Structure of H-DL-IsoSer-OH
CAS No.: 565-71-9
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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: 3-Amino-2-hydroxypropanoic acid
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| CAS No. : | 565-71-9 |
| Formula : | C3H7NO3 |
| M.W : | 105.09 |
| SMILES Code : | NCC(O)C(O)=O |
| Synonyms : |
3-Amino-2-hydroxypropanoic acid
|
| MDL No. : | MFCD00008138 |
| InChI Key : | BMYNFMYTOJXKLE-UHFFFAOYSA-N |
| Pubchem ID : | 11267 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
| Num. heavy atoms | 7 |
| Num. arom. heavy atoms | 0 |
| Fraction Csp3 | 0.67 |
| Num. rotatable bonds | 2 |
| Num. H-bond acceptors | 4.0 |
| Num. H-bond donors | 3.0 |
| Molar Refractivity | 22.18 |
| TPSA ? Topological Polar Surface Area: Calculated from |
83.55 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.11 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-4.05 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.61 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.7 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.45 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-1.74 |
| Log S (ESOL):? ESOL: Topological method implemented from |
2.19 |
| Solubility | 16300.0 mg/ml ; 156.0 mol/l |
| Class? Solubility class: Log S scale |
Highly soluble |
| Log S (Ali)? Ali: Topological method implemented from |
2.9 |
| Solubility | 82900.0 mg/ml ; 789.0 mol/l |
| Class? Solubility class: Log S scale |
Highly soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
1.3 |
| Solubility | 2080.0 mg/ml ; 19.8 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 |
-9.82 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 |
3.0 |
| 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 |
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) |
1.44 |
* 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 |
|---|---|---|
| 85% | With sodium hydroxide; In tetrahydrofuran; water; at 20℃; for 9h; | (S)-isoserine 15a (21 g, 0.20 mol) was dissolved in tetrahydrofuran (100 mL)And a mixed solvent of 10percent aqueous sodium hydroxide solution (100 mL),Di-tert-butyl dicarbonate (50 mL, 0.22 mol) was added dropwise.The reaction was carried out at room temperature for 9 hours.The aqueous phase was adjusted to pH 2 with 4 mol/L hydrochloric acid, and extracted with dichloromethane/methanol (v/v = 5/1, 50 mL × 3) and dried over anhydrous sodium sulfate.Filter by suction, concentrate under reduced pressure,The title compound 15b was obtained as a colorless oil (35 g, yield: 85percent). |
| 81.5% | To a stirring solution of S-isoserine (4.0 g, 0.038 mol) in dioxane: H2O (100 mL, 1:1 v/v) at 0° C was added N-methylmorpholine (4.77 mL, 0.043 mol), followed by BoC2O (11.28 mL, 0.049 mol) and the reaction was stirred overnight with gradual warming to room temperature. Glycine (1.0 g, 0.013 mol) was then added and the reaction was stirred for 20 min. The reaction was cooled to O0C and sat aq. NaHCO3 (75 mL) was added. The aqueous layer was washed with ethyl acetate (2 x 60 mL) and then acidified to pH 1 with NaHSO4. This solution was then extracted with ethyl acetate (3 x 70 mL) and these combined organic layers were dried over Na2SO4, filtered and concentrated to dryness to give the desired N-Boc-3-ammo-2(S)-hydroxy- propanoic acid (6.30 g, 0.031 mmol, 81.5 percent yield): 1H NMR (400 MHz, CDC13) delta 7.45 (bs, 1 H), 5.28 (bs, 1 H), 4.26 (m, 1 H), 3.40-3.62 (m, 2 H), 2.09 (s, 1 H), 1.42 (s, 9 H); 13C NMR (IOO MHz, CDC13) delta 174.72, 158.17, 82, 71.85, 44.28, 28.45. | |
| 81.5% | To a stirring solution of S-isoserine (4.0 g, 0.038 mol) in dioxane: H20 (100 mL, 1 :1 v/v) at 0° C was added N-methylmorpholine (4.77 mL, 0.043 mol), followed by Boc20 (11.28 mL, 0.049 mol) and the reaction was stirred overnight with gradual warming to room temperature. Glycine (1.0 g, 0.013 mol) was then added and the reaction was stirred for 20 min. The reaction was cooled to 0°C and sat aq. NaHC03 (75 mL) was added. The aqueous layer was washed with ethyl acetate (2 x 60 mL) and then acidified to pH 1 with NaHS04. This solution was then extracted with ethyl acetate (3 x 70 mL) and these combined organic layers were dried over Na2S04, filtered and concentrated to dryness to give the desired N-Boc-3-amino-2(S)-hydroxy- propanoic acid (6.30 g, 0.031 mmol, 81.5 percent yield): 1H NMR (400 MHz, CDC13) delta 7.45 (bs, 1 H), 5.28 (bs, 1 H), 4.26 (m, 1 H), 3.40-3.62 (m, 2 H), 2.09 (s, 1 H), 1.42 (s, 9 H); 13C NMR (100 MHz, CDC13) delta 174.72, 158.17, 82, 71.85, 44.28, 28.45. |
| 81.5% | To a stirring solution of S-isoserine (4.0 g, 0.038 mol) in dioxane: 3/40 (100 mL, 1:1 v/v) at 0° C was added N-methylmorpholine (4.77 mL, 0.043 mol), followed by B0C2O (11.28 mL, 0.049 mol) and the reaction was stirred overnight with gradual warming to room temperature. Glycine (1.0 g, 0.013 mol) was then added and the reaction was stirred for 20 min. The reaction was cooled to 0°C and sat aq. NaHC<3/4 (75 mL) was added. The aqueous layer was washed with ethyl acetate (2 x 60 mL) and then acidified to pH 1 with NaHS04. This solution was then extracted with ethyl acetate (3 x 70 mL) and these combined organic layers were dried over Na2SC filtered and concentrated to dryness to give the desired N-Boc-3-amino-2(5)-hydroxy- propanoic acid (6.30 g, 0.031 mmol, 81.5 percent yield): [H NM (400 MHz, CDC13) delta 7.45 (bs, 1 H), 5.28 (bs, 1 H), 4.26 (m, 1 H), 3.40-3.62 (m, 2 H), 2.09 (s, 1 H), 1.42 (s, 9 H); 13C NMR (100 MHz, CDC13) delta 174.72, 158.17, 82, 71.85, 44.28, 28.45. | |
| 81.5% | With 4-methyl-morpholine; In 1,4-dioxane; water; at 0 - 20℃; | N-Boc-3-amino-2(S)-hydroxy-propionic acid ; <n="62"/>To a stirring solution of S-isoserine (4.0 g, 0.038 mol) in dioxane: H2O (100 mL, 1 :1 v/v) at 0° C was added N-methylmorpholine (4.77 mL, 0.043 mol), followed by BoC2O (11.28 mL, 0.049 mol) and the reaction was stirred overnight with gradual warming to room temperature. Glycine (1.0 g, 0.013 mol) was then added and the reaction was stirred for 20 min. The reaction was cooled to 0°C and sat aq. NaHCO3 (75 mL) was added. The aqueous layer was washed with ethyl acetate (2 x 60 mL) and then acidified to pH 1 with NaHSO4. This solution was then extracted with ethyl acetate (3 x 70 mL) and these combined organic layers were dried over Na2SO4, filtered and concentrated to dryness to give the desired N-Boc-3-amino-2(5)-hydroxy- propanoic acid (6.30 g, 0.031 mmol, 81.5 percent yield): 1H NMR (400 MHz, CDC13) delta 7.45 (bs, 1 H), 5.28 (bs, 1 H), 4.26 (m, 1 H), 3.40-3.62 (m, 2 H), 2.09 (s, 1 H), 1.42 (s, 9 H); 13C NMR (100 MHz, CDC13) delta 174.72, 158.17, 82, 71.85, 44.28, 28.45. |
| 81.5% | N-Boc-3-amino-2 (^-hydroxy-propionic acid OHTo a stirring solution of S-isoserine (4.0 g, 0.038 mol) in dioxane: H2O (100 mL, 1 :1 v/v) at 0° C was added N-methylmorpholine (4.77 mL, 0.043 mol), followed by BoC2O (11.28 mL, 0.049 mol) and the reaction was stirred overnight with gradual warming to room temperature. Glycine (1.0 g, 0.013 mol) was then added and the reaction was stirred for 20 min. The reaction was cooled to 0°C and sat aq. NaHCO3 (75 mL) was added. The aqueous layer was washed with ethyl acetate (2 x 60 mL) and then acidified to pH 1 with NaHSO4. This solution was then extracted with ethyl acetate (3 x 70 mL) and these combined organic layers were dried over Na2SO4, filtered and concentrated to dryness to give the desired N-Boc-3-amino-2(5)-hydroxy- propanoic acid (6.30 g, 0.031 mmol, 81.5 percent yield): 1H NMR (400 MHz, CDC13) delta 7.45 (bs, 1 H), 5.28 (bs, 1 H), 4.26 (m, 1 H), 3.40-3.62 (m, 2 H), 2.09 (s, 1 H), 1.42 (s, 9 H); 13C NMR (100 MHz, CDC13) delta 174.72, 158.17, 82, 71.85, 44.28, 28.45. | |
| 81.5% | With 4-methyl-morpholine; In 1,4-dioxane; water; at 0 - 20℃; | N-Boc-3-amino-2(5)-hydroxy-propionic acid To a stirring solution of S-isoserine (4.0 g, 0.038 mol) in dioxane: H2O (100 mL, 1:1 v/v) at 0° C was added N-methylmorpholine (4.77 mL, 0.043 mol), followed by BoC2O (11.28 mL, 0.049 mol) and the reaction was stirred overnight with gradual warming to room temperature. Glycine (1.0 g, 0.013 mol) was then added and the reaction was stirred for 20 min. The reaction was cooled to 0°C and sat aq. NaHCO3 (75 mL) was added. The aqueous layer was washed with ethyl acetate (2 x 60 mL) and then acidified to pH 1 with NaHSO4. This solution was then extracted with ethyl acetate (3 x 70 mL) and these combined organic layers were dried over Na2SO4, filtered and concentrated to dryness to give the desired N-Boc-3-amino-2(5)-hydroxy- propanoic acid (6.30 g, 0.031 mmol, 81.5 percent yield): 1H NMR (400 MHz, CDC13) delta 7.45 (bs, 1 H), 5.28 (bs, 1 H), 4.26 (m, 1 H), 3.40-3.62 (m, 2 H), 2.09 (s, 1 H), 1.42 (s, 9 H); 13C NMR (100 MHz, CDC13) delta 174.72, 158.17, 82, 71.85, 44.28, 28.45. |
| 80% | Part I - Synthesis of (S)-3-((ter^butoxycarbonyl)amino)-2-hydroxypropanoic acid [0261] To (L)-isoserine (1.0 g, 9.5 mmol) in tetrahydrofuran (10 mL) and 2M sodium hydroxide (9.75 mL, 19.5 mmol) was added di-tert-butyl dicarbonate (0.78 g, 10 mmol). The resulting mixture was stirred vigorously at ambient temperature overnight. Then, the reaction mixture was acidified with 1M hydrogen chloride (20 mL) and stirred for 20 minutes until gas evolution ceased. The resulting mixture was partitioned between ethyl acetate and water, washed with brine, dried with sodium sulfate, filtered and concentrated in vacuo to yield title compound. (1.57 g, 80percent yield) | |
| To a stirring solution of S-isoserine (4.0 g, 0.038 mol) in dioxane: H20 (100 mL, 1 : 1 v/v) at 0° C was added N-methylmorpholine (4.77 mL, 0.043 mol), followed by Boc20 (1 1.28 mL, 0.049 mol) and the reaction was stirred overnight with gradual warming to room temperature. Glycine (1.0 g, 0.013 mol) was then added and the reaction was stirred for 20 min. The reaction was cooled to 0°C and sat aq. NaHC03 (75 mL) was added. The aqueous layer was washed with ethyl acetate (2 x 60 mL) and then acidified to pH 1 with NaHS04. This solution was then extracted with ethyl acetate (3 x 70 mL) and these combined organic layers were dried over Na2S04, filtered and concentrated to dryness to give the desired N-Boc-3-amino-2(5)-hydroxy- propanoic acid (6.30 g, 0.031 mmol, 81.5 percent yield): 1H NMR (400 MHz, CDC13) delta 7.45 (bs, 1 H), 5.28 (bs, 1 H), 4.26 (m, 1 H), 3.40-3.62 (m, 2 H), 2.09 (s, 1 H), 1.42 (s, 9 H); 13C NMR (100 MHz, CDC13) delta 174.72, 158.17, 82, 71.85, 44.28, 28.45. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 81.5% | N-Boc-3-amino-2 (^-hydroxy-propionic acid OHTo a stirring solution of S-isoserine (4.0 g, 0.038 mol) in dioxane: H2O (100 mL, 1 :1 v/v) at 0° C was added N-methylmorpholine (4.77 mL, 0.043 mol), followed by BoC2O (11.28 mL, 0.049 mol) and the reaction was stirred overnight with gradual warming to room temperature. Glycine (1.0 g, 0.013 mol) was then added and the reaction was stirred for 20 min. The reaction was cooled to 0°C and sat aq. NaHCO3 (75 mL) was added. The aqueous layer was washed with ethyl acetate (2 x 60 mL) and then acidified to pH 1 with NaHSO4. This solution was then extracted with ethyl acetate (3 x 70 mL) and these combined organic layers were dried over Na2SO4, filtered and concentrated to dryness to give the desired N-Boc-3-amino-2(5)-hydroxy- propanoic acid (6.30 g, 0.031 mmol, 81.5 percent yield): 1H NMR (400 MHz, CDC13) delta 7.45 (bs, 1 H), 5.28 (bs, 1 H), 4.26 (m, 1 H), 3.40-3.62 (m, 2 H), 2.09 (s, 1 H), 1.42 (s, 9 H); 13C NMR (100 MHz, CDC13) delta 174.72, 158.17, 82, 71.85, 44.28, 28.45. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 92% | With sodium methylate; In methanol; at 120℃; for 1h;Microwave irradiation; | A mixture of 4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester(90 mg, 0.31 mmol) and 2-(S)-hydroxy-3-amino-propionic acid (Sigma-Aldrich) (96 mg, 0.92 mmol) in 0.5 N NaOMe in MeOH solution (1.22 mL, 0.61 mmol) was microwaved at 120 °C for 1 h and concentrated. Residue was dissolved in water (70 mL) and acidified by 1 N HC1 solution to pH = 3-4. It was extracted with EtOAc, Organic layer was washed with brine, dried over MgSO/t, filtered and concentrated to give the title compound (105 mg, 0.29 mmol) in 92percent yield. LC-MS ESI-: 366.99 (M- 1)-. |