml). The reaction mixture was stirred for 30 minutes at room temperature, diluted with [CHUCK] (100 [ML),] washed with aqueous HCl (100 [ML] ; [10%)] and sodium bicarbonate solution (100 [ML)] then dried and evaporated in vacuo to give DC-0058B as an off white powder (0.536g, 80%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A library of compounds in which R4 was various groups having the formula [CONHR »] was prepared by the process described above using 4-fluoro-3-nitrobenzoic acid, as follows: [72] Aldehyde resin was mixed with a primary amine (R17-NH2) in [DICHLOROETHANE] (DCE), triethylorthoformate (TEOF), and DMF (containing [1%] acetic acid) in a 1: 1: 1 ratio. After shaken overnight, sodium triacetoxyborohydride (20 eq. ) dissolved in DMF was added (Abdel-Magid, A. F. , et al., Tetrahedron Lett, 3 1: 5595-5598 (1990) ). After the mixture was shaken at room temperature overnight, the resin was filtered and washed with DMF (3 x 5 mL), [MEOH] [(3 X 5] mL), DMF [(3 X 5] mL), [MEOH] [(3 X 5] mL), and [CH2CL2] [(3 X 5] mL). The resin was washed twice with 5 mL DMF containing [1%] Hunig's base. To the filtered resin was added a mixture of 4-fluoro-3-nitrobenzoic acid (FNBA, 10 eq. ) and diisopropylcarbodiimide (DIC, 5 eq. ) in 2: 1 DMF : DCM. After shaking at room temperature overnight, the resin was filtered and washed with DMF (3 x 5 mL) and [CH2C12] (3 x 5 mL). [73] The resin was shaken with a primary amine [(R2-NH2)] in DMF for 8 hrs, filtered, and washed with DMF (6 x 5 mL), [MEOH] [(3 X 5] mL), and CH2C12 (3 x 5 mL). The aryl nitro group was reduced by the addition of tin (II) chloride dihydrate (20 eq. , >2 M) and N-methyl morpholine (NMM, 20 eq. ) in N-methyl pyrrolidinone (NMP). After shaken at room temperature overnight, the resin was filtered and washed with NMP (3 x 5 mL), [MEOH] (3 x 5 mL), and [CH2CI2 (3 X 5] mL). The resulting resin was shaken at room temperature with cyanogen bromide (5 eq. ) overnight, filtered, and washed with CH2Cl2 (3 x 5 mL), [MEOH] (3 x 5 mL), and CH2CI2 (3 x 5 mL). To produce a free amine, the resin was shaken for 30 min. in CHCl2 with the addition of sodium methoxide in methanol, filtered, and washed with CH2Cl2 [(4 X 5] mL). [[74]] In the final diversification step, the resin was heated at 500 C in DMF with a mono- substituted epoxide [[RLCH (-CH2O-)].] After shaking for 2 to 4 days the resin was filtered and washed with DMF (5 x 5 mL), [MEOH] [(3 X 5] mL), and CH2Cl2 (3 x 5 mL). T he resin-bound benzimidazole was cleaved from the solid-support by treatment with TFA: [CH2C12] (2: 3) for 1 hour at room temperature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | General procedure: To solutions of the corresponding 2-phenoxyalkylcarboxylicacids in DMF (5 mL/mmol) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI; 1.1 equiv) and 1-hydroxy-7-azabenzotriazole (1.1 equiv). The solutions were stirredat room temperature for 30 min, then the corresponding benzylamines(1.2 equiv) and diisopropylethylamine (3.0 equiv) wereadded. The resulting mixtures were stirred at room temperaturefor an additional 16 h, then poured into 10% aqueous citric acidsolutions. The aqueous mixtures were extracted with EtOAc, andthe extracts were washed with 5% aqueous NaHCO3 and brine, thendried over MgSO4, filtered, and evaporated to provide white solids.The solids were crystallized from EtOAc/hexane to provide theproducts 1, 2, and 6a. | |
45% | To a solution of (i?)-2-(2,4-dichlorophenoxy)propionic acid (compound 10a; 128 mg, 0.55 mmol), l-hydroxy-7-azabenzotriazole (82 mg, 0.60 mmol, 1.1 eq), and JV-(3- dimethylaminopropyl)-Lambda/"-ethylcarbodiimide hydrochloride (115 mg, 0.60 mmol, 1.1 eq) in dry DMF (3 mL) was added piperonylamine (0.81 mL, 0.65 mmol, 1.2 eq). The solution was stirred at room temperature for 30 minutes. Diisopropylethylamine (0.28 mL, 1.7 mmol, 3.0 eq) was then added, and the solution was stirred at room temperature for 16 hours. The reaction was poured into 10% aqueous citric acid (20 mL) and extracted with EtOAc (30 mL x 3). The combined organic extracts were dried over Na2SO4, and evaporated to provide a residue which was subjected to chromatography on silica gel with 20% EtOAc/hexane. The fractions were pooled and evaporated to yield 91 mg (45%) of compound 11a (designated MBX 1684) as a white solid: Rf 0.52 (50% EtOAc-Hexanes); mp 136-138 C; MS (ESI) m/z 368.0 [M+H]+; 1H NMR (CDCl3) delta 7.37 (d, IH), 7.19 (dd, IH), 6.91 (s, IH), 6.85 (d, IH), 6.76-6.68 (m, 3H), 5.95 (s, 2H), 4.73 (q, IH), 4.39 (m, 2H), 1.64 (d, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80.3% | In ethyl acetate; at 20℃; | 4-Chloroisobenzofuran-1,3-dione (230 mg, 1.25 mmol) dissolved in 5 mL of ethyl acetate and stirred at room temperatureSolution, drop into piperine (188mg, 1.25mmol), will immediately produce a large amount of white solids, TLC monitoring, after the reaction is completed, staticThe mixture was filtered and dried to give Compound 4 in a yield: 80.3%. |