Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:5][C:6](=[O:56])[CH:7]([NH:18][C:19](=[O:55])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[S:26][S:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34](=[O:54])[NH:35][CH:36]([C:47]([O:49]C(C)(C)C)=[O:48])[CH2:37][CH2:38][CH2:39][C:40]([O:42]C(C)(C)C)=[O:41])[CH2:8][CH2:9][CH2:10][C:11]([O:13]C(C)(C)C)=[O:12])(C)(C)C.FC(F)(F)C(O)=O.C1(OC)C=CC=CC=1>ClCCl>[C:6]([CH:7]([NH:18][C:19]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[S:26][S:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34]([NH:35][CH:36]([CH2:37][CH2:38][CH2:39][C:40]([OH:42])=[O:41])[C:47]([OH:49])=[O:48])=[O:54])=[O:55])[CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12])([OH:56])=[O:5]
Reactant: CC(C)(C)OC(=O)CCCC(NC(=O)c1ccccc1SSc1ccccc1C(=O)NC(CCCC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: COc1ccccc1
Product: O=C(O)CCCC(NC(=O)c1ccccc1SSc1ccccc1C(=O)NC(CCCC(=O)O)C(=O)O)C(=O)O

Procedure:
This compound was prepared according to the procedure described in Example 50 using [S-(R*,R*)]-2-{2-[2-(1,4-bis-tert-butoxycarbonyl-butylcarbamoyl)phenyldisulfanyl]-benzoylamino}-hexanedioic acid di-tert-butyl ester (1.1 g, 1.4 mmol) from Example 10 mL dichloromethane, 10 mL trifluoroacetic acid, and 1 mL anisole. The crude product was recrystallized from methanol/dimethylformamide/water to afford 0.6 of the title compound, mp 259°-260° C.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH2:11][CH:12]2[O:16][C:15](=[O:17])[NH:14][C:13]2=[O:18])=[CH:4][C:3]=1[O:19][CH3:20].Cl[CH2:22][C:23]1[N:24]=[C:25](/[CH:29]=[CH:30]/[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[O:26][C:27]=1C>>[CH3:20][O:19][C:3]1[CH:4]=[C:5]([CH2:8][CH2:9][CH2:10][CH2:11][CH:12]2[O:16][C:15](=[O:17])[NH:14][C:13]2=[O:18])[CH:6]=[CH:7][C:2]=1[O:1][CH2:22][C:23]1[N:24]=[C:25](/[CH:29]=[CH:30]/[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[O:26][CH:27]=1
Reactant: COc1cc(CCCCC2OC(=O)NC2=O)ccc1O
Reactant: Cc1oc(/C=C/c2ccccc2)nc1CCl
Product: COc1cc(CCCCC2OC(=O)NC2=O)ccc1OCc1coc(/C=C/c2ccccc2)n1

Procedure:
In substantially the same manner as in Working Example 9, 5-[4-(4-hydroxy-3-methoxyphenyl)butyl]-2,4-oxazolidinedione was reacted with 4-chloromethyl-5-methyl-2-[(E)-styryl]oxazole to obtain 5-[4-[3-methoxy-4-[2-[(E)-styryl]-4-oxazolylmethoxy]phenyl]butyl]-2,4-oxazolidinedione, which was recrystallized from ethyl acetate-hexane to give colorless prisms, m.p.171-172° C.
Reaction SMILES: ClS([N:5]=[C:6]=[O:7])(=O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][C:16]=1[Cl:17])[CH:12]=[CH2:13]>C(OCC)C>[Cl:8][C:9]1[CH:10]=[C:11]([CH:12]2[NH:5][C:6](=[O:7])[CH2:13]2)[CH:14]=[CH:15][C:16]=1[Cl:17]
Reactant: C=Cc1ccc(Cl)c(Cl)c1
Reactant: O=C=NS(=O)(=O)Cl
Solvent: CCOCC
Product: O=C1CC(c2ccc(Cl)c(Cl)c2)N1
Temperature: 70 °C
Reaction time: 16 h

Procedure:
To chlorosulfonyl isocyanate (CSI) (2.46 ml) in diethyl ether (8 ml) was added dropwise with stirring 3,4-dichlorostyrene (4.89 g, 28.3 mmol). The reaction was heated to 35° C. for 90 min after which time a further 1 ml CSI was added. The reaction was left for 16 h at 35° C., then the oil bath temperature was increased to 70° C. and the ether distilled off. The reaction was stirred at 70° C. for 1 h then cooled and slurried in dichloromethane (50 ml), and added portionwise with stirring to water containing sodium bisulfite (10 g) and potassium carbonate (15 g), using an ice bath for cooling. After stirring for 30 min. the phases were separated and the organic phase dried (MgSO4) to give a yellow oil (4 g). Purification by column chromatography on silica gel eluting with 0-50% dichloromethane in hexane gave the title compound as a white solid, (2.6 g, 43%). δH (CDCl3) 2.85 (1H, dd), 3.45 (1H, m), 4.7 (1H, m), 6.35 (1H, bs), 7.25 (1H, m), 7.45 (2H, m).
Reaction SMILES: [CH:1]1(B(O)O)[CH2:3][CH2:2]1.Br[C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1>[CH:1]1([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=2)[CH2:3][CH2:2]1
Reactant: OB(O)C1CC1
Reactant: O=[N+]([O-])c1ccc(Br)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: O=[N+]([O-])c1ccc(C2CC2)cc1
Yield: 92855.4 %

Procedure:
To a solution of cyclopropyl boronic acid (0.637 g, 0.00742 mmol) in dry toluene, were added 4-bromo nitrobenzene (1.00 g, 0.00495 mmol) and tetrakis triphenylphosphine palladium (0.099 g, 0.0099 mol). Degassed the reaction mixture for 30 minutes then added potassium carbonate (1.36 g, 0.009 mmol). The reaction mass was refluxed for 48 h. The excess of solvent was removed under vacuum and the reaction mass was diluted with water and extracted with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulphate and concentrated. The obtained crude was purified by column chromatography on silica gel eluting with 4% DCM: MeOH to afford 0.750 g of the desired product. 1HNMR (DMSO-d6): δ 0.82-0.84 (m, 2H), 1.09-1.13 (m, 2H), 2.01 (m, 1H), 7.32 (d, J=8.7 Hz, 2H), 8.09 (d, J=8.7 Hz, 2H).
Reaction SMILES: C([N:11]1[CH2:18][C@@H:17]([C:19]([OH:21])=[O:20])[CH2:16][C@H:12]1[C:13]([OH:15])=[O:14])(OCC1C=CC=CC=1)=O>CO.[Pd]>[C:19]([C@@H:17]1[CH2:18][NH:11][C@H:12]([C:13]([OH:15])=[O:14])[CH2:16]1)([OH:21])=[O:20]
Reactant: O=C(O)[C@H]1C[C@@H](C(=O)O)N(C(=O)OCc2ccccc2)C1
Agent: [Pd]
Solvent: CO
Product: O=C(O)[C@@H]1CN[C@H](C(=O)O)C1
Reaction time: 0.5 h
Yield: 83.5 %

Procedure:
N-CBZ-cis-4-carboxy-L-proline (0.455 g, 1.55 mmol) was dissolved in methanol (37 mL) and transferred into a Parr shaker bottle. After adding 10% Pd-C (0.080 g), the mixture was shaken under an atmosphere of hydrogen at 48-50 psi for 0.5 h on the Parr apparatus. The catalyst was removed by filtration through Celite. The filter-cake was washed with water and the combined filtrate and washings were concentrated in vacuo to yield a white solid, which was recrystallized from H2O-ethanol-acetone to yield 0.206 g (84%) of 4 as colorless prisms: mp 225°-226° C.; [α]25D -40° (c 1.02, H2O); 1H NMR (250 MHz, D2O) δ 4.25 (dd, J=8.6, 7.4 Hz, 1 H, H-2), 3.72 (dd, J=12.0, 6.7 Hz, 1 H, H-5), 3.57 (dd, J=12.0, 8.0 Hz, 1 H, H-5), 3.38 (m, 1H, H-4), 2.71 (app dt, J=13.7, 8.6 Hz, 1 H, H-3), 2.35 (app overlapping dt, J=13.7, 7.4 Hz, 1 H,H-3); 13C NMR (75.5 MHz, D2O) δ 178.75, 176.25, 63.87, 50.16, 45.43, 34.78; IR (KBr) 3600-2200 (broad), 3080, 1690, 1560, 1340, 1230 cm-1 ; MS (CI, 70 eV, methane) m/e 160 (MH+, 14), 114 (100). Anal. Calcd for C6H9NO4 : C, 45.28; H, 5.70; N, 8.80. Found: C, 45.31; H, 5.51; N, 8.75.
Reaction SMILES: CC([O-])(C)C.[K+].[C:7]([O:11][C:12](=[O:26])[NH:13][CH2:14][C:15]12[CH2:24][CH:19]3[CH2:20][CH:21]([CH2:23][CH:17]([CH:18]3O)[CH2:16]1)[CH2:22]2)([CH3:10])([CH3:9])[CH3:8].CC1C=CC(S([CH2:37][N+:38]#[C-])(=O)=O)=CC=1.CCO>COCCOC>[C:7]([O:11][C:12](=[O:26])[NH:13][CH2:14][C:15]12[CH2:24][CH:19]3[CH2:20][CH:21]([CH2:23][CH:17]([CH:18]3[C:37]#[N:38])[CH2:16]1)[CH2:22]2)([CH3:10])([CH3:9])[CH3:8]
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Reactant: CC(C)(C)OC(=O)NCC12CC3CC(C1)C(O)C(C3)C2
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCO
Solvent: COCCOC
Product: CC(C)(C)OC(=O)NCC12CC3CC(C1)C(C#N)C(C3)C2
Temperature: 25 °C
Yield: 65.3 %

Procedure:
Solid t-BuOK (240 mg, 2.15 mmol) was added as 6 portions to a solution of ketone 1B (300 mg, 1.07 mmol) and TosMIC (273 mg, 1.40 mmol) in a mixture of DME (5.0 mL) and absolute EtOH (1 mL) while keeping the temperature between 5 and 10° C. The reaction mixture was allowed to warm to rt and was maintained for 30 min. The reaction mixture was then heated at 35-40° C. for 30 min and was then allowed to cool to rt. The precipitate (TosK) was removed by filtration and the filter cake was washed with DME. The combined organic layers were concentrated and the residue was purified by column chromatography (0/100 to 10/90 MeOH/EtOAc) to provide nitrile 17A (203 mg, 70%) as a mixture of equatorial and axial isomers. Data: LC/MS (ESR) m/z=291 [M+H]+.
Reaction SMILES: [C:1]([C:5]1[CH:31]=[CH:30][C:8]([CH2:9][N:10]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[N:12]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([N+:26]([O-])=O)=[CH:22][CH:21]=3)[C:11]2=[O:29])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[H][H]>[Pd].CO>[NH2:26][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][N:12]2[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[N:10]([CH2:9][C:8]3[CH:7]=[CH:6][C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:31][CH:30]=3)[C:11]2=[O:29])=[CH:25][CH:24]=1
Reactant: CC(C)(C)c1ccc(Cn2c(=O)n(Cc3ccc([N+](=O)[O-])cc3)c3ccccc32)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)c1ccc(Cn2c(=O)n(Cc3ccc(N)cc3)c3ccccc32)cc1

Procedure:
Palladium-on-charcoal (5%, 650 mg) was added to a solution of 1-(4-tert-butylbenzyl)-3-(4-nitrobenzyl)-1,3-dihydrobenzimidazol-2-one (P) (1.13 g, 2.73 mmol) in abs. MeOH (60 mL). The reaction mixture was subjected to a hydrogen pressure of 3 bar for 20 min at RT. The catalyst was separated by filtration, and the filtrate was concentrated in vacuo. The residue was taken up in EtOAc (10 mL) and filtered through a frit with kieselguhr (layer thickness 1 cm). The frit was washed with ethyl acetate (4×20 mL). The desired product 1-(4-aminobenzyl)-3-(4-tert-butylbenzyl)-1,3-dihydrobenzimidazol-2-one (Q) was obtained in a yield of 960 mg (91% of theory). The corresponding hydrochloride was obtained by reaction of 1-(4-aminobenzyl)-3-(4-tert-butylbenzyl)-1,3-dihydrobenzimidazol-2-one (Q) with chlorotrimethylsilane (1 mL, 7.9 mmol) in DCM (50 mL). The reaction mixture was stirred over a period of 17 h without exclusion of moisture, and the resulting solid matter was separated with the aid of a frit and then dried. The hydrochloride was obtained as solid matter (750 mg, 68% of theory, mp: 198-219° C.).
Reaction SMILES: C(OC(=O)[NH:7][CH:8]1[CH2:12][C:11](=[CH2:13])[CH2:10][CH:9]1[C:14](=[O:23])[NH:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)(C)(C)C>C(Cl)Cl.FC(F)(F)C(O)=O>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([NH:15][C:14]([CH:9]2[CH2:10][C:11](=[CH2:13])[CH2:12][CH:8]2[NH2:7])=[O:23])=[CH:17][CH:18]=1
Reactant: C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)Nc2ccc(Cl)cc2)C1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: C=C1CC(N)C(C(=O)Nc2ccc(Cl)cc2)C1
Yield: 68.5 %

Procedure:
A solution of 0.98 g of 35c in 10 ml of CH2Cl2 and 1.07 ml of trifluoroacetic acid was stirred at 22° C. for 2 h. The solution was evaporated and the residue partitioned between H2O and CH2Cl2. The aqueous layer was treated slowly with NaHCO3 until pH═8, the suspension was filtered, the residue washed with H2O and dried to give 0.48 g (69%) of the title compound 35d. MS: 251.3 (M+H)+.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=[C:4]([S:14][CH2:15][C:16]#[N:17])[N:3]=1.[CH2:18]([NH2:28])[C:19]1[CH:27]=[CH:26][C:25]2[O:24][CH2:23][O:22][C:21]=2[CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C>[O:24]1[C:25]2[CH:26]=[CH:27][C:19]([CH2:18][NH:28][C:2]3[CH:7]=[C:6]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[N:5]=[C:4]([S:14][CH2:15][C:16]#[N:17])[N:3]=3)=[CH:20][C:21]=2[O:22][CH2:23]1
Reactant: N#CCSc1nc(Cl)cc(-c2ccccc2)n1
Reactant: NCc1ccc2c(c1)OCO2
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Product: N#CCSc1nc(NCc2ccc3c(c2)OCO3)cc(-c2ccccc2)n1
Yield: 57.4 %

Procedure:
A stirred suspension of 19.5 g (0.075 mole) of (4-chloro-6-phenyl-2-pyrimidinylthio)acetonitrile, 11.3 g (0.074 mole) of piperonylamine and 7.95 g (0.075 mole) of sodium carbonate was heated under reflux in 250 ml of ethanol for six hours. The mixture was filtered and the filtrate was cooled in ice. The precipitate was collected and recrystallized from ethanol to give 16 g of product, mp. 140°-142°.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([N+:9]([O-:11])=[O:10])[CH:4]=1.[NH:12]1[CH2:16][CH2:15][CH2:14][CH2:13]1.C([O-])([O-])=O.[K+].[K+]>C1COCC1>[N+:9]([C:5]1[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=1)[CH2:2][N:12]1[CH2:16][CH2:15][CH2:14][CH2:13]1)([O-:11])=[O:10]
Reactant: O=[N+]([O-])c1cccc(CBr)c1
Reactant: C1CCNC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: O=[N+]([O-])c1cccc(CN2CCCC2)c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
1-(Bromomethyl)-3-nitrobenzene (51; 5 g, 23.1 mmol) was taken up in 100 mL of anhydrous THF along with pyrrolidine (2.3 mL, 27.72 mmol) and K2CO3 (4.8 g, 34.6 mmol). The reaction mixture was stirred at room temperature for 18 h and then filtered. The filtrate was concentrated under reduced pressure to afford 1-(3-nitrobenzyl)pyrrolidine 52. This material 52 was taken up in 100 mL of absolute EtOH and 10% Pd on C (300 mg) was added. The resulting reaction mixture was stirred at room temperature under 1 atm of hydrogen for 18 h. The mixture was then filtered through a pad of Celite and the filtrate was concentrated under reduced pressure to afford 2.81 g of 3-(pyrrolidin-1-ylmethyl)aniline 53 (70%).
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[CH2:6][C:5]2[C:7]([CH3:15])=[C:8]([CH3:14])[C:9]([CH:12]=O)=[C:10]([CH3:11])[C:4]=2[O:3]1.O.[OH-].[Na+].[CH3:20][C:21]([CH3:23])=[O:22]>>[CH3:1][C:2]1([CH3:16])[CH2:6][C:5]2[C:7]([CH3:15])=[C:8]([CH3:14])[C:9]([CH:12]=[CH:20][C:21](=[O:22])[CH3:23])=[C:10]([CH3:11])[C:4]=2[O:3]1
Reactant: CC(C)=O
Reactant: Cc1c(C)c2c(c(C)c1C=O)OC(C)(C)C2
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(=O)C=Cc1c(C)c(C)c2c(c1C)OC(C)(C)C2

Procedure:
To a solution of 37 g of the 2,3-dihydro-2,2,4,5,7-pentamethylbenzofuran-6-carboxaldehyde in 125 ml of acetone was added 60 ml of water and 68 g of 2% aqueous solution of sodium hydroxide. After refluxing for 20 hours, the reaction mixture was quenched with 10 ml of 2N aqueous solution of hydrochloric acid and the aqueous layer was extracted with dichloromethane. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to afford a crude product. Final purification was carried by recrystallization to afford 42.4 g of 4-(2,3-dihydro-2,2,4,5,7-pentamethylbenzofuran-6-yl)-3-butene-2-one.
Reaction SMILES: P(Cl)(Cl)Cl.[CH3:5][CH:6]1[CH:11]=[C:10]([C:12]([O:14][CH2:15][C:16]([Cl:19])([Cl:18])[Cl:17])=[O:13])[N:9]2[C:20](=[O:32])[CH:21]([NH:22][C:23](=[O:31])[CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C@H:8]2[S:7]1=O.C(OCC)(=O)C>CN(C)C=O>[CH3:5][CH:6]1[CH:11]=[C:10]([C:12]([O:14][CH2:15][C:16]([Cl:17])([Cl:18])[Cl:19])=[O:13])[N:9]2[C:20](=[O:32])[CH:21]([NH:22][C:23](=[O:31])[CH2:24][C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C@H:8]2[S:7]1
Reactant: CC1C=C(C(=O)OCC(Cl)(Cl)Cl)N2C(=O)C(NC(=O)Cc3ccccc3)[C@H]2S1=O
Solvent: ClP(Cl)Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC1C=C(C(=O)OCC(Cl)(Cl)Cl)N2C(=O)C(NC(=O)Cc3ccccc3)[C@H]2S1
Temperature: 0 °C
Reaction time: 1 h
Yield: 61.8 %

Procedure:
Phosphorus trichloride (0.5 ml.) was dropwise added under ice-cooling to a solution of 2,2,2-trichloroethyl 2-methyl-7-(2-phenylacetamido)-3-cephem-4-carboxylate-1-oxide (0.72 g.) in dimethylformamide (5 ml.) and the mixture was stirred for 1 hour at the same temperature. After the reaction, the reaction mixture was poured into a mixture of ethyl acetate (40 ml.) and ice-water (40 ml.), and the ethyl acetate layer was separated. The aqueous layer was further extracted with ethyl acetate (10 ml.), and the ethyl acetate layer was combined. The combined solution was washed in turn with 5% hydrochloric acid, a sodium bicarbonate aqueous solution and a saturated sodium chloride aqueous solution, and dried over magnesium sulfate. The dried solution was treated with activated charcoal and the solvent was distilled off. The residue was crystallized with a small amount of ether to give 2,2,2-trichloroethyl 2-methyl-7-(2-phenylacetamido)-3-cephem-4-carboxylate (0.43 g.), mp 175° to 178° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:16])([CH3:15])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])=[CH:4][C:3]=1[O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[Mg].[CH2:26]([CH:29]1[CH2:34][CH2:33][C:32](=[O:35])[CH:31]=[CH:30]1)[CH:27]=[CH2:28]>O1CCCC1>[CH2:18]([O:17][C:3]1[CH:4]=[C:5]([C:8]([CH3:16])([CH3:15])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH:6]=[CH:7][C:2]=1[C@H:30]1[C@H:29]([CH2:26][CH:27]=[CH2:28])[CH2:34][CH2:33][C:32](=[O:35])[CH2:31]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: CCCCCCC(C)(C)c1ccc(Br)c(OCc2ccccc2)c1
Reactant: C=CCC1C=CC(=O)CC1
Agent: [Mg]
Solvent: C1CCOC1
Product: C=CC[C@@H]1CCC(=O)C[C@H]1c1ccc(C(C)(C)CCCCCC)cc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 70 %

Procedure:
A solution of 73.0 g. (0.188 mole) of 1-bromo-2-benzyloxy-4-(1,1-dimethylheptyl)benzene (BrZ') in 350 ml. of tetrahydrofuran was slowly added to 9.0 g. (0.375 mole) of 70-80 mesh magnesium metal. After a 5 minute initiation period the rate of addition was adjusted so as to just maintain reflux. The reaction was stirred 1.5 hours longer following completion of addition while cooling to 25° C. The reaction was cooled to -20° C. and 1.78 g. (9.38 mmoles) of cuprous iodide added. The resultant mixture was stirred 5 minutes and then a solution of 25.5 g. (0.188 mole) of 4-(2-propenyl)-2-cyclohexen-1-one (enone) in 30 ml. of tetrahydrofuran added dropwise while the reaction temperature was maintained at about -18° C. Additional 1.78 g. (9.38 mmoles) portions of cuprous iodide were added following addition of 1/3 and 2/3 of the enone reactant. The reaction was stirred 5 minutes longer at -20° C. and then added to 1000 ml. of ice cold saturated ammonium chloride. The quenched mixture was extracted with 1000 ml. of ether and the organic extract washed twice with 500 ml. of saturated ammonium chloride, once with 500 ml. of saturated sodium chloride, dried over magnesium sulfate and evaporated (aspirator) to an oil. The crude oil was purified via column chromatography on 1 kg. of silica gel eluted with 20% etherhexane to yield 58.3 g. (70%) of the title compound as an oil.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[O:7][CH2:6][CH2:5]2.[B-](F)(F)(F)[CH:14]=[CH2:15].[K+].ClCCl.C(N(CC)CC)C>C(O)C>[CH:14]([C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[O:7][CH2:6][CH2:5]2)=[CH2:15]
Reactant: O=C1OCCc2cc(Br)ccc21
Reactant: C=C[B-](F)(F)F
Agent: [K+]
Solvent: CCN(CC)CC
Solvent: CCO
Solvent: ClCCl
Product: C=Cc1ccc2c(c1)CCOC2=O
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a 100 mL round bottom flask was added 6-bromo-3,4-dihydro-1H-isochromen-1-one (20 g, 88 mmol, 1.0 eq), potassium trifluoro(vinyl)borate (23.6 g, 176 mmol, 2.0 eq), [1,1′-bis(diphenylposphino)-ferrocene]dichloropalladium(II) complex with dichloromethane(1:1) (7.2 g, 8.8 mmol, 0.1 eq) and triethylamine (24.5 mL, 2.0 eq). To above mixture was added ethanol (400 mL). The flask was degassed and filled with nitrogen. The reaction was heated to reflux under N2 for 10 hr, then cooled and stirred at r.t. for 5 hr. The mixture was then diluted with EtOAc, filtered through a pad of Celite® and washed with brine. The organic phase was dried over Na2SO4, filtered and purified by flash column chromatography using Biotage and the solvent systems (0-50% EtOAc/Hexane). The fractions containing desired product were collected and concentrated to give 6-vinyl-3,4-dihydro-1H-isochromen-1-one.
Reaction SMILES: CC.[CH2:3]=[CH:4][CH2:5]/[CH:6]=[CH:7]\[CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]1[CH:23]=[C:22]([OH:24])[CH:21]=[CH:20][CH:19]=1.[CH:25]([O-])([O-])[O:26]CC>>[CH2:17]([C:18]1[CH:23]=[C:22]([OH:24])[C:21](=[CH:20][CH:19]=1)[CH:25]=[O:26])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH3:3]
Reactant: CCOC([O-])[O-]
Reactant: C=CC/C=C\C/C=C\CCCCCCCc1cccc(O)c1
Agent: CC
Product: CCCCCCCCCCCCCCCc1ccc(C=O)c(O)c1

Procedure:
(15:0)-Cardanol (10.2 g) is added to an equivalent proportion of ethyl magnesium bromide in dry ethereal solution to form the phenoxy magnesium bromide, completion of which is observed when evolution of ethane ceases. Ethyl orthoformate (10 cm3) is added and the ether removed by distillation so that the temperature rises to 100° C. After refluxing for three hours, the mixture is decomposed with dilute hydrochloric acid and warmed to effect the hydrolysis of the intermediate acetal formed. Etheral extraction and recovery gives a mixture of some unchanged (15:0)-cardanol and the formylated product, 4-pentadecylsalicylaldehyde which is separated by chromatography.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[CH:15]=[C:16]([S:20](Cl)(=[O:22])=[O:21])[CH:17]=[CH:18][CH:19]=3)[N:9]=2)[CH:5]=[C:4]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=2)[CH:3]=1.[F:34][C:35]([F:39])([F:38])[CH2:36][NH2:37].C(N(CC)CC)C>C1COCC1.CCOC(C)=O>[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[CH:15]=[C:16]([S:20]([NH:37][CH2:36][C:35]([F:39])([F:38])[F:34])(=[O:22])=[O:21])[CH:17]=[CH:18][CH:19]=3)[N:9]=2)[CH:5]=[C:4]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=2)[CH:3]=1
Reactant: NCC(F)(F)F
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)cc(-c2cccc(-c3cccc(S(=O)(=O)Cl)c3)n2)n1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)cc(-c2cccc(-c3cccc(S(=O)(=O)NCC(F)(F)F)c3)n2)n1
Yield: 41.9 %

Procedure:
The title compound was prepared from 3-[6′-methyl-4′-(4-trifluoromethyl-phenyl)-[2,2′]bipyridinyl-6-yl]-benzenesulfonyl chloride (example I.2) (0.465 g, 0.951 mmol) by treatment with commercially available 2,2,2-trifluorethylamine [CAS-no. 753-90-2] (0.15 ml, 1.9 mmol) and triethylamine (1.33 ml, 9.51 mmol) in THF (5 ml) at 23° C. for 16 h. Diluted with EtOAc, washed with 5% citric acid, sat. NaHCO3-sol. and brine, dried organic layer over Na2SO4. Removal of the solvent in vacuum left a crude product, which was purified by silica gel column chromatography with EtOAc followed by trituration with diethyl ether/heptane to give the title compound (0.220 g, 46%) as an off-white solid. MS (ISP) 552.2 [(M+H)+]; mp 198° C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:28])[NH:20][C:21]([CH3:27])=[CH:22][C:23]=2[CH2:24][CH2:25][CH3:26])=[O:15])[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.[CH3:29][O:30][C:31]1[N:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1>>[CH3:12][CH:11]([N:8]1[C:9]2[CH:10]=[C:2]([C:34]3[CH:35]=[N:36][C:31]([O:30][CH3:29])=[CH:32][CH:33]=3)[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]3[C:19](=[O:28])[NH:20][C:21]([CH3:27])=[CH:22][C:23]=3[CH2:24][CH2:25][CH3:26])=[O:15])[C:5]=2[CH:6]=[N:7]1)[CH3:13]
Reactant: COc1ccc(B(O)O)cn1
Reactant: CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(Br)cc2c1cnn2C(C)C
Product: CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(-c2ccc(OC)nc2)cc2c1cnn2C(C)C

Procedure:
The title compound was prepared in the same manner as described for example 75 from 6-bromo-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (100 mg, 0.225 mmol) and [6-(methyloxy)-3-pyridinyl]boronic acid (52 mg, 0.337 mmol). The final product was collected as a white solid (72 mg, 67%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.55 (br. s., 1H) 8.68 (br. s., 1H) 8.62 (br. s., 1H) 8.39 (s, 1H) 8.21 (br. s., 1H) 8.14 (s, 1H) 7.86 (s, 1H) 6.97 (d, J=8.59 Hz, 1H) 5.92 (s, 1H) 5.09-5.21 (m, 1H) 4.37-4.48 (m, 2H) 3.92 (s, 3H) 2.54 (br. s., 2H) 2.14 (s, 3H) 1.55 (m, 2H) 1.51 (br. s., 3H) 1.50 (br. s., 3H) 0.88 (t, J=7.20 Hz, 3H). LC-MS (ES) m/z=474.0