Route of Synthesis (ROS) of 3 6 12 15-Tetraoxa-9-azaheptadecanoic acid 17-amino-10-oxo-1 1-dimethylethyl ester CAS 2409545-30-6
Conditions
Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; diisopropylamine In dichloromethane at 0 – 20℃; for 6h;
Experimental Procedure 2.2-1.3 Step 3: Preparation of Compound II-1e Compound II-1d (305 mg, 830 umol)II-1a 8- (Fluorenylmethoxycarbonyl-amino) -3,6-dioxaotanoic acid (478 mg, 1.24 mmol)Dichloromethane (20 mL)After melting in, At 0 to room temperatureI- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (318 mg, 1.66 mmol), hydroxybenzotriazole (224 mg, 1.66 mmol) and diisopropylamine (423 μl, 2.49 mmol) Was added. The reaction mixture was stirred at room temperature for 6 hours. After completion of the reaction and extracted with distilled water and brine, the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrated residue was purified by silica gel column chromatography (dichloromethane: methanol = 10: 1 volume ratio) to give the title compound II-1e (570 mg, 92%) as a yellow oil.
92%
Safety and Hazards
No data availabile
Other Data
Storage
Store at 2~8° for long time, away from light
Shelf Life
1 year
Druglikeness
Lipinski rules component
分子量
364.439
logP
-1.151
HBA
9
HBD
2
Matching Lipinski Rules
4
Veber rules component
Polar Surface Area (PSA)
118.34
Rotatable Bond (RotB)
18
Matching Veber Rules
1
Use Pattern
AEEA-AEEA-tBu/3,6,12,15-Tetraoxa-9-azaheptadecanoic acid,17-amino-10-oxo-,1,1-dimethylethyl ester CAS#: 2409545-30-6 as an intermediate in the synthesis of semaglutide. And 3,6,12,15-Tetraoxa-9-azaheptadecanoic acid,17-amino-10-oxo-,1,1-dimethylethyl ester likely plays a crucial role in the production process. Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used in the treatment of type 2 diabetes.
Route of Synthesis (ROS) of17-Amino-10-oxo-361215-tetraoxa-9-azaheptadecanoic Acid CAS 1143516-05-5
Conditions
Yield
With N-ethyl-N,N-diisopropylamine In ethanol at 20℃;
Experimental Procedure To a solution of 2-(1 9-tert-l3utoxycarbonylnonade- canoylamino)pentanedioic acid 1 -tert-butyl ester 5-(2,5-di- oxopyrrolidin-1-yl) ester (2.50 g) and [2-(2-{2-[2-(2-amino- ethoxy)-ethoxy]acetylamino}ethoxy)ethoxy]acetic acid (alternative name: H-OEG-OEG-OH)(1 .47 g) in ethanol (40 mE) was added DIPEA (1.26 mE). The mixture was stirred at room temperature overnight and then concentrated in vacuo. To the residue was added aqueous 0.1 N HC1 (150 mE) and ethyl acetate (200 mE). The layers were separated and the aqueous layer was extracted with ethyl acetate (100 mE). The combined organic layers were washed with water and brine, dried (magnesium sulphate) and concentrated in vacuo to give an oil, which crystallised on standing. Yield 96% (3.1 g). ECMS: Theoretical mass: 874.2.Found: 874.49.
96%
With N-ethyl-N,N-diisopropylamine In ethanol at 20℃;
Experimental Procedure 16.1 Step 1: 19-{(S)-1-tert-Butoxycarbonyl-3-[2-(2-{[2-(2-carboxymethoxy-ethoxy)-ethylcarbamoyl]-methoxy}-ethoxy)-ethylcarbamoyl]-propylcarbamoyl}-nonadecanoic acid tert-butyl ester Step 1: 19-{(S)-1-tert-Butoxycarbonyl-3-[2-(2-{[2-(2-carboxymethoxy-ethoxy)-ethylcarbamoyl]-methoxy}-ethoxy)-ethylcarbamoyl]-propylcarbamoyl}-nonadecanoic acid tert-butyl ester (0556) (0557) To a solution of 2-(19-tert-Butoxycarbonylnonadecanoylamino)pentanedioic acid 1-tert-butyl ester 5-(2,5-dioxopyrrolidin-1-yl) ester (2.50 g, (prepared similarly as described in WO 2005/012347) and [2-(2-{2-[2-(2-Aminoethoxyl)ethoxy]acetylamino}ethoxy)ethoxy]acetic acid (1.47 g, alternative name: ∈-amino-3,6-dioxaoctanoic acid dimer, IRIS Biotech GmbH, Cat. No. PEG1221) in ethanol (40 ml) was added DIPEA (1.26 ml). The mixture was stirred at room temperature over night and then concentrated in vacuo. To the residue was added aqueous 0.1 N HCl (150 ml) and ethyl acetate (200 ml). The layers were separated and the aqueous layer was extracted with ethyl acetate (100 ml). The combined organic layers were washed with water and brine, dried (magnesium sulphate) and concentrated in vacuo to give an oil, which crystallized on standing. Yield 96% (3.1 g). LC-MS (electrospray): m/z=874.49.
96%
With N-ethyl-N,N-diisopropylamine In ethanol at 20℃;
96%
Safety and Hazards
No data available
Other Data
Transportation
Storage at 2~8°, Away from light.
Storage
Storage at 2~8°, Away from light.
Shelf Life
1 year
Druglikeness
Lipinski rules component
分子量
308.332
logP
-2.772
HBA
9
HBD
3
Matching Lipinski Rules
4
Veber rules component
Polar Surface Area (PSA)
129.34
Rotatable Bond (RotB)
16
Matching Veber Rules
1
Use Pattern
17-Amino-10-oxo-3,6,12,15-tetraoxa-9-azaheptadecanoic Acid CAS#: 1143516-05-5 as an intermediate in the synthesis of semaglutide, developing an efficient synthesis route with this intermediate could contribute to the cost-effectiveness of producing semaglutide.
Route of Synthesis (ROS) of [2-[2-(Fmoc-amino)ethoxy]ethoxy]acetic acid CAS# 166108-71-0
Conditions
Yield
With anhydrous sodium carbonate In tetrahydrofuran at 15 – 20℃; for 3h;
Experimental Procedure Compound A3 (0.2g, 1.23mmol), 2mL of tetrahydrofuran, 2mL of water and sodium carbonate (0.2g, 1.84mmol) were added to the reaction kettle, the reaction temperature was maintained at 15-20°C, and fluorene methoxycarbonyl succinimide was added. (abbreviated as Fmoc-Osu, 0.4 g, 1.23 mmol) to carry out acylation reaction, after 3 hours of reaction, spot plate to confirm the end point of the reaction, then add ethyl acetate to the reaction solution, adjust pH=2-3 with hydrochloric acid, stand for fractionation The organic phase was washed three times with saturated brine, dried over sodium sulfate, and concentrated to obtain Fmoc-AEEA (0.43 g, yield 91%, purity 99.8%).The purity of Fmoc-AEEA synthesized in this example is 99.8%, and the total yield is 88%×91%×93%×91%=67.78%.
91%
With Sodium hydrogenocarbonate In ethanol; lithium hydroxide monohydrate for 6h; pH=9;
Experimental Procedure Add sodium bicarbonate solid to adjust the product pH of step d to be about 9, then add 140mL of water, 140ml of ethanol, add 42.5g of Fmoc-osu in batches, react 6h after TLC monitoring, after the completion of the reaction; concentrate most of the ethanol under reduced pressure , the pH was adjusted to 2 with hydrochloric acid, crystal seeds were added for crystallization, the solid was precipitated and the crystallization continued for 2 h, filtered and dried to obtain 41.6 g of a white solid, namely [2-[1-(Fmoc-amino)ethoxy]ethoxy base]acetic acid.Result detection: the obtained [2-[1-(Fmoc-amino)ethoxy]ethoxy]acetic acid has a purity of 99.6% and a yield of 63.2%.
63.2%
With potassium carbonate In lithium hydroxide monohydrate for 16h;
Safety and Hazards
Pictogram(s)
Signal
Warning
GHS Hazard Statements
H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation] H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation] H335 (100%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]
Precautionary Statement Codes
P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (The corresponding statement to each P-code can be found at the GHS Classification page.)
Other Data
Transportation
At room temperature away from light
Storage
At room temperature away from light
Shelf Life
1 year
Market Price
Druglikeness
Lipinski rules component
分子量
385.417
logP
2.159
HBA
7
HBD
2
Matching Lipinski Rules
4
Veber rules component
Polar Surface Area (PSA)
94.09
Rotatable Bond (RotB)
12
Matching Veber Rules
1
Use Pattern
[2-[2-(Fmoc-amino)ethoxy]ethoxy]acetic acid CAS#: 166108-71-0 is an intermediate of API Sermaglutide.
![Route of Synthesis (ROS) of [2-[2-(Fmoc-amino)ethoxy]ethoxy]acetic acid CAS# 166108-71-0](http://www.chemwhat.com/wp-content/uploads/2017/12/Route-of-Synthesis-ROS-of-2-2-Fmoc-aminoethoxyethoxyacetic-acid-CAS-166108-71-0.png)
