Structure of 171879-99-5
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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. : | 171879-99-5 |
Formula : | C8H7ClN2 |
M.W : | 166.61 |
SMILES Code : | CC1=CC(Cl)=C2C(NC=C2)=N1 |
MDL No. : | MFCD09880146 |
InChI Key : | KPYXZCLJFKCACT-UHFFFAOYSA-N |
Pubchem ID : | 24729584 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 46.07 |
TPSA ? Topological Polar Surface Area: Calculated from |
28.68 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.81 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.34 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.52 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.9 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.12 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.34 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.95 |
Solubility | 0.186 mg/ml ; 0.00112 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.58 |
Solubility | 0.437 mg/ml ; 0.00262 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.91 |
Solubility | 0.0207 mg/ml ; 0.000124 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 |
-5.65 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) |
1.39 |
* 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 |
---|---|---|
55% | With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 4.0h; | To a 0 C suspension of <strong>[171879-99-5]4-chloro-6-methyl-1H-pyrrolo[2,3-b]pyridine</strong> (1.7 g, 10mmol) in N,N-dimethylformamide (20 mL) was added potassium hydroxide (1.14 g, 20.3 mmol), followed by iodine (2.54 g, 10.0 mmol). The reaction mixture was allowed to warm to room temperature and stir for 4 hours, whereupon it was diluted with water and filtered, to afford the product as a white solid. Yield: 1.6 g, 5.5 mmol, 55%. H NMR (400 MHz, CD3OD) oe 7.47 (s, 1 H), 7.04 (s, 1 H), 2.54 (s, 3H). |
With N-iodo-succinimide; In dichloromethane; at 0 - 20℃; for 18.0h; | D124-chloro-3-iodo-6-methyl-lH-pyrrolo[2,To a stirred solution of 4-chloro-6-methyl-lH-pyrrolo[2,3-b]pyridine (4.06 g, 24.37 mmol) in DCM (80 mL) at 0 C, was added NIS (6.22 g, 27.6 mmol). The reaction mixture was then warmed to RT and stirred for 18 hours. The reaction mixture was then filtered (washed with excess DCM) to give the title compound (4.01 g). LCMS (A): m/z (M+H)+ 293, C8H6C1IN2 requires 292 (acidic). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With toluene-4-sulfonic acid; In water; acetonitrile; at 20 - 150℃; for 4.0h;Inert atmosphere; Microwave irradiation; | To a solution of 4-chloro-6-methyl-lH-pyrrolo[2,3-]pyridine (0.5 g, 3 mmol) in MeCN (15 mL) was added 2,6-difluorobenzylamine (2 eq) and pTSA.H20 (2 eq) under N2 at room temperature. The reaction mixture was heated at 150 C in a CEM microwave reactor for 4 hours. The mixture was diluted with sat. aq. NaHC03 (20 mL) solution and EtOAc (20 mL). The organic layer was separated, washed with brine, dried over MgSC^ and concentrated in vacuo. The residue was purified via flash chromatography using MeOH and DCM as eluent to give the product (0.521 g, 1.90 mmol, 63%) as yellow solid. 1H NMR (399 MHz, DMSO-d6) delta 10.96 (s, 1H), 7.43 (tt, 1H), 7.20 - 7.08 (m, 2H), 6.95 (d, 1H), 6.77 (t, 1H), 6.53 (d, 1H), 6.15 (s, 1H), 4.44 (d, 2H), 2.35 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9.5% | With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; caesium carbonate; XPhos; In 1,4-dioxane; at 100℃; for 4.0h; | Into a 50-mL round-bottom flask, was placed 4-chloro-6-methyl-lH- pyrrolo[2,3-b]pyridine (150 mg, 0.90 mmol, 1 equiv), 5-methoxy-4-[3-(pyrrolidin-l- yl)propoxy]pyridin-2-amine (228 mg, 0.91 mmol, 1 equiv), CS2CO3 (884 mg, 2.71 mmol, 3.00 equiv), Pd2(dba)3-CHC13 (50 mg), X-phos (50 mg), 1,4-dioxane (10 mL). The resulting solution was stirred for 4 h at 100 C. The crude product was purified by Flash-Prep-HPLC A 1 : 1. This resulted in 35.9 mg (9.5%) of N-(5-methoxy-4-(3-(pyrrolidin-l-yl)propoxy)pyridin- 2-yl)-6-methyl-lH-pyrrolo[2,3-b]pyridin-4-amine as a light yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With methanesulfonyl chloride; In N,N-dimethyl-formamide; at 75℃; | A suspension of 6-methyl-1 H-pyrrolo[2,3-b]pyridine 7-oxide (100mg, 0.68mmol) in anhydrous DMF (3ml) was treated with methanesulfonyl chloride (0.13ml, 1.7mmol) and heated at 75C overnight. After cooling to room temperature it was neutralised with 6N NaOH, resulting suspension filtered, and washed with water. The aqueous was extracted with ethyl acetate and the organic extracts were combined, washed with saturated sodium bicarbonate, brine, dried (Na2S04) and concentrated in vacuo. The crude product was dissolved in DCM / MeOH, preadsorbed onto HMN and purified by FCC eluting with a gradient from 0-30% EtOAc / DCM to afford the title compound as a white solid (50mg, 42%) LCMS (Method 3): Rt 1.14 min, m/z 167.1 [MH+]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | With methanesulfonic acid(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl)]palladium(II); In ethanol; water; at 140℃; for 0.5h;Microwave irradiation; | A mixture of 4-chloro-6-methyl-1 H-pyrrolo[2,3-b]pyridine (47mg, 0.291 mmol), 3-(4,4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyrazolo[1 ,5-b]pyridazine (107mg, 0.436mmol), X Phos Pd G3 (19.6mg, 0.023mmol) and potassium phosphate (124mg, 0.582mmol) in degassed ethanol (3.0ml_) and water (1.5ml_) was heated at 140C for 30 mins in the microwave. After cooling it was partitioned between ethyl acetate and water and the organic layer was separated, washed with brine, dried (Na2S04) and concentrated in vacuo. The crude product was purified by MDAP (Basic) to afford the title compound as a glass (27mg, 37%) LCMS (Method 1): Rt 2.12 min, m/z 249.8 [MH+]. 1 H NMR (400 MHz, d6-DMSO): 2.59 (3H, s), 6.56 (1 H, d, J=3.5 Hz), 7.19 (1 H, s), 7.34 (1 H, dd, J=4.4, 9.1 Hz), 7.43 (1 H, d, J=3.5 Hz), 8.48 (1 H, dd, J=1.8, 9.2 Hz), 8.56- 8.58 (2H, m), 11.59 (1 H, s) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; dimethyl zinc(II); In tetrahydrofuran; toluene; at 70℃; for 16.0h;Inert atmosphere; | A solution of dimethylzinc in toluene (4 mL, 4 mmol, 1 M) was slowly added dropwise under nitrogen. (6-Bromo-4-chloro-1H-pyrrolo[2,3-b]pyridin-1-yl)(phenyl)methanone (1.7 g, 5 mmol) And [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (365 mg, 0.5 mmol) in tetrahydrofuran (20 mL). The reaction solution was reacted at 70 C for 16 hours under a nitrogen atmosphere. (25mL * 2) After the reaction solution was cooled and extracted with saturated sodium bicarbonate solution (10 mL) was quenched with ethyl acetate, the organic phases were combined, dried and concentrated to give a crude product. The crude product was separated by column (ethyl acetate: petroleum ether = 1:1). 4-Chloro-6-methyl-1H-pyrrolo[2,3-b]pyridine (290 mg, yield 35%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 120℃; for 0.5h;Inert atmosphere; | N-(4-(2,4-difluorophenoxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene Ethyl sulfonamide (395 mg, 0.9 mmol), 4-Chloro-6-methyl-1H-pyrrolo[2,3-b]pyridine (100 mg, 0.6 mmol), tetrakistriphenylphosphine palladium (69 mg, 0.06 mmol) and potassium carbonate (414 mg, 3 mmol) Ethanol/toluene/water (v/v/v = 9:3:1, 10 mL). The reaction solution was subjected to microwave reaction at 120 C for 0.5 hour under a nitrogen atmosphere. The reaction solution was evaporated to dryness, and the crude material was purified (yield: ethyl ether: 1:1) N-(4-(2,4-difluorophenoxy)-3-(6-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)phenyl)ethanesulfonamide (190 mg) , yield 71%). |
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