Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)S(O)(=O)=O.[C:9]([C:17]1[CH:43]=[CH:42][C:20]([O:21][CH2:22][CH:23]([OH:41])[CH2:24][O:25][C:26]2[CH:31]=[CH:30][C:29]([C:32](=[O:39])[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[C:28]([OH:40])[CH:27]=2)=[CH:19][C:18]=1[OH:44])(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[C:45](O)(=[O:48])[CH:46]=[CH2:47]>C1(C)C=CC=CC=1.C1(C=CC(O)=CC=1)O.COC1C=CC(O)=CC=1>[C:45]([O:41][CH:23]([CH2:22][O:21][C:20]1[CH:42]=[CH:43][C:17]([C:9](=[O:16])[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[C:18]([OH:44])[CH:19]=1)[CH2:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([C:32](=[O:39])[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[C:28]([OH:40])[CH:27]=1)(=[O:48])[CH:46]=[CH2:47]
Reactant: C=CC(=O)O
Reactant: O=C(c1ccccc1)c1ccc(OCC(O)COc2ccc(C(=O)c3ccccc3)c(O)c2)cc1O
Agent: COc1ccc(O)cc1
Agent: O=S(=O)(O)C(F)(F)F
Agent: Oc1ccc(O)cc1
Solvent: Cc1ccccc1
Product: C=CC(=O)OC(COc1ccc(C(=O)c2ccccc2)c(O)c1)COc1ccc(C(=O)c2ccccc2)c(O)c1
Temperature: 25 °C
Yield: 74.3 %

Procedure:
3 g of trifluoromethanesulfonic acid, 0.1 g of hydroquinone and 0.1 g of hydroquinone monomethyl ether were added to a solution of 48.5 g (0.1 mole) of 1,3-bis-(4-benzoyl-3-hydroxyphenoxy)-2-propanol and 43.6 g (0.6 mole) of acrylic acid in 600 ml of toluene, and the solution was heated for 3 hours at a temperature of 105° to 110° C. After cooling to room temperature, the reaction mixture was washed with 1.5 liters of water. The toluene was then distilled off from the reaction mixture under a pressure of 20 mbar. The oily residue remaining was dissolved in hot ethanol. Cooling this solution to room temperature gave 40 g (75 percent of theory) of 1,3-bis-(4-benzoyl-3-hydroxyphenoxy)-prop-2-yl acrylate in the form of colorless crystals having a melting point of 98° to 100° C. and a purity of 99 percent (HPLC). The UV spectrum gave two absorption maxima at wave lengths of 287 nm (extinction 0.520; extinction coefficient 28,100) and 324 nm (extinction 0.335; extinction coefficient 18,100).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:19])=[C:6]([C:8]2[NH:17][C:16](=O)[C:15]3[C:10](=[N:11][CH:12]=[CH:13][N:14]=3)[N:9]=2)[CH:7]=1.[CH3:20][C:21]1[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=1[NH2:23].C(N(C1C=CN=CC=1)C1C2C(=NC=CN=2)N=C(C2C=C(Br)C=CC=2F)N=1)CCC>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:19])=[C:6]([C:8]2[N:17]=[C:16]([NH:23][C:22]3[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=3[CH3:20])[C:15]3[C:10](=[N:11][CH:12]=[CH:13][N:14]=3)[N:9]=2)[CH:7]=1
Reactant: Cc1ccccc1N
Reactant: O=c1[nH]c(-c2cc(Br)ccc2F)nc2nccnc12
Agent: CCCCN(c1ccncc1)c1nc(-c2cc(Br)ccc2F)nc2nccnc12
Product: Cc1ccccc1Nc1nc(-c2cc(Br)ccc2F)nc2nccnc12

Procedure:
The title product was synthesized by reaction of the 2-(5-bromo-2-fluorophenyl)-pteridin-4-one 104 with 2-methylaniline following the procedure described for 4-[(butyl)(4-pyridyl)amino]-2-(5-bromo-2-fluorophenyl)pteridine 3.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[S:12][CH2:13][CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[NH:24][C:23](=[O:28])[CH2:22][CH2:21]2.[OH:29]O>C(Cl)CCl.CO>[CH3:1][C:2]1[CH:7]=[C:6]([C:8]([CH3:11])([CH3:9])[CH3:10])[CH:5]=[CH:4][C:3]=1[S:12]([CH2:13][CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[NH:24][C:23](=[O:28])[CH2:22][CH2:21]2)=[O:29]
Reactant: OO
Reactant: Cc1cc(C(C)(C)C)ccc1SCCCCOc1ccc2c(c1)CCC(=O)N2
Solvent: CO
Solvent: ClCCCl
Product: Cc1cc(C(C)(C)C)ccc1S(=O)CCCCOc1ccc2c(c1)CCC(=O)N2

Procedure:
Prepared analogous to Example 123 from 6-[4-(2-methyl-4-tert. butylphenyl-mercapto)-butoxy]-3,4-dihydro-carbostyril and hydrogen peroxide. Resinous substance. Rf -value: 0.54 (silica gel fluorescent plate; eluant: ethylene chloride/methanol=95/5).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([O:26][CH2:27][CH:28]=[C:29]([Cl:31])[Cl:30])[CH:5]=[C:6]([Cl:25])[C:7]=1[O:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][CH:16](O)[C:17](Cl)([Cl:22])[C:18]([F:21])([F:20])[F:19].N1C=CC=CC=1.C(OC(=O)C)(=O)C.Cl>CN(C1C=CN=CC=1)C.[Zn].CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([O:26][CH2:27][CH:28]=[C:29]([Cl:31])[Cl:30])[CH:5]=[C:6]([Cl:25])[C:7]=1[O:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15]/[CH:16]=[C:17](\[Cl:22])/[C:18]([F:21])([F:20])[F:19]
Reactant: OC(CCOCCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl)C(Cl)(Cl)C(F)(F)F
Agent: CN(C)c1ccncc1
Agent: Cl
Agent: [Zn]
Solvent: CC(=O)OC(C)=O
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: FC(F)(F)/C(Cl)=C/CCOCCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 79.2 %

Procedure:
A mixture of 0.57 g of 3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-(4-(4,4-dichloro-5,5,5-trifluoro-3-hydroxypentyloxy)butyloxy)benzene, 0.16 g of pyridine, 0.12 g of acetic anhydride, 10 mg of N,N-dimethyl-4-aminopyridine and 20 ml of N,N-dimethylformamide was stirred at room temperature for 30 minutes, to which 0.078 g of zinc dust was added. The reaction mixture was further stirred at room temperature for 1 hour, poured into 20 ml of diluted hydrochloric acid and extracted twice with 50 ml of diethyl ether. The diethyl ether layers were combined, washed with water, dried over magnesium sulfate and then evaporated to give a crude product. The crude product was subjected to silica gel chromatography, which afforded 0.41 g of (Z)-3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-(4-(4-chloro-5,5,5-trifluoro-3-pentenyloxy)butyloxy)benzene [the integrated CF3 signal ratio of Z/E=93/7 as determined by 19F-NMR (CDCl3 /CFCl3)] (yield, 79%), nD30.0 1.5057.
Reaction SMILES: [C:1]([O:4][C:5]1[C:6]([O:14][CH3:15])=[CH:7][C:8]([CH2:11][CH:12]=[CH2:13])=[CH:9][CH:10]=1)(=[O:3])[CH3:2].C1(OC)C(=CC=C(C=1)CC=C)O.C(OC(=O)C)(=O)C.[CH3:35][SiH:36]([CH3:38])[Cl:37]>>[C:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][CH2:13][Si:36]([CH3:38])([CH3:35])[Cl:37])=[CH:7][C:6]=1[O:14][CH3:15])(=[O:3])[CH3:2]
Reactant: C[SiH](C)Cl
Reactant: C=CCc1ccc(OC(C)=O)c(OC)c1
Agent: C=CCc1ccc(O)c(OC)c1
Solvent: CC(=O)OC(C)=O
Product: COc1cc(CCC[Si](C)(C)Cl)ccc1OC(C)=O
Reaction time: 1.5 h
Yield: 87.7 %

Procedure:
A 100 mL round bottomed flask was charged with eugenol acetate (16.5 g, 80 mmol), which had been prepared from the reaction of eugenol with acetic anhydride, and 25 microliters of Karstedt's catalyst. Dimethylchlorosilane (7.56 g, 80 mmol) was added slowly over 20 minutes. After 1.5 hr the reaction was complete (as judged by 1H-NMR) and 3-(4-acetoxy-3-methoxyphenyl)prop-1-yl dimethylchlorosilane (21.1 g, 88% yield) was isolated by vacuum distillation (boiling point (bp)=150° C./0.5 mmHg). A 100 mL round bottomed flask was charged with 3-(4-acetoxy-3-methoxyphenyl)prop-1-yl dimethylchlorosilane (15.0 g, 50 mmol) and 25 mL of toluene. A 65 weight percent solution of sodium bis(2-methoxyethoxy)aluminum hydride in toluene (7.0 mL, 50 mmol) was added over 30 minutes. After quenching in 6N HCl (100 mL), the product in toluene was washed 3 times with water, dried over MgSO4 and the toluene removed under reduced pressure. Vacuum distillation gave 3-(4-acetoxy-3-methoxyphenyl)prop-1-yl dimethylsilane (8.5 g, bp 90° C./0.5 mmHg). A 100 mL Morton flask was charged with 3-(4-acetoxy-3-methoxyphenyl)prop-1-yl dimethylsilane (8.0 g, 30 mmol), eugenol (6.56 g, 40 mmol), toluene (25 mL) and platinum on carbon (5% Pt on C, 0.05 g). After heating at reflux for 1.5 hr, the reaction mixture was cooled and filtered. The toluene was removed and the crude product stripped of volatiles at 125° C. at a pressure of 0.5 mmHg. Residual acetate groups were removed by treating the coupled product with K2CO3 in methanol/water, diluting the reaction mixture to 5 weight percent HCl, extracting with ether, drying the organic layer over MgSO4 and concentrating under reduced pressure to afford eugenol siloxane bisphenol (8.0 g) wherein p is zero.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:17][CH2:18][C:19]([O:21]C)=[O:20])[C:11]=2[CH:15]=O)[CH:6]=1)=[O:4].[F:23][C:24]([F:35])([F:34])[O:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][NH2:31])=[CH:28][CH:27]=1>>[C:19]([CH2:18][O:17][C:10]1[C:11]([CH2:15][NH:31][CH2:30][C:29]2[CH:32]=[CH:33][C:26]([O:25][C:24]([F:23])([F:34])[F:35])=[CH:27][CH:28]=2)=[C:12]2[C:7](=[CH:8][CH:9]=1)[CH:6]=[C:5]([C:3]([OH:2])=[O:4])[CH:14]=[CH:13]2)([OH:21])=[O:20]
Reactant: COC(=O)COc1ccc2cc(C(=O)OC)ccc2c1C=O
Reactant: NCc1ccc(OC(F)(F)F)cc1
Product: O=C(O)COc1ccc2cc(C(=O)O)ccc2c1CNCc1ccc(OC(F)(F)F)cc1

Procedure:
The title compound was prepared as a white solid (0.050 g, 58% for two steps) from 6-methoxycarbonylmethoxy-5-formyl-2-naphthoic acid methyl ester using 4-trifluoromethoxy-benzyl amine and a procedure similar to steps 3-4 of Example 1, mp >266° C. (decomp.); 1H NMR (DMSO-d6) δ4.31 (s, 2H), 4.58 (s, 2H), 4.77 (s, 2H), 7.42 (d, J=8.4 Hz, 2H), 7.62 (d, J=9.3 Hz,1 H), 7.68 (d, J=8.7 Hz, 2H), 8.00 (dd, J=1.5, 8.9 Hz, 1H), 8.17 (d, J=9.0 Hz, 1H), 8.21 (d, J=9.3 Hz, 1H), 8.58 (d, J=1.2 Hz, 1H), 10.05-10.54 (bs, 1H), 12.74-13.46 (bs, 1H); IR (neat) 2450-3200, 1695, 1630, 1600, 1575, 1510, 1485, 1440, 1310, 1265, 1215, 1170, and 1110 cm−1; mass spectrum [(+) ESI], m/z 450 (M+H)+ and [(−) ESI], m/z 448 (M−H)−; Anal. Calcd. for C22H18F3NO6.1.0H2O: C, 56.54; H, 4.31; N, 3.00, Found: C, 56.16; H, 4.26; N, 2.86.
Reaction SMILES: [C:1]1(B(O)O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[Br:14][C:15]1[CH:16]=[C:17](I)[CH:18]=[CH:19][CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1>[Br:14][C:15]1[CH:20]=[C:19]([C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][CH:2]=2)[CH:18]=[CH:17][CH:16]=1
Reactant: Brc1cccc(I)c1
Reactant: OB(O)c1cccc2ccccc12
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: Brc1cccc(-c2cccc3ccccc23)c1
Reaction time: 24 h
Yield: 76 %

Procedure:
Under an argon gas atmosphere, 200.0 g (1.163 mol) of 1-naphthaleneboronic acid, 329.0 g (1.163 mol) of 3-bromoiodobenzene, 26.9 g (23.3 mmol) of tetrakis(triphenylphosphine) palladium(0), 3.7 L of toluene and 1.74 L of 2M sodium carbonate solution were mixed, and stirred for 24 hours while being refluxed. After the reaction in the mixture was over, the mixture experienced filtration, through which aqueous phase thereof was eliminated. After organic phase thereof was cleansed by water and dried with magnesium sulfate, toluene was distilled away under reduced pressure. Residue thereof was refined by silica-gel column chromatography, such that 250 g of 1-(3-bromophenyl)naphthalene was obtained with an yield of 76%.
Reaction SMILES: [C:1]([CH:4]([CH2:14][C:15]#[C:16][C:17]1([OH:25])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12])(=[O:3])[CH3:2].C(C(CC#C[C@@H](O)CCCCC)CCCCCCC(O)=O)(=O)C>>[C:1]([CH:4]([CH2:14][CH2:15][CH2:16][C:17]1([OH:25])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12])(=[O:3])[CH3:2]
Reactant: CC(=O)C(CC#CC1(O)CCCCCCC1)CCCCCCC(=O)O
Agent: CCCCC[C@H](O)C#CCC(CCCCCCC(=O)O)C(C)=O
Product: CC(=O)C(CCCCCCC(=O)O)CCCC1(O)CCCCCCC1

Procedure:
This compound is prepared essentially by the same hydrogenation procedure described in Example 36, Step C, except that 8-acetyl-11-(1-hydroxycyclooctyl)-10-undecynoic acid (Example 41) is substituted for 8-acetyl-12(S)-hydroxy-10-heptadecynoic acid. The product is obtained as a colorless viscous oil.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]=1[C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][C:16]=1[P:25]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=O)(=O)[CH3:2]>O1CCCC1>[CH2:1]([NH:4][C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]=1[C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][C:16]=1[P:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[CH3:2]
Reactant: CC(=O)Nc1ccc2ccccc2c1-c1c(P(=O)(c2ccccc2)c2ccccc2)ccc2ccccc12
Solvent: C1CCOC1
Product: CCNc1ccc2ccccc2c1-c1c(P(c2ccccc2)c2ccccc2)ccc2ccccc12
Temperature: 25 °C
Reaction time: 3 h
Yield: 75.6 %

Procedure:
127 mg (0.25 mmol) of (−)-2-acetylamino-2′-diphenylphosphinyl-1,1′-binaphthyl (the formula (1-2a-1)) was dissolved in 6 ml of tetrahydrofuran under the flow of nitrogen. To the solution, 620 μl (1.24 mmol) of tetrahydrofuran solution (2M) of boranedimethyl sulfide complex was added at 0° C., followed by the stirring for 18 hours at 88° C. The reaction solution was extracted with 50 ml of ethyl acetate, washed with 10 ml of saturated aqueous solution of ammonium chloride and 10 ml of brine, and then dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure. To the residue, 6 ml of diethylamine was added and stirred under room temperature for 3 hours. Diethylamine was evaporated under a reduced pressure and the residue was purified using a silica gel column chromatography (eluent: 1:50 mixture of ethyl acetate and hexane) to obtain 91 mg of the titled compound.
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:24]=[CH:23][C:8]([C:9](=[O:22])[CH2:10][CH:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:7][CH:6]=1.[CH:25]1([O:30][C:31]2[CH:32]=[C:33]([CH:36]=[CH:37][C:38]=2[O:39][CH3:40])[CH2:34]Cl)[CH2:29][CH2:28][CH2:27][CH2:26]1.[I-].[Na+].Cl>O1CCCC1>[CH:25]1([O:30][C:31]2[CH:32]=[C:33]([CH:36]=[CH:37][C:38]=2[O:39][CH3:40])[CH2:34][C:11]([CH2:10][C:9]([C:8]2[CH:7]=[CH:6][C:5]([O:4][CH3:3])=[CH:24][CH:23]=2)=[O:22])([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:26][CH2:27][CH2:28][CH2:29]1
Reactant: COc1ccc(CCl)cc1OC1CCCC1
Reactant: CCOC(=O)C(CC(=O)c1ccc(OC)cc1)C(=O)OCC
Agent: Cl
Agent: [H-]
Agent: [I-]
Solvent: C1CCOC1
Product: CCOC(=O)C(CC(=O)c1ccc(OC)cc1)(Cc1ccc(OC)c(OC2CCCC2)c1)C(=O)OCC
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 73.5 %

Procedure:
0.29 g (7.1 mmol) of sodium hydride (as a 60% w/w dispersion in mineral oil) was added to 50 ml of anhydrous tetrahydrofuran, whilst ice-cooling, and then the mixture was stirred for 10 minutes. At the end of this time, a solution of 2.00 g (6.5 mmol) of diethyl α-(4-methoxyphenacyl)malonate [prepared as described in step (i) above] in 20 ml of anhydrous tetrahydrofuran was slowly added dropwise to the mixture, whilst ice-cooling. The mixture was then stirred for 30 minutes. A solution of 1.72 g (7.1 mmol) of 3-cyclopentyloxy-4-methoxybenzyl chloride in 20 ml of anhydrous tetrahydrofuran and 0.97 g (6.5 mmol) of sodium iodide were then added to the mixture, and the resulting mixture was heated under reflux for 2 hours. At the end of this time, the mixture was cooled to room temperature and was then acidified by the addition of 3N aqueous hydrochloric acid and extracted with ethyl acetate. The organic extract was washed with water and dried over anhydrous magnesium sulfate, and then the solvent was removed by distillation under reduced pressure. The residue thus obtained was applied to a silica gel chromatography column and eluted with a 1:4 by volume mixture of ethyl acetate and hexane, to give 2.45 g of the title compound as a pale yellow oily substance.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[O:9][C:10]([CH3:12])=[CH:11][C:7]=2[CH:6]=[CH:5][CH:4]=1.[CH3:13][O:14]C(Cl)Cl>C(Cl)Cl>[CH3:1][O:2][C:3]1[C:8]2[O:9][C:10]([CH3:12])=[CH:11][C:7]=2[C:6]([CH:13]=[O:14])=[CH:5][CH:4]=1
Reactant: COc1cccc2cc(C)oc12
Reactant: COC(Cl)Cl
Solvent: ClCCl
Product: COc1ccc(C=O)c2cc(C)oc12
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 30.2 %

Procedure:
To a well stirred solution of 7-methoxy-2-methylbenzo[b]furan (from step 2) (6.5 g, 40.07 mmol) in DCM (70.0 mL) was added stannous chloride (17.7 g, 68.26 mmol) followed by slow addition of 1,1-dichloromethyl methyl ether (4.6 g, 40.07 mmol) at −10-0° C. and stirred for 1-2 hrs. Ice cold water (100 mL) was added with vigorous stirring, the organic layer was separated and washed with water (2×50 mL) and dried over anhydrous sodium sulfate. Removal of solvent gave crude product (7.0 g). The crude product was purified by silica gel column using petroleum ether:ethyl acetate (9:1) as an eluent to afford the product as pale yellow oil (2.3 g).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[CH2:14](I)[CH2:15][CH3:16]>>[CH2:14]([O:1][C:2]1[CH:9]=[C:8]([C:10]([F:11])([F:12])[F:13])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5])[CH2:15][CH3:16]
Reactant: O=Cc1ccc(C(F)(F)F)cc1O
Reactant: CCCI
Product: CCCOc1cc(C(F)(F)F)ccc1C=O

Procedure:
Using 2-hydroxy-4-(trifluoromethyl)benzaldehyde and propyl iodide, 2-propoxy-4-(trifluoromethyl)benzaldehyde was obtained in the same method as in Production Example 283a).
Reaction SMILES: [C:1]([NH:3][C:4](=[N:7][CH2:8][CH2:9][S:10][CH2:11][C:12]1[NH:16][CH:15]=[N:14][C:13]=1[CH3:17])SC)#[N:2]>CN(C)C=O.[N+]([O-])([O-])=O.[Ag+]>[C:1]([NH:3][C:4]([NH:7][CH2:8][CH2:9][S:10][CH2:11][C:12]1[NH:16][CH:15]=[N:14][C:13]=1[CH3:17])=[N:7][CH2:8][CH2:9][S:10][CH2:11][C:12]1[NH:16][CH:15]=[N:14][C:13]=1[CH3:17])#[N:2]
Reactant: CSC(=NCCSCc1[nH]cnc1C)NC#N
Agent: [Ag+]
Agent: O=[N+]([O-])[O-]
Solvent: CN(C)C=O
Product: Cc1nc[nH]c1CSCCN=C(NC#N)NCCSCc1[nH]cnc1C
Yield: 33.6 %

Procedure:
A solution of silver nitrate (3.06 g.) in dimethyl formamide (20 ml.) was added to a solution of N-cyano-N'-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]-S-methyl isothiourea (4.9 g.) in dimethylformamide (30 ml.). The resultant solution was kept at room temperature for 1 hour cooled and filtered to remove silver methylmercaptide, 4-methyl-5-((2-aminoethyl)thiomethyl)imidazole (3.07 g.) in dimethyl formamide (10 ml.) was added and this solution was heated overnight on the steam bath. Concentration followed by chromatographic purification of the product on a column of silica gel afforded the title compound (1.2 g.), m.p. 90°-94°, containing a small amount of water.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([CH3:10])[CH:3]=1.[C:11](Cl)(=[O:15])[C:12]([CH3:14])=[CH2:13]>>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([NH:1][C:11](=[O:15])[C:12]([CH3:14])=[CH2:13])=[CH:3][C:4]=1[CH3:10])#[N:7]
Reactant: C=C(C)C(=O)Cl
Reactant: Cc1cc(N)ccc1C#N
Product: C=C(C)C(=O)Nc1ccc(C#N)c(C)c1

Procedure:
N-(4-Cyano-3-methylphenyl)-2-methylacrylamide was prepared as described in Example 1 starting from 4-amino-2-methylbenzonitrile and methacryloyl chloride.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[C:13]([C:18]([F:21])([F:20])[F:19])[CH:14]=[CH:15][CH:16]=3)[N:11]=[CH:10][C:9]=2[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:23])[CH:5]=[CH:6][CH:7]=1.Br[CH2:31][C:32]1[CH:41]=[CH:40][C:35]([C:36]([O:38]C)=[O:37])=[CH:34][CH:33]=1.C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[C:22]([C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:8]=1[C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=1)[O:1][CH2:31][C:32]1[CH:41]=[CH:40][C:35]([C:36]([OH:38])=[O:37])=[CH:34][CH:33]=1)=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([F:21])([F:19])[F:20])(=[O:23])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: O=C(c1ccccc1)c1cnc2c(C(F)(F)F)cccc2c1-c1cccc(O)c1
Reactant: COC(=O)c1ccc(CBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: O=C(O)c1ccc(COc2cccc(-c3c(C(=O)c4ccccc4)cnc4c(C(F)(F)F)cccc34)c2)cc1
Reaction time: 2 h
Yield: 75.8 %

Procedure:
A solution of 4-(3-hydroxyphenyl)-8-(trifluoromethyl)quinolin-3-yl](phenyl)methanone (Example 42, 1.0 g, 2.5 mmol), methyl 4-bromomethylbenzoate (0.57 g, 2.5 mmol) and K2CO3 (1.38 g, 10 mmol) in acetone (25 ml) was heated to reflux. After 2 hr, the reaction was cooled, filtered and concentrated. The resulting oil was taken up into THF/MeOH (20 ml) and 2N NaOH (2 ml) was added and the reaction was refluxed. After 2 hr, the reaction was cooled, poured into 2N HCl and extracted with EtOAc. The EtOAc was dried concentrated and the product was purified by column chromatography (eluent 40% EtOAc/hexane) to give the desired product as a foam (1.00 g, Yield=77%); MS (ESI) m/z 528 ([M+H]+); 1H NMR (DMSO) δ 12.97 (s, 1H), 9.14 (s, 1H), 8.33 (d, 1H, J=6.6 Hz), 7.94-7.88 (m, 3H), 7.76 (t, 1H, J=8.0 Hz), 7.63 (d, 2H, J=7.1 Hz), 7.54-7.47 (m, 1H), 7.46 (d, 2H, J=8.5 Hz), 7.37-7.33 (m, 2H), 7.27 (t, 1H, J=7.8 Hz), 7.05-6.98 (m, 2H), 6.87 (m, 1H),
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[CH2:9][CH2:8][CH2:7]2.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH2:25][C:26](Cl)=[O:27])[CH:20]=[CH:21][C:22]=1[O:23][CH3:24].C(=O)(O)[O-].[K+]>>[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH2:25][C:26]([NH:1][CH2:2][CH2:3][C:4]2[CH:5]=[C:6]3[C:10](=[CH:11][C:12]=2[O:13][CH3:14])[CH2:9][CH2:8][CH2:7]3)=[O:27])[CH:20]=[CH:21][C:22]=1[O:23][CH3:24]
Reactant: COc1cc2c(cc1CCN)CCC2
Reactant: COc1ccc(CC(=O)Cl)cc1OC
Agent: O=C([O-])O
Agent: [K+]
Product: COc1cc2c(cc1CCNC(=O)Cc1ccc(OC)c(OC)c1)CCC2

Procedure:
5-Aminoethyl-6-methoxyindan and 3,4-dimethoxyphenylacetyl chloride were reacted following the procedure of Example 1, except that potassium bicarbonate was used in place of triethylamine, to produce the desired product. After recrystallization from ethanol it melted at 115° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:7]([OH:9])=O)[S:5][CH:6]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[F:22][C:23]([F:38])([F:37])[C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[N:29]([C:33]([NH2:35])=[O:34])[C:28](=[O:36])[CH2:27]2>CN(C1C=CN=CC=1)C>[F:38][C:23]([F:22])([F:37])[C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[N:29]([C:33]([NH2:35])=[O:34])[C:28](=[O:36])[CH:27]2[C:7](=[O:9])[C:4]1[S:5][CH:6]=[C:2]([Cl:1])[CH:3]=1
Reactant: NC(=O)N1C(=O)Cc2cc(C(F)(F)F)ccc21
Reactant: O=C(O)c1cc(Cl)cs1
Agent: CN(C)c1ccncc1
Agent: O=C(n1ccnc1)n1ccnc1
Product: NC(=O)N1C(=O)C(C(=O)c2cc(Cl)cs2)c2cc(C(F)(F)F)ccc21
Yield: 82 %

Procedure:
The experimental procedure used to produce the title compound was adopted from Example 55. A 388 mg (2.39 mmole) sample of 4-chloro-2-thiophenecarboxylic acid (prepared according to Iriarte, J., et al., J. Het. Chem., 13, 393 (1976)) was transformed into the acyl imidazole by reaction with 420 mg (2.59 mmole) of 1,1'-carbonyldiimidazole. The intermediate 4-chloro-2-thiophene-(1-imidazo)carboxamide coupled directly with 486 mg (1.99 mmole) of 5-trifluoromethyl-2-oxindole-1-carboxamide in the presence of 657 mg (5.37 mmole) of 4-(N,N-dimethylamino)pyridine to give 634 mg (1.63 mmole, 82%) of the title compound as a yellow solid m.p. 164°-6° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[C:4]([F:9])[C:3]=1F.Br.[Na].[CH2:13]([OH:16])[CH2:14][OH:15].Cl>O>[F:9][C:4]1[C:5]([F:8])=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[O:15][CH2:14][CH2:13][OH:16]
Reactant: Fc1ccc(F)c(F)c1F
Reactant: OCCO
Agent: Br
Agent: Cl
Agent: [Na]
Solvent: O
Product: OCCOc1c(F)ccc(F)c1F
Reaction time: 3 h

Procedure:
1,2,3,4-Tetrafluorobenzene (67.7 g), sodium hydrobromide (20.8 g), and 200 ml of ethyleneglycol are refluxed with good stirring for 3 hours. The reaction mixture is poured into water (800 ml), acidified with 10% hydrochloric acid and then extracted with ether. The ether is washed with dilute sodium hydroxide and water, and then distilled under vacuum to give 2-(2,3,6-trifluorophenoxy) ethanol), b.p. about 100° at 15 min.