Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:5][C:6](=[O:18])[CH2:7][NH:8][C:9](=[O:17])[C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)(C)(C)C.[F:19][C:20]([F:31])([F:30])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28]O)=[CH:23][CH:22]=1>>[F:19][C:20]([F:30])([F:31])[C:21]1[CH:22]=[CH:23][C:24]([CH2:27][CH2:28][O:16][C:13]2[CH:12]=[CH:11][C:10]([C:9]([NH:8][CH2:7][C:6]([OH:5])=[O:18])=[O:17])=[CH:15][CH:14]=2)=[CH:25][CH:26]=1
Reactant: CC(C)(C)OC(=O)CNC(=O)c1ccc(O)cc1
Reactant: OCCc1ccc(C(F)(F)F)cc1
Product: O=C(O)CNC(=O)c1ccc(OCCc2ccc(C(F)(F)F)cc2)cc1
Yield: 75.7 %

Procedure:
The same reaction as in Example 1 (1b) was conducted using N-(4-hydroxybenzoyl)glycine tert-butyl ester (251 mg, 1.00 mmol) prepared in Example 1 (1a) and 2-[4-(trifluoromethyl)phenyl]ethanol (209 mg, 1.10 mmol) prepared according to the method disclosed in the document (J. Med. Chem., (2002), 45, 4321-4335) to give 278 mg of the title compound (white powder, yield: quantitative).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[NH:9][C:10]([C:12]1[N:16]([CH3:17])[N:15]=[C:14]([CH3:18])[CH:13]=1)=[O:11].Br[C:20]1[CH:21]=[CH:22][C:23]([N+:26]([O-:28])=[O:27])=[N:24][CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O>O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:20]2[CH:25]=[N:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)=[CH:4][C:3]=1[NH:9][C:10]([C:12]1[N:16]([CH3:17])[N:15]=[C:14]([CH3:18])[CH:13]=1)=[O:11]
Reactant: Cc1cc(C(=O)Nc2cc(O)ccc2F)n(C)n1
Reactant: O=[N+]([O-])c1ccc(Br)cn1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1cc(C(=O)Nc2cc(Oc3ccc([N+](=O)[O-])nc3)ccc2F)n(C)n1
Temperature: 25 °C
Reaction time: 15 h
Yield: 58.9 %

Procedure:
A mixture of N-(2-fluoro-5-hydroxyphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide (9.80 g, 39.3 mmol), 5-bromo-2-nitropyridine (7.14 g, 35.1 mmol), cesium carbonate (14.8 g, 45.3 mmol) and N,N-dimethylformamide (80 mL) was stirred at room temperature for 15 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel, hexane/ethyl acetate=90/10→0/100) to give N-{2-fluoro-5-[(6-nitropyridin-3-yl)oxy]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide (7.68 g, 59%) as a white solid. To a solution of N-{2-fluoro-5-[(6-nitropyridin-3-yl)oxy]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide (7.68 g, 20.7 mmol) thus-obtained in methanol (50 mL) was added palladium carbon (50% water-containing product, 700 mg), and the mixture was stirred under a hydrogen atmosphere at room temperature for 2 hr. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was collected by filtration and washed with ethyl acetate-hexane to give the title compound (6.20 g, 88%) as a white solid.
Reaction SMILES: [BH4-].[Na+].[CH2:3]([O:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]=1[CH2:16][C:17]1[C:18]([CH2:34][CH3:35])=[N:19][N:20]([C:24]2[C:31]([CH3:32])=[CH:30][C:27]([CH:28]=[O:29])=[CH:26][C:25]=2[CH3:33])[C:21]=1[CH2:22][CH3:23])[CH3:4]>CO>[CH2:3]([O:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]=1[CH2:16][C:17]1[C:18]([CH2:34][CH3:35])=[N:19][N:20]([C:24]2[C:25]([CH3:33])=[CH:26][C:27]([CH2:28][OH:29])=[CH:30][C:31]=2[CH3:32])[C:21]=1[CH2:22][CH3:23])[CH3:4]
Reactant: CCOc1ccc2ccccc2c1Cc1c(CC)nn(-c2c(C)cc(C=O)cc2C)c1CC
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CCOc1ccc2ccccc2c1Cc1c(CC)nn(-c2c(C)cc(CO)cc2C)c1CC
Reaction time: 0.5 h
Yield: 13.2 %

Procedure:
Sodium borohydride (0.127 g, 3.35 mmol) was added to a solution of 4-[4-(2-ethoxy-naphthalen-1-ylmethyl)-3,5-diethyl-pyrazol-1-yl]-3,5-dimethyl-benzaldehyde (0.370 g, 8.4 mmol) in 10 ml of methanol. After stirring 30 minutes, the reaction was quenched by addition of 1 ml of brine. The solvent was removed in vacuo, and the residue was extracted with methylene chloride/brine (10 ml of each). The aqueous phase was then twice extracted with 10 ml portions of fresh methylene chloride. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo to afford an oil (490 mg). Flash chromatography of the entire sample (silica gel, 40 micron mesh; elution with ethyl acetate/hexanes=1:1 in volume) yielded the title compound (380 mg) as an oily colorless solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([NH2:12])[CH:5]=1.Cl.C(O)CCC.[C:20]1(Cl)[C:26](=O)[C:25](Cl)=[C:24](Cl)[C:22](=O)[C:21]=1Cl>O1CCCC1.[Cl-].[Zn+2].[Cl-]>[CH3:1][O:2][C:3]([C:4]1[C:5]2[CH:26]=[CH:20][C:21]([CH2:22][CH2:24][CH3:25])=[N:12][C:6]=2[C:7]([O:10][CH3:11])=[CH:8][CH:9]=1)=[O:13]
Reactant: COC(=O)c1ccc(OC)c(N)c1
Reactant: O=C1C(Cl)=C(Cl)C(=O)C(Cl)=C1Cl
Agent: Cl
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CCCCO
Solvent: C1CCOC1
Product: CCCc1ccc2c(C(=O)OC)ccc(OC)c2n1
Temperature: 25 °C
Yield: 10.5 %

Procedure:
Methyl-3-amino-4-methoxybenzoate (10.0 g) was treated with concentrated hydrochloric acid (14 ml) and n-butanol (10 ml), under nitrogen, with stirring. The stirred mixture was treated with p-chloranil (13.65 g) and then heated at reflux whilst a mixture of trans-2-hexanal (8 ml) and n-butanol (5 ml) was added dropwise over 2 hours using a syringe pump. After heating at reflux for a further 30 minutes the mixture was treated with a solution of anhydrous zinc chloride (7.52 g) in tetrahydrofuran (60 ml), then allowed to cool slowly to room temperature and then cooled to 0° C. for 18 hours. The reaction mixture was evaporated, then diluted with hydrochloric acid (1M) and then washed with diethyl ether. The pH of the solution was adjusted to 6 and the resulting emulsion was treated with ammonium hydroxide and the solution extracted with diethyl ether. The combined dark green extracts were dried over magnesium sulphate then evaporated. The resulting dark green oil was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (3:7, v/v) to give the title compound (1.5 g) as an orange oil. NMR(CDCl3): δ9.36(d,J=8.9 Hz,1 H), 8.26(d,J=8.4 Hz,1 H), 7.47(d,J=8.9 Hz,1 H), 7.03(d,J=8.4 Hz,1 H), 4.14(s,3 H), 3.97(s,3 H), 3.02(m,2 H), 1.86(m,2 H), 1.03(t,J=7.3 Hz,3 H).
Reaction SMILES: Br[CH:2]1[CH2:8][CH2:7][CH2:6][CH2:5][N:4]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:3]1=[O:21].N1C(C)=CC=CC=1C>C1(C)C=CC=CC=1>[CH2:9]([N:4]1[CH2:5][CH2:6][CH:7]=[CH:8][CH2:2][C:3]1=[O:21])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CCCCCCCCCCCCN1CCCCC(Br)C1=O
Solvent: Cc1cccc(C)n1
Solvent: Cc1ccccc1
Product: CCCCCCCCCCCCN1CCC=CCC1=O
Temperature: 25 °C

Procedure:
A solution of 10.0 g (28 mmol) of 3-bromo-1-dodecylazacycloheptan-2-one (Example 1-A) and 5.1 g 47 mmol) of 2,6-lutidine was refluxed for 3 hours. The reaction was cooled to room temperature, 100 ml of toluene was added, and the mixture was filtered. The filtrate was concentrated in vacuo and the residue subjected to flash chromatography (silica gel, 7:3 petroleum ether/EtOAc V/V) to yield the product as a white solid, Rf =0.5; Kuglerohr distilled at 155°-160° C./0.2 mm Hg.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.Br[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1>>[CH3:14][O:13][C:10]1[CH:11]=[CH:12][C:7]([C:2]2[O:1][CH:5]=[CH:4][N:3]=2)=[CH:8][CH:9]=1
Reactant: COc1ccc(Br)cc1
Reactant: c1cocn1
Product: COc1ccc(-c2ncco2)cc1
Yield: 8.5 %

Procedure:
The title compound (0.16 g, 33%) was prepared from oxazole (0.74 g, 10.7 mmol) and 4-bromoanisole (2.0 g, 10.7 mmol) using the procedure of Example 146, step 1; 1HNMR (400 MHz, CDCl3) δ 8.0 (d, J=9.2 Hz, 2H), 7.66 (d, J=1.2 Hz, 1H), 7.19 (d, J=0.8 Hz, 1H), 6.97 (d, J=8.8 Hz, 2H), 3.87 (s, 3H).
Reaction SMILES: Cl.Cl[CH2:3][CH2:4][NH2:5].C([O-])([O-])=O.[K+].[K+].[C:12]([C:16]1[CH:21]=[CH:20][C:19]([SH:22])=[CH:18][CH:17]=1)([CH3:15])([CH3:14])[CH3:13]>C(Cl)(Cl)Cl>[C:12]([C:16]1[CH:17]=[CH:18][C:19]([S:22][CH2:3][CH2:4][NH2:5])=[CH:20][CH:21]=1)([CH3:15])([CH3:13])[CH3:14]
Reactant: CC(C)(C)c1ccc(S)cc1
Reactant: NCCCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Product: CC(C)(C)c1ccc(SCCN)cc1
Temperature: 50 °C
Reaction time: 8 h
Yield: 74.1 %

Procedure:
To a stirring mixture of 4.36 g (38.0 mmol) of 2-chloroethylamine hydrochloride and 12.00 g (87.0 mmol) of K2CO3 in 30 mL of CHCl3 was added 4.82 g (29.0 mmol) of 4-t-butylbenzenethiol. The mixture was stirred at 50° C. in a sealed vial overnight. The mixture was washed three times with distilled water, dried with MgSO4 and filtered. Volatiles were removed in vacuo leaving 4.50 g (74%) of clear oil. 1H NMR (300 MHz, CDCl3): δ=7.32, m, 4H; 2.93, m, 4H; 1.42, broad singlet, 2H; 1.30, s, 9H.
Reaction SMILES: [OH:1][C@@H:2]1[CH:7]2[CH2:8][CH2:9][N:4]([CH2:5][CH2:6]2)[CH2:3]1.I[C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:13][CH:12]=1>>[O:17]([C:18]1[CH:19]=[CH:20][C:21]([O:1][C@@H:2]2[CH:7]3[CH2:8][CH2:9][N:4]([CH2:5][CH2:6]3)[CH2:3]2)=[CH:22][CH:23]=1)[C:14]1[CH:15]=[CH:16][CH:11]=[CH:12][CH:13]=1
Reactant: Ic1ccc(Oc2ccccc2)cc1
Reactant: O[C@H]1CN2CCC1CC2
Product: c1ccc(Oc2ccc(O[C@H]3CN4CCC3CC4)cc2)cc1

Procedure:
3-(R)-Hydroxy-quinuclidine (the product of Reference Example 1, 152 mg, 1.2 mmol), was coupled with 1-iodo-4-phenoxy-benzene (178 mg, 0.6 mmol) according to the procedure of Example 3A. The title product was purified by chromatography (SiO2, CH2Cl2:MeOH:NH3.H2O, 90:10:1, Rf. 0.20) as oil (25 mg, yield, 14%). 1H NMR (MeOH-d4, 300 MHz) δ 1.45–1.58 (m, 1H), 1.64–1.85 (m, 2H), 2.00–2.15 (m, 1H), 2.20–2.30 (m, 1H), 2.70–3.10 (m, 5H), 3.34–3.40 (m, 1H), 4.52 (m, 1H), 6.83–6.98 (m, 6H), 7.03 (tt, J=7.5, 1.0 Hz, 1H), 7.30 (t, J=7.5 Hz, 2H) ppm. MS (DC m/z 296 (M+H)+.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[Cl:12])[CH:7]=O)([O-:3])=[O:2].[Br-].[CH3:14][O:15][C:16]1[CH:17]=[C:18]([CH:39]=[C:40]([O:44][CH3:45])[C:41]=1[O:42][CH3:43])[CH2:19]P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[H-].[Na+].[Cl-].[Na+]>C1C=CC=CC=1.C(O)(=O)C>[N+:1]([C:4]1[CH:5]=[C:6](/[CH:7]=[CH:19]\[C:18]2[CH:39]=[C:40]([O:44][CH3:45])[C:41]([O:42][CH3:43])=[C:16]([O:15][CH3:14])[CH:17]=2)[CH:9]=[CH:10][C:11]=1[Cl:12])([O-:3])=[O:2]
Reactant: COc1cc(C[PH](c2ccccc2)(c2ccccc2)c2ccccc2)cc(OC)c1OC
Reactant: O=Cc1ccc(Cl)c([N+](=O)[O-])c1
Agent: [Br-]
Agent: [Cl-]
Agent: [H-]
Solvent: CC(=O)O
Solvent: c1ccccc1
Product: COc1cc(/C=C\c2ccc(Cl)c([N+](=O)[O-])c2)cc(OC)c1OC
Yield: 50.9 %

Procedure:
1.0 g of 3-nitro-4-chlorobenzaldehyde and 2.8 g of 3,4,5-trimethoxybenzyltriphenylphosphine bromide were dissolved in 50 ml of benzene, and a benzene solution containing 260 mg of sodium hydride dispersed therein was added thereto and reacted for 15 hours at room temperature. The reaction liquid was neutralized with acetic acid, saturated sodium chloride solution was added thereto, and the resulting liquid was extracted with dichloromethane. The extract was dried with anhydrous sodium sulfate, concentrated and then purified by silica gel column chromatography diethyl (ether:hexane--1:2 by volume) to obtain 0.95 g of the intended compound. The yield of the product was 50.4%.
Reaction SMILES: [Li][CH2:2]CCC.[F:6][C:7]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[CH:9][C:8]=1[C:15]1([CH3:20])[O:19]CCO1.IC.C(O)(=O)C>C1COCC1.CCOCC>[F:6][C:7]1[C:12]([CH3:2])=[C:11]([O:13][CH3:14])[CH:10]=[CH:9][C:8]=1[C:15](=[O:19])[CH3:20]
Reactant: COc1ccc(C2(C)OCCO2)c(F)c1
Reactant: [Li]CCCC
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: COc1ccc(C(C)=O)c(F)c1C
Reaction time: 0.5 h
Yield: 43.5 %

Procedure:
17.69 ml (1.6 M in n-hexane, 28.30 mmol) n-BuLi were added slowly to a cooled solution (−78° C.) of the above prepared 4.29 g (20.21 mmol) 2-(2-fluoro-4-methoxy-phenyl)-2-methyl-[1,3]-dioxolane in 100 ml THF. The reaction was stirred for 30 min at this temperature. 5.03 ml (80.86 mmol) of iodomethane were then added over 20 min and after 6 h at −78° C. the reaction was stopped with 3.24 ml (56.60 mmol) of acetic acid in 5 ml ether. The reaction mixture was taken up in ether and washed with aqueous 10% KHSO4 solution and aqueous 10% NaCl solution. The water phases were extracted with ether (two times). The organic phase was dried (Na2SO4) and evaporated. The crude product was dissolved in 30 ml dioxane and treated slowly with 6.74 ml of aqueous 6M HCl. After 2 h, the reaction was taken up in ether and washed with aqueous 10% NaCl solution (two times). The water phases were extracted with ether (two times). The organic phase was dried (Na2SO4), evaporated and purified by flash chromatography (SiO2; n-heptane/CH2Cl2=4:1) to give 1.60 g of the title compound.
Reaction SMILES: N#N.[H-].[Na+].[Cl:5][C:6]1[CH:7]=[C:8]([OH:13])[CH:9]=[CH:10][C:11]=1[Cl:12].[C:14]([NH:17][C:18]1[CH:28]=[CH:27][C:21]([O:22][CH2:23][CH2:24][CH2:25]Cl)=[CH:20][CH:19]=1)(=[O:16])[CH3:15]>CN(C=O)C>[C:14]([NH:17][C:18]1[CH:28]=[CH:27][C:21]([O:22][CH2:23][CH2:24][CH2:25][O:13][C:8]2[CH:9]=[CH:10][C:11]([Cl:12])=[C:6]([Cl:5])[CH:7]=2)=[CH:20][CH:19]=1)(=[O:16])[CH3:15]
Reactant: CC(=O)Nc1ccc(OCCCCl)cc1
Reactant: Oc1ccc(Cl)c(Cl)c1
Agent: N#N
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(=O)Nc1ccc(OCCCOc2ccc(Cl)c(Cl)c2)cc1
Temperature: 80 °C

Procedure:
In a round bottomed flask equipped with magnetic stirring, reflux condenser, N2 atmosphere, and a heating mantle was placed DMF (80 ml) and to this was added cautiously NaH (60% by weight in oil, 1.76 g) followed by 3,4-dichlorophenol (7.15 g). This mixture was stirred for ten minutes then 1-[4-acetamidophenoxy]-3-chloropropane of Formula XXI (10.0 g) was added; and the reaction mixture heated at 80° C. overnight. The mixture was cooled and the DMF removed in vacuo. The residue was poured into ice water and the precipitated brown solid was collected by filtration. The crude product was recrystallized from ethanol to give an off white solid (9.8 g), mp 135°-7° C.
Reaction SMILES: [C:1]([N:4]1[CH2:9][CH2:8][C:7]2[C:10]([CH2:14][CH2:15]Cl)=[C:11]([CH3:13])[S:12][C:6]=2[CH2:5]1)(=[O:3])[CH3:2].[S:17]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[C:19]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[N:18]1.C(O)(=O)C(O)=O.S1C2C=CC=CC=2C(N2CCN(CCCC(C3SC4SCCNC(=O)C=4C=3)=O)CC2)=N1>>[C:1]([N:4]1[CH2:9][CH2:8][C:7]2[C:10]([CH2:14][CH2:15][N:29]3[CH2:30][CH2:31][N:26]([C:19]4[C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=5[S:17][N:18]=4)[CH2:27][CH2:28]3)=[C:11]([CH3:13])[S:12][C:6]=2[CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1CCc2c(sc(C)c2CCCl)C1
Reactant: c1ccc2c(N3CCNCC3)nsc2c1
Agent: O=C(CCCN1CCN(c2nsc3ccccc23)CC1)c1cc2c(s1)SCCNC2=O
Agent: O=C(O)C(=O)O
Product: CC(=O)N1CCc2c(sc(C)c2CCN2CCN(c3nsc4ccccc34)CC2)C1
Yield: 58.5 %

Procedure:
The reaction and procedure were conducted in a similar manner as in Example 14 using 1.0 g of 6-acetyl-3-(2-chloroethyl)-4,5,6,7-tetrahydro-2-methylthieno[2,3-c]pyridine and 0.88 g of 1-(1,2-benzoisothiazol- 3-yl)piperazine to give 1.0 g of 6-acetyl-3-(2-(4-(1,2-benzisothiazol-3-yl)piperazin-1-yl)ethyl)-4,5,6,7-tetrahydro-2-methylthieno[2,3-c]pyridine as an oil, m.p. 190°-192° C. (decomposition) as an oxalate 1/2 hydrate thereof.
Reaction SMILES: [CH3:1][Si:2]([CH3:9])([CH3:8])[N-:3][Si:4]([CH3:7])([CH3:6])[CH3:5].C([Li:14])CCC>>[CH3:1][Si:2]([CH3:9])([CH3:8])[N-:3][Si:4]([CH3:7])([CH3:6])[CH3:5].[Li+:14]
Reactant: [Li]CCCC
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Product: [Li+]
Temperature: 0 °C

Procedure:
In a dry 100 mL 3-neck flask, equipped with a magnetic stirrer, was placed 5 mL of the replacement solvent to be investigated. To this was added hexamethyldisilazide (HMDS, 0.360 mL, 1.17 mmol). The mixture is cooled to 0° C. and n-butyl lithium was added in a 1:1 mole ratio. The reaction is stirred (ca. {fraction (1/2)}h) to obtain lithium hexamethyldisilazide (LHMDS).
Reaction SMILES: Br/[C:2](/[F:16])=[C:3](/[F:15])\[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([N+:12]([O-:14])=[O:13])[CH:5]=1.[CH3:17][O:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[C:23]([O:27][CH3:28])[C:24]=1[O:25][CH3:26].C([O-])([O-])=O.[Na+].[Na+].CC(C)=O>C1(C)C=CC=CC=1.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>[F:16]/[C:2](/[C:21]1[CH:22]=[C:23]([O:27][CH3:28])[C:24]([O:25][CH3:26])=[C:19]([O:18][CH3:17])[CH:20]=1)=[C:3](\[F:15])/[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([N+:12]([O-:14])=[O:13])[CH:5]=1
Reactant: COc1cc(B(O)O)cc(OC)c1OC
Reactant: COc1ccc(/C(F)=C(/F)Br)cc1[N+](=O)[O-]
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: [Na+]
Solvent: Cc1ccccc1
Solvent: CC(C)=O
Product: COc1ccc(/C(F)=C(/F)c2cc(OC)c(OC)c(OC)c2)cc1[N+](=O)[O-]
Temperature: 25 °C

Procedure:
A mixture of 90 mg (0.31 mmol; 1 eq.) of (9), 198 mg (0.93 mmol; 3 eq.) of 3,4,5-trimethoxyphenyl-boronic acid, 0.6 mL of Na2CO3 2M aqueous solution and 19 mg (0.0016 mmol; 0.05 eq.) of Pd(Ph3P)4 in 4 mL toluene was refluxed for 2.5 h. The solution was then cooled down to room temperature, dried over anhydrous sodium sulfate and the crude mixture was passed through a short silica gel column to remove catalyst. The crude product was purified by chromatography on silica gel with Hexane/Acetone 8:2 to give 57 mg (0.15 mmol; 48%) of a yellow oil. Rf=0.17 in Hex./Acetone 8:2.
Reaction SMILES: C([O:3][C:4](=O)[C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[C:8]([O:21][CH2:22][CH2:23][OH:24])=[C:7]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[CH:6]=1)C.[C:34]1([CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][NH2:46])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>>[C:34]1([CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][NH:46][C:4](=[O:3])[C:5]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:18])([F:19])[F:20])[CH:12]=3)[C:8]([O:21][CH2:22][CH2:23][OH:24])=[C:7]([C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)[CH:6]=2)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
Reactant: CCOC(=O)c1cc(-c2ccc(OC)cc2)c(OCCO)c(-c2cccc(C(F)(F)F)c2)c1
Reactant: NCCCCCCc1ccccc1
Product: COc1ccc(-c2cc(C(=O)NCCCCCCc3ccccc3)cc(-c3cccc(C(F)(F)F)c3)c2OCCO)cc1

Procedure:
The product was prepared as a yellow gum (0.191 g, 74%) from 3-(4-methoxyphenyl)-5-(3-trifluoromethylphenyl)-4-(2-hydroxyethoxy)benzoic acid ethyl ester and 6-phenylhexylamine using a procedure similar to step 2 of example 1; 1H NMR (300 MHz, DMSO-d6) δ 1.27–1.38 (m, 4H), 1.47–1.60 (m, 4H), 2.55 (t, J=7.5 Hz, 2H), 3.10 (q, J=7 Hz, 2H), 3.20–3.30 (m, 4H), 3.80 (s, 3H), 4.38 (t, J=6 Hz, 1H), 7.02–7.08 (m, 2H), 7.10–7.18 (m, 3H), 7.23–7.26 (m, 2H), 7.55–7.60 (m, 2H), 7.68–7.78 (m, 2H), 7.83–7.88 (m, 2H), 7.91–7.96 (m, 2H), 8.55 (t, J=4 Hz, 1H); mass spectrum [(+)ESI], m/z 592 (M+H)+.
Reaction SMILES: O[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=2[C:11]#[N:12])=[N:7][CH:8]=1.O=S(Cl)[Cl:19]>O1CCOCC1.CCOCC.[Cl-].[Cl-].[Zn+2]>[Cl:19][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=2[C:11]#[N:12])=[N:7][CH:8]=1
Reactant: N#Cc1ccccc1-c1ccc(CO)cn1
Reactant: O=S(Cl)Cl
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CCOCC
Solvent: C1COCCO1
Product: N#Cc1ccccc1-c1ccc(CCl)cn1
Temperature: 0 °C
Reaction time: 18 h
Yield: 94 %

Procedure:
To a cooled (0° C.), stirred solution of 2-[5-(hydroxymethyl)pyridin-2-yl]benzonitrile (4.3 g, 0.020 mol) and ZnCl2 (0.09 g, 0.61 mmol) in p-dioxane (40 mL) was added SOCl2 (1.50 mL, 0.020 mol) dropwise. The mixture was stirred at room temperature for 18 h, diluted with ether, washed with water and brine, dried (MgSO4), and concentrated to give 4.30 g (92%) of product as a brown solid, mp 97°-98° C.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([N:16]([CH3:23])[C:17](=[O:22])[C:18]([F:21])([F:20])[F:19])[CH:7]=[C:8]([S:10]([F:15])([F:14])([F:13])([F:12])[F:11])[CH:9]=1)(=[O:3])[CH3:2].[Br-:24].[Br-].[Br-].C1([N+](C)(C)C)C=CC=CC=1.C1([N+](C)(C)C)C=CC=CC=1.C1([N+](C)(C)C)C=CC=CC=1.S(=O)(=O)(O)O>CO.C1COCC1.[Br-].[Br-].[Br-].C1([N+](C)(C)C)C=CC=CC=1.C1([N+](C)(C)C)C=CC=CC=1.C1([N+](C)(C)C)C=CC=CC=1>[Br:24][CH2:2][C:1]([C:4]1[CH:5]=[C:6]([N:16]([CH3:23])[C:17](=[O:22])[C:18]([F:21])([F:19])[F:20])[CH:7]=[C:8]([S:10]([F:14])([F:15])([F:13])([F:12])[F:11])[CH:9]=1)=[O:3]
Reactant: CC(=O)c1cc(N(C)C(=O)C(F)(F)F)cc(S(F)(F)(F)(F)F)c1
Reactant: [Br-]
Agent: C[N+](C)(C)c1ccccc1
Agent: O=S(=O)(O)O
Solvent: CO
Solvent: C1CCOC1
Product: CN(C(=O)C(F)(F)F)c1cc(C(=O)CBr)cc(S(F)(F)(F)(F)F)c1
Temperature: 60 °C
Reaction time: 8 h
Yield: 164.6 %

Procedure:
N-[3-Acetyl-5-(pentafluorosulfanyl)phenyl]-2,2,2-trifluoro-N-methylacetamide (O2.075; 1.03 g) was dissolved in a mixture of methanol (20 ml) and THF (20 ml). Phenyltrimethylammonium tribromide (1.05 g) was added while stirring. After stirring at RT for 5 h, the mixture was left to stand overnight, then further phenyltrimethylammonium tribromide (100 mg) was added and the mixture was heated to 60° C. for 2 h. After cooling, the reaction mixture was added to 2 N sulfuric acid and stirred for 10 min. Then the aqueous phase was extracted three times with EA. The combined organic phases were dried over magnesium sulfate and, after the desiccant had been filtered off, dried under reduced pressure. 1.2 g of the title compound were obtained, which had sufficient purity for the next reactions.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:22]=[CH:23][CH:24]=1)[O:8][CH2:9][C:10]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:11]=1[C:12]([OH:14])=O)(=[O:3])[CH3:2]>S1(CCCC1)(=O)=O>[C:1]([NH:4][C:5]1[CH:24]=[CH:23][C:22]2[C:12](=[O:14])[C:11]3[CH:15]=[CH:16][C:17]([N+:19]([O-:21])=[O:20])=[CH:18][C:10]=3[CH2:9][O:8][C:7]=2[CH:6]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1cccc(OCc2cc([N+](=O)[O-])ccc2C(=O)O)c1
Solvent: O=S1(=O)CCCC1
Product: CC(=O)Nc1ccc2c(c1)OCc1cc([N+](=O)[O-])ccc1C2=O

Procedure:
In accordance with general method W, 0.80 g (2.42 mmol) of (4) is partly dissolved in 10 ml of sulfolane at 100° C. 15 ml (30.0 g) of polyphosphoric acid are then added to the reaction mixture. Yield: 0.50 g (66.2%); melting point: 171.4° C.
Reaction SMILES: Br[C:2]1[CH:19]=[CH:18][C:5]([O:6][CH2:7][CH2:8][CH2:9][O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])=[CH:4][CH:3]=1.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][CH:23]=1.CC(C)([O-])C.[Na+]>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1(C)C=CC=CC=1>[Si:11]([O:10][CH2:9][CH2:8][CH2:7][O:6][C:5]1[CH:18]=[CH:19][C:2]([NH:28][C:25]2[CH:26]=[CH:27][C:22]([O:21][CH3:20])=[CH:23][CH:24]=2)=[CH:3][CH:4]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12]
Reactant: CC(C)(C)[Si](C)(C)OCCCOc1ccc(Br)cc1
Reactant: COc1ccc(N)cc1
Agent: [Fe+2]
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: COc1ccc(Nc2ccc(OCCCO[Si](C)(C)C(C)(C)C)cc2)cc1
Temperature: 90 °C
Reaction time: 8 h

Procedure:
5. To a dry 500 mL round bottom flask under nitrogen was added (3-(4-bromophenoxy)propoxy)(tert-butyl)dimethylsilane (12.1 g, 35.0 mmol), 4-anisidine (5.17 g, 42.0 mmol), and 20 mL anhydrous toluene. The mixture was degassed for 10 minutes before addition of dibenzylideneacetone di palladium Pd2(dba)3 (0.64 g, 0.70 mmol), 1,1′-Bis(diphenylphosphino)ferrocene (DPPF) (0.68 g, 1.2 mmol), and 20 mL anhydrous toluene. After 10 minutes of mixing, sodium tert-butoxide (4.7 g, 49.0 mmol) was added with 10 mL anhydrous toluene. The reaction mixture was heated to 90° C. and allowed to stir overnight while being monitored by thin layer chromatography. Upon disappearance of the starting material the reaction mixture was filtered through a plug of silica gel eluting with dichloromethane (Reaction Time=22 h). The product was purified by flash chromatography (silica gel, 5:1 hexanes:ethyl acetate). The solvent was removed under reduced pressure. The residual solvent was removed in vacuo (11.3 g, 83.0%). 1H NMR (300 MHz, CDCl3) δ 7.06 (d, J=3.3 Hz, 2H), 7.03 (d, J=3.3 Hz, 2H), 6.91 (d, J=3.3 Hz, 2H), 6.88 (d, J=3.3 Hz, 2H), 6.85 (s, 1H), 4.10 (t, 6.3 Hz, 2H), 3.90 (t, J=6.0 Hz, 2H), 3.81 (s, 3H), 2.01 (q, J=6.3 Hz, 2H), 0.97 (s, 9H), 0.14 (s, 6H).