Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]([N:3]1[CH:12]2[CH:7]([N:8]([N+:16]([O-:18])=[O:17])[CH2:9][CH2:10][N:11]2[N+:13]([O-:15])=[O:14])[N:6]([N+:19]([O-:21])=[O:20])[CH2:5][CH2:4]1)=[O:2].[N+]([O-])(O)=[O:23]>>[N+:16]([N:8]1[CH:7]2[CH:12]([N:3]([N+:1]([O-:23])=[O:2])[CH2:4][CH2:5][N:6]2[N+:19]([O-:21])=[O:20])[N:11]([N+:13]([O-:15])=[O:14])[CH2:10][CH2:9]1)([O-:18])=[O:17]
Reactant: O=NN1CCN([N+](=O)[O-])C2C1N([N+](=O)[O-])CCN2[N+](=O)[O-]
Reactant: O=[N+]([O-])O
Product: O=[N+]([O-])N1CCN([N+](=O)[O-])C2C1N([N+](=O)[O-])CCN2[N+](=O)[O-]
Temperature: 0 °C

Procedure:
A portion of 8-nitroso-1,4,5-trinitro-1,4,5,8-tetraazadecalin (1.0 g, 3.3 mmoles) was slowly added to 10 ml of well-stirred 100% nitric acid maintained at 0° C. over a 15-minute time period. The solution developed a light-yellow color. It was stirred for 5 additional minutes at 0° C., then the coupling bath was removed. The stirring was continued for 5 more minutes. The reaction mixture was quenched by pouring onto 20 g of ice. A white precipitate formed and was collected by vacuum filtration. It was washed well with water and dried. It weighed 0.72 g (2.2 mmoles, 68%) and decomposed at 236° C., but darkened above 200° C. It could be recrystallized to fine crystals by dissolving in hot cyclohexanone (1 g/10 ml) and adding an equal volume of ethanol. ##STR5##
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][NH:3][C:2]1=[O:6].C([O-])([O-])=O.[K+].[K+].[Cl:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][C:21]=1[Cl:22])[CH2:17]Cl.O>CS(C)=O>[Cl:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][C:21]=1[Cl:22])[CH2:17][N:1]1[CH2:5][CH2:4][NH:3][C:2]1=[O:6]
Reactant: O=C1NCCN1
Reactant: ClCc1ccc(Cl)c(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: O=C1NCCN1Cc1ccc(Cl)c(Cl)c1
Yield: 23 %

Procedure:
A 21.5 g (0.25 mole) portion of 2-imidazolidinone in 250 ml of dimethylsulfoxide was treated with 34.5 g (0.25 mole) of K2CO3, 10.0 g (0.06 mole of KI and 49.0 g (0.25 mole) of 3,4-Dichlorobenzyl chloride. The reaction mixture was heated at 100° for 3 hours and poured into 1.8 1 of H2O. The aqueous mixture was extracted with 1.3 1 of chloroform. The chloroform extract was washed with 500 ml of H2O, dried over MgSO4 overnight and filtered. The filtrate was concentrated to dryness to give 14 g (23%) of a light yellow semisolid. The crude product was crystallized using 20 ml of acetonitrile, filtered, washed with ether, air dried and dried at 60° for 2 hrs to give 10.5 g (17%) of a white solid, m.p. 129°-130°. An analytical sample, m.p. 129°- 130°, was a portion of the above crystallized product.
Reaction SMILES: [C:1]([C:5]1[CH:26]=[CH:25][C:8]([CH2:9][N:10]([CH2:12][C:13]2[CH:14]=[C:15]([C:19](O)([CH:21]([CH3:23])[CH3:22])[CH3:20])[CH:16]=[CH:17][CH:18]=2)[CH3:11])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[C:1]([C:5]1[CH:26]=[CH:25][C:8]([CH2:9][N:10]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([CH:21]([CH3:22])[CH3:23])=[CH2:20])[CH:14]=2)[CH3:11])=[CH:7][CH:6]=1)([CH3:3])([CH3:2])[CH3:4]
Reactant: CC(C)C(C)(O)c1cccc(CN(C)Cc2ccc(C(C)(C)C)cc2)c1
Solvent: O=P(Cl)(Cl)Cl
Solvent: c1ccncc1
Product: C=C(c1cccc(CN(C)Cc2ccc(C(C)(C)C)cc2)c1)C(C)C
Temperature: 25 °C
Yield: 64.9 %

Procedure:
Compound 89 (0.30 g; 8.73×10−1 mmol) was dissolved in pyridine (20 ml). While the solution was stirred at room temperature, phosphorus oxychloride (1.34 g; 8.73 mmol) was added dropwise. After completion of the addition, the mixture was stirred for 6 hours at 100° C., and left to cool to room temperature. The mixture was poured into ice+saturated aqueous sodium bicarbonate solution, and extracted with chloroform (100 ml). The organic layer was washed with saturated aqueous sodium bicarbonate solution and then with saturated brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=10:1), to thereby yield 0.19 g of the target compound as yellow oily matter (yield: 64.9%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11](=O)[C:10](=[CH:13]N(C)C)[CH2:9][C:8](=[O:17])[NH:7][C:6]=2[CH:18]=1.[N+]([O-])(O)=O.[OH:23][CH2:24][CH2:25][C:26]1[CH:27]=[C:28]([NH:32][C:33]([NH2:35])=[NH:34])[CH:29]=[CH:30][CH:31]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[N:34]=[C:33]([NH:32][C:28]4[CH:29]=[CH:30][CH:31]=[C:26]([CH2:25][CH2:24][OH:23])[CH:27]=4)[N:35]=[CH:13][C:10]=3[CH2:9][C:8](=[O:17])[NH:7][C:6]=2[CH:18]=1
Reactant: N=C(N)Nc1cccc(CCO)c1
Reactant: CN(C)C=C1CC(=O)Nc2cc(Cl)ccc2C1=O
Solvent: O=[N+]([O-])O
Product: O=C1Cc2cnc(Nc3cccc(CCO)c3)nc2-c2ccc(Cl)cc2N1

Procedure:
In a manner similar to that described for method I, 8-chloro-4-dimethylaminomethylene-3,4-dihydro-1H-benzo[b]azepine-2,5-dione (v-j) and N-[3-(2-hydroxy-ethyl)-phenyl]-guanidine nitrate were converted to I-80 (65%): HRMS Calcd. for C20H17ClN4O2: 381.1118, Found 381.1126.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([Cl:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[NH:6]2.[OH-].[Na+].[I:19]I>C(O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]([Cl:11])[CH:8]=[C:7]2[C:3]=1[C:4]([I:19])=[C:5]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[NH:6]2
Reactant: CCOC(=O)c1cc2c(Cl)cc(Cl)cc2[nH]1
Reactant: II
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CCO
Product: CCOC(=O)c1[nH]c2cc(Cl)cc(Cl)c2c1I
Reaction time: 1 h

Procedure:
Combine 4,6-dichloro-indole-2-carboxylic acid, ethyl ester (5.2 g, 20.0 mmol) and sodium hydroxide (0.80 g, 20 mmol) in ethanol (250 mL). Add iodine (5.1 g, 20.0 mmol) as a solution in ethanol (100 mL). After 1 hour, concentrate the reaction mixture in vacuo to obtain a residue. Dissolve the residue in ethyl acetate and extract with 1M hydrochloric acid solution and then with saturated sodium chloride solution. Dry the organic layer over magnesium sulfate and evaporate in vacuo. Chromatograph on silica gel eluting with 25% ethyl acetate/hexane. Combine the product containing fractions and evaporate in vacuo. Recrystallize form ethyl acetate/hexane to give the title compound as a solid; mp: 218°-220° C. Elem. Anal. calculated for C11H8Cl2INO2 : C, 34.41; H, 2.10; N, 3.65. Found: C, 34.67; H, 2.09; N, 3.68.
Reaction SMILES: [H][H].[F:3][C:4]([F:23])=[C:5]([F:22])[C:6]([F:21])([F:20])[C:7]([F:19])([F:18])[C:8]([F:17])([F:16])[C:9]([F:15])([F:14])[C:10]([F:13])([F:12])[F:11]>>[F:3][CH:4]([F:23])[C:5]([F:22])([C:5]([F:22])([CH:4]([F:3])[F:23])[C:6]([F:21])([F:20])[C:7]([F:19])([F:18])[C:8]([F:17])([F:16])[C:9]([F:15])([F:14])[C:10]([F:13])([F:12])[F:11])[C:6]([F:20])([F:21])[C:7]([F:18])([F:19])[C:8]([F:16])([F:17])[C:9]([F:15])([F:14])[C:10]([F:13])([F:12])[F:11]
Reactant: [H][H]
Reactant: FC(F)=C(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Product: FC(F)C(F)(C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)C(F)(C(F)F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Reaction time: 25 h

Procedure:
A stream of hydrogen (30 ml/min) saturated with perfluoro-1-heptene was passed into the photoreactor and photolyzed for 25 hours. 5.7 g of crude product consisted of a mixture of dimers (GC-MS) whose major component (55%) was the title compound, which shows the characteristic CF2H-CFRR' moiety by 1H-NMR (in d6 -acetone: 6.30 8;J1H-F =51.5 Hz, J2H-F =4.5 Hz).
Reaction SMILES: [Cl:1][C:2]1[C:3]([O:21][CH2:22][C:23]([OH:25])=[O:24])=[CH:4][C:5]2[CH2:6][CH2:7][C:8]3([CH2:18][CH2:19][CH3:20])[C:13]([C:14]=2[C:15]=1[Cl:16])=[CH:12][C:11](=[O:17])[CH2:10][CH2:9]3.C(N1C=CN=C1)(N1C=CN=C1)=O.O[C:39]([CH3:44])([CH3:43])[C:40]([OH:42])=[O:41]>O1CCCC1>[Cl:1][C:2]1[C:3]([O:21][CH2:22][C:23]([O:25][C:39]([C:40]([OH:42])=[O:41])([CH3:44])[CH3:43])=[O:24])=[CH:4][C:5]2[CH2:6][CH2:7][C:8]3([CH2:18][CH2:19][CH3:20])[C:13]([C:14]=2[C:15]=1[Cl:16])=[CH:12][C:11](=[O:17])[CH2:10][CH2:9]3
Reactant: CC(C)(O)C(=O)O
Reactant: CCCC12CCC(=O)C=C1c1c(cc(OCC(=O)O)c(Cl)c1Cl)CC2
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CCCC12CCC(=O)C=C1c1c(cc(OCC(=O)OC(C)(C)C(=O)O)c(Cl)c1Cl)CC2
Temperature: 25 °C

Procedure:
[(3,4-Dichloro-6,7,8,8a,9,10-hexahydro-6-oxo-8a-propyl-2-phenanthrenyl)oxy]acetic acid (351 mg, 1 mmole) is dissolved in tetrahydrofuran (10 ml) and treated with 1,1'-carbonyldiimidazole (160 mg, 1 mmole) and the mixture stirred at room temperature for an hour. 2-Hydroxy-2-methylpropionic acid (105 mg, 1 mmole) is added and the mixture stirred for 18 hours at room temperature. The solvent is removed by evaporation in vacuo and the residue purified by column chromatography on silica gel using dichloromethane/tetrahydrofuran/acetic acid 100/2/1, v.v.v. to give 1-carboxy-1-methylethyl [(3,4-dichloro-6,7,8,8a,9,10-hexahydro-6-oxo-8a-propyl-2-phenanthrenyl)oxy]acetate.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]=[C:10]=[O:11].[F:12][C:13]1[CH:23]=[C:17]([C:18](OCC)=[O:19])[C:16]([NH2:24])=[CH:15][CH:14]=1.C[O-].[Na+]>CC(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:18](=[O:19])[C:17]2[C:16](=[CH:15][CH:14]=[C:13]([F:12])[CH:23]=2)[NH:24][C:10]1=[O:11]
Reactant: O=C=Nc1ccc(Cl)cc1Cl
Reactant: CCOC(=O)c1cc(F)ccc1N
Agent: C[O-]
Agent: [Na+]
Solvent: CC(C)=O
Product: O=c1[nH]c2ccc(F)cc2c(=O)n1-c1ccc(Cl)cc1Cl
Temperature: 90 °C
Reaction time: 2.5 h
Yield: 97.5 %

Procedure:
A solution of 2,4-dichlorophenyl isocyanate (18.8 g, 0.10 mol) in acetone (50 ml) is metered at room temperature into a solution of ethyl 5-fluoroanthranilate (18.3 g, 0.10 mol) in acetone (70 ml). After addition is complete the mixture is stirred at 90° C. for 2.5 hours. 1.80 ml of a 30% strength solution of methanolic sodium methoxide (0.010 mol) are metered in and the mixture is stirred under reflux for a further 2 hours. After cooling, the product is filtered off with suction and washed with 3×15 ml of acetone. The acetone-moist precipitate is treated with dilute hydrochloric acid and the residual acetone is removed by azeotropic distillation. The product is then filtered off with suction, washed with water and dried. 31.7 g of 3-(2,4-dichlorophenyl)-6-fluoro-2,4(1H,3H)-quinazolinedione (yield: 97.5% of theory) of melting point 313° to 314° C. are obtained.
Reaction SMILES: [Li]CCCC.Br[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])=[CH:9][N:8]=1.CN([CH:26]=[O:27])C.[BH4-].[Na+]>C1COCC1.CO>[Si:16]([O:15][CH2:14][CH2:13][C:10]1[CH:11]=[CH:12][C:7]([CH2:26][OH:27])=[N:8][CH:9]=1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]
Reactant: CC(C)(C)[Si](C)(C)OCCc1ccc(Br)nc1
Reactant: CN(C)C=O
Agent: [BH4-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OCCc1ccc(CO)nc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
BuLi (14.6 ml of a 1.6 M solution in hexanes, 23 mmol) was added to a stirred solution of 2-bromo-5-[2-(tert-butyldimethylsilyloxy)ethyl]pyridine (4.92 g, 15.6 mmol) in THF (100 ml) at −78° C. The resulting pale yellow solution was stirred for 1 h and then DMF (3.6 ml, 46.6 mmol) was added in one portion. The reaction mixture was warmed to room temperature and stirred for 90 min. MeOH (70 ml) was added, followed by NaBH4 (589 mg, 15.6 mmol) and stirring was continued for a further 1 h. The reaction was quenched by cautious addition of NH4Cl (sat. 100 ml) and the organics extracted with EtOAc (3×100 ml). The combined extracts were then washed with H2O (70 ml) and brine (70 ml), dried (MgSO4) and concentrated under reduced pressure. The material was used crude without further purification.
Reaction SMILES: O[CH2:2][C:3](=[CH2:9])[C:4]([O:6][CH2:7][CH3:8])=[O:5].CCN(S(F)(F)[F:16])CC.C([O-])(O)=O.[Na+].C(OCC)(=O)C>C(Cl)Cl>[F:16][CH2:2][C:3](=[CH2:9])[C:4]([O:6][CH2:7][CH3:8])=[O:5]
Reactant: CCN(CC)S(F)(F)F
Reactant: C=C(CO)C(=O)OCC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: C=C(CF)C(=O)OCC
Temperature: -78 °C
Reaction time: 1 h
Yield: 55.8 %

Procedure:
To a solution of ethyl 2-(hydroxymethyl)acrylate (5 g, 38 mmol) in 50 mL of methylene chloride was added DAST (6.0 mL, 46.1 mmol) at −78° C. The reaction mixture was stirred at −78° C. for 1 h, then warmed up to room temperature and continuously stirred overnight. 20 mL of saturated NaHCO3 aqueous solution and 20 mL of ethyl acetate were added to quench the reaction. The organic layer was separated, and the aqueous layer was extracted twice with EtOAc (20 ml×2). The combined organic extracts were dried over MgSO4 and evaporated to give an oil residue (2.8 g, yield: 56%). MS (m/z): 131 (M+1)+.
Reaction SMILES: C([O:4][C@@H:5]1[C@H:9]([O:10]C(=O)C)[C@@H:8]([C:14]2[O:18][N:17]=[C:16]([CH2:19][O:20]C(=O)C)[CH:15]=2)[O:7][C@H:6]1[N:24]1[CH:32]=[N:31][C:30]2[C:25]1=[N:26][C:27]([Cl:42])=[N:28][C:29]=2[NH:33][C:34]1[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][C:35]=1[F:41])(=O)C.C(N)(C)(C)C>CO>[Cl:42][C:27]1[N:26]=[C:25]2[C:30]([N:31]=[CH:32][N:24]2[C@H:6]2[C@H:5]([OH:4])[C@H:9]([OH:10])[C@@H:8]([C:14]3[O:18][N:17]=[C:16]([CH2:19][OH:20])[CH:15]=3)[O:7]2)=[C:29]([NH:33][C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][C:35]=2[F:41])[N:28]=1
Reactant: CC(=O)OCc1cc([C@H]2O[C@@H](n3cnc4c(Nc5ccc(Cl)cc5F)nc(Cl)nc43)[C@H](OC(C)=O)[C@@H]2OC(C)=O)on1
Solvent: CC(C)(C)N
Solvent: CO
Product: OCc1cc([C@H]2O[C@@H](n3cnc4c(Nc5ccc(Cl)cc5F)nc(Cl)nc43)[C@H](O)[C@@H]2O)on1
Reaction time: 3 h
Yield: 77.3 %

Procedure:
To (2R,3R,4R,5S)4-(acetyloxy)-5-{3-[(acetyloxy)methyl]isoxazol-5-yl}-2-[2-chloro-6-(4-chloro-2-fluoroanilino)-9H-purin-9-yl]tetrahydrofuran-3-yl acetate (4.02 mg) in methanol (2 ml) at 0° C. was added tert-butylamine (0.012 ml), and the mixture was allowed to stand at 0° C. for 3 h. The solvent was evaporated in vacuo to furnish the title compound as a yellow gum (2.48 mg).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[CH3:16][O:17][C:18]1[CH:27]=[C:26]2[C:21]([CH:22]=[CH:23][C:24]([OH:28])=[CH:25]2)=[CH:20][CH:19]=1>>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH3:15])[N:5]=[CH:4][CH:3]=[C:2]2[O:28][C:24]1[CH:23]=[CH:22][C:21]2[C:26](=[CH:27][C:18]([O:17][CH3:16])=[CH:19][CH:20]=2)[CH:25]=1
Reactant: COc1cc2nccc(Cl)c2cc1OC
Reactant: COc1ccc2ccc(O)cc2c1
Product: COc1ccc2ccc(Oc3ccnc4cc(OC)c(OC)cc34)cc2c1
Temperature: 180 °C
Reaction time: 0.5 h
Yield: 41 %

Procedure:
4-Chloro-6,7-dimethoxyquinoline (89 mg) and commercially available 7-methoxy-2-naphthol (209 mg) were mixed and stirred at 180° C. for 30 minutes, and the reaction mixture was then purified in the same manner as described in Example 2 to obtain 59 mg of the title compound (yield: 41%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=1.[CH2:23]1C[O:26][CH2:25][CH2:24]1.C(N(CC)CC)C.C(Cl)(=O)C=C>CN(C=O)C>[C:12]([C:6]1[CH:7]=[N:8][C:9]2[C:4]([C:5]=1[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=1)=[CH:3][C:2]([NH:1][C:25](=[O:26])[CH:24]=[CH2:23])=[CH:11][CH:10]=2)#[N:13]
Reactant: C1CCOC1
Reactant: COc1cccc(Nc2c(C#N)cnc3ccc(N)cc23)c1
Agent: C=CC(=O)Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: C=CC(=O)Nc1ccc2ncc(C#N)c(Nc3cccc(OC)c3)c2c1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
Dissolved 500 mg (1.72 mmol) 6-amino-4-[(3-methoxyphenyl)amino]-3-quinolinecarbonitrile in 2 ml hot DMF, added 6 ml THF, and chilled to 0° C. Added 264 μl (1.90 mmol) triethylamine and 158 μl (1.90 mmol) acryloyl chloride. Removed ice bath at 15 minutes. Stripped solvent at 2 hours. Washed residue with dilute sodium bicarbonate, collected solids, washed with water, and air dried. Boiled solids in ethyl acetate, collected and dried in vacuo, giving 288 mg of yellow-orange solid: mass spectrum (electrospray m/e): M+H=345.2.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([CH:12]2[S:16][C:15](=[O:17])[NH:14][C:13]2=[O:18])(=[O:11])=[O:10])=[CH:5][CH:4]=1.Br[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[C:29]([C:37]([F:40])([F:39])[F:38])[CH:28]=2)=[CH:23][CH:22]=1.C(OCC)C>CN(C)C=O>[F:34][C:33]([F:35])([F:36])[C:31]1[CH:32]=[C:27]([CH:28]=[C:29]([C:37]([F:40])([F:38])[F:39])[CH:30]=1)[C:24]1[CH:25]=[CH:26][C:21]([CH2:20][C:12]2([S:9]([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)(=[O:10])=[O:11])[S:16][C:15](=[O:17])[NH:14][C:13]2=[O:18])=[CH:22][CH:23]=1
Reactant: COc1ccc(S(=O)(=O)C2SC(=O)NC2=O)cc1
Reactant: FC(F)(F)c1cc(-c2ccc(CBr)cc2)cc(C(F)(F)F)c1
Solvent: CN(C)C=O
Solvent: CCOCC
Product: COc1ccc(S(=O)(=O)C2(Cc3ccc(-c4cc(C(F)(F)F)cc(C(F)(F)F)c4)cc3)SC(=O)NC2=O)cc1

Procedure:
Prepared analogously to Example 9 from from 5-(4-methoxybenzenesulfonyl)thiazolidine-2,4-dione and 4′-bromomethyl-3,5-bis(trifluoromethyl)biphenyl in N,N-dimethylformamide. Trituration with diethyl ether provided a white solid. 1H NMR: δ 8.43 (br s, 1H), 7.91-7.99 (m, 4H), 7.85 (s, 1H), 7.53 (dd, J=6.5, 1.8 Hz, 2H), 7.33 (d, J=8.3 Hz, 2H), 7.07 (dm, J=9.0 Hz, 2H), 4.00 (A of AB, J=13.7 Hz, 1H), 3.93 (s, 3H), 3.42 (B of AB), J=13.7 Hz, 1H). MS (m/e): 588.5 (M−H)−. Anal: Calc for C25H17F6NO5S2.C3H7NO: 50.75% C, 3.65% H, 4.23% N; Found: 50.70% C, 3.60% H, 4.01% N. MP: 122-125° C.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][CH:3]([CH:6]=[O:7])[CH2:2]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[F:26][C:27]([Si](C)(C)C)([F:29])[F:28]>O1CCCC1>[F:26][C:27]([F:29])([F:28])[CH:6]([CH:3]1[CH2:4][CH2:5][O:1][CH2:2]1)[OH:7]
Reactant: O=CC1CCOC1
Reactant: C[Si](C)(C)C(F)(F)F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: OC(C1CCOC1)C(F)(F)F
Yield: 31.3 %

Procedure:
According to Reference Example 8-12, by use of a 50 wt % aqueous tetrahydrofuran-3-carbaldehyde solution (1.00 g, 5.00 mmol) dissolved in tetrahydrofuran (15 mL), a 1 mol/L solution of tetrabutylammonium fluoride in tetrahydrofuran (1.00 mL, 1.00 mmol) and (trifluoromethyl)trimethylsilane (0.887 mL, 6.00 mmol), the mixture was stirred and reacted at room temperature for 1.8 hours. Then, purification by extraction gave 2,2,2-trifluoro-1-(tetrahydrofuran-3-yl)ethanol (Compound EJ) (266 mg, yield: 31%).
Reaction SMILES: [C:1]1([CH:7]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:11][CH:10]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:19](Cl)(=[O:21])[CH3:20]>>[C:19]([C:4]1[CH:3]=[CH:2][C:1]([CH:7]([C:9]2[CH:10]=[CH:11][C:12]([C:15]([CH3:17])([CH3:16])[CH3:18])=[CH:13][CH:14]=2)[CH3:8])=[CH:6][CH:5]=1)(=[O:21])[CH3:20]
Reactant: CC(c1ccccc1)c1ccc(C(C)(C)C)cc1
Reactant: CC(=O)Cl
Product: CC(=O)c1ccc(C(C)c2ccc(C(C)(C)C)cc2)cc1

Procedure:
In like manner as in Preparation Example 1, 200 g of this 1-phenyl-1-(4'-tert-butylphenyl)ethane was reacted with acetyl chloride to obtain 1-(4-acetylphenyl)-1-(4'-tert-butylphenyl)ethane. Also in like manner as in Preparation Example 1, this compound was converted into an alcohol by using sodium borohydride, and the product was then dehydrated with potassium hydrogensulfate to obtain 1-(4-tert-butylphenyl)-1-(4'-vinylphenyl)ethane in a yield of 69.2% (b.p. 171° C./10 mmHg, 130° C./2 mmHg).
Reaction SMILES: [C:1]([O:7][CH2:8][C@H:9]([C:15]1[C:16](Br)=[C:17]2[C:22](=[CH:23][C:24]=1[CH3:25])[NH:21][C:20](=[O:26])[CH:19]=[CH:18]2)[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[Cl:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C([O-])([O-])=O.[K+].[K+]>COCCOC.C(OCC)(=O)C.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>[C:1]([O:7][CH2:8][C@@H:9]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[C:15]1[C:16]([C:32]2[CH:33]=[CH:34][C:29]([Cl:28])=[CH:30][CH:31]=2)=[C:17]2[C:22](=[CH:23][C:24]=1[CH3:25])[NH:21][C:20](=[O:26])[CH:19]=[CH:18]2)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]
Reactant: Cc1cc2[nH]c(=O)ccc2c(Br)c1[C@@H](COC(=O)C(C)(C)C)OC(C)(C)C
Reactant: OB(O)c1ccc(Cl)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: COCCOC
Solvent: CCOC(C)=O
Product: Cc1cc2[nH]c(=O)ccc2c(-c2ccc(Cl)cc2)c1[C@@H](COC(=O)C(C)(C)C)OC(C)(C)C
Temperature: 100 °C

Procedure:
The mixture of (S)-2-(5-bromo-7-methyl-2-oxo-1,2-dihydroquinolin-6-yl)-2-tert-butoxyethyl pivalate (34 mg, 0.078 mmol), Pd(PPh3)4 (9 mg), 4-chlorophenylboronic acid (16 mg, 0.1 mmol), aqueous K2CO3 solution (0.15 mL, 2 M, 0.3 mmol) in 1,2-dimethoxyethane (2 mL) was heated at 100° C. for 90 minutes. The residue was diluted with ethyl acetate (100 mL), washed with NaHCO3 solution, water and brine, dried over Na2SO4. Concentration and purification gave (S)-2-tert-butoxy-2-(5-(4-chlorophenyl)-7-methyl-2-oxo-1,2-dihydroquinolin-6-yl)ethyl pivalate. LCMS-ESI+ (m/z): 470.3 (M+H)+.
Reaction SMILES: C(N(C(C)C)C(C)C)C.Cl.[OH:11][C:12]1[CH:18]=[C:17]([OH:19])[CH:16]=[CH:15][C:13]=1[NH2:14].[C:20]12([CH2:30][C:31](O)=[O:32])[CH2:29][CH:24]3[CH2:25][CH:26]([CH2:28][CH:22]([CH2:23]3)[CH2:21]1)[CH2:27]2.CCCP(=O)=O>ClCCl>[C:20]12([CH2:30][C:31]([NH:14][C:13]3[CH:15]=[CH:16][C:17]([OH:19])=[CH:18][C:12]=3[OH:11])=[O:32])[CH2:27][CH:26]3[CH2:25][CH:24]([CH2:23][CH:22]([CH2:28]3)[CH2:21]1)[CH2:29]2
Reactant: Nc1ccc(O)cc1O
Reactant: O=C(O)CC12CC3CC(CC(C3)C1)C2
Agent: CCCP(=O)=O
Agent: Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C(CC12CC3CC(CC(C3)C1)C2)Nc1ccc(O)cc1O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
1.05 ml of N-ethyl-diisopropylamine is added to a solution of 323 mg 2,4-dihydroxyaniline hydrochloride (formula V), 388 mg (adamantan-1-yl)acetic acid (formula R3COOH) and 1.2 ml of propylphosphonic anhydride (50% in ethyl acetate) in 20 ml of dry dichloromethane at 0°. The mixture obtained is stirred for about 18 hours at room temperature and the solvent is evaporated off. The residue is dissolved in 50 ml of ethyl acetate and extracted with 1 M aqueous hydrochloric acid, saturated aqueous NaHCO3 solution and brine. The organic layer is dried and the solvent is evaporated off. The title compound is obtained (m.p. 195-197°).
Reaction SMILES: [CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[C:11]([O:13][C@H:14]1[CH2:18][C@@H:17]([C:19](=[O:40])[NH:20][C@@H:21]([C:36]([CH3:39])([CH3:38])[CH3:37])[C:22]([NH:24][C@@H:25]([CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[C:26]([NH:28][CH3:29])=[O:27])=[O:23])[N:16](CC)[CH2:15]1)=[O:12].C(Cl)Cl.C(O)(C(F)(F)F)=O>>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[C:11]([O:13][C@H:14]1[CH2:18][C@@H:17]([C:19](=[O:40])[NH:20][C@@H:21]([C:36]([CH3:38])([CH3:37])[CH3:39])[C:22]([NH:24][C@@H:25]([CH:30]2[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]2)[C:26]([NH:28][CH3:29])=[O:27])=[O:23])[NH:16][CH2:15]1)=[O:12]
Reactant: CCN1C[C@@H](OC(=O)N2CCc3ccccc3C2)C[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)NC)C1CCCCC1)C(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]1C[C@H](OC(=O)N2CCc3ccccc3C2)CN1)C(C)(C)C)C1CCCCC1
Yield: 111.7 %

Procedure:
Compound 30 (0.238 g) is treated with DCM-TFA (3 ml-1.5 ml) at 0° C. for 1 h. The volatiles are evaporated to dryness. Compound 31 (crude, 0.253 g) is obtained as white foam for use in the next step.