Structure of 84758-55-4
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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. : | 84758-55-4 |
| Formula : | C10H19NO4 |
| M.W : | 217.26 |
| SMILES Code : | CC(C)(NC(OC(C)(C)C)=O)C(OC)=O |
| English Name : | Methyl 2-((tert-butoxycarbonyl)amino)-2-methylpropanoate |
| MDL No. : | MFCD20484740 |
| InChI Key : | OXGSYLWMSHXMLT-UHFFFAOYSA-N |
| Pubchem ID : | 15853247 |
| Num. heavy atoms | 15 |
| Num. arom. heavy atoms | 0 |
| Fraction Csp3 | 0.8 |
| Num. rotatable bonds | 6 |
| Num. H-bond acceptors | 4.0 |
| Num. H-bond donors | 1.0 |
| Molar Refractivity | 56.02 |
| TPSA ? Topological Polar Surface Area: Calculated from |
64.63 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.72 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.44 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.46 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.13 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.65 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.48 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-1.7 |
| Solubility | 4.35 mg/ml ; 0.02 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-2.4 |
| Solubility | 0.86 mg/ml ; 0.00396 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.74 |
| Solubility | 3.97 mg/ml ; 0.0183 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 |
-6.6 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) |
2.38 |
* 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 |
|---|---|---|
| 99% | Stage #1: N-(tert-butoxycarbonyl)-α-methylalanine methyl ester With lithium hydroxide In tetrahydrofuran; methanol; water at 20℃; for 12h; Stage #2: With hydrogenchloride In tetrahydrofuran; methanol; water | 3.1 Preparation Example 1. Synthesis of 4-[2-(2-cyano-benzenesulfonylamino)-2-methyl-propionylamino]-adamantane-1-carboxylic acid amide (compound 130) In a 50-mL flask, methyl-2-aminobutoxycarbonyl-2-methylpropanoate (327 mg, 1.50 mmol) was charged, and dissolved through addition of tetrahydrofuran (15 ml), and methanol (15 ml). Lithium hydroxide dissolved in purified water (15 ml) was added thereto, followed by stirring for 12 hours at room temperature. After stirring for 12 hours, the resultant solution was vacuum-evaporated, neutralized with 2N-hydrochloric acid aqueous solution, and extracted with ethyl acetate (20mL). The organic layer was dried with magnesium sulfate, and filtered. Through vacuum distillation, the solvent was removed so as to obtain methyl-2-aminobutoxycarbonyl-2-methylpropanoic acid compound (335mg, 99 %).[615] 1H NMR (400 MHz, DMSO-d6) δ 12.1 (s, HO-CO-, 1H), 7.05 (s, -NH-CO2-, 1H), 1.40 (s, C3H9-O-, 9H), 1.25 (s, 6H). |
| 99% | With water; lithium hydroxide In tetrahydrofuran; methanol | 3.1.335 In a 50-mL flask, methyl-2-aminobutoxycarbonyl-2-methylpropanoate (327 mg, 1.50 mmol) was charged, and dissolved through addition of tetrahydrofuran (15 ml), and methanol (15 ml). Lithium hydroxide dissolved in purified water (15 ml) was added thereto, followed by stirring for 12 hours at room temperature. After stirring for 12 hours, the resultant solution was vacuum-evaporated, neutralized with 2N-hydrochloric acid aqueous solution, and extracted with ethyl acetate (20 mL). The organic layer was dried with magnesium sulfate, and filtered. Through vacuum distillation, the solvent was removed so as to obtain methyl-2-aminobutoxycarbonyl-2-methylpropanoic acid compound (335 mg, 99%). [0336] 1H NMR (400 MHz, DMSO-d6) δ 12.1 (s, HO-CO-, 1H), 7.05 (s, -NH-CO2-, 1H), 1.40 (s, C3H9-O-, 9H), 1.25 (s, 6H). |
| 40% | With hydroxide |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 86.7% | With lithium borohydride In ethanol |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 72% | With hydrazine In methanol at 55℃; for 24h; | |
| With hydrazine hydrate In isopropyl alcohol | 17.2 Step 2: Step 2: tert-Butyl (2-hydrazino-1,1-dimethyl-2-oxoethyl)carbamate (P2) To a solution of P1 in 2-Propanol (0.56 M) was added hydrazine monohydrate (10 eq) and the mixture was stirred overnight at 90° C. Volatiles were removed under high vacuum and the obtained crude was used as such in the next step. MS (ES) C9H19N3O3 requires: 217, found: 240 (M+Na)+. | |
| With hydrazine In isopropyl alcohol at 90℃; | 17.2 Step 2: tert-Butyl (2-hydrazino-1,1-dimethyl-2-oxoethyl)carbamate (P2) To a solution of P1 in 2-Propanol (0.56 M) was added hydrazine monohydrate (10 eq) and the mixture was stirred overnight at 90° C. Volatiles were removed under high vacuum and the obtained crude was used as such in the next step. MS (ES) C9H19N3O3 requires: 217, found: 240 (M+Na)+. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 96.6% | With potassium hydrogencarbonate In N,N-dimethyl-formamide for 5h; Ambient temperature; | |
| With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 6h; | 17.1 Step 1: Methyl N-(tert-butoxycarbonyl)-2-methylalaninate (P1) To a solution of Boc-α-methylalanine in DMF (0.4 M) was added K2CO3 (1 eq) and MeI (1.2 eq). The mixture was stirred at RT for 6 h and then diluted with EtOAc, washed with water and sat. aq. NaHCO3. The organic phase was dried over Na2SO4, filtered and concentrated under vacuum to provide the title compound as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ: 7.20 (1H, br. s), 3.58 (3H, s), 1.40-1.27 (15H, m). MS (ES) C10H19NO4 requires: 217, found: 240 (M+Na)+. | |
| 96 % | With potassium carbonate In N,N-dimethyl-formamide at 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 100% | With lithium hydroxide In tetrahydrofuran for 2h; Heating; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 94% | With 4-methyl-morpholine; 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride | |
| 83.3% | With sulfuric acid at 60℃; for 5h; | 238.B methyl 2-(tert-butoxycarbonylamino)-2-methylpropanoate To a round bottom flask were added 2-(teri-butoxycarbonylamino)-2-methylpropanoic acid (2.0 g, 9.8 mmol), concentrated H2SO4 (0.1 mL), and MeOH (20 mL) and stirred at 60 °C for 5 h. The mixture was concentrated to dryness, the residue was diluted with EtOAc, washed with saturated NaHC03 and brine, dried over anhydrous Na2S04, filtered, and concentrated to dryness to give the title compound as a white solid 1.78 g, 83.3% yield). |
| 83.3% | With sulfuric acid at 60℃; for 5h; | 238.B Step B: Methyl 2- (tert-butoxycarbonylamino) -2-methylpropanoate. To a round bottom flask were added 2- (tert-butoxycarbonylamino) -2-methylpropanoic acid (2.0 g, 9.8 mmol) , concentrated H2SO4(0.1 mL) , and MeOH (20 mL) and stirred at 60 for 5 h. The mixture was concentrated to dryness, the residue was diluted with EtOAc, washed with saturated NaHCO3and brine, dried over anhydrous Na2SO4, filtered, and concentrated to dryness to give the title compound as a white solid 1.78 g, 83.3yield) . |
| With dmap; Isopropenyl chloroformate; TEA In dichloromethane at 0 - 20℃; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With trifluoroacetic acid In dichloromethane at 20℃; for 2h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: TFA / CH2Cl2 / 2 h / 20 °C 2: TEA / CH2Cl2 / 2 h / -10 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: TFA / CH2Cl2 / 2 h / 20 °C 2: TEA / CH2Cl2 / 2 h / -10 °C 3: 1-methylimidazole / CH2Cl2 / 20 h / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: TFA / CH2Cl2 / 2 h / 20 °C 2: TEA / CH2Cl2 / 2 h / -10 °C 3: 1-methylimidazole / CH2Cl2 / 20 h / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: 72 percent / N2H4 / methanol / 24 h / 55 °C 2: DMAP / tetrahydrofuran; hexane / 20 h 3: TBAF / tetrahydrofuran / 0.67 h / 22 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: 72 percent / N2H4 / methanol / 24 h / 55 °C 2: DMAP / tetrahydrofuran; hexane / 20 h |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: 53.4 percent 2: 96.6 percent / potassium hydrogen carbonate / dimethylformamide / 5 h / Ambient temperature | ||
| Multi-step reaction with 2 steps 1: water; sodium hydroxide / tetrahydrofuran / 20 °C / Inert atmosphere 2: sulfuric acid / 5 h / 60 °C | ||
| Multi-step reaction with 2 steps 1: sodium hydroxide / water; tetrahydrofuran / 20 °C 2: sulfuric acid / 5 h / 60 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: 86.7 percent / lithium borohydride / ethanol 2: 85 percent / triethylamine / CH2Cl2 / 1 h / 0 °C |

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