Structure of 2851-13-0
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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. : | 2851-13-0 |
Formula : | C9H11N3 |
M.W : | 161.20 |
SMILES Code : | CN(C)C1=NC2=CC=CC=C2N1 |
MDL No. : | MFCD01231011 |
InChI Key : | NMTCCVZABWWGSB-UHFFFAOYSA-N |
Pubchem ID : | 17846 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 50.3 |
TPSA ? Topological Polar Surface Area: Calculated from |
31.92 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.53 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.71 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.63 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.43 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.55 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.57 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.41 |
Solubility | 0.633 mg/ml ; 0.00393 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.0 |
Solubility | 1.63 mg/ml ; 0.0101 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.01 |
Solubility | 0.157 mg/ml ; 0.000975 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) |
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 |
-6.07 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) |
1.58 |
* 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 |
---|---|---|
89% | In water; N,N-dimethyl-formamide; at 200℃; for 0.5h; | Commercially available 2-chloro-1H-benzo[d]imidazole (250 mg, 1.64 mmol) was dissolved in DMF (4.7 mL), dimethylamine (50% aqueous solution, 0.50 mL, 4.92 mmol) was added, and the mixture was stirred with heating at 200C for 30 min in an Emrys Optimizer microwave synthesizer. Water was added to the mixture, and the precipitated crystals were collected by suction filtration to give N,N-dimethyl-1H-benzo[d]imidazole-2-amine (234 mg, 89%). ESIMS m/z: 162 (M + H)+; 1H NMR (270 MHz, DMSO-d6, delta): 3.03 (s, 6H), 6.79-6.97 (m, 2H), 7.07-7.20 (m, 2H), 11.17 (br s, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); XPhos; In N,N-dimethyl-formamide; at 140 - 150℃; for 0.5h;Microwave; | Scheme 3 exemplifies a method of forming compounds of Formula I. Chloro purines (4) (1 mmol) can be coupled with R3-H (for example, wherein R3 is benzimidazol-1-yl) (1.03-1.30 mmol), under Buchwald conditions, for example tris(dibenzylideneacetone)-dipalladium(0) (0.02-0.05 mmol), XPhos (0.10-0.20 mmol), cesium carbonate (2 mmol) in DMF (7-10 mL) with heating under microwave at 140-150 C. for 30 minutes to form purines of Formula I. Formula I purines can be further purified by diluting with EtOAc, filtering the contents of the reaction, concentrating and purifying with flash chromatography or reverse phase HPLC. Formula I purines can be further derivatized in subsequent transformations to functionalize R1, for example by deprotecting any protected functional groups (for example deprotecting BOC-protected amine groups followed by additional steps, such as reductive amination, amide coupling or acylation to form additional compounds of Formula I.Example 131 1-(3-(2-(2-(dimethylamino)-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yloxy)azetidin-1-yl)-2-methylpropan-1-one 131 The compound was prepared from 1-(3-(2-chloro-9-methyl-6-morpholino-9H-purin-8-yloxy)azetidin-1-yl)-2-methylpropan-1-one and <strong>[2851-13-0]N,N-dimethyl-1H-benzo[d]imidazol-2-amine</strong> following General Procedure of Buchwald coupling shown in Scheme 3. 1H NMR (400 MHz, CDCl3) delta 8.29 (s, OH), 7.58 (d, J=7.5 Hz, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.15 (dd, J=11.0, 4.3 Hz, 1H), 7.01 (dd, J=10.1, 4.2 Hz, 1H), 5.58-5.45 (m, 1H), 4.60 (d, J=7.2 Hz, 2H), 4.53-4.39 (m, 2H), 4.31 (d, J=9.6 Hz, 1H), 4.19 (s, 5H), 3.88-3.74 (m, 4H), 3.65 (s, 2H), 3.60 (s, 1H), 3.17 (s, 1H), 2.98 (s, 4H), 2.56-2.42 (m, 1H), 1.14 (d, J=6.8 Hz, 5H). LCMS: M+H+=520.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | In ethanol; at 60℃; for 48.0h; | 2-Acetylpyridine (1.12 cm3, 9.9 mmol) was added consecutively by syringe, to a solution of 2-(1-methylhydrazinyl)-1Hbenzo[d]imidazole (1.62 g, 9.9 mmol) in ethanol. The mixture was stirred and heated at 60 C for 48 h. The product was isolated by evaporation of the solvent and recrystallization of the residue from a minimum volume of CH3CN by the gradual addition of diethyl ether. Yield: 83% (2.19 g). ESI-MS: m/z (%) = 266 (100) [L+H]+, 288(30) [L+Na]+. 1H NMR (300 MHz, CD3CN): 8.21 (d, J = 4.5 Hz, 1H),7.73 (d, J = 8.0 Hz, 1H), 7.57 (t, J = 7.8 Hz, 1H), 7.06-7.23 (m, 5H),3.48 (s, 3H, CH3-N), 3.48 (s, 3H, CH3-CN) ppm. 13C NMR (CD3CN,100 MHz): 162.04, 157.09, 155.16, 148.93, 148.72, 136.81, 136.29,127.07, 124.41, 121.62, 77.31, 76.99, 76.54, 40.26, 16.38 ppm. IR (KBr): m(C-H)ar 3075m, 3058s, 3029s, m(CC) 1580m, 1564m,1517w, 1456s; m(CN) 1442s, 1400m, 1346w, 1311s, q(C-H)1198s, 1170vs, 1143m, 1085s, 990s, 952s, 885vs; c(C-H) 837s,806m, 789s, 762m, 735m, 641s, 608s, 548m, 438s, 414s cm1. Anal.Calc. for C15H15N5 (265.32): C, 67.90; H, 5.70; N, 26.4. Found: C,67.82; H, 5.77; N, 26.32%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With triethylsilane; palladium 10% on activated carbon; In tetrahydrofuran; at 20℃; for 48.0h;Inert atmosphere; | General procedure: A 16 mL vial with a PTFE/silicone septum and a nitrogen-bubbler line was charged with N-benzylbenzimidazole (208.1 mg, 1.0 mmol), Pd/C (10 wt %, dry powder, reduced) (20 mg) and THF (5 mL). The mixture was treated at rt with triethylsilane (320 muL, 2.0 mmol) and then stirred under nitrogen for 14 h at rt. The mixture was filtered through a 0.45 muM PTFE syringe filter and the filtrate was concentrated in vacuo. The residue was purified by column chromatography (0 to 10% MeOH/ dichloromethane) to afford benzimidazole as a colorless solid (117.6 mg, 0.996 mmol 99%). The reactions generally exhibit an induction period of 5 to 30 min as indicated by the initiation of gas release (i.e., bubbling) from the reaction mixture. The use of Pd/C on a dry matrix is imperative as wet Pd/C results in decreased yield or no reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With pyridine; copper(l) iodide; sodium hydroxide; at 60℃; for 0.166667h;Microwave irradiation; Green chemistry; | Add 1 mmol of o-phenylenediamine to the reaction vessel.Add 0.05 mmol of cuprous iodide sequentially.1 mmol of sodium hydroxide, N,N-dimethylaminothioformyl chloride 2.5 mmol,3 ml pyridine.Heated to 60 C at 120 W in a microwave reactorContinuous reaction for 10 min.After the reaction is completed, it is cooled to room temperature.Concentrated under reduced pressure,The product is purified by column chromatography.A white solid was obtained in 88% yield. |
87% | With iron(III) chloride; caesium carbonate; In tetrahydrofuran; at 60℃; for 5.0h;Green chemistry; | Add 1 mmol of o-phenylenediamine to the reaction vessel.Add 0.1 mmol of ferric chloride in sequence,Cesium carbonate 1 mmol,N,N-dimethylaminothioformyl chloride 2.5 mmol,3 ml of tetrahydrofuran. Heat to 60 C for 5 h. After the reaction is completed, it is cooled to room temperature.Concentrated under reduced pressure, the product was purified by column chromatography.A white solid was obtained in a yield of 87%. |
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