Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=1.[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>ClCCl>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[O:9])=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=1
Reactant: Cc1ccc(CO)c([N+](=O)[O-])c1
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: Cc1ccc(C=O)c([N+](=O)[O-])c1

Procedure:
(4-Methyl-2-nitrophenyl)methanol D139 (1.028 g, 6.15 mmol), pyridinium dichromate (3.47 g, 9.22 mmol)+molecular sieves (7 g, 6.15 mmol) in dry dichloromethane (DCM) (14 mL) was stirred under argon at R. T. overnight. The reaction mixture was filtered by silica/kieselguhr (1:1) and extracted with water and DCM. Organic layers were combined and evaporated to give a pale yellow solid which was used without further purification (0.665 g, 65.5%).
Reaction SMILES: C1CCN2C(=NCCC2)CC1.[CH2:12]([O:14][C:15](=[O:22])[CH2:16][C:17]([CH:19]1[CH2:21][CH2:20]1)=O)[CH3:13].[N:23]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[F:32])=[N+:24]=[N-:25].O>CN(C=O)C>[CH:19]1([C:17]2[N:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[F:32])[N:24]=[N:25][C:16]=2[C:15]([O:14][CH2:12][CH3:13])=[O:22])[CH2:21][CH2:20]1
Reactant: CCOC(=O)CC(=O)C1CC1
Reactant: [N-]=[N+]=Nc1ccccc1F
Solvent: C1CCC2=NCCCN2CC1
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)c1nnn(-c2ccccc2F)c1C1CC1
Reaction time: 0.25 h

Procedure:
DBU (2.99 ml; 20.06 mmol; 1.10 eq.) was dissolved in DMF (37.5 ml) and put under nitrogen atmosphere. 3-Cyclopropyl-3-oxo-propionic acid ethyl ester (Betapharma, 3.132 g; 20.06 mmol; 1.10 eq.) was added to the mixture and it was stirred for 15 min. Then a solution of 1-azido-2-fluorobenzene prepared according to Platz, M. S. et al. J. Org. Chem. 1989, 54, 5938-5945, (2.5 g; 18.23 mmol; 1 eq.) in DMF (5 mL) was added dropwise to the solution at room temperature. Water (50 mL) was added to the cooled reaction mixture and the aqueous layer was extracted with EtOAc (3×50 mL). Combined organics were washed with water and brine, dried over MgSO4 and concentrated under vacuum affording the title compound as a brown oil. It was used in the next step without further purification. LC/MS (Method B): 276.1 (M+H)+.
Reaction SMILES: [CH:1]1([NH2:4])[CH2:3][CH2:2]1.[Cl:5][C:6]1[CH:17]=[CH:16][C:9]([CH2:10][NH:11][C:12](=[O:15])[CH2:13][CH3:14])=[CH:8][C:7]=1[CH:18]=O.[BH4-].[Na+].[OH-].[Na+]>CO>[Cl:5][C:6]1[CH:17]=[CH:16][C:9]([CH2:10][NH:11][C:12](=[O:15])[CH2:13][CH3:14])=[CH:8][C:7]=1[CH2:18][NH:4][CH:1]1[CH2:3][CH2:2]1
Reactant: CCC(=O)NCc1ccc(Cl)c(C=O)c1
Reactant: NC1CC1
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCC(=O)NCc1ccc(Cl)c(CNC2CC2)c1
Reaction time: 8 h
Yield: 81.2 %

Procedure:
Cyclopropylamine (1.28 mL, 18.2 mmol) was added to a sol. of N-(4-chloro-3-formyl-benzyl)-propionamide (2.74 g, 12.1 mmol) in MeOH (42 mL). The mixture was stirred overnight, and NaBH4 (918 mg, 24.3 mmol) was added in portions. The mixture was stirred for 4 h, and aq. 1M NaOH (70 mL) was added. The solvents were partially removed under reduced pressure, and the aq. residue was extracted with EtOAc (2×). The combined org. extracts were washed with brine, dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC(CH2Cl2→MeOH/CH2Cl2 1:9) yielded the title compound (2.62 g, 81%). LC-MS: tR=0.58 min; ES+: 267.38.
Reaction SMILES: O1CCCCC1[O:7][CH2:8][CH2:9][CH2:10][CH2:11][N:12]1[C:20](=[O:21])[C:19]2[C:14](=[CH:15][N:16]=[CH:17][CH:18]=2)[S:13]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[OH:7][CH2:8][CH2:9][CH2:10][CH2:11][N:12]1[C:20](=[O:21])[C:19]2[C:14](=[CH:15][N:16]=[CH:17][CH:18]=2)[S:13]1
Reactant: O=c1c2ccncc2sn1CCCCOC1CCCCO1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: O
Product: O=c1c2ccncc2sn1CCCCO
Yield: 100.4 %

Procedure:
A solution of 1 g of 2-(4-(2-tetrahydropyranyloxy)butyl)-isothiazolo[5,4-c]pyridin-3(2H)-one and 0.1 g of p-toluenesulfonic acid monohydrate in 50 mL of methanol was stirred overnight at ambient temperature and concentrated to dryness under reduced pressure. The residue was dissolved in 200 mL of ethyl acetate, washed with 4 mL of saturated sodium bicarbonate, dried over MgSO4 and concentrated under reduced pressure. Drying under vacuum overnight gave 0.73 g (78%) of 2-(4-hydroxybutyl)-isothiazolo[5,4-c]pyridin-3(2H)-one as an oil: 1H NMR (400 MHz, CDCl3): 9.28 (s, 1H), 9.15 (d, J=5 Hz, 1H), 7.98 (d, J=5Hz, 1H), 3.86 (t, J=7.5 Hz, 2H), 3.71 (t, J=6.4 Hz, 2H), 2.36 (br s, 1H), 1.98 (m, 2H), 1.27 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:9][CH2:10][N:11]([CH3:16])[CH2:12][CH2:13][CH2:14][NH2:15])=[CH:4][CH:3]=1.[C:23](N1C=CN=C1)(N1C=CN=C1)=[O:24].[NH:35]([C:39]1[S:40][CH:41]=[C:42]([CH2:44][S:45][CH2:46][CH2:47][NH2:48])[N:43]=1)[C:36]([NH2:38])=[NH:37]>C(OCC)(=O)C.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:9][CH2:10][N:11]([CH2:12][CH2:13][CH2:14][NH:15][C:23]([NH:48][CH2:47][CH2:46][S:45][CH2:44][C:42]2[N:43]=[C:39]([NH:35][C:36]([NH2:38])=[NH:37])[S:40][CH:41]=2)=[O:24])[CH3:16])=[CH:4][CH:3]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CN(CCCN)CCC(c1ccc(Cl)cc1)c1ccccn1
Reactant: N=C(N)Nc1nc(CSCCN)cs1
Solvent: CO
Solvent: CCOC(C)=O
Product: CN(CCCNC(=O)NCCSCc1csc(NC(=N)N)n1)CCC(c1ccc(Cl)cc1)c1ccccn1

Procedure:
Preparation is effected analogously to Example 63, using 0.9 g (2.8 mmol) of N-[3-(4-chlorophenyl)-3-(2-pyridyl)propyl]-N-methyl-1,3-propanediamine, an equimolar amount of 1,1'-carbonyldiimidazole and 0.73 g (3.1 mmol) of 2-[[(2-guanidino-4-thiazolyl)methyl]thio]ethaneamine as starting materials. Working up by chromatography (eluant: ethyl acetate/methanol 85+15) analogously to Example 63 yields the purified title compound in the form of a dry foam; MS (+FAB method): m/z (rel. int.[%])=575 ([M+H]+, 3), 155 (22), 230 (100); IR (KBr): 1646 cm-1 (C=O).
Reaction SMILES: [CH2:1]([C:13]1[O:14][CH:15]=[CH:16][CH:17]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].CCCCCC.C([Li])CCC.[C:29](=[O:31])=[O:30]>CCOCC>[CH2:1]([C:13]1[O:14][C:15]([C:29]([OH:31])=[O:30])=[CH:16][CH:17]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: O=C=O
Reactant: CCCCCCCCCCCCc1ccco1
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: CCCCCC
Product: CCCCCCCCCCCCc1ccc(C(=O)O)o1
Reaction time: 1 h

Procedure:
A solution of 30.4 g (0.2 moles) of 2-dodecylfuran in 300 ml of anhydrous ether is stirred at -20° C. after which 0.22 moles (92 ml of a 2.4 molar hexane solution) of butyllithium is added slowly with stirring. The reaction mixture is stirred for 1 hour then poured over 200 g of crushed dry ice (solid CO2) after which the mixture is allowed to stand for 1 hour prior to dilution with a saturated ammonium chloride solution The organic layer is separated, washed with water and brine, dried over sodium sulfate and evaporated to give 5-dodecyl-2-furancarboxylic acid. The thus obtained acid in 500 ml of anhydrous ether is stirred at room temperature during which time 200 ml of a 2 molar solution of methyllithium in ether is added slowly. The reaction mixture is allowed to stand at room temperature for 2 hours after which it is poured into a saturated ammonium chloride solution The organic layer is separated and washed with water and brine, dried over sodium sulfate and evaporated to dryness to give white crystals of methyl 2-(5-dodecylfuryl) ketone. M.P. 35°-7° C.
Reaction SMILES: O[C:2]1([CH2:26][O:27][CH3:28])[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][NH:20][C:21](=[O:23])[CH3:22])[O:16][C:15]3=[O:24])=[CH:10][C:9]=2[F:25])[CH2:4][CH2:3]1.CCN(S(F)(F)[F:35])CC>ClCCl>[F:35][C:2]1([CH2:26][O:27][CH3:28])[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][NH:20][C:21](=[O:23])[CH3:22])[O:16][C:15]3=[O:24])=[CH:10][C:9]=2[F:25])[CH2:4][CH2:3]1
Reactant: COCC1(O)CCN(c2ccc(N3C[C@H](CNC(C)=O)OC3=O)cc2F)CC1
Reactant: CCN(CC)S(F)(F)F
Solvent: ClCCl
Product: COCC1(F)CCN(c2ccc(N3C[C@H](CNC(C)=O)OC3=O)cc2F)CC1
Yield: 68 %

Procedure:
The title compound was prepared by reacting ((S)-N-{3-[4-(4-hydroxy-4-methoxymethylpiperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1.37 mmol) with DAST (4.10 mmol) in dichloromethane (10 ml) at a temperature 0° C. for one hour and by purifying the compound by silica gel column chromatography in 68% yield.
Reaction SMILES: [C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[C@H:19]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[CH:26][CH:25]=2)[CH2:18]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=O.[OH-:36].[Li+].C(COC)[O:39]C>O>[C:1]([NH:8][C@@H:9]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C@@H:17]([OH:39])[CH2:18][C@@H:19]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[CH:26][CH:25]=1)[C:20]([OH:21])=[O:22])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:36]
Reactant: [OH-]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@@H]1C[C@@H](Cc2ccc(-c3ccccc3)cc2)C(=O)O1
Reactant: COCCOC
Agent: [Li+]
Solvent: O
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@@H](O)C[C@@H](Cc1ccc(-c2ccccc2)cc1)C(=O)O
Reaction time: 16 h

Procedure:
1.3 g (2.76 mmol) of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]-3(R)-[(4-biphenylyl)methyl]dihydrofuran-2-(3H)-one are hydrolysed, in 28 ml of dimethoxyethane, with 11 ml of a 1M solution of lithium hydroxide in water. After 16 h at RT, the dimethoxyethane is evaporated off on a RE and the residue is treated with an ice-cold mixture of 15 ml of sat. NH4Cl solution, 80 ml of 10% citric acid solution and methylene chloride. The aqueous phase is separated off and extracted 2× with methylene chloride. The organic phases are washed with saline, dried with Na2SO4 and evaporated to give the title compound: TLC Rf (B)=0.4; tRet (II)=16.4 min.
Reaction SMILES: C(OC(=O)[N:7]([CH2:9][CH:10]([OH:13])[CH2:11][OH:12])[CH3:8])(C)(C)C.N1C=CC=CC=1.[C:21]([Cl:26])(=[O:25])[O:22][CH2:23][CH3:24].[C:27]([O:30][CH2:31][CH3:32])(=[O:29])C>>[ClH:26].[C:21](=[O:25])([O:12][CH2:11][CH:10]([O:13][C:27](=[O:29])[O:30][CH2:31][CH3:32])[CH2:9][NH:7][CH3:8])[O:22][CH2:23][CH3:24]
Reactant: CN(CC(O)CO)C(=O)OC(C)(C)C
Reactant: CCOC(C)=O
Reactant: CCOC(=O)Cl
Solvent: c1ccncc1
Product: CCOC(=O)OCC(CNC)OC(=O)OCC
Product: Cl
Temperature: 25 °C
Reaction time: 96 h

Procedure:
To a mixture of tert-butyl(2,3-dihydroxypropyl)methylcarbamate (15.53 g) obtained in Reference Example 45 and ethyl acetate (100 mL) were added pyridine (18.35 mL) and ethyl chlorocarbonate (24.62 g) under ice-cooling, and the mixture was stirred at room temperature for 96 hrs. Ethyl acetate (300 mL) was added to the reaction mixture, and the mixture was washed with water (150 mL), an aqueous copper sulfate solution (100 mL), water (100 mL) and saturated brine (100 mL), and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel column chromatography (eluted with ethyl acetate:hexane=1:6). To the purified product was added a 4N hydrogen chloride—ethyl acetate solution (80 mL), and the mixture was stirred at room temperature for 3 hrs. Diethyl ether (200 mL) was added, and the precipitated solid was collected by filtration. The solid was dried under reduced pressure to give the title compound (5.93 g) as a white solid.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH:8]=[CH2:9].[OH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([O:25][CH2:26][CH:27]([CH3:30])[CH2:28][CH3:29])=[O:24])=[CH:19][CH:18]=2)=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.ClCCl>[CH2:2]([O:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([O:25][CH2:26][CH:27]([CH3:30])[CH2:28][CH3:29])=[O:24])=[CH:19][CH:18]=2)=[CH:15][CH:16]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH:8]=[CH2:9]
Reactant: C=CCCCCCCBr
Reactant: CCC(C)COC(=O)c1ccc(-c2ccc(O)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CC(C)=O
Product: C=CCCCCCCOc1ccc(-c2ccc(C(=O)OCC(C)CC)cc2)cc1
Yield: 72.7 %

Procedure:
5.0 g of 8-bromo-1-octene, 8.2 g of 2-methylbutyl 4'-hydroxybiphenyl-4-carboxylate obtained in Example 1.(1), and 4.0 g pf potassium carbonate were refluxed in acetone for 20 hours. After the reaction the resulting reaction mixture was diluted with dichloromethane, and the inorganic substance was filtered out. Subsequently, the solvent was distilled out under reduced pressure, and the resulting residue was purified by column chromatography to obtain 7.5 g of the objective biphenyl derivative. (Yield : 73%).
Reaction SMILES: [CH:1]1([CH2:7][NH:8][C:9]2[C:14]([N+:15]([O-])=O)=[CH:13][C:12]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:11]([N:25]3[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]3)[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H][H]>C1COCC1.[Pd]>[CH:1]1([CH2:7][NH:8][C:9]2[C:14]([NH2:15])=[CH:13][C:12]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:11]([N:25]3[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]3)[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CN1CCN(c2cc(NCC3CCCCC3)c([N+](=O)[O-])cc2Nc2ccccc2)CC1
Reactant: [H][H]
Agent: [Pd]
Solvent: C1CCOC1
Product: CN1CCN(c2cc(NCC3CCCCC3)c(N)cc2Nc2ccccc2)CC1
Reaction time: 0.05 h
Yield: 47.9 %

Procedure:
To a solution of N4-cyclohexylmethyl-2-(4-methyl-piperazin-1-yl)-5-nitro-N1-phenyl-benzene-1,4-diamine (0.22 g, 0.53 mmol) in THF (5.00 mL) was added 10% palladium on activated carbon (0.22 g). The reaction flask was equipped with a septum and was placed under vacuum for 3 min. This flask was placed under hydrogen atmosphere (balloon inflated with hydrogen) and the reaction mixture was stirred for 18 h. The palladium was filtered off through a plug of diatomaceous earth and washed with EtOAc. The solvent was removed via rotary evaporation. The resulting residue was flash chromatographed (5% MeOH/CH2Cl2), yielding N1-cyclohexylmethyl-5-(4-methyl-piperazin-1-yl)-N4-phenyl-benzene-1,2,4-triamine (0.10 g, 49.5% yield). M+, 392
Reaction SMILES: [NH2:1][C@H:2]([CH3:24])[C:3]([N:5]1[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:23])[CH3:22])=[CH:17][CH:16]=2)[CH2:7][CH2:6]1)=[O:4].[C:25](Cl)(=[O:27])[CH3:26]>ClCCl>[C:21]([C:18]1[CH:17]=[CH:16][C:15]([O:14][CH2:13][CH2:12][CH2:11][N:8]2[CH2:9][CH2:10][N:5]([C:3](=[O:4])[C@H:2]([NH:1][C:25](=[O:27])[CH3:26])[CH3:24])[CH2:6][CH2:7]2)=[CH:20][CH:19]=1)(=[O:23])[CH3:22]
Reactant: CC(=O)Cl
Reactant: CC(=O)c1ccc(OCCCN2CCN(C(=O)[C@@H](C)N)CC2)cc1
Solvent: ClCCl
Product: CC(=O)N[C@H](C)C(=O)N1CCN(CCCOc2ccc(C(C)=O)cc2)CC1
Temperature: 0 °C
Reaction time: 4 h
Yield: 83 %

Procedure:
A 0° C. solution of Example 29 (1 mmol) and TEA (1.1 mmol) in dichloromethane (10 mL) was treated with acetyl chloride (1 mmol). After stirring for four hours at 0° C., the reaction mixture was quenched with water and extracted with dichloromethane. The combined dichloromethane layers were washed with brine, dried (Na2SO4), filtered and concentrated. The crude material was purified through silica gel chromatography to afford the desired product in 83% yield.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[O:11])=[CH:2]1.[H-].[Na+].[CH2:14](Br)[CH:15]=[CH2:16]>CN(C=O)C>[CH2:16]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[O:11])=[CH:2]1)[CH:15]=[CH2:14]
Reactant: O=Cc1c[nH]c2ccccc12
Reactant: C=CCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=CCn1cc(C=O)c2ccccc21
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
Indole-3-carbaldehyde (1 eq.) was dissolved in DMF (0.46 M). Sodium hydride was added (2.5 eq.) and the resulting solution was stirred at RT for 20 min. Allyl bromide (1 eq.) was then added and the reaction solution was allowed to stir at RT for 20 h. The reaction mixture was subsequently quenched with brine and extracted with EtOAc. The combined organic extracts were dried over MgSO4. Filtration and concentration of the filtrate in vacuo afforded a yellow oil. Purification of the crude product thus obtained by way of flash chromatography (SiO2, 4:1 (v/v) Hex:EtOAc→3:7 (v/v) Hex:EtOAc) afforded the title compound as a light yellow oil.
Reaction SMILES: S(OC)(O[CH3:5])(=O)=O.CSC.[Cl:11][C:12]1[CH:30]=[CH:29][C:15]([O:16][C:17]([C:20]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)=[O:21])([CH3:19])[CH3:18])=[CH:14][CH:13]=1.C[O-].[Na+]>C(#N)C>[Cl:28][C:25]1[CH:26]=[CH:27][C:22]([C:20]2([C:17]([O:16][C:15]3[CH:14]=[CH:13][C:12]([Cl:11])=[CH:30][CH:29]=3)([CH3:19])[CH3:18])[CH2:5][O:21]2)=[CH:23][CH:24]=1
Reactant: CC(C)(Oc1ccc(Cl)cc1)C(=O)c1ccc(Cl)cc1
Reactant: COS(=O)(=O)OC
Agent: C[O-]
Agent: [Na+]
Solvent: CC#N
Solvent: CSC
Product: CC(C)(Oc1ccc(Cl)cc1)C1(c2ccc(Cl)cc2)CO1
Temperature: 25 °C
Reaction time: 120 h
Yield: 53.9 %

Procedure:
A solution of 59.2 g (0.47 mole) of dimethyl sulphate and 32 g (0.517 mole) of dimethyl sulphide in 270 ml of acetonitrile is allowed to stir at room temperature for 5 days. Then, at 20° to 25° C., a solution of 87 g of 4-chlorophenyl 2-(p-chlorophenoxy)-2-propyl ketone in 80 ml of acetonitrile is added dropwise within about 2 hours. At the same temperature, 28.7 g (0.53 mole) of sodium methylate are added, the mixture is allowed to stir for 12 hours and then evaporated. The residue is vigorously stirred with a mixture of 200 ml of ethyl acetate and 150 ml of water overnight. The organic phase is separated off, dried over sodium sulphate and evaporated in vacuo. 49 g (76% of theory) of crude 2-(4-chlorophenyl)-2-[2-(p-chlorophenoxy)-2-propyl]oxirane are obtained, and this is immediately reacted further. ##STR47##
Reaction SMILES: [CH2:1](/[C:3](=[CH:9]\[CH3:10])/[CH:4]=[CH:5]/[C:6](O)=[O:7])[CH3:2].C([N:13](CC)CC)C.ClC(OC(C)C)=O.N>ClCCl>[CH2:1](/[C:3](=[CH:9]\[CH3:10])/[CH:4]=[CH:5]/[C:6]([NH2:13])=[O:7])[CH3:2]
Reactant: C/C=C(/C=C/C(=O)O)CC
Reactant: CCN(CC)CC
Agent: CC(C)OC(=O)Cl
Agent: N
Solvent: ClCCl
Product: C/C=C(/C=C/C(N)=O)CC
Reaction time: 1 h
Yield: 75 %

Procedure:
To a solution of 16.0 kg (114 mol) of (E,E)-4-ethyl-2,4-hexadienoic acid and 11.5 kg (114 mol) of triethylamine in 112 l of dichloromethane is added dropwise 14.0 kg (114 mol) of isopropyl chloroformate at -5°~-10° C. and the reaction is continued for 1 hour at same temperature. To this solution is introduced 7.4 kg (435 mol) of anhydrous ammonia gas and allowed to stand overnight at 20°-30° C. The solvent and excess ammonia gas is removed under reduced pressure. The residue is dissolved in 128 l of ethyl acetate and washed with 80 l of 5%-sodium chloride solution, 80 l of 5%-hydrochloric acid solution, 80 l of 5%-sodium chloride solution, 80l of 7%-sodium hydroxide solution and 80 l of 5%-sodium chloride solution respectively. The solvent is removed under reduced pressure to give 11.9 kg of (E,E)-4-ethyl-2,4 -hexadienamide as a yellow oil (Yield 74.7%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:41]=[CH:42][CH:43]=1)[CH2:5][N:6]1[CH:10]=[C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[CH:21]=[C:22]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH:23]=[CH:24][CH:25]=4)[CH:18]=3)[N:13](S(C3C=CC(C)=CC=3)(=O)=O)[CH:12]=2)[CH:8]=[N:7]1.[OH-].[Li+]>C1COCC1.O.CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:41]=[CH:42][CH:43]=1)[CH2:5][N:6]1[CH:10]=[C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[CH:21]=[C:22]([NH:26][S:27]([CH3:30])(=[O:28])=[O:29])[CH:23]=[CH:24][CH:25]=4)[CH:18]=3)[NH:13][CH:12]=2)[CH:8]=[N:7]1
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3cnn(Cc4cccc(Cl)c4)c3)c3cc(-c4cccc(NS(C)(=O)=O)c4)cnc32)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: CS(=O)(=O)Nc1cccc(-c2cnc3[nH]cc(-c4cnn(Cc5cccc(Cl)c5)c4)c3c2)c1
Yield: 17.9 %

Procedure:
Using similar reaction conditions as described in step-iii of example-1, N-(3-(3-(1-(3-chlorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)methane sulfonamide (90 mg, 0.14 mmol) was hydrolyzed with lithium hydroxide (18 mg, 0.42 mmol) in THF/water/methanol (1/0.5/1 ml) mixture to afford 12 mg (18% yield) of the pure product after purification by preparative TLC (Silicagel-1000 micron) using 10% ethyl acetate in hexane as eluent. 1H NMR (DMSO-d6, 400 MHz): δ 11.83 (s, 1H), 9.85 (s, 1H), 8.48-8.47 (d, 1H), 8.43 (s, 1H), 8.346-8.342 (d, 1H), 7.90 (s, 1H), 7.80-7.79 (d, 1H), 7.51-7.25 (m, 8H), 5.40 (s, 2H), 3.06 (s, 3H). MS: m/z=478.2 (M+1), HPLC: 92.01% (method B).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[OH:11].CC(C)([O-])C.[K+].[Br:18][C:19](Br)([F:21])[F:20].O>CN1CCN(C)C1=O>[Br:18][C:19]([F:21])([F:20])[O:11][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]([O:9][CH3:10])[C:3]=1[O:2][CH3:1]
Reactant: COc1cccc(O)c1OC
Reactant: FC(F)(Br)Br
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN1CCN(C)C1=O
Solvent: O
Product: COc1cccc(OC(F)(F)Br)c1OC
Temperature: 55 °C
Reaction time: 3 h
Yield: 24.1 %

Procedure:
To a solution of 5.0 g of 2,3-dimethoxy phenol in 1,3-dimethyl-2-imidazolidinone (65 ml) was added 7.28 g of potassium tert-butoxide, and was added dropwise a solution of 41.5 g of dibromo difluoromethane in 1,3-dimethyl-2-imidazolidinone (20 ml) over 30 minutes. The solution was stirred at 55° C. for 3 hours, and then water was added and the resulting mixture was extracted with Et2O. The organic layer was sequentially washed with 1 mol/L hydrochloric acid, water, and saturated brine, dried over MgSO4, then, the drying agent was separated by filtration and the solvent was evaporated under reduced pressure. The obtained residue was purified by column chromatography (silicagel 60; mobile phase: EtOAc/n-hexane=1/9 to 1/4; v/v) to obtain 2.21 g of the title compound (colorless oil).
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10][C:11]2[CH:16]=[CH:15][C:14]([C:17](=[O:19])[CH3:18])=[CH:13][CH:12]=2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].C(O)(=[O:22])C.ClC(Cl)C.OO>[Cl-].[Cl-].[Cl-].[Ti+3].O>[C:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([C:11]2[CH:16]=[CH:15][C:14]([C:17](=[O:19])[CH3:18])=[CH:13][CH:12]=2)=[O:22])=[CH:8][CH:9]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)O
Reactant: CC(=O)c1ccc(Sc2ccc(C(C)=O)cc2)cc1
Agent: [Ti+3]
Agent: OO
Agent: [Cl-]
Solvent: CC(Cl)Cl
Solvent: O
Product: CC(=O)c1ccc(S(=O)c2ccc(C(C)=O)cc2)cc1
Temperature: 10 °C
Reaction time: 2 h
Yield: 97 %

Procedure:
To a 300 mL four-necked flask, 20.0 g (0.107 mole) of diphenyl sulfide and 140.0 g of chlorobenzene were fed, and the resulting mixture was stirred and allowed to dissolve. To the resulting solution, 31.5 g (0.236 mole) of aluminum chloride was added, and the resulting mixture was cooled to 10° C., followed by addition of 17.7 g (0.225 mole) of acetyl chloride dropwise thereto while keeping a temperature of not more than 20° C., and allowing the resulting mixture to react by stirring thereof at 10° C. for 2 hours. The reaction solution was added to a mixture of 1000 g of ice water and 1000 mL of methylene chloride with stirring at a temperature of not more than 30° C. The methylene chloride layer was washed 3 times with 1000 mL of water and concentrated under reduced pressure, followed by addition of 1000 mL of methanol to the resultant, collection of the yielded crystals by filtration and drying thereof to obtain 19.67 g of bis(4-acetylphenyl)sulfide. The yield was 68%. To a 100 mL four-necked flask, 6.22 g (0.023 mole) of bis(4-acetylphenyl)sulfide, 60.0 g of acetic acid and 40 g of dichloroethane were fed, and the resulting mixture was allowed to dissolve under heat. To the resulting solution, 0.18 g (0.001 mole) of 20% aqueous solution of titanium trichloride was added, and 2.07 g (0.018 mole) of 30% aqueous hydrogen peroxide solution was added thereto dropwise, followed by stirring the resulting mixture for 2 hours. To this mixture, 100 mL of water was added, and the resulting mixture was cooled to 10° C., followed by collection of yielded crystals by filtration. These crystals were washed with 30 mL of methanol and collected by filtration, followed by drying thereof to obtain 6.39 g of bis(4-acetylphenyl)sulfoxide. The yield was 97%. By following the same procedure as in Example 1 except that 5.73 g (0.020 mole) of bis(4-acetylphenyl)sulfoxide was used instead of bis(hydroxyphenyl)sulfoxide, the compound No. 8 was obtained. The yielded amount was 3.98 g, and the yield was 26%.