Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS(Cl)(=O)=O.O[C:7]([C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]([CH:24]2[O:28][N:27]=[C:26]([C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)[CH2:25]2)=[O:23])=[CH:17][CH:16]=1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:8].C(N(CC)CC)C.O>C(Cl)Cl>[C:9]1([C:7]([C:15]2[CH:16]=[CH:17][C:18]([NH:21][C:22]([CH:24]3[O:28][N:27]=[C:26]([C:29]4[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=4)[CH2:25]3)=[O:23])=[CH:19][CH:20]=2)=[CH2:8])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CC(O)(c1ccccc1)c1ccc(NC(=O)C2CC(c3cccnc3)=NO2)cc1
Agent: CS(=O)(=O)Cl
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C=C(c1ccccc1)c1ccc(NC(=O)C2CC(c3cccnc3)=NO2)cc1
Temperature: 0 °C
Yield: 27.1 %

Procedure:
) Methanesulfonyl chloride (0.010 mol) was added to a solution of compound (51) (0.005 mol) and triethylamine (0.013 mol) in CH2Cl2 (100 ml, dried over MgSO4), stirred at 0° C. The resulting reaction mixture was stirred for 1 hour at 10° C. Water was added. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by short column chromatography over silica gel (eluent: CH2Cl2/CH3OH 97/3). The pure fractions were collected and the solvent was evaporated under reduced pressure. The residue was crystallized from EtOAc. The precipitate was filtered off, washed with EtOAc, then dried, yielding 0.5 g (27%) of (±)-4,5-dihydro-N-[4-(1-phenylethenyl)phenyl]-3-(3-pyridinyl)-5-isoxazolecarboxamide (compound 378).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].C(N(C(C)C)CC)(C)C.[NH:24]1[CH:28]=[CH:27][N:26]=[CH:25]1>C(#N)C>[N+:12]([C:3]1[CH:4]=[C:5]([C:8]([F:11])([F:10])[F:9])[CH:6]=[CH:7][C:2]=1[N:24]1[CH:28]=[CH:27][N:26]=[CH:25]1)([O-:14])=[O:13]
Reactant: c1c[nH]cn1
Reactant: O=[N+]([O-])c1cc(C(F)(F)F)ccc1F
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: O=[N+]([O-])c1cc(C(F)(F)F)ccc1-n1ccnc1
Yield: 95.4 %

Procedure:
To a solution of 1-fluoro-2-nitro-4-(trifluoromethyl)benzene (15.00 g; 71.8 mmol; 1 eq) and diisopropylethylamine (12.5 mL; 71.8 mmol; 1 eq) in anhydrous acetonitrile (650 mL), imidazole (4.88 g; 71.8 mmol; 1 eq) is added under argon. The reaction mixture is allowed to stir under reflux for 20 hours until 1-fluoro-2-nitro-4-(trifluoromethyl)benzene has completely reacted. The crude mixture is concentrated under vacuum and the resulting powder dissolved in ethyl acetate (250 mL). The organic phase is then washed with water (100 mL), brine (100 mL) and dried over sodium sulfate to provide an orange powder after concentration under vacuum. Further purification by flash chromatography on silica gel (ethyl acetate/cyclohexane 5:5) afforded the title compound (17.7 g; 68.5 mmol; 96%) as a brown powder.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([NH2:17])[C:14]=1[O:15][CH3:16])[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1.[CH3:18][N:19]([CH3:31])[CH2:20][CH2:21][N:22]1[C:26](=[O:27])[CH2:25][CH:24]([C:28](O)=[O:29])[CH2:23]1>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([NH:17][C:28]([CH:24]3[CH2:25][C:26](=[O:27])[N:22]([CH2:21][CH2:20][N:19]([CH3:31])[CH3:18])[CH2:23]3)=[O:29])[C:14]=1[O:15][CH3:16])[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1
Reactant: COc1c(Cl)cc2c([nH]c3cnccc32)c1N
Reactant: CN(C)CCN1CC(C(=O)O)CC1=O
Product: COc1c(Cl)cc2c([nH]c3cnccc32)c1NC(=O)C1CC(=O)N(CCN(C)C)C1
Yield: 60 %

Procedure:
Prepared according to Method A from 6-chloro-7-methoxy-9H-β-carboline-8-ylamine and 1-(2-dimethylamino-ethyl)-5-oxo-pyrrolidine-3-carboxylic acid in 60% yield following purification using a semi-preparative Chiralcel OD column with 85/7.5/7.5 hexane/EtOH/MeOH as the eluant. 1H-NMR (300 MHz, DMSO-d6): δ 2.44 (s, 6H), 2.75 (t, 2H), 2.88 (d, 2H), 3.56 (t, 2H), 3.66 (m, 1H), 3.85 (m, 2H), 3.90 (s, 3H), 8.03 (d, 1H), 8.21 (s, 1H), 8.28 (d,1H), 8.79 (s,1H). Retention Time (LC, method: ammonium acetate standard): 1.42 min. MS (M+H+): 430.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=2[CH:23]=O)[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1.[NH2:26][C@@H:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:29][CH2:28]1>>[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:20])[F:22])=[CH:15][C:14]=2[CH2:23][NH:26][C@@H:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29][CH2:28]2)[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1
Reactant: N[C@H]1CCc2ccccc21
Reactant: COC(=O)Cc1ccc(OC)c(-c2ccc(C(F)(F)F)cc2C=O)c1
Product: COC(=O)Cc1ccc(OC)c(-c2ccc(C(F)(F)F)cc2CN[C@H]2CCc3ccccc32)c1

Procedure:
Prepared according to the procedure described in Example 4, Step 1, using the following starting materials: (2′-formyl-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester and (S)-(+)-1-aminoindan.
Reaction SMILES: [C:1](=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([OH:18])[CH:14]=2)[CH:9]=1.S(OC)(OC)(=O)=O.Cl>CN(C)C=O>[CH3:1][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[CH:14]=[C:13]([OH:18])[CH:12]=[CH:11]2
Reactant: Oc1ccc2cc(O)ccc2c1
Reactant: O=C([O-])[O-]
Agent: Cl
Agent: [K+]
Solvent: COS(=O)(=O)OC
Solvent: CN(C)C=O
Product: COc1ccc2cc(O)ccc2c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 29.4 %

Procedure:
Potassium carbonate (1.244 g) was added to a solution of commercially available 2,6-dihydroxynaphthalene (961 mg) in N,N-dimethylformamide (100 ml), and the admixture was stirred at room temperature for 30 minutes. Dimethyl sulfate (1.14 ml) was slowly added dropwise to the mixture and the resulting mixture was further stirred at room temperature overnight. The reaction mixture thus prepared was neutralized with a 2N HCl solution and then partitioned between water and ethyl acetate, and the ethyl acetate layer was dried with anhydrous magnesium sulfate. After removing the solvent by distillation under reduced pressure, the resulting residue was purified by column chromatography on silica gel (eluting with chloroform/ethyl acetate) to obtain 307 mg of the title compound (yield: 29%).
Reaction SMILES: [C:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9]C)=[O:8])=[CH:5][C:4]=1[N:13]1[CH:17]=[CH:16][CH:15]=[N:14]1)#[N:2].Cl>O1CCCC1.O.[OH-].[Li+].O>[C:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([OH:9])=[O:8])=[CH:5][C:4]=1[N:13]1[CH:17]=[CH:16][CH:15]=[N:14]1)#[N:2]
Reactant: COC(=O)c1ccc(C#N)c(-n2cccn2)c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: N#Cc1ccc(C(=O)O)cc1-n1cccn1
Reaction time: 2 h
Yield: 90.8 %

Procedure:
Methyl 4-cyano-3-(1H-pyrazol-1-yl)benzoate (0.27 g) was dissolved in tetrahydrofuran (10 ml). To the solution, a solution in which lithium hydroxide monohydrate (0.10 g) is dissolved in water (10 ml) was added at room temperature. The reaction mixture was stirred for 2 hours. The reaction solution was acidified with 2 N hydrochloric acid, and then extracted twice with ethyl acetate. The organic phases were combined, washed with water, and then dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the solvent was distilled off under reduced pressure to obtain a crude product of 4-cyano-3-(1H-pyrazol-1-yl)benzoic acid (0.23 g). The crude product was used for the next step without further purification.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:11])[CH2:4][CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][NH:6]1.[CH3:12][C:13]1[S:14][C:15]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[C:16]([C:18](O)=[O:19])[N:17]=1>>[CH3:1][O:2][C:3](=[O:11])[CH2:4][CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][N:6]1[C:18]([C:16]1[N:17]=[C:13]([CH3:12])[S:14][C:15]=1[C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)=[O:19]
Reactant: Cc1nc(C(=O)O)c(-c2ccc(F)cc2)s1
Reactant: COC(=O)CC1CCCCN1
Product: COC(=O)CC1CCCCN1C(=O)c1nc(C)sc1-c1ccc(F)cc1
Yield: 60.2 %

Procedure:
The title compound (2.1 g) was prepared from piperidin-2-yl-acetic acid methyl ester (3.4 g) and 2-methyl-5-(4-fluorophenyl)-thiazole-4-carboxylic acid (2.20 g) according to the method of description 20.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10](=[O:12])[CH3:11])([O-:3])=[O:2].[CH:13]([CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)=O>O1CCCC1.[O-]CC.[Na+].C(O)C>[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10](=[O:12])/[CH:11]=[CH:13]\[CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH2:17][CH2:16]1)([O-:3])=[O:2]
Reactant: CC(C)(C)OC(=O)N1CCC(C=O)CC1
Reactant: CC(=O)c1ccccc1[N+](=O)[O-]
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(/C=C\C(=O)c2ccccc2[N+](=O)[O-])CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 57.3 %

Procedure:
1-(2-Nitrophenyl)ethanone (1.04 g) and tert-butyl 4-formylpiperidine-1-carboxylate (1.47 g) were suspended in dry tetrahydrofuran (20 mL) and 20 drops of sodium ethoxide in ethanol (21% by weight) was added. The reaction mixture was stirred at room temperature for 18 hours and concentrated under reduced pressure to afford the crude material, which was purified by flash column chromatography (eluant: 15% ethyl acetate/hexane) to furnish the title compound (1.30 g) with the following physical properties.
Reaction SMILES: C(O[CH:5]1[O:13][CH2:12][CH:11]2[C:6]1([CH3:15])[CH:7]1[CH2:14][CH:10]2[CH2:9][CH2:8]1)(=O)C.[C:16]([OH:21])(=[O:20])[C:17]([CH3:19])=[CH2:18]>C(C1C(O)=C(C(C)(C)C)C=C(C)C=1)C1C(O)=C(C(C)(C)C)C=C(C)C=1>[C:16]([O:21][CH:5]1[O:13][CH2:12][CH:11]2[C:6]1([CH3:15])[CH:7]1[CH2:14][CH:10]2[CH2:9][CH2:8]1)(=[O:20])[C:17]([CH3:19])=[CH2:18]
Reactant: C=C(C)C(=O)O
Reactant: CC(=O)OC1OCC2C3CCC(C3)C12C
Agent: Cc1cc(Cc2cc(C)cc(C(C)(C)C)c2O)c(O)c(C(C)(C)C)c1
Product: C=C(C)C(=O)OC1OCC2C3CCC(C3)C12C
Temperature: 50 °C
Yield: 87.8 %

Procedure:
A mixture of 73 g of 2-methyl-4-oxatricyclo[5.2.1.02,6]decan-3-yl acetate, 150 g of methacrylic acid, and 40 mg of 2,2′-methylenebis(6-t-butyl-p-cresol) was heated at 50° C. under atmospheric pressure for 30 minutes, after which under a reduced pressure of 0.20 kPa, the reaction mixture was heated for 18 hours for distilling off the acetic acid formed. The reaction mixture was purified by distillation, obtaining 72 g (yield 91%) of the target compound.
Reaction SMILES: [CH3:1][NH2:2].CO.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[F:13][C:14]([F:55])([F:54])[C:15]1[CH:16]=[C:17]([CH:51]=[CH:52][CH:53]=1)[CH2:18][NH:19][C:20](=[O:50])[C:21]1[CH:26]=[CH:25][N:24]=[C:23]([C:27]2[CH:32]=[C:31]([N:33]3[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]3)[CH:30]=[CH:29][C:28]=2[NH:39][C:40](=[O:49])[C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47]Br)[CH:42]=2)[CH:22]=1>CN(C)C=O.O>[F:13][C:14]([F:55])([F:54])[C:15]1[CH:16]=[C:17]([CH:51]=[CH:52][CH:53]=1)[CH2:18][NH:19][C:20](=[O:50])[C:21]1[CH:26]=[CH:25][N:24]=[C:23]([C:27]2[CH:32]=[C:31]([N:33]3[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]3)[CH:30]=[CH:29][C:28]=2[NH:39][C:40](=[O:49])[C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][NH:2][CH3:1])[CH:42]=2)[CH:22]=1
Reactant: O=C(NCc1cccc(C(F)(F)F)c1)c1ccnc(-c2cc(N3CCCCC3)ccc2NC(=O)c2cccc(CBr)c2)c1
Reactant: CN
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CO
Solvent: O
Product: CNCc1cccc(C(=O)Nc2ccc(N3CCCCC3)cc2-c2cc(C(=O)NCc3cccc(C(F)(F)F)c3)ccn2)c1
Temperature: 70 °C
Reaction time: 3 h

Procedure:
Into a 100-mL round-bottom flask, was placed a solution of methylamine in methanol (126 mg, 1.22 mmol, 4.00 equiv, 30%), potassium carbonate (124 mg, 0.90 mmol, 3.00 equiv), potassium iodide (10 mg, 0.06 mmol, 0.20 equiv), and a solution of N-(3-(trifluoromethyl)benzyl)-2-(2-(3-(bromomethyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide (200 mg, 0.31 mmol, 1.00 equiv) in N,N-dimethylformamide (15 mL). The resulting solution was stirred for 3 h at 70° C. in an oil bath. The resulting solution was diluted with 250 mL of water. The resulting solution was extracted with 4×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2×50 mL of brine, dried over sodium sulfate, and concentrated under vacuum. This resulted in 200 mg (crude) of N-(3-(trifluoromethyl)benzyl)-2-(2-(3-((methylamino)methyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide as a yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[C:4]=1[O:5][CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8].[N+:18]([O-])([OH:20])=[O:19]>C(Cl)Cl>[CH3:17][O:16][C:12]1[CH:13]=[C:14]([N+:18]([O-:20])=[O:19])[CH:15]=[C:3]([O:2][CH3:1])[C:4]=1[O:5][CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8]
Reactant: CCOC(=O)COc1c(OC)cccc1OC
Reactant: O=[N+]([O-])O
Solvent: ClCCl
Product: CCOC(=O)COc1c(OC)cc([N+](=O)[O-])cc1OC
Temperature: 25 °C
Reaction time: 1 h
Yield: 98 %

Procedure:
To a solution of 2,6-dimethoxyphenol (1.54 g, 10 mmol) and ethyl bromoacetate (2.00 g, 12 mmol) in 15 mL of anhydrous DMF, was added 2.76 g (20 mmol) of K2CO3. The reaction mixture was stirred at 30° C. for 20 hours. The mixture was concentrated in vacuo to remove volatiles. The resulting residue was extracted with EtOAc, washed with brine, dried over anhydrous sodium sulfate and then concentrated in vacou to give 2.2 g (91.6%) of ethyl 2-(2,6-dimethoxyphenoxy)acetate. The obtained ester (1.2 g, 5 mmol) was dissolved in a suspension of Silica Gel (2.0 g) in 20 mL of DCM. To this was dropwise added of a solution of concentrated HNO3 (20 mL) in 20 mL of DCM at rt. After being stirred at room temperature for 1 hour, it was transferred into a separatory funnel and then brown bottom layer was discarded into 100 g of ice. The remaining top organic layer was washed with brine, dried over anhydrous sodium sulfate, and then concentrated in vacou to give 1.4 g (98%) of ethyl 2-(2,6-dimethoxy-4-nitrophenoxy)acetate as a brown solid. The obtained nitrophenoxy ester (1.34 g, 4.7 mmol) was dissolved in anhydrous THF (20 mL). To this, was slowly added of 1M DIBAL solution (10.3 mL, 10.3 mmol) in toluene with ice bath cooling. After 1 hour at rt, the reaction was quenched by addition of 1N-NaOH solution, and then extracted with EtOAc. The obtained organic layer was dried over anhydrous sodium sulfate, and passed through Silica Gel pad. The resulting filtrate was concentrated in vacuo to afford 2-(2,6-dimethoxy-4-nitrophenoxy)ethanol (1.01 g, 88%) as a pale yellow solid; MS (ESI) m/z 326 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([I:17])[CH:15]=3)[C:10]([C:18]([OH:20])=O)=[N:9]2)[CH:5]=[CH:4][N:3]=1.S(Cl)(Cl)=O.[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl.CN(C=O)C>[I:17][C:14]1[CH:15]=[C:16]2[C:11]([C:10]([C:18]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[O:20])=[N:9][N:8]2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH2:1])[N:7]=2)=[CH:12][CH:13]=1
Reactant: Nc1nccc(-n2nc(C(=O)O)c3ccc(I)cc32)n1
Reactant: C1COCCN1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: Nc1nccc(-n2nc(C(=O)N3CCOCC3)c3ccc(I)cc32)n1
Temperature: 50 °C

Procedure:
To a solution of 1-(2-aminopyrimidin-4-yl)-6-iodo-1H-indazole-3-carboxylic acid (3.00 g, 7.87 mmol) in dry DCM (40 mL) was introduced thionyl chloride (6.85 mL, 94.46 mmol) and DMF (3 drops, cat.). The reaction mixture was warmed to 50° C. for 1 hr. After cooling to RT, the reaction mixture was concentrated in vacuo. The residue was re-dissolved in dry DCM (20 mL) and concentrated in vacuo (twice). After suspending the residue in dry DCM (30 mL), the solution was cooled to 0° C. under an atmosphere of nitrogen, and morpholine (1.37 mL, 15.74 mmol) added dropwise. The reaction mixture was warmed to RT for 16 hr. Following dilution with DCM (25 mL), 2M aqueous sodium carbonate (35 mL) was introduced. The resulting precipitate was collected by filtration and washed on the filter with DCM (5 mL) and dried. After suspension of the precipitate in 3:1 water/acetonitrile (10 mL), the slurry was collected by filtration and washed on the filter with further 3:1 water/acetonitrile (2×1 mL washes). The filter cake was dried under vacuum to furnish the title compound as an off-white solid: 1H NMR (500 MHz, DMSO) delta 3.41-3.76 (6H, m), 3.85-3.97 (2H, m), 7.05 (1H, d, J=5.5 Hz), 7.18 (2H, s), 7.74 (1H, dd, J=8.4, 1.1 Hz), 7.80 (1H, d, J=8.4 Hz), 8.34 (1H, d, J=5.5 Hz), 9.33 (1H, s); LC-MS: m/z=+450.90 (M+H)+.
Reaction SMILES: [CH2:1]1COCC1.[C:6]1([CH:12]2[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>C1(C)C=CC=CC=1>[C:6]1([CH:12]2[CH2:17][CH2:16][C:15](=[CH2:1])[CH2:14][CH2:13]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: O=C1CCC(c2ccccc2)CC1
Reactant: C1CCOC1
Solvent: Cc1ccccc1
Product: C=C1CCC(c2ccccc2)CC1
Reaction time: 0.17 h
Yield: 78 %

Procedure:
BDAM (3.00 grams) was suspended in 40 milliliters of toluene and 2 molar equivalents of THF were added at 0° C. After a homogeneous solution was formed, 1 molar equivalent (2 milliliters) of TEAL was added. After 10 minutes of stirring, 2.50 grams of 4-phenylcyclohexanone were added. After 3 hours of stirring, the reaction mixture was hydrolyzed and worked up as described in Example 1. A total of 1.93 grams of 4-phenyl-1-methylenecyclohexane was isolated (78% yield).
Reaction SMILES: [CH3:1][N:2]1[C:7]([CH3:8])=[CH:6][C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]1=[O:13].FC(F)(F)C(O)=O.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C1C(=O)N([I:41])C(=O)C1>>[CH3:1][N:2]1[C:7]([CH3:8])=[CH:6][C:5]([C:9]([F:12])([F:10])[F:11])=[C:4]([I:41])[C:3]1=[O:13]
Reactant: O=C1CCC(=O)N1I
Reactant: Cc1cc(C(F)(F)F)cc(=O)n1C
Solvent: O=C(O)C(F)(F)F
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: Cc1cc(C(F)(F)F)c(I)c(=O)n1C
Temperature: 25 °C
Reaction time: 15 h
Yield: 61.8 %

Procedure:
A mixture containing 1,6-dimethyl-4-(trifluoromethyl)-2-pyridone (2.1 g, 10.98 mmol), trifluoroacetic acid (18 mL) and trifluoroacetic anhydride (3.5 mL) was refluxed for 5 min. Then, NIS (3.15 g, 14 mmol) was added and the reaction mixture was stirred for 15 h. The reaction mixture was cooled to room temperature and the solvent was removed under vacuum. The residue was diluted with ethyl acetate (100 mL), was washed with saturated sodium bicarbonate solution (2×100 mL) and brine solution (100 mL) and was dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration gave a crude product, which was purified by silica gel chromatography on a Biotage (40m) column to afford 2.15 g (62% yield) of 1,6-dimethyl-3-iodo-4-(trifluoromethyl)-2-pyridone as an amorphous white solid. EI-HRMS m/e calcd for C8H7F3INO (M+) 316.9524, found 316.9527.
Reaction SMILES: [Si:1]([O:8][CH2:9][C@H:10]1[C@@H:14]([OH:15])[CH:13]=[CH:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(Cl)Cl.N1C=CN=C1.[Si:24](Cl)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]>>[C:4]([Si:1]([O:8][CH2:9][C@@H:10]1[CH2:11][CH:12]=[CH:13][C@@H:14]1[O:15][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])([CH3:3])[CH3:2])([CH3:7])([CH3:6])[CH3:5]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CC(C)(C)[Si](C)(C)OC[C@@H]1CC=C[C@@H]1O
Agent: c1c[nH]cn1
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OC[C@@H]1CC=C[C@@H]1O[Si](C)(C)C(C)(C)C
Reaction time: 18 h
Yield: 108.3 %

Procedure:
In an oven-dried 2 L two-neck flask, cooled under nitrogen, to a solution of (1S,5S)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopent-2-en-1-ol (11) (98.07 g, 0.3864 mol) in methylene chloride (500 mL, 8 mol) was added 1H-imidazole (31.57 g, 0.4637 mol). To the resulting yellow solution was added a solution of tert-butyldimethylsilyl chloride (58.2 g, 0.386 mol) in methylene chloride (300 mL, 5 mol) via addition funnel over ˜30 min. The mixture was stirred mechanically for 18 hours. The reaction was quenched via addition of water (500 mL) and the layers were separated. The organic layer was washed with water (2×500 mL), dried over MgSO4, filtered, and concentrated in vacuo to afford tert-butyl[((1S,2S)-2-{[tert-butyl(dimethyl)silyl]oxy}cyclopent-3-en-1-yl)methoxy]dimethylsilane (143.3 g) as a crude residue that was used without further purification.
Reaction SMILES: [OH:1][C:2]1[C:10]([CH:11]=[O:12])=[CH:9][C:8]([I:13])=[C:7]2[C:3]=1[CH:4]([O:24][CH3:25])[N:5]([C:15]([CH3:23])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:16])[C:6]2=[O:14].C(N(CC)CC)C.[CH3:33][S:34](Cl)(=[O:36])=[O:35]>ClCCl>[CH3:33][S:34]([O:1][C:2]1[C:10]([CH:11]=[O:12])=[CH:9][C:8]([I:13])=[C:7]2[C:3]=1[CH:4]([O:24][CH3:25])[N:5]([C:15]([CH3:16])([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH3:23])[C:6]2=[O:14])(=[O:36])=[O:35]
Reactant: COC1c2c(O)c(C=O)cc(I)c2C(=O)N1C(C)(C)c1ccccc1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC1c2c(OS(C)(=O)=O)c(C=O)cc(I)c2C(=O)N1C(C)(C)c1ccccc1
Yield: 100 %

Procedure:
In a similar manner to Step 1 of Example 289, 4-hydroxy-5-formyl-3-methoxy-7-iodo-2-(1-methyl-1-phenylethyl)isoindolinone (325 mg, 0.720 mmol) was dissolved in dichloromethane (10 mL), and the solution was treated with triethylamine (0.401 mL, 2.88 mmol) and methanesulfonyl chloride (0.111 mL, 1.43 mmol), followed by purification by flash column chromatography (hexane/ethyl acetate=95/5 to 80/20) to obtain 4-methanesulfonyloxy-5-formyl-3-methoxy-7-iodo-2-(1-methyl-1-phenylethyl)isoindolinone (381 mg, yield 58%).
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)=[N:4][C:5]([NH2:11])=[N:6][C:7]=1[S:8]([CH3:10])=O.SC[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=1.C1CCN2C(=NCCC2)CC1>O1CCOCC1>[Cl:1][C:2]1[C:3]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)=[N:4][C:5]([NH2:11])=[N:6][C:7]=1[S:8][CH2:10][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=1
Reactant: SCCc1ccccn1
Reactant: CS(=O)c1nc(N)nc(-c2ccco2)c1Cl
Solvent: C1CCC2=NCCCN2CC1
Solvent: C1COCCO1
Product: Nc1nc(SCCc2ccccn2)c(Cl)c(-c2ccco2)n1

Procedure:
From 5-chloro-4-furan-2-yl-6-methanesulfinyl-pyrimidin-2-yl-amine, 2-mercaptoethylpyridine and DBU in dioxane. ES-MS m/e (%): 335 (M{37Cl}+H+, 30), 333 (M{35Cl}+H+, 100).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C@:3]2([C:21]3[C:12](=[CH:13][C:14]4[O:19][CH2:18][CH2:17][O:16][C:15]=4[CH:20]=3)[O:11][CH2:10]2)[C:2]1=[O:22].N1C2C(=CC=CC=2)C2(C3=CC4OCOC=4C=C3OC2)C1=O.I[CH2:45][C@@H:46]1[CH2:51][O:50][CH2:49][CH2:48][O:47]1.CC1C=CC(S(OC[C@H]2COCCO2)(=O)=O)=CC=1>>[O:47]1[CH2:48][CH2:49][O:50][CH2:51][C@H:46]1[CH2:45][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C@:3]2([C:21]3[C:12](=[CH:13][C:14]4[O:19][CH2:18][CH2:17][O:16][C:15]=4[CH:20]=3)[O:11][CH2:10]2)[C:2]1=[O:22]
Reactant: O=C1Nc2ccccc2[C@@]12COc1cc3c(cc12)OCCO3
Reactant: IC[C@@H]1COCCO1
Agent: Cc1ccc(S(=O)(=O)OC[C@H]2COCCO2)cc1
Agent: O=C1Nc2ccccc2C12COc1cc3c(cc12)OCO3
Product: O=C1N(C[C@@H]2COCCO2)c2ccccc2[C@@]12COc1cc3c(cc12)OCCO3

Procedure:
Following the procedure as described in EXAMPLE 8 and making non-critical variations using (R)-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one to replace spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one, and (S)-2-(iodomethyl)-1,4-dioxane (Kim, H. Y. et al., Bioorg. Med. Chem. Lett. (2005), 15:3207-11) to replace (R)-(1,4-dioxan-2-yl)methyl 4-methylbenzenesulfonate, (8R)-1′-[(2R)-1,4-dioxan-2-ylmethyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one was obtained (51%) as a colorless solid: mp 198-199° C. (diethyl ether/hexanes); 1H NMR (300 MHz, CDCl3) δ7.30 (ddd, J=7.8, 7.8, 1.1 Hz, 1H), 7.16 (d, J=7.8 Hz, 1H), 7.08-7.02 (m, 2H), 6.49 (s, 1H), 6.24 (s, 1H), 4.88 (d, J=9.0 Hz, 1H), 4.64 (d, J=9.0 Hz, 1H), 4.22-4.16 (m, 2H), 4.13-4.08 (m, 2H), 3.98-3.78 (m, 4H), 3.75-3.56 (m, 4H), 3.47-3.38 (m, 1H); 13C NMR (75 MHz, CDCl3) δ177.9, 155.3, 144.7, 142.7, 138.4, 132.4, 128.9, 123.8, 123.5, 121.3, 111.7, 109.6, 99.5, 80.1, 73.3, 69.2, 66.7, 66.5, 64.6, 64.0, 58.1, 41.8; MS (ES+) m/z 396.0 (M+1).