Structure of Boc-Sar-OMe
CAS No.: 42492-57-9
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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.
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CAS No. : | 42492-57-9 |
Formula : | C9H17NO4 |
M.W : | 203.24 |
SMILES Code : | O=C(OC)CN(C(OC(C)(C)C)=O)C |
MDL No. : | MFCD04973115 |
InChI Key : | LTBDTYJYKRLTRN-UHFFFAOYSA-N |
Pubchem ID : | 14018930 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.78 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 51.27 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.84 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.63 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.03 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.03 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.83 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.11 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.13 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.35 |
Solubility | 9.02 mg/ml ; 0.0444 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.79 |
Solubility | 3.28 mg/ml ; 0.0161 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.99 |
Solubility | 20.8 mg/ml ; 0.102 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 |
-6.81 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) |
2.36 |
* 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 |
---|---|---|
90% | With triethylamine In dichloromethane at 0 - 20℃; for 48 h; Inert atmosphere | To a suspension of sarcosine (35.64 g, 0.40 mol) in 350 mL MeOH was added thionyl chloride (29.02 mL, 0.40 mol) dropwise at 0 °C. After complete addition the cooling bath was removed and the reaction mixture was stirred for 30 min at r.t. and refluxed for further 6 h. The resulting solution was concentrated in vacuum and the residue was dried in high vacuum over night at r.t. to afford sarcosine methyl ester.HCl as a white powder which was used in the next step without further purification; yield: 56.14 g (quant.); mp. 102 °C. 1H-NMR (300 MHz, CDCl3): δ = 9.76 (s, 2 H, NH2), 3.88 (t, J = 5.6 Hz, 2 H, H-2), 3.82 (s, 3 H, H-4)), 2.83 (t, J = 5.2 Hz, 3 H, H-3). 13C-NMR(75 MHz, CDCl3): δ = 166.7 (C-1), 53.3 (C-2), 48.9 (C-3), 33.4 (C-4).1 To a suspension of sarcosine methylester.HCl (59.80 g, 0.43 mol) and (Boc)2O (138.01 mL, 0.65 mol) in 1.0 L CH2Cl2 TEA (119.09 mL, 0.86 mol) was added dropwise at 0 °C. After complete addition the cooling bath was removed and the reaction mixture was stirred for two days at r.t. Aq. HCl (1 M) was added until the aqueous layer showed pH = 6. The resulting two layers were separated and the organic layer was washed with dist. H2O, dried (Na2SO4), concentrated in vacuum and volatile impurities were removed in high vacuum over night at r.t. to afford a clear oil; yield: 78.65 g (90 percent) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | at 0℃; for 0.5 h; | Boc-N-sarcosine methyl ester (18) was prepared by treating a solution of Boc-Sar- OH (1.0 g, 5.3 mmol) in 1 : 1 DCM/MeOH (25 mL) cooled to 0° C portionwise with diazomethane (2M solution, excess) until the reaction mixture turned slight yellow. The reaction was kept at 0° C for 30 min and then HOAc (2 drops) was added. The organic solvents were removed to afford 1.0 g (90percent) of 18. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | Stage #1: With sodium hydrogencarbonate In tetrahydrofuran; water for 18 h; Stage #2: With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5 h; Stage #3: at 20℃; for 48 h; |
Glycine methyl ester hydrochloride (50.0 g, 0.398 mol, 1 eq.) was added to a 1 L flask containing water (300 mL) and THF (200 mL). Sodium bicarbonate (37.8 g, 0.438 mol) was added portionwise, followed by di-tert-butyl dicarbonate (83.4 g, 0.382 mol). The reaction was stirred for 18 h, and then the separated organic phase was concentrated. The mixture was redissolved in EtOAC, washed with brine, dried over Na2SO4, and evaporated to give an oily product (72 g, 95percent). The oily product was dissolved in DMF (500 mL) and cooled to 0° C. To the mixture was added NaH (60percent, 18.3 g, 0.457 mol) portionwise. The mixture was then stirred for 30 min and MeI (81.1 g, 0.571 mol) was added at such a rate as to maintain a reaction temperature below 20° C. The mixture was stirred at RT for 48 h. The mixture was poured into ice water (1.5 L), extracted with MTBE (300 mL×2). The combined organics were washed with brine, dried over Na2SO4, and evaporated. Silica gel chromatography (PE:EtOAc 7:1) gave N-Boc-N-methyl glycine methyl ester (21 g, 27percent). |