Structure of 345311-03-7
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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. : | 345311-03-7 |
Formula : | C11H17N3O2 |
M.W : | 223.27 |
SMILES Code : | O=C(N1CC2=NC=CN2CC1)OC(C)(C)C |
MDL No. : | MFCD09878590 |
InChI Key : | WDHIKONIOJKMIK-UHFFFAOYSA-N |
Pubchem ID : | 21955306 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.64 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 63.71 |
TPSA ? Topological Polar Surface Area: Calculated from |
47.36 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.37 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.44 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.1 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.48 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.36 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.95 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.53 |
Solubility | 6.52 mg/ml ; 0.0292 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.0 |
Solubility | 22.2 mg/ml ; 0.0995 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.48 |
Solubility | 7.34 mg/ml ; 0.0329 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 |
-7.35 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 |
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) |
2.6 |
* 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 |
---|---|---|
In dichloromethane; at 0 - 20℃; for 1.0h; | 1,1-Dimethylethyl 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-7-carboxylate (Description 163, 505 mg, 2.26 mmol) in dichloromethane (2.5 mL) was added to stirred, cooled (0 C.) trifluoroacetic acid (5 mL) and the mixture was stirred at 0 C. for 15 minutes, then at room temperature for 45 minutes. The solvent was evaporated under reduced pressure to give the title compound. m/z (ES+) 124 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With tetrabutyl ammonium fluoride; In tetrahydrofuran; for 21.5h;Heating / reflux; | Tetrabutylammonium fluoride (1M in tetrahydrofuran, 7.1 mL, 7.1 mmol) was added to a solution of 1,1-dimethylethyl N-(2-chloroethyl)-N-(1-[2-trimethylsilyl)ethoxy]methyl}-1H-imdazole-2-ylmethyl)carbamate (Description 162, 2.52 g, 6.5 mmol) in tetrahydrofuran (50 mL) and the mixture was heated under reflux for 1.5 hours. Further tetrabutylammonium fluoride (1M in tetrahydrofuran, 7.1 mL, 7.1 mmol) was added and the mixture was heated under reflux for 20 hours. The mixture was cooled and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with CH2Cl2/MeOH (97:3), to give the title compound (505 mg, 35%). m/z (ES+) 224 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tin(IV) chloride; In 1,3,5-trimethyl-benzene;Reflux; | EXAMPLE E; Preparation of Compounds E of Formula 1 ^N^s^ Br+ General Process for the Preparation of Compound E-In-2 from E-In- 1 :[00127] A round bottom flask was charged with E-In-I (1 eq.), CH2CI2, mesitylene and Tin(IV) chloride (0.3 eq.). The mixture was brought to reflux then aminoacetaldehyde diethyl acetal (2 eq.) was added slowly. The reaction was refluxed for 2 - 3d. The reaction was diluted with CH2CI2 and filtered through activated charcoal and the filtrate was evaporated giving a solid which was purified by trituration, or recrystallization, or silica gel column chromatography, or Shimadzu automated preparative HPLC system, to afford E-In-2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-Bromosuccinimide; In tetrachloromethane; for 0.5h;Reflux; | General Process for the Preparation of Compound E-In-3 from E-In-2: [00128] A round bottom flask was charged with E-In-2 (1 eq.), CCl4 and N- bromosuccinimide (1 eq.). The solution was refluxed for 30 minutes then allowed to cool. The CCl4 solution was decanted off a brown solid and evaporated. The residue was purified by trituration, or recrystallization, or silica gel column chromatography, or Shimadzu automated preparative HPLC system, to afford E-In-3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 20℃; for 48.0h; | 5,6,7,8-Tetrahydroimidazo[1 ,2-a]pyrazine(l17) (4.53 g, 36.8 mmol) and triethylamine (6.16 mL, 44.2 mmol) were dissolved in dichloromethane (DCM) (200 mL) and treated with di-tert-butyl dicarbonate (10.25 mL, 44.2 mmol). The solution was stirred at RT for 48 h and concentrated in vacuo to afford a crude oil. The crude product was purified by flash chromatography (Isolera, 340 g, 0-100% 2M ammonia in methanokdichloromethane (1 :9)/dichloromethane) to afford 3 fractions. Fraction 2 was identified by LC/MS as containing desired product. The residue was dissolved in ethyl acetate (300 ml), washed with saturated sodium bicarbonate solution (50 ml_), water (2 x 50 ml_), brine (50 ml_), dried over anhydrous sodium sulfate and concentrated to afford product in 6.77g. LC/MS = 224 (M+H)+, retention time = 0.71 minutes (2 minute method (high pH)). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-chloro-succinimide; In toluene; at 80℃; for 2.0h; | 1 ,1-Dimethylethyl 5,6-dihydroimidazo[1 ,2-a]pyrazine-7(8/-/)-carboxylate (118) (1.563 g, 7 mmol) and NCS (0.935 g, 7.00 mmol) were heated at 80 0C for 2 h in toluene (30 ml_). The solvents were removed in vacuo and the residue was purified by flash chromatography (Isolera, 50 g, 0-100% ethyl acetate/iso-hexane) to afford product in 1.55 g. LC/MS = 258/260 (M+H)+, retention time = 0.64 minutes (2 minute method). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); palladium diacetate; In N,N-dimethyl-formamide; at 140℃; for 3.0h;Inert atmosphere; Sealed vial; | 7-Bromo-N-(3-ethyl-l-((6-methylpyridin-2-yl)methyl)-lH-indazol-4- yl)imidazo[l,2-a]pyridine-3-carboxamide (prepared as in Example 127, Step A; 50 mg, 0.10 mmol) in DMF (4 mL) was added tert-butyl 5,6-dihydroimidazo[l,2-a]pyrazine-7(8H)- carboxylate (68 mg, 0.31 mmol), Pd(PPh3) 4 (12 mg, 0.01 mmol), palladium diacetate (2.3 mg, 0.010 mmol) and K2C03 (42 mg, 0.31 mmol). The reaction mixture was purged with argon and the reaction vial was sealed and the mixture was heated to 140 C for 3 hours. The mixture was cooled to ambient temperature and diluted with DCM (20 mL). The solution was washed with H20, dried (Na2S04) and concentrated under reduced pressure. The residue was purified by silica gel chromatography (DCM/MeOH/NH4OH 10: 1 :0.1) to provide the final product (14 mg). MS (ES+APCI) m/z = 532 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | With potassium carbonate;palladium diacetate; triphenylphosphine; In 1,4-dioxane; at 95℃; for 5.0h; | Example 563-Cyclopropyl-3-(4-(7-f 5,6 J,8-tetrahydroimidazo[ 1 ,2-alpyrazin-3-yl)imidazo|T 2- clpyrimidin-5-yl)- 1 H-pyrazol- 1 -vDpropanenitrile[00698] To 3-(4-(7-chloroimidazo[l,2-c]pyrimidin-5-yl)-lH-pyrazol-l-yl)-3- cyclopropyl-propanenitrile (Preparation M; 100 mg, 0.320 mmol) in dioxane (10 mL) was added K2C0 (88.4 mg, 0.639 mmol), diacetoxypalladium (7.18 mg, 0.0320 mmol), triphenylphosphine (16.8 mg, 0.0639 mmol) and tert-butyl 5,6-dihydroimidazo[l,2- a]pyrazine-7(8H)-carboxylate (107 mg, 0.480 mmol). The reaction was sealed and heated to 95 C for 5 hours. The reaction was cooled to ambient temperature and concentrated under reduced pressure. The residue was purified by silica gel chromatography (DCM/MeOH/NH4OH 10:1 :0.1) to give the final product (33 mg, 26% yield). MS (apci) m/z = 400.4 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
500 mg | With palladium diacetate; potassium carbonate; tricyclohexylphosphine; Trimethylacetic acid; In N,N-dimethyl acetamide; at 100℃; for 6.0h; | A mixture of <strong>[345311-03-7]tert-butyl 6,8-dihydro-5H-imidazo[1,2-a]pyrazine-7-carboxylate</strong> (1.0 g, 4.48 mmol), 8-chloro-7-fluoro-6-iodo-isoquinolin-3-amine (1.5 g, 4.65 mmol), potassium carbonate (1.0 g, 7.25 mmol), palladium acetate (122 mg, 0.37 mmol), tricyclohexyl phosphine (210 mg, 0.75 mmol) and trimethylacetic acid (115 mg, 1.13 mmol) in N,N-dimethylacetamide (20 mL) was stirred for 6 hours at 100 C. The resulting mixture was cooled to room temperature and then filtered. The filtrate was concentrated under vacuum. The residue was purified by reverse phase chromatography (acetonitrile 0-55/0.05% sodium bicarbonate in water) to afford tert-butyl 3-(3-amino-8-chloro-7-fluoro-6-isoquinolyl)-6, 8-dihydro-5H-imidazo[1,2-a]pyrazine-7-carboxylate (500 mg, 1.20 mmol) as a yellow solid. LCMS (ESI) [M+H]+=418.1. |
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