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Structure of 2752-17-2 * Storage: {[proInfo.prStorage]}
* 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.
Reference：
[1] Chemical Communications, 2017, vol. 53, # 62, p. 8751 - 8754
[2] European Journal of Organic Chemistry, 2015, vol. 2015, # 29, p. 6458 - 6465
[3] New Journal of Chemistry, 2018, vol. 42, # 12, p. 9369 - 9372
[4] Tetrahedron, 1992, vol. 48, # 8, p. 1497 - 1506
[5] Journal of Organic Chemistry, 1985, vol. 50, # 19, p. 3453 - 3457
[6] Patent: WO2008/8797, 2008, A2, . Location in patent: Page/Page column 63
[7] Patent: WO2011/25790, 2011, A1, . Location in patent: Page/Page column 50
[8] Patent: WO2011/37610, 2011, A1, . Location in patent: Page/Page column 57
4
[ 43113-25-3 ]
[ 2752-17-2 ]
Yield
Reaction Conditions
Operation in experiment
93%
With hydrazine hydrate In chloroform for 4 h; Reflux
A mixture of 15 (575 mg, 0.83 mmol) and 80percent hydrazine hydrate (8.3 mmol) was stirred under reflux for 4 h in CHCl3 (10 mL). The reaction mixture was treated with water and extracted with CHCl3, and then dried (MgSO4). After evaporation of the solvent, distillation gave the product 9a in a 93percent yield; bp 75-79 °C/5 mmHg (lit.31 bp 55-60 °C/2 mmHg); 1H NMR (500 MHz, DMSO-d6): δ 8.31 (4H, br s), 3.32 (4H, t, J=5.5 Hz), 2.63 (4H, t, J=5.5 Hz); 13C NMR (500 MHz, DMSO-d6): δ 72.7, 41.3; MS (FAB) m/z: 105 [M+H].
Reference：
[1] Tetrahedron, 2016, vol. 72, # 29, p. 4258 - 4272
[2] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1982, vol. 18, # 2, p. 193 - 196[3] Khimiya Geterotsiklicheskikh Soedinenii, 1982, # 2, p. 246 - 249
[4] Journal of Organic Chemistry USSR (English Translation), 1980, vol. 16, p. 1124 - 1129[5] Zhurnal Organicheskoi Khimii, 1980, vol. 16, # 6, p. 1301 - 1307
[6] Journal of the Chemical Society, Dalton Transactions: Inorganic Chemistry (1972-1999), 1983, p. 2525 - 2528
[7] European Journal of Medicinal Chemistry, 2009, vol. 44, # 9, p. 3665 - 3671
[8] Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences, 2013, vol. 68, # 3, p. 257 - 266
[9] Journal of Coordination Chemistry, 2014, vol. 67, # 18, p. 3054 - 3066
[10] Journal of the Chinese Chemical Society, 2015, vol. 62, # 11, p. 1028 - 1034
[11] Journal of Coordination Chemistry, 2017, vol. 70, # 12, p. 2015 - 2028
[12] European Journal of Medicinal Chemistry, 2013, vol. 63, p. 907 - 923
[13] Journal of Chemical Research, 2014, vol. 38, # 4, p. 211 - 217
[14] Research on Chemical Intermediates, 2015, vol. 41, # 6, p. 3375 - 3388
[15] Journal of Coordination Chemistry, 2013, vol. 66, # 15, p. 2634 - 2646
[16] Zeitschrift fur Anorganische und Allgemeine Chemie, 2017, vol. 643, # 5, p. 379 - 386
Reference：
[1] Journal of the American Chemical Society, 1986, vol. 108, # 11, p. 2989 - 2998
[2] Patent: US2005/43532, 2005, A1, . Location in patent: Page/Page column 5
EXAMPLE 38 Preparation of 1,5-diamino-3-oxapentane 1,5-Dichloro-3-oxapentane is treated with potassium phthalimid, followed by hydrazinolysis of the resulting diphthalimido-derivative and consecutive acidification whereby the bis-hydrochloride of the title compound is obtained. The bis-hydrochloride is treated with a very concentrated (approx. 10N) solution of potassium hydroxide in water and continuously extracted with benzene in a liquid-liquid extractor for several (three to five) days. The solvent is evaporated and the liquid residue is distilled under reduced pressure giving the desire compound. b.p.: 48° - 50° /1mm Hg Yield 30percent (from the initial 1,5-dichloro-3-oxapentane). PMR (CDCl3): --NH2: 1.30 ppm (singlet: 4H); --CH2 --N: 2.90 ppm (triplet: 4H); --CH2 --O: 3.50 ppm (triplet: 4H).
30%
With potassium hydroxide In water
EXAMPLE 38 Preparation of 1,5-diamino-3-oxapentane 1,5-Dichloro-3-oxapentane is treated with potassium phthalimid, followed by hydrazinolysis of the resulting diphthalimido-derivative and consecutive acidification whereby the bis-hydrochloride of the title compound is obtained. The bis-hydrochloride is treated with a very concentrated (approx. 10N) solution of potassium hydroxide in water and continuously extracted with benzene in a liquid-liquid extractor for several (three to five) days. The solvent is evaporated and the liquid residue is distilled under reduced pressure giving the desire compound. b.p.: 48° - 50°11mm Hg: Yield 30percent (from the initial 1,5-dichloro-3-oxapentane); PMR (CDCl3): --NH2: 1.30 ppm (singlet: 4H); --CH2 --N: 2.90 ppm (triplet: 4H); --CH2 --O: 3.50 ppm (triplet: 4H).
Reference：
[1] Patent: US4156683, 1979, A,
[2] Patent: US3966766, 1976, A,
11
[ 141-43-5 ]
[ 2752-17-2 ]
Reference：
[1] Patent: US4083873, 1978, A,
12
[ 81539-80-2 ]
[ 2752-17-2 ]
[ 61020-43-7 ]
Reference：
[1] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1982, vol. 18, # 2, p. 193 - 196[2] Khimiya Geterotsiklicheskikh Soedinenii, 1982, # 2, p. 246 - 249
13
[ 136918-14-4 ]
[ 2752-17-2 ]
Reference：
[1] Zeitschrift fuer Anorganische und Allgemeine Chemie, 2014, vol. 640, # 10, p. 2062 - 2071,10
14
[ 111-44-4 ]
[ 2752-17-2 ]
Reference：
[1] Chemistry - A European Journal, 2012, vol. 18, # 25, p. 7680 - 7685
15
[ 141-43-5 ]
[ 110-85-0 ]
[ 2752-17-2 ]
Reference：
[1] Yakugaku Zasshi, 1955, vol. 75, p. 1318,1319,1321[2] Chem.Abstr., 1956, p. 10106
16
[ 7647-01-0 ]
[ 43113-25-3 ]
[ 64-19-7 ]
[ 2752-17-2 ]
[ 88-99-3 ]
Reference：
[1] Chemische Berichte, 1905, vol. 38, p. 3413
17
[ 2752-17-2 ]
[ 60792-79-2 ]
Reference：
[1] European Journal of Medicinal Chemistry, 2009, vol. 44, # 9, p. 3665 - 3671
18
[ 2752-17-2 ]
[ 24424-99-5 ]
[ 127828-22-2 ]
Yield
Reaction Conditions
Operation in experiment
71.5%
at 0 - 20℃;
This compound was synthesized according to the procedure described previously with slight modifications.25 To a cooled (0 °C) solution of 2,2'-oxybis(ethylamine) (10.0 mL, 94.1 mmol) in methanol (1000 mL) was added dropwise a solution of di-tert-butyl dicarbonate ((Boc)2O; 10.3 g, 47.0 mmol) in THF (300 mL), and the mixture was stirred for 1 h at the same temperature and additional 24 h at room temperature. After removing the solvent in vacuo, the residue was dissolved in 1 N NaOH (200 mL), and extracted with chloroform (300 mL .x. 3). The organic phases were combined, dried over anhydrous MgSO4. The solvent was removed in vacuo to provide 1 as a colorless oil (6.88 g, 71.5percent). 1H NMR (CDCl3): δ 1.39 (9H, s, Boc), 2.79-2.82 (2H, t, CH2), 3.24-3.28 (2H, dd, CH2), 3.41-3.43 (2H, t, CH2), 3.44-3.47 (2H, t, CH2), 5.00 (1H, d, NH). ESI-MS (M+H)+: m/z 205, found: 205
Reference：
[1] Tetrahedron Letters, 2006, vol. 47, # 17, p. 2915 - 2919
[2] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 2, p. 978 - 984
[3] Journal of the American Chemical Society, 2010, vol. 132, # 21, p. 7291 - 7293
[4] Chemical Communications, 2017, vol. 53, # 62, p. 8751 - 8754
[5] Chemistry - An Asian Journal, 2012, vol. 7, # 2, p. 272 - 276
1 EXAMPLE 1
EXAMPLE 1 Following the reaction scheme STR17 a solution (500 ml) of 2,2-oxybis(acetyl chloride) (2) (24.5 g, 0.14 mole) in anhydrous benzene and a solution (500 ml) of 1,5-diamino-3-oxapentane (3) (30.0 g, 0.28 mole) in anhydrous benzene were added simultaneously to 1 liter of violently stirred anhydrous benzene at a rate of 2.5 ml per minute at room temperature. The precipitate was filtered and washed with hot CHCl3, and the filtrates were evaporated to give a residue which was recrystallized from chloroform-heptane to afford 15.5 g (58%) of 5,9-dioxo-1,7-dioxa-4,10-diazacyclododecane, mp 169°-171° C.
General procedure: All macrocyclic compounds were obtained as previously described. 20,21 The corresponding diester (1-3) (10 mmol) and diamine (4-8) (10 mmol) were dissolved in MeOH (100 ml). The reaction mixture was stirred for 7 d at rt. After completion of the reaction (monitored by TLC), the solvent was evaporated and the residue was puriofied by chromatography on a silica gel column using 0-5% solutions of MeOH/CH2Cl2. Analytical and spectroscopic data are collected in the Supplementary Materials.
With hydrogen;palladium 10% on activated carbon; In ethanol; water; at 25℃; under 38002.6 Torr;
3-Oxapentane-l,5-diamine (5LIO-amine); This amine was available from Aldrich as hydrochloride salt form at high cost. However the following modified literature procedure was quite easy to preparation good amount of the free amine.; A mixture of 34.7 g (0.5mol) OfNaN3 and catalytical amount of KI ( 1 g) in 75 mL of H2O and 6.8 g (0.02 mol) of cety lpyridinium chloride in 42.9 g (0.3 mol) of 1 ,5-dichloro- 3-oxapentan we refluxed and stirred for 20 h. The reaction mixture was filtered, the organic phase of the filtrate separated and the aqueous phase extracted with dichloromethane three times. The combined organic solution was extracted with 10 % solution of Na2S2theta^ to removed any iodine in the organic phase. The organic phase was then loaded onto a flash silica gel plug to remove the pyridinium salt and residual water. Evaporation under vacuo at 25 0C affords 45 g of crude diazide. It was dissolved in 60 mL of 95% ethanol and hydrogenated at 25 0C (cooling with a water bath) and 50 atm in the presence of 10% Pd/C (1.5 g). Filtration of the catalyst, evaporation of the solvent, and distillation gave 25 g (80%) of 5LIO-amine: bp 48-50 0C (1 torr)]. [0249] 1H NMR (300MHz, CDCl3): delta 1.33(s,br, 4H), 2.83(t, 4H), 3.45(t, 4H).
With hydrogenchloride; triphenylphosphine; In tetrahydrofuran; diethyl ether; water; at 20℃; for 60h;
To a solution of bis(2-hydroxyethyl)ether (1.0 eqs) and 'Pr2NEt (4.0 eqs.) in CH2C12 (24 mL) was added MsCl (2.2 eqs.). The reaction mixture was stirred at ambient temperature for 1 h. The reaction mixture was partitioned between water and CH2C12, the layers separated, and the aqueous layer extracted with CH2C12 (3x). The combined organics were dried over Na2S04, filtered and concentrated in vacuo. The residue was used without further purification. [000121] To a solution of the residue (1.0 eq.) and Nal (0.2 eqs.) in DMF (24 mL) was added NaN3 (2.3 eqs.). The reaction mixture was warmed to 65 C and stirred overnight. The reaction mixture was cooled to ambient temperature and partitioned between water and ether. The layers were separated and the aqueous extracted with ether (3x). The combined organics were dried over Na2S04, filtered and concentrated in vacuo. The residue was used without further purification.[000122] To a solution of the residue (1.0 eq.) in THF (0.6 mL), ether (3 mL) and 1.0 M HC1 (3 mL, aqueous) was added PPh3 (1.05 eqs.). The reaction mixture was stirred at ambient temperature for 60 hours. Subsequently, the organics were removed from the reaction mixture in vacuo. Diethyl ether was added and the layers separated and the ethereal layer washed with 4.0 M HC1 in water (50 mL). The combined aqueous layers were extracted with ether (2x) and the aqueous layer basicified to a pH~14 by addition of solid NaOH. The aqueous layer was then extracted with CH2C12 (3x) and the combined dichloromethane layers dried over Na2S04, filtered and concentrated in vacuo. The obtained residue was used without further purification.[000123] A solution of the residue (1.0 eq.) and Boc20 (1.1 eqs.) in CH2C12 (70 mL) was added TEA (2.0 eqs.). The reaction mixture was stirred at ambient temperature for 2.0 hours. The reaction mixture was concentrated in vacuo. The residue was filtered over a plug of silica gel (2: l/hex:EtOAc) and the obtained residue (1.27 g, 38%) used with any further purification.[000124] To a biphasic solution of the residue (1.0 eq.) in THF (23 mL) and water (6.6 mL) was added PMe3 (5.0 eqs.). The reaction mixture was stirred for 2 hours. Subsequently, the reaction mixture was concentrated in vacuo and the residue dissolved in CH2C12 (53 mL). To the reaction mixture was added trifluoroacetic anhydride (1.2 eqs.) followed by TEA (2.0 eqs.). The reaction mixture was stirred at ambient temperature overnight. The mixture was then partitioned between water and CH2C12, the layers separated and the aqueous extracted with CH2C12 (3x). The combined organics were dried over Na2S04, filtered and concentrated in vacuo. The residue was used without any further purification.[000125] To a solution of the residue (1.0 eq.) in EtOAc (40 mL) was added concentrated HC1 (13.6 mL). The reaction mixture was stirred at ambient temperature for 1 hour. The reaction mixture was then concentrated in vacuo and the obtained amine 16 was used without any further purification.
With hydrazine hydrate; In chloroform; for 4h;Reflux;
A mixture of 15 (575 mg, 0.83 mmol) and 80% hydrazine hydrate (8.3 mmol) was stirred under reflux for 4 h in CHCl3 (10 mL). The reaction mixture was treated with water and extracted with CHCl3, and then dried (MgSO4). After evaporation of the solvent, distillation gave the product 9a in a 93% yield; bp 75-79 C/5 mmHg (lit.31 bp 55-60 C/2 mmHg); 1H NMR (500 MHz, DMSO-d6): delta 8.31 (4H, br s), 3.32 (4H, t, J=5.5 Hz), 2.63 (4H, t, J=5.5 Hz); 13C NMR (500 MHz, DMSO-d6): delta 72.7, 41.3; MS (FAB) m/z: 105 [M+H].
67.55%
With hydrazine hydrate; In ethanol; at 75℃; for 2h;
100 g of dried 2,2'-diphthalimido diethyl ether and 75 g of hydrazine hydrate were placed in a 2 L round bottom flask, and 1 L of absolute ethanol solvent was added thereto. The mixture was stirred at 75 C for 2 h, and the white solid was slowly dissolved. The solution became clear and a large amount of creamy solid appeared afterwards. Stop heating, slowly add concentrated hydrochloric acid, adjust the pH to 3, filter the filtrate, then steam to concentrate about 100 mL, add 100 mL of deionized water, remove insoluble solids by filtration, continue to vortex to 100 mL, if there is still Insoluble substances appear to be still filtered. The filtrate was concentrated by rotary evaporation to obtain 2'-oxydiethylamine hydrochloride. To the obtained crude amine hydrochloride was added sodium hydroxide solution, pH was adjusted to 11 and extracted with 300 mL of isopropanol, and the upper liquid was collected. Isopropanol was recovered by rotary distillation under reduced pressure at 40 C to obtain a pure product of 2'-oxydiethylamine (19.3 g). The purity of the product was 95.08%, and the yield was 67.55%.
With hydrogenchloride; In ethanol; water;
3-Oxapentane-1,5-diamine was synthesized following the procedure [26]. 1,5-Dichloro-3-oxapentane was prepared by the reaction of diethylene glycol and thionyl chloride. Dichloride, potassium phthalimide, and diethylamine were heated together at 140 C for 3 h to synthesize 3-oxapentane-1,5-diphthalimide. After a series of hydrolysis, acidification, and distillation, a colorless oil was obtained.
0.5 g (0.0028 mole) of 2,2' oxybis(ethylamine) dihydrochloride was dissolved in 2.5 g of distilled water. Sodium bicarbonate (0.475 g, 0.0057 mole) was added to neutralize the HCl resulting in the liberation of the diamine starting material.
With sodium hydroxide; In diethyl ether; water;pH 12.0;
The commercially available Bis-(2-aminoethyl)-ether (5.50 g, 5.28 mmol, 1 equivalent) was dissolved in 50 ml water. The pH of the solution was adjusted to 12 by using solid NaOH. Tosyl chloride (22.85 g, 12.03 mmol, 2.27 equiv.) was dissolved in diethyl ether and added dropwise to the vigorously stirred aqueous solution of amine. After evaporation of the ether a brownish precipitate formed which was collected by careful decantation of the remaining aqueous solution. The yellowish precipitate was dissolved in 20 mL mixture of methanol and chloroform (1 :9 ratio by volume) and purified by flash chromatography on silica gel. The fraction containing the desired product was evaporated under reduced pressure and the residue was recrystallized twice from ethanol. Yield: 4.85 g (30.7%). 1H MR (CDC13): delta 2.42 (s, 6H), 3.07 (m, 4H), 3.37 (t, 4H), 5.26 (t, 2H), 7.30 (d, 4H), 7.75 (d, 4H)
2,8,14-trioxa-5,11-diazabicyclo[13.3.1]nonadeca-1(18),15(19),16-triene-4,12-dione[ No CAS ]
2,8,14,20,26,32-hexaoxa-5,11,23,29-tetraazatricyclo[31.3.1.115,19]octatriaconta-1(36),15(38),16,18,33(37),34-hexaene-4,12,22,30-tetraone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
25%; 4%
In methanol; at 20℃; for 168h;
General procedure: All macrocyclic compounds were obtained as previously described. 20,21 The corresponding diester (1-3) (10 mmol) and diamine (4-8) (10 mmol) were dissolved in MeOH (100 ml). The reaction mixture was stirred for 7 d at rt. After completion of the reaction (monitored by TLC), the solvent was evaporated and the residue was puriofied by chromatography on a silica gel column using 0-5% solutions of MeOH/CH2Cl2. Analytical and spectroscopic data are collected in the Supplementary Materials.
This compound was synthesized according to the procedure described previously with slight modifications.25 To a cooled (0 C) solution of 2,2'-oxybis(ethylamine) (10.0 mL, 94.1 mmol) in methanol (1000 mL) was added dropwise a solution of di-tert-butyl dicarbonate ((Boc)2O; 10.3 g, 47.0 mmol) in THF (300 mL), and the mixture was stirred for 1 h at the same temperature and additional 24 h at room temperature. After removing the solvent in vacuo, the residue was dissolved in 1 N NaOH (200 mL), and extracted with chloroform (300 mL × 3). The organic phases were combined, dried over anhydrous MgSO4. The solvent was removed in vacuo to provide 1 as a colorless oil (6.88 g, 71.5%). 1H NMR (CDCl3): delta 1.39 (9H, s, Boc), 2.79-2.82 (2H, t, CH2), 3.24-3.28 (2H, dd, CH2), 3.41-3.43 (2H, t, CH2), 3.44-3.47 (2H, t, CH2), 5.00 (1H, d, NH). ESI-MS (M+H)+: m/z 205, found: 205
5LlO-l,2-HOPOBn; To a solution of l ,2-HOPO(Bn)-thiazolide (644 mg, 2.1 mmol) in dry methylene chloride (20 mL), was added neat 5LIO-amine ( 104 mg, 1.0 mmol). The mixture was stirred overnight, after which time the solvent was removed and the residue was loaded onto a flash silica column. Elution with 2-6% methanol in methylene chloride allowed for the separation and isolation of the benzyl-protected 5L1O- 1 , 2-HOPO(Bn) to give a pale yellow oil (447 mg. 85 % based on amine). <n="65"/>[0251] 1 H NMR (500MHz, CDCl3): delta 3.22(s, 8H, CH2), 5.24(s, 4H, benzyl CH2), 6.26(dd, J= I, .2 Hz, 2H, HOPO H), 6.3 l (d, 2H, J = 9.0 Hz, HOPO H), 7.24(dd, 2H, J= 9.0, 2 Hz, ArH), 7.26-7.45(m, 12H, ArH), 7.74(s,br, 2H, amideH). 1 3C NMR ( 125 MHz, CDCI3): delta 38.8, 68.1 , 78.2, 104.7, 121.7, 127.7, 128.3, 129.0, 132.9, 138.3, 143.2, 157.8, 160.0. MS(FAB+): 559.2 (MH ').
H(5O,2)-CBZ; Several approaches were tried to synthesize the N,N,N',N'-Tetrakis-(2-amino-ethyl)- 3-oxapentane- l ,5-diamine [H(5O,2)-amine]. It was found that the reaction of 5LIO-amine with CBZ-aziridine provides clean H(5O,2)-CBZ.; 5LIO-amine (0.21 g, 2 mmol) and CbZ-aziridine ( 1.77 g, 10 mmol) were mixed in tert- butanol (30 ml.) at room temperature under N2. The mixture was stirred under a N2 atmosphere at 8O0C for 16 hrs. when TLC showed the completeness of the reaction. The volatile were removed under vacuum and the residue was dissolved in dichloromethane. The appropriate fractions of a gradient flash silica gel column ( 1 -7% methanol in dicholoromethane) were collected and evaporated to dryness to give a pale beige thick oil, yield: 1.28 g, 79%.[0301] ' H NMR(300MHz, CDCl3): delta 2.53(s,br, 12H), 3.17(s,br, 4H), 3.83(s, br, 8H), 5.04(s, 8H), 7.29(s,br, 20H). 1 3C NMR (300MHz, CDCI3): delta 38.8, 53.0, 53.6, 69.3, 128.0, 128.1 , 128.4, 136.6, 156.4. MS(FAB+, DTT/DTE): 813.5 (MH+).
In 1-methyl-pyrrolidin-2-one; at 200℃; for 1h;Microwave irradiation;
Intermediate 11; : 9-({2-r(2-aminoethyl)oxylethyl)amino)-5-(ft,S)-methyl-1 -oxo-6 J- dihvdro-1H,5H-pyridor3,2,1-//]quinoline-2-carboxylic acid; A solution of <strong>[42835-25-6]flumequine</strong> (0.13 g, 0.5 mmol) and {2-[(2-aminoethyl)oxy]ethyl}amine (0.25 mL) in Lambda/-methyl-2-pyrrolidinone (0.25 mL) was microwaved at 2000C for 1 h. The reaction mixture was purified by preparative reverse phase HPLC (MeCN/H2O/0.1%HCO2H eluent) to give the title compound as a yellow oil (0.14 g). ESMS m/z 346.4 [M+H]+.
rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid[ No CAS ]
rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid [2-(2-amino-ethoxy)-ethyl]-amide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
19.6%
With N-ethyl-N,N-diisopropylamine; HATU; In dichloromethane; at 20℃;
Example 189Preparation of rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid [2-(2-amino-ethoxy)-ethyl]-amide; A mixture of rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (86.2 mg, 0.20 mmol), <strong>[2752-17-2]2,2'-oxybis(ethylamine)</strong> (31.3 mg, 0.3 mmol), 2-(7-azabenzotriazol-1-yl)-n,n,n',n'-tetramethyluronium hexafluorophosphate (HATU, 76 mg, 0.2 mmol) and iPr2NEt (0.1 mL, 0.55 mmol) in CH2Cl2 (2 mL) was stirred at rt overnight. The mixture was then diluted with CH2Cl2 and washed with water, brine. The organic phase was separated, filtered and dried over Na2SO4. The mixture was then concentrated and purified by reverse phase chromatography (20-95% of ACN/water) to give rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid [2-(2-amino-ethoxy)-ethyl]-amide (20.3 mg, 19.6%) as an off-white powder. HRMS (ES+) m/z Calcd for C27H34Cl2N4O2+H [(M+H)+]: 517.2132, found: 517.2133
14.2) N,N'-(oxydiethane-2,1-diyl)bis(5-methoxy-4-nitro-1,3-benzothiazole-2-carboxamide) 3.03 g (6.5 mmol; 1.1 eq.) of bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBroP) is added to 1.5 g (5.9 mmol) of 5-methoxy-4-nitro-1,3-benzothiazole-2-carboxylic acid and 1.13 ml (6.5 mmol; 1.1 eq.) of diisopropylethylamine in solution in 100 ml of dichloromethane. The reaction mixture is maintained for 10 minutes under stirring at ambient temperature, then 0.31 g (2.9 mmol; 0.5 eq.) of 2.2'-oxybis(ethylamine) and a spatula tip's worth of dimethylaminopyridine are added to the medium which is maintained under stirring for 18 hours at ambient temperature. The insoluble matter is filtered and the solvent is evaporated off under reduced pressure. The residue is then purified on a silica column (eluent:ethyl acetate/heptane: 4/1) and 250 mg of expected product (yield=8%) is obtained in the form of beige powder. MS-LC: MH+=577.11; r.t.=10.27 min.
2-{4-[2-(2-aminoethoxy)ethyl]-3-nitrophenyl}-3-hydroxyquinolin-4(1H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
72%
With 1-methyl-pyrrolidin-2-one; at 110℃; for 2h;
Compounds 1 and 2 were prepared by the following procedure: 2-(4-chloro-3-nitrophenyl)-2-oxoethyl 2-aminobenzoate or 2-(4-amino-3-nitrophenyl)-2-oxoethyl 2-aminobenzoate (44.8 mmol) was suspended in polyphosphoric acid (167.3 g). The reaction mixture was heated to 100 C and stirred for 90 min. The mixture was then poured into H2O/crushed ice (700 ml). The precipitated product was filtered, washed with H2O, dried and recrystallized from 2-methoxyethanol. Compounds 3-17 were prepared by the following general procedure: quinolinone 1 (200 mg, 0.63 mmol) was added to a solution of amine (6.3 mmol) and N-methylpyrrolidone (1.0 ml) and the mixture was stirred at 110 C for 2 h. After cooling to room temperature, H2O (20 ml) was added and the pH adjusted to 7 with dilute HCl (1:3). The precipitated solid was collected by suction, washed thoroughly with H2O and dried at 80 C. The crude product was recrystallized from 2-methoxyethanol.
General procedure: The precursor quinoline tetramer acid (100 mg, 0.1 mmol, 2.05 equiv), HBTU (114 mg, 0.3 mmol, 3 equiv), and HOBt (27 mg, 0.2 mmol, 2 equiv) were dissolved in anhydrous DMF under nitrogen. DIEA (173 muL, 1 mmol, 10 equiv) was added and the reaction mixture was stirred at room temperature for 30 min. The diamine (1 equiv) was added and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was poured into water, extracted three times with toluene, dried over Na2SO4, filtered, and concentrated. The crude was purified by silica-gel chromatography eluting with toluene/ethyl acetate 90/10 v/v, yielding the expected compound as a yellow solid.
With ammonia;chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); In toluene; at 155℃; under 31278.1 Torr; for 15h;Autoclave; Inert atmosphere;
Catalyst complex XIVb (for preparation, see below, weighed out under an inert atmosphere), solvent (such an amount that the total solvent volume is 50 ml) and the alcohol to be reacted were placed under an argon atmosphere in a 160 ml Parr autoclave (stainless steel V4A) having a magnetically coupled inclined blade stirrer (stirring speed: 200-500 revolutions/minute). The indicated amount of ammonia was introduced at room temperature either in precondensed form or directly from the pressurized NH3 gas bottle. If hydrogen was used, this was effected by iterative differential pressure metering. The steel autoclave was electrically heated to the temperature indicated and heated for the time indicated while stirring (500 revolutions/minute) (internal temperature measurement). After cooling to room temperature, venting the autoclave and outgassing the ammonia at atmospheric pressure, the reaction mixture was analyzed by GC (30m RTX5 amine 0.32 mm 1.5 mum). Purification of the particular products can, for example, be carried out by distillation. The results for the amination of 1,4-butanediol (table 1a, 1b), diethylene glycol (table 2) and monoethylene glycol (table 3), 2,5-furandimethanol (table 4), alkyldiols (table 5), 1,4-bis(hydroxymethyl)-cyclohexane (table 6) and aminoalcohols (table 7) are given below.
With chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); ammonia; In toluene; at 155℃; under 31278.1 Torr; for 15h;Autoclave; Inert atmosphere;
General procedure: Example General Rules on the catalyst amination of alcohol with ammoniaaccording to the present invention (See below for manufacturing, initialweighed under an inert atmosphere) catalyst complex XIVb and, with the solvent(amount of up to solvent total amount reaches the 50ml), and the alcohol thatthe reaction is, under an argon atmosphere, magnetic coupling type tilt wingsParr autoclave of 160ml equipped with a stirrer (made of special steel V4A)(stirring speed: 200 to 500 rev / min) were charged in. At described the amountof ammonia at room temperature, it has been directly metered from thepreliminary condensed with or NH 3 gas cylinder. If hydrogen is used, this wasdone by repeated differential-pressure volume. Steel autoclave is electricheating heated to the temperature indicated, for a period of time described, ithas been heated under stirring (500 rev / min) (internal temperaturemeasurement). The autoclave was cooled to room temperature, depressurized,after performing outgassing of ammonia at atmospheric pressure, the reactionmixture was analyzed by GC (30m RTX5 Amin 0.32mm, 1.5mum). The desired product,for example, can be isolated by distillation
With ammonia;C28H44BNOP2Ru; In toluene; at 155℃; under 30528.1 Torr; for 12h;Autoclave; Inert atmosphere;Product distribution / selectivity;
Catalyst complex XIVb (for preparation, see below, weighed out under an inert atmosphere), solvent (such an amount that the total solvent volume is 50 ml) and the alcohol to be reacted were placed under an argon atmosphere in a 160 ml Parr autoclave (stainless steel V4A) having a magnetically coupled inclined blade stirrer (stirring speed: 200-500 revolutions/minute). The indicated amount of ammonia was introduced at room temperature either in precondensed form or directly from the pressurized NH3 gas bottle. If hydrogen was used, this was effected by iterative differential pressure metering. The steel autoclave was electrically heated to the temperature indicated and heated for the time indicated while stirring (500 revolutions/minute) (internal temperature measurement). After cooling to room temperature, venting the autoclave and outgassing the ammonia at atmospheric pressure, the reaction mixture was analyzed by GC (30m RTX5 amine 0.32 mm 1.5 mum). Purification of the particular products can, for example, be carried out by distillation. The results for the amination of 1,4-butanediol (table 1a, 1b), diethylene glycol (table 2) and monoethylene glycol (table 3), 2,5-furandimethanol (table 4), alkyldiols (table 5), 1,4-bis(hydroxymethyl)-cyclohexane (table 6) and aminoalcohols (table 7) are given below.
With ammonia;chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); In para-xylene; at 155℃; under 33003.3 Torr; for 24h;Autoclave; Inert atmosphere;Product distribution / selectivity;
Catalyst complex XIVb (for preparation, see below, weighed out under an inert atmosphere), solvent (such an amount that the total solvent volume is 50 ml) and the alcohol to be reacted were placed under an argon atmosphere in a 160 ml Parr autoclave (stainless steel V4A) having a magnetically coupled inclined blade stirrer (stirring speed: 200-500 revolutions/minute). The indicated amount of ammonia was introduced at room temperature either in precondensed form or directly from the pressurized NH3 gas bottle. If hydrogen was used, this was effected by iterative differential pressure metering. The steel autoclave was electrically heated to the temperature indicated and heated for the time indicated while stirring (500 revolutions/minute) (internal temperature measurement). After cooling to room temperature, venting the autoclave and outgassing the ammonia at atmospheric pressure, the reaction mixture was analyzed by GC (30m RTX5 amine 0.32 mm 1.5 mum). Purification of the particular products can, for example, be carried out by distillation. The results for the amination of 1,4-butanediol (table 1a, 1b), diethylene glycol (table 2) and monoethylene glycol (table 3), 2,5-furandimethanol (table 4), alkyldiols (table 5), 1,4-bis(hydroxymethyl)-cyclohexane (table 6) and aminoalcohols (table 7) are given below.
With ammonia;chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); In toluene; at 155℃; under 32253.2 Torr; for 12h;Autoclave;Product distribution / selectivity;
EXAMPLES; General Procedure for the Catalytic Amination According to the Invention of Alcohols with AmmoniaLigand L, metal salt M or catalyst complex XIVb (for preparation see below, weighing in under inert atmosphere), solvent (sufficient for the total solvent volume to be 50 ml) and the alcohol to be reacted were introduced as initial charge under an Ar atmosphere in a 160 ml Parr autoclave (stainless steel V4A) with magnetically coupled slanted-blade stirrer (stirring speed: 200-500 revolutions/minute). The stated amount of ammonia was either precondensed at room temperature or directly metered in from the NH3 pressurized-gas bottle. If hydrogen was used, this was carried out by means of iterative differential pressure metering. The steel autoclave was heated electrically up to the stated temperature and heated (internal temperature measurement) for the stated time with stirring (500 revolutions/minute). After cooling to room temperature, decompressing the autoclave and outgassing the ammonia at atmospheric pressure, 5 or 50 ml of water were added, whereupon two liquid phases were obtained, which were separated by means of phase separation. The reaction mixture was analyzed by means of GC (30 m RTX5 amine 0.32 mm 1.5 mum). The ruthenium content of the respective liquid phase was ascertained by means of atomic absorption spectroscopy. The results for the amination of 1,4-butanediol (Table 1), diethylene glycol (Table 2) and monoethylene glycol (Table 3) are given below:
With ammonia; hydrogen;(carbonyl)chloro(hydrido)tris(triphenylphosphine)ruthenium(II); [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine]; In toluene; at 180℃; under 45829.6 Torr; for 12h;Autoclave; Cooling;Product distribution / selectivity;
EXAMPLES; General Procedure for the Catalytic Amination According to the Invention of Alcohols with AmmoniaLigand L, metal salt M or catalyst complex XIVb (for preparation see below, weighing in under inert atmosphere), solvent (sufficient for the total solvent volume to be 50 ml) and the alcohol to be reacted were introduced as initial charge under an Ar atmosphere in a 160 ml Parr autoclave (stainless steel V4A) with magnetically coupled slanted-blade stirrer (stirring speed: 200-500 revolutions/minute). The stated amount of ammonia was either precondensed at room temperature or directly metered in from the NH3 pressurized-gas bottle. If hydrogen was used, this was carried out by means of iterative differential pressure metering. The steel autoclave was heated electrically up to the stated temperature and heated (internal temperature measurement) for the stated time with stirring (500 revolutions/minute). After cooling to room temperature, decompressing the autoclave and outgassing the ammonia at atmospheric pressure, 5 or 50 ml of water were added, whereupon two liquid phases were obtained, which were separated by means of phase separation. The reaction mixture was analyzed by means of GC (30 m RTX5 amine 0.32 mm 1.5 mum). The ruthenium content of the respective liquid phase was ascertained by means of atomic absorption spectroscopy. The results for the amination of 1,4-butanediol (Table 1), diethylene glycol (Table 2) and monoethylene glycol (Table 3) are given below:
With ammonia; hydrogen;chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); In toluene; at 180℃; under 56705.7 Torr; for 12h;Autoclave; Cooling;Product distribution / selectivity;
EXAMPLES; General Procedure for the Catalytic Amination According to the Invention of Alcohols with AmmoniaLigand L, metal salt M or catalyst complex XIVb (for preparation see below, weighing in under inert atmosphere), solvent (sufficient for the total solvent volume to be 50 ml) and the alcohol to be reacted were introduced as initial charge under an Ar atmosphere in a 160 ml Parr autoclave (stainless steel V4A) with magnetically coupled slanted-blade stirrer (stirring speed: 200-500 revolutions/minute). The stated amount of ammonia was either precondensed at room temperature or directly metered in from the NH3 pressurized-gas bottle. If hydrogen was used, this was carried out by means of iterative differential pressure metering. The steel autoclave was heated electrically up to the stated temperature and heated (internal temperature measurement) for the stated time with stirring (500 revolutions/minute). After cooling to room temperature, decompressing the autoclave and outgassing the ammonia at atmospheric pressure, 5 or 50 ml of water were added, whereupon two liquid phases were obtained, which were separated by means of phase separation. The reaction mixture was analyzed by means of GC (30 m RTX5 amine 0.32 mm 1.5 mum). The ruthenium content of the respective liquid phase was ascertained by means of atomic absorption spectroscopy. The results for the amination of 1,4-butanediol (Table 1), diethylene glycol (Table 2) and monoethylene glycol (Table 3) are given below:
With ammonia; hydrogen;chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); In toluene; at 155℃; under 49505 Torr; for 12h;Autoclave;Product distribution / selectivity;
EXAMPLE; General method for the catalytic amination of alcohols by means of ammonia according to the inventionLigand L, metal salt M or catalyst complex XIVb (for preparation, see below, weighed out under an inert atmosphere), solvent and the alcohol to be reacted were placed under an Ar atmosphere in a 160 ml Parr autoclave (stainless steel V4A) having a magnetically coupled inclined blade stirrer (stirring speed: 200-500 revolutions/minute). The indicated amount of ammonia was introduced at room temperature either in precondensed form or directly from the pressurized NH3 gas bottle. If hydrogen was used, this was effected by iterative differential pressure metering. The steel autoclave was electrically heated to the temperature indicated and heated for the time indicated while stirring (500 revolutions/minute) (internal temperature measurement). After cooling to room temperature, venting the autoclave and outgassing the ammonia at atmospheric pressure, the reaction mixture was analyzed by GC (30m RTX5 amine 0.32 mm 1.5 mum). The results for the amination of 1,4-butanediol (tables 1a, 1b and 2), diethylene glycol (tables 3a, 3b and 4), monoethylene glycol (table 5) and diethanolamine (table 6), 1,5-pentanediol, 1,9-nonanediol, 1,6-hexanediol and 1,10-decanediol (table 7) and 2,5-(dimethanol)-furan (table 8) are given below.
With ammonia;(carbonyl)chloro(hydrido)tris(triphenylphosphine)ruthenium(II); [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine]; In toluene; at 180℃; under 30753.1 Torr; for 12h;Inert atmosphere;Product distribution / selectivity;
Ligand L, metal salt M, solvent and the stated alcohol were introduced as initial charge under an Ar atmosphere in a 160 ml Parr autoclave (hte, (stainless steel V4A)) with magnetically coupled slanted-blade stirrer (stirring speed: 200-500 revolutions/minute). The stated amount of ammonia was either precondensed at room temperature or directly metered in from the NH3 pressurized-gas bottle. If hydrogen was used, this was carried out by means of iterative differential pressure metering. The steel autoclave was heated electrically up to the stated temperature and heated (internal temperature measurement) for the stated time with stirring (500 revolutions/minute). After cooling to room temperature, decompressing the autoclave and outgassing the ammonia at atmospheric pressure, the reaction mixture was analyzed by means of GC (30 m RTX5 amine 0.32 mm 1.5 mum). Purification of the particular product can be carried out, for example, by distillation. The results for the amination of octanol (Table 1a and 1b), 1,4-butanediol (Table 2), diethylene glycol (Table 3), 1,9-nonanediol, 1,6-hexanediol, 1,10-decandiol (Table 4) and 1,2-dimethanolfuran (Table 5) are given below:
With chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); ammonia; at 155℃; for 12h;Inert atmosphere; Autoclave;
General procedure: the Ligand L, metal saltM or Catalyst complex XlVb (Forpreparation of the following, weighing in an inert atmosphere), solvent (the sufficienttotal volume of solvent is 50ml) and alcohol reaction as a initialfeedunderargonatmosphereaddedwithmagneticcouplingobliqueinclinedstirrer(mixingspeed:200-500/min)of160ml PARR autoclaves (stainless steel V4A).the mentioned amount of ammonia is Pre-condensedat room temperature or directly from NH3 pressurized gas was added ina measured bottle. Ifhydrogenisused,thenthisis addedthrough the iterationpartial pressure measurement. The steel autoclave under stirring through electricheating mode (500 revolutions per minute)and heated to the mentionedtemperature and reaches the heat time (internal temperature detection). Aftercooling to room temperature, the autoclave was decompressed and dischargedammonia under atmospheric pressure, then added 5 or 50ml of water, wherein theobtaining two liquid phases, they were separated by phase separation. Thereaction mixture was analyzed by GC analysis (30m RTX5 amine 0. 32mml.5mum).Ruthenium content of the corresponding liquid phase is determined throughatomic absorption spectrometry. The results of amine are shown below for 1,4-butanediol(table 1), Diethylene glycol(table 2)and mono Ethylene glycol (table 3).
With chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); ammonia; In toluene; at 165℃; under 33828.4 Torr; for 12h;Autoclave; Inert atmosphere;Catalytic behavior;
General procedure: Example General Rules on the catalyst amination of alcohol with ammoniaaccording to the present invention (See below for manufacturing, initialweighed under an inert atmosphere) catalyst complex XIVb and, with the solvent(amount of up to solvent total amount reaches the 50ml), and the alcohol thatthe reaction is, under an argon atmosphere, magnetic coupling type tilt wingsParr autoclave of 160ml equipped with a stirrer (made of special steel V4A)(stirring speed: 200 to 500 rev / min) were charged in. At described the amountof ammonia at room temperature, it has been directly metered from thepreliminary condensed with or NH 3 gas cylinder. If hydrogen is used, this wasdone by repeated differential-pressure volume. Steel autoclave is electricheating heated to the temperature indicated, for a period of time described, ithas been heated under stirring (500 rev / min) (internal temperaturemeasurement). The autoclave was cooled to room temperature, depressurized,after performing outgassing of ammonia at atmospheric pressure, the reactionmixture was analyzed by GC (30m RTX5 Amin 0.32mm, 1.5mum). The desired product,for example, can be isolated by distillation.
With (carbonyl)chloro(hydrido)tris(triphenylphosphine)ruthenium(II); ammonia; hydrogen; [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine]; In toluene; at 180℃; under 3750.38 - 48754.9 Torr; for 12h;Inert atmosphere; Autoclave;
General procedure: Ligand L, see below for the metal salt M or catalyst complex XIVb (manufacturing, inert atmosphere initial mass below), solvent and an alcohol of the reaction, under an argon atmosphere, a magnetic coupling type Parr autoclave of 160ml equipped with atilt wing stirrer (made of special steel V4A) (Stirring speed: were charged to the 200 to 500 rev / min) in. It described theamount of ammonia at room temperature, It is directly metered from the preliminarycondensed with or NH3 gas cylinder. Hydrogenis used Case, this was done by an iterative difference-pressure amount. Power to the temperature indicated the steel autoclave is NetsuNoboru temperature, for a period of time described, has been heated under stirring (500 rev / min) (internal temperature Measurement). The autoclave was cooled to room temperature, depressurized, row outgassing of ammonia at atmospheric pressure after becoming, the reaction mixture was analyzed by GC (30m RTX5 Amin 0.32mm,1.5mum). The amination of 1,4-butanediol result (the first 1a, 1b and the second table), diethylene glycol of the same result (the first 3a, 3b and Table 4), the resultof monoethylene glycol (Table 5), diethanolamine same result (table 6), 1,5-pentanediol, 1,9-nonanediol, 1,6-hexanediol and 1,10-decanediol same result of (table 7), as well as furan-2,5-dimethanol same result (table 8) are as described below.
With (carbonyl)chloro(hydrido)tris(triphenylphosphine)ruthenium(II); ammonia; [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine]; In toluene; at 180℃; under 30753.1 Torr; for 12h;Autoclave; Inert atmosphere;
General procedure: The ligand L, the metal salt M, the solvent and the alcohol were introduced as an initial feed into a 160 ml Parr autoclave (hte) having a magnetically coupled tilt blade stirrer (stirring rate: 200 to 500 rpm) in an Ar atmosphere , (Stainless steel V4A)). The amount of ammonia is pre-concentrated at room temperature or directly from a cylinder pressurized with NH3. If hydrogen is used, this is done by adding a repeated differential pressure differential. The steel autoclave was electrically heated to the temperature and heated for the time (internal temperature measurement) with stirring (500 revolutions per minute). After cooling to room temperature, the autoclave was decompressed and ammonia was withdrawn at atmospheric pressure, and the reaction mixture (30 m RTX5 amine 0.32 mml. 5 [mu] [pi]) was analyzed by GC. Purification of a specific product can be carried out, for example, by distillation. Octyl alcohol (Table 1), 1,9-nonanediol, 1,6-hexanediol, 1,10_ The amination results of diols (Table 4) and 2,5-dimethanolfuran (Table 5) are given below.
With ammonia;chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); In tetrahydrofuran; at 180℃; under 36828.7 Torr; for 12h;Autoclave; Inert atmosphere;Product distribution / selectivity;
Catalyst complex XIVb (for preparation, see below, weighed out under an inert atmosphere), solvent (such an amount that the total solvent volume is 50 ml) and the alcohol to be reacted were placed under an argon atmosphere in a 160 ml Parr autoclave (stainless steel V4A) having a magnetically coupled inclined blade stirrer (stirring speed: 200-500 revolutions/minute). The indicated amount of ammonia was introduced at room temperature either in precondensed form or directly from the pressurized NH3 gas bottle. If hydrogen was used, this was effected by iterative differential pressure metering. The steel autoclave was electrically heated to the temperature indicated and heated for the time indicated while stirring (500 revolutions/minute) (internal temperature measurement). After cooling to room temperature, venting the autoclave and outgassing the ammonia at atmospheric pressure, the reaction mixture was analyzed by GC (30m RTX5 amine 0.32 mm 1.5 mum). Purification of the particular products can, for example, be carried out by distillation. The results for the amination of 1,4-butanediol (table 1a, 1b), diethylene glycol (table 2) and monoethylene glycol (table 3), 2,5-furandimethanol (table 4), alkyldiols (table 5), 1,4-bis(hydroxymethyl)-cyclohexane (table 6) and aminoalcohols (table 7) are given below.
With ammonia;chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); In para-xylene; water; at 180℃; under 37503.8 Torr; for 12h;Autoclave;Product distribution / selectivity;
EXAMPLES; General Procedure for the Catalytic Amination According to the Invention of Alcohols with AmmoniaLigand L, metal salt M or catalyst complex XIVb (for preparation see below, weighing in under inert atmosphere), solvent (sufficient for the total solvent volume to be 50 ml) and the alcohol to be reacted were introduced as initial charge under an Ar atmosphere in a 160 ml Parr autoclave (stainless steel V4A) with magnetically coupled slanted-blade stirrer (stirring speed: 200-500 revolutions/minute). The stated amount of ammonia was either precondensed at room temperature or directly metered in from the NH3 pressurized-gas bottle. If hydrogen was used, this was carried out by means of iterative differential pressure metering. The steel autoclave was heated electrically up to the stated temperature and heated (internal temperature measurement) for the stated time with stirring (500 revolutions/minute). After cooling to room temperature, decompressing the autoclave and outgassing the ammonia at atmospheric pressure, 5 or 50 ml of water were added, whereupon two liquid phases were obtained, which were separated by means of phase separation. The reaction mixture was analyzed by means of GC (30 m RTX5 amine 0.32 mm 1.5 mum). The ruthenium content of the respective liquid phase was ascertained by means of atomic absorption spectroscopy. The results for the amination of 1,4-butanediol (Table 1), diethylene glycol (Table 2) and monoethylene glycol (Table 3) are given below:
With ammonia;chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); In para-xylene; water; at 180℃; under 37503.8 Torr; for 12h;Autoclave;Product distribution / selectivity;
EXAMPLE; General method for the catalytic amination of alcohols by means of ammonia according to the inventionLigand L, metal salt M or catalyst complex XIVb (for preparation, see below, weighed out under an inert atmosphere), solvent and the alcohol to be reacted were placed under an Ar atmosphere in a 160 ml Parr autoclave (stainless steel V4A) having a magnetically coupled inclined blade stirrer (stirring speed: 200-500 revolutions/minute). The indicated amount of ammonia was introduced at room temperature either in precondensed form or directly from the pressurized NH3 gas bottle. If hydrogen was used, this was effected by iterative differential pressure metering. The steel autoclave was electrically heated to the temperature indicated and heated for the time indicated while stirring (500 revolutions/minute) (internal temperature measurement). After cooling to room temperature, venting the autoclave and outgassing the ammonia at atmospheric pressure, the reaction mixture was analyzed by GC (30m RTX5 amine 0.32 mm 1.5 mum). The results for the amination of 1,4-butanediol (tables 1a, 1b and 2), diethylene glycol (tables 3a, 3b and 4), monoethylene glycol (table 5) and diethanolamine (table 6), 1,5-pentanediol, 1,9-nonanediol, 1,6-hexanediol and 1,10-decanediol (table 7) and 2,5-(dimethanol)-furan (table 8) are given below.
With chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); ammonia; In tetrahydrofuran; at 180℃; under 36828.7 Torr; for 12h;Autoclave; Inert atmosphere;Catalytic behavior;
General procedure: Example General Rules on the catalyst amination of alcohol with ammoniaaccording to the present invention (See below for manufacturing, initialweighed under an inert atmosphere) catalyst complex XIVb and, with the solvent(amount of up to solvent total amount reaches the 50ml), and the alcohol thatthe reaction is, under an argon atmosphere, magnetic coupling type tilt wingsParr autoclave of 160ml equipped with a stirrer (made of special steel V4A)(stirring speed: 200 to 500 rev / min) were charged in. At described the amountof ammonia at room temperature, it has been directly metered from thepreliminary condensed with or NH 3 gas cylinder. If hydrogen is used, this wasdone by repeated differential-pressure volume. Steel autoclave is electricheating heated to the temperature indicated, for a period of time described, ithas been heated under stirring (500 rev / min) (internal temperaturemeasurement). The autoclave was cooled to room temperature, depressurized,after performing outgassing of ammonia at atmospheric pressure, the reactionmixture was analyzed by GC (30m RTX5 Amin 0.32mm, 1.5mum). The desired product,for example, can be isolated by distillation.
With chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); ammonia; In para-xylene; water; at 180℃; under 37503.8 Torr; for 12h;Inert atmosphere; Autoclave;
General procedure: Ligand L, see below for the metal salt M or catalyst complex XIVb (manufacturing, inert atmosphere initial mass below), solvent and an alcohol of the reaction, under an argon atmosphere, a magnetic coupling type Parr autoclave of 160ml equipped with atilt wing stirrer (made of special steel V4A) (Stirring speed: were charged to the 200 to 500 rev / min) in. It described theamount of ammonia at room temperature, It is directly metered from the preliminarycondensed with or NH3 gas cylinder. Hydrogenis used Case, this was done by an iterative difference-pressure amount. Power to the temperature indicated the steel autoclave is NetsuNoboru temperature, for a period of time described, has been heated under stirring (500 rev / min) (internal temperature Measurement). The autoclave was cooled to room temperature, depressurized, row outgassing of ammonia at atmospheric pressure after becoming, the reaction mixture was analyzed by GC (30m RTX5 Amin 0.32mm,1.5mum). The amination of 1,4-butanediol result (the first 1a, 1b and the second table), diethylene glycol of the same result (the first 3a, 3b and Table 4), the resultof monoethylene glycol (Table 5), diethanolamine same result (table 6), 1,5-pentanediol, 1,9-nonanediol, 1,6-hexanediol and 1,10-decanediol same result of (table 7), as well as furan-2,5-dimethanol same result (table 8) are as described below.
With ammonia; hydrogen;chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); In toluene; at 135℃; under 42829.3 Torr; for 12h;Autoclave; Cooling;Product distribution / selectivity;
EXAMPLES; General Procedure for the Catalytic Amination According to the Invention of Alcohols with AmmoniaLigand L, metal salt M or catalyst complex XIVb (for preparation see below, weighing in under inert atmosphere), solvent (sufficient for the total solvent volume to be 50 ml) and the alcohol to be reacted were introduced as initial charge under an Ar atmosphere in a 160 ml Parr autoclave (stainless steel V4A) with magnetically coupled slanted-blade stirrer (stirring speed: 200-500 revolutions/minute). The stated amount of ammonia was either precondensed at room temperature or directly metered in from the NH3 pressurized-gas bottle. If hydrogen was used, this was carried out by means of iterative differential pressure metering. The steel autoclave was heated electrically up to the stated temperature and heated (internal temperature measurement) for the stated time with stirring (500 revolutions/minute). After cooling to room temperature, decompressing the autoclave and outgassing the ammonia at atmospheric pressure, 5 or 50 ml of water were added, whereupon two liquid phases were obtained, which were separated by means of phase separation. The reaction mixture was analyzed by means of GC (30 m RTX5 amine 0.32 mm 1.5 mum). The ruthenium content of the respective liquid phase was ascertained by means of atomic absorption spectroscopy. The results for the amination of 1,4-butanediol (Table 1), diethylene glycol (Table 2) and monoethylene glycol (Table 3) are given below:
With chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); ammonia; at 155℃; for 12h;Inert atmosphere; Autoclave;
General procedure: the Ligand L, metal saltM or Catalyst complex XlVb (Forpreparation of the following, weighing in an inert atmosphere), solvent (the sufficienttotal volume of solvent is 50ml) and alcohol reaction as a initialfeedunderargonatmosphereaddedwithmagneticcouplingobliqueinclinedstirrer(mixingspeed:200-500/min)of160ml PARR autoclaves (stainless steel V4A).the mentioned amount of ammonia is Pre-condensedat room temperature or directly from NH3 pressurized gas was added ina measured bottle. Ifhydrogenisused,thenthisis addedthrough the iterationpartial pressure measurement. The steel autoclave under stirring through electricheating mode (500 revolutions per minute)and heated to the mentionedtemperature and reaches the heat time (internal temperature detection). Aftercooling to room temperature, the autoclave was decompressed and dischargedammonia under atmospheric pressure, then added 5 or 50ml of water, wherein theobtaining two liquid phases, they were separated by phase separation. Thereaction mixture was analyzed by GC analysis (30m RTX5 amine 0. 32mml.5mum).Ruthenium content of the corresponding liquid phase is determined throughatomic absorption spectrometry. The results of amine are shown below for 1,4-butanediol(table 1), Diethylene glycol(table 2)and mono Ethylene glycol (table 3).
With sodium carbonate; In tetrahydrofuran; water; at 0℃; for 1.5h;
To a mixture of sodium carbonate (0.210 g, 2 mmol) and 2,2?-oxybis(ethylamine) (0.520 g, 5 mmol) in THF/H2O (3:3 mL), was added a solution of compound 2.4 (MSTLC-NCA) (0.210 g, 0.5 mmol) in THF (6 mL) at 0 C. over 30 min and allowed to stir at room temperature for 1 h as is illustrated in Scheme Q. The reaction mixture was concentrated and water (25 mL) was added. The resulting precipitate was filtered and dried. The crude solid was purified by silica gel column chromatography using methanol/methylene chloride (20:80) to isolate the product compound 4.2 MSTLCB (0.041 g, 55%). IR (KBr, cm-1): 3391, 2954, 1658, 1384, 1250. 1H NMR (300 MHz, CDCl3) delta 7.45-7.17 (m, 12H), 6.85-6.75 (m, 2H), 3.78 (s, 3H), 3.55-3.30 (m, 6H), 3.10-3.00 (dd, J=8.37, 3.97 Hz, 1H), 2.85-2.78 (t, J=5.06 Hz, 2H), 2.76-2.67 (dd, J=4.11, 4.11 (12.62, 4.11) Hz, 1H), 2.60-2.50 (dd, J=12.62, 8.36 Hz, 1H), 1.76 (s, 2H); 13C NMR (75 MHz, CDCl3) delta 172.97, 158.11, 144.86, 136.61, 130.73, 129.46, 127.89, 126.68, 113.16, 72.69, 69.48, 66.41, 55.19, 54.02, 41.53, 38.89, 37.47. HPLC-MS: Elution with 20-80% CH3CN in H2O (gradient 1.5% min-1), exhibited a single peak at 8.32 min. ESI-MS m/z [ES+] calcd for C27H34N3O3S [M+H]+480.17; found 480.22.
For the synthesis of H2L, salicylaldehyde (10 mM, 1.22 g) in EtOH (5 mL) was addeddropwise to a 5 mL EtOH solution of 3-oxapentane-1,5-diamine (10 mM, 1.04 g). Aftercompletion of addition, the solution was stirred for an additional 4 h at 78 C. After coolingto room temperature, the precipitate was filtered. The product was dried in vacuo, giving ayellow crystalline solid. The synthetic route for H2L is shown in scheme 1. Yield: 1.65 g(73.0%). -C18H20O3N2 (312.4): (Found (%): C, 69.30; H, 6.51; N, 8.89. Calcd (%): C,69.21; H, 6.45; N, 8.97). Selected IR data: (KBr nu (cm-1)), 1637(nuC=N), 1286(nuC-O-C), 3458(nuOH), stretching frequency, respectively. UV-vis (DMF): lambda = 275, 311 nm.
68.5%
In ethanol; at 78℃; for 4h;
Salicylicaldehyde (10 mmol, 1.22 g) in EtOH (5 mL) was added dropwise toan EtOH solution (5 mL) of 3-oxapentane-1,5-diamine (5 mmol,0.52 g). After the completion of addition, the solution was stirredfor an additional 4 h at 78 C. After cooling to room temperature,the precipitate was filtered. The product was dried in vacuo, togive a yellow crystalline solid. Yield: 1.2 g (68.5%). Anal. calcd for C18H20O3N2: C, 69.2; H, 6.4; N, 9.0; found: C, 69.1; H, 6.5; N, 8.8%. 1H NMR (CDCl3 400 MHz) delta/ppm: 8.30 (s, 2H, N=C-H), 6.79-7.33 (m,8H, H-benzene ring), 3.66-3.74 (m, 8H, O-(CH2)2-N=C). UV-Vis (lambda,nm): 268, 316. FT-IR (KBr nu/cm-1): 1637, nu(C=N); 1286, nu(C-O-C);3458, nu(OH).
68.5%
In ethanol; at 78℃; for 4h;
For the synthesis of H2L, salicylic aldehyde (10 mM, 1.22 g) in EtOH (5 mL) was added dropwise to 5mL of an EtOH solution of 3-oxapentane-1,5-diamine (5 mM, 0.52 g). After completion of addition, the solution was stirred for an additional 4 h at 78 C. After cooling to room temperature, the precipitate was filtered. The product was dried in vacuo, giving a yellow crystalline solid. Yield: 1.19 g (68.5%).
68.5%
In ethanol; at 78℃; for 4h;
For the synthesis of H2L, salicylic aldehyde (10 mmol, 1.22 g) in EtOH (5 mL) was added dropwise to a 5 mL EtOH solution of 3-oxapentane-1,5-diamine (5 mmol, 0.52 g). After the completion of addition, the solution was stirred for an additional 4 h at 78 C. After cooling to room temperature, the precipitate was filtered. The product was dried in vacuo, and obtained yellow crystalline solid. Yied: 1.19 g (68.5%). Found (%): C, 69.09; H, 6.54; N, 8.83.Calcd. (%) for C18H20O3N2: C, 69.21; H, 6.45; N, 8.97. 1H NMR (CDCl3 400 MHz) delta/ppm: 8.30 (s, 2H, N-C=H), 6.79-7.33 (m, 8H, H-benzene ring), 3.66-3.74 (m, 8H, O-(CH2)2-N=C). UV-Vis (lambda,nm): 268, 316. FT-IR (KBr nu/cm-1): 1637, nu(C=N); 1286, nu(C-O-C); 3458, nu(OH) stretching frequency, respectively.
68.5%
For the synthesis of H2L, salicylic aldehyde (10 mmol, 1.22 g) in EtOH(5 mL) was added dropwise into a 5-mL EtOH solution of 3-oxapentane-1,5-diamine (5 mmol,0.52 g). Then, the solution was stirred for 4 h at 78 C. After cooling to room temperature, the precipitate was filtered. The product was dried in vacuo, and a yellow crystalline solid obtained. Yield: 1.19 g (68.5 %). Calcd. (%) forC18H20O3N2: C, 69.21; H, 6.45; N, 8.97. Found (%): C, 69.09; H, 6.54; N, 8.83.1H NMR (CDCl3 400 MHz) d/ppm: 8.30 (s, 2H, N=C-H), 6.79-7.33 (m, 8H,H-benzene ring), 3.66-3.74 (m, 8H, O-(CH2)2-N=C). UV-Vis (k, nm): 268, 316.FT-IR (KBr m/cm-1): 1,637, m(C=N); 1,286, m(C-O-C); 3,458, m(OH) stretching frequency, respectively.
A 250 mL round bottom schlenk flask was charged with 2,2'-Oxybis(ethylamine) (1.00 mL, 9.4 mmol) and 100 mL of THF and stirred under nitrogen. Triethylamine (14.38 g, 19.81 mL, 141.14 mmol) was added to the flask and the reaction mixture was stirred for 1 hour. Neat chlorodiisopropylphosphine (3.00 mL, 18.82 mmol) was added to the stirring solution dropwise over 5 minutes giving a cloudy white solution. The reaction mixture was stirred for an additional 24 hours before being dried in vacuo. The white solid was then combined with toluene and stirred before being filtered through celite. The clear colourless solution was dried in vacuo giving the desired product as an oily solid. Yield of Ligand (11): 2.61 g (83%).1H NMR(CD2Cl2): 3.45 (t, 4H, 3JHH= 5.55 Hz, O-CH2), 3.11 (d of quart, 4H, 3JHH= 5.55 Hz,3JHP= 8.61 Hz,-CH2-N), 1.61 (sept, 4H, 3JHH = 7.04 Hz,(CH3)2CH), 1.41 (m, 2H, NH), 1.05 (m, 24H, (CH3)2CH). 31P{1H} NMR (CD2Cl2): 65.713C{1H} NMR (CD2Cl2): 73.5 (d, 3JCP = 5.87 Hz, ), 48.9 (d, 2JCP = 24.21 Hz, -CH2-N ), 27.1 (d, 1JCP = 11.74 Hz, (CH3)2CH)), 19.5 (d, 2JCP = 20.54 Hz, (CH3)2CH), 17.7 (d, 2JCP = 8.07 Hz, (CH3)2CH)).
2-(adamantan-1-yl)-N-(2-(2-aminoethoxy)ethyl) acetamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
35%
To a round bottom flask with stirbar was charged 1-adamantaneaceticacid (1.0 g, 9.7 mmol), EDC (1.43 g, 7.5 mmol), HOBt (1.16 g, 7.5 mmol), and 20mL dichloromethane. After 15 minutes of stirring diamine (1.1 g, 10.0 mmol) was5 added and the mixture left stir for 16 h upon which the mixture was diluted with 30mL dichloromethane and washed with saturated Na2C03 (2 X 50 mL). The organiclayer was dried with Na2S04 and concentrated down to yield a crude oil that waspurified by silica gel chromatography ( dichloromethane to 4:1dichloromethane:MeOH (0.5 N NH3)) to yield 520 mg (35% yield) of pure product as10 an amber oil. 1H NMR (300 MHz, CDCh) o 3.50-3.33 (m, 8H), 2.78 (t, J= 5.1,2H), 1,95-1.85 (m, 6H), 1.65-1.45 (m, 9H); 13C NMR (75 MHz, CDCh) o 171.1,77.3, 72.7, 69.7, 51.4, 42,5, 38.9, 36.7, 32.6, 28.6; LRMS (ESI) 281.3 (M+H)+.
2-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)thio)-benzoyl chloride[ No CAS ]
[ 1531591-30-6 ]
[ 1531591-34-0 ]
Yield
Reaction Conditions
Operation in experiment
52.6%; 29.2%
With triethylamine; In dichloromethane; at 0℃; for 1.5h;
General procedure: The parent compound 9 (0.36g, 1mmol) was dissolved in CH2Cl2 (6mL), then oxalyl chloride (4mmol) was added dropwise. The mixture was stirred for 4h at the room temperature. The solvent and excess oxalyl chloride was evaporated to obtain the crude farnesylthiosalicyl chloride. Then to a mixture of different diamines (1.5mmol) and TEA (0.45mmol) in 10mL CH2Cl2 was added dropwise the CH2Cl2 solution (5mL) of farnesylthiosalicyl chloride (1.12g, 0.3mmol) at 0C over 1h. After stirring for another 0.5h the reaction was quenched by adding 20mL water. The mixture was extracted with CH2Cl2 (20mL×3) and the organic layer was combined, washed with brine, dried with anhydrous Na2SO4 and concentrated in vacuo. The crude product was separated by silica gel chromatography (petroleum ether/ethyl acetate=1:1 v/v; then CH2Cl2-MeOH=4:1 as the eluent) to afford compound 10a-g and 11a-g as yellowish oil.
With sodium carbonate; In N,N-dimethyl-formamide; at 20℃;
General procedure for the preparation of compounds 10-15 (B) (0016) The appropriate diamines were added to compound 1a and Na2CO3 (2eq.) with stirring in DMF (5mL). The mixture was stirred overnight at room temperature. After completion, as judged by TLC, the solvent was evaporated under reduced pressure. The mixture was resolved in EtOAc and washed twice with water and brine. The organic layer was dried over Na2SO4, then filtered and concentrated. The crude product was purified by column chromatography (CH2Cl2/MeOH, 25/1 v/v) to give the target compound as a white solid.
3-(4-(3-((benzyloxy)carbonyl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinolin-7-yl)piperazine-1-yl)propanoic acid trifluoroacetate[ No CAS ]
C58H64F2N8O9[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
33%
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In ethyl acetate; N,N-dimethyl-formamide; at 0 - 20℃; for 4h;
DIPEA (0.144 mL, 0.823 mmol) was added to a mixture of 6 (100.0 mg, 0.165 mmol) and 2,2'-oxydiethanamine (14.6 mg, 0.082 mmol) in DMF (0.82 mL) at rt. The mixture was cooled to 0 C before dropwise addition of T3P (0.145 mL, 50 wt % in EtOAc, 0.247 mmol), then let to gradually warm to rt. At 4 hr, volatiles were evaporated, and the reaction quenched with water and MeOH. The mixture was basified with NH4OH, filtered, and purified by reverse-phase HPLC (25-50% ACN in water, 5 mM NH4OH modifier) to afford 33% yield of white solid.
(2E,2<SUP>,</SUP>E)-diethyl 3,3<SUP>,</SUP>-(2,2<SUP>,</SUP>-oxybis(ethane-2,1-diyl)bis-(azandiyl))dibut-2-enoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
In toluene; at 90℃; for 20h;
Mixed nanosized TiO2-SiO2 oxide (0.27 g, 1.9 mmol) was added to a solution of acetoacetic ester (2) (3.75 g,28.8 mmol), <strong>[2752-17-2]1,5-diamino-3-oxapentane</strong> (1a) (1.00 g, 9.6 mmol), and toluene (6 ml). The reaction mixture was stirred for 20 h at 90C. After the reaction was complete (TLC control, eluent 5:4:1 EtOAc-hexane-CHCl3), the nanosized oxide was separated by centrifugation, and toluene was removed by distillation. The obtained oil was purified by silica gel column chromatography, using CHCl3 as eluent, and dried under ambient conditions. Yield 2.33 g (74%), yellow oil. IR spectrum, nu, cm-1: 1141 (nuas, --Alk); 3291 (N-H); 1652,1505 (-O-N); 2930, 2978 (Alk-). 1H NMR spectrum,delta, ppm: 1.12-1.14 (6H, m, 2CH3); 1.90 (6H, s, 2CH3); 3.35-3.39 (4H, m, 2NCH2CH2); 3.51-3.55 (4H, m, 2NCH2CH2); 3.92-3.97 (4H, m, 232); 4.34-4.35 (2, m, 2); 8.59 (2H, s, 2NH). Found, %: 58.46; 8.43; N 8.69.16H28N2O5. Calculated, %: 58.51; 8.59; N 8.53.
9,9'-((1E,1'E)-((oxybis(ethane-2,1-diyl))bis(azanylylidene))bis(methanylylidene))bis(2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-8-ol)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
65%
With hydrogenchloride; In ethanol; water; at 20℃; for 24h;
8-hydroxyjulolidine-9-carboxaldehyde0.91 g (4 mmol) was dissolved in 10 mL of ethanol,With two drops of hydrochloric acid2,2'-oxybis (ethylamine)0.22 mL (2 mmol) was slowly added to the solution. The mixture was stirred at room temperature for one day so that the mixed solution was well mixed. After the solvent was removed under reduced pressure, the crude product obtained was purified by column chromatography using a mixed solution of methylene chloride and methanol (MC: MeOH = 10: 1, v / v) to obtain 0.65 g of pure product. It was analyzed by 1 H-NMR, 13 C-NMR, ESI-MS, and EA to confirm that it had the structure of Formula 1, and the yield was 65%.
bis(3-methoxysalicylidene)-3-oxapentane-1,5-diamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
In ethanol; at 78℃; for 4h;
o-Vanillin (1.82 g, 12 mmol) in EtOH (5 mL) was added dropwise to a 5 mL EtOH solution of3-oxapentane-1,5-diamine (0.52 g, 5 mmol). After the completion of addition, the solutionwas stirred for an additional 4 h at 78C. After cooling to room temperature, the precipitatewas filtered off. The product was dried in vacuo and obtained as a yellow crystalline solid.Yield: 1.59 g (68.0%). Anal. C20H24O5N2: Calcd C, 64.50; H, 6.50; N, 7.52%; found: C, 64.30; H,6.51; N, 7.51%. Selected IR data (KBr, nu/cm-1), 1629(nuC=N), 1256(nuC-O-C), 1047(nuOH). UV-vis(DMF): lambda = 271, 330 nm. Lambdam (DMF, 297 K): 1.7 S cm2 mol-1.
(5) Synthesis of Compound 1 Intermediate 5 (200 mg, 0.35 mmol) and dimethylformamide (4 mL) were added to a 250 mL single-neck reactor and stirred for 5 minutes at room temperature. TSTU (106 mg, 0.35 mmol) and triethylamine (50 muL, 0.35 mmol) were then added to the reactor, followed by stirring at room temperature for 15 minutes. Then, triethylamine (50 muL, 0.35 mmol) and 2,2?-oxybisethylamine (13 muL, 0.119 mmol) were added to the reactor. The mixture was stirred at room temperature for 3 days and poured into ethyl acetate (40 mL) to precipitate a solid. The precipitated solid was filtered and purified by column to obtain Compound 1 (110 mg, 0.0906 mmol, 26%). 1H-NMR (400 MHz, MeOD) delta 8.25 (d, J=6.8 Hz, 2H), 7.77-7.80 (m, 2H), 7.68-7.73 (m, 2H), 7.51-7.54 (m, 4H), 7.41 (t, 2H, J=8.8 Hz, 2H), 7.29-7.35 (m, 2H), 7.16-7.20 (m, 2H), 7.01 (d, J=7.6 Hz, 2H), 5.04-5.11 (m, 2H), 4.60-4.63 (m, 2H), 4.32-4.43 (m, 4H), 4.00-4.09 (m, 2H), 3.44-3.47 (m, 4H), 3.30-3.32 (m, 4H), 2.79-2.82 (m, 2H), 2.35-2.45 (m, 2H), 2.21 (t, J=7.2 Hz, 4H), 1.85-1.92 (m, 4H), 1.61-1.69 (m, 4H), 1.39-1.45 (m, 4H).
Intermediate 5 (507 mg, 1 mmol) and dimethylforamamide (5 mL) were added to a 25 mL 1-necked reactor, and the mixture was stirred at room temperature for 5 minutes. The reactor was charged with TSTU (301 mg, 1 mmol),triethylamine (140 uL, 1 mmol)And the mixture was stirred at room temperature for 15 minutes. Then, in the reactortriethylamine (140 [mu] L, 1 mmol),2,2'-oxybisethylamine (36 mg, 0.340 mmol) was added thereto, followed by stirring at room temperature for 3 days. next, The reaction mixture was poured into ethylacetate (40 mL) to precipitate a solid. The precipitated solid was filtered and the column was purified to obtain the compound1 (170 mg, 0.157 mmol, 15%).
Weigh the product (3) 5g (0.019mol) in a round bottom flask,Add 100ml DMF placed in an ice bath and stirred to dissolve,N-hydroxysuccinimide (NHS, 2.3 g, 0.02 mol)Join the reaction flask to dissolve;(1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC, 3.82 g, 0.02 mol) was added and dissolved with stirring,The reaction was stirred at room temperature for 4h,The carboxyl group in (3) is activated.Then 2,2'-oxybis (ethylamine) (0.88 g, 0.008 mol) was added to the reaction solution,Stir overnight at room temperature.After the reaction was completed, the DMF was removed by rotary evaporation,After adding 50ml of water precipitated a white solid,Stir well and filter to give a white solid, which is dried in vacuo to give product (4) (4.37 g, 82%).
(3β)-N-[2-(2-aminoethoxy)ethyl]-3-acetyloxy-urs-12-en-28-amide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
General procedure: Compound 9 (0.5 mmol) was dissolved in dry DCM (10 mL), cooled to 0 C and oxalyl chloride (3.2 mmol) and dry DMF (2 drops) were added. After warming to 25 C, the mixture was stirred for 1 h. The solvent was removed under reduced pressure, re-evaporated with dry THF (4 15 mL), and the residue was immediately resolved in dry DCM (10 mL). This mixture was then added dropwise to a solution of the amine (3.0 mmol) in dry DCM (2 mL) and stirred at 25 C for 2 h. After usual aqueous work-up, the solvent was removed under reduced pressure, and the crude products were subjected to column chromatography (silica gel, chloroform/methanol mixtures). Compounds 10 and 16-18 were each obtained as colorless solids (78-82%).
N,N'-(oxybis(ethane-2,1-diyl))diacrylamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
52%
With triethylamine; sodium hydroxide; In dichloromethane; water; at 0 - 20℃;Inert atmosphere;
General procedure: (Y., K.; Y et al., Polyacrylamide pseudo crown ethers via hydrogen bond-assisted cyclopolymerization. Journal of Polymer Science Part A: Polymer Chemistry 2016, 54, 3294-3302): In a 25 mL round-bottomed flask, acryloyl chloride (2.5 equiv) was added dropwise to the solution of bis-amine (1.0 equiv) and triethylamine (2.5 equiv) or 6N NaOH solution in water (2.5 equiv) in dichloromethane (0.3-0.5 M) at 0 C under argon. The reaction mixture was stirred at room temperature overnight and the solid obtained was filtered. The filtrate was concentrated and the residue obtained was purified with S1O2 chromatography eluting with MeOH in EtOAc (gradient elution) to effort the title compound as colorless oil.
1 Preparation of non-ionic fluorocarbon surfactant C9F19CONHC2H5OC2H5NHCOC9F19 (abbreviated as CL-1) (amidation reaction)
Take 25-35 mL of toluene into a 100 mL three-necked flask, add 0.52 g (5 mmol) of 2,2'-oxybis(ethylamine), 6.17 g (12 mmol) of perfluorodecanoic acid, and react at reflux at elevated temperature for 48 h. After the reaction is over, cool to room temperature, use a rotary evaporator to remove volatile solvents and water at 70 °C, recrystallize with dichloromethane: ethanol at a ratio of 3:1, filter under reduced pressure, and finally obtain the product by vacuum drying The white powdery solid non-ionic fluorocarbon surfactant C9F19CONHC2H5OC2H5NHCOC9F19 has a yield of 84.61%.
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