Structure of tert-Butyl 3-bromopropanoate
CAS No.: 55666-43-8
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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. : | 55666-43-8 |
Formula : | C7H13BrO2 |
M.W : | 209.08 |
SMILES Code : | O=C(OC(C)(C)C)CCBr |
MDL No. : | MFCD04974087 |
InChI Key : | RMWVUWLBLWBQDS-UHFFFAOYSA-N |
Pubchem ID : | 256128 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H227-H302-H315-H319-H335 |
Precautionary Statements: | P210-P261-P264-P270-P271-P280-P301+P312+P330-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P370+P378-P403+P233-P403+P235-P405-P501 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.86 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 44.96 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.58 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.79 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.11 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.12 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.81 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.08 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.0 |
Solubility | 2.09 mg/ml ; 0.01 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.96 |
Solubility | 2.29 mg/ml ; 0.0109 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.45 |
Solubility | 0.745 mg/ml ; 0.00356 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 |
-6.3 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) |
2.12 |
* 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 |
---|---|---|
60% | With 2,6-dimethylpyridine; In toluene; for 48h;Reflux; | A solution of 9.26 g (42.4 mmol) of <strong>[64628-73-5]3-chloro-4-trifluoromethoxy-phenylamine</strong> and 4.39 ml (42.4 mmol) of 2,6-lutidine in 50 ml of toluene was treated slowly with 7.30 ml (42.4 mmol) of tert-butyl 3-bromopropionate and stirred 2 days at reflux temperature. The reaction was then partitioned between aqueous 10% KHS04 and EtOAc (3x). The organic phases were washed with 10%> NaCl, dried over Na2S04 evaporated and purified by flash silica gel column (n -heptane :EtO Ac 9:1) to yield 9.59 g (60%>) of the title compound as brown liquid. MS: 339 (M+, CI). |
60% | With 2,6-dimethylpyridine; In toluene; for 48h;Reflux; | A) 3-(3-Chloro-4-trifluoromethoxy-phenylamino)-propionic acid tert-butyl ester A solution of 9.26 g (42.4 mmol) of <strong>[64628-73-5]3-chloro-4-trifluoromethoxy-phenylamine</strong> and 4.39 ml (42.4 mmol) of 2,6-lutidine in 50 ml of toluene was treated slowly with 7.30 ml (42.4 mmol) of tert-butyl 3-bromopropionate and stirred 2 days at reflux temperature. The reaction was then partitioned between aqueous 10% KHSO4 and EtOAc (3*). The organic phases were washed with 10% NaCl, dried over Na2SO4 evaporated and purified by flash silica gel column (n-heptane:EtOAc 9:1) to yield 9.59 g (60%) of the title compound as brown liquid. MS: 339 (M+, Cl). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | [0585] To a solution of (2-chloro-6-fluorophenyl)acetonitrile (2.00 g, 11.8 mmol) in THF (15 ml) under argon was added gradually while stirring, at -78C., a 2 M solution of LDA in THF (8.8 ml, 18 mmol). The mixture was allowed to come to 0C. and, after 15 min, cooled back down again to -78C. Subsequently, tert-butyl 3-bromopropanoate (2.2 ml, 14 mmol) was slowly added dropwise thereto at -78C. while stirring. Stirring of the mixture was continued overnight, in the course of which the cooling bath (dry ice/acetone) was allowed to come gradually to RT. Subsequently, water was added gradually to the mixture, which was extracted twice with ethyl acetate. The combined organic phases were washed once with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated, and the residue was prepurified by flash column chromatography (50 g silica gel Biotage Snap-Cartridge KP-Sil, cyclohexane/ethyl acetate gradient 93:7→6:4, Isolera One). This was followed by repurification by preparative HPLC (Method 16). The combined target fractions were concentrated and the residue was dried under reduced pressure. This gave 1.45 g (100% purity, 41% of theory) of the title compound. [0586] LC-MS (Method 1): Rt=2.16 min; MS (ESIpos): m/z=298 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.22 g | [0604] To a solution of <strong>[326-62-5](2-fluorophenyl)acetonitrile</strong> (5.00 g, 37.0 mmol) in THF (35 ml) under argon was added gradually while stirring, at -78C., a 2 M solution of LDA in THF (22 ml, 44 mmol). The mixture was allowed to come to 0C. and, after 15 min, cooled back down again to -78C. Subsequently, a solution of tert-butyl 3-bromopropanoate (7.0 ml, 44 mmol) in THF (10 ml) was slowly added dropwise thereto at -78C. while stirring. Stirring of the mixture was continued overnight, in the course of which the cooling bath (dry ice/acetone) was allowed to come gradually to RT. Subsequently, water and ethyl acetate (100 ml of each) were gradually added at about 0C. to the mixture, which was agitated. After phase separation, the aqueous phase was extracted once with ethyl acetate (100 ml). The combined organic phases were washed once with saturated aqueous sodium chloride solution (150 ml), dried over sodium sulfate, filtered and concentrated, and the residue was taken up in dichloromethane and purified by flash column chromatography (100 g silica gel Biotage Snap-Cartridge Ultra, cyclohexane/ethyl acetate gradient 93:7?7:3, Isolera One). The combined target fractions were concentrated and the residue was dried under reduced pressure. This gave 4.22 g (69% purity, 29% of theory) of the title compound. [0605] LC-MS (Method 1): Rt=2.08 min; MS (ESIpos): m/z=264 [M+H]+ |
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