Home Cart 0 Sign in  

[ CAS No. 126456-43-7 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 126456-43-7
Chemical Structure| 126456-43-7
Structure of 126456-43-7 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 126456-43-7 ]

Related Doc. of [ 126456-43-7 ]

Alternatived Products of [ 126456-43-7 ]

Product Details of [ 126456-43-7 ]

CAS No. :126456-43-7 MDL No. :MFCD00216655
Formula : C9H11NO Boiling Point : -
Linear Structure Formula :- InChI Key :LOPKSXMQWBYUOI-BDAKNGLRSA-N
M.W : 149.19 Pubchem ID :9866743
Synonyms :

Calculated chemistry of [ 126456-43-7 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.33
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 2.0
Molar Refractivity : 42.94
TPSA : 46.25 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.05 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.55
Log Po/w (XLOGP3) : 0.23
Log Po/w (WLOGP) : 0.28
Log Po/w (MLOGP) : 0.87
Log Po/w (SILICOS-IT) : 1.04
Consensus Log Po/w : 0.79

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.31
Solubility : 7.25 mg/ml ; 0.0486 mol/l
Class : Very soluble
Log S (Ali) : -0.76
Solubility : 25.9 mg/ml ; 0.173 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.81
Solubility : 2.29 mg/ml ; 0.0154 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.08

Safety of [ 126456-43-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P264-P271-P280-P302+P352-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 126456-43-7 ]

* 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 [ 126456-43-7 ]

[ 126456-43-7 ] Synthesis Path-Downstream   1~30

  • 1
  • [ 126456-43-7 ]
  • [ 98-59-9 ]
  • [ 171562-32-6 ]
YieldReaction ConditionsOperation in experiment
92% With dmap; triethylamine In dichloromethane at 23℃; for 2h;
With dmap; triethylamine In dichloromethane at 23℃; for 12h; Yield given;
With dmap In dichloromethane at 23℃; for 1h;
With triethylamine In tetrahydrofuran at 15 - 27℃; for 1h; Magnesium turnings were placed in a 5,000 mL three-neck flask equipped with a mechanical stirrer and one addition funnel. The flask was heated to 120° C. under vacuum and then flushed with nitrogen while cooling to ambient temperature. After cooling to ambient (room) temperature, the flask was kept under constant nitrogen flush. Then 1000 mL of anhydrous diethyl ether were added and the mixture was stirred at 260 rpm. Dibromoethane (87.0 g, 0.46 mol) was loaded in the addition funnel and was added slowly to the flask while the temperature was kept between 22° C.-25° C. with a water bath (note: the addition of dibromoethane to the flask is quite exothermic). When finished (approximately 1.5 hours), the magnesium turned grey. 2-(2-Chloro-1,1-dimethylethyl)-4-fluoro-1-methoxybenzene (100.0 g, 0.46 mole) and 87.0 g (0.46 mole) of dibromoethane dissolved in 1000 mL of anhydrous ether were loaded in the addition funnel and the solution was added to the reaction flask while the temperature was kept between 22° C.-25° C. When finished (approximately 3 hours), the reaction was stirred at room temperature for 15 hours. HPLC analysis indicated that there was no starting chloride left. The solution was stirred at 350 rpm while cooling to -10° C. 2,2,2-Trifluoro-N-methoxy-N-methylacetamide (72.0 g, 0.46 mole) was then added while the temperature was kept below -5° C. When finished, the slurry was warmed up to room temperature and stirred for 4 hours. 2 N HCl (600 mL, 1.20 mole) and 500 mL of water were added to the slurry while stirring at 300 rpm for 0.5 hour. After the phase separation, the organic layer was washed successively with 500 mL of water, 500 mL of saturated aqueous sodium bicarbonate (NaHCO3), and 500 mL of brine. Filtration and concentration gave 128.2 g (80% yield) of crude 1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-one as a slightly yellow liquid that was readily purified by vacuum distillation. In a 500 mL flask, (1S,2R)-1-amino-2-indanol (22.3 g, 150 mmol) was added at room temperature, followed by 100 mL of anhydrous THF and triethylamine (62.7 mL, 450 mmol). The addition funnel was rinsed with 10 mL of THF. Tosyl chloride (28.6 g, 150 mmol) solution in THF (80 mL) was slowly added in so that the temperature did not exceed 27° C. The addition funnel was rinsed with THF (35 mL). The reaction was stirred at 15° C. for 1 hour and HPLC showed the complete conversion to the desired tosylate. To the above reaction mixture was added 4-dimethylaminopyridine (DMAP) (0.92 g, 7.5 mmol) solution in THF (15 mL), followed by slow addition of acetic anhydride (17.0 mL, 180 mmol) and a THF rinse (10 mL) over 15 minutes, while maintaining the temperature below 27° C. The reaction was stirred at 15° C. for 1 hour and HPLC showed the complete conversion to the desired acetate ester. The reaction was quenched with 100 mL of 5% sodium bicarbonate solution (temperature rose to 30° C.) and the mixture was stirred for 40 minutes. The organic layer was diluted with 250 mL of tert-butyl methyl ether (MTBE), washed with two 250 mL portions of 2 N HCl solution, a 125 mL portion of water, a 125 mL portion of 5% sodium bicarbonate solution, and a 125 mL portion of brine. The organic layer was separated and concentrated to about 100 g of a thick oil. Recrystallization from 200 mL of hexane afforded the desired acetic acid (1S,2R)-1-(toluene-4-sulfonylamino)indan-2-yl ester (49 g, 95% yield) as a white solid. To a stirred solution of the above chiral ester (103.6 g, 0.3 mol) in 200 mL of dry THF was added a 1 M solution of lithium bis(trimethylsilyl)amide (750 mL, 0.75 mol) in THF via cannula, under nitrogen gas at 30° C. The resulting brown solution was stirred for 30 minutes at -30° C. A solution of 1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-pentan-2-one (83.47 g, 0.3 mol) in 200 mL of THF was added to this solution slowly while the reaction temperature was maintained at -30° C. The resulting reaction mixture was stirred at -30° C. for 30 minutes, and then was quenched by addition of about 700 mL of 2 M aqueous HCl solution to bring the pH to 7. The organic layer was concentrated under reduced pressure and the residual water was removed by azeotropic distillation of EtOAc to afford the desired crude aldol product. Silica gel chromatography (20% EtOAc/hexane) of crude product afforded a mixture of two diastereomers. Recrystallization (10% EtOAc acetate/hexane) gave the major isomer, (R)-5-(5-fluoro-2-methoxyphenyl)-3-hydroxy-5-methyl-3-trifluoromethylhexanoic acid (1S,2R)-1-(toluene-4-sulfonylamino)indan-2-yl ester (48 g, 25% yield, 98.5% e.e.) as a white solid. The above recrystallized aldol product (44.0 g, 70.55 mmol) was dissolved in 440 mL of MeOH in a dry flask. 1.0 mL (4.4 mmol) of 25% NaOMe in MeOH solution was then added in one portion. The clear solution was stirred at ambient temperature for 15 hours. HPLC analysis showed that all starting material had been consumed. 10 mL of saturated ammonium chloride (NH4Cl) solution was then added and the pH changed from 13 to 8. The solvent was then removed under vacuum to give a white solid. 200 mL of MTBE and 500 mL of hexane were added and the mixture was stirred for 1 hour at ambient temperature. The solid was filtered off and washed with two 20 mL portions of hexane. The filtrate was washed with 200 mL of 2 N NaOH, 200 mL of saturated ammonium chloride solution, 200 mL of brine, and then dried over magnesium sulfate (MgSO4). The solvent was removed under vacuum to give (R)-3-hydroxy-5-(2-methoxy-5-methylphenyl)-5-methyl-3-trifluoromethylhexanoic acid methyl ester (24.6 g, 99% yield) as a colorless oil which solidified slowly. The above methyl ester (22.6 g, 64.1 mmol) and 10.9 g (160 mmol) imidazole were dissolved in 100 mL of anhydrous DMF and cooled to -10° C. Trimethylsilyl chloride (TMSiCl, 10.5 g) was added over 10 minutes while the internal temperature was kept below -10° C. The solution was allowed to warm up to ambient temperature and was stirred for 60 hours. HPLC analysis showed no starting material was left. 200 mL of hexane and 100 mL of saturated sodium bicarbonate were then added and the mixture was stirred for 10 minutes. The layers were separated and the organic layer was washed with two 100 mL portions of water and a 100 mL portion of brine, and then dried over magnesium sulfate. Solvent was removed under vacuum to yield 26.6 g of the desired trimethylsilyl ether (98% yield) as a colorless oil. 3-Amino-4-picoline (2.16 g, 20.0 mmol) was dissolved in 80 mL of anhydrous THF in a dry flask under a nitrogen blanket. The solution was cooled to -70° C. sec-BuLi (1.4 M, 43 mL, 60.0 mmol) in cyclohexane was added via syringe over 20 minutes. The mixture was then warmed to 21° C. and stirred for 3 hours. After cooling back to -70° C., the above trimethylsilyl ether (2.54 g, 5.8 mmol) in 5 mL of anhydrous THF was added over 20 minutes. The solution darkened and after stirring 20 minutes, the solution was warmed to -40° C. and stirred an additional 20 minutes. The solution was then cooled back to -70° C. 2 N HCl (50 mL) was then added over 15 minutes and the mixture was allowed to warm up to 0° C. and stir for 30 minutes. The bright yellow slurry had a pH of less than 2. 50 mL of 1 N NaOH was then added and the pH was adjusted to greater than 10. 200 mL of MeOH was also added and the mixture was stirred for 1 hour to allow all the intermediates to convert to product. Then 100 mL of saturated ammonium chloride solution was added and the pH was adjusted to 7. The organic solvent was removed under vacuum and 200 mL of MTBE and 100 mL of saturated sodium bicarbonate solution were added. The layers were separated and the organic layer was washed with three 100 mL portions of water and a 100 mL portion of brine and then the organic layer was dried over magnesium sulfate. The solvent was evaporated under vacuum to yield 2.43 g yellow foamy solid, which was crystallized using MTBE to give the title compound (1.28 g, 55% isolated yield).
With triethylamine In dichloromethane at 20℃; for 16h;

  • 2
  • [ 24424-99-5 ]
  • [ 126456-43-7 ]
  • [ 218151-53-2 ]
YieldReaction ConditionsOperation in experiment
100% With sodium carbonate In tetrahydrofuran; water at 0 - 20℃; for 3h; Inert atmosphere;
100% With sodium carbonate In tetrahydrofuran; water at 0 - 20℃; for 3h;
99.7% With N-ethyl-N,N-diisopropylamine In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 2h; 20.a (1S, 2R)-(-)-Cis-1-amino-2-indanol (2.98 g, 20 mmol) was dissolved in anhydrous DMF (10 ml) by heating with a heat gun. After the solution was cooled to room temperature, anhydrous THF (20 ml) and DIPEA (2.59 g, 20 mmol) were added. To this well-stirred solution was slowly added di-tert-butyl- dicarbonate (5.46 g, 25 mmol). Upon the addition, a white gel was formed and it was manually broken into small pieces. The reaction became a clear solution after 2-hours stirring at room temperature. It was then extracted with water (50 ml) and hexane (50 ml). The aqueous layer was back-extracted with EtOAc (50 ml). The combined organic layers were dried over Na2SO4 and concentrated by rotary evaporation. The residue was purified by silica gel column chromatography (120 g column, 10% to 45 % (1430) EtOAc/hexane). Yield 4.97 g, 99.7%. Ion found by LCMS: [M - Boc]+ = 150, [M - H]- = 248.9.
98% In methanol for 1h; Heating;
With triethylamine In tetrahydrofuran
With triethylamine In dichloromethane at 20℃;
With sodium carbonate In tetrahydrofuran; water at 0 - 25℃; for 12h; 1.1 To a solution of (1S,2R)-1-amino-2,3-dihydro-1H-inden-2-ol (1 g, 6.70 mmol, 1 eq) and Na2CO3( (2.13 g, 20.11 mmol, 3 eq) in THF (tetrahydrofuran; 30 mL) and H2O (6 mL) was added BOC2O (di-t-butyl dicarbonate; 1.90 g, 8.71 mmol, 2.00 mL, 1.3 eq) at 0 °C. Then the mixture was stirred at 25 °C for 12 h. The reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (30 mLx4). The combined organic phase was washed with brine (30 mL), dried with anhydrous Na2S04, filtered and concentrated in vacuum. The residue was purified by silica gel chromatography (PE: EtOAc (ethyl acetate) = 99:1-50:50) to afford tert- butyl ((1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl)carbamate (1.6 g, 5.78 mmol, 86.17% yield, 90% purity) as light yellow solid.
Stage #1: (1S,2R)-1-amino-2-indanol With sodium hydrogencarbonate In tetrahydrofuran; water for 0.0833333h; Stage #2: di-<i>tert</i>-butyl dicarbonate In tetrahydrofuran; water at 20℃; for 24h;

Reference: [1]Guo, Rongwei; Lu, Shuiming; Chen, Xuanhua; Tsang, Chi-Wing; Jia, Wenli; Sui-Seng, Christine; Amoroso, Dino; Abdur-Rashid, Kamaluddin [Journal of Organic Chemistry, 2010, vol. 75, # 3, p. 937 - 940]
[2]Gao, Yaojun; Ren, Qiao; Wu, Hao; Li, Maoguo; Wang, Jian [Chemical Communications, 2010, vol. 46, # 48, p. 9232 - 9234] Ren, Qiao; Gao, Yaojun; Wang, Jian [Chemistry - A European Journal, 2010, vol. 16, # 46, p. 13594 - 13598]
[3]Current Patent Assignee: CHIDALA TREAT COMPANIES; CIDARA THERAPEUTICS INC - WO2020/252393, 2020, A1 Location in patent: Page/Page column 327
[4]Bit, Christelle; Mitrochkine, Anton A.; Gil, Gerard; Pierrot, Marcel; Reglier, Marius [Tetrahedron Asymmetry, 1998, vol. 9, # 18, p. 3263 - 3273]
[5]Qiao, Jennifer X.; Wang, Tammy C.; Wang, Gren Z.; Cheney, Daniel L.; He, Kan; Rendina, Alan R.; Xin, Baomin; Luettgen, Joseph M.; Knabb, Robert M.; Wexler, Ruth R.; Lam, Patrick Y.S. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 18, p. 5041 - 5048]
[6]Gardelli, Cristina; Wada, Hiroki; Ray, Asim; Caffrey, Moya; Llinas, Antonio; Shamovsky, Igor; Tholander, Joakim; Larsson, Joakim; Sivars, Ulf; Hultin, Leif; Andersson, Ulf; Sanganee, Hitesh J.; Stenvall, Kristina; Leidvik, Brith; Gedda, Karin; Jinton, Lisa; Rydén Landergren, Marie; Karabelas, Kostas [Journal of Medicinal Chemistry, 2018, vol. 61, # 14, p. 5974 - 5987]
[7]Current Patent Assignee: SYROS PHARMACEUTICALS INC - WO2019/143730, 2019, A1 Location in patent: Paragraph 116
[8]Dinh, Andrew N.; Maddox, Sean M.; Vaidya, Sagar D.; Saputra, Mirza A.; Nalbandian, Christopher J.; Gustafson, Jeffrey L. [Journal of Organic Chemistry, 2020, vol. 85, # 21, p. 13895 - 13905]
  • 3
  • [ 55309-58-5 ]
  • [ 7480-35-5 ]
  • [ 185346-09-2 ]
  • 4
  • [ 7321-55-3 ]
  • [ 126456-43-7 ]
  • [ CAS Unavailable ]
  • [ 175166-51-5 ]
  • [ 220886-58-8 ]
YieldReaction ConditionsOperation in experiment
1: 75 % Spectr. 2: 4 % Spectr. 3: 17 % Spectr. With zinc diacetate In toluene at 110℃; for 6h;
  • 5
  • [ 126456-43-7 ]
  • [ 175166-51-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / CH2Cl2 / 2 h / 0 °C 2: 100 g / Ti(OiPr)4 / 8 h / 145 °C
Multi-step reaction with 2 steps 1.1: dichloromethane / 24 h / 40 °C 2.1: N,N,N,N,-tetramethylethylenediamine; diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -20 - 20 °C / Inert atmosphere 2.2: -20 - 20 °C / Inert atmosphere
  • 6
  • [ 126456-43-7 ]
  • [ 182122-08-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 81 percent / tetrahydrofuran / 4 h 2: 85 percent / LiHMDS / tetrahydrofuran
  • 7
  • [ 7480-35-5 ]
  • [ 185346-09-2 ]
  • 8
  • N-methyl-3-(thien-2-yl)-3-morpholino-propylamine hydrochloride [ No CAS ]
  • [ 7480-35-5 ]
  • [ 116539-55-0 ]
  • [ 116539-57-2 ]
YieldReaction ConditionsOperation in experiment
39% With sodium hydroxide;(p-cymene)-ruthenium(II) chloride dimer; In isopropyl alcohol; at 20 - 85℃; for 5h; A mixture of [(LS, 2R)-(-)-CIS-1-AMINO-2-INDANOL] (17.7 mg, 0.119 mmol), (p-cymene)- ruthenium (II) chloride dimer (20.0 mg, 0.032 mmol) and degassed isopropanol (10 mL) was stirred for 20 min at 85 C under nitrogen atmosphere and then cooled to [20 C.] A mixture of 3-N-methylamino-1-(2-thienyl)-1-propanone hydrochloride obtained as described in example 1 (content: 71%, 2.10 g, 7.24 mmol), sodium hydroxide (content: 98%, 0.44 g, 10.78 mmol) and degassed isopropanol (78 mL) was stirred for 1 h at [20 C] under nitrogen atmosphere, and then the above catalyst solution was added. The reaction mixture was stirred for 4 h at [20 C] under nitrogen atmosphere. After this time, the starting material, [3-N-METHYLAMINO-1-(2-THIENYL)-1-PROPANONE,] had completely reacted (as determined [BY LH-NMR). (S)-3-N-METHYLAMINO-1-(2-THIENYL)-1-PROPANOL] having an e. e. of 70% (as determined by chiral HPLC) was formed in a yield of 39% (as determined [BY'H-NMR).]
  • 9
  • [ 126456-43-7 ]
  • [ 872703-52-1 ]
YieldReaction ConditionsOperation in experiment
68% Stage #1: 2-Benzyl-2-propenoic acid With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In ethyl acetate at 20℃; for 0.5h; Stage #2: (1S,2R)-1-amino-2-indanol In ethyl acetate 1 2-Benzyl acrylic acid (J. Organomet, Chem. 646, 212-222, 2002) (2.72 g, 16.8 mmol) was dissolved in EtOAc (50 mL) and EDAC (3.54 g, 18.5 mmol), HOBT (2.49 g, 18.4 mmol) and ΝMM (2.21 mL, 20.1 mmol) were added. The reaction mixture was stirred at room temperature for 30 min and then (lδ')2i?)-l-amino-2-indanol (2.75 g, 18.4 mmol) was added and the stirring was continued over night. Washing with saturated NaHCO3 (aq.) and brine followed by drying (Na2SO4) and evaporation of the organic solvent afforded the crude product, which were subjected to column chromatography (silica, EtOAc/pentane, 40:60-50:50) yielding 2 (3.34 g, 68%) as a white solid.[α]D22 +23.9° (c 0.77, MeOH); 1H NMR (CDCl3) δ 7.40-7.11 (m, 8H), 6.97 (m, IH), 6.42 (d, J= 8.27 Hz, IH), 5.87 (s, IH), 5.35 (m, 2H), 4.55 (m, IH), 3.77 (d, J= 15.6 Hz, IH), 3.70 (d, J= 15.6 Hz, IH), 3.14 (dd, J= 5.21, 16.6 Hz, IH), 2.89 (dd, J= 1.89, 16.6 Hz, IH), 2.18 (d, J= 4.90 Hz, IH); 13C NMR (CDCl3) δ 168.9, 144.3, 140.7, 140.1, 138.5, 129.2, 128.9, 128.4, 127.4, 126.9, 125.5, 124.6, 120.5, 73.7, 57.9, 40.0, 39.2. MS (m/z 294, M + H+, 587); Anal. (C19H19NO2) C, H, N.
  • 10
  • [ CAS Unavailable ]
  • [ 30071-93-3 ]
  • [ 126456-43-7 ]
  • [ 127852-28-2 ]
YieldReaction ConditionsOperation in experiment
70% With sodium hydroxide In isopropyl alcohol 4 EXAMPLE 4 EXAMPLE 4 (R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-ol A solution of [Cp*RhCl2]2 (Cp=pentamethylcyclopentadienyl; 6.0 g), (1S,2R)-cis-1-amino-2-indanol (3.0 g) and 1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-one (1.0 kg) in 2-propanol (7 L) was stirred for 30 min and thoroughly degassed under vacuum. Then 5 M sodium hydroxide (9 mL) was added and the mixture was aged for 3-4 h to achieve complete conversion of the starting material. The reaction mixture was poured into 1 N HCl (7 L) and extracted with heptane (2*3.5 L). The combined organic layers were washed with brine (5 L) and 1,4-diazabicyclo[2.2.2]-octane (240 g) was added. The solution was concentrated to approximately 4 mL/g of alcohol (KF<200 μg/mL; 2-propanol <5 vol %). The mixture was seeded at 40° C., allowed to cool to RT to from a seedbed and then cooled to 0° C. The crystalline product was filtered, washed with cold heptane and dried to provide the DABCO complex (70% yield; e.e.>99%).
70% With sodium hydroxide In isopropyl alcohol 4 (R)-1 -(3,5-Bis(trifluoromethyl)phenyl)ethan-1-ol EXAMPLE 4 (R)-1 -(3,5-Bis(trifluoromethyl)phenyl)ethan-1-ol A solution of [Cp*RhCl2]2 (Cp=pentamethylcyclopentadienyl; 6.0 g), (1S,2R)-cis-1-amino-2-indanol (3.0 g) and 1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-one (1.0 kg) in 2-propanol (7 L) was stirred for 30 min and thoroughly degassed under vacuum. Then 5 M sodium hydroxide (9 mL) was added and the mixture was aged for 3-4 h to achieve complete conversion of the starting material. The reaction mixture was poured into 1 N HCl (7 L) and extracted with heptane (2*3.5 L). The combined organic layers were washed with brine (5 L) and 1,4-diazabicyclo[2.2.2]octane (240 g) was added. The solution was concentrated to approximateky 4 mL/g of alcohol (KF<200 μg/mL; 2-propanol <5 vol %). The mixture was seeded at 40° C., allowed to cool to RT to form a seedbed and then cooled to 0° C. The crystalline product was filtered, washed with cold heptane and dried to provide the DABCO complex (70% yield; e.e.>99%).
70% With sodium hydroxide In isopropyl alcohol 4 (R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-ol EXAMPLE 4 (R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-ol A solution of [Cp*RhCl2]2 (Cp=pentamethylcyclopentadienyl; 6.0 g), (1S,2R)-cis-1-amino-2-indanol (3.0 g) and 1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-one (1.0 kg) in 2-propanol (7 L) was stirred for 30 min and thoroughly degassed under vacuum. Then 5 M sodium hydroxide (9 mL) was added and the mixture was aged for 3-4 h to achieve complete conversion of the starting material. The reaction mixture was poured into 1 N HCl (7 L) and extracted with heptane (2*3.5 L). The combined organic layers were washed with brine (5 L) and 1,4-diazabicyclo[2.2.2]-octane (240 g) was added. The solution was concentrated to approximately 4 mL/g of alcohol (KF<200 μg/mL; 2-propanol<5 vol %). The mixture was seeded at 40° C., allowed to cool to RT to from a seedbed and then cooled to 0° C. The crystalline product was filtered, washed with cold heptane and dried to provide the DABCO complex (70% yield; e.e.>99%).
70% With sodium hydroxide In isopropyl alcohol 4 (R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-ol EXAMPLE 4 (R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-ol A solution of [Cp*RhCl2]2 (Cp=pentamethylcyclopentadienyl; 6.0 g), (1S,2R)-cis-1-amino-2-indanol (3.0 g) and 1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-one (1.0 kg) in 2-propanol (7 L) was stirred for 30 minutes and thoroughly degassed under vacuum. Then 5 M sodium hydroxide (9 mL) was added and the mixture was aged for 3-4 hours to achieve complete conversion of the starting material. The reaction mixture was poured into 1 N HCl (7 L) and extracted with heptane (2*3.5 L). The combined organic layers were washed with brine (5 L) and 1,4-diazabicyclo [2.2.2]-octane (240 g) was added. The solution was concentrated to approximately 4 ml/g of alcohol (KF<200 μg/mL; 2-propanol <5 vol %). The mixture was seeded at 40° C., allowed to cool to room temperature to form a seedbed and then cooled to 0° C. The crystalline product was filtered, washed with cold heptane and dried to provide the DABCO complex (70% yield; e.e.>99%).

  • 11
  • [ 30071-93-3 ]
  • [ 126456-43-7 ]
  • [ 127852-28-2 ]
YieldReaction ConditionsOperation in experiment
75% With sodium hydroxide In isopropyl alcohol 5 EXAMPLE 5 EXAMPLE 5 (R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-ol A solution of [RuCl2(p-cymene)]2 (18.4 g), (1S,2R)-cis-1-amino-2-indanol (9.0 g) and 1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-one (3 kg) in 2-propanol (21 L) was stirred for 30 min and thoroughly degassed under vacuum. Then 5 M sodium hydroxide (28 mL) was added and the mixture was aged for 4-6 h to achieve complete conversion of the starting material. The reaction mixture was poured into 1 N HCl (21 L) and extracted with heptane (2*10.5 L). The combined organic layers were washed with brine and 1,4-diazabicyclo[2.2.2]octane (740 g) was added. The solution was concentrated to approximateky 4 mL/g of alcohol (KF<200 μg/mL; 2-propanol <5 vol %). The mixture was seeded at 40° C., allowed to cool to RT to from a seedbed and then cooled to 0° C. The crystalline product was filtered, washed with cold heptane and dried to provide the DABCO complex (75-80% yield; e.e.>99%).
75% With sodium hydroxide In isopropyl alcohol 5 (R)-1 -(3,5-Bis(trifluoromethyl)phenyl)ethan-1-ol EXAMPLE 5 (R)-1 -(3,5-Bis(trifluoromethyl)phenyl)ethan-1-ol A solution of [RuCl2(p-cymene)]2 (18.4 g), (1S,2R)-cis-1-amino-2-indanol (9.0 g) and 1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-one (3 kg) in 2-propanol (21 L) was stirred for 30 min and thoroughly degassed under vacuum. Then 5 M sodium hydroxide (28 mL) was added and the mixture was aged for 4-6 h to achieve complete conversion of the starting material. The reaction mixture was poured into 1 N HCl (21 L) and extracted with heptane (2*10.5 L). The combined organic layers were washed with brine and 1,4-diazabicyclo[2.2.2]octane (740 g) was added. The solution was concentrated to approximateky 4 mL/g of alcohol (KF<200 μg/mL; 2-propanol <5 vol %). The mixture was seeded at 40° C., allowed to cool to RT to from a seedbed and then cooled to 0° C. The crystalline product was filtered, washed with cold heptane and dried to provide the DABCO complex (75-80% yield; e.e.>99%).
75% With sodium hydroxide In isopropyl alcohol 5 (R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-ol EXAMPLE 5 (R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-ol A solution of [RuCl2(p-cymene)]2 (18.4 g), (1S,2R)-cis-1-amino-2-indanol (9.0 g) and 1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-one (3 kg) in 2-propanol (21 L) was stirred for 30 min and thoroughly degassed under vacuum. Then 5 M sodium hydroxide (28 mL) was added and the mixture was aged for 4-6 h to achieve complete conversion of the starting material. The reaction mixture was poured into 1 N HCl (21 L) and extracted with heptane (2*10.5 L). The combined organic layers were washed with brine and 1,4-diazabicyclo[2.2.2]octane (740 g) was added. The solution was concentrated to approximateky 4 ml/g of alcohol (KF<200 μg/mL; 2-propanol<5 vol %). The mixture was seeded at 40° C., allowed to cool to RT to from a seedbed and then cooled to 0° C. The crystalline product was filtered, washed with cold heptane and dried to provide the DABCO complex (75-80% yield; e.e.>99%).
75% With sodium hydroxide In isopropyl alcohol 9 (DABCO) EXAMPLE 9 (R)-1-(3,5-bis(Trifluoromethyl)phenyl)ethan-1-ol (DABCO) A solution of [RuCl2(p-cymene)]2 (18.4 g), (1S,2R)-cis-1-amino-2-indanol (9.0 g) and 1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-one (3 kg) in 2-propanol (21 L) was stirred for 30 min and thoroughly degassed under vacuum. Then M sodium hydroxide (28 mL) was added and the mixture was aged for 4-6 h to achieve complete conversion of the starting material. The reaction mixture was poured into 1 N HCl (21 L) and extracted with heptane (2*10.5 L). The combined organic layers were washed with brine and 1,4-diazabicyclo[2.2.2]octane (740 g) was added. The solution was concentrated to approximately 4 mL/g of alcohol (KF<200 μg/mL; 2-propanol<5 vol %). The mixture was seeded at 40° C., allowed to cool to RT to from a seedbed and then cooled to 0° C. The crystalline product was filtered, washed with cold heptane and dried to provide the DABCO complex (75-80% yield; e.e.>99%).
75% With sodium hydroxide In isopropyl alcohol 5 (R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-ol EXAMPLE 5 (R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-ol A solution of [RuCl2(p-cymene)]2 (18.4 g), (1S,2R)-cis-1-amino-2-indanol (9.0 g) and 1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-one (3 kg) in 2-propanol (21 L) was stirred for 30 minutes and thoroughly degassed under vacuum. Then 5 M sodium hydroxide (28 mL) was added and the mixture was aged for 4-6 hours to achieve complete conversion of the starting material. The reaction mixture was poured into 1 N HCl (21 L) and extracted with heptane (2*10.5 L). The combined organic layers were washed with brine and 1,4-diazabicyclo[2.2.2]octane (740 g) was added. The solution was concentrated to approximately 4 mL/g of alcohol (KF<200 μg/mL; 2-propanol <5 vol %). The mixture was seeded at 40° C., allowed to cool to room temperature to form a seedbed and then cooled to 0° C. The crystalline product was filtered, washed with cold heptane and dried to provide the DABCO complex (75-80% yield; e.e.>99%).

  • 12
  • [ 50-00-0 ]
  • [ 126456-43-7 ]
  • [ 767292-14-8 ]
YieldReaction ConditionsOperation in experiment
100% In formic acid; water at 115℃; for 17.5h; 32.a a) (lS,2R)-l-(dimethylamino)-2,3-dihydro-lH-inden-2-ol (Compound of Formula 2-IV, Scheme 2) (Org. Lett. 2012, 14 , 812) A mixture of (l3) 7.34 - 7.18 (4H, m), 4.48 - 4.41 (1H, m), 4.07 (1H, d, J=7.8 Hz), 3.26 (1H, dd, J=8.1, 16.4 Hz), 2.80 (1H, dd, J=7.7, 16.3 Hz), 2.28 (6H, s).
99% With formic acid In water at 95℃; Inert atmosphere;
95% In formic acid; water Reflux;
91% With formic acid In water for 6.5h; Reflux; Inert atmosphere;
With acetic acid; zinc In water at 20℃; for 3h; 15 Example 15(1S, 2R) -1--dimethylamino-2-indanol was prepared Example 15(1S, 2R) -1--dimethylamino-2-indanol was prepared At room temperature, 20 mL of water was added 2.5mL of acetic acid, was added 5mL formaldehyde solution, 1.490g (1S, 2R) -1- amino-2-indanol, 2.600g zinc. After the reaction was stirred at room temperature for 3h, quenched with 15mL aqueous ammonia, extracted with methylene chloride, dried over anhydrous sodium sulfate, and flash column chromatography (EA: PE = 1: 2,210mL; methanol: DCM = 1: 10,330mL), yield 78.2%. 1HNMR (400MHz, CDCl3) δ7.25 (ddd, J = 24.5,16.2,7.4Hz, 4H), 4.59 (dd, J = 22.0,13.4Hz, 1H), 4.44 (q, J = 7.9Hz, 1H), 4.07 (d, J = 7.9Hz, 1H), 3.26 (dd, J = 16.3,8.2Hz, 1H), 2.80 (dd, J = 16.3,7.6Hz, 1H).

  • 13
  • [ 7321-55-3 ]
  • (1S,2R)-1-amino-2-indanol [ No CAS ]
  • (3aS,3a'S,8aR,8a'R)-2,2'-(propane-2,2-diyl)bis(3a,8a-dihydro-8H-indeno[1,2-d]oxazole) [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% With zinc trifluoromethanesulfonate In toluene for 48h; Inert atmosphere; Reflux;
  • 14
  • [ 24424-99-5 ]
  • [ 126456-43-7 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine In dichloromethane at 20℃; for 0.5h; 57.1 Step 1: tert-butyl[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]carbamate Di-tert-butyldicarbonate (0.80 g, 3.7 mmol) was added to a solution of (1S,2R)-1-aminoindan-2-ol (0.50 g, 3.4 mmol) (Aldrich, Cat. #440833) and triethylamine (0.70 mL, 5.0 mmol) in methylene chloride (7.0 mL) at r.t. The reaction mixture was stirred at r.t. for 30 min The mixture was quenched with aqueous Na2CO3, and extracted with ethyl acetate (3*10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with MeOH in dichloromethane (0-10%) to afford the desired product (0.88 g, 100%). Analytic LCMS (M+Na)+: m/z=272.1.
  • 15
  • (1S,2R)-1-amino-2-indanol [ No CAS ]
  • [ 105-39-5 ]
  • [ 862095-79-2 ]
YieldReaction ConditionsOperation in experiment
100% To a flame dried 3.0L flask with a magnetic stir bar was added sodium hydride (7.1 g, 168 mmol, 1.25 equiv., 57-61% oil dispersion). The sodium hydride was washed twice with 200 mL of dry pentane, which was removed each time via cannula. Anhydrous THF (2.0 L) was added and the mixture cooled to 0 0C in an ice bath. To the stirring mixture was added (IS, 2R)-(-)-c/s-l-amino-2-indanol (20 g, 0.134 mol, 1 equiv.) in two equal portions 15 minutes apart. The flask was equipped with a reflux condensor and the mixture heated to 70 0C for 40 minutes, during which time the mixture beacame light purple in color. The mixture was cooled again to 0 0C and ethyl chloroacetate (18.5 mL, 0.134 mol, 1 equiv.) was added dropwise over 30 minutes. The resulting dark purple solution was then refuxed for 2 hours under N2(g). After cooling to room temperature, the solution washed with brine (2 x 700 mL). The combined aqueous fractions were back extracted with ethyl acetate (2 x 500 mL). The combined organic fractions were stirred vigorously over MgSO4 (150 g) for 12 hours. The mixture was then filtered and concentrated in vacuo to afford the crude product as a light tan or grey solid in quantitative yield. The product was suitable for the next reaction without further purification. The opposite enantiomer was prepared in the same manner.
  • 16
  • [ 126456-43-7 ]
  • [ 106-96-7 ]
  • [ 1258392-59-4 ]
YieldReaction ConditionsOperation in experiment
50% Stage #1: (1S,2R)-1-amino-2-indanol With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 0.5h; Stage #2: propargyl bromide In tetrahydrofuran; toluene for 1h; Reflux;
47.8% With sodium hydride In tetrahydrofuran; paraffin oil at 70℃; 13.1 Step 1: (1S,2R)-2-(prop-2-yn-1-yloxy)-2,3-dihydro-1H-inden-1-amine To a solution of (1S,2R)-1-amino-2,3-dihydro-1H-inden-2-ol (2 g, 13.4 mmol) in tetrahydrofuran (50 mL) at 0oC was added portion wise sodium hydride (60%, dispersion in Paraffin Liquid) (0.59 g, 14.7 mmol). The mixture was allowed to warm to room temperature. 3-Bromoprop-1-yne (1.75 g, 14.7 mmol) was then added and the resulting mixture was heated to 70oC. It was stirred at 70oC overnight. The mixture was quenched with ice water (50 mL) and extracted with ethyl acetate (3 × 30 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The crude was purified by silica gel chromatography [petroleum ether/ethyl acetate (3:2 v/v)] to afford (1S,2R)-2-(prop-2-yn-1-yloxy)-2,3-dihydro-1H-inden-1-amine (1.2 g, 6.4 mmol, 47.8 % yield) as black oil. LCMS (ES, m/z): 187.1, 188.1 [M+H]+, retention time 0.942 min.1H NMR (400 MHz, DMSO-d6) d ppm 7.36- 7.29 (m, 1H), 7.22- 7.13 (m, 3H), 4.25 (dd, J = 4.2, 2.4 Hz, 2H), 4.22- 4.15 (m, 2H), 3.43 (t, J = 2.4 Hz, 1H), 2.93 (qd, J = 16.1, 3.5 Hz, 2H), 1.75 (s, 2H)
In tetrahydrofuran; toluene; mineral oil (1S,2R)-2-(Prop-2-ynyloxy)-2,3-dihydro-1H-inden-1-amine (1S,2R)-2-(Prop-2-ynyloxy)-2,3-dihydro-1H-inden-1-amine Sodium hydride (60% dispersion in mineral oil; 977 mg, 24.4 mmol) was washed by mixing with hexanes, allowing to settle and removing the supernatant via syringe. Tetrahydrofuran (THF) (60 mL) was then added, and the suspension was cooled to 0° C. (1S,2R)-(-)-cis-1-Amino-2-indanol (Aldrich; 3.00 g, 20.11 mmol) was added in portions over 5 minutes (min) (gas evolution observed). The resulting mixture was warmed to room temperature until hydrogen evolution ceased, and the resulting thick suspension was heated to 70° C. A solution of propargyl bromide (80% in toluene; 2.50 mL, 22.4 mmol) in THF (20 mL) was added dropwise over 20 min. The reaction mixture was heated to reflux for 45 min. The reaction was quenched with H2O and extracted with ethyl acetate (EtOAc). The organics were washed with saturated (sat) NaCl and then dried with solid (s) Na2SO4. The solvents were removed under reduced pressure. The crude material was carried on without any further purification; m/z 188.
  • 18
  • (1S,2R)-1-amino-2-indanol [ No CAS ]
  • [ 105-39-5 ]
  • [ 913718-34-0 ]
YieldReaction ConditionsOperation in experiment
63% Stage #1: (1S,2R)-1-amino-2-indanol With sodium tetrahydroborate In tetrahydrofuran at 0 - 70℃; Stage #2: chloroacetic acid ethyl ester In tetrahydrofuran at 0℃; for 2.5h; Reflux; 4.5.5. (5aR,10bS)-2-Phenyl-4,5a,6,10b-tetrahydroindeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]-oxazinium tetrafluoroborate 45 Sodium hydride (60% wt in mineral oil, 273 mg, 6.84 mmol) was suspended in hexane (10 mL) and then left to stand for 5 min before removal of the supernatant via cannula. This procedure was repeated two times and then THF (100 mL) was added. The mixture was cooled to 0 °C then (1S,2R)-1-amino-2,3-dihydro-1H-inden-2-ol (500 mg, 3.35 mmol) was added. The mixture was stirred for 15 min and then further aminoindanol (500 mg, 3.35 mmol) was added. The mixture was heated to 70 °C for 40 min and then cooled to 0 °C before ethyl chloroacetate (0.732 mL, 6.84 mmol) was added slowly. The mixture was stirred for 30 min and then heated at reflux for 2 h. After cooling to ambient temperature, the solution was washed with brine (20 mL × 2) and the aqueous layers combined and back-extracted with EtOAc (10 mL × 2). The combined organics were dried (MgSO4) with vigorous stirring over 16 h then filtered and concentrated in vacuo to afford a pale orange/brown solid. Hexane (30 mL) was added to the crude solid and the heterogeneous mixture heated at reflux for 2 h, cooled to ambient temperature and then the hexanes removed by filtration. Final trituration with cold (-78 °C) EtOAc (10 mL) gave the morpholinone as a colourless solid (799 mg, 63%); mp§ 198-200 °C decomp; inlMMLBox (c 0.2, CHCl3); δH (400 MHz, CDCl3) 7.86 (1H, br d, J 4.4, NH), 7.39-7.24 (4H, m, ArH), 4.78 (1H, t, J 4.4, H-4a), 4.54 (1H, t, J 4.4, H-9a), 4.17 (2H, s, CH2-2), 3.23 (1H, dd, J 17.0 and 4.4, HA-9) and 3.10 (1H, d, J 17.0, HB-9); δC§ (100 MHz, CDCl3) 169.8 (CO), 140.7 (C-8a), 139.2 (C-4b), 128.3 (CH-8), 127.4 (CH-6), 125.1 (CH-7), 123.9 (CH-5), 76.1 (CH-9a), 66.4 (CH2-2), 58.6 (CH-4a) and 37.6 (CH2-9). IR§ νmax (KBr)/cm-1 3425 (br, H-bonded NH), 3183 (free NH), 2934 (C-H), 2928, 2843, 1641 (CO), 1462 (C-H), 1372 (C-H) and 1103 (C-O). Spectroscopic data (1H NMR) are in accordance with the literature.34
  • 20
  • [ 126456-43-7 ]
  • [ 1258392-53-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: 4-methyl-morpholine; chloroformic acid ethyl ester / ethyl acetate / 0.5 h / 0 °C 1.2: 0 - 20 °C 2.1: potassium hydroxide / N,N-dimethyl-formamide; toluene / 1.08 h / 0 °C 3.1: dichloromethane / 3 h / 20 °C 4.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / N,N-dimethyl-formamide / 0 - 20 °C 5.1: hydrogenchloride / 1,4-dioxane / 1 h / 20 °C 6.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / N,N-dimethyl-formamide / 0 - 20 °C 7.1: copper diacetate; pyridine / acetonitrile / 1 h / 80 °C 8.1: hydrogenchloride / 1,4-dioxane / 1 h / 20 °C
Multi-step reaction with 8 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 20 °C 1.2: 1 h / Reflux 2.1: 4-methyl-morpholine; chloroformic acid ethyl ester / ethyl acetate / 0.5 h / 0 °C 2.2: 0 - 20 °C 3.1: dichloromethane / 3 h / 20 °C 4.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / N,N-dimethyl-formamide / 0 - 20 °C 5.1: hydrogenchloride / 1,4-dioxane / 1 h / 20 °C 6.1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 4-methyl-morpholine / N,N-dimethyl-formamide / 0 - 20 °C 7.1: copper diacetate; pyridine / acetonitrile / 1 h / 80 °C 8.1: hydrogenchloride / 1,4-dioxane / 1 h / 20 °C
  • 21
  • [ 645387-42-4 ]
  • [ 126456-43-7 ]
  • [ 1643378-62-4 ]
YieldReaction ConditionsOperation in experiment
88% With triethylamine In ethanol at 20℃; for 10h; Reflux; Inert atmosphere; Synthesis of C2-symmertric chiral shift reagent 3. General procedure: To a solution of compound 6 (230 mg, 0.5mmol) in ethanol with triethylamine (158 uL, 1.1 mmol) was added (1R, 2S)-1-amino-2-indanol(163 mg, 1.1 mmol) at one time, after stirred in room temperature for 6 h, the reaction mixture was refluxed for another 4 h, a white precipitate was obtained. After the mixture was cooled toroom temperature, it was filtered and the residue was washed with ethanol (3 × 5 mL).Compound 2 was obtained as a white solid, 90% yield, (mp > 360 C).
  • 22
  • [ 79271-56-0 ]
  • [ 126456-43-7 ]
  • [ 2088920-44-7 ]
YieldReaction ConditionsOperation in experiment
92% With triethylamine In dichloromethane at 0 - 20℃; 3.2 Example 3 2nd step, the (1S, 2R) - yinyin the amine is mellow (2.98g, 20mmol) and triethylamine (3.03g, 30mmol) by adding 25 ml of dichloromethane, temperature control 0 - 5 °C, drop into the trifluoromethyl sulfonic acid triethyl silicate (22mmol), is dropped at room temperature stirring, TLC detection reaction finishes, water quenching, sodium bicarbonate solution washing, saturated salt water washing, the organic layer turns on lathe does (1S, 2R) - yinyin the amine is mellow triethyl silicon ether 4.0g, yield 92%,
  • 23
  • [ 126456-43-7 ]
  • [ 172881-85-5 ]
YieldReaction ConditionsOperation in experiment
75% With 1H-imidazole-1-sulfonyl azide hydrochloride; Cupric sulfate; potassium carbonate In methanol at 20℃; for 18h; (1S,2R)-1-azido-2,3-dihydro-1H-inden-2-ol (Cas No. 172881-85-5) Cis-(1S,2R)-1,2-aminoindanol (1.006 g, 6.71 mmol) was dissolved in a suspension of K2CO3 (1.39 g, 10.065 mmol) and CuSO4 x 5H2O (0.017 mg, 0.068 mmol) in MeOH (50 mL). Imidazole-1-sulfonyl azide hydrochloride (0.84 g, 4.00 mmol) was added and the mixture stirred at r.t. for 18 hours. The solvent was removed under reduced pressure, then the solid was dissolved in H2O (20 mL), acidified with HCl (40 mL, 1 M) and extracted with CH2Cl2 (5 × 50 mL). The combined organic layers were dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography on silica gel (starting from 10% of EtOAc in petroleum ether) to provide the product, after removal of solvent under reduced pressure, as a clear yellow oil (0.876 g, 5.006 mmol, 75% yield). [α]D20 = 98.9 (c = 0.425, CHCl3). IR (KBr tablet) ν: 3406 (br m), 3027 (w), 2921 (m), 2102 (s), 1610 (w), 1478 (m), 1461 (m), 1432 (w), 1321 (s), 1256 (s), 1206 (m), 1091 (s), 1054 (m), 992 (w), 906 (w), 886 (w), 750 (s) cm-1. 1H NMR (400 MHz, CDCl3) δ 7.40 (dd, J = 7.1, 1.8 Hz, 1H), 7.37 - 7.26 (m, 3H), 4.79 (d, J = 5.3 Hz, 1H), 4.60 (dq, J = 7.8, 6.0 Hz, 1H), 3.17 (dd, J = 15.9, 6.3 Hz, 1H), 2.94 (dd, J = 15.9, 6.0 Hz, 1H), 2.36 (d, J = 7.9 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 140.6, 137.7, 129.6, 127.4, 125.7, 125.2, 74.2, 67.9, 39.1. HRMS (ESI): m/z [M-N2+H]+ calcd for C9H10NO: 148.0757; found 148,0760.
With N-diazosulfamoyl fluoride; Potassium bicarbonate In tert-butyl methyl ether; lithium hydroxide monohydrate; dimethyl sulfoxide at 30℃; for 1h; Sealed tube; 5 Example 5 A 1,2,3-triazole compound library is obtained directly through diazonium transfer and copper-catalyzed azide-terminated alkyne cycloaddition reaction (CuAAC) using a primary amine compound library. General procedure: Each of the 96-well plates of 1128 primary amine compound libraries prepared in Example 2 (that is, primary amine compound structures corresponding to azide compounds of plates 1-7 and 10-14 of Example 2) Take 50 μl (100 mM, solvent is dimethylsulfoxide, 5 μmol primary amine) from the well and transfer to the corresponding position in a new 96-well plate. Subsequently, in each well of the plate containing this fresh primary amine solution, potassium bicarbonate aqueous solution (3.0 M, 6.7 μl, 20 μmol potassium bicarbonate containing), fluorosulfonylazide solution (see Example 1, dimethylsulfoxide/ Methyl t-butyl ether 1:1; 200 mM, 25 μl, diluted with a solvent system containing 5 μmol fluorosulfonylazide) and dimethylsulfoxide (18 μl) were sequentially added, resulting in a total volume of about 100 μl. The 96-well plate is sealed at a temperature of 30 °C and shaken for 1 h at 800 rpm rotation speed.
  • 24
  • [ 126456-43-7 ]
  • [ 407-25-0 ]
  • [ 1867509-77-0 ]
YieldReaction ConditionsOperation in experiment
93% With dmap; triethylamine In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere; 2,2,2-trifluoro-N-((1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl)acetamide (Cas No. 1867509-77-0) cis-(1S,2R)-1-amino-2-indanol (0.180 g, 1.21 mmol) was dissolved in CH2Cl2 (6 mL), triethylamine (0.673 mL, 4.84 mmol) and DMAP (0.015 g, 0.121 mmol) were added under argon atmosphere. The reaction mixture was cooled to 0 °C and trifluoroacetic anhydride (0.168 mL, 1.21 mmol) was added dropwise. Then allowed to warm and stirred at r.t. for 2 hours. The reaction mixture was diluted with CH2Cl2 (10 mL), after which an aqueous solution of saturated NaHCO3 (10 mL) was added and the phases separated. The aqueous phase was extracted additionally with CH2Cl2 (4 x 10 mL) and the combined organic phases were dried over Na2SO4. Filtration and removal of the solvent under reduced pressure provided the crude product which was purified by column chromatography on silica gel (starting from 20% of EtOAc in petroleum ether) to provide the product as colourless crystals (0.274 g, 1.12 mmol, 93% yield). Mp 153-154 °C; [α]D20 = 143.4 (c = 0.26, CHCl3). IR (KBr tablet) ν: 3417 (br m), 3271 (s), 3089 (w), 2941 (w), 1698 (s), 1555 (m), 1461 (w), 1340 (w), 1308 (w), 1188 (s), 1094 (m), 1054 (m), 958 (w), 935 (w), 758 (m), 723 (w) cm-1. 1H NMR (400 MHz, CDCl3) δ 7.34 - 7.26 (m, 4H), 7.12 (s, 1H), 5.41 (dd, J = 8.4, 5.1 Hz, 1H), 4.70 (qd, J = 5.2, 1.9 Hz, 1H), 3.25 (dd, J = 16.8, 5.0 Hz, 1H), 2.99 (dd, J = 16.7, 1.8 Hz, 1H), 2.02 - 1.93 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 157.7 (q, J = 37.4 Hz), 139.5, 138.9, 128.9, 127.6, 125.5, 124.6, 116.0 (q, J = 287.9 Hz), 73.0, 57.5, 40.2. HRMS (ESI): m/z [M + H]+ calcd for C11H11F3NO2: 246.0736; found 246.0748.
  • 25
  • [ 6624-49-3 ]
  • [ 7480-35-5 ]
  • C19H16N2O2 [ No CAS ]
  • 26
  • (1S,2R)-1-amino-2-indanol [ No CAS ]
  • [ 19547-38-7 ]
  • [ 205647-96-7 ]
YieldReaction ConditionsOperation in experiment
347 mg With toluene-4-sulfonic acid In toluene at 80℃; for 1h; Inert atmosphere; Schlenk technique;
  • 27
  • [ 100-70-9 ]
  • (1S,2R)-1-amino-2-indanol [ No CAS ]
  • [ 205647-96-7 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2-Cyanopyridine With sodium methylate In methanol at 20℃; Stage #2: (1S,2R)-1-amino-2-indanol In toluene at 80℃;
  • 28
  • [ 13541-18-9 ]
  • [ 126456-43-7 ]
  • [ 2788833-57-6 ]
YieldReaction ConditionsOperation in experiment
90% With 1,4-diaza-bicyclo[2.2.2]octane In acetonitrile at 25℃; for 3h; stereoselective reaction; Characterization of 4a-4m General procedure: To a dry Schlenk tube were added 1 (0.2 mmol), 4 (0.3 mmol), DABCO (0.4 mmol), MeCN (1.0 mL), at room temperature and the resulting solution was stirred at 25 °C for 3 h. The resulting mixture and the solvent were evaporated under vacuum. The residue was purified by flash column chromatography on silica gel (eluent: dichloromethane/methanol) to give the 4a-4m.
  • 29
  • [ 2893-33-6 ]
  • [ 126456-43-7 ]
  • [ 357209-32-6 ]
YieldReaction ConditionsOperation in experiment
With zinc trifluoromethanesulfonate In toluene Reflux;
  • 30
  • [ 626-17-5 ]
  • [ 126456-43-7 ]
  • [ 2893146-40-0 ]
  • [ 175733-74-1 ]
YieldReaction ConditionsOperation in experiment
1: 27 % 2: 67 % With cobalt(II) bromide In chlorobenzene at 200℃; Microwave irradiation; Molecular sieve; Green chemistry;
Same Skeleton Products
Historical Records

Similar Product of
[ 126456-43-7 ]

Chemical Structure| 136030-00-7

A186673[ 136030-00-7 ]

(1R,2S)-1-Amino-2,3-dihydro-1H-inden-2-ol

Reason: Optical isomers

Related Functional Groups of
[ 126456-43-7 ]

Aryls

Chemical Structure| 103028-83-7

[ 103028-83-7 ]

1-Amino-1,2,3,4-tetrahydronaphthalen-2-ol hydrochloride

Similarity: 0.93

Chemical Structure| 255060-27-6

[ 255060-27-6 ]

(1R,2R)-1-Amino-1-phenylpropan-2-ol hydrochloride

Similarity: 0.93

Chemical Structure| 88784-91-2

[ 88784-91-2 ]

(1R,2S)-1-Amino-1-phenylpropan-2-ol hydrochloride

Similarity: 0.93

Chemical Structure| 926292-63-9

[ 926292-63-9 ]

(R)-2-Amino-2-(m-tolyl)ethanol

Similarity: 0.85

Chemical Structure| 2095772-93-1

[ 2095772-93-1 ]

(S)-2-Amino-2-(m-tolyl)ethanol hydrochloride

Similarity: 0.83

Alcohols

Chemical Structure| 103028-83-7

[ 103028-83-7 ]

1-Amino-1,2,3,4-tetrahydronaphthalen-2-ol hydrochloride

Similarity: 0.93

Chemical Structure| 255060-27-6

[ 255060-27-6 ]

(1R,2R)-1-Amino-1-phenylpropan-2-ol hydrochloride

Similarity: 0.93

Chemical Structure| 88784-91-2

[ 88784-91-2 ]

(1R,2S)-1-Amino-1-phenylpropan-2-ol hydrochloride

Similarity: 0.93

Chemical Structure| 926292-63-9

[ 926292-63-9 ]

(R)-2-Amino-2-(m-tolyl)ethanol

Similarity: 0.85

Chemical Structure| 2095772-93-1

[ 2095772-93-1 ]

(S)-2-Amino-2-(m-tolyl)ethanol hydrochloride

Similarity: 0.83

Amines

Chemical Structure| 103028-83-7

[ 103028-83-7 ]

1-Amino-1,2,3,4-tetrahydronaphthalen-2-ol hydrochloride

Similarity: 0.93

Chemical Structure| 255060-27-6

[ 255060-27-6 ]

(1R,2R)-1-Amino-1-phenylpropan-2-ol hydrochloride

Similarity: 0.93

Chemical Structure| 88784-91-2

[ 88784-91-2 ]

(1R,2S)-1-Amino-1-phenylpropan-2-ol hydrochloride

Similarity: 0.93

Chemical Structure| 926292-63-9

[ 926292-63-9 ]

(R)-2-Amino-2-(m-tolyl)ethanol

Similarity: 0.85

Chemical Structure| 2095772-93-1

[ 2095772-93-1 ]

(S)-2-Amino-2-(m-tolyl)ethanol hydrochloride

Similarity: 0.83