Structure of 105752-11-2
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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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Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 105752-11-2 |
Formula : | C5H5IN2 |
M.W : | 220.01 |
SMILES Code : | C1=NC=CC(=C1N)I |
MDL No. : | MFCD04971334 |
InChI Key : | ZJRSKTXMSIVNAU-UHFFFAOYSA-N |
Pubchem ID : | 819132 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 41.36 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.91 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.26 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.82 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.28 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.75 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.69 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.16 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.28 |
Solubility | 1.17 mg/ml ; 0.0053 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.22 |
Solubility | 13.3 mg/ml ; 0.0604 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.62 |
Solubility | 0.524 mg/ml ; 0.00238 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 |
-7.06 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) |
1.67 |
* 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 |
---|---|---|
92% | iV-(4-Iodo-pyridin-3-yl)-2,2-dimethyl-propionamide (20.00 g, 65.76 mmol) was charged to a 2 L round-bottom flask and 24% sulfuric acid in water (640 mL) was added carefully. The mixture was heated to 100 C for 4 hours. The reaction was determined complete by analyitical HPLC. The mixture was allowed to cool to room temperature and then carefully adjusted to pH 7-8 with 4Ν NaOH (approximately 700 mL). Saturated sodium bicarbonate was added to the mixture and the product extracted into dichloromethane (3 X 500 mL). The organic layers were combined and concentrated to give 3-amino-4-iodo- pyridine (13.3 g, 92%). | |
90% | With sulfuric acid; In water; for 1h;Heating / reflux; | The product of preparation 22 (4.69g, 15.4mmol) and dilute sulphuric acid (24%, 120mL) were heated under reflux for 1 hour. The mixture was then cooled, basified with solid sodium hydrogen carbonate to pH8 and extracted with dichloromethane (3x200mL). The combined organic solutions were dried over magnesium sulfate and concentrated in vacuo. Purification of the residue by column chromatography on silica gel, eluding with dichloromethane:methanol, 100:0 to 90:10, afforded the title compound as a brown solid in 90% yield, 3.04g. 1H-NMR(CDCl3, 400MHz) δ: 4.11 (bs, 2H), 7.56(d, 1H), 7.61 (d, 1H), 8.05(s, 1H) MS APCI+ m/z 221 [MH]+ |
75% | The reaction was performed according to a procedure in the literature (Tetrahedron Lett. 2005, 46, 6363). A 1 L three-neck round-bottom flask was equipped with a mechanical stirrer, thermocouple, nitrogen inlet, and drying tube and placed in a heating mantle. The flask was charged with N-(4-iodo(3-pyridyl))-2,2-dimethylpropanamide (43, 45 g) and 25% sulfuric acid (270 mL). The solubility of starting material in 25% sulfuric acid was very high and formed light yellow clear solution. The reaction mixture was heated to 80 C. for 8 h. The reaction mixture was stirred continually at 80 C. until deemed to be complete, i.e., upon complete disappearance of starting material (N-(4-iodo(3-pyridyl))-2,2-dimethylpropanamide, 43). If reaction was not complete, stirring was continued at 80 C. for additional 6 h then monitored again, and repeated until complete. Typically, reaction was complete within 4-6 h. The reaction was monitored by TLC (SiO2, 100% EtOAc, UV) by partitioning an aliquot of reaction mixture (1 mL) between 50% NaOH solution (2 mL) and EtOAc (4 mL), agitating, allowing the layers to separate, and spotting the organic layer on TLC. The starting material (N-(4-iodo(3-pyridyl))-2,2-dimethylpropanamide, 43) had an RF of 0.55, and the product (4-iodo-3-pyridylamine, 44) had an RF of 0.35. Materials used to synthesize 4-iodo-3-pyridylamine (44) are shown in Table 35.To isolate the product (4-iodo-3-pyridylamine, 44), the flask was cooled to -10 C. and the mixture was cautiously basified (pH 10-11) with 50% NaOH solution (45 g) while maintaining a temperature below 10 C. Additional ethyl acetate (200 mL) was added, the reaction was stirred for 10 minutes, and the layers were allowed to separate. The organic layer was collected, and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layer was dried over MgSO4 and charcoal, filtered through a glass fiber filter paper, and concentrated to dryness. The residue was diluted with MTBE (50 mL) and the solids were filtered, rinsing with MTBE (10 mL). The product was air-dried for 2 h and then dried under high vacuum at room temperature to constant weight.4-Iodo-3-pyridylamine (44, lot No. 1358-86-1) was an off-white solid, synthesized with a yield of 24 g (75%). 4-Iodo-3-pyridylamine (44) was analyzed using HPLC (PLX-LC3, 220), and according to results, it was 100% pure. 1H-NMR (300 MHz, CDCl3) was used to confirm the identity of 4-iodo-3-pyridylamine (44). |
3-(tert-Butylcarbonylamino)-4-iodo-pyridine (20.00 g, 65.76 mmol) was charged to a 2 L round-bottom flask, and sulfuric acid, 24% in water (640 mL) was carefully added. The reaction was heated to 100 0C. After 4 hours, the reaction was shown to be complete as determined by HPLC. After cooling to room temperature, the solution was carefully neutralized with 4 M NaOH until a pH of 7-8 was achieved. Saturated bicarbonate was added to the reaction mixture, and the product extracted into dichloromethane (3 X 500 mL). The organic layers were combined and concentrated to give 13.3 g of 3-amino-4-iodo-pyridine. | ||
A solution of N-(4-iodo-pyridin-3-yl)-2,2-dimethyl-propionamide (6 g, 19.73 mmol) in aqueous 3M HCl (50 mL) was heated to 100 C. for 18 hours. After the completion of reaction, the reaction mass was washed with EtOAc. Under cooling the pH of the aqueous layer was adjusted to pH 9 using solid Na2CO3 and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford 4-iodo-pyridin-3-ylamine (3.2 g crude, 73%) as a brown sticky solid that was used in the next step without further purification. | ||
A solution of N-(4-iodo-pyridin-3-yl)-2,2-dimethyl-propionamide (6 g, 19.73 mmol) in aqueous 3M HC1 (50 mL) was heated to 100 C for 18 hours. After the completion of reaction, the reaction mass was washed with EtOAc. Under cooling the pH of the aqueous layer was adjusted to pH 9 using solid Na2C03 and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2S04, filtered, and concentrated in vacuo to afford 4-iodo-pyridin-3-ylamine (3.2g crude, 73%) as a brown sticky solid that was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With calcium oxide;tris(dibenzylideneacetone)dipalladium(0) chloroform complex; 1,1'-bis(diphenylphosphino)ferrocene; In acetonitrile; at 60℃;Inert atmosphere; | A solution of 3-amino-4-iodopyridine (500 mg, 2.27 mmol), tris(dibenzylideneacetone)dipalladium(0) (63.6 mg, 0.07 mmol), dppf (155 mg, 0.28 mmol), calcium (II) oxide (255 mg, 4.55 mmol) and tert-butyl-2-amino-2-thioxoethylcarbamate (600 mg, 3.15 mmol) in anhydrous acetonitrile (4.5 mL) was degassed and stirred under argon atmosphere at 60C overnight. The solution was filtered over a pad of celite, rinsed with dichloromethane, methanol, ethyl acetate, and evaporated. Purification by flash chromatography (silica gel, dichloromethane/methanol 1/0 to 95/5) led to tert-butyl [1,3]thiazolo[4,5-c]pyridin-2-ylmethylcarbamate (500 mg, 83%) as a yellow oil. ESI-MS m/z 266 (M+H)+. |
61.6% | To a stirred solution of 4-iodopyridin-3-amine (500 mg, 2.2 mmol) in acetonitrile (5 mL) wasadded tert-butyl (2-amino-2-thioethoxyethyl)carbamate (561 mg, 2.9 mmol) and CaO (255 mg,4.5 mmol) at room temperature. The reaction mixture was purged with argon for 15 minutes,then dppf (151 mg, 0.27 mmol) and Pd2(dba)3 (64 mg, 0.06 mmol) was added to the reactionmixture. The reaction mixture was purged with argon for further 5 minutes and stirred in sealedtube at 60 C for 16 h. The reaction mixture was filtered through celite pad and washed the pad |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate; In 1,4-dioxane; water; at 100℃; for 16h;Inert atmosphere; Sealed tube; | 2,6-dichloro-[3,4'-bipyridin]-3'-amine (i64): To a stirred solution of 4-iodopyridin-3-amine (2 g, 9.0 mmol) in 1 ,4-dioxane (84 ml_), (2,6- dichloropyridin-3-yl) boronic acid (2.4 g, 12.5 mmol) and K3P04 (5.6 g, 26.0 mmol) solution in water (28 mL) were added and the reaction was degassed with argon for 20 min. PdCI2(PPh3)2 (0.7 g, 0.99 mmol) was added and the reaction was heated in a sealed tube at 100C for 16 h. The progress of the reaction was monitored by TLC. After completion, the reaction was diluted with water and filtered. The aqueous layer was extracted with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude product was purified by silica gel (100:200 mesh) column chromatography using 2% methanol in dichloromethane as eluent to afford 2,6-dichloro-[3,4'-bipyridin]-3'-amine (64) (1 .08 g, Yield 51 %). 1 H NMR (400 MHz, DMSO-d6) delta 5.26 (s, 2H), 6.93 (d, J = 4.9 Hz, 1 H), 7.51 -7.68 (m, 1 H), 7.79- 7.89 (m, 2H), 8.08 (s, 1 H), MS (ESI) m/e (M+1 )+: 240.00 |
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