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Chemical Structure| 36805-97-7 Chemical Structure| 36805-97-7

Structure of 36805-97-7

Chemical Structure| 36805-97-7

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Product Citations

Product Citations

Artem Chayka ; Michal Česnek ; Erika Kužmová ; Jaroslav Kozák ; Eva Tloušt' ; ová , et al.

Abstract: Yohimbine, a natural alkaloid and a nonselective adrenoceptor antagonist, possesses potential benefits in treating inflammatory disorders and sepsis. Nevertheless, its broader clinical use faces challenges due to its low receptor selectivity. A structure–activity relationship study of novel yohimbine analogues identified amino of yohimbic acid as potent and selective ADRA2A antagonists. Specifically, amino 4n, in comparison to yohimbine, showed a 6-fold higher ADRA1A/ADRA2A selectivity index (SI > 556 for 4n) and a 25-fold higher ADRA2B/ADRA2A selectivity index. Compound 4n also demonstrated high plasma and microsomal stability, moderate-to-low membrane permeability determining its limited ability to cross the blood–brain barrier, and negligible toxicity on nontumor normal human dermal fibroblasts. Compound 4n represents an important complementary pharmacological tool to study the involvement of adrenoceptor subtypes in pathophysiologic conditions such as inflammation and sepsis and a novel candidate for further preclinical development to treat ADRA2A-mediated pathologies.

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Product Details of [ 36805-97-7 ]

CAS No. :36805-97-7
Formula : C11H25NO2
M.W : 203.32
SMILES Code : CN(C)C(OC(C)(C)C)OC(C)(C)C
MDL No. :MFCD00015002
InChI Key :DBNQIOANXZVWIP-UHFFFAOYSA-N
Pubchem ID :547712

Safety of [ 36805-97-7 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H315-H319
Precautionary Statements:P501-P240-P210-P233-P243-P241-P242-P264-P280-P370+P378-P337+P313-P305+P351+P338-P362+P364-P303+P361+P353-P332+P313-P403+P235
Class:3
UN#:1993
Packing Group:

Application In Synthesis of [ 36805-97-7 ]

* 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.

  • Downstream synthetic route of [ 36805-97-7 ]

[ 36805-97-7 ] Synthesis Path-Downstream   1~15

  • 1
  • [ 403-45-2 ]
  • [ 36805-97-7 ]
  • [ 676560-01-3 ]
  • 2
  • [ 32501-05-6 ]
  • [ 36805-97-7 ]
  • [ 295327-36-5 ]
YieldReaction ConditionsOperation in experiment
In DMF (N,N-dimethyl-formamide); at 20℃; for 1h; This monomer was generated in situ (during library synthesis) from 4-aza-oxindole and dimethylformamide di-t-butylacetal in DMF.Monomer 9 and Monomer 10 were generated in situ by preparing stock solutions of the corresponding aza-oxindole. For example, 20.1 mg of 4-aza-oxindole was dissolved in 4.0 mL of ethanol. Both of the precursors for monomers 9 and 10 were transferred (0.20 ml/well) to a 96-well dry heating block (vwrBRAND Dry Block Heater, cat No.13259-066) according to the map below where M represents the monomer and A represents the amine. The ethanol was evaporated off at 50 C. until it was clear that there was no solvent remaining. DMF (0.20 mL) was added followed by the addition of dimethylformamide di-t-butylacetal (0.003 mL) and this remained at room temperature for 1 h.
  • 3
  • [ 5654-97-7 ]
  • [ 36805-97-7 ]
  • [ 295327-35-4 ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; Monomer 9: 3-Dimethylaminomethylene-<strong>[5654-97-7]7-azaoxindole</strong> This monomer was generated in situ (during library synthesis) from <strong>[5654-97-7]7-azaoxindole</strong> and dimethylformamide di-t-butylacetal in DMF.
In DMF (N,N-dimethyl-formamide); at 20℃; for 1h; This monomer was generated in situ (during library synthesis) from 7-aza-oxindole and dimethylformamide di-t-butylacetal in DMF.Monomer 9 and Monomer 10 were generated in situ by preparing stock solutions of the corresponding aza-oxindole. For example, 20.1 mg of 4-aza-oxindole was dissolved in 4.0 mL of ethanol. Both of the precursors for monomers 9 and 10 were transferred (0.20 ml/well) to a 96-well dry heating block (vwrBRAND Dry Block Heater, cat No.13259-066) according to the map below where M represents the monomer and A represents the amine. The ethanol was evaporated off at 50 C. until it was clear that there was no solvent remaining. DMF (0.20 mL) was added followed by the addition of dimethylformamide di-t-butylacetal (0.003 mL) and this remained at room temperature for 1 h.
  • 4
  • [ 1798-06-7 ]
  • [ 36805-97-7 ]
  • [ 856250-87-8 ]
YieldReaction ConditionsOperation in experiment
44% In toluene; at 80℃; for 2h; A solution of 4-iodo phenyl acetic acid (Lancaster, 1. 31g, 5mmmmol) in anhydrous toluene (10mL) was heated to 80C and treated with a solution of N, N- dimethyl fonnamide di-t-butyl acetal. After 2 h the reaction mixture was cooled to ambient temperature and subjected to flash column chromatography on silica gel (23-400 mesh) using 10% ethyl acetate in hexane as the eluent to afford the title compound (0.7g, 44%). 1H NMR (300 MHz, CDCl3) : 8 7.62 (d, 2H, J= 8.2Hz), 7.01 (d, 2H, J= 8.2Hz), 3. 45 (s, 2H), 1.43 (s, 9H).
44% In toluene; at 80℃; for 2h; 4-Iodo-tert-butyl phenvl acetate (Reagent 10); A solution of 4-iodo phenyl acetic acid (Lancaster, 1. 31g, 5mmmol) in anhydrous toluene (lOmL) was heated to 80C and treated with a solution of N, N- dimethyl formamide di-t-butyl acetal. After 2 h the reaction mixture was cooled to ambient temperature and subjected to flash column chromatography on silica gel (23-400 mesh) using 10% ethyl acetate in hexane as the eluent to afford the title compound (0.7g, 44%). IH NMR (300 MHz, CDCl3) : 8 7.62 (d, 2H, J= 8. 2Hz), 7.01 (d, 2H, J= 8. 2Hz), 3.45 (s, 2H), 1.43 (s, 9H).
  • 5
  • [ 32501-05-6 ]
  • [ 36805-97-7 ]
  • 3-[(dimethylamino)methylidene]-1H-pyrrolo[3,2-b]pyridin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; 3-[(Dimethylamino)methylidene]-1H-pyrrolo[3,2-b]pyridin-2-one This monomer was generated in situ (during library synthesis) from <strong>[32501-05-6]1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one</strong> and dimethylformamide di-t-butylacetal in DMF.
  • 6
  • [ 5654-97-7 ]
  • [ 63-74-1 ]
  • [ 36805-97-7 ]
  • [ 295327-24-1 ]
YieldReaction ConditionsOperation in experiment
36 mg (21%) With methanesulfonic acid; sodium hydrogencarbonate; In methanol; ethanol; water; N,N-dimethyl-formamide; Example 3A 4-[(2-Oxo-1,2-dihydro-3H-pyrrolo[2,3-b]pyridin-3-ylidene)methyl]amino}benzenesulfonamide Dimethylformamide di-tert-butyl acetal (180 mg, 0.89 mmol) was added to a solution of 1,2-dihydro-3H-pyrrolo[2,3-b]pyridin-2-one (70 mg, 0.52 mmol) in 0.25 ml DMF, and the reaction mixture was slowly warmed to 100 C. The cooled solution was then diluted with 5 ml of ethanol. Sulfanilamide (172 mg, 1.00 mmol) and methanesulfonic acid (60 mg, 0.63 mmol) were added, and the reaction mixture was stirred at reflux for 2 hours. The cooled solution was diluted with 4 ml of water, treated with NaHCO3 (70 mg, 0.83 mmol) and stirred 10 min. The resulting solid was filtered, washed with water and ethanol, and then suspended in boiling methanol and filtered upon cooling. Inorganics were removed by filtration through a short silica gel column, eluding with DMF. The resulting solution was diluted with an equal volume of ice water, and the suspension was refrigerated overnight. The solid was isolated by filtration and dried to give 36 mg (21%) of the title compound as a yellow solid: 1H NMR (400 MHz, DMSO-d6) (4:1 ratio of Z:E isomers): delta (Z) 11.07 (s, 1H), 10.76 (d, J=12.4 Hz, 1H), 8.67 (d, J=12.5 Hz, 1H), 7.92 (d, J=5.1 Hz, 1H), 7.84 (d, J=7.3 Hz,
36 mg (21%) With methanesulfonic acid; sodium hydrogencarbonate; In methanol; ethanol; water; N,N-dimethyl-formamide; EXAMPLE 3 4-[(2-oxo-1,2-Dihydro-3H-pyrrolo[2,3-b]pyridin-3-ylidene)methyl]amino}benzenesulfonamide Dimethylformamide di-tert-butyl acetal (180 mg, 0.89 mmol) was added to a solution of 1,2-dihydro-3H-pyrrolo[2,3-b]pyridin-2-one (70 mg, 0.52 mmol) in 0.25 ml DMF, and the reaction mixture was slowly warmed to 100 C. The cooled solution was then diluted with 5 ml of ethanol. Sulfanilamide (172 mg, 1.00 mmol) and methanesulfonic acid (60 mg, 0.63 mmol) were added, and the reaction mixture was stirred at reflux for 2 h. The cooled solution was diluted with 4 ml of water, treated with NaHCO3 (70 mg, 0.83 mmol) and stirred 10 min. The resulting solid was filtered, washed with water and ethanol, and then suspended in boiling methanol and filtered upon cooling. Inorganics were removed by filtration through a short silica gel column, eluding with DMF. The resulting solution was diluted with an equal volume of ice water, and the suspension was refrigerated overnight. The solid was isolated by filtration and dried to give 36 mg (21%) of the title compound as a yellow solid: 1H NMR (400 MHz, DMSO-d6) (4:1 ratio of Z:E isomers): delta (Z) 11.07 (s, 1H), 10.76 (d, J=12.4 Hz, 1H), 8.67 (d, J=12.5 Hz, 1H), 7.92 (d, J=5.1 Hz, 1H), 7.84 (d, J=7.3 Hz, 1H), 7.77 (d, J=8.7 Hz, 2H), 7.55 (d, J=8.6 Hz, 2H), 7.25 (s, 2H), 6.93 (dd, J=7.3, 5.1 Hz, 1H); (E) 10.79 (s, 1H), 9.70 (d, J=13.4 Hz, 1H), 8.23 (d, J=7.3 Hz, 1H). ESI-MS m/z 315 (M-H). Anal. Calcd. for C14H12N4O3S. 0.5 H2O: C, 51.68; H, 4.03; N, 17.03. Found: C, 51.75; H, 3.95; N, 17.26.
  • 7
  • [ 5654-97-7 ]
  • [ 36805-97-7 ]
  • 3-dimethylaminomethylene-1,3-dihydropyrrolo[2,3-b]pyridin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; 3-[(Dimethylamino)methylidene]-1H-pyrrolo[2,3-b]pyridin-2-one This compound was prepared in situ (during library synthesis) from <strong>[5654-97-7]1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one</strong> and dimethylformamide di-t-butylacetal in DMF.
  • 8
  • [ 403-45-2 ]
  • [ 75-65-0 ]
  • [ 36805-97-7 ]
  • [ 676560-01-3 ]
YieldReaction ConditionsOperation in experiment
In hexane; benzene; Example 40A 6-Fluoro-nicotinic acid tert-butyl ester To a stirred and refluxed solution of 6-fluoro-nicotinic acid (0.092 g, 6.52 mmol) in benzene and 2-methyl-propan-2-ol (2:1, 15:7 mL) was added dropwise N,N-dimethylformamide di-tert-butyl acetal (8.2 mL, 29.6 mmol). The reaction mixture was refluxed for 3 hours, cooled to room temperature and partitioned between aqueous NaHCO3 and dichloromethane. The organic layer was washed with water and brine, dried (MgSO4), filtered, concentrated under reduced pressure and purified by flash chromatography with 15% to 30% ethyl acetate in hexane to provide the titled compound. MS (CI) m/z 197 (M+1)+; 1H NMR (300 MHz, CDCl3) delta ppm 8.82(d, 1H), 8.38(m, 1H), 6.98(d, 1H), 1.64 (s, 9H).
  • 9
  • [ 37718-11-9 ]
  • [ 36805-97-7 ]
  • [ 611239-23-7 ]
YieldReaction ConditionsOperation in experiment
In toluene; at 70 - 78℃; for 21.25h; Description 13: 1 H-Pvrazole-4-carboxylic acid ter-butyl ester A stirred suspension of 1 H-<strong>[37718-11-9]pyrazole-4-carboxylic acid</strong> (1. 12g) in dry toluene (20ml) was heated at 70°C for 15min under an atmosphere of nitrogen. To the hot suspension was added a solution of N, N-dimethylformamide-di-tert-butyl acetal (8ml) in dry toluene (8ml). The resultant solution was heated at 78°C for 21 hrs. After cooling, the mixture was diluted with ethyl acetate (100ml) and washed with saturated aqueous brine solution (5x25mi). The organic phase was dried over magnesium sulphate, filtered, and evaporated to dryness to give a gum. The gum was purified by flash column chromatography on silica gel (60g of Merck 9385) and eluted with dichloromethane/methanol 50: 1. The required fractions were combined and evaporated to dryness to give the title compound as a gum which solidified upon standing (0.481g). Mpt. 96-97 °C
  • 10
  • [ 15855-06-8 ]
  • [ 36805-97-7 ]
  • [ 537032-06-7 ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; at 80 - 100℃; for 48h; A solution of 10.0 g (53.3 mmol) 2-Chloro-6-methoxy-isonicotinic acid in 60 ml DMF is heated to 100 C. for 4 h, then to 80 C. for another 44 h. In total 99 ml (410 mmol, 7.8 eq) N,N-dimethylformamide di-tert-butylacetal is added in 12 portions over time. After cooling to rt the mixture is diluted with EtOAc, washed with aq. bicarbonate and brine, and dried over sodium sulfate. The residue is purified by chromatography on silica (flashmaster, hexane to hexane/EtOAc 95/5) to give the product in the form of a white solid.MS (LC/MS): 188=[M+H-tBu]+ 1H-NMR (300 MHz, CDCl3): 7.37 (s, 1H), 7.16 (s, 1H), 3.97 (s, 3H), 1.59 (s, 9H).
  • 11
  • [ 586-89-0 ]
  • [ 36805-97-7 ]
  • [ 105580-41-4 ]
YieldReaction ConditionsOperation in experiment
35% In toluene; at 85℃; for 19h; The carboxylic acid (10 g, 60.9 mmol) and Me2NCH(OtBu)2 (25 g) were heated in toluene (300 ml_) for 5 hours (85 0C). More Me2NCH(OtBu)2 (25 g) was added, and the reaction was heated at 85 0C for 14 hours. The solution was partitioned between EtOAc and sat. NaHCO3(aq.). The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine and dried over MgSO4. The solution residue was filtered through a plug of SiO2 rinsing with CH2CI2. This afforded 4.7 g (35 %) of the tert-butyl ester as a solid.
  • 12
  • [ 453-71-4 ]
  • [ 36805-97-7 ]
  • [ 579514-75-3 ]
YieldReaction ConditionsOperation in experiment
16% In toluene; at 100℃; for 20h; To a 2L high pressure vessel were added 4-fluoro-3-nitrobenzoic acid (25 g, 135 mmol), dimethylformamide di-t-butylacetal (162 ml, 675 mmol), and toluene (200 ml). The vessel was sealed and heated to 1000C for 20 hours. The mixture was cooled to ambient temperature. The mixture was transferred to 100 mL of EtOAc and 100 ml of IN HCl and the layers were separated. The organic layer was washed with IN HCl, water, and brine, dried over MgSO4, filtered through a medium frit filter, and concentrated. The crude was purified on silica gel (EtOAc in hexanes gradient) to provide 5. Ig of the title compound were obtained as light yellow solid (16%).
  • 13
  • [ 149057-19-2 ]
  • [ 36805-97-7 ]
  • 4-benzyl 1,2-di-tert-butyl piperazine-1,2,4-tricarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% In toluene; at 80℃; for 2h;Inert atmosphere; Stage 1. 4-Benzyl 1 ,2-di-teit-butyl piperazine-1 ,2,4-tricarboxylate 4-[(Benzyloxy)carbonyl]- 1 -(teit-butoxycarbonyl)piperazi ne-2-carboxyl ic acid (1.0 g,2.74 mmol) was dissolved in toluene (10 mL) and heated to 80C under a nitrogen atmosphere. DMF di teit-butyl acetal was then added dropwise (2.6 mL, 11 mmol) and stirring continued for 2 hrs. The reaction mixture was cooled and partitioned between EtOAc (200 mL) and water (200 mL). The organic layer was separated and the aqueous layer re-extracted with EtOAc (2 x 100 mL). The combined organic layers were dried over Mg504, concentrated in vacuo and the residue was purified by automated column chromatography (0-100% EtOAc/heptane) to give the title compound as a colourless oil (1.08 g, 94%).LCMS: m/z 443 [M+Na].
  • 14
  • [ 30651-24-2 ]
  • [ 36805-97-7 ]
  • tert-butyl 5-nitropyridine-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
In toluene; at 60 - 100℃; General procedure: [0497] A solution of the appropriate carboxylic acid (1 eq.) in toluene (0.15-0.05 M) was heated to 60 to 100° C., and N,N-dimethylformamide di-tert-butyl acetal (4 eq.) was added dropwise. The reaction mixture was stirred at 60 to 100° C. for ito 5 hand cooled to RT, and ethyl acetate was added. The organic phase was washed with saturated aqueous sodium hydrogencarbonate solution and with saturated aqueous sodium chloride solution, dried (sodium sulphate), filtered and concentrated under reduced pressure. The crude product was used in the next stage without purification.; [0513] According to General Method 10A, 1000mg (5.95mmol) of <strong>[30651-24-2]5-nitropyridine-2-carboxylic acid</strong> were reacted.The crude product was used in the next stage withoutpurification. Yield: 600 mg (45percent of theory)10514] HPLC [Method 1]: R=0.89 mm,10515] ?H-NMR (400 MHz, DMSO-d5): oe [ppm]=9.44 (d,1H), 8.73 (dd, 1H), 8.22 (d, 1H), 1.58 (s, 9H).
  • 15
  • [ 5985-24-0 ]
  • [ 36805-97-7 ]
  • [ 576170-38-2 ]
YieldReaction ConditionsOperation in experiment
60.7% Into the reaction vessel was added pyridine (50 mL) and <strong>[5985-24-0]dimethyl 4-hydroxyisophthalate</strong> (3.6 g, 17 mmol). The mixture was stirred at reflux for 17h andconcentrated. The residue was acidified with 1M HC1 (50 mL) and extracted with EtOAc (3OmL x 3). The organic phase was dried over Na2504, concentrated, and dissolved in DCM (10 mL). 1,1 -Di-tert-butoxy-N,N-dimethylmethanarnine (10.45 g, 51 .40 mmol) was then added and the reaction was stirred at rt for 12h. After diluted with EtOAc (30 mL), the organic phase was washed with sat NaHCO3 (20 mL x 3), dried over Na2SO4, andconcentrated to produce 1A (2.62 g, 10.40 mmol, 60.7percent yield) as a white solid which was used for next step without further purification. LCMS Anal. Calc?d for C13H1605 252.10,found [M+H] 253.1; 1H NMR (500MHz, chloroform-d) 8 11.56 (s, 1H), 8.58-8.46 (m, 1H), 8.16 - 8.08 (m, 1H), 7.02 (s, 1H), 3.93 (s, 3H), 1.66 (s, 9H).
 

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