Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:19])[N:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:8]([SH:12])=[N:9]2)=[CH:4][CH:3]=1.Cl[Sn:21]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(N(CC)CC)C>C(Cl)Cl>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:19])[N:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:8]([S:12][Sn:21]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)=[N:9]2)=[CH:4][CH:3]=1
Reactant: Cl[Sn](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=c1c2ccc(Cl)cc2nc(S)n1-c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=c1c2ccc(Cl)cc2nc(S[Sn](c2ccccc2)(c2ccccc2)c2ccccc2)n1-c1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred mixture of 4 g (0.014 mole) 7-chloro-2-mercapto-3-phenyl-4(3H)-quinazolinone (the product of Example 3) and 5.4 g (0.014 mole) chlorotriphenyl tin in methylene chloride (about 75 ml), 1.4 g (0.014 mole) triethylamine in methylene chloride (about 25 ml) was added dropwise. The resulting mixture was stirred for about one hour at ambient temperature, refluxed about 5 hours, stirred overnight, refluxed about 4 hours and cooled. The mixture was washed with water. The organic fraction was dried and stripped to give the above-identified product as a solid, melting point 110° to 112° C.
Reaction SMILES: [N:1]#CN.[Pb].C[NH:6][C:7]([NH:9][CH2:10][CH2:11][S:12][CH2:13][C:14]1[NH:18][CH:17]=[N:16][C:15]=1[CH3:19])=S.CN(C)C=O>C(#N)C>[CH3:19][C:15]1[N:16]=[CH:17][NH:18][C:14]=1[CH2:13][S:12][CH2:11][CH2:10][NH:9][C:7]([NH2:1])=[NH:6]
Reactant: N#CN
Reactant: CNC(=S)NCCSCc1[nH]cnc1C
Agent: [Pb]
Solvent: CN(C)C=O
Solvent: CC#N
Product: Cc1nc[nH]c1CSCCNC(=N)N
Reaction time: 24 h

Procedure:
Lead cyanamide (3.0 g.) was added to a solution of N-methyl-N'-[2-((4-methyl-5-imidazolyl)methylthio)-ethyl]thiourea (2.44 g.) in acetonitrile (50 ml.). Dimethylformamide (20 ml.) was added subsequently and the suspension was heated under reflux, with stirring, for 24 hours. Filtration, followed by concentration under reduced pressure and purification of the product by chromatography on a column of silica gel with acetonitrile as eluant and recrystallisation from the same solvent afforded N-cyano-N'-methyl- N"[2-((4-methyl-5-imidazolyl)-methylthio)ethyl]guanidine, m.p. 139°-141°.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH3:15][O:16][C:17]1[CH:22]=[C:21]([NH2:23])[CH:20]=[CH:19][N:18]=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.C1CCCCC1>O.[Cl-].[Na+].O>[F:1][C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([NH:23][C:21]1[CH:20]=[CH:19][N:18]=[C:17]([O:16][CH3:15])[CH:22]=1)=[O:6]
Reactant: COc1cc(N)ccn1
Reactant: O=C(O)c1ccc(C(F)(F)F)cc1F
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: C1CCCCC1
Product: COc1cc(NC(=O)c2ccc(C(F)(F)F)cc2F)ccn1
Temperature: 35 °C
Reaction time: 2 h
Yield: 82.8 %

Procedure:
A 50 liter jacketed glass reactor was fitted with an N2 inlet, a mechanical stirrer, and a condenser. With the stirrer set to 150 rpm and the jacket temperature set at 40° C., 2-Me-THF (6.000 L, 3.0 vol), 2-fluoro-4-(trifluoromethyl)benzoic acid (2000 g, 9.610 mol), 2-methoxypyridin-4-amine (1.278 kg, 10.09 mol), and TEA (2.917 kg, 4.018 L, 28.83 mol) were added to the reactor, which resulted in a slightly hazy, light amber solution. The reactor was switched to reaction control and heated to 35° C. To the solution was added T3P in 2-Me-THF (9.176 kg, 9.176 L of 50% w/w, 14.42 mol) over 30-45 min, which resulted in a light amber solution. After 2 hours, the reaction was judged to be complete by HPLC analysis (<2% of 1 remaining). The reaction was quenched with water (1.000 L, 0.5 vol), which was added via addition funnel over a period of 10 minutes in order to control the exothermic quenching reaction. The mixture was then diluted with 2-Me-THF (8.000 L, 4.0 vol) and water (8.000 L, 4.0 vol) and stirred for 30 minutes at 30-40° C. After stirring was stopped, the layers were allowed to separate, and the aqueous layer was removed. The organic layer was washed with 10% aqueous NaOH (6.000 L, 3.0 vol), stirring resulted in an emulsion. Brine (500.0 mL, 0.25 vol) was added, and the mixture was stirred for about 5 minutes. The layers were separated, and the aqueous layer removed. The organic layer was washed again with brine (10.00 L, 5.0 vol), and the aqueous layer was drained. The organic layer was dried over Na2SO4, and filtered through diatomaceous earth (Celite). The filter cake was washed with 2-Me-THF (4.000 L, 2.0 vol) and pulled dry. The filtrate was transferred to a rotovap, and partial distillation of solvent was begun at a bath temperature of 40° C. and a pressure of 150 mbar, resulting in the formation of solids in the mixture. Cyclohexane (10.00 L, 5.0 vol) was added portionwise during the partial distillation. Distillation was stopped, the reaction mixture (˜8 liter) was slurried on the rotovap, and the bath temperature was reduced to room temperature. The mixture was filtered, and the filter cake was washed with cyclohexane (2.000 L, 1.0 vol) and pulled dry under a nitrogen blanket to afford a light yellow solid. The solid was scooped out of the funnel and dried in vacuo (40° C., <30 mbar, rotovap) to afford 2-fluoro-N-(2-methoxypyridin-4-yl)-4-(trifluoromethyl)benzamide (2,501 g, 7.959 mol, 83%) as a fine, off-white solid.
Reaction SMILES: [OH-].[Na+].[CH2:3]([C:5]1(C)[CH:11]=[CH:10][CH:9]=[CH:8][CH:6]1[NH2:7])[CH3:4].[Br:13][CH:14]([CH3:18])[C:15](Br)=[O:16].[C:19]1(C)C=CC=CC=1>>[Br:13][CH:14]([CH3:18])[C:15]([NH:7][C:6]1[C:8]([CH3:19])=[CH:9][CH:10]=[CH:11][C:5]=1[CH2:3][CH3:4])=[O:16]
Reactant: CC(Br)C(=O)Br
Reactant: Cc1ccccc1
Reactant: CCC1(C)C=CC=CC1N
Agent: [Na+]
Agent: [OH-]
Product: CCc1cccc(C)c1NC(=O)C(C)Br
Reaction time: 0.25 h

Procedure:
To a two-phase system, containing an aqueous sodium hydroxide solution (20 g sodium hydroxide in 200 ml water) and a mixture of 13.5 g 2-ethyl-2-methylaniline and 75 ml toluene (cooled to 8° C.), was added dropwise with stirring 25 g 2-bromopropionyl bromide. After this addition, stirring was continued for 15 min. and the formed crystals were filtered off. (Addition of petroleum ether to the filtrate precipitates more product, which can be added to the first crop). Total yield: 22.8 g (84%). After recrystallization from ether-petroleum ether, it melted at 181°-182° C.
Reaction SMILES: [ClH:1].[CH3:2][N:3]([CH3:23])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([C:14]2[CH:19]=[CH:18][C:17]([N:20]([CH3:22])[CH3:21])=[CH:16][CH:15]=2)=[CH:11][CH:12]=O)=[CH:6][CH:5]=1.[CH3:24][N:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([CH3:35])([CH3:34])[C:26]1=[CH2:36]>C(O)(=O)C>[Cl-:1].[CH3:2][N:3]([CH3:23])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([C:14]2[CH:19]=[CH:18][C:17]([N:20]([CH3:22])[CH3:21])=[CH:16][CH:15]=2)=[CH:11][CH:12]=[CH:36][CH:26]2[C:27]([CH3:35])([CH3:34])[C:28]3[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=3)[NH+:25]2[CH3:24])=[CH:6][CH:5]=1
Reactant: CN(C)c1ccc(C(=CC=O)c2ccc(N(C)C)cc2)cc1
Reactant: Cl
Reactant: C=C1N(C)c2ccccc2C1(C)C
Solvent: CC(=O)O
Product: CN(C)c1ccc(C(=CC=CC2[NH+](C)c3ccccc3C2(C)C)c2ccc(N(C)C)cc2)cc1
Product: [Cl-]

Procedure:
In a suitable container equipped with an air condenser and a drying tube to exclude atmospheric moisture and heated by a steam bath, are placed 50 parts glacial acetic acid, 2 parts of concentrated hydrochloric acid, 7.07 parts of 3,3-bis(4-dimethylaminophenyl)acrolein (0.024 moles) and 4.16 parts of 1,3,3-trimethyl-2-methylene-indoline (0.024 moles). The mixture is heated for 18 hours during which time it takes on a deep blue coloration. The solution is concentrated to about one-half its initial volume, diluted to 600 parts by volume with water and salted out with a mixture of sodium chloride and sodium acetate. After filtering and drying, the solid is extracted with chloroform in a Soxhlet extractor to remove salt and the chloroform concentrate evaporated to yield 11.7 parts of green-grey microcrystals of 2-(4,4-bis-(4-dimethylaminophenyl)butadienyl)-1,3,3-trimethylindolinium chloride.
Reaction SMILES: [Br:1][C:2]1[C:3]([NH2:29])=[N:4][CH:5]=[N:6][C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[NH:15][CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=3)[N:18]=2)[CH2:10][CH2:9]1.[F:30]C1C=CC(C2N=C(C3CCNCC3)NC=2)=CC=1C(F)(F)F>>[Br:1][C:2]1[C:3]([NH2:29])=[N:4][CH:5]=[N:6][C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[NH:15][CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([F:30])=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=3)[N:18]=2)[CH2:10][CH2:9]1
Reactant: Fc1ccc(-c2c[nH]c(C3CCNCC3)n2)cc1C(F)(F)F
Reactant: Nc1ncnc(N2CCC(c3nc(-c4cccc(C(F)(F)F)c4)c[nH]3)CC2)c1Br
Product: Nc1ncnc(N2CCC(c3nc(-c4ccc(F)c(C(F)(F)F)c4)c[nH]3)CC2)c1Br

Procedure:
The title compound was prepared in an analogous manner as 5-bromo-6-{4-[4-(3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidin-1-yl}-pyrimidin-4-ylamine using 4-{4-[4-fluoro-3-(trifluoromethyl)phenyl]-1H-imidazol-2-yl}piperidine instead of 4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1h-imidazol-2-yl]-piperidine. LC-MS: (M+1=485, obsd.=485).
Reaction SMILES: [CH3:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][CH:7]2[CH2:12][CH2:11][N:10]([CH:13](C)[C:14]#[CH:15])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.I[C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=1.[CH2:27](N)CCC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH:7]2[CH2:8][CH2:9][N:10]([CH2:13][CH2:14][C:15]#[C:27][C:20]3[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=3)[CH2:11][CH2:12]2)=[CH:17][CH:18]=1
Reactant: CCCCN
Reactant: C#CC(C)N1CCC(Cc2ccc(C)cc2)CC1
Reactant: Oc1ccc(I)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: Cc1ccc(CC2CCN(CCC#Cc3ccc(O)cc3)CC2)cc1
Temperature: 55 °C
Reaction time: 24 h
Yield: 27 %

Procedure:
To a solution of 4-(4-methylbenzyl)-1-(1-butyn-3-yl)piperidine (400 mg, 1.66 mmol) and 4-iodophenol (347 mg 1.57 mmol) in 10 mL of butylamine is added 80 mg of Pd(PPh3)4. The resulting solution is allowed to stir at 55° C. for 24 hr. The solvent is evaporated in vacuo and the residue is purified by flash chromatography (20% EtOAc in hexane) to give 150 mg (27%) of the title product as a brown oil. 1H NMR (CDCl3) 1.34 (m, 2 H), 1.50 (m, 1 H), 1.65 (d, J=11.7 Hz, 2 H), 2.08 (t, J=12.0 Hz, 2 H), 2.33 (s, 3 H), 2.47 (d, J=6.9 Hz, 2 H), 2.60 (t, J=7.2 Hz, 2 H), 2.68 (t, J=7.5 Hz, 2 H), 3.02 (d, J=11.1 Hz, 2 H), 3.49 (brs, 1 H), 6.68 (d, J=8.1 Hz, 2 H), 7.01 (d, J=7.5 Hz, 2 H), 7.08 (d, J=7.5 Hz, 2 H), 7.20 (d, J=8.1 Hz, 2 H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]([NH:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=1)[CH2:12][OH:13].[OH-].[Na+].[Cl:29][CH2:30][C:31](Cl)=[O:32]>C(Cl)Cl.O>[Cl:29][CH2:30][C:31]([N:14]([CH:11]([C:4]1[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][C:5]=1[O:9][CH3:10])[CH2:12][OH:13])[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]([F:25])([F:24])[F:26])=[CH:18][CH:17]=1)=[O:32]
Reactant: COc1cccc(OC)c1C(CO)NCc1ccc(OC(F)(F)F)cc1
Reactant: O=C(Cl)CCl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: COc1cccc(OC)c1C(CO)N(Cc1ccc(OC(F)(F)F)cc1)C(=O)CCl
Temperature: -10 °C
Reaction time: 0.25 h

Procedure:
A cooled (−10° C.) mixture of 2-(2,6-dimethoxyphenyl)-2-((4-(trifluoromethoxy)benzyl)-amino)ethanol (32 mg; 0.08 mmol) and NaOH (7 mg; 0.17 mmol) in DCM (1 ml) and water (0.5 ml) was treated with 2-chloroacetyl chloride (12 mg; 0.10 mmol). The resulting mixture was further stirred at −10° C., under nitrogen, for 15 min. Water and DCM were added, and the separated aq. layer was further extracted with DCM. The mixed organic layers were washed with brine, dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure affording 2-chloro-N-(1-(2,6-dimethoxyphenyl)-2-hydroxyethyl)-N-(4-(trifluoromethoxy)benzyl)-acetamide as a yellow oil. LC-MS (conditions E): tR=0.75 min.; [M+H]+: 447.98 g/mol.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[CH:8]([C:12]([O:14][CH3:15])=[O:13])[CH2:7][CH2:6][CH2:5][C:4]=2[N:3]=1.[CH:16](OCC)(OCC)OCC.[N-:26]=[N+:27]=[N-:28].[Na+]>C(O)(=O)C>[N:1]1([C:2]2[CH:11]=[CH:10][C:9]3[CH:8]([C:12]([O:14][CH3:15])=[O:13])[CH2:7][CH2:6][CH2:5][C:4]=3[N:3]=2)[CH:16]=[N:28][N:27]=[N:26]1
Reactant: [N-]=[N+]=[N-]
Reactant: CCOC(OCC)OCC
Reactant: COC(=O)C1CCCc2nc(N)ccc21
Agent: [Na+]
Solvent: CC(=O)O
Product: COC(=O)C1CCCc2nc(-n3cnnn3)ccc21
Temperature: 80 °C

Procedure:
Methyl 2-amino-5,6,7,8-tetrahydroquinoline-5-carboxylate (850 mg, 4.12 mmol) was stirred in acetic acid (15 ml) and tri-ethyl orthoformate (1.373 ml, 8.24 mmol) followed by sodium azide (482 mg, 7.42 mmol) then heated to 80° C. for 3 hrs. The reaction was cooled and evaporated to dryness. The mixture was taken up in DCM and washed with saturated NaHCO3 solution, then with brine. The organic layer was dried over Na2SO4, filtered and evaporated to dryness. The residue was chromatographed through a 40 g ISCO Redi-sep column and eluted with ethyl acetate:hexane (2:3) to yield methyl 2-(1H-tetrazol-1-yl)-5,6,7,8-tetrahydroquinoline-5-carboxylate. 1H-NMR (600 MHz, DMSO): δ ppm 10.07 (s, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.82 (d, J=8.4 Hz, 1H), 4.06 (t, J=5.4 Hz, 1H), 3.65 (s, 3H), 2.83-2.93 (m, 2H), 2.07-2.12 (b, 1H), 1.95-2.0 (m, 1H), 1.86-1.90 (m, 2H).
Reaction SMILES: CO[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9][CH2:10][CH2:11][CH2:12][N:13]([C@H:29]1[CH2:34][CH2:33][C@H:32]([CH3:35])[CH2:31][CH2:30]1)[C:14](=[O:28])[NH:15][C:16]1[S:17][C:18]([S:21][C:22]([CH3:27])([CH3:26])[C:23]([OH:25])=[O:24])=[CH:19][N:20]=1.C(OC(=O)C(SC1SC(N)=NC=1)(C)C)C.[Cl:51]C1C=CC=CC=1S>>[Cl:51][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9][CH2:10][CH2:11][CH2:12][N:13]([C@H:29]1[CH2:34][CH2:33][C@H:32]([CH3:35])[CH2:31][CH2:30]1)[C:14](=[O:28])[NH:15][C:16]1[S:17][C:18]([S:21][C:22]([CH3:27])([CH3:26])[C:23]([OH:25])=[O:24])=[CH:19][N:20]=1
Reactant: COc1ccccc1SCCCN(C(=O)Nc1ncc(SC(C)(C)C(=O)O)s1)[C@H]1CC[C@H](C)CC1
Reactant: Sc1ccccc1Cl
Agent: CCOC(=O)C(C)(C)Sc1cnc(N)s1
Product: CC(C)(Sc1cnc(NC(=O)N(CCCSc2ccccc2Cl)[C@H]2CC[C@H](C)CC2)s1)C(=O)O

Procedure:
The compound was prepared following an analogous procedure to the one described for the synthesis 2-{2-[3-[3-(2-methoxy-phenylsulfanyl)-propyl]-3-(trans-4-methyl-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-2-methyl-propionic acid using 2-(2-amino-thiazol-5-ylsulfanyl)-2-methyl-propionic acid ethyl ester and 2-chloro-thiophenol.
Reaction SMILES: [NH:1]([C:3]1[N:4]=[N:5][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:7][CH:8]=1)[NH2:2].C([O-])(=O)C.[Na+].[CH3:20][C:21](=O)[CH2:22][CH2:23][C:24](=O)[CH3:25]>>[CH3:25][C:24]1[N:2]([NH:1][C:3]2[N:4]=[N:5][C:6]([N:9]3[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]3)=[CH:7][CH:8]=2)[C:21]([CH3:20])=[CH:22][CH:23]=1
Reactant: NNc1ccc(N2CCCCC2)nn1
Reactant: CC(=O)CCC(C)=O
Agent: CC(=O)[O-]
Agent: [Na+]
Product: Cc1ccc(C)n1Nc1ccc(N2CCCCC2)nn1
Temperature: 65 °C

Procedure:
A mixture of 7.4 g (28 m moles) of 3-hydrazino-6-piperidino-pyridazine, 2.3 g of sodium acetate and 3.7 g 2,5-hexanedione is heated for two hours at 65° C. The solvent is evaporated off under vacuum and the solid residue is dissolved in water and neutralized with sodium hydroxide. The product is purified by chromatography through a silicagel column using as the eluent a mixture methanol-chloroform 2.5:97.5. The solid recovered by evaporation of the eluate is crystallized from ethyl acetate yielding 2 g (27%) of the product of the title which melts at 185°-187° C.
Reaction SMILES: [C:1]1([S:7]([NH:10][C:11]2C=CC(I)=CC=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[K+].[K+].[CH3:24][I:25]>CN(C=O)C>[CH3:11][NH:10][S:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][C:6]=1[C:1]1[CH:6]=[CH:5][C:24]([I:25])=[CH:3][CH:2]=1)(=[O:8])=[O:9]
Reactant: CI
Reactant: O=S(=O)(Nc1ccc(I)cc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CNS(=O)(=O)c1ccccc1-c1ccc(I)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 196.6 %

Procedure:
To compound 28 (from Example 18) (500 mg, 1.39 mmol) in DMF (10 mL) were added at room temperature K2CO3 (962 mg, 6.96 mmol), followed by methyl iodide (395 mg, 2.78 mmol). The resulting reaction mixture was stirred at room temperature for 16 hours. The solvent is then removed and water was added. The resulting mixture was extracted with ethyl acetate, and the combined organic phases were dried and concentrated. Purification by flash chromatography using hexane:ethyl acetate (8:2) afforded 510 mg (98%) of the title compound as a white solid.
Reaction SMILES: [NH2:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=[C:4]([CH3:14])[CH:3]=1.[C:15]([N:18]1[CH2:22][CH:21]=[N:20][C:19]1=O)(=[O:17])[CH3:16]>>[C:15]([N:18]1[CH2:22][CH2:21][N:20]=[C:19]1[NH:1][C:2]1[N:6]([CH2:7][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:5]=[C:4]([CH3:14])[CH:3]=1)(=[O:17])[CH3:16]
Reactant: Cc1cc(N)n(Cc2ccccc2)n1
Reactant: CC(=O)N1CC=NC1=O
Product: CC(=O)N1CCN=C1Nc1cc(C)nn1Cc1ccccc1

Procedure:
5-Amino-1-benzyl-3-methylpyrazole (J. Gen. Chem. USSR, 31, 2307, 1961) (17.0 g.) and 1-acetyl-3-imidazolinone (14.0 g.) were reacted as described in Example I to give 11.7 g. of product, mp 148°-149°.
Reaction SMILES: [C:1]12([C:11]3[CH:21]=[CH:20][C:14]([O:15][CH2:16][C:17](O)=[O:18])=[CH:13][CH:12]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH3:22][O:23][C:24](=[O:32])[C:25]1[CH:30]=[CH:29][C:28]([NH2:31])=[CH:27][CH:26]=1.Cl.C(N=C=N)C.OS1C2C=CC=CC=2N=C1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH3:22][O:23][C:24](=[O:32])[C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:17](=[O:18])[CH2:16][O:15][C:14]2[CH:13]=[CH:12][C:11]([C:1]34[CH2:10][CH:5]5[CH2:4][CH:3]([CH2:9][CH:7]([CH2:6]5)[CH2:8]3)[CH2:2]4)=[CH:21][CH:20]=2)=[CH:27][CH:26]=1
Reactant: O=C(O)COc1ccc(C23CC4CC(CC(C4)C2)C3)cc1
Reactant: COC(=O)c1ccc(N)cc1
Agent: CCN=C=N
Agent: Cl
Agent: O[SH]1C=Nc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(NC(=O)COc2ccc(C34CC5CC(CC(C5)C3)C4)cc2)cc1
Reaction time: 8 h
Yield: 51.6 %

Procedure:
To a mixture of [4-(1-adamantyl)phenoxy]acetic acid (143.2 mg, 0.5 mmol), 4-aminobenzoic acid methyl ester (113.4 mg, 0.5 mmol), N-3-dimethylaminopropyl)-N′-ethyl carbodiimide HCl (EDC) (143.8 mg, 0.75 mmol) and 1-hydroxybenzothiazole (HOBt) (101.4 mg, 0.75 mmol) in DMF (6 mL) was added N,N-diisopropylethylamine, redistilled (DIPEA) (97.0 mg, 0.13 mL, 0.75 mmol). The mixture was stirred overnight, and then partitioned between ethyl acetate and 10% HCl. The organic phase was washed with brine, dried (MgSO4 anh), and concentrated. The residue was purified by silica gel flash column chromatography (n-Hexane:Ethyl acetate:MeOH=6:3:1) to give 4-[2-(4-Adamantan-1-yl-phenoxy)-acetylamino]-benzoic acid methyl ester as a white solid (108.3 mg, 51.7% yield).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH:15]=[CH:16][CH:17]=[CH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[Cl:25])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>O1CCCC1.C(O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:15][CH2:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[Cl:25])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Clc1ccccc1C=CC=Cc1ccccc1OCc1ccccc1
Solvent: CCO
Solvent: C1CCOC1
Product: Clc1ccccc1CCCCc1ccccc1OCc1ccccc1
Yield: 62.4 %

Procedure:
Following a procedure similar to that described in the latter part of Preparation 3, 4.53 g of this 1-(2-benzyloxyphenyl)-4-(2-chlorophenyl)butadiene were dissolved in a 4:1 by volume mixture of tetrahydrofuran and ethanol and were hydrogenated, whilst ice-cooling. The reaction mixture was then worked up as described in the latter part of Preparation 3, to give 2.86 g (yield 62%) of 1-(2-benzyloxyphenyl)-4-(2-chlorophenyl)butane.