Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([OH:14])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.F[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=1.[H-].[Na+]>CN(C=O)C.O>[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([O:14][C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: OC1CCCN(Cc2ccccc2)C1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccc(OC2CCCN(Cc3ccccc3)C2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 94.3 %

Procedure:
A mixture of 1-benzyl-3-hydroxypiperidine (2.0 g, 10 mmoles), p-fluoro-nitrobenzene (1.06 ml, 12 mmoles) and sodium hydride (0.285 g, 12 mmoles) in DMF was stirred at room temperature for 3 hours, diluted with H2O and extracted with EtOAc. The extracts were combined, washed sequentially with water and brine, dried over Na2SO4 and concentrated under vacuum. The resultant residue was purified by flash chromatography using as eluent 50% EtOAc/hexane to afford the title compound (3.0 g, 9.43 mmoles).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][S:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[NH:13]1[CH2:18][CH2:17][CH:16]([C:19]2[CH:20]=[C:21]([NH:25][C:26](=[O:29])[CH2:27][CH3:28])[CH:22]=[CH:23][CH:24]=2)[CH2:15][CH2:14]1>>[C:7]1([S:6][CH2:5][CH2:4][CH2:3][CH2:2][N:13]2[CH2:18][CH2:17][CH:16]([C:19]3[CH:20]=[C:21]([NH:25][C:26](=[O:29])[CH2:27][CH3:28])[CH:22]=[CH:23][CH:24]=3)[CH2:15][CH2:14]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: ClCCCCSc1ccccc1
Reactant: CCC(=O)Nc1cccc(C2CCNCC2)c1
Product: CCC(=O)Nc1cccc(C2CCN(CCCCSc3ccccc3)CC2)c1

Procedure:
Prepared by Procedure G and Scheme B using [(4-chlorobutyl)sulfanyl]benzene and N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 396.8 (M+H)+.
Reaction SMILES: [CH2:1]([C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][C:13]=1[OH:14])[C:7]([O:9][CH3:10])=[O:8])[CH:2]=[CH2:3].[Br:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]Br>>[CH2:1]([C:4]1[CH:5]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:11]=[CH:12][C:13]=1[O:14][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][Br:15])[CH:2]=[CH2:3]
Reactant: C=CCc1cc(C(=O)OC)ccc1O
Reactant: BrCCCCCBr
Product: C=CCc1cc(C(=O)OC)ccc1OCCCCCBr
Yield: 69.2 %

Procedure:
Using the procedure of Example 1, 5.62 g (29.2 mmole) of methyl 3-allyl-4-hydroxybenzoate and 13.8 g (60 mmole) of 1,5-dibromopentane gave 6.9 g (69%) of the title compound as an oil. Calc: C, 56.32; H, 6.20; Found; C, 55.91; H, 6.20.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:6]([C:7]([OH:9])=[O:8])[C:5]([NH2:11])=[C:4]([OH:12])[CH:3]=1.[C:13](Cl)(=O)[CH3:14].C(N(CC)CC)C.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C1(C)C(C)=CC=CC=1.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[O:12][C:13]([CH3:14])=[N:11][C:5]2=[C:6]([C:7]([OH:9])=[O:8])[CH:10]=1
Reactant: CC(=O)Cl
Reactant: Nc1c(O)cc(Br)cc1C(=O)O
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1C
Solvent: CCN(CC)CC
Product: Cc1nc2c(C(=O)O)cc(Br)cc2o1
Temperature: 25 °C

Procedure:
To a solution of 5-bromo-3-hydroxyanthranilic acid (prepared as described in Eur. J. Med. Chem., 1999, 34, 729) (400 mg) in xylene (30 mL), were added acetyl chloride (135 μL), triethylamine (265 μL) and pyridinium p-toluenesulfonate (130 mg), and the mixture was heated at reflux for 8 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed sequentially with water and brine, and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified on silica gel column chromatography to obtain the titled compound (471 mg).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:17]=[CH:16][C:7](/[CH:8]=[C:9]2/[C:10](=[O:15])[NH:11][C:12](=[O:14])[S:13]/2)=[CH:6][CH:5]=1)[CH3:2].[CH2:18](O)[CH2:19][OH:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>>[CH2:1]([O:3][C:4]1[CH:17]=[CH:16][C:7](/[CH:8]=[C:9]2/[C:10](=[O:15])[N:11]([CH2:18][CH2:19][OH:20])[C:12](=[O:14])[S:13]/2)=[CH:6][CH:5]=1)[CH3:2]
Reactant: OCCO
Reactant: CCOc1ccc(/C=C2\SC(=O)NC2=O)cc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CCOc1ccc(/C=C2\SC(=O)N(CCO)C2=O)cc1

Procedure:
The title compound 28e was prepared from compound 2 (249 mg, 1.00 mmol), ethane-1,2-diol (111 μL, 2.00 mmol), triphenylphosphine (524 mg, 2.00 mmmol) and DIAD (394 μL, 2.00 mmol) in a manner similar to that described for 9 in 95.2% (279 mg) yield as a white solid.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH:2]1[O:4][CH2:3]1.[CH3:12][C:13]([NH2:25])([CH3:24])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=1>>[OH:4][CH:2]([CH2:1][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:3][NH:25][C:13]([CH3:24])([CH3:12])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=1
Reactant: c1ccc(OCC2CO2)cc1
Reactant: COc1ccc(CC(C)(C)N)cc1F
Product: COc1ccc(CC(C)(C)NCC(O)COc2ccccc2)cc1F

Procedure:
Using the method of Example 6, supra, phenyl glycidyl ether (150 mg, 1.1 mmol) and 1,1-dimethyl-2-(3-fluoro-4-methoxyphenyl)ethylamine (197 mg, 1 mmol) were used to prepare the title compound. The title compound crystallized on standing to yield 169 mg of small crystals: GC/EI-MS, m/z (rel. int.) 332 (M+−15, 0.1), 209 (16), 208 (100), 139 (13), 133 (5), 114 (7), 107 (6), 77 (11), 71 (12), 70 (20), 58 (9).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([CH3:11])[C:9]=1[OH:10])[CH:5]=O.[N:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[S:18]([CH2:21][C:22]#[N:23])(=[O:20])=[O:19]>>[CH3:1][C:2]1[CH:3]=[C:4](/[CH:5]=[C:21](/[S:18]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][N:12]=2)(=[O:20])=[O:19])\[C:22]#[N:23])[CH:7]=[C:8]([CH3:11])[C:9]=1[OH:10]
Reactant: N#CCS(=O)(=O)c1ccccn1
Reactant: Cc1cc(C=O)cc(C)c1O
Product: Cc1cc(/C=C(\C#N)S(=O)(=O)c2ccccn2)cc(C)c1O

Procedure:
The titled compound was prepared with 3,5-dimethyl-4-hydroxybenzaldehyde and (pyrid-2-yl)sulphonyl acetonitrile under the similar conditions as described for EXAMPLE 1.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][CH:27]=2)[C:7](=[O:24])[C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][C:18]([CH:21]=[O:22])=[CH:17][CH:16]=1)=[CH:12][C:11]([Cl:23])=[CH:10][CH:9]=2)=[O:4].[CH3:36][Mg]Br.S([O-])(O)(=O)=O.[K+]>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:25][C:26]2[CH:27]=[CH:28][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:30][CH:31]=2)[C:7](=[O:24])[C:8]2[C:13]([C:14]=1[C:15]1[CH:16]=[CH:17][C:18]([CH:21]([OH:22])[CH3:36])=[CH:19][CH:20]=1)=[CH:12][C:11]([Cl:23])=[CH:10][CH:9]=2)=[O:4]
Reactant: COC(=O)c1c(-c2ccc(C=O)cc2)c2cc(Cl)ccc2c(=O)n1Cc1ccc(S(C)(=O)=O)cc1
Reactant: C[Mg]Br
Agent: O=S(=O)([O-])O
Agent: [K+]
Solvent: C1CCOC1
Product: COC(=O)c1c(-c2ccc(C(C)O)cc2)c2cc(Cl)ccc2c(=O)n1Cc1ccc(S(C)(=O)=O)cc1

Procedure:
To a solution (2.6 ml) of 6-chloro-4-(4-formylphenyl)-2-(4-methanesulfonylbenzyl)-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester (130 mg) in THF was added a solution (3 mol/l, 0.10 ml) of methyl magnesium bromide in THF at room temperature with stirring, and the mixture was stirred at room temperature for 1 hr. After the completion of the reaction, 5% aqueous potassium hydrogensulfate solution was added to the mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by medium pressure preparative LC (hexane/ethyl acetate=1/2-ethyl acetate) to give the title compound (72 mg) as colorless crystals.
Reaction SMILES: [I-].C[N+]1C=CN([C:8](=[O:30])/[N:9]=[C:10]2\[S:11][C:12]([CH3:29])=[CH:13][N:14]\2[C:15]2[CH:28]=[CH:27][C:18]3[O:19][C:20]([F:26])([F:25])[C:21]([F:24])([F:23])[O:22][C:17]=3[CH:16]=2)C=1.Cl.[F:32][C@@H:33]1[CH2:37][CH2:36][NH:35][CH2:34]1.CCN(C(C)C)C(C)C>C(#N)C>[F:32][C@@H:33]1[CH2:37][CH2:36][N:35]([C:8](/[N:9]=[C:10]2\[S:11][C:12]([CH3:29])=[CH:13][N:14]\2[C:15]2[CH:28]=[CH:27][C:18]3[O:19][C:20]([F:26])([F:25])[C:21]([F:23])([F:24])[O:22][C:17]=3[CH:16]=2)=[O:30])[CH2:34]1
Reactant: Cc1cn(-c2ccc3c(c2)OC(F)(F)C(F)(F)O3)/c(=N/C(=O)n2cc[n+](C)c2)s1
Reactant: F[C@@H]1CCNC1
Agent: Cl
Agent: [I-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: Cc1cn(-c2ccc3c(c2)OC(F)(F)C(F)(F)O3)/c(=N/C(=O)N2CC[C@@H](F)C2)s1
Temperature: 30 °C
Reaction time: 12 h

Procedure:
(Z)-3-Methyl-1-(5-methyl-3-(2,2,3,3-tetrafluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)thiazol-2(3H)-ylidenecarbamoyl)-1H-imidazol-3-ium iodide (Example 81A, 250 mg, 0.45 mmol), (R)-3-fluoropyrrolidine hydrochloride (62 mg, 0.49 mmol) and Hunig's base (0.078 mL, 0.45 mmol) in acetonitrile (5 mL) were stirred at 55° C. for 3 hours. The reaction mixture was then cooled to 30° C. with continued stirring for 12 hours. The mixture was evaporated to dryness and purified by reverse phase HPLC to give the title compound. 1H NMR (CDCl3) δ ppm 2.00 (2H), 2.20 (3H), 3.35-3.85 (4H), 5.10-5.30 (1H), 6.60 (1H), 7.20 (1H), 7.35 (1H), 7.45 (1H); MS (ESI) m/z 436(M+H)+.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[N:8]=[CH:7][N:6]=[C:5]([NH2:9])[CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:22][O:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[C:34]1[C:43]2[C:38](=[CH:39][C:40]([S:44](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:46])=[O:45])=[CH:41][CH:42]=2)[CH:37]=[CH:36][N:35]=1>C1COCC1>[CH3:22][O:23][C:24]1[CH:29]=[C:28]([C:30]([F:31])([F:32])[F:33])[CH:27]=[CH:26][C:25]=1[C:34]1[C:43]2[C:38](=[CH:39][C:40]([S:44]([NH:9][C:5]3[CH:4]=[C:3]([C:2]([F:1])([F:10])[F:11])[N:8]=[CH:7][N:6]=3)(=[O:46])=[O:45])=[CH:41][CH:42]=2)[CH:37]=[CH:36][N:35]=1
Reactant: COc1cc(C(F)(F)F)ccc1-c1nccc2cc(S(=O)(=O)Oc3c(F)c(F)c(F)c(F)c3F)ccc12
Reactant: Nc1cc(C(F)(F)F)ncn1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1cc(C(F)(F)F)ccc1-c1nccc2cc(S(=O)(=O)Nc3cc(C(F)(F)F)ncn3)ccc12
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 15.4 %

Procedure:
A round-bottom flask was charged with 6-(trifluoromethyl)pyrimidin-4-amine (0.030 g, 0.182 mmol)) and THF (0.910 ml), and the vessel was cooled to −78° C. for 15 minutes. Lithium bis(trimethylsilyl)amide (0.218 ml, 0.218 mmol),) was then added drop wise over 1 minute. The reaction was stirred for 10 minutes, and then a solution of perfluorophenyl 1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline-6-sulfonate (Intermediate LLL; 0.100 g, 0.182 mmol) in THF (1.6 mL) was added drop wise. The bath was removed, and the resulting mixture was stirred for 45 minutes. The reaction was diluted with saturated ammonium chloride (aq.) solution (30 mL), and was washed with ethyl acetate (20 mL×3). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated. The resulting material was purified via silica gel chromatography (ISCO, 40 g), eluting with 0 to 100% ethyl acetate in heptanes. The fractions were concentrated under reduced pressure to yield 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(6-(trifluoromethyl)pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.015 g, 0.028 mmol, 15.60% yield). m/z (ESI) 528.9 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.[CH2:11](O)[CH2:12][OH:13].C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C=CC=CC=1>[CH3:9][C:8]1([C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=2)[O:13][CH2:12][CH2:11][O:10]1
Reactant: CC(=O)c1ccc(Br)cc1
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CC1(c2ccc(Br)cc2)OCCO1

Procedure:
In 1200 milliliters of toluene in a flask equipped with a Dean-Stark tube are dissolved 100 grams of p-bromoacetophenone and to this solution is added 140 grams of ethylene glycol and 5 grams of p-toluenesulphonic acid. This mixture is refluxed until no further water collects in the Dean-Stark tube. After distilling off 600 milliliters of toluene, the remaining solution is decanted off and evaporated to dryness in vacuo to obtain 2-methyl-2-(p-bromophenyl)-1,3-dioxolane.
Reaction SMILES: [C:1]([C:5]1[C:10]2[O:11][CH2:12][C:13]([CH3:15])([CH3:14])[C:9]=2[CH:8]=[C:7]([C:16](=[O:18])[CH3:17])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.C[Si](OS(C(F)(F)F)(=O)=O)(C)C.[CH3:40][C:41]([CH3:43])=[O:42]>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[C:1]([C:5]1[C:10]2[O:11][CH2:12][C:13]([CH3:15])([CH3:14])[C:9]=2[CH:8]=[C:7]([C:16](=[O:18])[CH2:17][C:41]([OH:42])([CH3:43])[CH3:40])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(=O)c1cc(C(C)(C)C)c2c(c1)C(C)(C)CO2
Reactant: CC(C)=O
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(O)CC(=O)c1cc(C(C)(C)C)c2c(c1)C(C)(C)CO2
Temperature: -78 °C
Reaction time: 0.17 h

Procedure:
A solution of 1-(7-tert-butyl-3,3-dimethyl-2,3-dihydrobenzo[b]furan-5-yl)-ethan-1-one (Example 2) (1.07 g, 4.3 mmol) in CH2Cl2 (65 mL) is cooled to -78° C., and diisopropylethylamine (0.97 mL, 5.6 mmol) and trimethylsilyltriflate (1.08 mL, 5.6 mmol) are added sequentially via syringe. The reaction is stirred at -78° C. for 10 min and then is allowed to warm to 24° C. and is stirred at that temperature for 45 min. The solution is once again cooled to -78° C., and acetone (0.54 mL, 4.3 mmol) is added, followed by TiCl4 (1M solution in CH2Cl2, 4.3 mL, 4.3 mmol). After 1 h at -78° C., the reaction mixture is allowed to warm to 24° C. and evaporated. The residue is partioned between MeOH/1N HCl and CH2Cl2. The CH2Cl2 layer is dried (MgSO4), filtered, evaporated, and chromatographed over SiO2 using EtOAc/hexane (1:6), to yield 1-(7-tert-butyl-3,3-dimethyl-2,3-dihydrobenzo[b]furan-5-yl)-3-hydroxy-3-methylbutan-1-one.
Reaction SMILES: [C:1]1([C@@H:7]2[CH2:9][C@H:8]2[C:10]([OH:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH3:14][O:15][NH:16][CH3:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH3:14][O:15][N:16]([CH3:17])[C:10]([C@@H:8]1[CH2:9][C@H:7]1[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:12]
Reactant: O=C(O)[C@@H]1C[C@H]1c1ccccc1
Reactant: CNOC
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
Solvent: O
Product: CON(C)C(=O)[C@@H]1C[C@H]1c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 42 %

Procedure:
To a stirred solution of 35 (117.5 g, 724.48 mmol, 1.00 equiv) in DMF (1.2 L) under N2 was added methoxy(methyl)amine hydrochloride (82.3 g, 844.10 mmol, 1.17 equiv), HATU (329 g, 775.58 mmol, 1.07 equiv), and DIPEA (117.5 mL). The reaction mixture was stirred under N2 at 25° C. overnight and then diluted with water (700 mL). The organic phase was extracted with EtOAc (3×1 L), and the combined organic layers were washed with water (3×1 L) and brine (1×1 L), dried (Na2SO4), filtered and concentrated in vacuo. The residue purified by SiO2 chromatography and eluted with EtOAc/petroleum ether (10 to 50% EtOAc) to afford 62.5 g (42%) of trans-N-methoxy-N-methyl-2-phenylcyclopropane-1-carboxamide (37) as a light yellow oil.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Br)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:17][O:18][C:19]1([CH3:25])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>C1COCC1>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:22]2[CH2:23][CH2:24][C:19]([O:18][CH3:17])([CH3:25])[CH2:20][CH2:21]2)=[CH:4][CH:3]=1
Reactant: COC1(C)CCNCC1
Reactant: BrCc1ccc(Br)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COC1(C)CCN(Cc2ccc(Br)cc2)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 96.4 %

Procedure:
A mixture of 4-bromobenzyl bromide (0.44 g, 1.74 mmol), triethylamine (0.37 mL, 2.61 mmol) and 4-methoxy-4-methylpiperidine (0.45 g, 3.49 mmol)in THF (10 mL) was stirred at ambient temperature for 16 h. The solvent was evaporated and the resultant residue was diluted with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate (2×50 mL). The combined organic layer was dried over sodium sulfate, filtered and evaporated to afford the title compound as a yellow oil (0.50 g, 96%). 1H NMR (CDCl3, 300 MHz): 7.45-7.39 (m, 2H), 7.22-7.17 (m, 2H), 3.44 (s, 2H), 3.17 (s, 3H), 2.52-2.42 (m, 2H), 2.36-2.25 (m, 2H), 1.79-1.70 (m, 2H), 1.59-1.47 (m, 2H), 1.13 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[CH:12]=[C:11]([O:13][CH2:14]/[CH:15]=[C:16](/[C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=2)\[C:17]2[CH:22]=[CH:21][C:20]([C:23]#[C:24][CH2:25][N:26]3CCO[CH2:28][CH2:27]3)=[CH:19][CH:18]=2)[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([OH:8])=[O:7].[C:39](C1C=CC=CN=1)#[CH:40].O1CCC[CH2:48]1>C(N(CC)CC)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.[Cu]I>[CH3:1][C:2]1[CH:12]=[C:11]([O:13][CH2:14]/[CH:15]=[C:16](/[C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=2)\[C:17]2[CH:18]=[CH:19][C:20]([C:23]#[C:24][C:25]3[CH:40]=[CH:39][CH:28]=[CH:27][N:26]=3)=[CH:21][CH:22]=2)[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([O:8][CH3:48])=[O:7]
Reactant: C1CCOC1
Reactant: Cc1ccc(/C(=C/COc2ccc(OCC(=O)O)c(C)c2)c2ccc(C#CCN3CCOCC3)cc2)cc1
Reactant: C#Cc1ccccn1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: COC(=O)COc1ccc(OC/C=C(/c2ccc(C)cc2)c2ccc(C#Cc3ccccn3)cc2)cc1C
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A solution of methyl (Z)-[2-methyl-4-[3-(4-iodophenyl)-3-(4-methylphenyl)]allyloxy]-phenoxy]acetate (310 mg, 0.587 mmol; example 3) in a mixture of tetrahydrofuran (9 mL) and triethylamine (9 mL) was degassed and 2-ethynylpyridine (121 mg, 1.17 mmol) was added in argon atmosphere. The solution was cooled down; tetrakis(triphenylphosphine)palladium (55 mg, 0.047 mmol) and copper(I) iodide (17.8 mg, 0.094 mmol) were added. The reaction mixture was stirred at ambient temperature for 48 h, then evaporated in vacuo and the residue was dissolved in ethyl acetate (20 mL). The solution was washed with water (3×15 mL), dried with anhydrous magnesium sulphate and evaporated in vacuo. The residue was purified by flash column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 7:3) yielding methyl (Z)-[2-methyl-4-[3-(4-methylphenyl)-3-[4-(pyridin-2-ylethynyl)phenyl]allyloxy]-phenoxy]acetate.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[CH2:9]([O:11][C:12]([C:14]1[N:15]=[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([CH3:22])[N:17]2[CH:23]=1)=[O:13])[CH3:10]>C(#N)C>[CH2:9]([O:11][C:12]([C:14]1[N:15]=[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([CH3:22])[N:17]2[C:23]=1[Br:1])=[O:13])[CH3:10]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)c1cn2c(C)cccc2n1
Solvent: CC#N
Product: CCOC(=O)c1nc2cccc(C)n2c1Br
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
N-Bromosuccinimide (0.288 g, 0.00162 mol) was added in portions to a solution of 5-methylimidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester (compound n, 0.3 g, 0.001 mol) in acetonitrile (7 mL) at 0° C. The reaction was stirred at 0° C. for 15 minutes. The solvent removed then water (10 mL) and ethyl acetate (10 mL) was added. The layers were separated and the organic layer dried (magnesium sulfate) then removed. The crude product was chromatographed using 30% ethyl acetate/hexanes to give 3-Bromo-5-methyl-imidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester as a light brown solid. Rf 0.35, 80% ethyl acetate/hexanes; MS m/z 284 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:17]=[C:16]([CH:18]=O)[C:15]([OH:20])=[C:14]([C:21]3[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[C:23]([Cl:31])[CH:22]=3)[CH:13]=2)[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].[C:32]([NH2:36])([CH3:35])([CH3:34])[CH3:33]>>[C:32]([NH:36][CH2:18][C:16]1[C:15]([OH:20])=[C:14]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:29])([F:28])[F:30])=[C:23]([Cl:31])[CH:22]=2)[CH:13]=[C:12]([C:4]2[CH:5]=[CH:6][C:7]([C:8]([F:11])([F:10])[F:9])=[C:2]([Cl:1])[CH:3]=2)[CH:17]=1)([CH3:35])([CH3:34])[CH3:33]
Reactant: CC(C)(C)N
Reactant: O=Cc1cc(-c2ccc(C(F)(F)F)c(Cl)c2)cc(-c2ccc(C(F)(F)F)c(Cl)c2)c1O
Product: CC(C)(C)NCc1cc(-c2ccc(C(F)(F)F)c(Cl)c2)cc(-c2ccc(C(F)(F)F)c(Cl)c2)c1O

Procedure:
5′-((tert-Butylamino)methyl)-3,3″-dichloro-4,4″-bis(trifluoromethyl)-[1,1′:3′,1″-terphenyl]-4′-ol was prepared as a white solid using the procedure described in Example 5 from 3,3″-dichloro-4′-hydroxy-4,4″-bis(trifluoromethyl)-[1,1′:3′,1″-terphenyl]-5′-carbaldehyde and tert-butylamine.
Reaction SMILES: [CH2:1]1[CH:5]2[CH:6]3C=CC([CH:4]2C=[CH:2]1)C3.[Br:11][C:12]([F:19])([F:18])[C:13]([F:17])([F:16])[CH:14]=[CH2:15]>C1(C)C=CC=CC=1.COC1C=CC(O)=CC=1>[Br:11][C:12]([F:19])([F:18])[C:13]([F:17])([F:16])[CH:14]1[CH2:4][CH:5]2[CH2:6][CH:15]1[CH:2]=[CH:1]2
Reactant: C=CC(F)(F)C(F)(F)Br
Reactant: C1=CC2C3C=CC(C3)C2C1
Agent: COc1ccc(O)cc1
Solvent: Cc1ccccc1
Product: FC(F)(Br)C(F)(F)C1CC2C=CC1C2
Temperature: 170 °C
Reaction time: 5 h
Yield: 145.5 %

Procedure:
An autoclave was charged with 108.5 g of dicyclopentadiene and 322.4 g of 1-bromo-1,1,2,2-tetrafluoro-3-butene. A solution of 0.3 g of 4-methoxyphenol dissolved in 5 ml of toluene was added to the autoclave as a polymerization inhibitor and the mixture was stirred for 5 hours at 170° C. The reaction product was purified by distillation under reduced pressure at 85° C. and 25 mmHg to obtain 326 g of 1-bromo-1,1,2,2-tetrafluoro-2-(norborn-5-en-2-yl)ethane as a clear liquid (hereinafter referred to as “compound (1-a)”).
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10](I)=[N:11][C:12]([CH2:15][OH:16])=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=O)C.[K+].[C:23]([O:27][CH2:28][CH3:29])(=[O:26])[CH:24]=[CH2:25]>CN(C=O)C.O>[CH2:1]([O:8][C:9]1[C:10]([C:24](=[CH2:25])[C:23]([O:27][CH2:28][CH3:29])=[O:26])=[N:11][C:12]([CH2:15][OH:16])=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCc1ccc(OCc2ccccc2)c(I)n1
Reactant: C=CC(=O)OCC
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: C=C(C(=O)OCC)c1nc(CO)ccc1OCc1ccccc1
Temperature: 120 °C
Yield: 62 %

Procedure:
To a solution of 3-benzyloxy-6-hydroxymethyl-2-iodopyridine (1.20 g, 3.50 mmol) in DMF (6.4 ml) and water (0.32 ml) were added potassium acetate (0.83 g, 8.5 mmol) palladium acetate (32 mg, 0.14 mmol) and ethyl acrylate (1.1 ml, 1.01 g, 10 mmol). The mixture was placed under nitrogen and stirred and heated at 120° C. for 1.25 h. By hplc the solution yield was 62%.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH3:6][C:7]1[O:11][C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:9][C:8]=1[CH2:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][OH:28])=[CH:22][CH:21]=1.C(N(CC)CC)C.C(OCC)(=O)C>O>[CH3:1][S:2]([O:28][CH2:27][CH2:26][C:23]1[CH:22]=[CH:21][C:20]([O:19][CH2:18][C:8]2[N:9]=[C:10]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[O:11][C:7]=2[CH3:6])=[CH:25][CH:24]=1)(=[O:4])=[O:3]
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(CCO)cc1
Reactant: CS(=O)(=O)Cl
Solvent: CCOC(C)=O
Solvent: O
Solvent: CCN(CC)CC
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(CCOS(C)(=O)=O)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 96.3 %

Procedure:
Methanesulfonyl chloride (3.37 g) was added dropwise to a mixture of 2-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]ethan-1-ol (7.0 g), triethylamine (2.97 g), and ethyl acetate (300 ml) at 0° C., and the mixture was stirred for 3 hours at room temperature. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium bicarbonate, 1N hydrochloric acid and then with saturated aqueous sodium chloride solution, then dried (MgSO4), and concentrated. The crystals obtained were collected by filtration to yield 2-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]ethyl methanesulfonate (8.44 g, yield: 96%). This was recrystallized from ethyl acetate-hexane. Melting point: 66–67° C.