Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N[C:2]1C=CC(C)=CC=1.COC1C=CC(N)=CC=1.[Br-].[CH2:19]([Br:28])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]>>[CH2:19]([Br:28])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH:26]([CH3:2])[CH3:27]
Reactant: Cc1ccc(N)cc1
Reactant: CCCCCCCCCBr
Agent: [Br-]
Solvent: COc1ccc(N)cc1
Product: CC(C)CCCCCCCBr

Procedure:
By the general procedure described in Example 1 using as appropriate p-toluidine, p-anisidine, or 3- or 4-chloroaniline and isoctyl bromide, nonyl bromide or isodecylbromide (complex mixture of isomers) there were obtained:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([C@H:13]([NH:24][C:25]3[C:26]([CH3:34])=[CH:27][C:28]([Cl:33])=[C:29]([CH:32]=3)[C:30]#[N:31])[C@@H:14]([O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH3:15])=[N:10][N:9]=2)=[CH:4][CH:3]=1.[C:35](Cl)(=[O:37])[CH3:36]>C(Cl)Cl.N1C=CC=CC=1>[Si:17]([O:16][C@@H:14]([CH3:15])[C@H:13]([C:11]1[O:12][C:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:35](=[O:37])[C:36]3[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=3)=[CH:7][CH:6]=2)=[N:9][N:10]=1)[NH:24][C:25]1[CH:32]=[C:29]([C:30]#[N:31])[C:28]([Cl:33])=[CH:27][C:26]=1[CH3:34])([C:20]([CH3:23])([CH3:21])[CH3:22])([CH3:19])[CH3:18]
Reactant: CC(=O)Cl
Reactant: Cc1cc(Cl)c(C#N)cc1N[C@@H](c1nnc(-c2ccc(N)cc2)o1)[C@H](C)O[Si](C)(C)C(C)(C)C
Solvent: c1ccncc1
Solvent: ClCCl
Product: Cc1cc(Cl)c(C#N)cc1N[C@@H](c1nnc(-c2ccc(NC(=O)c3ccccc3)cc2)o1)[C@H](C)O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 23 h

Procedure:
To a pre-cooled (0° C.) solution of 5-((1R,2S)-1-(5-(4-aminophenyl)-1,3,4-oxadiazol-2-yl)-2-(tert-butyldimethylsilyloxy)propylamino)-2-chloro-4-methyl-benzonitrile (290 mg, 0.58 mmol) in CH2Cl2 (10.0 mL) and pyridine (1.2 mL) was added, portion wise, acetyl chloride (0.34 mL, 2.9 mmol). Upon complete addition the reaction mixture was warmed slowly to room temperature and stirred for 23 h. The reaction mixture was then cooled to 0° C. and quenched with 10% aq HCl (5 mL) then H2O (15 mL) was added. The solution was extracted with CH2Cl2 (2×40 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to provide an orange oil, which was used without further purification (400 mg). 1H NMR (400 MHz, d6-acetone, δ in ppm) 8.36 (d, J=8.4 Hz, 2H), 8.27 (br s, 1H), 8.16 (d, J=8.6 Hz, 2H), 8.08 (d, J=8.2 Hz, 1H), 8.02 (d, J=8.6 Hz, 2H), 7.94-7.83 (m, 3H), 7.53 (d, J=8.2 Hz, 1H), 5.57 (d, J=8.9 Hz, 1H), 4.99 (dd, J=1.8, 8.9 Hz, 1H), 4.76-4.68 (m, 1H), 2.58 (s, 3H), 1.61 (d, J=6.3 Hz, 3H), 1.09 (s, 9H), 0.26 (s, 3H), 0.01 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([O:24][CH3:25])[C:5]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=2)=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[C:7]2[CH3:12].[C:26]1(=O)[O:31][C:29](=[O:30])[C:28]2=[CH:32][CH:33]=[CH:34][CH:35]=[C:27]12.O>C1(C)C(C)=CC=CC=1>[CH3:25][O:24][C:4]1[C:5]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:21])([F:22])[F:23])[CH:15]=2)=[C:6]2[C:11](=[C:2]([N:1]3[C:29](=[O:30])[C:28]4=[CH:32][CH:33]=[CH:34][CH:35]=[C:27]4[C:26]3=[O:31])[CH:3]=1)[N:10]=[CH:9][CH:8]=[C:7]2[CH3:12]
Reactant: COc1cc(N)c2nccc(C)c2c1Oc1cccc(C(F)(F)F)c1
Reactant: O=C1OC(=O)c2ccccc21
Solvent: O
Solvent: Cc1ccccc1C
Product: COc1cc(N2C(=O)c3ccccc3C2=O)c2nccc(C)c2c1Oc1cccc(C(F)(F)F)c1
Yield: 99.3 %

Procedure:
A mixture of 8-amino-6-methoxy-4-methyl-5-(3-trifluoromethylphenoxy)quinoline (I) (6.96 g, 20 mmol) and phthalic anhydride (3.25 g, 22 mmol) in xylene (100 mL) was refluxed with water removal via a Dean-Stark trap for 24 hours. After cooling, filtration gave 9.5 g (100%) of the title compound, mp 228°-30° C. Recrystallization from ethanol raised the mp to 228°-31° C.
Reaction SMILES: [CH:1]1([C:7]([OH:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.C(NC(C)C)(C)C.[CH3:30][O:31][CH2:32]Cl>CCCCCC.C1COCC1>[CH3:30][O:31][CH2:32][C:1]1([C:7]([OH:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COCCl
Reactant: O=C(O)C1CCCCC1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: COCC1(C(=O)O)CCCCC1
Temperature: 60 °C

Procedure:
11.8 g (0.093 mole) of cyclohexylcarboxylic acid were added to a solution of lithium diisopropylamide prepared using 125 cm3 of a 1.50 M solution of butyllithium in hexane, 18.9 g of diisopropylamine and 200 cm3 of THF as the starting materials. After the mixture had been heated at 60° C. for 2 hours, 8 g of methoxymethyl chloride were added, at a temperature of -30° C. After the customary treatment, methoxymethylcyclohexylcarboxylic acid was distilled; this was in the form of a colourless liquid which crystallised on cooling.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([CH:14]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:15]([OH:17])=O)[NH:12][CH:13]=2)=[CH:5][CH:4]=1)#[N:2].C(N(CC)CC)C.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.[NH2:59][C:60]1[CH:68]=[CH:67][C:63]([C:64]([NH2:66])=[O:65])=[CH:62][CH:61]=1>C1COCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:10]=[C:11]([CH:14]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:15]([NH:59][C:60]3[CH:68]=[CH:67][C:63]([C:64]([NH2:66])=[O:65])=[CH:62][CH:61]=3)=[O:17])[NH:12][CH:13]=2)=[CH:7][CH:8]=1)#[N:2]
Reactant: NC(=O)c1ccc(N)cc1
Reactant: N#Cc1ccc(-c2c[nH]c(C(Cc3ccccc3)C(=O)O)n2)cc1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: N#Cc1ccc(-c2c[nH]c(C(Cc3ccccc3)C(=O)Nc3ccc(C(N)=O)cc3)n2)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 32 %

Procedure:
The acid from Example 59 Part A (100 mg, 0.32 mmol), triethylamine (150 μL, 1.2 mmol), and BOP reagent (210 mg, 0.48 mmol) were dissolved in THF (9 mL). The mixture was stirred at rt for 15 min and 4-aminobenzamide (47 mg, 0.35 mmol) was added. The resulting mixture was heated at 70° C. under N2 for 1 h. The mixture was concentrated and then re-dissolved in EtOAc. It was washed with water and brine, dried over Na2SO4, concentrated, and purified by flash chromatography (silica gel, EtOAc/hexane) to give 45 mg of the desired product (32%). MS 436.3 (M+H)+.
Reaction SMILES: ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[CH2:13]([O:15][C:16]([CH:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)=[O:17])[CH3:14].C(N(CC)C(C)C)(C)C.O.[NH2:34][NH2:35]>C1COCC1>[CH2:13]([O:15][C:16]([CH:18]1[CH2:23][CH2:22][N:21]([C:5]([NH:34][NH2:35])=[O:11])[CH2:20][CH2:19]1)=[O:17])[CH3:14]
Reactant: CCOC(=O)C1CCNCC1
Reactant: NN
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: CCOC(=O)C1CCN(C(=O)NN)CC1
Temperature: 2.5 °C
Reaction time: 18 h
Yield: 195.8 %

Procedure:
A solution of triphosgene (9.44 g, 31.8 mmol) in THF (100 ml) was cooled to 0° C. and piperidine-4-carboxylic acid ethyl ester (10.0 g, 63.6 mmol) was added over 15 minutes while the temperature was maintained between 0-5° C. Then N,N-diisopropyl ethyl amine (33 ml, 191 mmol) was added over 60 minutes. The suspension was stirred for 18 h at rt. The suspension was filtered off and washed with THF (50 ml). The filtrate was transferred into a dropping funnel and added dropwise over 60 minutes to hydrazine monohydrate (9.3 ml, 191 mmol) at 5-10° C. The suspension was stirred for 3 h at 5° C. The reaction mixture was washed twice with brine (100 ml). The aq. layers were extracted with EtOAc (100 ml). The combined organic layers were dried over Na2SO4 and concentrated under vacuo to yield 13.4 g (98%) of the title product as a brown oil. ES-MS m/e: 216.3 (M+H+).
Reaction SMILES: [Br:1]Br.C1(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:34]=[CH:33][C:32]=1[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45]O>ClCCl.C(OCC)C.CCCCC>[Br:1][CH2:45][CH2:44][CH2:43][CH2:42][CH2:41][C:32]1[CH:33]=[CH:34][C:35]2[C:40](=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:31]=1
Reactant: OCCCCCc1ccc2ccccc2c1
Reactant: BrBr
Agent: c1ccc(P(CCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCOCC
Solvent: CCCCC
Product: BrCCCCCc1ccc2ccccc2c1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
Bromine (a 2M solution in dichloromethane; 955 mg, 5.97 mmol) was added to a solution of 1,2-bis (diphenyl)phosphinoethane (1.16 g, 2.99 mmol) in dichloromethane (15 ml) at 0°. A solution of 5-(2-napthyl)pentan-1-ol (513 mg, 2.39 mmol) in dichloromethane (5 ml) was added to the 0° solution. The solution was warmed to room temperature and stirred for 1.5 hours. The solution was diluted with ethyl ether/pentane (1:3), filtered through a thin pad of celite and the solvent evaporated. The resulting oil was purified by flash chromatography (hexane) giving the title compound as a colorless oil.
Reaction SMILES: O[CH2:2][C:3]1[N:4]([CH:18]([CH3:20])[CH3:19])[S:5](=[O:17])(=[O:16])[C:6]2[S:11][C:10]([S:12]([NH2:15])(=[O:14])=[O:13])=[CH:9][C:7]=2[CH:8]=1.[CH2:21]([N:23](CC)[CH2:24][CH3:25])[CH3:22].C1(C)C=CC(S(Cl)(=O)=[O:35])=CC=1>C1COCC1>[CH3:19][CH:18]([N:4]1[C:3]([CH2:2][N:23]2[CH2:24][CH2:25][O:35][CH2:22][CH2:21]2)=[CH:8][C:7]2[CH:9]=[C:10]([S:12]([NH2:15])(=[O:14])=[O:13])[S:11][C:6]=2[S:5]1(=[O:17])=[O:16])[CH3:20]
Reactant: CC(C)N1C(CO)=Cc2cc(S(N)(=O)=O)sc2S1(=O)=O
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(C)N1C(CN2CCOCC2)=Cc2cc(S(N)(=O)=O)sc2S1(=O)=O
Temperature: 25 °C
Yield: 15.7 %

Procedure:
To a solution of the product from Step E (2.16 g, 6.39 mmol) and triethylamine (2.58 g, 25.6 mmol) in anhydrous THF (100 mL) at 0° C. was added p-toluenesulfonyl chloride (2.44 g, 12.8 mmol) with stirring. After 1 h the reaction mixture was warmed to ambient temperature and maintained at this temperature for 4 h. Half of the reaction mixture was removed, cooled on an ice bath and morpholine (3 mL) was added with stirring. The reaction mixture was stirred for 18 h and evaporated to a residue which was mixed with ethyl acetate (200 mL); this solution was washed with a saturated solution of sodium bicarbonate (100 mL), dried (MgSO4), filtered and evaporated to a residue which was purified by colunmn chromatography (silica, 4% methanol/methylene chloride) to give a viscous oil which crystalized from methylene chloride/hexane to afford a yellowish solid (0.41 g, 32%): mp 196°-198° C. Analysis: Calculated for C14H21N3O5S3 : C, 41.26; H, 5.19 N, 10.31. Found: C, 41.35; H, 5.10; N, 10.28.
Reaction SMILES: [CH2:1]1[O:11][C:4]2([CH2:9][CH2:8][C:7](=[O:10])[CH2:6][CH2:5]2)[O:3][CH2:2]1.[H-].[Na+]>C(=O)(OC)OC.C1(C)C=CC=CC=1>[O:10]=[C:7]1[CH2:6][CH2:5][C:4]2([O:3][CH2:2][CH2:1][O:11]2)[CH2:9][CH:8]1[C:4]([O:3][CH3:2])=[O:11]
Reactant: O=C1CCC2(CC1)OCCO2
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: COC(=O)OC
Product: COC(=O)C1CC2(CCC1=O)OCCO2
Temperature: 80 °C
Reaction time: 3 h

Procedure:
To a stirred solution of 1,4-cyclohexanedione monoethylene ketal (1.00 g, 6.4 mmol) in dimethyl carbonate (6 mL) at room temperature was added sodium hydride (0.31 g, 7.7 mmol). The mixture was heated at 80° C. for 20 min and then diluted with dry toluene (20 mL). The mixture was stirred for an additional 3 h at 80° C., cooled to room temperature, quenched with water, and then extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and evaporated to yield the crude product which was purified by Biotage® chromatography (silica gel, ethyl acetate in hexanes gradient 30-42%) to yield the title compound.
Reaction SMILES: [OH:1][C:2]1[C:7]([CH3:8])=[C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[O:5][C:4](=[O:15])[C:3]=1[C:16]1[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][C:17]=1[CH3:24].C(N(CC)CC)C.[CH2:32]([O:35][CH2:36]Cl)[C:33]#[CH:34]>C(OCC)(=O)C>[CH3:8][C:7]1[C:2]([O:1][CH2:36][O:35][CH2:32][C:33]#[CH:34])=[C:3]([C:16]2[C:17]([CH3:24])=[CH:18][C:19]([CH3:23])=[CH:20][C:21]=2[CH3:22])[C:4](=[O:15])[O:5][C:6]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1
Reactant: Cc1cc(C)c(-c2c(O)c(C)c(-c3ccccn3)oc2=O)c(C)c1
Reactant: C#CCOCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: C#CCOCOc1c(C)c(-c2ccccn2)oc(=O)c1-c1c(C)cc(C)cc1C
Temperature: 20 °C
Reaction time: 20 h
Yield: 82.2 %

Procedure:
6.4 g (20 mmol) of 4-hydroxy-5-methyl-6-(2-pyridyl)-3-(2,4,6-trimethylphenyl)-2-pyrone in 50 ml of ethyl acetate are introduced in the absence of moisture. 2.02 g (20 mmol) of triethylamine are added thereto at 20° C. and a solution of 2.1 g (20 mmol) of propargyloxychloromethane in 20 ml of ethyl acetate is added dropwise at 0° C. with cooling. The mixture is further stirred for 20 h at 20° C. and the reaction is followed by thin-layer chromatography. The solution is filtered off from the precipitated triethylamine hydrochloride with suction and washed with ethyl acetate. The combined mother liquors are washed twice, each time with 50 ml of half-saturated common salt solution, dried over magnesium sulfate and evaporated in vacuo. 8 g of crude product are obtained. 6.4 g (82% of theory) of 5-methyl-6-(2-pyridyl)-4-propargyloxymethoxy-3-(2,4,6-trimethylphenyl)-2-pyrone are obtained as an oil by flash chromatography on 500 g of silica gel 60 (35-70 μm) using toluene:acetone 20:1 as mobile phase.
Reaction SMILES: FC(F)(F)S([O-])(=O)=O.[Br:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15](=[O:20])[C:14]([I+]C1C=CC=CC=1)=[C:13]2[OH:28].[NH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>C(Cl)Cl>[Br:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15](=[O:20])[C:14]([NH:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[C:13]2[OH:28]
Reactant: O=c1[nH]c2ccc(Br)cc2c(O)c1[I+]c1ccccc1
Reactant: Nc1ccccc1
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: ClCCl
Product: O=c1[nH]c2ccc(Br)cc2c(O)c1Nc1ccccc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A mixture of (6-bromo-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)(phenyl)iodoniumtrifluoromethane sulfonate (1.40 g, 2.36 mmol, Intermediate 8, step b) and aniline (1 mL) was stirred for 4 hours at room temperature. To this was added DCM and the resulting suspension was filtered. The solid was washed first with DCM followed by water and air dried under vacuum at 50° C. to yield the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=1[SH:12])[CH3:2].F[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N+:21]([O-:23])=[O:22]>>[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=1[S:12][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N+:21]([O-:23])=[O:22])[CH3:2]
Reactant: O=[N+]([O-])c1ccccc1F
Reactant: CCOC(=O)c1cc(F)ccc1S
Product: CCOC(=O)c1cc(F)ccc1Sc1ccccc1[N+](=O)[O-]

Procedure:
Thus, in a five-step process: 5-fluoro-2-mercapto-benzoic acid ethyl ester may be reacted with 1-fluoro-2-nitrobenzene to form 5-fluoro-2-(2-nitro-phenylsulfanyl)-benzoic acid ethyl ester; the ethyl ester may be converted to 5-fluoro-2-(2-amino-phenylsulfanyl)-benzoic acid ethyl ester; the aminophenyl compound may be cyclized to form 2-fluoro-10H-dibenzo[b,f][1,4]thiazepin-11-one, that may be converted to 11-chloro-2-fluoro-dibenzo[b,f][1,4]thiazepine, and that may be then reacted with piperazine to form the title compound.
Reaction SMILES: [CH3:1][CH:2]1[O:6][CH:5]([C:7]([OH:9])=O)[CH2:4][CH2:3]1.[C:10](Cl)(=O)C(Cl)=O.[BrH:16]>ClCCl.CN(C)C=O>[Br:16][CH2:10][C:7]([CH:5]1[CH2:4][CH2:3][CH:2]([CH3:1])[O:6]1)=[O:9]
Reactant: CC1CCC(C(=O)O)O1
Reactant: O=C(Cl)C(=O)Cl
Reactant: Br
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC1CCC(C(=O)CBr)O1
Reaction time: 1.25 h
Yield: 58.2 %

Procedure:
A solution of 5-methyl-2-tetrahydrofuroic acid (1.80 g, 13.85 mmol) in dichloromethane (25 ml) was treated with oxalyl chloride (2.4 ml, 27.51 mmol) in the presence of dimethylformamide (3 drops). After stirring for 1.25 h, the solvent was evaporated in vacuo. The residue was redissolved in dichloromethane and concentrated again. Excess diazomethane was then bubbled through a solution of the resulting acid chloride in dichloromethane (30 ml) at 0° C. When the addition was complete, the mixture was stirred for 10 min. at 0° C. and then treated with 48% aqueous hydrogen bromide (2.6 ml, 15.41 mmol). The mixture was stirred for 15 min. at room temperature, washed with water (×2), dried and concentrated in vacuo to yield the crude title compound as a brown oil (1.67 g, 58%); νmax (CH2Cl2) 1735, 1387 and 1086 cm-1 ; δH (CDCl3, 90 MHz) 1.33 (3H, d, J 6.0 Hz), 1.48 (1H, m), 1.90-2.35 (3H, m), 4.10 (1H, m), 4.25 (2H, s) and 4.48 (1H, m).
Reaction SMILES: C([O:3][C:4](=[O:28])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][CH2:14][C:15]2[CH:20]=[C:19]([O:21][CH2:22][CH:23]([CH3:25])[CH3:24])[CH:18]=[C:17](Br)[CH:16]=2)=[CH:9][C:8]=1[CH3:27])C.[C:29]([C:31]1[CH:36]=[CH:35][C:34]([S:37]([CH3:40])(=[O:39])=[O:38])=[CH:33][CH:32]=1)#[CH:30].C(OC(=O)COC1C=CC(SC2C=C(C#CC3C=CC(CO)=CC=3)C=C(OCCC3C=CC(Cl)=CC=3)C=2)=CC=1C)C>>[CH2:22]([O:21][C:19]1[CH:20]=[C:15]([CH:16]=[C:17]([C:30]#[C:29][C:31]2[CH:32]=[CH:33][C:34]([S:37]([CH3:40])(=[O:39])=[O:38])=[CH:35][CH:36]=2)[CH:18]=1)[CH2:14][S:13][C:10]1[CH:11]=[CH:12][C:7]([O:6][CH2:5][C:4]([OH:3])=[O:28])=[C:8]([CH3:27])[CH:9]=1)[CH:23]([CH3:24])[CH3:25]
Reactant: CCOC(=O)COc1ccc(SCc2cc(Br)cc(OCC(C)C)c2)cc1C
Reactant: C#Cc1ccc(S(C)(=O)=O)cc1
Agent: CCOC(=O)COc1ccc(Sc2cc(C#Cc3ccc(CO)cc3)cc(OCCc3ccc(Cl)cc3)c2)cc1C
Product: Cc1cc(SCc2cc(C#Cc3ccc(S(C)(=O)=O)cc3)cc(OCC(C)C)c2)ccc1OCC(=O)O

Procedure:
The title product was prepared from [4-(3-Bromo-5-isobutoxy-benzylsulfanyl)-2-methyl-phenoxy]-acetic acid ethyl ester (300 mg; 0.64 mmol) and 1-Ethynyl-4-methanesulfonyl-benzene (347.0 mg; 1.93 mmol) applying the procedure described for {4-[3-[2-(4-Chloro-phenyl)-ethoxy]-5-(4-hydroxymethyl-phenylethynyl)-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid ethyl ester. The crude product was purified by preparative HPLC (method A). Yield: 260 mg (72%). HPLC-MS: m/z: 567.6 (M+H)+; Rt: 2.77 min
Reaction SMILES: Cl.Cl.[NH2:3][CH2:4][C:5]1[C:14]([O:15][C@@H:16]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:17][N:18]2[CH:22]=[CH:21][N:20]=[CH:19]2)=[CH:13][CH:12]=[C:11]2[C:6]=1[CH2:7][CH2:8][CH2:9][C:10]2=[O:29].[CH3:30][O:31][C:32]1[CH:37]=[CH:36][C:35]([S:38](Cl)(=[O:40])=[O:39])=[CH:34][CH:33]=1>C(Cl)Cl.N1C=CC=CC=1>[N:18]1([CH2:17][C@H:16]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[O:15][C:14]2[CH:13]=[CH:12][C:11]3[C:10](=[O:29])[CH2:9][CH2:8][CH2:7][C:6]=3[C:5]=2[CH2:4][NH:3][S:38]([C:35]2[CH:34]=[CH:33][C:32]([O:31][CH3:30])=[CH:37][CH:36]=2)(=[O:40])=[O:39])[CH:22]=[CH:21][N:20]=[CH:19]1
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Reactant: NCc1c(O[C@H](Cn2ccnc2)c2ccccc2)ccc2c1CCCC2=O
Agent: Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: COc1ccc(S(=O)(=O)NCc2c(O[C@H](Cn3ccnc3)c3ccccc3)ccc3c2CCCC3=O)cc1
Reaction time: 8 h
Yield: 66 %

Procedure:
To a solution of 5-aminomethyl-6-((S)-2-imidazol-1-yl-1-phenyl-ethoxy)-3,4-dihydro-2H-naphthalen-1-one bis-hydrochloride (40 mg, 0.092 mmole) in CH2Cl2 (1 mL) and pyridine (1 mL) was added 4-methoxybenzenesulfonyl chloride (0.75 mL, 0.4 M solution in trifluorotoluene, 3 equiv). The reaction was shaken overnight. A polyamine resin was added to quench the excess sulfonyl chloride. The mixture was filtered and concentrated. The residue was dissolved in EtOAc and washed with 1 M NaOH and brine, dried over Na2SO4 and concentrated to give a light brown oil. Purification by chromatography (5% MeOH/CH2Cl2 with 1% NH4OH) gave the title compound as an off-white foam (32 mg, 0.060 mmol, 66%). The structure was confirmed by NMR and mass spectrometry. MS m/z 532 (M++H).
Reaction SMILES: N[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.ClC1C=C2C([O:34][C:35](=O)[NH:36]C2=CC=1)=O>O1CCCC1>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C:35]([NH2:36])=[O:34])=[N:3][CH:4]=1
Reactant: Nc1ccc(Cl)cn1
Reactant: O=c1[nH]c2ccc(Cl)cc2c(=O)o1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: NC(=O)c1ccc(Cl)cn1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 177.8 %

Procedure:
To a solution of 2-amino-5-chloropyridine (328 mg, 2.55 mmol) in tetrahydrofuran (5 ml) was 0.5M potassium bis(trimethylsilyl)amide in toluene (10 ml, 5.05 mmol) dropwise at −78° C. After stirred for additional 0.5 hr at −78° C., the mixture was added 5-chloroisatoic anhydride (0.5 g, 2.55 mmol) at −78° C. The mixture was warmed up to r.t gradually and stirred overnight. After quenched by saturated ammonium chloride solution, the mixture was extracted by ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated to give (2-amino-5-chlorophenyl)-N-(5-chloro(2-pyridyl)carboxamide (0.71 g. 100%). MS found for C12H9Cl2N3O M+=282, (M+2)+=284. Step 2: To a solution of the compound of (2-amino-5-chlorophenyl)-N-(5-chloro(2-pyridyl)carboxamide (0.71 g, 2.52 mmol) in dichloromethane (10 ml) was added 3-cyanobenzoly chloride (417 mg, 2.52 mmol) and pyridine (0.611 ml, 7.55 mmol). The mixture was stirred at r.t. overnight. The precipitate was filtered and washed with dichloromethane to give N-[4-chloro-2-[N-(5-chloro(2-pyridyl)carbamoyl]phenyl](4-cyanophenyl)carboxamide as a solid (683 mg, 66%). MS found for C20H12Cl2N4O2 M+=411, (M+2)+=413. Step 3: To a solution of the compound of N-{4-chloro-2-[N-(5-chloro(2-pyridyl)carbamoyl]phenyl}(4-cyanophenyl)carboxamide (683 mg, 1.66 mmol) in anhydrous pyridine (10 ml) and triethyl amine (1 ml) was saturated with hydrogen sulfide gas at 0° C. The mixture was stirred at r.t. overnight. After the evaporated the solvent, the residue was dissolved in anhydrous acetone (5 ml) and iodomethane (1 ml, 16.6 mmol) was added. The mixture was stirred under reflux condition for 2 hrs. After the evaporation of solvent, the residue was dissolved in anhydrous methanol (5 ml) and added a solution of N-methylethylenediamine (0.732 ml, 8.3 mmol) and acetic acid (1.5 ml) in anhydrous methanol (5 ml). The mixture was stirred under reflux condition for 2 hrs. After the evaporation of solvent, the crude residue was purified by RP-HPLC to give N-{4-chloro-2-[N-(5-chloro(2-pyridyl))carbamoyl]phenyl}[4-(1-methyl(2-imidazolin-2-yl))phenyl]carboxamide as a white powder. MS found for C23H19Cl2N5O2 M+=468 (M+2)+=470.
Reaction SMILES: S[CH2:2][CH2:3][OH:4].CN1[CH2:10][CH2:9][CH2:8][C:7]1=[O:11].CC(O)C[N:15]([CH2:20][CH:21](O)[CH3:22])[CH2:16][CH:17](O)[CH3:18].Cl>O>[CH:16]1[CH:18]=[C:17]2[CH:22]=[CH:21][C:20]([CH:2]3[C:7](=[O:11])[C:8]4[C:20](=[CH:21][CH:22]=[CH:10][CH:9]=4)[C:3]3=[O:4])=[N:15][C:16]2=[CH:18][CH:17]=1
Reactant: CN1CCCC1=O
Reactant: OCCS
Reactant: CC(O)CN(CC(C)O)CC(C)O
Agent: Cl
Solvent: O
Product: O=C1c2ccccc2C(=O)C1c1ccc2ccccc2n1
Temperature: 180 °C

Procedure:
23 parts of the reaction product obtained according to Example 15 are reacted with 10 parts of 2-mercaptoethanol in 50 parts of volume of N-methylpyrrolidone with an addition of 32 parts of triisopropanolamine by heating for 8 hours at 180°C while stirring. The whole is dripped into a mixture of 1500 parts of water, 1500 parts of ice and 40 parts of 10N hydrochloric acid while stirring well. The dye thus precipitated is suction filtered, washed with water and dried. The quinophthalone derivative obtained as a yellow powder colors polyesters yellow hues having outstanding fastness properties. It probably has the formula: ##SPC17##