Structure of Boc-D-Ser(tBu)-OH
CAS No.: 248921-66-6
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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. : | 248921-66-6 |
| Formula : | C12H23NO5 |
| M.W : | 261.31 |
| SMILES Code : | O=C(O)[C@H](NC(OC(C)(C)C)=O)COC(C)(C)C |
| MDL No. : | MFCD09751020 |
| InChI Key : | BPYLRGKEIUPMRJ-MRVPVSSYSA-N |
| Pubchem ID : | 6992546 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302-H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
| Num. heavy atoms | 18 |
| Num. arom. heavy atoms | 0 |
| Fraction Csp3 | 0.83 |
| Num. rotatable bonds | 8 |
| Num. H-bond acceptors | 5.0 |
| Num. H-bond donors | 2.0 |
| Molar Refractivity | 67.21 |
| TPSA ? Topological Polar Surface Area: Calculated from |
84.86 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.65 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.39 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.78 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.89 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.77 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.5 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-1.81 |
| Solubility | 4.07 mg/ml ; 0.0156 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-2.78 |
| Solubility | 0.438 mg/ml ; 0.00168 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.61 |
| Solubility | 6.37 mg/ml ; 0.0244 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 |
-6.91 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 |
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) |
3.35 |
* 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 |
|---|---|---|
| 480 mg (100%) | With triethylamine; In dichloromethane; ethyl acetate; | Step A: 2(R)-t-Butoxycarbonylamino-3-(t-butoxy)-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide To a solution of 200 mg (1.13 mmol) of 3(R)-amino-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (Example 1, Step B) in 8 mL of dry methylene chloride was added 0.206 mL (1.48 mmol) of triethylamine, 553 mg (1.25 mmol) of <strong>[248921-66-6]BOC-D-serine t-butyl ether</strong> followed by 602 mg (1.36 mmol) of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate. The reaction mixture was stirred at room temperature for 2 hours then diluted with 100 mL of ethyl acetate, washed with 25 mL of 5% aqueous citric acid, 25 mL of saturated sodium bicarbonate and 25 mL of brine. The organic layer was dried over magnesium sulfate, filtered and the solvents removed under vacuum. The residue was purified by flash chromatography on silica gel, eluding with ethyl acetate/hexane (55:45) to afford 480 mg (100%) of the product as a white foam. 1 H NMR (200 MHz,CDCl3): 1.20 (s,9H), 1.47 (s,9H), 1.92 (m,1H), 2.55-3.02 (m,3H), 3.38 (t,8 Hz,1H), 3.78 (m,1H), 4.15 (m,1H), 4.52 (m,1H), 5.45 (s,1H), 7.00 (m,1H), 7.10-7.35 (m,3H), 7.68 (d,4 Hz,1H), 8.05 (s,1H). FAB-MS: calculated for C22 H33 N3 O5 419; found 420 (M+H,20%), 426 (M+Li,40%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine; In dichloromethane; at 0 - 20℃; | STEP A: (l-fe/t-Butoxymethyl-2-morpholin-4-yl-2-oxo-ethyl)-(J?)-carbamic acid fert-butyl ester To an ice cooled solution of morpholine (0.6 mL, 6.9 mmol) , <strong>[248921-66-6]Boc-D-Ser(tBu)-OH</strong> (3 g, 6.8 mmol) and HOBT (1.2 g, 9 mmol) in CH2Cl2 (50 mL), TEA (1.9 mL) was added followed by addition of 1,3-dimethylamino propyl-3-ethylcarbodiimide (EDC, 1.7 g, 8.6 mmol). The reaction mixture was allowed to warm to room temperature and was then stirred overnight. EtOAc (200 mL) was added to the reaction mixture. This resulting solution was washed with dilute HCl solution, NaHCO3 (aq.) solution, and NaCl (aq.) solution. The organic <n="109"/>layer was dried over MgSO4, filtered, and evaporated to yield (l-tert-butoxymethyl-2- morpholin-4-yl-2-oxo-ethyl)-(/?J-carbamic acid tert-butyl ester as a crude oil. MH+ 331.2 |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 79% | 2-[2-Amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]-4,5-difluorobenzyl (R)-3-tert-butoxy-2-tert-butoxycarbonylaminopropionate (?A93?) [0808] 954 mg of dicyclohexylcarbodiimide are added to a solution of 2.4 g of <strong>[248921-66-6](R)-3-tert-butoxy-2-tert-butoxycarbonylaminopropionic acid</strong> in 50 ml of dichloromethane, and the mixture is stirred at 25 C. for 1 h. The precipitate is filtered off, and the filtrate is added to a solution of 1 g of [2-amino-6-(4,5-difluoro-2-hydroxymethylphenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone and 14 mg of 4-(dimethylamino)pyridine (DMAP) in 50 ml of tetrahydrofuran. The mixture is stirred at 25 C. for 48 h, undissolved material is filtered off, and the filtrate is evaporated to dryness. The residue is purified by normal-phase chromatography. [0809] Yield: 1.2 g (79%) of 2-[2-amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]-4,5-difluorobenzyl (R)-3-tert-butoxy-2-tert-butoxycarbonylaminopropionate; LC-MS retention time: 2.79 min. |