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Chemical Structure| 144690-33-5 Chemical Structure| 144690-33-5

Structure of 144690-33-5

Chemical Structure| 144690-33-5

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Product Details of [ 144690-33-5 ]

CAS No. :144690-33-5
Formula : C45H44N6O3
M.W : 716.87
SMILES Code : CCCC1=NC(C(C)(C)O)=C(C(OCC)=O)N1CC2=CC=C(C3=CC=CC=C3C4=NN=NN4C(C5=CC=CC=C5)(C6=CC=CC=C6)C7=CC=CC=C7)C=C2
MDL No. :MFCD11973634
InChI Key :TZQDBKJBKJIHPR-UHFFFAOYSA-N
Pubchem ID :19036118

Safety of [ 144690-33-5 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H315-H319-H228
Precautionary Statements:P240-P210-P241-P264-P280-P302+P352-P370+P378-P337+P313-P305+P351+P338-P362+P364-P332+P313
Class:4.1
UN#:1325
Packing Group:

Application In Synthesis of [ 144690-33-5 ]

* 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.

  • Upstream synthesis route of [ 144690-33-5 ]
  • Downstream synthetic route of [ 144690-33-5 ]

[ 144690-33-5 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 144690-33-5 ]
  • [ 80841-78-7 ]
  • [ 144690-92-6 ]
YieldReaction ConditionsOperation in experiment
88%
Stage #1: With sodium hydroxide In ethanol at 20 - 25℃;
Stage #2: With potassium carbonate In N,N-dimethyl acetamide at 45 - 50℃; for 4 h;
Example 5: The reaction part was charged with ethyl 4- (1-hydroxy-1-methylethyl) -2-propyl-1- {4- [2- (trityltetrazol-5-yl) phenyl] 22 g of 5-carboxylate (Formula 4), 3.1 g of sodium hydroxide and 90 mL of ethanol were added and the mixture was stirred at 20 to 25 ° C for 4 to 5 hours. When the reaction was completed, the reaction solution was concentrated. To the residue were added 50 mL of ethyl acetate and 50 mL of purified water. The mixture was stirred for 1 hour and then layered. The separated organic layer was washed twice with an aqueous solution containing 30 g of salt and 170 mL of purified water. 1 g of activated carbon and 20 g of anhydrous sodium sulfate were added to the organic layer, followed by stirring for 30 minutes to 1 hour, followed by filtration Respectively. After the filtrate was concentrated under reduced pressure, 50 mL of N, N-dimethylacetamide was added to the residue, the temperature was adjusted to 5 to 10 DEG C 4 g of potassium carbonate was added and 6.2 g of 4- (chloromethyl) -5-methyl-1,3-dioxol-2-one (Formula 6) was dissolved in N, N-dimethylacetamide 6 ML was added dropwise, and the mixture was reacted at 45 to 50 ° C for 4 hours with stirring. When the reaction is completed, the reaction solution is cooled to 20 to 25 After cooling, 220 mL of ethyl acetate, 30 g of salt and 170 mL of purified water were added successively. The organic layer was separated And then washed once more with an aqueous solution containing 30 g of salt and 170 mL of purified water. The organic layer was washed with 1 g of activated carbon, 20 g of sodium was added and stirred for 30 minutes to 1 hour, followed by filtration. The filtrate was concentrated under reduced pressure, and then acetone 100 mL of i-tril was added, and the mixture was stirred at 50 to 55 ° C for 1 hour. The crystals were cooled to 0 to 5 [deg.] C and stirred for 2 hours. Followed by washing with 50 mL of isopropyl alcohol, followed by drying to obtain 21.6 g (yield: 88percent) of tritylolemecanemethoxysilane (formula 1a) Purity 99.97percent) was obtained
85.8%
Stage #1: With sodium hydroxide In acetone at 50 - 60℃; for 5 h; Green chemistry
Stage #2: With potassium iodide In acetone at 20 - 60℃; for 1 h; Green chemistry
1L glass reaction flask was added with 600ml of acetone, 114.8g of intermediate 1 was added with stirring, then 12.8g of sodium hydroxide was added, the temperature was raised to 50-60 °C, and the reaction was incubated for 5 hours, and the reaction was monitored by HPLC. To 20-30 °C, add 2.8g potassium iodide, 36.0g 4-chloromethyl-5-methyl-1,3-dioxol-2-one, and increase the temperature to 50-60 °C after the addition After 1 hour of heat preservation reaction, the temperature was lowered to 20-30 ° C, filtered, and the filter cake was rinsed with 115 ml of acetone, and the filtrate was combined. The filtrate was concentrated under reduced pressure at 40-50 °C until no obvious solvent flowed out, and 320 ml of acetonitrile was added to cool down. The mixture was decanted to 20-30 °C for 1 hour, filtered, and the filter cake was rinsed with 320 ml of acetonitrile. The filter cake was blast dried at 40-50 °C for 12 hours to obtain a white solid 110.0 g (intermediate 2). The rate was 85.8percent, HPLC: 99.2percent.
309 g
Stage #1: Reflux
Stage #2: Reflux
To the flask was added 2000 g of acetone, 160 g of ethyl 4- (1-hydroxy-1-methylethyl) -2-propylimidazole-5-carboxylate (II), 150 g of K2CO3, 460 g of 4- [2- (Trityltetrazol-5-yl) phenyl] benzyl bromide (III), 20g KI, the temperature was raised to reflux, the reaction was incubated for 34-38 hours under stirring.Then add 102g KOH, reflux reaction 6 ~ 8h. Cool to 10 ~ 20 , add 170g DMDO-Cl, incubated for 30 ~ 60min.Heating to reflux, the reaction 22 to 26 hours.After the reaction was added 40g of diatomaceous earth, stirring for 30 to 60 minutes, suction filtration, 200g acetone rinse cake. To the filtrate was added 800g of drinking water and 200g of refined hydrochloric acid, the reaction at room temperature for 2 to 4 hours, filtered to remove by-product triphenylcarbinol. Dropping 10percent K2CO3 aqueous solution, adjusting feedstock pH to 4, cooling to 10 ~ 20 , stirring crystallization 2h, filtration, the filter cake with a mixture of pre-cooled 45g acetone and 230g of drinking water washing and drying, to obtain Olmesartan Medoxomil 309 g, total yield 83.1percent (relative to ethyl-4- (1-hydroxy-1-methylethyl) -2-propylimidazole-5- carboxylate (II)), purity: 99.27percent of the main peak, 0.08percent of the olmesartan acid, 0.14percent of the triphenylmethanol, and 0.13percent of the largest unidentified one.
References: [1] Patent: KR101526249, 2015, B1, . Location in patent: Paragraph 0071; 0072.
[2] Patent: CN108341804, 2018, A, . Location in patent: Paragraph 0015; 0033; 0034.
[3] Patent: WO2008/43996, 2008, A2, . Location in patent: Page/Page column 16-17; 18.
[4] Patent: WO2008/43996, 2008, A2, . Location in patent: Page/Page column 17-18.
[5] Patent: WO2008/43996, 2008, A2, . Location in patent: Page/Page column 18-19.
[6] Patent: US2009/131680, 2009, A1, . Location in patent: Page/Page column 8.
[7] Patent: WO2007/17135, 2007, A2, . Location in patent: Page/Page column 5; 21-22.
[8] Patent: EP1816131, 2007, A1, . Location in patent: Page/Page column 12.
[9] Patent: WO2011/14611, 2011, A2, . Location in patent: Page/Page column 11.
[10] Patent: WO2012/55994, 2012, A1, . Location in patent: Page/Page column 19.
[11] Patent: CN107311990, 2017, A, . Location in patent: Paragraph 0043; 0044; 0045; 0046.
  • 2
  • [ 144690-33-5 ]
  • [ 144690-92-6 ]
References: [1] Patent: WO2012/1694, 2012, A1, .
[2] Patent: EP2891650, 2015, A1, .
[3] Patent: CN105481842, 2016, A, .
[4] Patent: CN105418593, 2016, A, .
[5] Patent: KR101526249, 2015, B1, .
[6] Patent: CN103304550, 2016, B, .
[7] Patent: CN107311989, 2017, A, .
[8] Patent: CN103012382, 2016, B, .
 

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