Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:15]=2[CH:21]2[CH2:23][CH2:22]2)[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:24].C(OCC)(=O)C>C(Cl)(Cl)Cl>[ClH:24].[CH:21]1([C:15]2[CH:16]=[C:17]([CH3:20])[CH:18]=[CH:19][C:14]=2[N:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)[CH2:22][CH2:23]1
Reactant: Cc1ccc(N2CCN(C(=O)OC(C)(C)C)CC2)c(C2CC2)c1
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: CCOC(C)=O
Product: Cc1ccc(N2CCNCC2)c(C2CC2)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a mixture of 4-(2-chloro-4-methylphenyl)piperazine-1-carboxylic acid tert-butyl ester (932 mg), bis(tricyclohexylphosphine)palladium (II) dichloride (132 mg), tripotassium phosphate (3.8 g) and cyclopropylboronic acid (688 mg) were added toluene (10 mL) and water (500 μL) and the mixture was refluxed for 5 hr. After cooling, the mixture was extracted with ethyl acetate, washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (chloroform) to give 4-(2-cyclopropyl-4-methylphenyl)piperazine-1carboxylic acid tert-butyl ester (1 g). 4-(2-Cyclopropyl-4-methylphenyl)piperazine-1carboxylic acid tert-butyl ester (1 g) was dissolved in chloroform (1 mL), 4N hydrogen chloride/ethyl acetate (1 mL) was added, and the mixture was stirred at room temperature for 3 hr. Filtration gave 1-(2-cyclopropyl-4-methylphenyl)piperazine hydrochloride (160 mg). To tetrahydrofuran (2 mL) were added 4-iodobenzoyl chloride (169 mg), 1-(2-cyclopropyl-4-methylphenyl)piperazine hydrochloride (160 mg) and 1N aqueous sodium hydroxide solution (2 mL), and the mixture was stirred at room temperature overnight. Ethyl acetate was added for partitioning, the organic layer was washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (chloroform) to give the title compound (280 mg).
Reaction SMILES: [N+]([C:4]1[CH:21]=[CH:20][C:7]([C:8]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[NH:15][C:14](=[O:19])[CH2:13]3)=[O:9])=[CH:6][CH:5]=1)([O-])=O.O=[N:23]C1C=CC=CC=1>CO.[Pd]>[NH2:23][C:5]1[CH:6]=[C:7]([CH:20]=[CH:21][CH:4]=1)[C:8]([C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][C:14](=[O:19])[CH2:13]2)=[O:9]
Reactant: O=Nc1ccccc1
Reactant: O=C1Cc2cc(C(=O)c3ccc([N+](=O)[O-])cc3)ccc2N1
Agent: [Pd]
Solvent: CO
Product: Nc1cccc(C(=O)c2ccc3c(c2)CC(=O)N3)c1
Reaction time: 0.08 h

Procedure:
5-(4-Nitro-benzoyl)-1,3-dihydro-indol-2-one (1.51 g, 5.28 mmol) was dissolved in MeOH (600 mL). 10% Pd/C (0.150 g) was added to the flask and then placed under vacuum to remove any O2(g). The reaction mixture was kept under reduced pressure for ˜5 min and was then charged with H2(g). This evacuation/H2(g) fill procedure was repeated twice. The reaction mixture changed from a cloudy grayish/black color to a translucent dark green/black color, signifying complete consumption of the starting material. As the desired ketone product was prone to over-reduction to the alcohol, stopping the reaction immediately upon complete consumption of the starting material limited the amount over-reduction that occurred. The reaction was allowed to run for 0.75-1.0 hours after which, the reaction mixture was filtered over celite and concentrated in vacuo resulting in a yellowish solid that contained the desired keto-aniline product plus ˜5% of the overreduced alcohol-aniline. The crude solid was purified by triturating with MeOH. The desired keto-aniline product, 5-(3-Amino-benzoyl)-1,3-dihydro-indol-2-one was soluble in MeOH and was filtered away from the insoluble over reduced alcohol by-product. In vacuo concentration of the methanolic filtrate provided pure 5-(3-Amino-benzoyl)-1,3-dihydro-indol-2-one in 72% (0.957 g, 3.80 mmol) yield.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C([CH:15](Br)[C:16]([O-:18])=[O:17])C1C=CC=CC=1.C(N(CC)CC)C>ClCCl>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:15][C:16]([OH:18])=[O:17])[CH2:4][CH2:3]1
Reactant: CN1CCNCC1
Reactant: O=C([O-])C(Br)Cc1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CN1CCN(CC(=O)O)CC1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A mixture of 1-methylpiperazine (10.7 g), benzylbromoacetate (24 g), triethylamine (28 ml) and dichloromethane (100 ml) was stirred at ambient temperature for 4 hours. The reaction was concentrated to dryness, taken up in tetrahydrofuran (100 ml), filtered, and the filtrate evaporated to dryness. The residue was taken up in methanol (100 ml), treated with aqueous sodium hydroxide solution (100 ml, 1M) and stirred at reflux for 24 hours. The reaction was concentrated to dryness, diluted with water (100 ml) and then acidified to pH6.0 by addition of concentrated hydrochloric acid. The mixture was evaporated.. A portion of the resulting brown oil (2.0 g) was taken up in water (100 ml), treated with Dowex 50WX8 resin (80 g) and stirred at ambient temperature for 10 minutes. The mixture was filtered and the resin washed with water until the washings were neutral. The resin was then stirred with 2.0M aqueous ammonia (3×100 ml) for 5 minutes and filtered. The combined ammonia washings were concentrated to leave the title compound as a white waxy solid (0.8 g).
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:10]2[C:5](=[CH:6][C:7]([C:11]#[N:12])=[CH:8][CH:9]=2)[NH:4][C:3]1=[O:13].[C:15]1(N)[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[NH2:21]>O.N>[CH3:1][C:2]1([CH3:14])[C:10]2[C:5](=[CH:6][C:7]([C:11]3[NH:21][C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=4[N:12]=3)=[CH:8][CH:9]=2)[NH:4][C:3]1=[O:13]
Reactant: Nc1ccccc1N
Reactant: CC1(C)C(=O)Nc2cc(C#N)ccc21
Agent: N
Solvent: O
Product: CC1(C)C(=O)Nc2cc(-c3nc4ccccc4[nH]3)ccc21
Yield: 10.3 %

Procedure:
One heated 3,3-dimethyl-2,3-dihydro-2-oxo-(1H)-6-indolecarbonitrile (2.6 g, preparation described in DE-A-3,818,830) and ortho-phenylenediamine (2.6 g) in polyphosphoric acid for 6 h at 160° C. One allowed to cool to 80°-90° C., added ice thereto, diluted with water to a volume of 1.2 l and neutralised with conc. ammonia. One extracted with a mixture of dichloromethane:methanol=10:1, removed the solvent in a vacuum and purified the residue column chromatographically (silica gel 60, dichloromethane:methanol. ammonia=20:1). One obtained 0.4 g of grey crystals which one recrystallised from ethanol/water. One obtained 195 mg of the title compound with the m.p. 326°-330° C.
Reaction SMILES: C(OP([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([OH:18])=[O:17])=[CH:12][CH:11]=1)(OCC)=O)C.CC(C)([O-])C.[K+].C1COCC1.[CH:30]([C:32]1[S:33][CH:34]=[CH:35][N:36]=1)=O>O>[S:33]1[CH:34]=[CH:35][N:36]=[C:32]1/[CH:30]=[CH:9]/[C:10]1[CH:11]=[CH:12][C:13]([C:16]([OH:18])=[O:17])=[CH:14][CH:15]=1
Reactant: CCOP(=O)(Cc1ccc(C(=O)O)cc1)OCC
Reactant: O=Cc1nccs1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1ccc(/C=C/c2nccs2)cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 1.9 %

Procedure:
A mixture of 4-(diethoxyphosphorylmethyl)benzenecarboxylic acid (440 mg) produced according to JP-A 11-60537, potassium tert-butoxide (340 mg) and THF (5.5 mL) was stirred at room temperature for about 1.5 hours, and then a THF solution (1.0 mL) of 2-formylthiazole (200 mg) was dropwise added thereto. After heated overnight under reflux, water was added to the reaction solution, and extracted with ethyl acetate. The organic layer was dried with anhydrous magnesium sulfate, and the solvent was evaporated off under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate/methanol=9/1), and the resulting purified product was further purified through reversed-phase HPLC to obtain the entitled compound (7 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[S:10][CH:11]=[C:12]([CH2:14][S:15](Cl)(=[O:17])=[O:16])[N:13]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[NH3:19]>>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[S:10][CH:11]=[C:12]([CH2:14][S:15]([NH2:19])(=[O:17])=[O:16])[N:13]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: O=S(=O)(Cl)Cc1csc(-c2ccc(Cl)c(Cl)c2)n1
Reactant: N
Product: NS(=O)(=O)Cc1csc(-c2ccc(Cl)c(Cl)c2)n1

Procedure:
The sulfonyl chloride intermediate prepared in Step C above (15.3 g., 0.049 mol) was allowed to react with concentrated ammonia (150 ml) at room temperature for 10 minutes. On filtration there was obtained 8.75 g. of sulfonamide intermediate, m.p. 165°-167° C. Recrystallization from tetrahydrofuran-ether-petroleum ether gave m.p. 168°-170° C. Anal. Calc'd. for C10H8Cl2N2O2S2 : % C, 37.16; % H, 2.49; % N, 8.67. Found: % C, 37.13; % H, 2.36; % N, 8.36.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2(O)[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:9]2)=[CH:4][CH:3]=1.Cl>C1COCC1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH2:16][C:15]3[C:10]([CH:9]=2)=[CH:11][CH:12]=[CH:13][CH:14]=3)=[CH:6][CH:7]=1
Reactant: OC1(c2ccc(F)cc2)Cc2ccccc2C1
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: Fc1ccc(C2=Cc3ccccc3C2)cc1
Temperature: 25 °C
Reaction time: 14 h
Yield: 70.8 %

Procedure:
To a solution of 2-(4-fluorophenyl)-2-indanol (21.0 g, 92.1 mmol) in THF (200 mL) was added a solution of concentrated hydrochloric acid (40 mL) in water (60 mL). The solution was stirred at room temperature overnight (14 h). The solid was collected and washed with pentane (50 mL) and then tetrahydrofuran (50 mL) to give 13.7 g of.yield 2-(4-fluorophenyl)-1H-indene. 1H-N.M.R. (CDCl3) d 3.78(br s, 2H), d 7.05 (br d, J=8.6 Hz, 2H), d 7.13(br s, 1H), d 7.17(tt, J=7.4, 1.2 Hz, 1H), d 7.7(br t J=7.4 Hz, 1H), d 7.38(br d, J=7.4Hz, 1H), d 7.45(br d, J=7.4 Hz, 1H), d 7.57(br dd, J=9.0, 5.4 Hz, 2H)
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:40])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24]CC3C=CC=CC=3)[C:19]=2[O:32]CC2C=CC=CC=2)=[CH:7][CH:6]=1)[CH3:2].[H][H]>C(OCC)(=O)C.[Pd]>[CH2:1]([O:3][C:4](=[O:40])[C:5]1[CH:6]=[CH:7][C:8]([O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([OH:24])[C:19]=2[OH:32])=[CH:9][CH:10]=1)[CH3:2]
Reactant: CCOC(=O)c1ccc(OCCCCCCc2cccc(OCc3ccccc3)c2OCc2ccccc2)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCOC(=O)c1ccc(OCCCCCCc2cccc(O)c2O)cc1
Yield: 85 %

Procedure:
A solution of 2.3 g of 4-[6-[2,3-bis(phenylmethoxy)phenyl]hexyloxy]benzoic acid ethyl ester in 50 mL of ethyl acetate and 0.3 g of 10% palladium on carbon was stirred in a hydrogen atmosphere for 22 hours. The reaction mixture was filtered through Celite and the filtrate was concentrated under reduced pressure to a solid. Recrystallization from ethyl acetate-hexane gave 1.3 g, mp 45°-47°, (85% yield) to 4-[6-(2,3-dihydroxyphenyl)hexyloxy]benzoic acid ethyl ester.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:16][CH:15]=1)[NH:8][CH2:7][CH2:6]2.[C:28]1(=O)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1>>[CH:28]1([N:8]2[CH2:7][CH2:6][C:5]3[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=3)[CH:9]2[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:16][CH:15]=2)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1
Reactant: O=C1CCCCC1
Reactant: COc1ccc2c(c1)CCNC2Cc1ccc(OCc2ccccc2)cc1
Product: COc1ccc2c(c1)CCN(C1CCCCC1)C2Cc1ccc(OCc2ccccc2)cc1
Yield: 52.8 %

Procedure:
The title compound was prepared as described in Example 14. C, using 6-methoxy-1-[4-(phenylmethoxy)benzyl]-1,2,3,4-tetrahydroisoquinoline (0.5 g, 1.39 mmol) and cyclohexanone (0.588 g. 6.0 mmol) to provide the title compound (0.324 g, 53% yield): ES-MS (m/z) 442 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH:16]1[CH2:21][CH2:20][CH:19]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:18][C:17]1=[O:27]>CC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH:16]2[CH2:21][CH2:20][CH:19]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:18][C:17]2=[O:27])=[CH:4][CH:3]=1
Reactant: CCOC(=O)C1CCC(Br)C(=O)C1
Reactant: Sc1ccc(Br)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)C1CCC(Sc2ccc(Br)cc2)C(=O)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 63.4 %

Procedure:
To a solution of 4-bromobenzenethiol (2.92 g, 15.45 mmol) in 20 mL acetone was added K2CO3 (2.2 g, 15.18 mmol) and a solution of ethyl 4-bromo-3-oxocyclohexanecarboxylate (3.73 g, 15 mmol) in acetone (10 mL). The resulting suspension was stirred at room temperature for 2 hour, and then was partitioned between water and hexane. The organic layer was washed with water, then brine, then was dried over MgSO4, filtered, and concentrated. Purification by chromatography on silica gel (15% EtOAc in hexane) afforded 3.4 g (61%) of the title compound as an oil: MS (ES) m/z=356 [M]+.
Reaction SMILES: Cl[C:2](=[C:7]([Cl:12])[C:8]([F:11])([F:10])[F:9])[C:3]([F:6])([F:5])[F:4].II>>[Cl:12][CH:7]([CH2:2][C:3]([F:4])([F:5])[F:6])[C:8]([F:11])([F:10])[F:9]
Reactant: FC(F)(F)C(Cl)=C(Cl)C(F)(F)F
Agent: II
Product: FC(F)(F)CC(Cl)C(F)(F)F
Temperature: 250 °C
Reaction time: 15 h
Yield: 40.7 %

Procedure:
2,3-Dichlorohexafluorobut-2-ene (100 g) and iodine (55 g) were added to a 400 mL shaker tube. The tube was sealed, cooled, evacuated, and charged with 1500 psi of hydrogen at room temperature. The tube was then heated to 230° C. for 1 hour, 250° C. for 2 hours, and 260° C. for 15 hours. The tube was then cooled to room temperature, vented, and opened. The purple liquid was washed with water and then analyzed by GC/IR. Analysis of the washed liquid showed that it contained about 84% 2-chloro-1,1,1,4,4,4-hexafluorobutane, about 13% 2,3-dichloro-1,1,1,4,4,4-hexafluorobutane and about 1% 1,1,1,4,4,4-hexafluorobutane. The liquid was distilled on a concentric tube column yielding 35 g (41% isolated yield) of 2-chloro-1,l,1,4,4,4-hexafluorobutane (HCFC-346 mdf) as a clear liquid with a b.p. of 50.9°-51.4° C. 1H NMR (CHCl3 as internal standard): 4.4 ppm, complex, 1H; 2.9 ppm, complex, IH; 2.7 ppm, complex, 1H. 19F NMR (CCl3F) as internal standard): 64.7 ppm, t, 1F; -76 ppm, d, 1F GC/IR showed an identical spectrum to an authentic sample.
Reaction SMILES: [C:1]([NH:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([NH2:14])[CH:12]=2)[N:7](C(OCC)=O)[C:6]=1[C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:3])[CH3:2].N1C=CC=CC=1.[CH3:34][S:35](Cl)(=[O:37])=[O:36]>ClCCl>[C:1]([NH:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([NH:14][S:35]([CH3:34])(=[O:37])=[O:36])[CH:12]=2)[NH:7][C:6]=1[C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:3])[CH3:2]
Reactant: CCOC(=O)n1c(C(=O)c2ccccc2)c(NC(C)=O)c2cc(N)ccc21
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(=O)Nc1c(C(=O)c2ccccc2)[nH]c2ccc(NS(C)(=O)=O)cc12
Reaction time: 1 h
Yield: 65.8 %

Procedure:
To a solution of 3-acetylamino-5-amino-2-benzoyl-1-ethoxycarbonylindole (Example 99, step 1: 100 mg, 0.27 mmol) in dichloromethane (5 ml) and pyridine (33 μl, 0.41 mmol) was added methanesulfonyl chloride (25 μl, 0.32 mmol) and the mixture was stirred for 1 h. The mixture was partitioned between 2N aqueous HCl (30 ml) and ethyl acetate (30 ml), the organic layer separated and washed cocnsecutively with brine (10 ml), saturated aqueous sodium bicarbonate (10 ml), brine (10 ml) and dried (MgSO4). After removal of solvent the residue was diluted with ethanol (10 ml) and water (5 ml), and potassium hydroxide (0.5 g) added. The mixture was stirred for 4 h, poured into a saturated aqueous ammonium chloride (30 ml) and extracted with ethyl acetate (50 ml×2). The organic layer was washed with brine (50 ml), dried (MgSO4), and solvent removed by evaporation. The residue was recrystallized from methanol/dichloromethane/hexane to give 66 mg of the title compound as a yellow solid. m.p.: 260-261° C. 1H-NMR (DMSO-d6) δ: 11.7 (1H, br s), 9.63 (1H, s), 7.81-8.22 (2H, m), 7.40-7.64 (7H, m), 2.90 (3H, s), 164 (3H, s).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[CH:8][CH:7]=1.S(=O)(=O)(O)O.[N+:23]([O-])([OH:25])=[O:24]>>[N+:23]([C:5]1[S:1][C:2]([C:6]2[CH:7]=[CH:8][C:9]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[CH:10][CH:11]=2)=[N:3][CH:4]=1)([O-:25])=[O:24]
Reactant: O=[N+]([O-])O
Reactant: c1csc(-c2ccc(N3CCOCC3)cc2)n1
Agent: O=S(=O)(O)O
Product: O=[N+]([O-])c1cnc(-c2ccc(N3CCOCC3)cc2)s1
Temperature: 0 °C
Reaction time: 4.5 h
Yield: 30 %

Procedure:
To a mixture of 4-(4-(thiazol-2-yl)phenyl)morpholine (2.00 g, 8.13 mmol) and concentrated sulfuric acid (25 mL) was added concentrated nitric acid (0.60 mL) at −10° C. The reaction mixture was stirred at 0° C. for 4.5 h, then poured into ice water, and extracted with CH2Cl2 (60 mL×3). The organic phase was dried over Na2SO4 and concentrated in vacuo to give the title compound as a yellow solid (0.70 g, 30%).
Reaction SMILES: C([N:9]1[C:14](=[O:15])[CH:13]=[CH:12][N:11]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:22]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:10]1=[O:41])(=O)C1C=CC=CC=1.CO[Na]>CO>[C:22]([NH:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][N:11]1[CH:12]=[CH:13][C:14](=[O:15])[NH:9][C:10]1=[O:41])([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1
Reactant: O=C(c1ccccc1)n1c(=O)ccn(CCCCCNC(c2ccccc2)(c2ccccc2)c2ccccc2)c1=O
Agent: CO[Na]
Solvent: CO
Product: O=c1ccn(CCCCCNC(c2ccccc2)(c2ccccc2)c2ccccc2)c(=O)[nH]1
Reaction time: 24 h
Yield: 156 %

Procedure:
Compound 18 (187 mg; 0.35 mmol) was dissolved and stirred in a solution of MeONa 0.2 M in MeOH (17 ml) at room temperature. After 24 hours the pH was adjusted to 7 with Dowex 50WX 8-200 ion exchange resin. The resin was removed by filtration and washed with MeOH. The solution was evaporated and the residue was purified by flash chromatography with DCM/MeOH 90:10 as eluent which gave the title compound as a white foam (240 mg, 52%). Rf: 0.50 in DCM/MeOH 90:10.
Reaction SMILES: C([O:5][C:6](=[O:45])[CH2:7][O:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=2)=[CH:13][C:12]([C:22](=[O:37])[NH:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:11][C:10]=1[C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([CH3:44])[CH:39]=1)(C)(C)C>C(O)=O>[CH3:21][C:17]1[CH:16]=[C:15]([C:14]2[CH:13]=[C:12]([C:22](=[O:37])[NH:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH:11]=[C:10]([C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([CH3:44])[CH:39]=3)[C:9]=2[O:8][CH2:7][C:6]([OH:45])=[O:5])[CH:20]=[CH:19][CH:18]=1
Reactant: Cc1cccc(-c2cc(C(=O)NCCCCCCCc3ccccc3)cc(-c3cccc(C)c3)c2OCC(=O)OC(C)(C)C)c1
Solvent: O=CO
Product: Cc1cccc(-c2cc(C(=O)NCCCCCCCc3ccccc3)cc(-c3cccc(C)c3)c2OCC(=O)O)c1
Yield: 99.4 %

Procedure:
A solution of [3,3″-Dimethyl-5′-(7-phenyl-heptylcarbamoyl)-[1,1′:3′,1″]terphenyl-2′-yloxy]acetic acid tert-butyl ester (180 mg, 0.311 mmol) in 3.5 mL HCOOH was stirred at room temperature until all of the ester was consumed by TLC (1:1 EtOAc:Hexanes). The excess HCOOH was removed in vacuo (first on a rotoevaporator then pumping under high vacuum) then crystallized from CH2Cl2/Hexanes to yield 170 mg, 100% of the acid as a yellow foam. mp 58-62° C.; 1H NMR (DMSO-d6) δ1.21-1.28 (m, 6H); 1.44-1.57 (m, 4H); 2.35 (s, 6H); 2.53 (t, J=7.69 Hz, 2H); 3.23 (quartet, J=6.37 Hz, 2H); 3.82 (s, 2H); 7.10-7.24 (m, 7H); 7.30-7.41 (m, 6H); 7.80 (s, 2H); 8.51 (t, J=5.49 Hz, 1H); 12.60 (bs, 1H); IR 3375, 3025, 2925, 2865, 1730, 1630, 1600, 1550, 1450, 1350, 1210, 1195, 1080, and 700 cm−1; mass spectrum [(−)ESI], m/z 548 [M−H]−; Anal Calcd. for C36H39NO4: C, 78.66: H, 7.15; N, 2.55; Found: C, 77.39; H, 7.42; N, 2.37.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8].[I:12][C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[I:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:15][CH:14]=1
Reactant: CCOC(=O)CCCCCBr
Reactant: Oc1ccc(I)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)CCCCCOc1ccc(I)cc1
Yield: 96.4 %

Procedure:
Ethyl 6-bromohexanoate (5.55 g, 25 mmol) in acetone (100 ml) was treated with 4-iodophenol (5.55 g, 25 mmol) and potassium carbonate (6.9 g 50 mmol). The stirred reaction was heated under reflux for 60 h. The reaction was then allowed to cool and the reaction concentrated in vacuum to a gum. The reaction was them partitioned between ethyl acetate (100 ml) and water (100 ml). The ethyl acetate layer was separated dried, over magnesium sulfate and concentrated in vacuo to give a colourless gum (8.71 g, 24.1 mmol, 96%), δH (CDCl3) 1.26 (3H, t, CO2CH2CH3), 1.46-1.81 (6H, m, 3,4,5-CH2), 2.33 (2H, t, 2-CH2), 3.91 (2H, t, 6-CH 2), 4.13 (2H, q, CO2CH2CH3), 6.66 (2H, dd, 2,6-ArH), 7.53 (2H, dd, 3,5-ArH), δH (CDCl3) 14.20, 24.60, 25.53, 28.75, 34.14, 60.20, 67.67, 82.44, 116.83,1 38.09, 158.84, and 173.52.
Reaction SMILES: [N:1]1([C:7]2[CH:12]=[CH:11][C:10]([S:13](Cl)(=[O:15])=[O:14])=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23].[OH-].[Na+].O1CCCC1>O>[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])(=[O:15])=[O:14])=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: NCCCCC(=O)O
Reactant: O=S(=O)(Cl)c1ccc(N2CCCCC2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)CCCCNS(=O)(=O)c1ccc(N2CCCCC2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 56.9 %

Procedure:
7.8 g of 4-piperidinylbenzenesulphonyl chloride are added to a solution comprising 3.51 g of 5-aminovaleric acid and 3.6 g of sodium hydroxide dissolved in 35 cm3 of water, followed by the addition of 35 cm3 of tetrahydrofuran in order to obtain a solution. The temperature rises to 35° C. The mixture is kept stirring for 4 hours at room temperature, the tetrahydrofuran is evaporated off, the reaction medium is acidified using acetic acid, diluted with 100 cm3 of water and extracted with chloroform, the organic phase is dried and the solvents are removed under reduced pressure. 5.8 g of expected product are obtained. M.p. 115°-120° C. After crystallization in an isopropanol/water mixture (1:1), the product, melting point 120°-122° C., is obtained.
Reaction SMILES: [C:1]([OH:7])(=[O:6])[CH2:2][CH2:3][C:4]#[CH:5].O[N:9]1[C:13](=[O:14])[CH2:12][CH2:11][C:10]1=[O:15].C1CCC(N=C=NC2CCCCC2)CC1.C(O)(=O)C>C1COCC1>[O:15]=[C:10]1[CH2:11][CH2:12][C:13](=[O:14])[N:9]1[O:6][C:1](=[O:7])[CH2:2][CH2:3][C:4]#[CH:5]
Reactant: O=C1CCC(=O)N1O
Reactant: C#CCCC(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: C#CCCC(=O)ON1C(=O)CCC1=O
Temperature: -10 °C
Reaction time: 1 h
Yield: 100.5 %

Procedure:
4-pentynoic acid (5.0 g, 51 mmol) and N-hydroxy succinimide (5.87 g, 51 mmol) were added to a solution of DCC (12.6 g, 61.2 mmol) in THF (125 ml) at −10° C. The mixture was then stirred for 1 h at −10° C. then left to stir at room temperature overnight. (A white precipitate was observed after 15 min). Acetic acid (0.63 ml) was then added. The resulting DCU was removed by filtration. The filtrate was then evaporated to give 10a (10 g, 100% crude yield).