Home Cart 0 Sign in  
X

[ CAS No. 78902-09-7 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 78902-09-7
Chemical Structure| 78902-09-7
Chemical Structure| 78902-09-7
Structure of 78902-09-7 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 78902-09-7 ]

Related Doc. of [ 78902-09-7 ]

Alternatived Products of [ 78902-09-7 ]
Product Citations

Product Details of [ 78902-09-7 ]

CAS No. :78902-09-7 MDL No. :MFCD00005901
Formula : C14H17NO4 Boiling Point : -
Linear Structure Formula :- InChI Key :GEFXJJJQUSEHLV-UHFFFAOYSA-N
M.W : 263.29 Pubchem ID :315286
Synonyms :

Calculated chemistry of [ 78902-09-7 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 19
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.43
Num. rotatable bonds : 6
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 72.93
TPSA : 55.84 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.42 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.65
Log Po/w (XLOGP3) : 2.09
Log Po/w (WLOGP) : 1.3
Log Po/w (MLOGP) : 1.7
Log Po/w (SILICOS-IT) : 2.1
Consensus Log Po/w : 1.97

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.63
Solubility : 0.622 mg/ml ; 0.00236 mol/l
Class : Soluble
Log S (Ali) : -2.89
Solubility : 0.337 mg/ml ; 0.00128 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.58
Solubility : 0.0688 mg/ml ; 0.000261 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 2.12

Safety of [ 78902-09-7 ]

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

Application In Synthesis of [ 78902-09-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 78902-09-7 ]
  • Downstream synthetic route of [ 78902-09-7 ]

[ 78902-09-7 ] Synthesis Path-Upstream   1~7

  • 1
  • [ 78902-09-7 ]
  • [ 2913-97-5 ]
YieldReaction ConditionsOperation in experiment
99% for 1 h; Heating / reflux Example 5 : Preparation of N-2-[4-(4-bromo-2-fluoro-phenylamino)-7-(l- methyl-piperidin-4-ylmethoxy)-quinazolin-6-ylamino]-ethyl-acrylamide<5-l> (l,3-dioxo-l,3-dihydro-isoindol-2-yl)-acetaldehyde; Phthalimidoacetaldehyde diethylacetal (1O g, 0.0379 mol) was dissolved in 100 ml of 1 N HCl aqueous solution, and the resulting solution was refluxed and stirred for 1 hour. When the reaction was terminated, the reacted solution was extracted with 200 mi of dichloromethane, washed with 100 mi of salt solution, and distilled under a reduced pressure to obtain the title compound 7.16 g (yield: 99percent).1H NMR (CDCl3) δ: 9.66 (s, IH), 7.90-7.84 (m, 2H), 7.78-7.73 (m, 2H), 4.56 (s, 2H).
95% at 60℃; for 24 h; Compound 1: HCl (0.1 N, 42 mL) was added to a solution of phthalimidoacetaldehyde diethyl acetal (4.18 g, 15.1 mmol) in AcOH (42 mL). The resulting suspension was heated at 60°C for 24 h. The solvent was evaporated and the mixture was dissolved in CH2Cl2. The organic phase was washed with sat. aq NaHCO3, H2O, dried over MgSO4 and evaporated to afford the title compound as a brown solid (2.72 g, 95 percent). The physical data are consistent with the previously reported ones.
95% With hydrogenchloride; acetic acid In water at 60℃; for 24 h; Compound 1 : HC1 (0.1 N, 42 mL) was added to a solution of phthalimidoacetaldehyde diethyl acetal (4.18 g, 15.1 mmol) in AcOH (42 mL). The resulting suspension was heated at 60°C for 24 h. The solvent was evaporated and the mixture was dissolved in CH2CI2. The organic phase was washed with sat. aq NaHC03, H20, dried over MgS04 and evaporated to afford the title compound as a brown solid (2.72 g, 95 percent). The physical data are consistent with the previously reported ones.
93% With trifluoroacetic acid In chloroform at 20℃; for 6 h; Inert atmosphere; Cooling with ice Compound 2 was prepared according to a modified method of Veale et al. (E. B. Veale, J. E. O'Brien, T. McCabe and T. Gunnlaugsson, Tetrahedron, 2008, 64, 6794-6800). In an ice/water bath, under a nitrogen atmosphere, to a solution of phthalimido-acetaldehydediethylacetal (13 g, 49 mmol) in CHCl3 (150 mL), TFA (100 mL) was added. The resulting solution was stirred for 1 h. Then the ice bath was removed and the reaction mixture was stirred at r.t. for a further 5 h. The solvent was removed in vacuo and co-evaporated with CH2Cl2 several times to remove the remaining traces of TFA. This yielded the product (Compound 2) as an off-white solid (9 g, 93percent). No purification was necessary. 1H NMR (CDCl3, 400 MHz) δ 9.68 (s, 1H, CHO), 7.91 (m, 2H), 7.78 (m, 2H), 4.59 (s, 2H); 13C NMR (CDCl3, 100 MHz): δ (100 MHz, CDCl3) 193.6, 167.6, 134.4, 131.9, 123.7, 47.4.
88% for 0.0833333 h; Heating / reflux EXAMPLE 28
7-(((Benzo[1,3]dioxole-5-carbonyl)amino)methyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid
Phthalimidoacetaldehyde diethyl acetal (100 g, 0.38 mol) and 1 N hydrochloric acid (600 ml) was mixture was stirred at reflux temperature for 5 min. or until a homogeneous solution is obtained.
The reaction mixture was cooled and the precipitate was filtered off and dried in vacuo at 50 °C for 16 hours, which afforded 63.3 g (88 percent) of phthalimido-acetaldehyde as a solid.
1H-NMR (300 MHz, CDCl3) δ 4.58 (s, 2H), 7.76 - 7.78(m, 2H), 7.90 - 7.92 (m, 2H), 9.67 (s, 1H).
88% for 0.0833333 h; Heating / reflux Example 28
7-(((Benzo[1,3]dioxole-5-carbonyl)amino)methyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid
Phthalimidoacetaldehyde diethyl acetal (100 g, 0.38 mol) and 1 N hydrochloric acid (600 ml) was mixture was stirred at reflux temperature for 5 min. or until a homogeneous solution is obtained.
The reaction mixture was cooled and the precipitate was filtered off and dried in vacuo at 50° C. for 16 hours, which afforded 63.3 g (88percent) of phthalimido-acetaldehyde as a solid.
1H-NMR (300 MHz, CDCl3) δ 4.58 (s, 2H), 7.76-7.78 (m, 2H), 7.90-7.92 (m, 2H), 9.67 (s, 1H).
88% for 0.0833333 h; Heating / reflux Example 28 7-(((Benzo[1,3]dioxole-5-carbonyl)-amino)-methyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; Phthalimidoacetaldehyde diethyl acetal (100 g, 0.38 mol) and 1 N hydrochloric acid (600 ml) was mixture was stirred at reflux temperature for 5 min. or until a homogeneous solution is obtained. The reaction mixture was cooled and the precipitate was filtered off and dried in vacuo at 50° C. for 16 h which afforded 63.3 g (88percent) of phthalimidoacetaldehyde as a solid.1H NMR (300 MHz, CDCl3) δ 4.58 (s, 2H), 7.76-7.78 (m, 2H), 7.90-7.92 (m, 2H), 9.67 (s, 1H).To a mixture of phthalimidoacetaldehyde (64 g, 0.34 mol) and trans-1-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (81.5 g, 0.38 mol) in benzene (600 ml) stirred for 15 min. under nitrogen was added dropwise a 45percent solution of zinc chloride diethyl ether complex in dichloromethane (55.5 ml, 0.17 mol) at 0° C. The reaction was allowed warm up to room temperature overnight. To the reaction mixture was added water (500 ml) and the resulting mixture was extracted with ethyl acetate (200 ml). The organic extract was washed successively with 1.0 N hydrochloric acid (2.x.200 ml) and brine (200 ml). The organic phase was dried (Na2SO4), filtered and the solvent evaporated in vacuo which afforded a slowly crystallising oil (98 g). To the solid was added a mixture of ethyl acetate and diethyl ether (400 ml, 1:1) and the resulting precipitate was filtered off, washed with a small portion of diethyl ether and dried at 50° C. for 1 h affording 59.8 g (69percent of 2-(4-oxo-3,4-dihydro-2H-pyran-2-ylmethyl)-isoindole-1,3-dione as a solid. The filtrate was evaporated in vacuo and the residue purified by column chromatography on silica gel (1 L) using a mixture of ethyl acetate and heptane (1:2) as eluant. Pure fractions were collected and the solvent evaporated in vacuo to almost dryness, the solid was filtered off and dried in vacuo at 50° C. for 16 h affording an additional 15 g (17percent) of 2-(4-oxo-3,4-dihydro-2H-pyran-2-ylmethyl)-isoindole-1,3-dione as a solid.1H NMR (300 MHz, CDCl3) δ 2.61 (d, 2H), 3.85 (dd, 1H), 4.18 (dd, 1H), 4.76 (m, 1H), 5.43 (d, 1H), 7.28 (d, 1H), 7.69-7.77 (m, 2H), 7.84-7.88 (m, 2H).2-(4-Oxo-3,4-dihydro-2H-pyran-2-ylmethyl)-isoindole-1,3-dione (13 g, 0.051 mol) was dissolved in ethyl acetate (250 ml) and placed in a Parr bottle. 10percent Pd/C (1.5 g) was carefully added and the mixture was shaken under a pressure of 30 psi of hydrogen for 6.5 h (Parr apparatus). Filtration followed by evaporation of the ethyl acetate in vacuo afforded a crude 11.5 g of 2-(4-oxo-tetrahydro-pyran-2-ylmethyl)-isoindole-1,3-dione pure enough for the next step. Analytical pure compound could be obtained by purification of a small sample (250 mg) by column chromatography on silica gel, utilising a mixture of hexane/ethyl acetate as a gradient (from 100/0 to 50/50). Pure fractions were collected and the solvent evaporated in vacuo affording 142 mg (55percent) of 2-(4-oxo-tetrahydro-pyran-2-ylmethyl)-isoindole-1,3-dione as a solid.1H NMR (400 MHz, CDCl3) δ 2.30-2.68 (m, 4H), 3.62 (m, 1H), 3.74 (m, 1H), 4.00 (m, 2H), 7.75 (m, 2H), 7.88 (m, 2H).To a mixture of 2-(4-oxo-tetrahydro-pyran-2-ylmethyl)-isoindole-1,3-dione (11.5 g, 44 mmol), tert-butyl cyanoacetate (6.9 g, 49 mmol) and elemental sulfur (1.6 g, 49 mmol) in ethanol (250 ml) was added morpholin (15 ml) and the resulting mixture was stirred at 50° C. for 16 h. The cooled reaction mixture was filtered and the precipitate filtered off and washed with diethyl ether and dried in vacuo affording 6.5 g (35percent) of 2-amino-5-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester as a solid.The filtrate was evaporated in vacuo and the residue was dissolved in ethyl acetate (200 ml) washed with water (2.x.100 ml), brine (100 ml), dried (Na2SO4), filtered and the solvent evaporated in vacuo affording 6.0 g (33percent) of almost regioisomer pure 2-amino-7-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester as a solid.2-amino-5-(1,3-dioxo-1,3'-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester1H NMR (300 MHz, CDCl3) δ1.50 (s, 9H), 2.54-2.63 (m, 1H), 2.84-2.90 (m, 1H), 3.79 (q, 1H), 3.96-4.04 (m, 2H), 4.48-4.62 (m, 2H), 5.91 (bs, 2H, NH2), 7.70 (m, 2H), 7.84 (m, 2H).2-amino-7-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester1H NMR (300 MHz, CDCl3) δ 1.50 (s, 9H), 2.71-2.90 (m, 2H), 3.67-3.77, (m, 2H), 4.02-4.15 (m, 2H), 4.90 (m, 1H), 6.04 (bs, 2H, NH2), 7.70 (m, 2H), 7.84 (m, 2H).To a solution of 2-amino-7-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (6.0 g, 0.014 mol) in ethanol (100 ml) was added hydrazine-hydrate (1.4 ml, 0.029 mol). The mixture was stirred at reflux temperature for 1 h. The cooled reaction mixture was filtered and the solvent evaporated in vacuo. The residue was dissolved in diethyl ether (200 ml) and washed with water (100 ml), brine (100 ml), dried (Na2SO4), filtered and the solvent evaporated in vacuo affording 2.9 g (71percent) of 2-amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester as an oil.To a ice cooled mixture of 2-amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (1.4 g, 4.92 mmol), triethylamine (2 ml) in dichloromethane (100 ml) was added dropwise a solution of benzo[1,3]dioxole-5-carbonyl chloride (1.0 g, 5.41 mmol) in dichloromethane (25 ml) during 1.5 h. The ice cooled reaction mixture was stirred for an additional 0.5 h. The volatiles were evaporated in vacuo and the residue was dissolved in ethyl acetate (200 ml) and washed with water (2.x.100 ml), brine (100 ml), dried (Na2SO4), filtered and the solvent evaporated in vacuo. The residue (2 g) was subjected to flash column chromatography (1 l silicagel) using a mixture of ethyl acetate/hexane (1:2) as eluant. Pure fractions were collected affording after evaporation in vacuo 0.3 g (14percent) of 2-amino-7-(((benzo[1,3]dioxole-5-carbonyl)amino)-methyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester as an oil.TLC: Rf=0.44 (ethyl acetate/heptane 1:1)A mixture of the above 2-amino-7-(((benzo[1,3]dioxole-5-carbonyl)amino)methyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl, ester (0.3 g, 0.69 mmol), imidazol-1-yl-oxo-acetic acid tert-butyl ester (0.16 g, 0.83 mmol) in dry tetrahydrofuran (50 ml) was stirred at room temperature for 16 h. The volatiles were evaporated in vacuo and the residue was dissolved in ethyl acetate (100 ml) and washed with water (2.x.50 ml), brine (50 ml), dried (Na2SO4), filtered and the solvent evaporated in vacuo. The residue (0.35 g) was subjected to flash column chromatography (500 ml silicagel) using a mixture of ethyl acetate/hexane (1:1) as eluant. Pure fractions were collected and the solvent evaporated in vacuo. The residue was trituated with diethyl ether (5 ml), filtered off and dried in vacuo at 50° C. for 5 h which afforded 0.17 g (44percent) of 7-(((benzo[1,3]dioxole-5-carbonyl)amino)methyl)-2-(tert-butoxyoxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester as a solid.TLC: Rf=0.37 (ethyl acetate/heptane 1.1).The above di-tert-butyl ester (0.17 g, 0.30 mmol) was dissolved in 25percent trifluoroacetic acid in dichloromethane (20 ml). The reaction was stirred at room temperature for 5.5 h. The volatiles were evaporated in vacuo and the residue trituated with diethyl ether (10 ml). The precipitate was filtered off, washed with diethyl ether, dried in vacuo at 50° C. for 72 h which afforded 100 mg (74percent) of the title compound as a solid.M.p.: 277-230° C.Calculated for C19H16N2O9S, 0.5.x.H2O; C, 49.89percent; H, 3.75percent; N, 6.12percent. Found: C, 50.02percent; H, 3.68percent; N, 5.98percent.
84% With trifluoroacetic acid In dichloromethane at 20 - 25℃; for 24 h; Step 1. Preparation of C95. A solution of C94 (50.0 g, 189.9 mmol) indichloromethane (100 mL) was treated with trifluoroacetic acid (50.0 mL, 661.3 mmol). The reaction mixture was stirred at room temperature for 24 hours. The dichloromethane and trifluoroacetic acid was displaced with toluene (4 x 150 mL) using vacuum, to a final volume of 120 mL. The solution was added to heptane (250 mL) and the solid was collected by filtration. The solid was washed with a mixture of toluene and heptane (1 : 3, 60 mL), followed by heptane (2 x 80 mL) and dried under vacuum at 50 °C for 19 hours to afford C95 as a solid. Yield: 30.0 g, 158 mmol, 84percent. 1H NMR (400 MHz, CDCI3) δ 9.66 (s, 1 H), 7.86 - 7.93 (m, 2H), 7.73 - 7.80 (m, 2H), 4.57 (s, 2H). HPLC retention time 5.1 minutes; column: Agilent Extended C-18 column (75 mm x 3 mm, 3.5 μηη); column temperature 45 °C; flow rate 1.0 mL / minute; detection UV 230 nm; mobile phase: solvent A = acetonitrile (100percent), solvent B = acetonitrile (5percent) in 10 mM ammonium acetate; gradient elusion: 0-1.5 minutes solvent B (100percent), 1.5-10.0 minutes solvent B (5percent), 10.0-13.0 minutes solvent B (100percent); total run time 13.0 minutes.
80% at 100℃; for 0.5 h; The foregoing compound (3 g) and hydrochloric acid (15mL) were heated at 100 °C for 30minutes with stirring. The product crystallised on cooling. It was collected and purified from diethyl ether. Yield 80percent;Elemental analysis calculated for C10H7NO3 (189.17): C 63.4,H 3.7, N 7.4; found: C 62.4, H 3.4, N 7.5. 1H NMR (300MHz, CDCl3): δ9.62 (s, 1H), 7.85–7.65 (m, 4H), 4.45 (s, 2H). ES-MS:m/z 190. IR: ν(C=O) 1721 cm−1.
56%
Stage #1: With hydrogenchloride; water In tetrahydrofuran at 20℃; for 20 h;
A.7.1 Synthesis of (1,3-dioxo-1 ,3-dihydro-isoindol-2-yl)-acetaldehydeTo a solution of phthalimideacetaldehyde diethylacetal (10 g) in dry THF (57 mL), was added aq 6N HCI (207 mL) and the mixture was stirred at rt for 20 h. The reaction mixture was concentrated in vacuo, treated carefully with sat. NaHCOs solution and extracted with DCM. The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo to yield the title compound as a white solid (4.53 g, 56percent).
56% With hydrogenchloride In tetrahydrofuran at 20℃; for 20 h; To a solution of phthalimideacetaldehyde diethylacetal (10 g) in dry THF (57 mL), was added aq 6N HCl (207 mL) and the mixture was stirred at rt for 20 h. The reaction mixture was concentrated in vacuo, treated carefully with sat. NaHCO3 solution and extracted with DCM. The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo to yield the title compound as a white solid (4.53 g, 56percent).1H-NMR (CDCl3): δ=4.55 (s, 2H); 7.75 (dd, 2H); 7.91 (dd, 2H); 9.6 (s, 1H).
55% for 2 h; Reflux Compound 3 was prepared by the condensation of commercially available aminoacetaldehyde diethyl acetal with the phthalic anhydride (1:1 mol ratio), using toluene under reflux, in the presence of a catalytic amount of DMAP (yield 52percent) for 2 h. In the next step, 2-(2,2-diethoxyethyl)isoindoline-1,3-dione (3) underwent acid hydrolysis (sulphuric acid at 70percent) in reflux for 2 h. After the reaction was completed, it was allowed to reach at room temperature and was then cooled to induce precipitation. The formed precipitate was filtered on a sintered funnel with distilled water, yielding 55percent of the pure product. For the synthesis of 5a and 5b, 2-(1,3-dioxoisoindol-2-yl) acetaldehyde (4) reacted with thiosemicarbazide (in the ratio 1:1) (for 5a) or 4-phenyl-3-thiosemicarbazide (for 5b), in ethanol, under reflux with catalytic amount of HCl (4 drops) for 4 h. The reactions were followed by thin layer chromatographic plate analysis. The formed precipitate was filtered on a sintered funnel with ethanol to yield the pure product (yield 76percent for 5a and 70percent for 5b).

Reference: [1] Tetrahedron, 2002, vol. 58, # 9, p. 1719 - 1737
[2] Tetrahedron, 2008, vol. 64, # 28, p. 6794 - 6800
[3] Patent: WO2007/55513, 2007, A1, . Location in patent: Page/Page column 29
[4] Angewandte Chemie - International Edition, 2015, vol. 54, # 33, p. 9668 - 9672[5] Angew. Chem., 2015, vol. 127, # 33, p. 9804 - 9808,5
[6] Journal of Medicinal Chemistry, 2013, vol. 56, # 23, p. 9709 - 9724
[7] ACS Medicinal Chemistry Letters, 2011, vol. 2, # 10, p. 747 - 751
[8] Patent: EP2537855, 2012, A1, . Location in patent: Page/Page column 19
[9] Patent: WO2012/175516, 2012, A1, . Location in patent: Page/Page column 25
[10] Organic Process Research and Development, 2018, vol. 22, # 2, p. 212 - 218
[11] Chemical Communications, 2014, vol. 50, # 2, p. 216 - 218
[12] Patent: US9605297, 2017, B2, . Location in patent: Page/Page column 10; 11
[13] Synthetic Communications, 2003, vol. 33, # 10, p. 1789 - 1795
[14] Patent: EP1214325, 2005, B1, . Location in patent: Page/Page column 47
[15] Patent: US7019026, 2006, B1, . Location in patent: Page/Page column 68
[16] Patent: US7115624, 2006, B1, . Location in patent: Page/Page column 82-84
[17] Patent: WO2012/73138, 2012, A1, . Location in patent: Page/Page column 82-83
[18] Journal of Medicinal Chemistry, 2013, vol. 56, # 13, p. 5541 - 5552
[19] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 15, p. 4667 - 4678
[20] Journal of Chemistry, 2015, vol. 2015,
[21] Journal of the Indian Chemical Society, 1998, vol. 75, # 1, p. 46 - 48
[22] Organic Process Research and Development, 2012, vol. 16, # 12, p. 1897 - 1904
[23] Patent: WO2010/4507, 2010, A1, . Location in patent: Page/Page column 69
[24] Patent: US2011/105491, 2011, A1, . Location in patent: Page/Page column 34-35
[25] European Journal of Medicinal Chemistry, 2016, vol. 111, p. 46 - 57
[26] Recueil des Travaux Chimiques des Pays-Bas, 1932, vol. 51, p. 483,487
[27] Journal of Pharmacy and Pharmacology, 1952, vol. 4, p. 693,705
[28] Tetrahedron, 2003, vol. 59, # 37, p. 7413 - 7422
[29] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 12, p. 4035 - 4046
[30] Patent: US2002/151561, 2002, A1,
[31] Patent: US2005/131017, 2005, A1, . Location in patent: Page/Page column 96
[32] Patent: US2005/131042, 2005, A1, . Location in patent: Page/Page column 65-66
[33] Patent: US2005/148623, 2005, A1, . Location in patent: Page/Page column 129
[34] Patent: WO2005/61487, 2005, A1, . Location in patent: Page/Page column 125
[35] Patent: US2005/159469, 2005, A1, . Location in patent: Page/Page column 64
[36] ChemMedChem, 2010, vol. 5, # 4, p. 523 - 528
[37] Biomacromolecules, 2014, vol. 15, # 5, p. 1612 - 1624
[38] European Journal of Medicinal Chemistry, 2015, vol. 96, p. 491 - 503
[39] Patent: US2015/225399, 2015, A1,
  • 2
  • [ 78902-09-7 ]
  • [ 76-05-1 ]
  • [ 2913-97-5 ]
Reference: [1] Patent: EP874849, 2001, B1,
[2] Patent: US5714487, 1998, A,
[3] Patent: US6284757, 2001, B1,
  • 3
  • [ 1074-82-4 ]
  • [ 2032-35-1 ]
  • [ 78902-09-7 ]
YieldReaction ConditionsOperation in experiment
70% With cetyltributylphosphonium bromide In toluene at 111℃; for 24 h; Inert atmosphere Potassium phthalimide (5 g,26.5mmol), bromoacetal (4.1 mL, 26.5mmol), and hexadecyltributylphosphoniumbromide (13.8 g, 26.5mmol) wereheated together in toluene (200mL) for 24 h at 111 °C under N2 atmosphere.The product was then filtered, and the filtratewas concentrated on a rotary evaporator to give yellow oil.Column chromatography using hexane : ether (1 : 1) allowedobtaining the desired compound. Yield 70percent; Elementalanalysis calculated for C14H17NO4 (263.29): C 63.8, H 6.4, N 5.3; found: C 64.6, H 6.5, N 5.3. 1H NMR (300MHz,CDCl3): δ7.8–7.6 (m, 4H), 4.79 (t, 1H), 3.75 (d, 2H), 3.62–3.42 (m, 4H), 1.06 (t, 6H). ES-MS: m/z 264. IR: ν(C-O-C)2800, ](C=O) 1721 cm−1.
64% at 150℃; for 4 h; intermediate 395 H-Isoindole- l ,3(2H)-dionc, potassium salt (1 : 1) (50 g, 221.9 mmol ) and 2-bromo- 1 , 1 - diethoxy-ethane (54.7 g, 277.4 mmol ) in DMF were stirred at 1 50 °C for 4 hours. The DMF was removed under reduced pressure. The residue was purified by column chromatography (elution: petroleum ether/ ethyl acetate ratio 5/ 1 ) to afford intermediate 395 (40 g, yield: 64percent) as a white solid.
Reference: [1] Russian Journal of General Chemistry, 2007, vol. 77, # 1, p. 98 - 102
[2] Journal of Chemistry, 2015, vol. 2015,
[3] Patent: WO2017/32840, 2017, A1, . Location in patent: Page/Page column 264; 265
[4] Journal of Pharmacy and Pharmacology, 1952, vol. 4, p. 693,705
  • 4
  • [ 85-44-9 ]
  • [ 645-36-3 ]
  • [ 78902-09-7 ]
YieldReaction ConditionsOperation in experiment
52% With dmap In toluene for 2 h; Reflux Compound 3 was prepared by the condensation of commercially available aminoacetaldehyde diethyl acetal with the phthalic anhydride (1:1 mol ratio), using toluene under reflux, in the presence of a catalytic amount of DMAP (yield 52percent) for 2 h. In the next step, 2-(2,2-diethoxyethyl)isoindoline-1,3-dione (3) underwent acid hydrolysis (sulphuric acid at 70percent) in reflux for 2 h. After the reaction was completed, it was allowed to reach at room temperature and was then cooled to induce precipitation. The formed precipitate was filtered on a sintered funnel with distilled water, yielding 55percent of the pure product. For the synthesis of 5a and 5b, 2-(1,3-dioxoisoindol-2-yl) acetaldehyde (4) reacted with thiosemicarbazide (in the ratio 1:1) (for 5a) or 4-phenyl-3-thiosemicarbazide (for 5b), in ethanol, under reflux with catalytic amount of HCl (4 drops) for 4 h. The reactions were followed by thin layer chromatographic plate analysis. The formed precipitate was filtered on a sintered funnel with ethanol to yield the pure product (yield 76percent for 5a and 70percent for 5b).
Reference: [1] Journal of the Indian Chemical Society, 1998, vol. 75, # 1, p. 46 - 48
[2] European Journal of Medicinal Chemistry, 2016, vol. 111, p. 46 - 57
[3] Recueil des Travaux Chimiques des Pays-Bas, 1932, vol. 51, p. 483,487
[4] ChemMedChem, 2010, vol. 5, # 4, p. 523 - 528
[5] European Journal of Medicinal Chemistry, 2015, vol. 96, p. 491 - 503
  • 5
  • [ 201230-82-2 ]
  • [ 100-52-7 ]
  • [ 645-36-3 ]
  • [ 78902-09-7 ]
Reference: [1] Journal of Organic Chemistry, 2018, vol. 83, # 1, p. 104 - 112
  • 6
  • [ 524-38-9 ]
  • [ 645-36-3 ]
  • [ 78902-09-7 ]
Reference: [1] Chemical Communications, 2015, vol. 51, # 3, p. 473 - 476
  • 7
  • [ 136918-14-4 ]
  • [ 2032-35-1 ]
  • [ 78902-09-7 ]
Reference: [1] ACS Medicinal Chemistry Letters, 2011, vol. 2, # 10, p. 747 - 751
Recommend Products
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 78902-09-7 ]

Ethers

Chemical Structure| 89314-87-4

[ 89314-87-4 ]

N-(2,2-Dimethoxyethyl)-2-phenylacetamide

Similarity: 0.73

Chemical Structure| 88150-75-8

[ 88150-75-8 ]

Ethyl 4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate

Similarity: 0.73

Chemical Structure| 72432-10-1

[ 72432-10-1 ]

1-(4-Methoxybenzoyl)pyrrolidin-2-one

Similarity: 0.67

Chemical Structure| 50727-04-3

[ 50727-04-3 ]

5-Methoxyisoindoline-1,3-dione

Similarity: 0.66

Chemical Structure| 22246-66-8

[ 22246-66-8 ]

5-Methoxyisoindolin-1-one

Similarity: 0.64

Ketones

Chemical Structure| 101207-45-8

[ 101207-45-8 ]

2-(4-Methylbenzyl)isoindoline-1,3-dione

Similarity: 0.75

Chemical Structure| 88150-75-8

[ 88150-75-8 ]

Ethyl 4-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)-3-oxobutanoate

Similarity: 0.73

Chemical Structure| 104618-32-8

[ 104618-32-8 ]

2-(4-Oxocyclohexyl)isoindoline-1,3-dione

Similarity: 0.66

Chemical Structure| 3416-57-7

[ 3416-57-7 ]

2-(2-Oxopropyl)isoindoline-1,3-dione

Similarity: 0.66

Chemical Structure| 1029691-06-2

[ 1029691-06-2 ]

2-(3-Oxocyclopentyl)isoindoline-1,3-dione

Similarity: 0.65

Related Parent Nucleus of
[ 78902-09-7 ]

Indolines

Chemical Structure| 161596-47-0

[ 161596-47-0 ]

(S)-2-(Oxiran-2-ylmethyl)isoindoline-1,3-dione

Similarity: 0.83

Chemical Structure| 84764-41-0

[ 84764-41-0 ]

2-(2-(2-Methyl-1,3-dioxolan-2-yl)ethyl)isoindoline-1,3-dione

Similarity: 0.81

Chemical Structure| 883-44-3

[ 883-44-3 ]

2-(3-Hydroxypropyl)isoindoline-1,3-dione

Similarity: 0.77

Chemical Structure| 4702-13-0

[ 4702-13-0 ]

N-Phthaloylglycine

Similarity: 0.77

Chemical Structure| 181140-34-1

[ 181140-34-1 ]

(R)-2-(Oxiran-2-ylmethyl)isoindoline-1,3-dione

Similarity: 0.76