Structure of Boc-Glu(OMe)-OH
CAS No.: 45214-91-3
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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.
Synonyms: (S)-2-((tert-Butoxycarbonyl)amino)-5-methoxy-5-oxopentanoic acid
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| CAS No. : | 45214-91-3 |
| Formula : | C11H19NO6 |
| M.W : | 261.27 |
| SMILES Code : | O=C(OC)CC[C@@H](C(O)=O)NC(OC(C)(C)C)=O |
| Synonyms : |
(S)-2-((tert-Butoxycarbonyl)amino)-5-methoxy-5-oxopentanoic acid
|
| English Name : | (S)-2-((tert-Butoxycarbonyl)amino)-5-methoxy-5-oxopentanoic acid |
| MDL No. : | MFCD00190794 |
| InChI Key : | OHYMUFVCRVPMEY-ZETCQYMHSA-N |
| Pubchem ID : | 7018756 |
| Num. heavy atoms | 18 |
| Num. arom. heavy atoms | 0 |
| Fraction Csp3 | 0.73 |
| Num. rotatable bonds | 9 |
| Num. H-bond acceptors | 6.0 |
| Num. H-bond donors | 2.0 |
| Molar Refractivity | 62.56 |
| TPSA ? Topological Polar Surface Area: Calculated from |
101.93 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.88 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.74 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.92 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.52 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.29 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.87 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-1.33 |
| Solubility | 12.2 mg/ml ; 0.0465 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-2.46 |
| Solubility | 0.907 mg/ml ; 0.00347 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.14 |
| Solubility | 18.8 mg/ml ; 0.0719 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 |
-7.37 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 |
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) |
3.03 |
* 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 |
|---|---|---|
| Multi-step reaction with 3 steps 1: DCC / ethyl acetate / 1.) 0 deg C, 2.) 3 h, room temperature 2: NaBH4 / ethanol; tetrahydrofuran / 0.25 h / 0 °C 3: 92 percent / dl-10-camphorsulphonic acid (CSA) / benzene / 3 h / Heating | ||
| Multi-step reaction with 3 steps 1: DCC / ethyl acetate 2: NaBH4 / tetrahydrofuran; ethanol / 0.25 h / 0 °C 3: 92 percent / d,l-10-camphorsulfonic(CSA) / benzene / 3 h / 80 °C | ||
| Multi-step reaction with 2 steps 1.1: chloroformic acid ethyl ester; 4-methyl-morpholine / tetrahydrofuran / 0.33 h / 0 - 20 °C 1.2: 3 h / 0 - 20 °C 2.1: acetic acid / toluene / 1 h / Reflux |
| Multi-step reaction with 2 steps 1.1: 4-methyl-morpholine; isobutyl chloroformate / tetrahydrofuran / 0.33 h / 0 °C 1.2: 0 - 20 °C 2.1: acetic acid / toluene / 5 h / Reflux |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With dicyclohexyl-carbodiimide In dichloromethane at -10 - 0℃; for 41h; | A1 Example A1 :Preparation of the compound of formula (B)222g (801 mmol) (2-amino-5-bromo-phenyl)-pyridin-2-yl-methanone of formula (A)(A) (prepared as described in European Journal of Organic Chemistry, 2006, 13, 2987- 2990) and 230g (881 mmol) 'Boc-Glu DMeJ-OH were mixed as solids and dissolved in 1200 ml dichloromethane and the solution was cooled to a temperature of - 10°C. A solution of coupling reagent dicyclohexylcarbodiimide DCC (165 g, 801 mmol) in 400 ml dichloromethane was added dropwise over a period of 1 hour while the internal temperature was kept at a temperature from - 10°C to - 5°C, then the solution was stirred for 40 hours at a temperature of - 5°C to 0 °C. The suspension was filtered, the filter cake was washed with 1000 ml dichloromethane and the filtrate was evaporated to a yellow residue, showing for the main product the following NMR data:1 H-NMR (CDCI3, 300 MHz) 11.29 (brs, 1 H); 8.65(dt, 1 H, J= 4.8, 1.4); 8.50 (d, 1 H, J= 9.0); 7.91(d, 1 H, J= 2.3); 7.86 (m, 2H); 7.59 (dd, 1 H, J= 9.0, 2.3) 7.45 (ddd, 1 H, J= 6.4, 4.0, 2.3); 5.27 (brd, 1 H, J=6.4); 4.27 (brm, 1 H); 3.60 (s, 3H); 2.52-2.14 (m, 2H); 2.04-1.82 (m, 2H); 1.36 (s, 9H), corresponding to the compound of formula (B). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: dicyclohexyl-carbodiimide / dichloromethane / 41 h / -10 - 0 °C 2: hydrogenchloride / 1,4-dioxane; methanol / 3.25 h / 10 - 15 °C / Industry scale 3: sodium hydrogencarbonate / acetonitrile / 4.17 h / 15 - 20 °C / Industry scale | ||
| Multi-step reaction with 3 steps 1: dicyclohexyl-carbodiimide / dichloromethane / -10 - 0 °C 2: hydrogenchloride; methanol / 1,4-dioxane / 3.25 h / 10 - 20 °C 3: sodium hydrogencarbonate / 1,4-dioxane; acetonitrile; methanol / 15 - 20 °C | ||
| Multi-step reaction with 2 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; 4-methyl-morpholine / N,N-dimethyl-formamide / 0.5 h / Cooling with ice 2: trifluoroacetic acid / dichloromethane / Cooling with ice |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With dicyclohexyl-carbodiimide In dichloromethane at -10 - 0℃; | A.1 222g (801 mmol) (2-amino-5-bromo-phenyl)-pyridin-2-yl-methanone of formula (A) (prepared as described in European Journal of Organic Chemistry, 2006, 13, 2987-2990) and 230g (881 mmol)'Boc-Glu(OMe)-OH were mixed as solids and dissolved in 1200 ml dichloromethane and the solution was cooled to a temperature of - 10°C. A solution of coupling reagent dicyclohexylcarbodiimide DCC (165 g, 801 mmol) in 400 ml dichloromethane was added dropwise over a period of 1 hour while the internal temperature was kept at a temperature from - 10°C to - 5°C, then the solution was stirred for 40 hours at a temperature of - 5°C to 0 °C. The suspension was filtered, the filter cake was washed with 1000 ml dichloromethane and the filtrate was evaporated to a yellow residue, showing for the main product the following NMR data: 1H-NMR (CDCl3, 300 MHz) 11.29 (brs, 1H); 8.65(dt, 1H, J= 4.8, 1.4); 8.50 (d. 1H, J= 9.0); 7.91 (d, 1H, J= 2.3); 7.86 (m, 2H); 7.59 (dd, 1H, J= 9.0, 2.3) 7.45 (ddd, 1H. J= 6.4, 4.0, 2.3); 5.27 (brd, 1H. J=6.4); 4.27 (brm, 1H): 3.60 (s, 3H); 2.52-2.14 (m, 2H); 2.04-1.82 (m, 2H); 1.36 (s, 9H), corresponding to the compound of formula (B). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 8 steps 1.1: pivaloyl chloride; 4-methyl-morpholine / Isopropyl acetate / 2 h / -5 - 5 °C / Inert atmosphere; Large scale 1.2: 1 h / -5 - 5 °C / Inert atmosphere; Large scale 2.1: hydrogenchloride / 1,4-dioxane; sulfolane / 4.5 h / 25 - 30 °C 3.1: 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 1.5 h / 20 - 25 °C / Inert atmosphere 4.1: potassium trimethylsilonate / tetrahydrofuran / 14 h / 25 - 30 °C / Inert atmosphere 5.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 15 h / 0 - 20 °C / Inert atmosphere; Large scale 6.1: 2.5 wt% Pd/C; triethylsilane; acetic acid / tetrahydrofuran / 7 h / 5 - 20 °C / Inert atmosphere 7.1: methanol; tetrahydrofuran / 2 h / -15 - -5 °C 7.2: 1 h / 15 - 25 °C 8.1: isopropyl alcohol; tetrahydrofuran / 15 h / 20 - 30 °C / Large scale | ||
| Multi-step reaction with 9 steps 1.1: pivaloyl chloride; 4-methyl-morpholine / Isopropyl acetate / 2 h / -5 - 5 °C / Inert atmosphere; Large scale 1.2: 1 h / -5 - 5 °C / Inert atmosphere; Large scale 2.1: hydrogenchloride / 1,4-dioxane; sulfolane / 4.5 h / 25 - 30 °C 3.1: 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 1.5 h / 20 - 25 °C / Inert atmosphere 4.1: potassium trimethylsilonate / tetrahydrofuran / 14 h / 25 - 30 °C / Inert atmosphere 5.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 15 h / 0 - 20 °C / Inert atmosphere 5.2: 20 - 30 °C 6.1: sodium carbonate / tert-butyl methyl ether; water / 4 h / 15 - 25 °C / Large scale 7.1: 2.5 wt% Pd/C; triethylsilane; acetic acid / tetrahydrofuran / 7 h / 5 - 20 °C / Inert atmosphere 8.1: methanol; tetrahydrofuran / 2 h / -15 - -5 °C 8.2: 1 h / 15 - 25 °C 9.1: isopropyl alcohol; tetrahydrofuran / 15 h / 20 - 30 °C / Large scale |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 67.3% | With dicyclohexyl-carbodiimide In dichloromethane at 0℃; for 24h; | 20.3 Step 3. Preparation of (S)-methyl 5-((4-chloro-2-picolinoylphenyl)amino)-4-((tert-butoxycarbonyl)amino)-5-oxopentanoate (Compound 20c) (2-Amino-5-chlorophenyl)(pyridin-2-yl)methanone (compound 20b, 4 g, 17.2 mmol) and 5-methyl N-tert-butoxycarbonyl-L-glutamate (6.7 g, 25.8 mmol) were dissolved in DCM (50 mL). The mixture was cooled to 0° C., and DCC (7.1 g, 34.4 mmol was added). The mixture was stirred for 24 h until LCMS indicated that the reaction was completed. The reaction mixture was poured into ice water, and extracted with ethyl acetate. The organic layer was washed with water for three times, dried and concentrated. The residue was purified through silica gel column chromatography to obtain (S)-methyl 5-((4-chloro-2-picolinoylphenyl)amino)-4-((tert-butoxycarbonyl)amino)-5-oxopentanoate (compound 20c, 5.5 g, yield 67.3%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 69% | Stage #1: (2S)-2-[(tert-butoxy)carbonylamino]-4-(methoxycarbonyl)butanoic acid With 4-methyl-morpholine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide for 0.5h; Cooling with ice; Stage #2: 2-amino-5-bromobenzoyl pyridine In N,N-dimethyl-formamide | 2.1 Step 1. Preparation of (S)-methyl 5-((4-bromo-2-nicotinoylphenyl)amino)-4-((tert-butoxycarbonyl)amino)-5-ozopentanoate (Compound 2b) HATU (45.6 g, 0.12 mol), N-methylmorpholine (20.2 g, 0.2 mol) and 5-methyl N-Boc-L-glutamate (16.1 g, 0.1 mol) were sequentially added to DMF (100 mL) in an ice bath. The resulted mixture was allowed to react for 30 min in an ice bath, and then (2-amino-5-bromophenyl)(pyridin-2-yl)methanone (compound 2a, 27.7 g, 0.1 mol) was added. Water was added to the reaction system after TLC indicated that the reaction was completed, and the mixture was extracted with ethyl acetate (20 mL*4). The ethyl acetate layer was evaporated to dry, and the residue was purified through silica gel column chromatography to obtain (S)-methyl 5-((4-bromo-2-nicotinoylphenyl)amino)-4-((tert-butoxycarbonyl)amino)-5-oxopentanoate (compound 2b, 36 g, yield: 69%). |

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