Structure of N-Ac-D-Val-OH
CAS No.: 17916-88-0
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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: N-Acetyl-D-valine
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| CAS No. : | 17916-88-0 |
| Formula : | C7H13NO3 |
| M.W : | 159.18 |
| SMILES Code : | [H][C@@](NC(C)=O)(C(C)C)C(O)=O |
| Synonyms : |
N-Acetyl-D-valine
|
| MDL No. : | MFCD00026457 |
| InChI Key : | IHYJTAOFMMMOPX-ZCFIWIBFSA-N |
| Pubchem ID : | 76475 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302 |
| Precautionary Statements: | P280-P305+P351+P338 |
| Num. heavy atoms | 11 |
| Num. arom. heavy atoms | 0 |
| Fraction Csp3 | 0.71 |
| Num. rotatable bonds | 4 |
| Num. H-bond acceptors | 3.0 |
| Num. H-bond donors | 2.0 |
| Molar Refractivity | 40.54 |
| TPSA ? Topological Polar Surface Area: Calculated from |
66.4 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.21 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.04 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.23 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.19 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.04 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.33 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-0.59 |
| Solubility | 41.1 mg/ml ; 0.258 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-0.99 |
| Solubility | 16.4 mg/ml ; 0.103 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.5 |
| Solubility | 50.2 mg/ml ; 0.316 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 |
-7.24 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 |
0.56 |
| 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<1.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.58 |
* 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 |
|---|---|---|
| Also catalytic actions on the following substrates were confirmed: N-acetyl-D-valine; N-acetyl-D-alanine; and N-acetyl-D-leucine. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 90% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In DMF (N,N-dimethyl-formamide); dichloromethane; at 20℃; | EXAMPLE 45; 7-((2-(R)-Acetylamino-3-methyl-butyrylamino)methyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid;. To a solution of <strong>[17916-88-0]Ac-D-Val-OH</strong> (0.17 g, 1.09 mmol) dissolved in dichloromethane (15 ml) was added N,N-dimethylformamide (1 ml), 1-hydroxybenzotriazole (0.15 g, 1.09 mmol) and 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride (0.21 g, 1.09 mmol). The reaction mixture was stirred for 15 min. at room temperature at which time a solution of 2-amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (0.31 g, 1.09 mmol) in dichloromethane (10 ml) was added followed by N,N-diisopropylethylamine (0.186 ml, 1.09 mmol). The resulting mixture was stirred over night at room temperature diluted with dichloromethane (10 ml) washed with 10 % aqueous citric acid (20 ml), sodium hydrogencarbonate, dried (MgSO4), filtered and the solvent was evaporated invacuo affording 415 mg (90 %) of 7-((2-(R)-acetylamino-3-methyl-butyrylamino)methyl)-2-amino-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester as an oil.1H-NMR (CDCl3) δ 0.88 (t, 3H), 0.98 (t, 2H), 1.55 (s, 9H), 2.02 (d, 1H), 2.77 m, (2H), 3.40 (m, 1H), 4.14 (m, 1H). LC-MS: Rt = 5.17 min., m/z: 426.4 [M+H]+ |
| 90% | Example 45 7-((2-Acetylamino-3-methyl-butyrylamino)methyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; To a solution of <strong>[17916-88-0]Ac-D-Val-OH</strong> (0.17 g, 1.09 mmol) dissolved in dichloromethane (15 ml) was added N,N-dimethylformamide (1 Ml), 1-hydroxybenzotriazole (0.15 g, 1.09 mmol) and 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride (0.21 g, 1.09 mmol). The reaction mixture was stirred for 15 min. at room temperature at which time a solution of 2-amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (0.31 g, 1.09 mmol) in dichloromethane (10 ml) was added followed by N-N-diisopropylethylamine (0.186 ml, 1.09 mmol). The resulting mixture was stirred over night at room temperature diluted with dichloromethane (10 ml) washed with 10% aqueous citric acid (20 ml), sodium hydrogencarbonate, dried (MgSO4), filtered and the solvent was evaporated in vacuo affording 415 mg (90%) of 7-((2-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester as an oil.1H NMR (CDCl3) δ 0.88 (t, 3H), 0.98 (t, 2H), 1.55 (s, 9) 2.02 (d, 1H), 2.77 m, (2H), 3.40 (m, 1H), 4.14 (m, 1H).To a mixture of 7-((2-acetylamino-3-methyl-butyrylamino)methyl)-2-amino-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (0.4 g, 0.94 mmol) dissolved in dichloromethane (10 ml) and triethylamine (0.26 g, 1.87 mmol) cooled to 0 C. was added a solution of imidazol-1-yl-oxo-acetic acid tert-butyl ester (0.37 g, 1.87 mmol) in dichloromethane (10 ml). The resulting mixture was stirred for 18 h at room temperature diluted with dichloromethane (20 ml) washed with 1N hydrochloric acid (15 ml), saturated sodium hydrogencarbonate, dried (MgSO4), filtered and the solvent evaporated in vacuo which afforded 515 mg (97%) of 7-((2-acetylamino-3-methyl-butyrylamino)methyl)-2-(tert-butoxyoxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester as an oil.LC-MS: Rt=7.11, Mw=554.4.HPLC: Rt=34.16, Area (%)=100, %.To a solution of the above 7-((2-acetylamino-3-methyl-butyrylamino)-methyl)-2-(tert-butoxyoxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (0.5 g, 0.90 mmol) dissolved in dichloromethane (3 ml) was added trifluoroacetic acid (1 ml) and the reaction mixture was stirred for 18 h at room temperature. Trifluoroacetic acid (4 ml) was added and the mixture was stirred for an additional 3 hours at room temperature. The volatiles were evaporated in vacuo (and stripped 3 times with dichloromethane) affording 282 mg (71%) of the title compound.Calculated for C18H23N3O8S, 2×H2O; C, 45.28%; H, 5.70%; N, 8.80%. Found: C, 45.20%; H, 5.50%; N, 8.80%.LC-MS: Rt=3.60, Mw=442.2 |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With 4-methyl-morpholine; triethylamine; In dichloromethane; N,N-dimethyl acetamide; water; | S. 2-[4-(N-Acetyl-D-valylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid imidazolide A suspension of 11.41 g (71.7 mmol) of <strong>[17916-88-0]N-acetyl-D-valine</strong> and 150 ml of dichloromethane is stirred at room temperature and 7.9 ml (71.7 mmol) of N-methylmorpholine is added. The resulting solution is cooled to -10 C. and 9.3 ml (71.7 mmol) of isobutyl chloroformate is added. The reaction mixture is stirred at -15+-5 C. for 45 min and an ice cold solution of 11.09 g (48 mmol) of 2-(4-aminophenyl)-4-hydroxy-5-pyrimidine carboxylic acid, 7.4 ml (52.8 mmol) of triethylamine, and 200 ml of N,N-dimethylacetamide is added while keeping the temperature below -10 C. The mixture is stirred at 0-5 C. for 2 hrs and overnight at room temperature. A small amount of solid is filtered and the filtrate is evaporated to dryness. Water is added to the residue and the resulting solid filtered, washed with water, ethyl acetate, and ether and dried to give 8.9 g of 2-[4-(N-acetyl-D-valylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid. A second crop, obtained from the aqueous filtrate, weighs 2.35 g. [α]D23 +4.50 (cl, pH 7). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With hydrogen;[(eta2-1,2,5,6)-1,5-cyclooctadiene][(Sp,S)-cis-2-(2-diphenylphosphinoethyl-kappaP)-(1-phenylphospholane-kappaP)]rhodium(I)hexafluoroantimonate; In methanol; at 20℃; for 3h;Product distribution / selectivity; | In a glove box, an autoclave with a 20 mL glass tube insert equipped with a magnetic stirring bar was charged with the hydrogenation substrate (1 mmol), anhydrous degassed solvent (7 mL) and the metal complex pre-catalyst (0.01 mmol). After 10 cycles of evacuation and filling with hydrogen, the autoclave was pressurised to an appropriate initial pressure of hydrogen. The reaction mixture was stirred at room temperature and after the appropriate time the autoclave was opened, the reaction mixture was filtered through silica gel, concentrated and the residue was analysed by enantioselective GC. | |
| With hydrogen;[(eta2-1,2,5,6)-1,5-cyclooctadiene][(Sp,R)-trans-2-(2-diphenylphosphinoethyl-kappaP)-(1-phenylphospholane-kappaP)]rhodium(I)hexafluoroantimonate; In tetrahydrofuran; at 20℃; for 3h;Product distribution / selectivity; | In a glove box, an autoclave with a 20 mL glass tube insert equipped with a magnetic stirring bar was charged with the hydrogenation substrate (1 mmol), anhydrous degassed solvent (7 mL) and the metal complex pre-catalyst (0.01 mmol). After 10 cycles of evacuation and filling with hydrogen, the autoclave was pressurised to an appropriate initial pressure of hydrogen. The reaction mixture was stirred at room temperature and after the appropriate time the autoclave was opened, the reaction mixture was filtered through silica gel, concentrated and the residue was analysed by enantioselective GC. | |
| With hydrogen;[(eta2-1,2,5,6)-1,5-cyclooctadiene][(Sp,R,R)-trans-2-(2-diphenylphosphino-2-methylethyl-kappaP)-(1-phenylphospholane-kappaP)]rhodium(I)hexafluoroantimonate; In tetrahydrofuran; at 20℃; for 3h;Product distribution / selectivity; | In a glove box, an autoclave with a 20 mL glass tube insert equipped with a magnetic stirring bar was charged with the hydrogenation substrate (1 mmol), anhydrous degassed solvent (7 mL) and the metal complex pre-catalyst (0.01 mmol). After 10 cycles of evacuation and filling with hydrogen, the autoclave was pressurised to an appropriate initial pressure of hydrogen. The reaction mixture was stirred at room temperature and after the appropriate time the autoclave was opened, the reaction mixture was filtered through silica gel, concentrated and the residue was analysed by enantioselective GC. |
| With hydrogen;[(eta2-1,2,5,6)-1,5-cyclooctadiene][(Sp,R,S)-trans-2-(2-diphenylphosphino-2-methylethyl-kappaP)-(1-phenylphospholane-kappaP)]rhodium(I)hexafluoroantimonate; In tetrahydrofuran; at 20℃; for 3h;Product distribution / selectivity; | In a glove box, an autoclave with a 20 mL glass tube insert equipped with a magnetic stirring bar was charged with the hydrogenation substrate (1 mmol), anhydrous degassed solvent (7 mL) and the metal complex pre-catalyst (0.01 mmol). After 10 cycles of evacuation and filling with hydrogen, the autoclave was pressurised to an appropriate initial pressure of hydrogen. The reaction mixture was stirred at room temperature and after the appropriate time the autoclave was opened, the reaction mixture was filtered through silica gel, concentrated and the residue was analysed by enantioselective GC. |
