Structure of 851784-82-2
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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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CAS No. : | 851784-82-2 |
Formula : | C15H17Cl2NO4 |
M.W : | 346.21 |
SMILES Code : | O=C(C1=C(Cl)C2=C(CN(C(OC(C)(C)C)=O)CC2)C=C1Cl)O |
MDL No. : | MFCD22370640 |
InChI Key : | JXBQRXIJBFUZMR-UHFFFAOYSA-N |
Pubchem ID : | 44514641 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 22 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.47 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 88.6 |
TPSA ? Topological Polar Surface Area: Calculated from |
66.84 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.88 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.42 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.45 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.13 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.2 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.21 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.08 |
Solubility | 0.0289 mg/ml ; 0.0000834 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.5 |
Solubility | 0.0109 mg/ml ; 0.0000313 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.03 |
Solubility | 0.0322 mg/ml ; 0.0000929 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
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 |
-5.98 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 |
0.56 |
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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.62 |
* 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 |
---|---|---|
91.8% | 2-(ieri-butoxycarbonyl)-5,7-dichloro- l,2,3,4-tetrahydroisoquinoline-6-carboxylic acid (20 g), HATU (27.5 g) was charged in DMF (60 ml) and diisopropyl ethylamine (22,2 g) was added. Reaction mass was cooled to 0-5C and added methyl (S)-2-amino-3-(3- (m.ethylsuIfonyl)phenyl)propanoate hydrochloride (17.6g) lot wise at 0-5C. Temperature of reaction mass was raised to room temperature. Stirred and reaction monitored by TLC. After completion of reaction, Water (100 ml) and MDC (100 ml) was added. Stirred and separated the layers. Organic layer washed with brine and 10% sodium carbonate solution. Organic layer distilled and charged 1 N HC1 (100 ml) to the residue. After complete hydrolysis pH of reaction mass was adjusted to 5.0-5.5 using sodium hydroxide solution. Reaction mass was filtered and solid so obtained was dried to get (S)-2-(5 ,7-dichloro- 1 ,2,3 ,4- tetrahydroisoquinoline-6-carb^ acid (25 g, (0185) 91.8% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2-(ieri-butoxycarbonyl)-5,7-dichloro- l,2,3,4-tetrahydroisoquinoline-6-carboxylic acid (20.0g) was added to 50.0 ml of DMF followed by addition of DIPEA (37.2 g), HATU (27.4g) and stirred the reaction mass for 30 min at room temperature. Charged methyl (S)-2- amino-3-(3-(methylsulfonyl)phenyl)propanoate hydrochloride (17.6g) and stirred the reaction mass at 100C for 1-2 hrs. After completion of reaction, cooled the reaction mass to 30-35C, charged the reaction mass to the mixture of ethyl acetate (200ml) and water (200 ml) and stirred for 15-30 min at 30-35C. Separated the ethyl acetate and washed with acidic water (200ml water + 18ml of cone. HC1) followed by washing with water. Distilled the ethyl acetate at 40-45C to get tert-butyl (S)-5,7-dichloro-6-((l-methoxy-3-(3- (xnethylsulfonyl)phenyl)- l-oxopropan-2-yl)carbamoyl)-3,4-dihydro isoquinoline-2( lH)- carboxylate (40g, crude). |
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