Structure of 117738-77-9
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CAS No. : | 117738-77-9 |
Formula : | C8H4ClNO2 |
M.W : | 181.58 |
SMILES Code : | O=C(O)C1=CC=C(C#N)C=C1Cl |
MDL No. : | MFCD11036377 |
InChI Key : | VTROYYKGGOPEPS-UHFFFAOYSA-N |
Pubchem ID : | 231894 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.13 |
TPSA ? Topological Polar Surface Area: Calculated from |
61.09 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.15 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.73 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.91 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.55 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.83 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.63 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.36 |
Solubility | 0.793 mg/ml ; 0.00437 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.63 |
Solubility | 0.426 mg/ml ; 0.00235 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.47 |
Solubility | 0.611 mg/ml ; 0.00337 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.18 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.59 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In N-methyl-acetamide; hexane; dichloromethane; ethyl acetate; | EXAMPLE 77 3-Chloro-4-(5H,11H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carbonyl)-benzonitrile To a cooled suspension of <strong>[117738-77-9]2-chloro-4-cyanobenzoic acid</strong> (9.1 g) in a mixture of dichloromethane (40 ml) and dimethylformamide (3.88 ml) was added dropwise a solution of oxalyl chloride (4.6 ml) in dichloromethane (10 ml) at 0 C. The stirred reaction was allowed to warm to room temperature over a one hour period. A cloudy solution of 2-chloro-4-cyanobenzoyl chloride was utilized without further purification. To a stirred suspension of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (7.32 g) and diisopropylethylamine (13.6 ml) in dichloromethane (35 ml) was added under nitrogen the cloudy solution of 2-chloro-4-cyanobenzoyl chloride. After one hour at room temperature, the mixture was diluted with dichloromethane and washed sequentially with water, 5% sodium bicarbonate, and 50% saturated brine, After drying over anhydrous sodium sulfate, the solvent was removed in vacuo to afford a crude product (18.0 g). Purification by column chromatography on silica gel (250 g), eluding with 20% ethyl acetate/hexane, followed by 25% ethyl acetate/hexane, yielded the title compound (13.56 g) as a straw yellow foam, MS (EI), m/z: 347 (M)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 12h; | Example 36: (+Hrans-2-Chloro-4-cyano-benzoic acid 2-(2-acetoxymethyl-1 -methylpyrrol- idin-3-yl)-6-acetyl-3,5-dimethoxy-phenyl ester; A mixture of the compound of example (6)(3.84 g, 10 mmol), 2-chloro-4-cyano- benzoic acid (2.48 g, 13 mmol), DCC (4.51 g, 21 mmol) and DMAP (1.34 g, 10 mmol) were dissolved in dichloromethane (50 ml_) and stirred at room temperature for 12 hrs. The reaction mixture is cooled to 0 0C, the precipitated dicyclohexylurea was filtered and the organic layer concentrated and the residue purified by column chromatography with 1 % methanol in chloroform and 0.01 % ammonia as eluent to give the compound, (+)-^rans-2-chloro-4- cyanobenzoic acid 2-(2-acetoxymethyl-1 -methylpyrrolidin-3-yl)-6-acetyl-3,5- dimethoxyphenyl ester. <n="58"/>Yield: 3.5 g (62 %);1H NMR (CDCI3, 300MHz): delta 8.19 (d, 1 H), 7.79 (s, 1 H), 7.69 (d, 1 H), 6.45 (s, 1 H), 4.10 (m, 1 H), 3.93 (s, 6H), 3.48 (m, 2H), 3.11 (m, 1 H), 2.72 (m, 1 H), 2.48 (s, 3H), 2.35 (s, 3H), 2.10 (m, 1 H), 1.92 (m, 2H), 1.74 (s, 3H); MS (ES+): m/z 515 (M+1 ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; toluene; at 0 - 20℃; for 2.5h; | <strong>[117738-77-9]2-Chloro-4-cyanobenzoic acid</strong> (58.2 mg, 320 muiotaetaomicron) was suspended in dichloromethane (5 mL), the suspension was cooled to 0-5C (ice bath) and oxalyl chloride (56.9 mg, 39.3 mu, 448 muiotaetaomicron) as well as dimethylformamide (0.308 M in toluene, 48 mu, 15 muiotaetaomicron) were added. The mixture was stirred for 2.5 h at room temperature. Then, it was concentrated in vacuo (40C, 5 mbar) and dried azeotropically by two cycles of addition of toluene (3 mL) followed by concentration in vacuo to afford 2-chloro-4-cyanobenzoyl chloride as yellow oil (64 mg, quant.). After that, tert-butyl ((3aS,4R,8R)-4-(5-amino-2-fluorophenyl)-4,7,7-trimethyl-8-oxido-3,3a,4,7- tetrahydro-2H-isothiazolo[l,5-a][l,4]thiazin-6-yl)carbamate (Int-16ABp, 80 mg, 188 muiotaetaomicron) was dissolved in dichloromethane (5 mL), the solution cooled to 10C and N,N- diisopropylethylamine (41.4 mg, 56 mu, 320 muiotaetaomicron) was added, followed by a solution of 2- chloro-4-cyanobenzoyl chloride (vide supra, 51 mg, 256 muiotaetaomicron) in dichloromethane (4 mL). The reaction mixture was stirred for 15 min at 10C. Then, methanol (2 mL) was added, the mixture was stirred for 5 min at room temperature and concentrated in vacuo. The crude was purified by column chromatography (silica gel, 12 g, eluting with ethyl acetate / n-heptane, gradient 35:65 to 100:0) to yield, after drying in vacuo (40C, 5 mbar), the title compound as a light yellow solid (96 mg, 87%). HPLC (method LCMS_fglm) tR = 1.22 min. MS (ES+) m/z 588.5 [M+H]. |
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 2 - 3h; | Example No.6: Preparation of 3-chloro-4-(3-(3-chloro-4-isopropoxyphenyl)-l,2,4- oxadiazol-5-yl)benzonitriIe; To a 25OmL RBF equi with a stir bar was charged with <strong>[117738-77-9]2-chloro-4-cyanobenzoic acid</strong> (3.0 g, 16.52 mmol), anhydrous DCM (80 mL), and DMF (0.064 mL, 0.826 mmol). Oxalyl chloride (8.26 mL, 16.52 mmol) (2M solution in DCM) was then added slowly and the mixture was stirred under nitrogen at ambient temperature. Upon addition of the oxalyl chloride, gas evolution began and the suspended solid began to dissolve. After about 2-3 hours, the reaction became translucent. The mixture was concentrated in vacuo. The resulting crude material was dissolved in pyridine (50 mL). To this was added (Z)-3-chloro-N'- hydroxy-4-isopropoxybenzimidamide (1.258 g, 5.50 mmol). The mixture was heated to about 100 0C under an atmosphere of nitrogen for about 16 hrs. The resulting mixture was cooled to ambient temperature. Pyridine was removed under reduced pressure and the resulting material was triturated in DCM and MeOH mixture (about 1: 1). The resulting precipitate was left standing for a few minutes at ambient temperature then was collected via filtration, washed with a mixture of 1:1 DCM/MeOH, and then with straight MeOH and dried in a vacuum oven for about 48 hrs to yield 3-chloro-4-(3-(3-chloro-4-isopropoxyphenyl)-l,2,4- oxadiazol-5-yl)benzonitrile (1.529g, 4.09 mmol) as a beige solid. 1H NMR (400 MHz, DMSO) delta ppm 8.39 (d, J = 1.53 Hz, IH), 8.35 (d, J = 8.15 Hz, IH), 8.09 (dd, J = 8.14, 1.53 Hz, IH), 8.05 (d, / = 2.11 Hz, IH), 8.00 (dd, J = 8.63, 2.12 Hz, IH), 7.39 (d, J = 8.82 Hz, IH), 4.82 (sept, J = 6.04 Hz, IH), 1.35 (d, J = 6.01 Hz, 6H). | |
With oxalyl dichloride; N,N-dimethyl-formamide; In hexane; dichloromethane; at 0 - 20℃; for 1h; | EXAMPLE 77 3-Chloro-4-(5H,11H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carbonyl)-benzonitrile To a cooled suspension of <strong>[117738-77-9]2-chloro-4-cyanobenzoic acid</strong> (9.1 g) in a mixture of dichloromethane (40 ml) and dimethylformamide (3.88 ml) was added dropwise a solution of oxalyl chloride (4.6 ml) in dichloromethane (10 ml) at 0 C. The stirred reaction was allowed to warm to room temperature over a one hour period.. A cloudy solution of 2-chloro-4-cyanobenzoyl chloride was utilized without further purification. |
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 1h; | To a cooled suspension of <strong>[117738-77-9]2-chloro-4-cyanobenzoic acid</strong> (9.1 g) in a mixture of dichloromethane (40 ml) and dimethylformamide (3.88 ml) was added dropwise a solution of oxalyl chloride (4.6 ml) in dichloromethane (10 ml) at 0 C. The stirred reaction was allowed to warm to room temperature over a one hour period. A cloudy solution of 2-chloro-4-cyanobenzoyl chloride was utilized without further purification. | |
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃;Inert atmosphere; | Preparation No.5: Preparation of 3-chloro-4-(3-(3-chloro-4-isopropoxyphenyl)-l,2,4- oxadiazol-5-yl)benzonitrile; To a 250 mL round bottom flask equipped with a stir bar and charged with 2-chloro-4- cyanobenzoic acid (3.0 g, 16.52 mmol), was added anhydrous DCM (80 mL), and DMF (0.064 mL, 0.826 mmol). Oxalyl chloride (8.26 mL, 16.52 mmol) (2M solution in DCM) was then added slowly and the mixture was stirred under nitrogen at ambient temperature. Upon addition of the oxalyl chloride, gas evolution began and the suspended solid began to dissolve. After about 2-3 h, the reaction became translucent. The mixture was concentrated in vacuo. The resulting crude material was dissolved in pyridine (50 mL). To this was added (Z)-3- chloro-A^-hydroxy-4-isopropoxybenzimidamide (1.258 g, 5.50 mmol). The mixture was heated to about 100 C under an atmosphere of nitrogen for about 16 h. The resulting mixture was cooled to ambient temperature. Pyridine was removed under reduced pressure and the resulting material was triturated in DCM and MeOH mixture (about 1 : 1). The resulting precipitate was left standing for a few minutes at ambient temperature then was collected via filtration, washed with a mixture of 1 : 1 DCM/MeOH, and then with straight MeOH and dried in a vacuum oven for about 48 h to yield 3-chloro-4-(3-(3-chloro-4-isopropoxyphenyl)- 1,2,4- oxadiazol-5-yl)benzonitrile (1.529g, 4.09 mmol, 25%) as a beige solid. .H NMR (400 MHz, DMSO) delta ppm 8.39 (d, J = 1.53 Hz, 1H), 8.35 (d, J = 8.15 Hz, 1H), 8.09 (dd, J = 8.14, 1.53 Hz, 1H), 8.05 (d, J = 2.11 Hz, 1H), 8.00 (dd, J = 8.63, 2.12 Hz, 1H), 7.39 (d, J = 8.82 Hz, 1H), 4.82 (sept, J = 6.04 Hz, 1H), 1.35 (d, J = 6.01 Hz, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | Lithium hydroxide (1.12 g, 26.69 mmol) was added to a solution of 2-chloro-4-cyano-benzoic acid methyl ester (2.60 g, 13.29 mmol) in dioxan/water (4:1, 100ml). The mixture was stirred at room temperature for 3h and concentrated in vacuo. The residue was partitioned between 1N hydrochloric acid and chloroform and the organic layer was washed with brine and concentratedin vacuo. The residue was recrystallised from a mixture of dioxan and pet. ether to give a pale orange solid identified as 2-chloro-4-cyanobenzoic acid (2.33 g, 97%). | |
63.3% | Intermediate 125b was dissolved in a 0.5molar 1 : 1 mixture of MeOH / THF and LiOH.H20 (302 mg, 7.21 mmol. The reaction was stirred for 5hrs before the solvent was removes under vaccuum.The residue was suspended in water and acidified with aqueous HCI (2M). A pink precipitate was filtered off and dried under HV + cold trap to yield intermediate 125c (569.2 mg, 3.04 mmol, 63.3 % yield) as pinkish solid.1 H NMR (400 MHz, DMSO-c 6) delta ppm 13.95 (br. S., 1 H), 8.18 (s, 1 H), 7.85 - 7.96 (m, 2 H). RtMSi= 1.21 min., [M+H]+ = 182.1. | |
55% | With lithium hydroxide; water; In tetrahydrofuran; for 18h; | 2-Chloro-4-cyanobenzoic acid Lithium hydroxide monohydrate (1.18g, 28mmol) was added to a solution of 2-chloro-4-cyanobenzoic acid methyl ester (2.61g, 13mmol) in a mixture of THF and water (4:1, 100ml) and stirred for 18h. The mixture was reduced in vacuo, the residue was acidified with 1N hydrochloric acid and extracted with a mixture of methanol and chloroform (5:95). The organic extracts were washed with brine, dried and reduced. The residue was recrystallized from dioxan/pet. ether to give a pale orange solid identified as 2-chloro-4-cyanobenzoic acid, yield 1.34g, 55%. |
With sodium hydroxide; In methanol; water; | EXAMPLE 76 2-Chloro-4-cyanobenzoic Acid To a stirred solution of 2-chloro-4-cyanobenzoic acid, methyl ester (24.3 g) in methanol (150 ml) was added 2.5N sodium hydroxide (54.5 ml). After stirring at room temperature. for 45 minutes, the solvent was removed in vacuo. The residue was dissolved in water, cooled in an ice bath, and made acidic with 2N hydrochloric acid (14 ml). The resulting precipitate was filtered and dried in vacuo to yield the title compound as a solid (22.55 g) m.p. 154-158 C. | |
To a stirred solution of 2-chloro-4-cyanobenzoic acid, methyl ester (24.3 g) in methanol (150 ml) was added 2.5N sodium hydroxide (54.5 ml). After stirring at room temperature. for 45 minutes, the solvent was removed in vacuo. The residue was dissolved in water, cooled in an ice bath, and made acidic with 2N hydrochloric acid (14 ml). The resulting precipitate was filtered and dried in vacuo to yield the title compound as a solid (22.55 g) m.p. 154-158 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | Example 294A 4-cyano-2-chlorobenzoic acid Under a nitrogen atmosphere, Zn(CN)2 (58 mg, 0.50 mmol) and 4-bromo-2-chlorobenzoic acid (200 mg, 0.90 mmol) were added to dry dimethylformamide (5 mL), followed by tetrakis(triphenylphosphine)palladium(0) (43 mg, 0.036 mmol). The resulting yellow slurry was heated to 80 C. overnight. After it was cooled to room temperature, it was diluted with ethyl ether (20 mL), and washed with water (2*10 mL). Then the ethereal portion was collected, dried with Na2SO4, filtered and concentrated in vacuo to give 2-chloro-4-cyanobenzoic acid (60 mg, 37% yield) as a white solid. Reference: Magidson, O. J.; Trawin, A. I. Chem Ber. 1936, 69, 537-544. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium carbonate; sodium nitrite; In water; ethyl acetate; | EXAMPLE 75 2-Chloro-4-cyanobenzoic Acid, Methyl Ester 2-chloro-4-aminobenzoic acid, methyl ester (13.95 g) was suspended in a mixture of water (65 ml) and concentrated hydrochloric acid (15.7 ml). After stirring at room temperature for 10 minutes, the suspension was cooled to 0 C. A solution of sodium nitrite (5.71 g) in water (37 ml) was gradually added over 20 minutes, maintaining a reaction temperature of 0 C. After stirring at 0 C. for 35 minutes, the reaction mixture was partially neutralized by the addition of solid sodium carbonate (3.16 g) to afford a cold solution of the diazonium salt. To a pre-cooled solution of copper(I) cyanide (8.4 g) and sodium cyanide (9.19 g) in water (112 ml) was gradually added the above solution of diazonium salt over a 45-50 minute period. The diazonium salt solution was maintained at 0 C. during the addition. The resulting mixture was stirred for 18 hours at room temperature. A precipitate was filtered, air-dried, dissolved in ethyl acetate (250 ml), and filtered to remove insoluble matter. The organic phase was dried over anhydrous magnesium sulfate, and the solvent removed in vacuo to afford a crude product as a brown solid (13.2)g). The crude product was purified by column chromatography on silica gel (250 g), eluding with 5-10% ethyl acetate/hexane to yield the title compound (10.9 g) as a solid, m.p. 90-92 C.; MS (EI), m/z: 195 (M)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; thionyl chloride; In tetrahydrofuran; hexane; toluene; | 5.7 g (31.4 mmol) of <strong>[117738-77-9]2-chloro-4-cyano-benzoic acid</strong>, which was prepared by oxidation of 3-chloro-4-methyl-benzonitrile (according to Chem. Ber. 1936, 69, 537, the disclosure of which is incorporated herein by reference), were dissolved in 300 ml toluene, and 10.25 g (86.2 mmol) thionyl chloride were added. After 4 hours heating with reflux the same amount of thionyl chloride was added and heating was continued overnight. The solvent was removed under reduced pressure, the residue dissolved in 100 ml toluene, and again it was concentrated in vacuo to leave the crude acid chloride as a yellow oil. Yield: 4.1 g (65%) A solution of 0.98 g (3.96 mmol) of the tetralone 98 and 3.3 ml dry pyridine in 33 ml dry THF was cooled with ice, and a solution of 1.0 g (5.0 mmol) of the crude 2-chloro-4-cyanobenzoyl chloride in 33 ml dry THF was added dropwise. The mixture was warmed slowly to room temperature, stirred over night, and poured into ice-cold water. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium bicarbonate and with brine, successively, and dried over sodium sulfate. The product was concentrated under reduced pressure, and the residue was stirred with hexane to give the crystalline nitrile (280), which was filtered and dried in vacuo at 50 C. Yield: 1.5 g (92%) of beige crystalline solid, m.p. 173-175 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium hydroxide; In ethanol; | (41-2) In 15 ml of ethanol was dissolved 1.1 g (5.0 mmol) of ethyl 2-chloro-4-cyanobenzoate, and 10 ml of a 1N aqueous sodium hydroxide solution was added to the solution and the resulting mixture was stirred overnight. To the resulting reaction mixture was added 11 ml of 1N hydrochloric acid and the mixture was extracted with 50 ml of ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 0.91 g (5.0 mmol) of the title compound as white crystal. 1H-NMR (CDCl3) delta; 8.05 (d, J=8.1 Hz, 1H), 7.79 (s, 1H), 7.64 (d, J=8.1 Hz, 1H). CI-MS (m/z); 182 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With urea; sodium nitrite; In water; | Synthesis of 2-chloro-4-cyanobenzoic acid (used in the synthesis of Compound 25) To a stirred suspension of 4-amino-2-chlorobenzoic acid (10 g, supplied by Aldrich) in water (150 ml) and concentrated sulphuric acid (20 ml) at -2C was added a solution of sodium nitrite (4.8 g) in water (75 ml) at -2C. After the solid had dissolved, urea was added to destroy excess nitrous acid. The resulting solution was added to a stirred solution of copper (I) cyanide (9.0 g) and potassium cyanide (13.0 g) in water (30 ml) at 60-70C and the mixture was heated to 85-90C for 1 hour. The hot mixture was filtered. The filtrates were cooled and the product was filtered off. 1.3 g of 2-chloro-4-cyanobenzoic acid was obtained. Nuclear magnetic resonance spectrum (NMR) was as follows: 'H (ppm from TMS in (CD3)2CO, integral, number of peaks): 7.85, 1H, dd; 8.0, 1H, d; 8.05 1H, d. Mass spectrum M+1 182. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 12h; | Example 36 (+)-trans-2-Chloro-4-cyano-benzoic Acid 2-(2-acetoxymethyl-1-methylpyrrolidin-3-yl)-6-acetyl-3,5-dimethoxy-phenyl Ester A mixture of the compound of example (6)(3.84 g, 10 mmol), <strong>[117738-77-9]2-chloro-4-cyano-benzoic acid</strong> (2.48 g, 13 mmol), DCC (4.51 g, 21 mmol) and DMAP (1.34 g, 10 mmol) were dissolved in dichloromethane (50 mL) and stirred at room temperature for 12 hrs. The reaction mixture is cooled to 0 C., the precipitated dicyclohexylurea was filtered and the organic layer concentrated and the residue purified by column chromatography with 1% methanol in chloroform and 0.01% ammonia as eluent to give the compound, (+)-trans-<strong>[117738-77-9]2-chloro-4-cyanobenzoic acid</strong> 2-(2-acetoxymethyl-1-methylpyrrolidin-3-yl)-6-acetyl-3,5-dimethoxyphenyl ester. Yield: 3.5 g (62%); 1H NMR (CDCl3, 300 MHz): delta 8.19 (d, 1H), 7.79 (s, 1H), 7.69 (d, 1H), 6.45 (s, 1H), 4.10 (m, 1H), 3.93 (s, 6H), 3.48 (m, 2H), 3.11 (m, 1H), 2.72 (m, 1H), 2.48 (s, 3H), 2.35 (s, 3H), 2.10 (m, 1H), 1.92 (m, 2H), 1.74 (s, 3H); MS (ES+): m/z 515 (M+1). |
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