2,3,4,6-Tetra-O-benzyl-D-glucopyranose

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CAS No.	4132-28-9
Chemical Name:	2,3,4,6-Tetra-O-benzyl-D-glucopyranose
Synonyms:	2,3,4,6-Tetra-O-benz;benzyl-D-glucopyranose;2,3,4,6-TETRABENZYL-D-GLUCOSE;Tetra-O-benzyl-D-glucopyranose;2,3,4,6-Tetra-O-benzyl-D-glucopyranose;2,3,4,6-TETRA-O-BENZYL-A-D-GLUCOPYRANOSIDE;2,3,4,6-TETRA-O-BENZYL-ALPHA-D-GLUCOPYRANOSE;2,3,4,6-Tetra-O-benzyl-D-glucopyranose, 98+%;2,3,4,6-Tetra-O-benzyl-α-D-glucopyranose ,97%;2,3,4,6-Tetrakis-O-(phenylmethyl)-D-glucopyranose
CBNumber:	CB7194124
Molecular Formula:	C34H36O6
Formula Weight:	540.65

 




 


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(2S) -N- tert-butoxycarbonylamino-1-amino-3- [[3-fluoro-4- (4-morpholinyl) phenyl] - acetamido] -2-propanol

Example 9

(2S) -N- tert-butoxycarbonylamino-1-amino-3- [[3-fluoro-4- (4-morpholinyl) phenyl] - acetamido] -2-propanol (8a) Preparation of The (27?) - # - t-butoxycarbonylamino-1-amino-3 - [[3-fluoro-4- (4-morpholinyl) phenyl] amino] -2-propanol (0.03 mol), two After 100 ml of methyl chloride and triethylamine (0.04 mol) added to the reaction flask, stir, set in an ice bath to cool to 0-5 ° C, was added dropwise acetyl chloride (0. 033 mol), stirred at room temperature for 3 hours The reaction was washed with aqueous NaHC03, washed with saturated aqueous NaCl, the organic layer was dried over anhydrous Na2S04, the solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 1/30 v / v), to give a pale yellow oil in a yield of 85.0%; 

Che NMR (CDC13,400MHz) 

8: 6. 92 (m, 3H, Ar-H), 

5. 23 (brs, 1H, NHCO) , 

3. 89 (t, J = 4. 4Hz, 4H, 2 X CH20), 

3. 85 (m, 1H, CHO), 

3. 83 (m, 1H, CH2N-Ar), 

3. 59 (d, J = 12Hz, 1H, CH2NAr), 

3. 33 (m, 1H, CH2NC0), 

3. 12 (t, / = 4. 8Hz, 4H, 2 X CH2N), 

3. 04 (m, 1H, CH2NC0), 

1. 89 (s, 3H, CH3), 

1. 43 (s, 9H, CH3). 

http://www.google.com/patents/CN103483294A?cl=zh

SiChuan university

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Rotigotine-2-Azidoacetate

Example 3 Synthesis of Rotigotine-2-Azidoacetate

In a 25 mL round bottom flask, was placed rotigotine (1 g, 3.17 mmol, 1 equiv.), 2-azidoacetic acid-DMAP salt (0.849 g, 3.80 mmol, 1.2 equiv.) and 32 mL of anhydrous dichloromethane (DCM) and the mixture stirred under argon. DMAP (0.077 g, 0.634 mmol, 0.2 equiv.) and DCC (0.785 g, 3.80 mmol, 1.2 equiv.) were added as solids. The mixture was stirred for 16 hours at room temperature. The mixture was then filtered to remove precipitated urea and concentrated using a rotary evaporator. The crude mixture was first purified by silica gel column chromatography using a mixture of ethyl acetate and hexanes (1:2) as an eluent to give a clear yellow oil (1.27 g, 92% yield).
A second purification was performed by reversed phase chromatography to remove free rotigotine and other small molecule impurities. A sample solution for loading was prepared by dissolving crude product (350 mg) in 0.1% TFA in acetonitrile (4.05 mL), followed by addition of 1 N HCl (0.91 mL) and 0.1% TFA in water (4.04 mL). The sample solution was filtered through a 0.2 μm PTFE syringe filter, and then loaded to a Waters SunFire Prep C18 OBD 30/250 Column (from Waters) on an ÄKTA Purifier system equipped with an UV detector at 214 nm. 0.1% TFA in water (A) and 0.1% TFA in acetonitrile (B) were used as mobile phase. The column was then eluted isocratically with 40% of mobile phase B at flow rate of 20 mL/min. The fractions that contained pure product were collected and pooled. Acetonitrile in the pooled fraction was evaporated by rotary-evaporation. The remaining aqueous solution was extracted with DCM (3×50 mL), dried over anhydrous sodium sulfate and filtered, followed by evaporation of the DCM. The residue was dried in vacuum (293 mg, 83%).

¹H NMR (Varian, 500 MHz, 10 mg/mL CDCl₃) showed peaks at 0.90 ppm (t, J=6.84 Hz, 3H), 1.25 (m, 1H), 1.29 (m, 1H), 1.49 (m, 1H), 1.59 (m, 1H), 2.05 (m, 2H), 2.54 (m, 3H), 2.82 (m, 3H), 2.97 (m, 3H), 4.156 N₃CH₂C(═O)O— (s, 2H), 6.81 (s, 1H), 6.88 (d, J=7.81 Hz, 1H), 6.92 (t, J=3.42 Hz, 1H), 7.02 (d, J=7.32 Hz, 1H), 7.13 (m, 2H).
RP-HPLC analysis showed that the product contained no free rotigotine. The HPLC chromatogram of product before (FIG. 1A) and after (FIG. 1B) reversed phase chromatography purification are shown.

 https://www.google.com/patents/US8383093

H-[(N-Ropinirole)10(EOZ)190]-COOH 20K

Example 9 Preparation of H-[(N-Ropinirole)₁₀(EOZ)₁₉₀]-COOH 20K by attachment of Ropinirole 3-azidocarbamate to Polyoxazoline 10 pendent acid 20K

Ropinirole-N-bromoethylcarboxylate To a solution of ropinerole ropinirole hydrochloride (0.558 g, 1.88 mmol) in dioxane (38 ml) was added triethylamine (2.10 ml, 15.1 mmol). After stirring for 5 minutes, 2-bromoethyl chloroformate (1.61 ml, 15.1 mmol) was added slowly and the mixture was allowed to stir overnight at room temperature. Water (40 mL) was added to give a mixture with pH of 9.5. After stirring overnight, the mixture was stirred with dichloromethane (40 mL) and brine solution (10 mL) for 10 minutes. The two layers were separated and the top layer was extracted with dichloromethane (40 mL). The combined organic phases were dried over Na₂SO₄, filtered, and concentrated to give dark red thick oil. Further purification was performed by silica gel column chromatography, eluting with dichloromethane/EtOAc (starting from 9:1, 4:1, and then 100% EtOAc) to give the desired N-acylated product as a dark red oil (0.170 g, 22.01% yield).). ¹H NMR (Varian, 500 MHz, 10 mg/mL DMSO-d₆, δ): 0.83 (t, J=7.5 Hz, 6H, —CH₂CH₂CH₃), 1.39 (m, 4H, —CH₂CH₂CH₃), 2.39 (t, J=7.5 Hz, 4H, —CH₂CH₂CH₃), 2.62 (m, 4H, Pr₂NCH₂CH₂—Ar), 3.80 (s, 2H, —CH₂C(═O)—), 3.80 (t, J=5.5 Hz, 2H, —OCH₂CH₂Br), 4.65 (t, 2H, —OCH₂CH₂Br), 7.04 (d, J=8.0 Hz, 1H, Ar H), 7.25 (t, J=8.0 Hz, 1H, Ar H), 7.63 (d, J=8.0 Hz, 1H, Ar H).
Ropinirole-N-azidoethylcarboxylate To a solution of Ropinirole-N-bromoethylcarboxylate (0.170 g, 0.414 mmol) in DMF (2 ml) was added sodium azide (0.027 g, 0.414 mmol) to give a clear yellow solution. After stirring overnight at room temperature, the mixture was quenched with 1 mL of 0.1 N HCl and then diluted with 2 mL of water. All the volatiles were removed using a rotary evaporator and the aqueous solution was extracted twice with dichloromethane (3 mL each). The combined organic phases were dried over Na₂SO₄, filtered, and concentrated to give Ropinirole-N-azidoethylcarboxylate (0.12 g, 78% yield) as thick yellow oil. ¹H NMR (Varian, 500 MHz, 10 mg/mL DMSO-d₆, δ): 0.93 (t, J=Hz, 6H, —CH₂CH₂CH₃), 1.70 (m, 4H, —CH₂CH₂CH₃), 2.99 (m, J=Hz, 4H, Pr₂NCH₂CH₂—Ar), 3.07 (m, 4H, —CH₂CH₂CH₃), 3.22 (m, 4H, Pr₂NCH₂CH₂—Ar), 3.92 (s, 2H, —CH₂C(═O)—), 3.98 (t, 2H, —OCH₂CH₂N₃), 4.48 (t, 2H, —OCH₂CH₂Br), 7.14 (d, J=7.5 Hz, 1H, Ar H), 7.33 (t, J=8.0 Hz, 1H, Ar H), 7.69 (d, J=8.0 Hz, 1H, Ar H).
H-[(N-Ropinirole)₁₀(EOZ)₁₉₀]-COOH 20K Ropinirole-N-azidoethylcarboxylate hydrochloride (0.12 g, 0.293 mmol) was dissolved in THF (15 ml). H-[(Ptyn)₁₀(Ethyl)₂₀₀]-T-PA (0.488 g, 0.024 mmol) was added and the mixture was stirred to form a solution. Cul (0.019 g, 0.098 mmol) and triethylamine (0.014 ml, 0.098 mmol) were added to give a clear red solution. After stirring for 16 hours at 45° C., the mixture was quenched with 2 mL of 0.1N HCl to give a solution with pH of 3. All the volatiles were removed and the residue was dissolved in methanol. The resulting mixture was passed through a Dowex and Amberlite IR-120 column using methanol as an eluent. After removing methanol, the resulting aqueous solution was extracted twice with dichloromethane (5 mL each). The organic solution was dried over Na₂SO₄, filtered, concentrated to 10 mL, and precipitated by adding into 70 mL of diethyl ether. The precipitate was filtered and dried in vacuo to give H-[(N-Ropinirole)₁₀(Ethyl)₂₀₀]-T-PA (0.50 g, 86% yield) as a pale yellow powder. In addition to the usual polymer backbone peaks, ¹H NMR (Varian, 500 MHz, 10 mg/mL DMSO-d₆, δ) shows the polymer chain contained an average of 6.4 units of rotigotine with major Ropinirole peaks at 0.97 (m, 6H, —CH₂CH₂CH₃), 4.62 (m, 2H, —OCH₂CH₂Br and m, 2H, —OCH₂CH₂-triazole ring), 7.19-7.39 (br m, 3H, Ar H), and 7.91 (m, 1H, triazole H).

 https://www.google.com/patents/US8383093