Home Cart 0 Sign in  

[ CAS No. 93-05-0 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
HazMat Fee +

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type HazMat fee for 500 gram (Estimated)
Excepted Quantity USD 0.00
Limited Quantity USD 15-60
Inaccessible (Haz class 6.1), Domestic USD 80+
Inaccessible (Haz class 6.1), International USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic USD 100+
Accessible (Haz class 3, 4, 5 or 8), International USD 200+
Chemical Structure| 93-05-0
Chemical Structure| 93-05-0
Structure of 93-05-0 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 93-05-0 ]

Related Doc. of [ 93-05-0 ]

Alternatived Products of [ 93-05-0 ]

Product Details of [ 93-05-0 ]

CAS No. :93-05-0 MDL No. :MFCD00007861
Formula : C10H16N2 Boiling Point : -
Linear Structure Formula :- InChI Key :QNGVNLMMEQUVQK-UHFFFAOYSA-N
M.W : 164.25 Pubchem ID :7120
Synonyms :

Calculated chemistry of [ 93-05-0 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.4
Num. rotatable bonds : 3
Num. H-bond acceptors : 0.0
Num. H-bond donors : 1.0
Molar Refractivity : 54.67
TPSA : 29.26 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.74 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.96
Log Po/w (XLOGP3) : 2.2
Log Po/w (WLOGP) : 2.12
Log Po/w (MLOGP) : 2.1
Log Po/w (SILICOS-IT) : 1.35
Consensus Log Po/w : 1.95

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.42
Solubility : 0.63 mg/ml ; 0.00383 mol/l
Class : Soluble
Log S (Ali) : -2.45
Solubility : 0.585 mg/ml ; 0.00356 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.95
Solubility : 0.185 mg/ml ; 0.00112 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 2.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.0

Safety of [ 93-05-0 ]

Signal Word:Danger Class:8,6.1
Precautionary Statements:P261-P280-P301+P310-P305+P351+P338-P310 UN#:2922
Hazard Statements:H301-H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 93-05-0 ]

* 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 [ 93-05-0 ]

[ 93-05-0 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 27412-71-1 ]
  • [ 93-05-0 ]
  • [ 138023-92-4 ]
  • 3
  • [ 120-22-9 ]
  • [ 93-05-0 ]
YieldReaction ConditionsOperation in experiment
86% With ammonium chloride; aluminium In methanol for 5h; Heating;
With palladium on activated charcoal at 85 - 95℃; Hydrogenation.unter Druck;
With palladium on activated charcoal; ethanol; hydrazine hydrate
With methanol; amalgamated zinc; ammonium chloride
With amalgamated zinc; ethanol; ammonium chloride
With hydrochloride of tin dichloride

  • 4
  • [ 75-03-6 ]
  • [ 93-05-0 ]
  • [ 18996-77-5 ]
YieldReaction ConditionsOperation in experiment
at 100℃;
  • 6
  • [ 90-15-3 ]
  • [ 93-05-0 ]
  • [ 2363-99-7 ]
YieldReaction ConditionsOperation in experiment
89% In acetonitrile at 25℃; aq. phosphate buffer; Electrochemical reaction;
With ethanol; sodium carbonate; silver(I) chloride
  • 7
  • [ 880-29-5 ]
  • [ 93-05-0 ]
  • [ 102321-98-2 ]
  • 8
  • [ 93-05-0 ]
  • [ 38985-79-4 ]
  • 6-bromo-3-(4-diethylamino-phenyl)-2-methyl-3<i>H</i>-quinazolin-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
43% N-Acetyl-5-Bromo anthranilic acid (6.45 g, 0.025 mol) was added to a solution of 4-N,N-(diethylamino) phenylenediamine (3.28 g, 0.025 mol) in toluene (70 ml). POCl3 (15 ml) was added dropwise during 30 min with stirring, and then the reaction mixture was refluxed for 8 h. After cooling to room temperature, the reaction mixture was diluted with cold water, basified with 10% sodium carbonate solution and extracted with chloroform. The organic extract was dried over anhyd. Na2SO4, concentrated and the crude was purified by SiO2 column chromatography. Elution with 70:30 CHCl3: pet ether gave 4.19 g ( 43%) of the product 3, mp. 112-114 C. 1H NMR (300 MHz, CDCl3): delta 1.2 (t, 6H), 3.3 (q, 4H), 6.7 (d, 1H, J=7.2), 7.0 (d, 1H, J=9.0), 7.5 (d, 1H, J=8.7), 7.7 (d, 1H, J=8.7) 7 8.7 (d, 1H). see SI-01Anal. Calc. for C19H20BrN3O; C, 59.08; H, 5.22; N, 10.88; Br, 20.68. Found: C, 59.31; H, 5.11; N, 11.09; Br, 20.44.
  • 9
  • [ 93-05-0 ]
  • [ 54749-15-4 ]
YieldReaction ConditionsOperation in experiment
With oxygen; sodium sulfite
With potassium dichromate; aluminum(III) sulfate; sodium thiosulfate; zinc(II) chloride In water for 2h; Cooling with ice; 1.1 Add p-diethylaminoaniline (6mmol)Dissolve with aluminum sulfate (6mmol) in 10mL water,Under stirring, add zinc chloride (6mmol) and sodium thiosulfate (12mmol) to it, ice-bath protection, add potassium dichromate (2mmol) to the mixed solution, after stirring for 2h, precipitation is seen, filter the reaction solution, take a filter It is heated to reflux in 100 mL methanol for 10 min, and filtered while it is hot to obtain an off-white solid, which can be directly used for the synthesis of phenothiazine dye.
  • 10
  • [ 93-05-0 ]
  • [ 2481-94-9 ]
  • [ 3588-91-8 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; nitrobenzene at 180℃;
  • 13
  • [ 93-05-0 ]
  • [ 108-95-2 ]
  • [ 4704-35-2 ]
YieldReaction ConditionsOperation in experiment
86% In acetonitrile at 25℃; aq. phosphate buffer; Electrochemical reaction;
With ammonium persulfate
With silver(I) chloride
  • 15
  • [ 529-86-2 ]
  • [ 93-05-0 ]
  • 10-<<4-(diethylamino)phenyl>imino>-9(10H)-anthracenone [ No CAS ]
  • 16
  • [ 99970-84-0 ]
  • [ 93-05-0 ]
  • 4,4'-bis((4-diethylaminophenylimino)methyl)-[2,2']-bipyridine [ No CAS ]
  • 17
  • [ 30169-25-6 ]
  • [ 93-05-0 ]
  • [ 67-51-6 ]
  • <i>N</i>-[6-(3,5-dimethyl-pyrazol-1-yl)-[1,2,4,5]tetrazin-3-yl]-<i>N</i>',<i>N</i>'-diethyl-benzene-1,4-diamine [ No CAS ]
  • 18
  • [ 3919-76-4 ]
  • [ 93-05-0 ]
  • [ 543686-34-6 ]
YieldReaction ConditionsOperation in experiment
83% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere;
45% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide for 2h;
45% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In N,N-dimethyl-formamide for 2h; 1 3-(2,6-dichlorophenyl)-N-[4-(diethylamino)phenyl]-5-methylisoxazole-4-carboxamide EXAMPLE 1 3-(2,6-dichlorophenyl)-N-[4-(diethylamino)phenyl]-5-methylisoxazole-4-carboxamide To 3-(2,6-dichloro-phenyl)-5-methyl-isoxazole-4-carboxylic acid (2.2 g, 8.0 mmol) in DMF (10 mL) was added N,N-diethylphenylene diamine (1.4 g, 8.0 mmol), Et3N (0.81 g, 8.0 mmol), and TBTU (2.6 g, 8.0 mmol) at 0° C. After 2 hours, ice chips and 100 mL ethyl acetate were added. Organic layer was washed with water (3*30 mL), dried over MgSO4, and then concentrated under reduced pressure. Purification by column chromatography provided the titled compound (1.5 g, 45%). 1H NMR (300 MHz, CDCl3) δ 7.53 (d, J =9.3 Hz, 1H), 7.53 (d, J=6.9 Hz, 1H), 7.46 (dd, J=6.3, 9.3 Hz, 1H), 7.03 (d, J=8.7 Hz, 2H), 6.69 (br s, 1H), 6.56 (d, J=9.0Hz, 2H), 3.29 (q, J=7.2 Hz, 4H), 2.85 (s, 3H), and 1.1 (t, J=7.2 Hz, 6H); MS (ESI) positive ion 418(M+H)+, 420 (M+H)+; negative ion 416 (M-H)-, 418 (M-H)-.
With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 20℃;
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;

  • 19
  • [ 93-05-0 ]
  • [ 774605-58-2 ]
  • 3-(2,6-dichlorophenyl)-N-[4-(diethylamino)phenyl]-5-isopropylisoxazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
45.7% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 14h; 14.C 3-(2,6-dichlorophenyl)-N-[4-(diethylamino)phenyl]-5-propylisoxazole-4-carboxamide EXAMPLE 14C 3-(2,6-dichlorophenyl)-N-[4-(diethylamino)phenyl]-5-propylisoxazole-4-carboxamide Compound 14B (308 mg, 1.08 mmol), N,N-diethyl-1,4-phenylenediamine (249 mg, 1.52 mmol), TBTU (485 mg, 1.51 mmol), and i-Pr2NEt (196 mg, 1.52 mmol) were dissolved in DMF (2 mL). The mixture was stirred for 14 hours and prurified by reverse phase HPLC (0-70% acetonitrile in 0.1% aqueous NH4OAc) providing the titled compound 14C (220 mg, 45.7%). 1H NMR (300 MHz, DMSO-d6) δ 1.04 (t, J=6.95 Hz, 6 H), 1.37 (d, J=7.12 Hz, 6 H), 3.28 (q, J=6.78 Hz, 4 H), 3.62 (m, J=6.78 Hz, 1 H), 6.59 (d, J=9.16 Hz, 2 H), 7.27 (d, J=8.82 Hz, 2 H), 7.53 (dd, J=9.49, 6.44 Hz, 1 H), 7.60 (d, J=6.78 Hz, 1 H), 7.61 (d, J=9.16 Hz, 1 H), 9.70 (s, 1 H). MS (ESI) positive ion; m/z 468 (M+Na)+, 446 (N+H)+, 417 (M-Et)+: negative ion; m/z 444 (M-H)-.
With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 20℃;
  • 20
  • [ 1136-45-4 ]
  • [ 93-05-0 ]
  • N-[4-(diethylamino)phenyl]-5-methyl-3-phenylisoxazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% A solution of <strong>[1136-45-4]5-methyl-3-phenylisoxazole-4-carboxylic acid</strong> (8.00 g, 39.4 mmol) and DMF (200 mL) was cooled to 0-10 C. N,N-Diethyl-p-phenylenediamine (6.47 g, 39.4 mmol) and O-ibenzotriazol- l-yl)-N,N,N',N' -tetramethyluronium tetrafluoroborate (TBTU, 15.17 g, 47.3 mmol, 1.2 equiv.) were added to the reaction mixture and the mixture was stirred at 0-10 C for 10 min. Nu,Nu-Diisopropylethylamine (DIPEA, 6.11 g, 47.3 mmol, 1.2 equiv.) was slowly added, and the mixture was stirred at 0-10C for 2.5 h. Ethyl acetate (400 mL) and a 5% aqueous NaHC03-solution (160 mL) were added to the reaction mixture and the mixture was stirred at ambient temperature for 15 min. The layers were separated and the organic phase was washed with water (3 x 200 mL) and brine (180 mL). The organic layer was dried with sodium sulphate, the drying agent was filtered off and the solution was evaporated to dryness to give 12.8 g of the crude product. The crude product was dissolved in warm ethyl acetate (300 mL) and activated carbon (0.5 g) was added to the solution. The mixture was stirred for 20 min and filtered through Celite. n-Heptane (120 mL) was added to the previous solution at 55 C and the mixture slowly cooled to 0-5 C. The precipitated product was filtered off, washed with n-heptane (2 x 50 mL) and dried in vacuo at 45 C overnight to give 8.52 g (62 %) off-white powder. M.p. 139.3-140.2 C. 1H NMR (200 MHz, DMSO-d6) delta 10.12 (s, 1H, NH), 7.71 (m, 2H, arom), 7.50-7.35 (m, 5H arom.), 6.63 (d, 2H, arom.), 3.30 (q, 4H, 2 x CH2), 2.55 (s, 3H, CH3), 1.05 (t, 6H, 2 x CH3) ppm. MS: m/z 350.2 (100%, M+l), 351.2 (25%).
  • 21
  • [ 91182-87-5 ]
  • [ 93-05-0 ]
  • 3-(4-chloro-phenyl)-5-methyl-isoxazole-4-carboxylic acid (4-diethylamino-phenyl)-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;
  • 22
  • [ 93041-44-2 ]
  • [ 93-05-0 ]
  • 3-(2-methoxy-phenyl)-5-methyl-isoxazole-4-carboxylic acid (4-diethylamino-phenyl)-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;
  • 23
  • [ 92545-95-4 ]
  • [ 93-05-0 ]
  • 3-(3-chloro-phenyl)-5-methyl-isoxazole-4-carboxylic acid (4-diethylamino-phenyl)-amide [ No CAS ]
  • 24
  • [ 6068-70-8 ]
  • [ 93-05-0 ]
  • <i>N</i>-(4-diethylamino-phenyl)-2,2,2-triphenyl-acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With dmap; triethylamine In dichloromethane for 48h;
  • 25
  • [ 93-05-0 ]
  • N,N-diethyl-p-phenylenediamine-N\-poly(ethylene glycol) amide, Mw ca. 2000 [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With dmap In dichloromethane at 20℃;
  • 26
  • [ 93-05-0 ]
  • [ 93739-14-1 ]
YieldReaction ConditionsOperation in experiment
72% With hydrogenchloride; potassium dichromate; aluminum(III) sulfate; sodium thiosulfate; zinc(II) chloride In methanol; water at 0 - 20℃; for 4h; 1 Embodiment 1 compound 7:2 - amino -5 - (diethyl amino) over oxygen sulfo- benzene sulphur acid O - (benzenesulfonoperoxothioic O - acid) The 1.2 ml HCl (10 mol/L) added to the N, N - diethyl-para-phenylene diamine - 6 (2.01 g, 12.0 mmol) of water and methanol (24 ml, H2 O/MeOH 4:1) in the solution, and the mixture stirred at room temperature. Aluminum sulfate solution (4.31 g, 12.6 mmol in 10 ml water), ZnCl2 (1.72 G, 12.6 mmol in 2 ml water) is added under stirring to the above solution. The reaction mixture is cooled to 0 °C, then add the new preparation of the sodium thiosulfate aqueous solution (3 N, 8 ml), stirring 5 min after, slowly add the new preparation of potassium dichromate solution (0.5 N, 7.2 ml) and in 0 °C under stirring 3 h, then raising the temperature to room temperature and stirring 1 h, obtain a thick precipitate. The reaction mixture is filtered, and water and acetone washing gray solid, under the vacuum drying, to obtain 7 gray solid (2.39 g, 72%), and in this connection is used for the next step.
60% With potassium dichromate; aluminum(III) sulfate; sodium thiosulfate; zinc(II) chloride
47% With potassium dichromate; aluminum(III) sulfate; Sodium thiosulfate pentahydrate; zinc(II) chloride In methanol; water for 2h; Cooling with ice; Reflux; 1.1 (1) Synthesis of Intermediate i In 10 mL aqueous solution, 4-amino-N,N-diethyl aniline (6.09 g) and aluminum sulfate (4.11 g) are added. Then, the sodium thiosulfate (2.21 g) and zinc chloride (0.872 g) are added into the flask under ice bath. After that, 4 mL potassium dichromate aqueous solution (0.42 mmol) is slowly added and, continue to stir for 2 hours. After the reaction is finished, the crude produces are filtered, getting t a gray-black solid. Then, the filter cake is washed with acetone and ether, and then refluxed in 10 mL methanol for 20 minutes. 0.76 g light grey solid product is obtained after filtering, with a yield of 47%.
45% With sodium persulfate; Sodium thiosulfate pentahydrate In methanol; water at 5 - 22℃; for 4.25h; 4 2-amino-5-diethylaminophenyl thiosulfonic acid (6)(i): Na2S2O3 SH2O, Na2S2O8, H2O, MeOH, 5 0CΛ/',Λ/'-diethyl-p-phenylenediamine (5 g, 0.030 mols) was added to a round bottom flask. To this was added de-ionised water (80 ml) and methanol (20 ml) and the solution was then cooled to 5 0C. Sodium thiosulfate (8.31 g, 0.033 mols) in water (20 ml) was added to the solution in one aliquot. Sodium persulfate (7.25 g, 0.030 mols) in water (40 ml) was added drop-wise over a 15 minute period. The reaction mixture was stirred for 3 hours at 5 0C and then warmed to 22°C over a period of 1 hour. The dark brown solid which precipitated was collected via filtration. The dark brown solid was washed with water (50 ml) then dried under vacuum (1000 mbar) at 40 0C for 16 hours, 4.43 g (52 %).2-amino-5-diethylaminophenyl thiosulfonic acid was added to a round bottom flask and ethyl acetate (240 ml) was added. The slurry was heated to reflux for one hour and then cooled to a temperature between 18-22 CC. Once the solution had cooled to the desired temperature the purple solid was collected via filtration. The purple solid was washed with ethyl acetate (50 ml) and the solid was dried under vacuum (1000 mbar) at 40 0C for 16 hours, 4.2 g.Final yield = 49 % Actual value = 45 % by NMR with internal standard (DSS)Mp: 203-204 0C vmax (KBr)/crτ1: 3434 (N-H, St)13336 (N-H1 St), 2985 (C-H, St), 1624 (C=C1 St), 1470(C-C OrO=S=O), 1182 (O=S=O), 1019 (O=S=O). δH(400 MHz1 DMSO-de) 1.021 (6 H1 1, N-CH2CH3), 3.44 (m, 4H1 N-CH2CH3 ), 6.86-6.88(d, 1 H1 Ar-H- J*8 = 8.0 Hz)1 7.16-7.18 (d, 1 H1 Ar-H J*B = 8.4 Hz), 7.40 (s, 1 H, Ar-H).Mass Spec (m/z) ESI high resolution: calculated: 299.0495, found: 299.0503 [M +Na]+; 197.1 1 12 [(M + H)-SO3J+.
Stage #1: N,N-diethylaniline With sodium dichromate; sulfuric acid; zinc(II) chloride In water Stage #2: With aluminum(III) sulfate; sodium thiosulfate In water at 40℃; 6 A stirred mixture of λ/,λ/-diethyl-p-phenylenediamine (5.0 g, 30.4 mmol) in H2O (100 cm3) and H2SO4 (cone, '98 %', 1 cm3) was treated with non-reducing ZnCI2 solution (ZnCI2, 7.60 g, 55 mmol in 15 cm3 of H2O with Na2Cr207.2H20, 100 mg) to produce a reddish reaction mixture. Additions of AI2(SO4)3.16H2O solution (5.80 g, 9.2 mmol in 10 cm3 of H2O), Na2S2O3.5H2O solution (8.0 g, 32.2 mmol in 10 cm3 H2O) and one-third of a solution of Na2Cr207.2H20 (8.7 g, 29.2 mmol in 15 cm3 of H2O) were followed by a rapid rise in temperature to 4O0C. A solution of N,λ/-diethylaniline (3.0 g, 20.1 mmol in cone. HCI, 4 cm3) was added, and followed by an addition of the remaining Na2Cr207.2H20 solution. A dark green precipitate was observed. The temperature was rapidly raised to 75°C, after which a slurry of activated MnO2 (3.80 g, 44.7 mmol in 5 cm3 of H2O) was added. The temperature was raised to 85°C, and left to stir at that temperature for 30 minutes. A blue solution with precipitate was observed. The reaction mixture was cooled to 500C and H2SO4 (cone, 11cm3) was slowly added. The reaction was further cooled to 2O0C, and vacuum filtered to recover the precipitate, which was then washed with brine (saturated salt water). This black solid was re-dissolved in H2O (250 cm3) at 1000C, and cooled, followed by vacuum filtration to remove insolubles. The filtrate was treated with ZnCI2 (4 g) and NaGI (23 g) and left in the refrigerator for 16 hours, after which the resulting precipitate was recovered by vacuum filtration, washed with brine (30 cm3), and dried in a vacuum oven for 3 hours, to give the title compound (5.7 g, 71 %) as a rusty red powder. δH (250 MHz, D2O): 1.20 (12H, br t, CH3), 3.50 (8H, br q, CH2), 6.80 (2H, s, ArH), 7.05 (2H, br d, ArH) and 7.30 (2H, br d, ArH). See, for example, Fierz-David and Blangley, 1949, "F. Oxazine and Thiazine Dyes," in: Fundamental Processes of Dye Chemistry, published by lnterscience (London, UK), pp. 308-314.
With hydrogenchloride; sodium hydroxide; sodium dichromate; sodium thiosulfate In water at 5℃; for 0.25h; 9; 11 Synthesis 9 Ethyl-thioninium iodide (ETI) A stirred mixture of /V,/V-diethyl-p-phenylenediamine (10.0 g, 61 mmol) in aqueous hydrochloric acid (0.5 M, 200 cm3) was adjusted to pH 2 with aqueous sodium hydroxide (10%). The diamine solution was cooled to 5°C before the addition of aqueous Na2S2O3-SH2O (16.65 g, 67 mmol in 20 cm3 H2O). An aqueous solution of Na2Cr207.2H20 (7.27 g, 24 mmol in 35 cm3 of H2O) was added dropwise to the mixture over a 15 minute period giving a black suspension. The suspension was stirred at 5°C for 1 hour (pH = 8.07, T = 3.7°C). A solution of λ/,λ/-diethylaniline (8.25 g, 61 mmol), H2SO4 (6 g) and water (10 cm3) was cooled to 5°C before addition to the suspension. An aqueous solution of Na2Cr207.2H20 (19.09 g, 64 mmol in 50 cm3 of H2O) was then added dropwise to the mixture over a 20 minute period giving a thick dark green suspension. The mixture was stirred at 5°C for 2 hours (pH = 6.75, T = 6°C) before filtering. The green purple solid obtained was washed with water (2 x 50 cm3). The solid was slurried in aqueous hydrochloric acid (300 cm3, pH 2) giving a suspension with a pH = 6.37 at 220C. To the suspension was added CuSO4 (1.52 g, 6.1 mmol) and the mixture heated to 900C where a deep blue solution formed. After stirring at this temperature for 1 hour the mixture was cooled to 250C and filtered. The solid was washed with water (2 x 50 cm3), the filtrate was adjusted from pH 6.33 to pH 2.00, T = 25°C with hydrochloric acid (5 M). The deep blue solution was heated to 8O0C and potassium iodide (14 g) was added and upon cooling an orange purple precipitate was deposited. Filtration gave a purple powder (8.8 g, 31%), which was recrystallised from hot ethanol (400 cm3) to give the title compound as fine purple needles. Mp 2110C; vmax (KBr)/cnT1: 3574 (CH), 3484 (CH), 3028 (CH), 2965 (CH), 1662 (C=C), 1539 (CH), 1474 (CH), 1346 (CH); δc (62.9 MHz, CDCI3): 1.33 (12H, t, 7, CH3), 3.72 (8H, q, 7, NCH2), 7.23 (2H, d, 9.75, ArH), 7.41 (2H, s, ArH), 7.83 (2H, d, 9.75, ArH); δH (62.9 MHz, CDCI3):152.4, 138.8, 135.7, 135.2, 118.3, 106.4, 46.8, 13.2.; Svnthesis 11 Ethyl-thioninium nitrate (ETN)A stirred mixture of λ/,λ/-diethyl-p-phenylenediamine (10.0 g, 61 mmol) in aqueous hydrochloric acid (0.5 M, 200 cm3) was adjusted to pH 2 with aqueous sodium hydroxide (10%). The diamine solution was cooled to 5°C before the addition of aqueous Na2S2O3-SH2O (16.65 g, 67 mmol in 20 cm3 H2O). An aqueous solution of Na2Cr207.2H20 (7.27 g, 24 mmol in 35 cm3 of H2O) was added dropwise to the mixture over a 15 minute period giving a black suspension. The suspension was stirred at 5°C for 1 hour (pH = 8.07, T = 3.70C). A solution of λ/,/V-diethylaniline (8.25 g, 61 mmol), H2SO4 (6 g) and water (10 cm3) was cooled to 50C before addition to the suspension. An aqueous solution of Na2Cr207.2H20 (19.09 g, 64 mmol in 50 cm3 of H2O) was then added dropwise to the mixture over a 20 minute period giving a thick dark green suspension. The mixture was stirred at 50C for 2 hours (pH = 6.75, T = 60C) before filtering. The green purple solid obtained was washed with water (2 x 50 cm3). The solid was slurried in aqueous hydrochloric acid (300 cm3, pH 2) giving a suspension with a pH = 6.37 at 22°C. To the suspension was added CuSO4 (1.52 g, 6.1 mmol) and the mixture heated to 90°C wherein a deep blue solution formed. After stirring at this temperature for 1 hour, the mixture was cooled to 25°C and filtered. The solid was washed with water (2 x 50 cm3), the and the filtrate was adjusted from pH 6.33 to pH 2.00, T = 25°C with hydrochloric acid (5 M). The deep blue solution was heated to 800C and had sodium nitrate (50 g) added and was allowed to cool to 25°C slowly while stirring gently. The product was filtered as green needles (6.80 g, 28%). δH (250 MHz, CDCI3): 1.36 (12H, t, 7, CH3), 3.72 (8H, q, 7, NCH2), 7.23 (2H, d, 9.5, ArH), 7.39 (2H, s, ArH), 7.89 (2H, d, 9.5, ArH); δH (62.9 MHz, CDCI3): 152.5, 138.8, 135.7, 135.6, 118.1, 106.4, 46.6, 12.9.
Stage #1: N,N-diethylaniline With sodium dichromate dihydrate; sulfuric acid; zinc(II) chloride In water Stage #2: With aluminum(III) sulfate; Sodium thiosulfate pentahydrate; sodium dichromate dihydrate In water at 40℃; 1.6 Ethyl-thioninium chloride zinc chloride double salt (ETZ) Ethyl-thioninium chloride zinc chloride double salt (ETZ) A stirred mixture of N,N-diethyl-p-phenylenediamine (5.0 g, 30.4 mmol) in H2O (100 cm3) and H2SO4 (conc., '98 %', 1 cm3) was treated with non-reducing ZnCl2 solution (ZnCl2, 7.60 g, 55 mmol in 15 cm3 of H2O with Na2Cr2O7.2H2O, 100 mg) to produce a reddish reaction mixture. Additions of Al2(SO4)3·16H2O solution (5.80 g, 9.2 mmol in 10 cm3 of H2O), Na2S2O3·5H2O solution (8.0 g, 32.2 mmol in 10 cm3 H2O) and one-third of a solution of Na2Cr2O7·2H2O (8.7 g, 29.2 mmol in 15 cm3 of H2O) were followed by a rapid rise in temperature to 40°C. A solution of N,N-diethylaniline (3.0 g, 20.1 mmol in conc. HCl, 4 cm3) was added, and followed by an addition of the remaining Na2Cr2O7·2H2O solution. A dark green precipitate was observed. The temperature was rapidly raised to 75°C, after which a slurry of activated MnO2 (3.80 g, 44.7 mmol in 5 cm3 of H2O) was added. The temperature was raised to 85°C, and left to stir at that temperature for 30 minutes. A blue solution with precipitate was observed. The reaction mixture was cooled to 50°C and H2SO4 (conc., 11cm3) was slowly added. The reaction was further cooled to 20°C, and vacuum filtered to recover the precipitate, which was then washed with brine (saturated salt water). This black solid was re-dissolved in H2O (250 cm3) at 100°C, and cooled, followed by vacuum filtration to remove insolubles. The filtrate was treated with ZnCl2 (4 g) and NaCl (23 g) and left in the refrigerator for 16 hours, after which the resulting precipitate was recovered by vacuum filtration, washed with brine (30 cm3), and dried in a vacuum oven for 3 hours, to give the title compound (5.7 g, 71 %) as a rusty red powder. δH (250 MHz, D2O): 1.20 (12H, br t, CH3), 3.50 (8H, br q, CH2), 6.80 (2H, s, ArH), 7.05 (2H, br d, ArH) and 7.30 (2H, br d, ArH). See, for example, .
Stage #1: N,N-diethylaniline With aluminum(III) sulfate Stage #2: With sodium thiosulfate; zinc(II) chloride Stage #3: With potassium dichromate

  • 27
  • [ 93-05-0 ]
  • 1-[5-[(Z)-2-cyano-2-(3,4-dimethoxy-phenyl)-vinyl]-thiophen-2-yl]-piperidin-4-yl N-(4-diethylamino-phenyl)-succinamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
49% Stage #1: mono-(1-{5-[(Z)-2-cyano-2-(3,4-dimethoxy-phenyl)-vinyl]-thiophen-2-yl}-piperidin-4-yl)succinate With 4-methyl-morpholine; 2-chloro-4,6-dimethoxy-1 ,3,5-triazine In dichloromethane at 0℃; for 0.5h; Stage #2: N,N-diethylaniline In dichloromethane at 20℃; for 17h; Production of 1-[5-[(Z)-2-cyano-2-(3,4-dimethoxy-phenyl)-vinyl]-thiophen-2-yl]-piperidin-4-yl N-(4-diethylaminophenyl)-succinamate (Compound 99) Production of 1-[5-[(Z)-2-cyano-2-(3,4-dimethoxy-phenyl)-vinyl]-thiophen-2-yl]-piperidin-4-yl N-(4-diethylaminophenyl)-succinamate (Compound 99) Compound 18 (500 mg) was dissolved in methylene chloride (10 mL), and 2-chloro-4,6-dimethoxy-1,3,5-triazine (224 mg) and N-methylmorpholine (129 mL) were added to the solution, followed by stirring with ice cooling for 30 minutes. Subsequently, N,N-diethyl-1,4-phenylenediamine (209 mL) and N-methylmorpholine (215 mL) were added to the mixture, followed by stirring at room temperature for 17 hours. The solvent was evaporated to dryness, and the residue was purified by silica gel column chromatography (CHCl3-MeOH), to thereby yield the target product (yield: 322 mg, 49%). Yellow powder MS(ESI,m/z):617(M+H)+ 1H-NMR(CDCl3)δ:7.91(1H,s),7.40(1H,d,J=4.4),7.30(2H,d,J=8.5), 7.17(1H,d,J=2.2),7.09(1H,dd,J=2.2,8.3),7.00(1H,d,J=8.8), 6.57(2H,d,J=8.8),6.27(1H,d,J=4.1),4.91-4.95(1H,m), 3.83(3H,s),3.78(3H,s),3.44-3.49(2H,m),3.25-3.30(6H,m), 2.57-2.60(4H,m),1.91-1.97(2H,m),1.71-1.74(2H,m), 1.03(6H,t,J=6.8)
  • 28
  • [ 145013-05-4 ]
  • [ 93-05-0 ]
  • N-[2,3-di(tert-butoxycarbonyl)guanidino]-4-(N,N-diethylamino)benzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With triethylamine; mercury dichloride In dichloromethane at 0 - 20℃; for 19h;
  • 29
  • [ 173300-83-9 ]
  • [ 93-05-0 ]
  • 1-[1,3-di(tert-butoxycarbonyl)-2-imidazolidinylimino]-4-(N,N-diethylamino)benzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With triethylamine; mercury dichloride In dichloromethane at 0 - 20℃; for 26h;
  • 30
  • C13H10FNO2 [ No CAS ]
  • [ 93-05-0 ]
  • N-(4-Diethylamino-phenyl)-2-(4-fluoro-phenyl)-2-pyridin-4-yl-acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 23℃; for 18h; 2.B Step B Step B: 1-(3-dimethylamino)propyl-3-ethylcarbodiimide hydrochloride (EDC, 136 mg, 0.71 mmol, 1.2 equiv) was added to a solution of the crude acid (0.59 mmol, 1.0 equiv), N,N-diethyl-1,4-phenylenediamine (97 mg, 0.59 mmol, 1.0 equiv) and 1-hydroxybenzotriazole (HOBT, 120 mg, 0.89 mmol, 1.5 equiv) in dichloromethane (6 mL) at 23° C. The reaction mixture was stirred at 23° C. for 18 hours, diluted with ethyl acetate (50 mL), washed once with 1N sodium hydroxide (25 mL) and once with 1N hydrochloric acid (25 mL). The organics were dried over magnesium sulfate and concentrated. The residue was purified by flash column chromatography (10% THF/hexanes grading to 20% THF/hexanes) to provide N-(4-Diethylamino-phenyl)-2-(4-fluoro-phenyl)-2-pyridin-4-yl-acetamide (50 mg). MS: 378 (M+1)
  • 31
  • [ 827022-71-9 ]
  • [ 93-05-0 ]
  • N-(4-(diethylamino)phenyl)-8-methoxy-2-methyl-1,2,3,4-tetrahydronaphthalene-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
8% With ethylmagnesium bromide In tetrahydrofuran at 0℃; for 3h; 2.B Example 2B, N-(4-(Diethylamino)phenyl)-8-methoxy-2-methyl-1,2,3,4-tetrahydronaphthalene-2-carboxamide Example 2B N-(4-(Diethylamino)phenyl)-8-methoxy-2-methyl-1,2,3,4-tetrahydronaphthalene-2-carboxamide The ester from Example 2A (170 mg, 0.73 mmol) was dissolved in THF (2.0 mL) and a solution (3.0 mL) of N,N-Diethyl-benzene-1,4-diamine (332 mg, 2 mmol) and EtMgBr (2.0 mmol) in THF was added at 0° C. The reaction mixture was quenched with aqueous NH4Cl after 3 hours. The mixture was extracted with ethyl acetate (3*1 5 mL) and the combined extracts were dried over MgSO4 and purified by column chromatography to provide the titled compound (30 mg, 8%). 1H NMR (400 MHz, DMSO-D6) δ 9.03 (s, 1H), 7.33 (d, J=9.2 Hz, 2H), 7.03 (t, J=8.0 Hz, 1H), 6.72 (d, J=7.6 Hz, 1H), 6.73 (d, J=8.0 Hz, 1H), 6.58 (d, J=9.2 Hz, 2H), 3.77 (s, 3H), 3.27 (q, J=7.2 Hz, 4H), 3.11 (d, J=17.2 Hz, 1H), 2.74 (t, J=6.4 Hz, 2H), 2.43 (d, J=17.2 Hz, 2H), 2.15 (ddd, J=6.4, 6.4, 13.2 Hz, 1H), 1.73 (ddd, J=7.2, 7.2, 13.6 Hz, 1H), 1.26 (s, 3H), and 1.04 (t, J=7.2 Hz, 6H). MS (ESI) positive ion 367 (M+H)+; negative ion 365 (M-H)-.
  • 32
  • [ 630-88-6 ]
  • [ 93-05-0 ]
  • C40H40N4O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With zinc(II) chloride; calcium oxide In 1-methyl-pyrrolidin-2-one at 150℃; for 96h; VIIIB EXAMPLE VIIIB The process of Example IB was repeated except that N,N-diethyl-1,4-phenylene diamine (obtained from Aldrich Chemical Co., Milwaukee, WI), of the formula [] was used instead of distearyl amine. The N,N-diethyl-1,4-phenylene diamine was present in an amount of 2.5 moles of N,N-diethyl-1,4-phenylene diamine per every one mole of dichlorofluorescein. In addition, 2 moles of zinc chloride were used per every one mole of dichlorofluorescein and 1 mole of calcium oxide was used per every one mole of dichlorofluorescein, the solvent was N-methyl pyrrolidone instead of tetramethylene sulfone, and the reaction mixture was heated to 150°C for 96 hours. The reaction product was then poured into water and filtered and washed with water. It is believed that the product was of the formula [] The ring-opened, or protonated, or free-base form of this colorant is believed to be of the formula [] wherein A is the anion corresponding to the acid used for protonaton. The zwitterionic form of this colorant is believed to be of the formula
  • 33
  • [ 105-45-3 ]
  • [ 93-05-0 ]
  • N-(4-diethylamino-phenyl)-3-oxo-butyramide [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% In xylene at 145℃; for 4h; 9.A N-(4-Diethylamino-phenyl)-3-oxo-butyramide EXAMPLE 9A N-(4-Diethylamino-phenyl)-3-oxo-butyramide N,N-diethyl-1,4-phenylenediamine (2.04 g, 12.2 mmol) and methyl-3-oxo-butanoate (2.82 g, 24.4 mmol) were added to xylenes (8 mL) and heated to 145° C. for 4 hours. The crude mixture was purified by column chromatography (30-60% Ethyl acetate in hexanes) to provide the titled compound 9A (1.36 g, 45%).
  • 34
  • [ 5305-59-9 ]
  • [ 93-05-0 ]
  • [ 872510-67-3 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-amino-6-chloropyrimidine; N,N-diethylaniline With hydrogenchloride In water; isopropyl alcohol at 90℃; for 36h; Stage #2: With potassium carbonate In water; ethyl acetate; isopropyl alcohol at 20℃; 105.A A mixture of 6-chloro-pyrimidin-4-ylamine (0.65 g, 5 mmol), 4-amino-N,N-diethylaniline (0.82mL, 5 mmol), 2-propanol (5 mL) and HCl cone. (0.225 mL, ~2.5 mmol) is shaken for 36 h at90°C. After cooling to room temperature, the reaction mixture is distributed between half-saturated K2CO3-solution and ethyl acetate. The precipitate thus formed is filtered off,washed with H2O and ethyl acetate and dried in vacuo to afford the title compound.Greyish solid, HPLC: tR = 2.37 min (gradient F), ESI-MS: 258.3 [MHf.
  • 35
  • [ 25784-91-2 ]
  • [ 93-05-0 ]
  • [ 352700-49-3 ]
YieldReaction ConditionsOperation in experiment
73% With 2,4-dichlorophenoxyacetic acid dimethylamine 172 N-(4-Diethylaminophenyl)-(2-chloro-5-nitrophenyl)carboxamide Example 172 N-(4-Diethylaminophenyl)-(2-chloro-5-nitrophenyl)carboxamide The title compound (0.66 g, yield 73%) was obtained according to the procedure described in Example 2 using 4-diethylaminoaniline (0.42 g, 2.58 mmol), DMA (5 ml) and 2-chloro-5-nitrobenzoyl chloride (0.62 g, 2.82 mmol). 1H-NMR (400 MHz, DMSO-d6, TMS): δ(ppm) 1.08 (6H, t, J=7.0 Hz), 3.32 (4H, q, J=7.0 Hz), 6.67 (2H, d, J=9.1 Hz), 7.48 (2H, d, J=9.1 Hz), 7.87 (1H, d, J=8.79 Hz), 8.31 (1H, dd, J=2.8, 8.8 Hz), 8.38 (1H, d, J=2.8 Hz), 10.33 (1H, s); MS(FAB) m/z: 347 (M)+, 348(M+H)+.
  • 36
  • [ 93-05-0 ]
  • N,N-diethyl-1,4-phenylenediamine dihydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With hydrogenchloride In diethyl ether; water 1 λ/,λ/-diethyl-p-phenylenediamine (5 g, 30.4 mmol) was dissolved in diethyl ether (25 cm3) and hydrochloric acid (6 cm3, 10 M) was added and the mixture was concentrated to give the title compound (7.22 g, 100%) as a red/brown solid. δH (250 MHz; D2O): 7.68 (4H, m, ArH), 3.69 (4H, q, 7.32, NCH2), 1.11 (6H, t, 7.32, CH3); δc (62.9 MHz; D2O): 12.1 (CH3), 56.4 (NCH2), 126.8 (ArC), 127.6 (ArC), 135.5 (ArC), 139.1 (ArC).
100% With hydrogenchloride In diethyl ether 1.1 N,N-diethyl-p-phenylenediamine dihydrochloride N,N-diethyl-p-phenylenediamine dihydrochloride N,N-diethyl-p-phenylenediamine (5 g, 30.4 mmol) was dissolved in diethyl ether (25 cm3) and hydrochloric acid (6 cm3, 10 M) was added and the mixture was concentrated to give the title compound (7.22 g, 100%) as a red/brown solid. δH (250 MHz; D2O): 7.68 (4H, m, ArH), 3.69 (4H, q, 7.32, NCH2), 1.11 (6H, t, 7.32, CH3); δC(62.9 MHz; D2O): 12.1 (CH3), 56.4 (NCH2), 126.8 (ArC), 127.6 (ArC), 135.5 (ArC), 139.1 (ArC).
With hydrogenchloride In diethyl ether; water 18 Example 18; Ethylthioninium Chloride (ETC) Synthesis using Sodium Sulphide and Iron(lll); ChlorideΛ/,Λ/-diethyl-p-phenylenediamine (H2NC6H4N(CH2CHs)2, MW 164.25, 40 g, 244 mmol) was dissolved in diethyl ether (200 cm3). Hydrochloric acid (40 cm3, 37%) was added. The resulting solution was concentrated by rotary evaporation to give Λ/,Λ/-diethyl-p- phenylenediamine dihydrochloride as a light brown solid (57.76 g, 100%). δH (250 MHz; D2O): 7.68 (2H, m, ArH), 3.45 (4H, q, 7.25, NCH2), 1.19 (6H, t, 7.25, CH3).
  • 37
  • [ 7693-46-1 ]
  • [ 93-05-0 ]
  • [ 916610-38-3 ]
YieldReaction ConditionsOperation in experiment
82% In dichloromethane at 20℃; for 0.5h; 18.a 1-(4-Diethylamino-phenyl)-3-(1-thieno [3,2-d]pyrimidin-4-yl-pyrrolidin-3-yl)-urea a. (4-Diethylamino-phenyl)-carbamic acid 4-nitro-phenyl ester hydrochloride A solution of N,N-diethyl-benzene-1,4-diamine (2.21 g, 13.5 mmol) in DCM (30 mL) was added rapidly dropwise under air over two minutes to a stirred solution of 4-nitrophenyl chloroformate (2.86 g, 14.2 mmol) in DCM (7.4 mL) in an open beaker with rt water bath cooling. The resulting mixture was stirred at rt for 30 min, then filtered. The filter cake was powdered with mortar and pestle, shaken for one minute with DCM (20 mL), filtered, and the filter cake powdered as before to provide the title compound as an easily-handled beige powder (4.037 g, 82%). 1H NMR (400 MHz, DMSO-d6) δ 12.77 (br s, 1H), 10.85 (br s, 1H), 8.33 (m, 2H), 7.81 (m, 2H), 7.72 (m, 2H), 7.57 (m, 2H), 3.52 (m, 4H), 1.04 (t, 6H).
82% In dichloromethane at 20℃; for 0.533333h; 18.a A solution of N,N-diethyl-benzene-1,4-diamine (2.21 g, 13.5 mmol) in DCM (30 mL) was added rapidly dropwise under air over two minutes to a stirred solution of 4-nitrophenyl chloroformate (2.86 g, 14.2 mmol) in DCM (7.4 mL) in an open beaker with rt water bath cooling. The resulting mixture was stirred at rt for 30 min, then filtered. The filter cake was powdered with mortar and pestle, shaken for one minute with DCM (20 mL), filtered, and the filter cake powdered as before to provide the title compound as an easily-handled beige powder (4.037 g, 82%). 1H NMR (400 MHz, DMSO-d6) δ 12.77 (br s, 1H), 10.85 (br s, 1H), 8.33 (m, 2H), 7.81 (m, 2H), 7.72 (m, 2H), 7.57 (m, 2H), 3.52 (m, 4H), 1.04 (t, 6H).
  • 38
  • [ 66826-78-6 ]
  • [ 93-05-0 ]
  • N'-(2,3-dihydro-1-benzofuran-5-yl)-N,N-diethylbenzene-1,4-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 80℃; for 48h; Example 6; Preparation of N'-(2,3-dihydro-1-benzofuran-5-yl)-N,N-diethylbenzene-1,4-diamine; [Show Image] To a flask equipped with a magnetic stirrer, reflux condensor, and nitrogen inlet was added N,N-diethyl-1,4-phenylenediamine (3.35 grams, 20.4 mmoles), <strong>[66826-78-6]5-bromo-2,3-dihydrobenzofuran</strong> (3.4 grams, 17.1 mmoles), tris(dibenzylideneacetone)dipalladium (0) (0.39 grams, 0.43 mmoles), rac-2,2'-bis(diphenylphosphino)-1,1'-binapthyl (2.1 grams, 3.4 mmoles), sodium tert-butoxide (0.71 grams, 1.28 mmoles) and anhydrous toluene (90 mL). The contents of the flask were heated to 80C for two days; cooled to room temperature; and filtered through a pad of silica gel. The silica gel pad was then eluted with dichloromethane (200 mL). The combined organic layers were concentrated in vacuo to yield a dark blue oil. The oil was chromatographed on silica gel, eluting with a hexane/ethyl acetate gradient to afford 4.2 grams of the desired product as a brown oil. 1H NMR (CDCl3) delta 6.6-7.0 (m, 7H), 5.15 (bs, 1H), 4.5 (t, 2H), 3.05-3.2 (m, 6H), 1.1 (t, 6H).
With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 80℃; for 48h; To a flask equipped with a magnetic stirrer, reflux condensor, and nitrogen inlet was added N,N-diethyl-1,4-phenylenediamine (3.35 grams, 20.4 mmoles), <strong>[66826-78-6]5-bromo-2,3-dihydrobenzofuran</strong> (3.4 grams, 17.1 mmoles), tris(dibenzylideneacetone)dipalladium (0) (0.39 grams, 0.43 mmoles), rac-2,2'-bis(diphenylphosphino)-1,1'-binapthyl (2.1 grams, 3.4 mmoles), sodium tert-butoxide (0.71 grams, 1.28 mmoles) and anhydrous toluene (90 mL). The contents of the flask were heated to 80 C. for two days; cooled to room temperature; and filtered through a pad of silica gel. The silica gel pad was then eluted with dichloromethane (200 mL). The combined organic layers were concentrated in vacuo to yield a dark blue oil. The oil was chromatographed on silica gel, eluting with a hexane/ethyl acetate gradient to afford 4.2 grams of the desired product as a brown oil. 1H NMR (CDCl3) delta 6.6-7.0 (m, 7H), 5.15 (bs, 1H), 4.5 (t, 2H), 3.05-3.2 (m, 6H), 1.1 (t, 6H).
  • 39
  • [ 66826-78-6 ]
  • tris(dibenzylideneacetone)dipalladium (0) [ No CAS ]
  • [ 93-05-0 ]
  • N'-(2,3-dihydro-1-benzofuran-5-yl)-N,N-diethylbenzene-1,4-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With nitrogen; sodium t-butanolate; In toluene; Example 6 Preparation of N'-(2,3-dihydro-1-benzofuran-5-yl)-N,N-diethylbenzene-1,4-diamine To a flask equipped with a magnetic stirrer, reflux condensor, and nitrogen inlet was added N,N-diethyl-1,4-phenylenediamine (3.35 grams, 20.4 mmoles), <strong>[66826-78-6]5-bromo-2,3-dihydrobenzofuran</strong> (3.4 grams, 17.1 mmoles), tris(dibenzylideneacetone)dipalladium (0) (0.39 grams, 0.43 mmoles), rac-2,2'-bis(diphenylphosphino)-1,1'-binapthyl (2.1 grams, 3.4 mmoles), sodium tert-butoxide (0.71 grams, 1.28 mmoles) and anhydrous toluene (90 mL). The contents of the flask were heated to 80 C. for two days; cooled to room temperature; and filtered through a pad of silica gel. The silica gel pad was then eluted with dichloromethane (200 mL). The combined organic layers were concentrated in vacuo to yield a dark blue oil. The oil was chromatographed on silica gel, eluding with a hexane/ethyl acetate gradient to afford 4.2 grams of the desired product as a brown oil. 1H NMR (CDCl3) delta 6.6-7.0 (m, 7H), 5.15 (bs, 1H), 4.5 (t, 2H), 3.05-3.2 (m, 6H), 1.1 (t, 6H).
  • 40
  • [ 1003-61-8 ]
  • [ 93-05-0 ]
  • 2-(4-diethylaminophenylazo)thiazole-5-carbaldehyde [ No CAS ]
  • 41
  • [ 79757-26-9 ]
  • [ 93-05-0 ]
  • N-(4-Diethylamino-phenyl)-2-phenyl-2-pyridin-4-yl-acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: N,N-diethylaniline With trimethylaluminum In 1,2-dichloro-ethane; toluene at 23℃; for 0.5h; Stage #2: α-phenyl-4-pyridine acetic acid ethyl ester In 1,2-dichloro-ethane; toluene at 23 - 60℃; for 19h; 1.B Step B Step B:Trimethylaluminum (2.0 mL of a 2.0 M solution in toluene, 4.0 mmol, 3.0 equiv) was added to a solution of N,N-diethyl-1,4-phenylenediamine (0.68 mL, 4.0 mmol, 3.0 equiv) in 1,2-dichloroethane (10 mL). The resultant solution was stirred at 23° C. for 30 minutes, and then phenyl-pyridin-4-yl-acetic acid ethyl ester (330 mg, 1.36 mmol, 1.0 equiv) was added. The reaction mixture was heated to 60° C. for 19 hours, cooled to 23° C., and quenched with 1 N aqueous tartaric acid. The pH of the reaction mixture was adjusted to 5, and the reaction mixture was extracted with three portions of ethyl acetate (50 mL). The combined organic extracts were dried over magnesium sulfate and were concentrated. Purification of the residue by flash column chromatography (20% THF/hexanes grading to 100% THF) provided N-(4-Diethylamino-phenyl)-2-phenyl-2-pyridin-4-yl-acetamide (160 mg). MS: 360 (M+1)
  • 43
  • [ 93-05-0 ]
  • [ 24573-95-3 ]
YieldReaction ConditionsOperation in experiment
87% Stage #1: N,N-diethylaniline With hydrogenchloride; sodium nitrite In water at 0 - 5℃; Stage #2: With sodium azide In water at 5 - 20℃; A solution of NaNO2 (2.07 g, 30 mmol) in 20 mL water was added drop wise to a solution of (4-amino phenyl) diethyl amine (2.0 g, 12 mmol) in 60 mL 4M HCl at 0-5° C. The mixture was stirred at this temperature for 45 min. A solution of NaN3 (1.5 g, 23 mmol) in 20 mL water was slowly added to the mixture at the same temperature. Stirring was continued for 30 min below 5° C. and then overnight at room temperature. The solution was extracted with dichloromethane (50*2) and dried over anhydrous MgSO4. The solvent was removed by rotary evaporation and the solid separated was recrystallized from dichloromethane/methanol. The product obtained as white solid. Yield: 500 mg (87%). mp: 145° C.; 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J=8 Hz 2H) 7.11 (d, J=8.4 Hz, 2H), 3.60 (bs, 2H), 3.24 (bs, 2H), 1.24 (t, J=7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 142.17, 133.51, 124.26, 120.64, 53.67, 10.23, IR (neat); 2977, 2121, 1604, 1312, 1275 cm-1. Anal. Calcd for C10H14N4: C, 63.13; H, 7.42; N, 29.45. Found: C, 63.48; H, 7.31; N, 29.24.
With hydrogenchloride; sodium azide; sodium nitrite In water at 0℃; for 3h;
  • 44
  • [ 24673-56-1 ]
  • [ 93-05-0 ]
  • [ 403710-54-3 ]
YieldReaction ConditionsOperation in experiment
64% To a stirring solution of 3-methylbenzofuran-2-carboxylic acid (50mg, 0.284 mmol) in DMF (2ml) were added HBTU (215mg, 0.568mmol) and HOBt (84mg, 0.624mmol) sequentially. The resulting mixture was stirred at room temperature for 15 mins, after which time N,N diethyl-p-phenylenediamine (103mg, 0.624mmol) was added. The resulting solution was stirred at room temperature for 16 hours. The crude reaction mixture was evaporated to dryness and purified by preparative HPLC-MS to furnish the title compound as colourless oil (58.7 mg, 64% yield). Method A HPLC-MS: MH+ requires m/z=323; Found: m/z=323, Rt=3.22 min (100%). 1H NMR (400 MHz, CDCl3) delta ppm 8.74 (1H, br s, NH), 7.94 (2H, d, J=8.0 Hz, ArH), 7.94 (1H, d, J=8.0 Hz, ArH), 7.45-7.57 (4H, m, ArH), 7.33 (1H, t, J=8.0 Hz, ArH), 3.50-3.60 (4H, q, J=8.0 Hz, -(CH2)2), 2.66 (3H, s, -CH3), 1.13 (6H, t, J=8.0 Hz, - (CH3)2).
  • 45
  • [ 174081-22-2 ]
  • [ 93-05-0 ]
  • [ 1229439-52-4 ]
YieldReaction ConditionsOperation in experiment
22% Stage #1: m-dimethylaminomethanesulfonanilide; N,N-diethylaniline With hydrogenchloride; potassium dichromate In methanol; water Reflux; Stage #2: With hydrogenchloride In water 27 Synthesis 27 3-Diethylamino- 7-dimethylaminophenazinium chloride 3-Diethylamino-7-dimethylaminophenazinium chlorideAdapted from D. F. Gloster, L Cincotta, J. W. Foley, J. Heterocyclic Chem., 36, 1999, 25.Λ/,Λ/-diethyl-1 ,4-phenylenediamine (1.00 g, 6.17 mmol) was added slowly to dilute HCI (700 μl, 32%) in H2O (100 cm3). The mixture was stirred until it was homogeneous. Λ/-[3-(dimethylamino)phenyl]methanesulphonamide (1.32 g, 6.17 mmol) in methanol (60 cm3) was added, followed by a saturated aqueous solution of potassium dichromate (2 cm3). The mixture refluxed for 15 min. The mixture was cooled and diluted with water (200 cm3), acidified with hydrochloric acid (1 M) and then extracted with chloroform (6 x 30 cm3). The combined extracts were dried over sodium sulphate, filtered and the solvent removed-under-reduced-pressure.-Column-chromatography- (1 :9 methanol/dichloromethane) gave the target material as a green solid (451 mg, 22%).δH (250 MHz, CDCI3): 7.85 (2H, d, J = 10 Hz, 2ArH), 7.30 - 7.25 (2H, m, 2ArH), 6.97 (2H, s, 2ArH)1 3.51 (4H, q, J = 7 Hz, 2CH2), 3.13 (6H, s, 2CH3), 1.26 (6H, J = 7 Hz, 2CH3); m/z (ESI): 295 (26%, [M-Cl]+), 324 (100%).
  • 46
  • [ 91-66-7 ]
  • [ 93-05-0 ]
  • ethylthioninium chloride zinc chloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: N,N-diethylaniline With sodium dichromate; sulfuric acid; zinc(II) chloride In water Stage #2: With aluminum(III) sulfate; sodium dichromate; sodium thiosulfate In water at 40℃; Heating / reflux; Stage #3: N,N-diethylaniline With hydrogenchloride; sodium dichromate; sodium chloride; zinc(II) chloride more than 3 stages; 20 Example 20; Ethylthioninium Chloride (ETC); Zinc Chloride (Double Salt)Synthesis using Manganese Dioxide; A stirred mixture of Λ/,Λ/-diethyl-p-phenylenediamine ((CH3CH2)NC6H4NH2, MW 164.25, 5.0 g, 30.4 mmol) in H2O (100 cm3) and sulfuric acid (H2SO4, concentrated, "98%", 1 cm3) was treated with non-reducing zinc chloride solution (ZnCI2, MW 136.29, 7.60 g, 55 mmol, in 15 cm3 of H2O with Na2Cr2O7^H2O, MW 298.00, 100 mg, 0.3 mmol) to produce a reddish reaction mixture.Additions of a solution of AI2(SO4)3.16H2O (5.80 g, 9.2 mmol) in H2O (10 cm3); a solution of sodium thiosulfate pentahydrate (Na2S2O3«5H2O, MW 248.18, 8.0 g, 32.2 mmol) in H2O (10 cm3); and one-third of a solution of sodium dichromate dihydrate (Na2Cr207«2H20, MW 298.00, 8.7 g, 29.2 mmol) in H2O (15 cm3) were followed by a rapid rise in temperature to 4O0C.A solution of Λ/,Λ/-diethylaniIine ((CH3CH2)2NC6H5, MW 149.24, 3.0 g, 20.1 mmol) in concentrated HCI (4 cm3) was added, followed by addition of the remaining sodium dichromate dihydrate solution. A dark green precipitate was formed. The temperature was rapidly increased to 75°C. A slurry of activated manganese dioxide (MnO2, MW EPO 86.94, 3.80 g, 43.7 mmol) in H2O (5 cm3) was added. The temperature was increased to 850C. The mixture was stirred at that temperature for 30 minutes. A blue solution with precipitate was observed.The mixture was cooled to 5O0C and concentrated sulfuric acid (H2SO4, 11cm3) was slowly added. The mixture was cooled to 20 0C. The mixture was vacuum filtered. The residue was collected, and washed with brine (saturated aqueous sodium chloride, NaCI). The black residue was re-dissolved in H2O (250 cm3) at 1000C, cooled to room temperature and vacuum filtered to remove insolubles. The filtrate was treated with zinc chloride (ZnCI2, MW 136.28, 4 g, 29 mmol) and sodium chloride (NaCI, MW 58.44, 23 g, 0.4 mol) and left to stand in a refrigerator for 16 hours. The resulting precipitate was recovered by vacuum filtration, washed with brine (saturated aqueous sodium chloride, NaCI, 30 cm3) and dried in a vacuum oven for 3 hour to give the product, ethylthioninium chloride (ETC) zinc chloride (double salt) (MW 547.70, 5.7 g, 10 mmol, 71 %) as a rusty red powder. δH (250 MHz, D2O): 1.20 (12H, br t, CH3), 3.50 (8H, br q, CH2), 6.80 (2H, s, Ph), 7.05 (2H, br d, Ph) and 7.30 (2H, br d, Ph).
  • 47
  • [ 885057-51-2 ]
  • [ 93-05-0 ]
  • 3-(2,6-dichlorophenyl)-N-[4-(diethylamino)phenyl]-5-[3-(dimethylamino)-3-oxopropyl]-isoxazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% Stage #1: N,N-diethylaniline With ethylmagnesium bromide In tetrahydrofuran; diethyl ether at 20℃; for 0.25h; Stage #2: 3-(2,6-dichlorophenyl)-5-[3-(dimethylamino)-3-(oxopropyl)]-4-ethyl carboxyisoxazole In tetrahydrofuran; diethyl ether at 20℃; 26.B 3-(2,6-dichlorophenyl)-N-[4-(diethylamino)phenyl]-5-r3-(dimethylamino)-3-oxopropyl]-isoxazole-4-carboxamide EXAMPLE 26B 3-(2,6-dichlorophenyl)-N-[4-(diethylamino)phenyl]-5-r3-(dimethylamino)-3-oxopropyl]-isoxazole-4-carboxamide Ethylmagnesium bromide (0.17 ml, 0.52 mmol, 3M in ethyl ether) was added to a solution of N,N-diethyl-1,4-phenylene diamine (85 mg, 0.52 mmol) in THF (5 ml) at 0° C. The mixture was stirred at room temperature for 15 minutes, then 3-(2,6-dichlorophenyl)-5-[3-(dimethylamino)-3-(oxopropyl]-4-ethyl carboxyisoxazole from Example 26A (100 mg, 0.26 mmol) in THF (2 ml) was added. The reaction mixture was stirred for overnight at room temperature and the solvent removed under reduced pressure. To the residue was added methylene chloride and aqueous of NH4Cl (10 ml, 1:1). The organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure and purified by prep-HPLC to provide 81 mg (62%) of the titled compound. 1H-NMR (CDCl3, 300 MHz), δ 10.82 (br s, 1H,CONH), 7.55 (d, J=9.0 Hz, 2H, Ar'-H), 6.63 (d, J=9.0 Hz, 2H, Ar'-H), 7.39-7.28 (m, 3H, Ar-H), 3.34 (t, J=6.0 Hz, 2H, CH2CH2), 3.01 (t, J=6.0 Hz, 2H, CH2CH2), 3.30 (q, J=6.0 Hz, 4H, NCCH3), 3.07 (s, 3H, 2NCH3), 3.00 (s, 3H, 2NCH3), 1.11 (t, J=6.0 Hz, 6H, 2 NCH2C3). MS (ESI) m/e 503.0, 501.1 (M)+.
  • 48
  • [ 108-45-2 ]
  • [ 93-05-0 ]
  • [ 121501-63-1 ]
YieldReaction ConditionsOperation in experiment
42% Stage #1: N,N-diethylaniline With hydrogenchloride; sodium nitrite In water at 0℃; for 0.25h; Stage #2: With ammonium sulfamate; sodium acetate In water for 0.25h; Stage #3: m-phenylenediamine With sodium hydroxide; ammonia; copper(II) sulfate more than 3 stages; 1 An aqueous solution (1OmL) of sodium nitrite (764mg, 1 l.lmmol) was added dropwise to a solution of N,N-diethyl-p-phenylenediamine (1.54mL, 9.3mmol) in 10% aqueous hydrochloric acid (5OmL) under ice cooling. After 15min, ammonium sulfamate (1.58g, 13.8mmol) was added and the resulting mixture was stirred for 15min. After adjusting the pH to pH 5 using sodium acetate, 1,3-phenylenediamine (Ig, 9.2mmol) was added; the mixture was further stirred for 2h and then basified to pH 9 using IM sodium hydroxide. Ethyl acetate was added and the organic layer washed twice with brine. The combined organic layers were dried over anhydrous MgSO4 and evaporated to afford a red solid. A solution of copper sulfate (1Og) in aqueous ammonia (3OmL of 28% ammonia in 3OmL of water) was added to the previously obtained red solid in pyridine (4OmL). The solution was then refluxed for 16h. After cooling, ethyl acetate was added, and the organic layer washed twice with brine. The combined organic layers were dried over anhydrous MgSO4 and evaporated down to get a dark red solid, which was triturated with diethyl ether to afford 1.09g (42%) of the title compound (LCMS RT= 7.06HUn5 MH+ 282.1)1H NMR (DMSO): 8.02 (2H, d, J 9.3 Hz), 7.68 (IH, d, J 9.1 Hz), 6.96 (IH, dd, J 9.1 2.0 Hz), 6.86 (2H, d, J 9.3 Hz), 6.75 (IH, dd, J 1.9 0.6 Hz), 5.55 (2H, br), 3.46 (4H, q, J7.1 Hz ), 1.19 (6H, t, J7.1 Hz)
Stage #1: m-phenylenediamine; N,N-diethylaniline With hydrogenchloride; ammonium sulphamate; sodium nitrite In water Stage #2: With pyridine; ammonia; copper(II) sulfate In water Reflux;
Multi-step reaction with 2 steps 1.1: sodium nitrite; hydrogenchloride / methanol; water / 0.17 h / 0 °C 1.2: 0.5 h / 0 - 5 °C 2.1: copper(II) acetate monohydrate; pyridine / acetonitrile / 0.5 h / Reflux
  • 49
  • [ 95-80-7 ]
  • [ 93-05-0 ]
  • [ 381208-40-8 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-methylbenzene-1,3-diamine; N,N-diethylaniline With hydrogenchloride; ammonium sulphamate; sodium nitrite In water Stage #2: With pyridine; ammonia; copper(II) sulfate In water Reflux;
  • 50
  • [ 368-66-1 ]
  • [ 88945-41-9 ]
  • [ 93-05-0 ]
  • [ 1340547-24-1 ]
YieldReaction ConditionsOperation in experiment
70% Stage #1: N-(Cyanmethyl)formimidsaeure-methylester; N,N-diethylaniline In dichloromethane for 2h; Inert atmosphere; Reflux; Stage #2: 2,4,6-tris(trifluoromethyl)-1,3,5-triazine With trimethylsilyl trifluoromethanesulfonate In dichloromethane at 0℃; Inert atmosphere; Reflux; 3.2. General procedure for the synthesis of purines 8-16 General procedure: To a Schlenck flask, set with reflux, CH2Cl2 (2.5 mL), primary amine 2 (0.00345 mol) and methyl N-(cyanomethyl)-formimidate 1 (0.338 g, 0.00345 mol) were added under an argon atmosphere at rt. The reaction mixture was kept under reflux and after that, the mixture was cooled down to rt, and then to 0 °C on an ice bath. Afterwards corresponding triazine (0.00345 mol) was added, and the mixture continued to stir at the same temperature for 15-20 min and then refluxed. After the product formation is completed, the solvent was evaporated to dryness and the residue was purified by column chromatography (EtOAc) to give purines. In a case of all aromatic and heteroaromatic amines, after the addition of triazine at 0 °C, catalytic amount of TMSOTf (about three drops) was added. For the synthesis of purines 8 the 20% excess of 4 was generated.
  • 51
  • [ 879-65-2 ]
  • [ 93-05-0 ]
  • [ 1222943-27-2 ]
  • 52
  • [ 50-00-0 ]
  • [ 6305-18-6 ]
  • [ 93-05-0 ]
  • [ 1380484-52-5 ]
YieldReaction ConditionsOperation in experiment
90% With hydrogenchloride In ethanol; acetonitrile at 20℃; for 12h;
  • 54
  • [ 1403888-69-6 ]
  • [ 93-05-0 ]
  • C29H31N5O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride In 1,4-dioxane; methanol at 140℃; for 0.0833333h; Microwave irradiation; 78 Example No. 78 Preparation of N, N-Diethyl-N ' - (8-methoxy-2H-pyrazolo [3,4- c] quinolin-4-yl) -benzene-1, 4-diamine4 -chloro-8 -methoxy-2- (4-methoxybenzyl) -2H-pyrazolo [3 , 4 - c]quinoline (0.16 mmol) and Nl , l -diethylbenzene- 1 , 4 -diamine (2 eq.,0.3 mmol) were suspended in MeOH (dry, 3mL) in a microwave vial (2-5mL) , HC1 in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140°C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3mL) . The reaction mixture was irradiated in a microwave reactor for 5 min at 140°C. The reaction mixture was concentrated and purified by semi- preparative HPLC-MS and freeze dried from water/t-BuOH 4/1. exact mass: 361.2265 g/molHPLC-MS: analytical method Brt : 1.77 min - found mass: 334.2 (m/z+H)
  • 55
  • [ 77846-07-2 ]
  • [ 93-05-0 ]
  • [ 1421739-68-5 ]
YieldReaction ConditionsOperation in experiment
79% With N-ethyl-N,N-diisopropylamine In dichloromethane Inert atmosphere; Cooling with ice; ii. 2-[(Benzyloxy)imino]-N-(2,4-dimethylphenyl)acetamide (7b) General procedure: 2-[(Benzyloxy)imino]acetylchloride (8) (0.89 g, 4.55 mmole) was dissolved in DCM (20 ml) and added dropwise to an ice bath cooled solution of the 2,4-dimethylaniline (0.524 g, 4.32 mmole, 0.54 ml, 0.95 eq.) in DCM (30 ml) and N,N-diisopropylethylamine (0.95ml, 5.5 mmole, 1.2 eq.). On completion of the addition, the cold bath was removed, and the reaction mixture was allowed to warm to room temperature. The crude product was partitioned between 1% HCl and DCM. The organic phase was separated, washed with brine, dried over Na2SO4, and the solvents were evaporated. The resulting tan solid was triturated with 10% ether in hexane, filtered, rinsed with cold solvent mixture, and dried under vacuum to yield 0.96 g (3.40 mmole, 75%) of the title compound as an off-white solid.
  • 56
  • [ 1204601-62-6 ]
  • [ 93-05-0 ]
  • [ 1422642-88-3 ]
YieldReaction ConditionsOperation in experiment
77% With tetrakis(triphenylphosphine) palladium(0); caesium carbonate In toluene at 90℃; for 6h; 4.2.2 Method B (for 3m-u) General procedure: A mixture of 2 (0.6 mmol), amine (0.7 mmol), Cs2CO3 (235 mg, 0.72 mmol), Pd(PPh3)4 (5 mol %), and toluene (10 ml) was heated at 90 °C for 6 h. The residue was purified by column chromatography on silica gel to afford the product.
  • 57
  • [ 1204601-58-0 ]
  • [ 93-05-0 ]
  • [ 1428144-09-5 ]
YieldReaction ConditionsOperation in experiment
66% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 110℃; for 5h; Inert atmosphere; 5 6.5 1-(3-(4-(Diethylamino)phenylamino)thiophen-2-yl)-3-phenylprop-2-yn-1-one (2h) Yellow solid, yield 66%, mp 124-126 °C. 1H NMR (300 MHz, CDCl3): δ=1.07 (t, J=7.1 Hz, 6H, 2Me), 3.25 (q, J=7.1 Hz, 4H, 2CH2), 6.57 (d, J=8.9 Hz, 2H), 6.76 (d, J=5.5 Hz, 1H), 7.00 (d, J=8.9 Hz, 2H), 7.26-7.35 (m, 4H), 7.54-7.57 (m, 2H), 9.75 (s, 1H, NH); 13C NMR (62.9 MHz, CDCl3): δ=12.5, 44.5, 87.6, 90.7, 112.4, 115.0, 117.6, 120.7, 124.4, 128.5, 128.6, 130.1, 132.7, 136.2, 145.6, 155.0, 168.8; GC-MS (EI, 70 eV): m/z (%)=374 (M+, 83), 359 (100), 329 (13), 302 (17), 272 (4), 226 (3), 180 (3), 137 (4); HRMS (ESI): calcd for C23H22N2OS 374.14474, found 374.14445; IR (ATR, cm-1): ν=3276 (w), 3078 (w), 2968 (m), 2927 (w), 2868 (w), 2198 (s), 1611 (m), 1566 (s), 1517 (s), 1488 (m), 1443 (w), 1381 (s), 1264 (s), 1235 (w), 1196 (m), 1154 (m), 1094 (w), 1076 (w), 1025 (w), 1011 (w), 979 (m), 919 (w), 852 (w), 802 (w), 761 (m).
  • 58
  • [ 1204601-58-0 ]
  • [ 93-05-0 ]
  • [ 1428144-17-5 ]
YieldReaction ConditionsOperation in experiment
80% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 110℃; Inert atmosphere; 14 General procedure for the synthesis of thieno[3,2-b]pyridones General procedure: To the ynone 1 (0.5 mmol), Cs2CO3 (0.7 mmol), Pd2(dba)3 (5 mol %), and BINAP (10 mol %) under argon was added toluene (10 ml) followed by arylamine/alkylamine (0.6 mmol), and the reaction was stirred at 110 °C for 10-12 h. After cooling to room temperature, the reaction mixture was preabsorbed onto silica gel and purified by column chromatography 6.14 4-(4-(Diethylamino)phenyl)-5-phenylthieno[3,2-b]pyridin-7(4H)-one (3h) Yellow solid, yield 80%, mp 194-196 °C. 1H NMR (250 MHz, CDCl3): δ=1.06 (t, J=7.2 Hz, 6H, 2Me), 3.24 (q, J=7.0 Hz, 4H, 2CH2), 6.38 (s, 1H), 6.43 (d, J=9.1 Hz, 2H), 6.63 (d, J=5.5 Hz, 1H), 6.84 (d, J=9.1 Hz, 2H), 7.11-7.19 (m, 5H, Ph), 7.46 (d, J=5.5 Hz, 1H); 13C NMR (62.9 MHz, CDCl3): δ=11.3, 43.3, 110.3, 112.2, 118.4, 126.8, 126.9, 127.4, 127.7, 128.0, 128.4, 130.0, 134.1, 146.5, 146.6, 151.4, 172.8; GC-MS (EI, 70 eV): m/z (%)=374 (M+, 67), 359 (100), 330 (9), 302 (8), 273 (3), 228 (3), 171 (6), 136 (4); HRMS (ESI): calcd for C23H22N2OS 374.14474, found 374.14439; IR (ATR, cm-1): ν=3541 (w), 3389 (w), 3050 (m), 2963 (m), 2925 (w), 1609 (s), 1591 (s), 1517 (s), 1475 (s), 1444 (w), 1422 (w), 1405 (w), 1377 (m), 1355 (m), 1317 (m), 1264 (s), 1197 (m), 1156 (m), 1108 (m), 1073 (m), 1048 (s), 1016 (w), 915 (w), 817 (m), 771 (s).
  • 59
  • [ 1332527-92-0 ]
  • [ 93-05-0 ]
  • [ 1332527-55-5 ]
YieldReaction ConditionsOperation in experiment
12% With triethylamine In dichloromethane at 20℃; for 1h; 4 4-[3-(4-diethylaminophenylsulfamoyl)benzenesulfonylamino]methyl}-piperidine-1-carboxylic acid tert-butyl ester (Y186) 4-Fluoronitrobenzene (316 mg, 2.2 mmol) was dissolved in DMSO (5 ml), potassium carbonate (464 mg, 3.4 mmol) and diethylamine (327 mg, 4.4 mmol) were added, and the mixture was stirred at 90° C. overnight. Then, water was added to the reaction solution, and the mixture was extracted twice with ethyl acetate. The organic layer was washed twice with saturated aqueous NaCl. The organic layer was dried over Na2CO3, the solvent was evaporated, and the obtained residue was purified by silica gel chromatography (eluent; hexane:ethyl acetate (2:1)) to give compound Y181 (yield; 386 mg, 89%). Compound Y181 (369 mg, 1.9 mmol) was dissolved in methanol (20 ml), Pd/C (141 mg) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature overnight. Then, the reaction solution was filtered through celite, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (eluent; hexane:ethyl acetate (1:1)) to give compound Y184 (yield; 280 mg, 90%). Compound Y491 (mentioned later) (158 mg, 0.35 mmol) was dissolved in dichloromethane (5 ml), compound Y184 (143 mg, 0.9 mmol) and triethylamine (145 μl, 1.0 mmol) were added, and the mixture was stirred at room temperature for 1 hr. Then, the solvent was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (eluent; chloroform:methanol (30:1)) to give the title compound (yield; 24 mg, 12%). 1H NMR (500 MHz, CDCl3) δ8.44 (s, 1H), 8.00 (d, 1H, J=8.0 Hz), 7.30 (d, 1H, J=8.0 Hz), 7.53 (t, 1H, J=8.0 Hz), 7.09 (bs, 1H), 6.87 (d, 2H, J=9.0 Hz), 6.49 (d, 2H, J=8.5 Hz), 5.45 (t, 1H, J=6.5 Hz), 4.06 (bs, 2H), 3.28 (dd, 4H, J=14.0, 7.0 Hz), 2.81-2.63 (m, 4H), 1.66-1.57 (m, 3H), 1.43 (s, 9H), 1.13 (t, 6H, J=7.0 Hz), 1.08-0.99 (m, 2H) 13C NMR (125 MHz, CDCl3) δ154.9, 147.1, 141.5, 141.1, 131.9, 131.0, 129.7, 126.9, 125.8, 122.8, 112.1, 79.6, 79.5, 77.4, 48.7, 44.5, 36.6, 29.6, 28.6, 12.6 HRMS (FAB-) m/z: [M-H]- calcd for C27H40N4O6S2, 579.2311. found, 579.2360
  • 60
  • [ 2216-15-1 ]
  • [ 93-05-0 ]
YieldReaction ConditionsOperation in experiment
90% With palladium on activated charcoal; hydrogen In methanol at 20℃; 4 4-Fluoronitrobenzene (316 mg, 2.2 mmol) was dissolved in DMSO (5 ml), potassium carbonate (464 mg, 3.4 mmol) and diethylamine (327 mg, 4.4 mmol) were added, and the mixture was stirred at 90° C. overnight. Then, water was added to the reaction solution, and the mixture was extracted twice with ethyl acetate. The organic layer was washed twice with saturated aqueous NaCl. The organic layer was dried over Na2CO3, the solvent was evaporated, and the obtained residue was purified by silica gel chromatography (eluent; hexane:ethyl acetate (2:1)) to give compound Y181 (yield; 386 mg, 89%). Compound Y181 (369 mg, 1.9 mmol) was dissolved in methanol (20 ml), Pd/C (141 mg) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature overnight. Then, the reaction solution was filtered through celite, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (eluent; hexane:ethyl acetate (1:1)) to give compound Y184 (yield; 280 mg, 90%). Compound Y491 (mentioned later) (158 mg, 0.35 mmol) was dissolved in dichloromethane (5 ml), compound Y184 (143 mg, 0.9 mmol) and triethylamine (145 μl, 1.0 mmol) were added, and the mixture was stirred at room temperature for 1 hr. Then, the solvent was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (eluent; chloroform:methanol (30:1)) to give the title compound (yield; 24 mg, 12%). 1H NMR (500 MHz, CDCl3) δ8.44 (s, 1H), 8.00 (d, 1H, J=8.0 Hz), 7.30 (d, 1H, J=8.0 Hz), 7.53 (t, 1H, J=8.0 Hz), 7.09 (bs, 1H), 6.87 (d, 2H, J=9.0 Hz), 6.49 (d, 2H, J=8.5 Hz), 5.45 (t, 1H, J=6.5 Hz), 4.06 (bs, 2H), 3.28 (dd, 4H, J=14.0, 7.0 Hz), 2.81-2.63 (m, 4H), 1.66-1.57 (m, 3H), 1.43 (s, 9H), 1.13 (t, 6H, J=7.0 Hz), 1.08-0.99 (m, 2H) 13C NMR (125 MHz, CDCl3) δ154.9, 147.1, 141.5, 141.1, 131.9, 131.0, 129.7, 126.9, 125.8, 122.8, 112.1, 79.6, 79.5, 77.4, 48.7, 44.5, 36.6, 29.6, 28.6, 12.6 HRMS (FAB-) m/z: [M-H]- calcd for C27H40N4O6S2, 579.2311. found, 579.2360
89% With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 5h;
85.2% With palladium on activated charcoal; hydrogen In ethanol at 20℃; for 4h;
68.4% With ammonium chloride; zinc In tetrahydrofuran; methanol at 0 - 20℃; for 18h; 4.1.2. General procedures for the preparation of compound 3a-r General procedure: Nitro compound 2a-r (3.0 mmol, 1 eq) was dissolved in amixture of THF (9 mL) and MeOH (6 mL) at 0 C. Subsequently, zincpowder (15.0 mmol, 5 eq), followed by ammonium chloride(15.0 mmol, 5 eq) were added and the reaction mixture was stirredat room temperature for 18 h. After completion of the reaction, theresulting mixture was filtered through Celite and the filtrate wasconcentrated in vacuo. The crude was purified by flash chromatographywith 97:3 (v/v) dichloromethane - methanol.
With FeO(OH)/C; hydrazine hydrate In ethanol at 0 - 80℃; for 4h; 4.1.9. Step 2 Tert-butyl 4-(4-aminophenyl)piperazine-1-carboxylate (2a) General procedure: To a solution of 1a (5 g, 22.5 mmol) in 95% ethanol (100 mL) wasadded goethite (FeO(OH))/C (1.0 g) at room temperature. And a solution of 80% hydrazine hydrate (25 mL, 400 mmol) in 95% ethanol (50 mL) was added dropwise to the mixture at 0 °C. The reaction mixture was stirred at 80 °C for 4 h. The solvent was removed in vacuo to give 2a (3.8 g, yield 74.5%). MS m/z: 278.2 [M+H]+.

  • 61
  • [ 93-05-0 ]
  • [ 57702-49-5 ]
YieldReaction ConditionsOperation in experiment
74% Stage #1: N,N-diethylaniline With water; sodium nitrite In neat (no solvent) at 20℃; Stage #2: With potassium iodide In neat (no solvent) at 20℃; Diazotization-iodination of aromatic amines General procedure: An aromaticamine (1 mmol), nanomagnetic-supported sulfonic acid (c-Fe2O3-SO3H)(0.65 g), NaNO2 (2 mmol, 0.138 g), and 0.2 mL of H2O were homogenized bygrinding in a mortar with a pestle for a few minutes. Formation of a reddishbrowngas was observed as soon as H2O was added. The diazotization reactionlasted for approximately 5-30 min. Next, KI (2.5 mmol, 0.415 g) was added tothe diazonium salt and grinding was continued for 10-20 min. After completionof the reaction, the mixture was triturated with EtOAc (5 mL). The c-Fe2O3-SO3K was separated from the solution using a magnetic bar. The organic layerwas treated with aq 10% Na2SO3 (15 mL), then dried over anhydrous Na2SO4.After evaporation of the solvent, the crude product was afforded. Purifiedproducts were obtained by recrystallization from ethanol or by flashchromatography (n-hexane-EtOAc, 95:5).
  • 62
  • [ 35578-47-3 ]
  • C15H19N2O6Pol [ No CAS ]
  • [ 93-05-0 ]
  • C39H40Br2N5O5Pol [ No CAS ]
  • 63
  • [ 1121-60-4 ]
  • [ 50-00-0 ]
  • [ 93-05-0 ]
  • 2-(4-(diethylamino)phenyl)-2H-imidazo[1,5-a]pyridin-4-ium hexafluorophosphate [ No CAS ]
YieldReaction ConditionsOperation in experiment
74.7% Stage #1: pyridine-2-carbaldehyde; formaldehyd; N,N-diethylaniline With hydrogenchloride In ethanol; water at 20 - 25℃; for 12h; Stage #2: With potassium hexafluorophosphate In water 2 Compound 2 was prepared according to general procedure (A) in which a reaction mixture was prepared by combining 186 μl ethanol formalin (2.48 mmol, 1.5 equiv) and freshly distilled 274.6 μl N,N-diethylbenzene-1,4-diamine (1.66 mmol, 1 equiv). Then, 158 μl picolinaldehyde (1.66 mmol, 1 equiv) and 1.09 μl 3.14 M hydrochloric acid in ethanol (3.31 mmol, 2 equiv) were simultaneously added to the reaction mixture and the reaction was maintained at room temperature for 12 hours. The solution was concentrated and the crude chloride salt subjected to salt metathesis with potassium hexafluorophosphate. The resulting precipitate was filtered and washed with water two times using 500 μl of water for each wash. The precipitate was then dried under high vacuum at 0.2 Torr, dissolved in 5 mL acetonitrile, and stirred with 800 mg sodium bicarbonate for 30 minutes at room temperature. The resulting suspension was filtered through a 0.2 μm nylon syringe tip filter and concentrated in vacuo to provide 509 mg 2-(4-(diethylamino)phenyl)-2H-imidazo[1,5-a]pyridin-4-ium hexafluorophosphate (1.24 mmol, at a 74.7% yield) as red solid. Crystals suitable for X-ray diffraction were obtained by layering a concentrated acetone solution of 2-(4-(diethylamino)phenyl)-2H-imidazo[1,5-a]pyridin-4-ium hexafluorophosphate with pentane.; General Procedure (A) for Preparing Imidazo[1,5-a]pyridine Fluorophores: [0151] Imidazo[1,5-a]pyridine fluorophores were prepared by adding 1 equivalent (equiv) of 3 M hydrochloric acid in ethanol (an additional equivalent of acid was used in reactions with basic substrates) and picolinaldehyde or other 2-acylpyridine to 1 equiv of a 0.5 M solution of 1 equiv of primary amine in dry ethanol or acetonitrile and 1.5 equiv of formalin. The reaction was stirred at room temperature for the specified period of time (i.e., from about 15 min to about 12 hours) and monitored by analytical thin layer chromatography (TLC) (10% methanol in DCM) for the appearance of a blue fluorescent product spot by UV light. Crude reaction mixtures were concentrated in vacuo (15 Torr) and dried under high vacuum at 0.2 Torr (for from 2 to 12 hours). [0152] Chloride salts were obtained through filtration of precipitate, recrystallization or trituration of the crude solid under conditions given. Hexafluorophosphate salts were obtained by salt metathesis with potassium hexafluorophosphate following the General Procedure for Salt Metathesis to Hexafluorophosphate Counterion. Tetraphenylborate salts were obtained by salt metathesis using sodium tetraphenylborate as described with respect to the compounds below that are in the form of tetraphenylborate salts.
  • 64
  • [ 1432130-74-9 ]
  • [ 93-05-0 ]
  • N-(4-[4-(diethylamino)phenyl]carbamoyl}phenyl)-2-[3-(morpholin-4-ylmethyl)benzoyl]amino}-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide dihydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
85 mg Stage #1: 4-[(2-[3-(morpholin-4-ylmethyl)benzoyl]amino}-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}benzoic acid; N,N-diethylaniline With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 3h; Stage #2: With hydrogenchloride In methanol; ethyl acetate 12 Example 12 A mixture of 150 mg of 4-[(2-[3-(morpholin-4-ylmethyl)benzoyl]amino}-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}benzoic acid, 57 mg ofN,N-diethyl-p-phenylenediamine, 61 mg of WSC·hydrochloride, 42 mg of HOBt, and 1.5 mL of methylene chloride was stirred for 3 hours at room temperature. Water was added to the reaction mixture, followed by extraction with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by basic silica gel column chromatography (2% methanol/chloroform), thereby obtaining an oily material. Methanol and 4.0 M hydrogen chloride/ethyl acetate solution were added to this material, and the solution was concentrated under reduced pressure. The residue was treated with ethyl acetate, thereby obtaining 85 mg of N-(4-[4-(diethylamino)phenyl]carbamoyl}phenyl)-2-[3-(morpholin-4-ylmethyl)benzoyl]amino}-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide dihydrochloride.
  • 65
  • C8H4N5O4(1+)*HO4S(1-) [ No CAS ]
  • [ 93-05-0 ]
  • (E)-6-((4-(diethylamino)phenyl)diazenyl)-7-nitro-2,3-dihydrophthalazine-1,4-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% In ethanol at 0 - 5℃; for 2h; 3.1.2 General method of coupling General procedure: The coupler a-c (10.1mmol) was dissolved in 100ml ethanol at 0-5°C. The diazonium salt 10mmol (3 and 4) was added dropwise to the coupler solution at 0-5°C over a period of 2h. After the addition was completed, the pH was adjusted between 5 and 6 by using cold aqueous 10% sodium hydroxide solution. The reaction mixture was stirred overnight and monitored by using H-acid and starch iodide paper. The precipitated product was filtered and washed with water, recrystalized from DMF/N,N-dimethylacetamide to give the dyes 3a-3c and 4a-4c respectively. The low solubility of the compounds 3a-3c and 4a-4c made the 13C-NMR characterization of these substrates not possible. Only the IR, 1H-NMR, mass and HRMS are recorded.
  • 66
  • C8H4N5O4(1+)*HO4S(1-) [ No CAS ]
  • [ 93-05-0 ]
  • (E)-6-((4-(diethylamino)phenyl)diazenyl)-5-nitro-2,3-dihydrophthalazine-1,4-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% In ethanol at 0 - 5℃; for 2h; 3.1.2 General method of coupling General procedure: The coupler a-c (10.1mmol) was dissolved in 100ml ethanol at 0-5°C. The diazonium salt 10mmol (3 and 4) was added dropwise to the coupler solution at 0-5°C over a period of 2h. After the addition was completed, the pH was adjusted between 5 and 6 by using cold aqueous 10% sodium hydroxide solution. The reaction mixture was stirred overnight and monitored by using H-acid and starch iodide paper. The precipitated product was filtered and washed with water, recrystalized from DMF/N,N-dimethylacetamide to give the dyes 3a-3c and 4a-4c respectively. The low solubility of the compounds 3a-3c and 4a-4c made the 13C-NMR characterization of these substrates not possible. Only the IR, 1H-NMR, mass and HRMS are recorded.
  • 67
  • [ 93-05-0 ]
  • [ 108602-20-6 ]
YieldReaction ConditionsOperation in experiment
6.2% Stage #1: N,N-diethylaniline With hydrogenchloride In diethyl ether; water at 20℃; for 0.25h; Stage #2: With hydrogenchloride; sodium sulfide; iron(III) chloride In water for 1h; Stage #3: With sodium chloride In water for 0.75h; Cooling with ice; The synthesis of ETC The synthesis of ETC N,N-diethyl-p-phenylenediamine (73.2 mmol) was dissolved in 60 ml diethyl ether. A volume of 12 ml HCl (32%) was subsequently added and the mixture was stirred for 15 min at room temperature. The resulting solution was concentrated by rotary evaporation to give N,N-diethyl-p-phenylenediamine dihydrochloride, which was subsequently dissolved in 360 ml H2O. The pH of the solution was adjusted to 1.6 using 10% aqueous HCl, and sodium sulphide (73.2 mmol) was added to the reaction. A solution of iron(III) chloride (109.5 mmol) in 120 ml H2O was prepared and added to the reaction upon which the reaction immediately turned blue. The reaction was subsequently aerated for 1 h and another portion of iron(III) chloride solution (109.5 mmol in 120 ml H2O) was added to the reaction. The reaction was cooled to 5 °C, and was subsequently filtered. The residue was washed with H2O (10 ml) and the filtrate fractions were pooled. Sodium chloride (2.07mol) was added to the filtrate and the resulting mixture was stirred for 15min, and subsequently cooled on ice for 30min. The mixture turned purple and a precipitate formed, which was collected by filtration. The solid residue was air-dried overnight and was dissolved in a mixture of 300ml CH2Cl2 and 30ml CH3OH. The solution was stirred at room temperature for 1h and subsequently filtered. The filtrate was concentrated under reduced pressure to give the product, ethylthioninium chloride (ETC) as a green solid. ETC (4.17mmol) was dissolved in 72ml H2O and heated to 60°C. The dark blue mixture was allowed to cool to room temperature. The mixture was treated with a solution of sodium sulphide (0.32mmol) dissolved in 6ml H2O, and stirring was continued for 15min. The mixture was filtered and the filtrate treated with 20ml HCl (32%) and 60ml tetrahydrofuran. The solution was allowed to recrystallize at room temperature for approximately 3weeks. Small dark green crystals of ETC were collected by filtration. Overall yields of 5.7-6.2% were typically obtained. TLC was performed and indicated a single blue spot with a retardation factor (Rf) of 0.53 (Wischik et al., 2006). 1H NMR (Bruker Avance III 600, D2O) δ 1.16 (12H); 3.39 (8H), 6.71 (2H), 6.91 (2H), 7.08 (2H), 13C NMR (Bruker Avance III 600, DMSO-d6) 12.5, 45.3, 105.7, 117.9, 132.5, 133.2, 137.0, 150.6. APCI-HRMS m/z: calcd for C20H26N3S (M+), 340.1842, found 340.1836.
Multi-step reaction with 2 steps 1: hydrogenchloride / diethyl ether 2: hydrogenchloride; sodium sulfide; iron(III) chloride / water / 1 h / 5 °C / pH 1.6
With iron(III) chloride; hydrogen sulfide
  • 68
  • [ 117-80-6 ]
  • [ 93-05-0 ]
  • [ 42262-97-5 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In chloroform at 20℃; General procedure: 1.0 g (4.4 mmol) 2,3-dichloro-1,4-naphthoquinone (1) and the correspondingnucleophile were stirred in CHCl3 (30 mL) with triethylamine (3 mL) solution for 2-3 h atroom temperature. The color of the solution quickly changed and the reaction was monitoredby TLC. Chloroform (30 mL) was added to the reaction mixture. The organic layer waswashed with water (4×30 mL), and dried over Na2SO4. After evaporation of the solvent, theresidue was purified by column chromatography on silica gel.
  • 69
  • [ 86-90-8 ]
  • [ 93-05-0 ]
  • 5-bromo-2-(4-(diethylamino)phenyl)isoindoline-1,3-dione [ No CAS ]
  • 70
  • 2-hydroxy-3-(morpholinomethyl)benzaldehyde [ No CAS ]
  • [ 93-05-0 ]
  • 2-(((4-(diethylamino)phenyl)imino)methyl)-6-(morpholinomethyl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% In ethanol Reflux; Typical procedure for the preparation of monoandbis-Schiff bases 3a-d, 5, 7, 9, 11a-b, 13, 15a-b,17a-f General procedure: A mixture of 2-hydroxy-3-(morpholinomethyl)benzaldehyde(0.5 mmol) and mono-aromatic amines (0.5 mmol)and aromatic diamines (0.25 mmol) was refluxed in ethanol(20 mL) for 3-5 h. Then, the solvent was evaporatedunder vacuum and crude oily Schiff bases 3b-c, 5, 7, 9, 13,17a-f and solid Schiff bases were obtained. Compounds3a, 3d, 11a-b, 15a-b were filtered and washed withethanol to afford pure solid Schiff bases.
  • 71
  • [ 117-80-6 ]
  • [ 109-79-5 ]
  • [ 93-05-0 ]
  • C24H28N2O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2,3-Dichloro-1,4-naphthoquinone; N,N-diethylaniline With triethylamine In chloroform at 20℃; Stage #2: n-butanethiol Procedure 1. 1.0 g (4.4 mmol) 2,3-dichloro-1,4-naphthoquinone (1) and the correspondingnucleophile were stirred in CHCl3 (30 mL) with triethylamine (3 mL) solution for 2-3 h atroom temperature. The color of the solution quickly changed and the reaction was monitoredby TLC. Chloroform (30 mL) was added to the reaction mixture. The organic layer waswashed with water (4×30 mL), and dried over Na2SO4. After evaporation of the solvent, theresidue was purified by column chromatography on silica gel.
  • 72
  • [ 117-80-6 ]
  • [ 107-03-9 ]
  • [ 93-05-0 ]
  • C23H26N2O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2,3-Dichloro-1,4-naphthoquinone; N,N-diethylaniline With triethylamine In chloroform at 20℃; Stage #2: 1-thiopropane Procedure 1. 1.0 g (4.4 mmol) 2,3-dichloro-1,4-naphthoquinone (1) and the correspondingnucleophile were stirred in CHCl3 (30 mL) with triethylamine (3 mL) solution for 2-3 h atroom temperature. The color of the solution quickly changed and the reaction was monitoredby TLC. Chloroform (30 mL) was added to the reaction mixture. The organic layer waswashed with water (4×30 mL), and dried over Na2SO4. After evaporation of the solvent, theresidue was purified by column chromatography on silica gel.
  • 73
  • [ 117-80-6 ]
  • [ 75-08-1 ]
  • [ 93-05-0 ]
  • C22H24N2O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2,3-Dichloro-1,4-naphthoquinone; N,N-diethylaniline With triethylamine In chloroform at 20℃; Stage #2: ethanethiol Procedure 1. 1.0 g (4.4 mmol) 2,3-dichloro-1,4-naphthoquinone (1) and the correspondingnucleophile were stirred in CHCl3 (30 mL) with triethylamine (3 mL) solution for 2-3 h atroom temperature. The color of the solution quickly changed and the reaction was monitoredby TLC. Chloroform (30 mL) was added to the reaction mixture. The organic layer waswashed with water (4×30 mL), and dried over Na2SO4. After evaporation of the solvent, theresidue was purified by column chromatography on silica gel.
  • 74
  • [ 117-80-6 ]
  • C10H10O2S [ No CAS ]
  • [ 93-05-0 ]
  • C30H28N2O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2,3-Dichloro-1,4-naphthoquinone; N,N-diethylaniline With triethylamine In chloroform at 20℃; Stage #2: C10H10O2S Procedure 1. 1.0 g (4.4 mmol) 2,3-dichloro-1,4-naphthoquinone (1) and the correspondingnucleophile were stirred in CHCl3 (30 mL) with triethylamine (3 mL) solution for 2-3 h atroom temperature. The color of the solution quickly changed and the reaction was monitoredby TLC. Chloroform (30 mL) was added to the reaction mixture. The organic layer waswashed with water (4×30 mL), and dried over Na2SO4. After evaporation of the solvent, theresidue was purified by column chromatography on silica gel.
  • 75
  • [ 117-80-6 ]
  • [ 111-88-6 ]
  • [ 93-05-0 ]
  • C28H36N2O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2,3-Dichloro-1,4-naphthoquinone; N,N-diethylaniline With triethylamine In chloroform at 20℃; Stage #2: Octanethiol Procedure 1. 1.0 g (4.4 mmol) 2,3-dichloro-1,4-naphthoquinone (1) and the correspondingnucleophile were stirred in CHCl3 (30 mL) with triethylamine (3 mL) solution for 2-3 h atroom temperature. The color of the solution quickly changed and the reaction was monitoredby TLC. Chloroform (30 mL) was added to the reaction mixture. The organic layer waswashed with water (4×30 mL), and dried over Na2SO4. After evaporation of the solvent, theresidue was purified by column chromatography on silica gel.
  • 76
  • (E)-2-(3-cyano-4-(2-(5-formylthiophen-2-yl)vinyl)-5,5-dimethylfuran-2(5H)-ylidene)malononitrile [ No CAS ]
  • [ 93-05-0 ]
  • C27H25N5OS [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.62 g With sodium sulfate In dichloromethane at 20℃; for 24h; 2.2.3. Synthesis of the chromophore 2-(3-cyano-4-((E)-2-(5-((E)-((4-(diethylamino)phenyl)imino)methyl)thiophen-2-yl)vinyl)-5,5-dimethylfuran-2(5H)-ylidene)malononitrile (BL) A mixture of key intermediate (0.5g, 1.56mmol), N,N-diethyl-p-phenylenediamine (0.29g, 1.71mmol) and Na2SO4 (1.5g, 1.71 mmol) was stirred for 24 h at room temperature in CH2Cl2 (10mL) whereby its color changed to green. It was then concentrated and the product was precipitated by adding pentane (10mL). The product was collected by filtration, washed with pentane twice and dried in vacuo as a green solid (0.62g, 85%). C27H25N5OS (467.59): calcd. C, 69.35; H, 5.39; N, 14.98, S, 6.86; found C, 69.57; H, 5.42; N, 15.03; S, 6.90. 1H NMR (CDCl3, 400.13MHz, 20°C): ||=1.20 (t, J=7.1Hz, 6H, H-21), 1.74 (s, 6H, H-9), 3.41 (m, 4H, H-20), 6.65-6.73 (m, 3H, H10, H18), 7.32 (d, J=9.1Hz, 2H, H-17), 7.37 (d, J=4.0Hz, 1H, H-12), 7.44 (d, J=4.0Hz, 1H, H-13), 7.88 (d, J=15.9Hz, 1H, H-7), 8.62 (s, 1H, H-15) ppm. 13C NMR (CDCl3, 100.61MHz, 20°C): ||=12.81, 26.42, 44.75, 97.53, 97.93, 110.83, 111.21, 111.89, 112.00, 114.05, 123.83, 130.82, 136.04, 137.69, 139.52, 141.59, 144.18, 148.15, 151.80, 172.81, 175.62ppm. MS (MALDI-TOF): m/z calcd for C27H25N5OS: 467.18 [M+H]+; found: 468.60.
  • 77
  • [ 93-05-0 ]
  • [ 86-51-1 ]
  • N1-(2,3-dimethoxybenzylidene)-N4,N4-diethylbenzene-1,4-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% In ethanol Reflux; General procedure for the preparation of Schiff bases 2a-q General procedure: A mixture of aldehyde (9 mmol) and aromatic amine (9 mmol) was refluxed in ethanol (20 mL) for 3-5 h. Then, the solvent was evaporated under vacuum and crude oily and solid Schiff bases were obtained. Crude solid Schiff bases were filtered and washed with ethanol to afford pure solid Schiff bases.
  • 78
  • [ 150-13-0 ]
  • [ 93-05-0 ]
  • C17H18FN3O [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-amino-benzoic acid With hydrogenchloride; sodium nitrite In water Cooling with ice; Stage #2: N,N-diethylaniline With sodium acetate In methanol; water Stage #3: With pyridine hydrogenfluoride; dicyclohexyl-carbodiimide In methanol; dichloromethane; water at 20℃; (2) Synthesis of dye containing acyl fluoride active group A mixture of 4-aminobenzoic acid and concentrated hydrochloric acid,Sodium nitrite in accordance with the dose of 1: 1: 1 dissolved in water, ice bath reaction 3-4h after the diazonium salt,The reaction solution was adjusted to pH 6-7 with sodium acetate; N, N-diethyl-1,4-phenylenediamine was dissolved in methanol,Slowly added to the above diazonium salt solution, low temperature reaction 2-3h after the azo compounds;The synthesized azo compound was reacted with hydrogen fluoride pyridine, DCC (dicyclohexylcarbodiimide)Was dissolved in dry methylene chloride at a dose of 1: 1.1: 1 and allowed to react at room temperature for 4-5 h.Get red dye, purified after the target dye.
  • 79
  • [ 643-79-8 ]
  • [ 93-05-0 ]
  • [ 102016-17-1 ]
YieldReaction ConditionsOperation in experiment
72% With 1,2,3-Benzotriazole; 2-hydroxyethanethiol In acetonitrile at 20℃; for 13h; Inert atmosphere; Preparation of 2-[p-(N,N-Diethylamino)phenyl]phthalimidine (1). To a solution of o-phthaldehyde (OPT; 1.341 g, 10 mmol) in MeCN (30 mL) was added successively (i) a solution of 2-mercaptoethanol (MET; 6.0 mL, 86 mmol) in MeCN (10 mL) over 3 min, (ii) a solution of N,N-diethylphenylenediamine (1.720 g, 10 mmol) in MeCN (10 mL) over 2 min, (iii)1,2,3-1H-benzotriazole (1.191 g, 10 mmol) portionwise over 2 min, and (iv) pH 9.6 buffer (0.05 MH3BO3-KCl-NaOH; 5 mL) over 3 min with stirring at room temperature. After the additions were complete, the mixture was further stirred at room temperature for 13 h under N2., and then evaporated. After storage in refrigerator for 3 h, the resulting solids were filtered, washed successively with ice-cold Et2O and water, and then dried in vacuo to give crude phthalimidine (1.956 g, mp 145-206 oC). The filtrate was evaporated and diluted with water (100 mL). The further resulting solids were filtered,washed successively with ice-cold Et2O and water, and then dried in vacuo to give another crop of crude product (0.376 g, mp 142-224 oC). Both of the crude samples were combined (2.432 g, 87%) andsubjected to recrystallization from MeOH to give the analytically pure sample of2-[4-(N,N-diethylamino)phenyl]phthalimidine (1; 2.094 g, 72%, mp 149-152 oC) as lemon-yellow needles.
  • 80
  • [ 93-05-0 ]
  • tetramethylammonium trifluoromethanethiolate [ No CAS ]
  • [ 84381-54-4 ]
YieldReaction ConditionsOperation in experiment
91% With triethylamine In dichloromethane at 20℃; for 0.166667h;
  • 81
  • [ 1885-14-9 ]
  • [ 93-05-0 ]
  • [ 20950-94-1 ]
YieldReaction ConditionsOperation in experiment
88% With sodium carbonate In tetrahydrofuran; water; ethyl acetate at 0 - 20℃; 4.1.6.1. Phenyl-(4-isopropoxyphenyl)carbamate (13a) General procedure: Into a stirringmixture of ethyl acetate (20 mL), tetrahydrofuran (4 mL), water(4 mL), sodium carbonate (0.8 g, 7.9 mmol, 0.6 equiv.), and 4-isopropoxyaniline (2.0 g, 13.2 mmol, 1 equiv.), phenyl chloroformate(2.3 g, 14.5 mmol, 1.1 equiv.) was added dropwise at 0° C.The reaction was stirred at room temperature overnight, then itwas evaporated under reduced pressure and the resultant wasadded into 20 mL water, the precipitate was filtered and washedwith water, then dried under vacuum to afford 3.2 g of 13a as whitesolid; yield: 90%.
With pyridine In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 3h;
  • 82
  • methyl 2-((2'R,3'S,4'S,5'S)-4-bromo-3'-(4-bromophenyl)-4'-formyl-2-oxo-3',4',5',6'-tetrahydrospiro[indoline-3,2'-thiopyran]-5'-yl)acetate [ No CAS ]
  • [ 93-05-0 ]
  • C32H35Br2N3O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: methyl 2-((2'R,3'S,4'S,5'S)-4-bromo-3'-(4-bromophenyl)-4'-formyl-2-oxo-3',4',5',6'-tetrahydrospiro[indoline-3,2'-thiopyran]-5'-yl)acetate; N,N-diethylaniline With acetic acid In methanol at 20℃; for 12h; Stage #2: With sodium cyanoborohydride In methanol at 20℃; for 1h; 18 General procedure for the preparation of compounds B1-B14 General procedure: To a stirred solution of lead compound 1 (166 mg, 0.3 mmol, 1.0equiv) in MeOH (10 mL) were added amine (0.45 mmol, 1.5 equiv)and AcOH (2 drops, catalytic amount). The resulting solution was stirred at room temperature overnight. Then sodium cyanoborohydride(57 mg, 0.9 mmol, 3.0 equiv) was added and the mixture wasstirred at room temperature for another 1 h. Then the solvent wasevaporated under reduced pressure. The residue was diluted withEtOAc (40 mL) and H2O (40 mL). The organic layer was separated,washed with saturated NaHCO3 (30 mL) and saturated NaCl solution(30 mL), dried over anhydrous Na2SO4 and concentrated underthe reduced pressure. The residue was used for the next step withoutpurification. It was diluted with DCM (10 mL) and TFA(0.75 mL) was added and the resulting solution was stirred at roomtemperature for 3 h. Then the reaction mixture was diluted with ofDCM (20 mL), washed with saturated NaHCO3 (20 mL) and NaCl(20 mL) solution, dried over anhydrous Na2SO4 and concentratedunder reduced pressure. The crude product was purified by columnchromatography (silica gel, DCM/MeOH = 100:2, v/v).
  • 83
  • 1-[4-(diethylamino)phenyl]-1H-1,2,3-triazole-4-carboxaldehyde [ No CAS ]
  • [ 93-05-0 ]
  • 4-diethylamino-N-[[1-[4-(diethylamino)phenyl]-1H-1,2,3-triazol-4-yl]methylene]benzenamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% In methanol; chloroform at 20℃; for 24h; Sealed tube; General procedure for condensation reactions at low temperature General procedure: Aldehyde (0.1 mmol) and amine (0.1 mmol) reactants were dissolved in 2.5 mL methanol and 2.5 mL chloroform and stirred at room temperature in a sealed vial. Products were isolated by air evaporation of solvent at room temperature.
With air In water; <i>tert</i>-butyl alcohol at 70℃; for 24h;
  • 84
  • [ 62-53-3 ]
  • [ 93-05-0 ]
  • [ 4569-86-2 ]
YieldReaction ConditionsOperation in experiment
35% With hydrogenchloride; potassium dichromate; sodium acetate; acetic acid In water at 105℃; for 3h; Inert atmosphere; Darkness; Synthesis of 3-Amino-7-(diethylamino)-5-phenylphenazinium (1) To a solution of 4'-amino-N,N-diethylaniline (5 g, 30.5mmol), aniline (5.8 g, 61.0 mmol), and concentrated hydrochloric acid (8 mL) in acetic acid/sodium acetate buffer solution (200 mL) was added to a large excess of potassium dichromate (19.7 g,67.1 mmol). The reaction mixture was stirred for 3 h at 105 °C, protected from light and atmospheric moisture. After cooling to room temperature, the mixture was filtered, affording 2.3 g of solid (yield 35 %). δH (400 MHz, CDCl3) 1.09 (t, J 7.1, 6H), 3.33(q, J 7.1, 4H), 5.63 (s, 1H), 5.99 (s, 1H), 7.13 (d, J 7.8, 1H), 7.32(d, J 7.8, 2H), 7.69-7.80 (m, 4H), 7.85 (d, J 8.9, 1H). δC(400 MHz, CDCl3) 149.3, 148.4, 143.8, 132.8, 130.2, 130.0,129.5, 125.6, 124.4, 118.5, 115.3, 113.3, 111.9, 47.4, 12.8. Anal.Calc. for C22H23N4Cl: C 69.74, H 6.12, N 14.79. Found: C69.59, H 6.24, N 14.65 %. νmax (KBr)/cm-1 3058, 1649 (NH2),1339, 1198 (C-NH2, N-H), 1601, 1524, 1484 (C=C, C-N),1069, 1006, 991, 874, 849, 812, 776, 704 (C-H), 1392 (-CH3). λmax (DMSO)/nm 560. m/z (ESI) 343.58 [M].
35% With hydrogenchloride; potassium dichromate In aq. acetate buffer at 105℃; for 3h;
  • 85
  • [ 201230-82-2 ]
  • [ 779-03-3 ]
  • [ 93-05-0 ]
  • C25H25N3O [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With 1,4-diaza-bicyclo[2.2.2]octane; oxygen; palladium; sodium iodide at 80℃; for 24h; 6 Example 6 Compound 6: 25mL reaction flask followed by palladium nano(0.001 mmol), amine 1f (0.5 mmol), amine 1f '(2.0 mmol), triethylenediamine (0.1 mmol), sodium iodide (0.25 mmol) and polyethylene glycol-400 (2.0 g), and a largeAtmospheric carbon monoxide and oxygen (1: 1) were reacted at 80 ° C for 24 h. Cool to room temperature, extract and evaporate the solvent under reduced pressureThe yield was isolated 81%.
Same Skeleton Products
Historical Records