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Structure of 179474-79-4
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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. : | 179474-79-4 |
Formula : | C9H20N2O |
M.W : | 172.27 |
SMILES Code : | COCCCN1CCC(N)CC1 |
MDL No. : | MFCD11104531 |
InChI Key : | HIXAJGFVNMKLML-UHFFFAOYSA-N |
Pubchem ID : | 12088093 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H312-H412-H314 |
Precautionary Statements: | P260-P264-P270-P273-P280-P301+P330+P331-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P405-P501 |
Class: | 8 |
UN#: | 2735 |
Packing Group: | Ⅱ |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 53.87 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.49 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.2 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.09 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.07 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.34 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.73 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.68 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.7 |
Solubility | 34.3 mg/ml ; 0.199 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.45 |
Solubility | 60.7 mg/ml ; 0.352 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.35 |
Solubility | 7.66 mg/ml ; 0.0445 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 |
No |
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 |
-7.29 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) |
1.51 |
* 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 |
---|---|---|
Example 6 5-AMINO-6-CHLORO-2-METHYL-N-{1-[3-(METHOXY)PROPYL]-4-PIPERIDINYL}IMIDAZO[1,2-a]PYRIDINE-8-CARBOXAMIDE The title compound was prepared according to the procedure described in the step 3 of EXAMPLE 5 using 1-[3-(methoxy)propyl]-4-piperidinamine instead of 1-(1-butyl-4-piperidinyl)methanamine. MS (EI) m/z: 379 (M+). m.p.: 190 C. IR (KBr) nu: 3477, 3304, 3148, 2932, 2808, 1636, 1601, 1560, 1545, 1512, 1439, 1381, 1319,1234,1119 cm-1. 1H-NMR (DMSO-d6) delta: 1.56-1.45 (2H, m), 1.66 (2H, quint, J=6.9 Hz), 1.92-1.88 (2H, m), 2.21-2.14 (2H, m), 2.34 (2H, t, J=7.4 Hz), 2.38 (3H, s), 2.75-2.65 (2H, m), 3.22 (3H, s), 3.37-3.32 (2H, m), 3.91-3.86 (1H, m), 7.58 (2H, br s), 7.84 (1H, s), 7.87 (1H, d, J=0.9 Hz), 9.99 (1H, d, J=8.1 Hz). Anal. Calcd. for C18H26ClN5O2: C, 56.91; H, 6.90; N, 18.44. Found: C, 56.87; H, 6.92; N, 18.40. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 5-Amino-N-[(1-butyl-4-piperidinyl)methyl]-6-chloro-2-methylimidazo; | Example 14 5-AMINO-6-CHLORO-2-ETHYL-N-{1-[3-(METHOXY)PROPYL]-4-PIPERIDINYL}IMIDAZO[1,2-a]PYRIDINE-8-CARBOXAMIDE The title compound was prepared according to the procedure described in the step 3 in EXAMPLE 5 using 5-amino-6-chloro-2-ethylimidazo[1,2-a]pyridine-8-carboxylic acid (EXAMPLE 10, Step 2) and 1-[3-(methyloxy)propyl]-4-piperidinamine (EXAMPLE 3). MS (EI) m/z: 393 (M+). m.p.: 179 C. IR (KBr) nu: 3329, 3169, 3055, 2938, 1653, 1630, 1583, 1540, 1513, 1427, 1337, 1324, 1122,745 cm-1. 1H-NMR (DMSO-d6) delta: 1.31 (3H, t, J=7.5 Hz), 1.40-1.55 (2H, m), 1.66 (2H, quint, J=6.9 Hz), 1.87-1.92 (2H, m), 2.16-2.28 (2H, m), 2.33 (2H, t, J=7.4 Hz), 2.66-2.71 (2H, m), 2.74 (2H, q, J=7.5 Hz), 3.22 (3H, s), 3.33-3.42 (2H, m), 3.88-3.95 (1H, m), 7.84 (1H, s), 7.90 (1H, s), 10.07 (1H, d, J=7.5 Hz). Anal. Calcd. for C19H28ClN5O2.0.1C4H10O: C, 58.06; H, 7.28; N, 17.45. Found: C, 58.08; H, 7.51; N, 17.08. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 5-Amino-N-[(1-butyl-4-piperidinyl)methyl]-6-chloro-2-methylimidazo; | Step 1, 5-amino-6-chloro-2-propyl-N-{1-[3-(methoxy)propyl]-4-piperidinyl}imidazo[1,2-a]pyridine-8-carboxamide The title compound was prepared according to the procedure described in the step 3 in EXAMPLE 5 using 5-amino-6-chloro-2-propylimidazo[1,2-a]pyridine-8-carboxylic acid (EXAMPLE 16, Step 2) and 1-[3-(methyloxy)propyl]-4-piperidinamine (EXAMPLE 3). MS (EI) m/z: 407 (M+). 1H-NMR (DMSO-d6) delta: 0.99 (3H, t, J=7.4 Hz), 1.43-1.57 (2H, m), 1.61-1.80 (4H, m), 1.82-1.96 (2H, m), 2.17-2.37 (4H, m), 2.59-2.72 (2H, m), 2.70 (2H, t, J=7.2 Hz), 3.22 (3H, s), 3.27-3.48 (2H, m), 3.85-4.01 (1H, m), 7.57 (2H, br s), 7.84 (1H, s), 7.90 (1H, s), 10.10 (1H, br). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; potassium hydroxide; In water; acetonitrile; at 5 - 25℃; for 13h; | A solution of 4-formamide-1- (3-methoxypropyl) -piperidine (III) (229 g, 1.14 mol), water (2.06 L) and acetonitrile (571.9 g)After adding KOH (287.3 g, 5.13 mol), the reaction was carried out at a temperature of not higher than 5 C by adding dibromohydantoin (180.2 g, 0.63 mol) and the temperature was raised to 15-25 C for 13 hours to stop the reaction.The reaction solution was concentrated under reduced pressure at 55 C to recover acetonitrile.The residue was extracted with DCM and the organic layer was dried over anhydrous sodium sulfate,And the organic phase was concentrated under reduced pressure at 50 C to give 178.2 g of a pale yellow liquid,The yield was 95% (in terms of II-1) and the GC purity was 98.6%.The product was placed in a distillation flask, the pump was decompressed (with a thorned distillation column)External temperature gradient temperature (5 / times),When the internal temperature rose to 72 ~ 73 ,The fractions were collected to give 148 g of colorless transparent liquid,The distillation yield was 83% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | THF, 4-amino-5-chloro-2,3-dihydrobenzofuran-7-carboxylic acid (1.0 g), a small amount of CDI was added, stirred for 25 min,(0.8 g, GC & gt; 98%) was added dropwise to a solution of 1- (3-methoxypropyl) -4-piperidinamine (I) at 45 C for 4 h, (30g), precipitate a large amount of solid, stirring at 25 for 1h; pumping, 20g of water rinse, collecting filter cake, drying, diclofenac 1.5g , Yield 85% (mp = 91-92 C).To the reaction flask was added paclitaxel (1.0 g) and 75% ethanol (5 mL), heated to 40 C, and succinic acid (0.35 g) was added with stirring and stirred for 3 h. The filter cake was recrystallized from 75% ethanol and dried to give 1.17 g of white granular crystals in 93% yield |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With hydrogenchloride; In water; at 0 - 20℃;pH 1 - 2; | Under nitrogen protection, the intermediate (26.4 g, 0.1 mol) was dissolved in 120 mL of anhydrous tetrahydrofuran in a 500 mL three-necked flask equipped with a temperature and dropping funnel.The reaction solution was cooled to 0 C, and 60% sodium hydride solid (6.0 g, 0.15 mol) was added in 3-5 batches,After the addition was complete, the incubation was maintained at 0 C for 30 minutes.Then will be3-Methoxybromopropane (16.8 g, 0.11 mol) was dissolved in 30 mL of tetrahydrofuran slowly dropwise to the reaction system,After completion of the dropwise addition, the reaction solution was spontaneously stirred at room temperature for 3 hours, and the TLC reaction was terminated.The reaction system was cooled to 0 C and about 2.0% by weight of 10% hydrochloric acid was added dropwise. The temperature was not more than 20 C during the dropwise addition,Followed by incubation until the TLC detection of protective groups removed, this time measuring system PH = 1-2,After adding 80mL of ethyl acetate, the organic layer was dried,After addition of n-heptane, 16.7 g of benzophenone was obtained and the recovery was 92%.Water layer by adding 1 M sodium hydroxide adjusted PH = 13-14, dichloromethane 100mL extraction twice,Anhydrous Na2SO4 dried, filtered,The organic layer was dried to give 13.9 g of 1- (3-methoxypropyl) piperidin-4-amine in 81% yield, GC: 97.2%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36.5 g | With tert.-butylhydroperoxide; calcium carbonate pentahydrate; In acetonitrile; at 80℃; for 8h; | Taking 4-amino-5-chloro-7-aldehyde-2,3-dihydrobenzofuran 19.7 g,1-(3-methoxypropyl)-4-piperidinamine 18.5 g, dissolved in 100 mL of acetonitrile,Add 54g of t-butyl hydroperoxide (TBHP), 20g of calcium carbonate,3g3gCuSO4·5H2O, reacted at 80 C for 8 h, after the reaction is over,Add 30 g of sodium sulfite and 100 mL of water, extract with ethyl acetate, and wash with water.The organic layer is dried over anhydrous sodium sulfate.The filtrate was filtered under reduced pressure to give a white solid (36.5 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33.6 g | With tert.-butylhydroperoxide; zinc(II) iodide; In acetonitrile; at 70℃; for 5h; | Take 19.9 g of 4-amino-5-chloro-7-hydroxymethyl-2,3-dihydrobenzofuran, 18.5 g of 1-(3-methoxypropyl)-4-piperidinamine, dissolved in In 70 mL of acetonitrile, 54 g of t-butyl hydroperoxide (TBHP) was added, and 1.6 g of zinc iodide was reacted at 70 C for 5 h. After the reaction was completed, 30 g of sodium sulfite and 100 mL of water were added, and the mixture was extracted with ethyl acetate. After drying, the filtrate was filtered under reduced pressure to give a white solid (36.5 g). |
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