Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[Si:11]([O:18][CH2:19][CH:20]([CH2:23][CH:24]=[CH2:25])[CH2:21]O)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12].C(N(CC)CC)C.[CH3:33][O:34][C:35]([CH:37]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:36]>C(Cl)Cl>[Si:11]([O:18][CH2:19][CH:20]([CH2:23][CH:24]=[CH2:25])/[CH:21]=[CH:37]/[C:35]([O:34][CH3:33])=[O:36])([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12]
Reactant: C=CCC(CO)CO[Si](C)(C)C(C)(C)C
Reactant: COC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C(Cl)C(=O)Cl
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=CCC(/C=C/C(=O)OC)CO[Si](C)(C)C(C)(C)C
Temperature: -78 °C

Procedure:
Dimethyl sulfoxide (4.71 mL, 66.3 mmol) was added to a methylene chloride solution (70 mL) of oxalyl chloride (2.84 mL, 33.2 mmol) with stirring at −78° C., and the mixture was stirred at this temperature for 5 minutes. Then, a methylene chloride solution (30 mL) of 2-({[tert-butyl(dimethyl)silyl]oxy}methyl)pent-4-en-1-ol (J. Chem. Soc., Perkin Trans. 1 1991, 2073) (5.10 g, 22.1 mmol) was added thereto. The mixture was stirred at this temperature for 15 minutes. Then, triethylamine (12.3 mL, 88.4 mmol) was added thereto, and the mixture was heated to room temperature and stirred. The mixture was separated into aqueous and organic layers by the addition of 0.1 M hydrochloric acid. The organic layer was washed with 0.1 M hydrochloric acid, water, and saturated saline and then dried over anhydrous magnesium sulfate. The residue was filtered and concentrated under reduced pressure, and the obtained residue was dissolved in toluene (50 mL). To the solution, (methoxycarbonylmethylene)triphenylphosphorane (11.1 g, 33.2 mmol) was added, and the mixture was stirred at room temperature for 4 hours and further stirred at 60° C. for 2 hours. The reaction solution was concentrated under reduced pressure, then filtered through Celite, and concentrated again under reduced pressure. Then, the obtained crude product was purified by silica gel column chromatography to obtain the compound of interest as an oil substance (5.69 g, 91%).
Reaction SMILES: [CH3:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([N+:13]([O-])=O)[C:3]=1[NH:4][CH2:5][CH2:6][S:7][CH3:8].O.O.[Sn](Cl)Cl.Cl.C1N=CN([C:27](N2C=NC=C2)=[O:28])C=1>C(O)C>[CH3:1][C:2]1[C:3]2[N:4]([CH2:5][CH2:6][S:7][CH3:8])[C:27](=[O:28])[NH:13][C:9]=2[CH:10]=[CH:11][CH:12]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CSCCNc1c(C)cccc1[N+](=O)[O-]
Agent: Cl
Agent: Cl[Sn]Cl
Solvent: O
Solvent: CCO
Product: CSCCn1c(=O)[nH]c2cccc(C)c21
Temperature: 25 °C
Reaction time: 12 h
Yield: 67.5 %

Procedure:
To a solution of 2-methyl-N-[2-(methylthio)ethyl]-6-nitroaniline (2.6 g, 12 mmol) in ethanol (6.0 mL) was added a solution of Tin(II) chloride dihydrate (7.9 g, 35 mmol) in concd. hydrochloric acid (8.0 mL) at 0° C. and warmed to rt. After 4h, the reaction was quenched by addition of 6N sodium hydroxide (100 mL) and extracted with ethyl acetate (100 mL×2), dried over sodium sulfate, filtered and concentrated. The crude material was dissolved in THF (50 mL) and to this solution was added CDI (2.3 g, 14 mmol) and the mixture was stirred at rt. After 12 h, to the mixture was added CDI (1.5 g, 6.7 mmol) and the reaction mixture was refluxed for 5 h. Then the mixture was cooled to rt and evaporated to dryness. To this was added water (100 mL) and extracted with ethyl acetate (100 mL×2). The combined organic layers were washed with water (50 mL), brine (50 mL), dried over sodium sulfate, filtered and concentrated. The obtained material was dissolved in methanol (30 mL) and to this solution was added 2N sodium hydroxide (3 mL) and stirred at rt for 2 h. Then the mixture was quenched by addition of sat. aq. sodium bicarbonate (50 mL) and extracted with ethyl acetate (100 mL×2). The combined organic layers were washed with water (50 mL), brine (50 mL), dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel eluting with dichloromethane/methanol (20/1-10/1) to afford 1.8 g (69%) of the title compound.
Reaction SMILES: Br[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[CH:23](/B(O)O)=[CH:24]\[CH2:25][CH2:26][CH2:27][CH3:28].C(Cl)Cl.CO.[NH4+].[OH-]>>[CH:23](/[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1)=[CH:24]\[CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: CCCC/C=C/B(O)O
Reactant: CC(C)(C)OC(=O)NCCCNc1ccc2ncc(Br)n2n1
Agent: [NH4+]
Agent: [OH-]
Solvent: CO
Solvent: ClCCl
Product: CCCC/C=C/c1cnc2ccc(NCCCNC(=O)OC(C)(C)C)nn12

Procedure:
Prepared from the product from step A and (E)-1-hexeneboronic acid according to general procedure 2 providing the crude Boc-protected olefin (122 mg, 96%) as a brown oil: Rf=0.71 (CH2Cl2/MeOH/NH4OH, 160:18:2); 1H NMR (500 MHz, CD3OD) δ 7.78 (d, J=9.7 Hz, 1H), 7.54 (s, 1H), 6.64-6.40 (m, 3H), 3.47 (q, J=6.3 Hz, 2H), 3.29-3.23 (m, 2H), 2.36-2.30 (m, 2H), 1.84-1.81 (m, 2H), 1.50-1.42 (m, 11H), 1.40-1.48 (m, 2H), 0.93 (t, J=7.3 Hz, 3H).
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13].[Li]C(C)(C)C.[CH3:26][S:27]SC>CCOCC>[CH3:26][S:27][C:5]1[N:6]([Si:11]([CH:15]([CH3:16])[CH3:17])([CH:12]([CH3:14])[CH3:13])[CH:18]([CH3:20])[CH3:19])[C:7]2[C:3]([CH:4]=1)=[CH:2][CH:10]=[CH:9][CH:8]=2
Reactant: CC(C)[Si](C(C)C)(C(C)C)n1ccc2c(Br)cccc21
Reactant: CSSC
Agent: [Li]C(C)(C)C
Solvent: CCOCC
Product: CSc1cc2ccccc2n1[Si](C(C)C)(C(C)C)C(C)C
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 97.8 %

Procedure:
To a solution of the indole of Step 2 (2.9 g, 8 mmol) in Et2O (50 mL) at −78° C. was added t-BuLi (11 mL, 18 mmol). The reaction mixture was stirred for 10 minutes at −78° C. and dimethyl disulfide (2.3 g, 25 mmol) was added. The reaction mixture was stirred for 30 minutes and the reaction was quenched with water. The phases were separated and the aqueous layer was extracted with Et2O. The combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography eluted with 5% EtOAc in Hexanes to provide 2.5 g of the title compound as a colorless oil.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:15]=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[CH3:16]O>>[CH3:16][O:12][C:11](=[O:13])[C:10]1[CH:14]=[CH:15][C:7]([CH:4]2[CH2:5][CH2:6][NH:1][CH2:2][CH2:3]2)=[CH:8][CH:9]=1
Reactant: CO
Reactant: O=C(O)c1ccc(C2CCNCC2)cc1
Product: COC(=O)c1ccc(C2CCNCC2)cc1

Procedure:
4-Piperidin-4-yl-benzoic acid (47 mmol) is dissolved in methanol (300 ml) and 1 ml of concentrated sulfonic acid is added. The mixture is heated under reflux overnight. After evaporation of the solvent, the residue is dissolved in a mixture of water and sodium carbonate (to ensure basic conditions) and extracted three times with ethyl acetate. The combined extract is dried over sodium sulfate and evaporated. A brown powder with Rf=0.18 (CH2Cl2/MeOH=9:1) is obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH:9]([C:13]([OH:15])=O)[CH2:10]2)=[CH:5][CH:4]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][C:18]=1[C:24]([F:27])([F:26])[F:25].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl>CN(C=O)C>[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH:21][C:13]([CH:9]2[CH2:8][CH2:7][C:6]3[C:11](=[CH:12][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[CH2:10]2)=[O:15])=[CH:19][C:18]=1[C:24]([F:25])([F:26])[F:27]
Reactant: Nc1ccc(Cl)c(C(F)(F)F)c1
Reactant: COc1ccc2c(c1)CC(C(=O)O)CC2
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc2c(c1)CC(C(=O)Nc1ccc(Cl)c(C(F)(F)F)c1)CC2
Temperature: 25 °C
Reaction time: 18 h
Yield: 50.2 %

Procedure:
To a solution of 7-methoxy-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (250 mg, 1.21 mmol), and 4-chloro-3-(trifluoromethyl)aniline (260 mg, 1.33 mmol) in DMF (12.0 mL) was added DIPEA (1.06 mL, 6.07 mmol) and then HATU (508 mg, 1.34 mmol). The solution was allowed to stir at rt for 18 h. 1N HCl was added and the mixture was extracted with EtOAc. The organic solution was washed with saturated NaHCO3 solution and brine, dried over Na2SO4, filtered and evaporated. The residue was purified by column chromatography to give N-[4-chloro-3-(trifluoromethyl)phenyl]-7-methoxy-1,2,3,4-tetrahydronaphthalene-2-carboxamide as a white solid (233 mg, 50%). LCMS: (FA) ES+ 384.1, ES− 382.1.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[CH:12]([O:15][CH3:16])[O:13][CH3:14])[NH:8][CH2:7][CH2:6][CH2:5]2.[CH3:17][CH:18]1[CH2:22][CH2:21][NH:20][C:19]1=[O:23].[O-]P([O-])([O-])=O.[K+].[K+].[K+].N[C@@H]1CCCC[C@H]1N>O1CCOCC1.C(OCC)(=O)C.O.[Cu]I>[CH3:14][O:13][CH:12]([O:15][CH3:16])[C:11]1[C:2]([N:20]2[CH2:21][CH2:22][CH:18]([CH3:17])[C:19]2=[O:23])=[CH:3][C:4]2[CH2:5][CH2:6][CH2:7][NH:8][C:9]=2[N:10]=1
Reactant: CC1CCNC1=O
Reactant: COC(OC)c1nc2c(cc1Br)CCCN2
Agent: [Cu]I
Agent: N[C@@H]1CCCC[C@H]1N
Agent: O=P([O-])([O-])[O-]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Solvent: O
Product: COC(OC)c1nc2c(cc1N1CCC(C)C1=O)CCCN2
Temperature: 120 °C
Reaction time: 10 h

Procedure:
A suspension of 6-bromo-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (intermediate 12, 150 mg, 0.522 mmol), (racemic) 3-methylpyrrolidin-2-one (75 mg, 0.719 mmol), K3PO4 (235 mg, 1.107 mmol) and CuI (10 mg, 0.053 mmol) in dioxane (1 ml) was heated to 120° C. for 135 min. The reaction mixture was cooled to room temperature, (1R,2R)-(−)-1,2-diaminocyclohexane (7 μL, 0.058 mmol) was added and the mixture was heated to 120° C. and stirred for 10 h. The reaction mixture was diluted with ethyl acetate and water, layers were separated and the aqueous layer was extracted with ethyl acetate. Organic layers were combined, washed with water and brine, dried using Na2SO4, filtered, evaporated. The crude product was purified by silica gel column chromatography eluting with a gradient of MeOH (1-10%) in DCM. Product fractions were combined, evaporated and dried to yield the title compound as a brown solid. (UPLC-MS 3) tR 0.55 min; ESI-MS 306.1 [M+H]+.
Reaction SMILES: [C:1]1(=[O:29])[N:5]([CH:6]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][CH3:21])=[C:13]([O:22][CH3:23])[CH:12]=2)[CH2:7][C:8](O)=[O:9])[C:4](=[O:24])[C:3]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:2]12.C(C1NC=CN=1)(C1[NH:33]C=CN=1)=O>>[C:1]1(=[O:29])[N:5]([CH:6]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][CH3:21])=[C:13]([O:22][CH3:23])[CH:12]=2)[CH2:7][C:8]([NH2:33])=[O:9])[C:4](=[O:24])[C:3]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:2]12
Reactant: O=C(c1ncc[nH]1)c1ncc[nH]1
Reactant: CCCCOc1ccc(C(CC(=O)O)N2C(=O)c3ccccc3C2=O)cc1OC
Product: CCCCOc1ccc(C(CC(N)=O)N2C(=O)c3ccccc3C2=O)cc1OC

Procedure:
The procedure of Example 65 is utilized starting with 3-phthalimido-3-(4'-butoxy-3'-methoxyphenyl)propionic acid and carbonyl diimidazole to afford 0.742 g (74%) of crude product as a pale yellow powder. The crude product was recrystallized from ethyl acetate (16 mL) to afford 0.517 (52%) of 3-phthalimido-3-(4'-butoxy-3'-methoxyphenyl)propionamide as fine fluffy white needles: HPLC 99.1%; 1H NMR (DMSO-d6) δ 7.95-7.75 (m, 4 H, Ar), 7.54 (br s, 1 H, CONH), 7.04 (s, 1 H, Ar), 7.0-6.75 (m, 2 H), 6.86 (br s, 1 H, CONH), 5.67 (t, 1 H, J=8 Hz), 3.90 (t, 2 H, J=6 Hz), 3.73 (s, 3 H), 3.20 (d, 1 H, J=8 Hz, CH2CO), 1.8-1.55 (m, 2 H) 1.5-1.3 (m, 2 H), 0.91 (t, 3 H, J=7 Hz); 13C NMR (DMSO-d6) δ 171.2, 167.6, 148.8, 147.7, 134.5, 131.6, 131.2, 123.0, 119.4, 112.8, 111.4, 67.8, 55.5, 50.3, 36.9, 30.7, 18.6, 13.6.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][N:5]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH:7][C:6]1=[O:16].[CH3:17][C:18](OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=[O:19]>>[CH3:1][O:2][CH2:3][CH2:4][N:5]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:7]([C:18](=[O:19])[CH3:17])[C:6]1=[O:16]
Reactant: COCCn1cc(-c2ccccc2)[nH]c1=O
Reactant: CC(=O)OCc1c2ccccc2c(COC(C)=O)c2ccccc12
Product: COCCn1cc(-c2ccccc2)n(C(C)=O)c1=O

Procedure:
Approximately 21.8 g of 1-(2-methoxyethyl)-4-phenyl-4-imidazolin-2-one and 120 ml. of acetic anhyride is refluxed together for four hours. The acetic anhydride is distilled out at reduced pressure. The residual semisolid is recrystallized from ether to yield the title compound as a white solid; m.p. 73°-75° C.
Reaction SMILES: Br[C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[O:4][CH2:5][C:6]([N:8]([CH:18]([CH3:20])[CH3:19])[NH:9][C:10](=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7].C([O-])([O-])=O.[Na+].[Na+].[CH2:32]([O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1B(O)O)[CH3:33]>COCCOC>[CH2:32]([O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[O:4][CH2:5][C:6]([N:8]([CH:18]([CH3:20])[CH3:19])[NH:9][C:10](=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])[CH3:33]
Reactant: CCOc1ccccc1B(O)O
Reactant: CC(C)N(NC(=O)c1ccccc1)C(=O)COc1ccc(F)cc1Br
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: CCOc1ccccc1-c1cc(F)ccc1OCC(=O)N(NC(=O)c1ccccc1)C(C)C
Yield: 29.1 %

Procedure:
A solution of benzoic acid N′-[2-(2-bromo-4-fluoro-phenoxy)-acetyl]-N′-isopropyl-hydrazide (50 mg, 0.122 mmol) in DME (3 ml)/2M Na2CO3 (0.215 ml, 0.427 mmol) was treated with 2-ethoxyphenylboronic acid (31 mg, 0.183 mmol) and Pd[PPh3]4 (28 mg, 0.0244 mmol) for 12 hours at 90° C. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude was absorbed on silica and purified on a silica gel column with a 30-50% ethyl acetate in hexanes gradient to afford the product as a white solid (16 mg, 29%). MS m/e 451.23 (M+H+)
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([N+:14]([O-:16])=[O:15])=[C:9]([CH:13]=1)[C:10](Cl)=[O:11].[P:25]([O:34]C(C)C)([O:30][CH:31]([CH3:33])[CH3:32])[O:26][CH:27]([CH3:29])[CH3:28].P([O-])([O-])[O-]>CCOCC>[Cl:1][C:2]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([N+:14]([O-:16])=[O:15])=[C:9]([CH:13]=1)[C:10]([P:25](=[O:34])([O:30][CH:31]([CH3:33])[CH3:32])[O:26][CH:27]([CH3:29])[CH3:28])=[O:11]
Reactant: CC(C)OP(OC(C)C)OC(C)C
Reactant: O=C(Cl)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Agent: [O-]P([O-])[O-]
Solvent: CCOCC
Product: CC(C)OP(=O)(OC(C)C)C(=O)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Reaction time: 2 h

Procedure:
To a stirred solution of 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoyl chloride (3.8 g, 0.01 mole) in ether (100 ml) was added triisopropyl phosphite (2.1 g, 0.01 mole). The reaction was refluxed for one hour and the disappearance of phosphite monitored by v.p.c.. The ether was stripped off and the resulting oil placed under vacuum (1.0 mm) at 40° C. for two hours. The resulting amber liquid amounted to 5.2 g.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[C:8]3[C:9]([C:14](=[O:23])[N:15]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[N:16]=3)=[CH:10][NH:11][C:12]=2[CH:13]=1)([O-:3])=[O:2].[Cl:24]C1C2C(=CC([N+]([O-])=O)=CC=2)N=CC=1C(OCC)=O.ClC1C=CC(NN)=CC=1>>[Cl:24][C:20]1[CH:21]=[CH:22][C:17]([N:15]2[C:14](=[O:23])[C:9]3=[CH:10][NH:11][C:12]4[CH:13]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=[CH:6][C:7]=4[C:8]3=[N:16]2)=[CH:18][CH:19]=1
Reactant: O=c1c2c[nH]c3cc([N+](=O)[O-])ccc3c-2nn1-c1ccccc1
Reactant: CCOC(=O)c1cnc2cc([N+](=O)[O-])ccc2c1Cl
Agent: NNc1ccc(Cl)cc1
Product: O=c1c2c[nH]c3cc([N+](=O)[O-])ccc3c-2nn1-c1ccc(Cl)cc1

Procedure:
The title compound was prepared following the procedure described for 12a using 11a and 4-chlorophenylhydrazine. 1H-NMR (DMSO-d6) δ (ppm): 7.48 (2H, d, m), 8.20 (2H, m), 8.26 (1H, dd, J=8.61, 2.08 Hz), 8.40 (1H, d, J=8.61 Hz), 8.52 (1H, d, J=2.08 Hz), 8.92 (1H, s). m/z 341.8 (MH+).
Reaction SMILES: [Cl:1]([O-:3])=[O:2].[Na+:4].[P:5]([O-:9])([OH:8])([OH:7])=[O:6].[Na+].[Cl:11][C:12]1[CH:20]=[C:19]2[C:15]([C:16]([CH:21]=[O:22])=[CH:17][NH:18]2)=[CH:14][C:13]=1[C:23]1[CH:28]=[N:27][C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:25][N:24]=1.CC(=CC)C.S([O-])([O-])=[O:41].[Na+].[Na+]>O.C(OCC)(=O)C.C(O)(C)(C)C.C1COCC1>[Cl:1]([O-:3])=[O:2].[Na+:4].[P:5]([O-:9])([OH:8])([OH:7])=[O:6].[Na+:4].[Cl:11][C:12]1[CH:20]=[C:19]2[C:15]([C:16]([C:21]([OH:41])=[O:22])=[CH:17][NH:18]2)=[CH:14][C:13]=1[C:23]1[CH:28]=[N:27][C:26]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)=[CH:25][N:24]=1
Reactant: O=Cc1c[nH]c2cc(Cl)c(-c3cnc(-c4ccccc4)cn3)cc12
Reactant: O=S([O-])[O-]
Agent: CC=C(C)C
Agent: O=P([O-])(O)O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC(C)(C)O
Solvent: C1CCOC1
Product: O=C(O)c1c[nH]c2cc(Cl)c(-c3cnc(-c4ccccc4)cn3)cc12
Temperature: 30 °C
Reaction time: 0.25 h

Procedure:
A solution of 2.5M/2.65M of sodium chlorite/sodium dihydrogen phosphate in water was prepared and 1.0 mL (2.5 mmol sodium chlorite and 2.6 mmol sodium dihydrogen phosphate) was added to a vial containing 6-chloro-5-(5-phenylpyrazin-2-yl)-1H-indole-3-carbaldehyde, 1.0 mL THF, 0.5 mL t-butanol, 0.5 mL 2-methyl-2-butene, and sealed then heated to 30° C. for 3 hours. Sodium sulfite (315 mg, 2.50 mmol) was then added and the mixture stirred for 15 min. Ethyl acetate was then added to extract (3×1 mL). The organic layer was separated and solvents removed by speedvac. The residue was purified by reverse phase HPLC to give the title compound. MS (AP−) 348 (M−H)−. RT=2.093 Column Xbridge C18 2.1×50 mm 5 μm, Temperature 50° C. Mobile Phase A=0.05% NH4OH in water. Mobile Phase B=100% acetonitrile. Gradient: Initial 5% B Time 0.00 mins, 5% B Time 0.50 mins, 5% B Time 3.40 mins, 100% B Time 4.20 mins, 100% B Time 4.21 mins, 5% B Time 4.70 mins, 5% B Flow rate, 0.8 mL/min Injection volume 2 μL. Agilent 1200 HPLC/1956 MSD/SEDEX 75 ELSD Ionization Mode API-ES Polarity Negative.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:27][CH2:28][S:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)/[C:9](/[F:26])=[C:10](\[F:25])/[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:13]=2)=[CH:4][CH:3]=1.ClC1C=CC=C(C(OO)=[O:44])C=1>C(Cl)Cl>[C:30]1([S:29]([CH2:28][CH2:27][CH:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)/[C:9](/[F:26])=[C:10](\[F:25])/[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:13]=2)=[O:44])[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: F/C(Cc1cccc(Oc2ccccc2)c1)=C(/F)C(CCSc1ccccc1)c1ccc(Cl)cc1
Solvent: ClCCl
Product: O=S(CCC(/C(F)=C(\F)Cc1cccc(Oc2ccccc2)c1)c1ccc(Cl)cc1)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.7 %

Procedure:
To a stirred solution of 1-[(2E)-4-(4-chlorophenyl)-2,3-difluoro-6-(phenylsulfanyl)-2-hexenyl]-3-phenoxybenzene (0.311 g, 0.61 mmol) in methylene chloride (13 ml) under nitrogen was added dropwise a solution of m-chloroperbenzoic acid (m-CPBA; 0.13 g, 0.65 mmol) in methylene chloride (2 ml) over one minute. The reaction mixture was stirred at room temperature for two hours, diluted with methylene chloride (50 ml) and washed successively with saturated aqueous sodium bicarbonate and water. The organic solution was dried over anhydrous sodium sulfate and concentrated in vacuo to afford the title compound as a colorless syrup (0.318 g), which was characterized by IR, 1HNMR, 19FNMR and mass spectral analysis, and used without further purification.
Reaction SMILES: OC1C=CC(C(C2C=CC(O)=CC=2)(C)C)=CC=1.ClC[Si](CCl)(C)O[Si](C)(C)C.C([O-])([O-])=O.[K+].[K+].[N+]([C:38]1[CH:39]=[C:40]([C:46]#[N:47])[C:41](=[CH:44][CH:45]=1)[C:42]#[N:43])([O-])=O.Cl>O.CS(C)=O>[C:46](#[N:47])[C:40]1[C:41](=[CH:44][CH:45]=[CH:38][CH:39]=1)[C:42]#[N:43]
Reactant: N#Cc1ccc([N+](=O)[O-])cc1C#N
Agent: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Agent: C[Si](C)(C)O[Si](C)(CCl)CCl
Agent: Cl
Solvent: O
Solvent: CS(C)=O
Product: N#Cc1ccccc1C#N
Temperature: 90 °C

Procedure:
To a 2000 mL, three-necked flask fitted with a thermometer and a nitrogen inlet were added bisphenol A (100 g, 0.298 mol), bis(chloromethyl)tetramethyl disiloxane (50.1 g, 0.217 mol), powdered anhydrous K2CO3 (150 g, 1.09 mol), and dimethylsulfoxide (DMSO) (1000 mL). The resulting mixture was degassed with nitrogen at ambient temperature and heated at 90° C. under a nitrogen atmosphere for 8-16 hr. The mixture was cooled to 50° C. At this time, 4-nitrophthalonitrile (77.7 g, 0.449 mol) was added in one portion and the reaction mixture was heated at 80° C. for 6-8 hr. The mixture was allowed to cool to ambient temperature and poured into 1000 mL of distilled water. The mixture was made acidic by the addition of 6 M aqueous HCl and the resin was extracted out of the water layer by toluene (200 mL). The toluene extracts were washed 3 times with 500 mL of distilled water and dried using magnesium sulfate. Removal of the toluene resulted in an amber oil, which was dried at 80° C. under vacuum. The 2:1 oligomeric phthalonitrile was isolated as an amber glassy solid (179 g, 94%). 1H-NMR [CDCl3]: λ 7.72 (m, aromatic-HR), 7.67 (m, aromatic-HR), 7.34 (m, aromatic-HR), 7.08 (m, aromatic-HR), 6.97 (m, aromatic-HR), 6.86 (m, aromatic-HR), 3.76 (m, aliphatic-HR), 3.50 (m, aliphatic-HR), 1.71 (s, aliphatic-HR), 1.64 (s, aliphatic-HR), 1.61 (s, aliphatic-HR), 0.20 (s, Si—CH3), 0.05 (s, Si−CH3).
Reaction SMILES: [CH2:1]([O:4][CH2:5][C:6]([CH2:17][OH:18])([CH2:12][O:13][CH2:14][CH:15]=[CH2:16])[CH2:7][O:8][CH2:9][CH:10]=[CH2:11])[CH:2]=[CH2:3].C(N(CC)CC)C.[C:26]1([CH:34]=[CH:35][C:36](Cl)=[O:37])[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[CH:27]=1>C1(C)C=CC=CC=1>[CH2:9]([O:8][CH2:7][C:6]([CH2:17][OH:18])([CH2:12][O:13][CH2:14][CH:15]=[CH2:16])[CH2:5][O:4][CH2:1][CH:2]=[CH2:3])[CH:10]=[CH2:11].[C:26]1([CH:34]=[CH:35][C:36]([OH:37])=[O:4])[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[CH:27]=1
Reactant: O=C(Cl)C=CC1=Cc2ccccc21
Agent: C=CCOCC(CO)(COCC=C)COCC=C
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: O=C(O)C=CC1=Cc2ccccc21
Temperature: 90 °C
Reaction time: 72 h

Procedure:
A 1000 mL three necked round bottomed flask outfitted with a mechanical stirrer (Teflon paddle), a pressure equalizing addition funnel was charged with pentaerythritol triallyl ether (NEOALLYL P-30) (111.9 g, 436.5 mmol), toluene (300 mL) and triethylamine (56.61 g, 559.4 mmol). The addition funnel was charged with a solution of BCB-AA acid chloride (88.96 g, 461.8 mmol) from Example 6 in toluene (100 mL), which was then added dropwise to the reaction mixture over 45 min. The solution was then heated to 90° C. for 9.5 hr. The solution was then filtered through a 38 mm (1.5 inch) thick silica gel plug on a 350 mL fritted glass funnel. Hexane:ethyl acetate (80:20, 200 mL) was used as the washing solvent. The filtrate was condensed to afford an orange colored viscous oil, which was taken up in hexanes (300 mL) and placed into a freezer for 3 days. The solution was filtered and condensed to afford the product as a viscous dark yellow colored oil. Yield: 178.0 g (93.97%). 1H NMR (500 MHz, Chloroform-d) δ 7.67 (dd, J=15.9, 3.1 Hz, 1H), 7.36 (dd, J=7.6, 1.5 Hz, 1H), 7.31-7.18 (m, 1H), 7.13-6.94 (m, 1H), 6.39 (d, J=16.0 Hz, 1H), 5.97-5.78 (m, 2H), 5.27 (dd, J=17.3, 1.7 Hz, 2H), 5.15 (dd, J=10.5, 1.6 Hz, 2H), 4.30 (s, 2H), 3.97 (d, J=5.4 Hz, 4H), 3.52 (s, 4H), 3.20 (s, 3H).
Reaction SMILES: [C:1]([NH2:4])(=[S:3])[CH3:2].[CH3:5][O:6][C:7](=[O:12])[C:8](=O)[CH2:9]Cl>CC#N>[CH3:5][O:6][C:7]([C:8]1[N:4]=[C:1]([CH3:2])[S:3][CH:9]=1)=[O:12]
Reactant: COC(=O)C(=O)CCl
Reactant: CC(N)=S
Solvent: CC#N
Product: COC(=O)c1csc(C)n1
Reaction time: 5 h

Procedure:
A solution of thioacetamide (132 mmol, 1.0 eq) in MeCN (250 mL) is added to a mixture of the respective 3-chloro-2-oxo-propionic acid methyl ester derivative (132 mmol, 1.0 eq) and molecular sieves (4 Å, 12 g) in MeCN (60 mL). After stirring for 5 h the mixture is cooled in an ice-bath and the obtained precipitate is filtered off. The residue is washed with cold MeCN, dried, dissolved in MeOH (280 mL) and stirred at 50° C. for 6 h. The solvents are removed in vacuo to give the corresponding 2-methyl-thiazole-4-carboxylic acid methyl ester derivatives.