Structure of 14464-30-3
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Search for reports by entering the product batch number.
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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 14464-30-3 |
Formula : | C12H19NO4 |
M.W : | 241.28 |
SMILES Code : | CCCCCCCC(ON1C(CCC1=O)=O)=O |
MDL No. : | MFCD00050404 |
InChI Key : | PEJVSXYBFAVPAQ-UHFFFAOYSA-N |
Pubchem ID : | 3542774 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.75 |
Num. rotatable bonds | 8 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 66.18 |
TPSA ? Topological Polar Surface Area: Calculated from |
63.68 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.66 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.22 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.57 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.62 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.06 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.03 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.21 |
Solubility | 1.5 mg/ml ; 0.00622 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.19 |
Solubility | 0.155 mg/ml ; 0.000642 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.62 |
Solubility | 0.586 mg/ml ; 0.00243 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) |
Yes |
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 |
-6.2 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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.69 |
* 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 |
---|---|---|
75% | With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 18 h; | A compound of formula (VII) (60 mg, 0.22 mmol) in 5 mL of N, N dimethylformamide,Add DIPEA (0.065 mL, 0.38 mmol),Then intermediate A (60 mg, 0.24 mmol),Room temperature 18h,After the TLC is displayed completely,Extracted with 20 mL of ethyl acetate and washed with water.Wash with saturated sodium chloride and dry over anhydrous sodium sulfate.Filtration, evaporation of the solvent, and column chromatography (PE: EA = 10: 1-DCM: MeOH = 10:1) afforded product 65mg, yield 75percent. |
74% | at 10 - 20℃; Inert atmosphere | (1 R, 2R)-2-Amino-1 -(2', 3'-dihydro-benzo [1 , 4] dioxin-6'-yl)-3-pyrrolidin-1 -yl-propan- 1 -ol (15g) obtained from above stage 5 was dissolved in dry dichloromethane (150ml) at room temperature under nitrogen atmosphere and cooled to 10-15° C. Octanoic acid N-hydroxy succinimide ester (13.0 g)was added to the above reaction mass at 10-15° C and stirred for 15 min. The reaction mixture was stirred at room temperature for 16h-18h. Progress of the reaction was monitored by thin layer chromatography. After completion of reaction, the reaction mixture was cooled to 15°C and diluted with 2M NaOH solution (100 ml_) and stirred for 20 min at 20 °C. The organic layer was separated and washed with 2M sodium hydroxide (3x90ml).The organic layer was dried over anhydrous sodium sulphate (30g) and concentrated under reduced pressure at a water bath temperature of 45°C to give the crude compound (20g).The crude is again dissolved in methyl tertiary butyl ether (25 ml_) and precipitated with Hexane (60ml). It is stirred for 10 min, filtered and dried under vacuum to afford Eliglustat as a white solid (16g). Yield: 74percent, Mass (m/zj: 404.7 HPLC (percent Area Method): 97.5 percent, ELSD (percent Area Method): 99.78percent, Chiral HPLC (percent Area Method): 99.78 percent. |
55% | at 20℃; for 20 h; Inert atmosphere | At 25 ~ 30 °C, the raw material EGS-SMA2.5g (1 eq) was dissolved in 50 ml of anhydrous DCM and the raw material EGS-SMB2.2g (1 eq) was dissolved in 25 ml of anhydrous DCM and replaced with nitrogen twice. Under nitrogen, the EGS-SMA solution was slowly added dropwise to the EGS-SMB solution at room temperature for 30 min. After the addition was completed, the reaction was continued for 20 hours at room temperature. 35 ml of 1 M NaOH was added to the reaction system and stirred for 45 min. After the completion of the reaction, the reaction system was separated, the organic phase was washed twice with 20 ml of 1 M NaOH, washed twice, and dried to dryness to obtain a viscous yellow liquid. And further adding 100 ml of a 5percent EA n-hexane solution to the reaction system, heating and refluxing to dissolve most of the crude product, cooling to 40 ° C, and pouring the liquid into another reaction flask. The remaining yellow viscous yellow liquid was further added to 20 ml of a 5percent EA solution of n-hexane, heated to reflux to dissolve most of the crude product, cooled to 40 ° C, poured out and repeated. The resulting n-hexane solution was stirred at room temperature for 4 h, filtered, and 10 ml of 5percent EA of n-hexane was washed twice to give 2 g of a white product as EGS-API in 55percent yield. |
39% | at 20℃; Inert atmosphere | Compound 6 (1R,2R)-Octanoic acid [2-(2',3'-dihydro-benzo[1,4]dioxin-6'-yl)-2-hydroxy-1-pyrrolidin-1-ylmethyl-ethyl]-amide To Intermediate 5 (22.36 g, 80.33 mmol) dissolved in anhydrous methylene chloride (300 mL) was added a solution of octanoic acid N-hydroxysuccinimide ester (19.4 g, 80.39 mmol) dissolved in anhydrous methylene chloride (150 mL) over 15-30 minutes under nitrogen at room temperature. The solution was stirred at room temperature for 18-20 hours. To the reaction was added 1M aqueous NaOH solution (200 mL). The two phase system was stirred at room temperature for 45 minutes. The layers were separated and the combined organic layers were washed twice with 1M NaOH (2*200 mL) and twice with water (2*100 mL). The organic layer was dried with sodium sulfate, filtered and rotoevaporated to a yellow oil. Most of the crude material was dissolved in 5percent ethyl acetate in heptane (1 L) at reflux. After cooling to 40° C., the hazy solution was separated from the yellow oil by decanting the solution into a new flask. The first flask was rinsed twice with 5percent ethyl acetate in heptane (2*250 mL) by the same process (reflux and cooling to 40° C. and decanting the solution from the oil). The combined solution was heated to reflux and allowed to cool to room temperature over 4 hours. The resulting white solid was filtered and washed with 5percent ethyl acetate in heptane (100 mL) and heptane (100 mL). The white solid (13.9 g) was dried under vacuum for 16-24 hours. This solid was mostly dissolved in 5percent ethyl acetate in heptane (800 mL) at reflux. After cooling to 50° C., the hazy solution was separated from the yellow oil by decanting the solution into a new flask. The first flask was rinsed with 5percent ethyl acetate in heptane (100 mL) by the same process (reflux and cooling to 50° C. and decanting the solution from the oil). The combined solution was heated to reflux and allowed to cool to room temperature over 4 hours. The resulting white solid was filtered and washed with 5percent ethyl acetate/heptane (50 mL) and heptane (50 mL). After drying at room temperature under vacuum for 2-3 days, Compound 6 was obtained in 39percent yield (12.57 g). Analytical chiral HPLC (column: Chirex (S)-VAL and (R)-NE, 4.6*250 mm) showed this material to be 99.9percent the desired R,R isomer. Analytical HPLC showed this material to be 99.6percent pure. mp 87-88° C. 1H NMR (CDCl3) δ 6.86-6.73 (m, 3H), 5.84 (d, J=7.3 Hz, 1H), 4.91 (d, J=3.4 Hz, 1H), 4.25 (s, 4H), 4.24-4.18 (m, 1H), 2.85-2.75 (m, 2H), 2.69-2.62 (m, 4H), 2.10 (t, J=7.3 Hz, 2H), 1.55-1.45 (m, 2H), 1.70-1.85 (m, 4H), 1.30-1.15 (m, 8H), 0.87 (t, J=6.9 Hz, 3H) ppm. |
0.3 g | With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 25℃; for 24 h; | 1 mmol of compound VIII (wherein R5 is a hydrogen atom) was dissolved in 30 ml of DMF, 1.5 mmol of DIPEA was added1.2 mmol of compound IX (wherein R6 is succinimidoyl). Plus 25, 24 hours under the reaction. After the reaction, add water quenchingAnd extracted twice with ethyl acetate. The combined organic phase was washed and dried and concentrated to give 0.3g of etilogluzide |
160 mg | With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 18 h; | Without furher purification, 7 (150 mg, 0.55 mmol) was dissolved in DMF (5 mL), DIPEA (0.16 mL, 0.95 mmol) was added to the mixture. The reaction was stirred for 5 min, then 2,5-dioxopyrrolidin-1-yl octanoate (150 mg, 0.6 mmol) was added and the mixture was stirred at room temperature for 18 h. Water was added to the reaction (15 mL) and extracted with EtOAc (3×30 mL). The combined organics were washed with brine, dried over Na2SO4, filtered, concentrated. The residue was purified by flash chromatography (EtOAc/ petroleum ether, 1:10 to DCM/MeOH, 10:1) to afford 1 (160 mg, 61percent for two steps) as a white solid. mp 85–87°C; [α]eq \o(\s\up 6(20),\s\do 2( D))20 D +13 (c, 0.23, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.76-6.85 (m, 3H), 5.83 (d, J = 7.2 Hz, 1H), 4.90 (d, J = 3.6 Hz, 1H), 4.24 (s, 4H), 4.16-4.20 (m, 1H), 2.74-2.84 (m, 2H), 2.62-2.67 (m, 4H), 2.08-2.12 (m, 2H), 1.77-1.80 (m, 4H), 1.52-1.55 (m, 2H), 1.20-1.30 (m, 10H), 0.87 (t, J = 6.8 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.4, 143.4, 142.8, 134.4, 118.9, 117.0, 115.0, 75.5, 64.3, 57.8, 55.2, 52.2, 36.8, 31.6, 29.1, 29.0, 25.6, 23.6, 22.6, 14.1. HR-MS (ESI) calcd for C23H37O4 N2 (M+H)+: 405.2748, found 405.2725. [1] |
Tags: 14464-30-3 synthesis path| 14464-30-3 SDS| 14464-30-3 COA| 14464-30-3 purity| 14464-30-3 application| 14464-30-3 NMR| 14464-30-3 COA| 14464-30-3 structure
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