Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10]O)=[CH:4][CH:3]=1.[Br:12]C(Br)(Br)Br.O>ClCCl>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][Br:12])=[CH:4][CH:3]=1
Reactant: OCCCc1ccc(O)cc1
Reactant: BrC(Br)(Br)Br
Solvent: ClCCl
Solvent: O
Product: Oc1ccc(CCCBr)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 3-(4-hydroxyphenyl)-1-propanol 3A (4.0 g) and tripohenylphosphine (7.96 g) in anhydrous dichloromethane (77 mL), cooled to 0° C., is added, dropwise, a solution of tetrabromomethane (9.59 g) in anhydrous dichloromethane (15.4 mL). The reaction mixture gradually warmed to room temperature and allowed to stir overnight. The solution is then poured into water and extracted with ethyl acetate. The combined organic layers are washed with brine and dried over magnesium sulfate. The solution is concentrated in vacuo.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[CH2:9][C:10]#[N:11].[CH:12](OCC)=[O:13].[K].CC(C)([O-])C>C1(C)C=CC=CC=1>[OH:13][CH:12]=[C:9]([C:3]1[C:4]([CH3:8])=[CH:5][CH:6]=[CH:7][C:2]=1[CH3:1])[C:10]#[N:11]
Reactant: CCOC=O
Reactant: Cc1cccc(C)c1CC#N
Agent: CC(C)(C)[O-]
Agent: [K]
Solvent: Cc1ccccc1
Product: Cc1cccc(C)c1C(C#N)=CO
Reaction time: 2 h

Procedure:
126 g (0.87 mol) of 2,6-dimethylphenylacetonitrile are dissolved in 450 ml toluene and combined with 450 ml of ethyl formate. The mixture is cooled to a temperature of −10° C. and 144 g (1.29 mol) of potassium-tert.-butoxide are added in batches, so that the temperature does not exceed −5° C. It is left to react for a period of 30 minutes (min) at −5° C. and then for 2 hours (h) at ambient temperature. It is then extracted twice with 500 ml of water, the aqueous phase is made acidic with 100 ml of concentrated hydrochloric acid and extracted twice more with 500 ml of methylene chloride (dichloromethane). The organic phase is dried and concentrated by evaporation in vacuo. The residue is recrystallised from petroleum ether. Yield: 139 g (92% of theory).
Reaction SMILES: Br[CH2:2][CH2:3][O:4][CH3:5].[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[OH:14].C([O-])([O-])=O.[K+].[K+]>CC#N>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[O:14][CH2:2][CH2:3][O:4][CH3:5]
Reactant: Oc1ccc(F)cc1Br
Reactant: COCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COCCOc1ccc(F)cc1Br
Temperature: 80 °C
Reaction time: 16 h

Procedure:
1-bromo-2-methoxyethane (5.49 g, 39.5 mmol) was added to a mixture of 2-bromo-4-fluoro phenol (5 g, 26.18 mmol) and K2CO3 (11.5 g, 83.25 mmol) in CH3CN (41.5 mL) and continued stirring at 80° C. for 16 hr. The reaction mixture was quenched with 1M aq.NaOH solution, extracted with diethyl ether (3×100 mL), dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the crude, which was purified by column chromatography (using silica gel and 2% ethyl acetate in hexane as eluent) to afford the desired compound (Int-42). 1H NMR (300 MHz, CDCl3) δ ppm 7.3 (1H, m), 6.9 (1H, m), 6.7 (1H, m), 4.1 (2H, t), 3.8 (2H, t), 3.5 (3H, s).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:22]2[CH2:26][C@H:25]([CH2:27][NH:28][C:29](=[O:31])[CH3:30])[O:24][C:23]2=[O:32])[CH:5]=[C:6]([F:21])[C:7]=1[N:8]1[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]1.FC(F)(F)C(O)=O.[CH3:40][O:41][CH2:42][CH2:43]Cl.C(=O)([O-])[O-].[K+].[K+]>ClCCl.C(#N)C>[F:21][C:6]1[CH:5]=[C:4]([N:22]2[CH2:26][C@H:25]([CH2:27][NH:28][C:29](=[O:31])[CH3:30])[O:24][C:23]2=[O:32])[CH:3]=[C:2]([F:1])[C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([CH2:43][CH2:42][O:41][CH3:40])[CH2:10][CH2:9]1
Reactant: CC(=O)NC[C@H]1CN(c2cc(F)c(N3CCN(C(=O)OC(C)(C)C)CC3)c(F)c2)C(=O)O1
Reactant: COCCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COCCN1CCN(c2c(F)cc(N3C[C@H](CNC(C)=O)OC3=O)cc2F)CC1
Temperature: 25 °C
Yield: 53.3 %

Procedure:
A solution of (S)-N-[[3-[3,5-difluoro-4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (0.200 g, 0.441 mmol) in dichloromethane (1 mL) was treated with trifluoroacetic acid (4 mL) at room temperature for 1 h. The reaction mixture was concentrated in vacuo and the resultant residue combined with 2-chloroethyl methyl ether (403 μL, 4.41 mmol), potassium carbonate (0.730 g, 5.28 mmol), and acetonitrile (9 mL) and the mixture heated to reflux for 15 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was triturated with dichloromethane, the solids filtered off, and the filtrate concentrated in vacuo to give the crude product. This crude material was chromatographed over silica gel (10 g), eluting with 1%, 3%, and then 5% methanol/chloroform, to afford, after concentration of appropriate fractions, 0.097 g (53%) of the title compound as an off-white solid with mp 162°-164° C.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[C:7]1(=[O:13])[NH:11][C:10](=[O:12])[CH2:9][CH2:8]1.[F:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19]Br)=[CH:17][CH:16]=1>CC(C)=O>[F:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][N:11]2[C:10](=[O:12])[CH2:9][CH2:8][C:7]2=[O:13])=[CH:17][CH:16]=1
Reactant: O=C1CCC(=O)N1
Reactant: Fc1ccc(CBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: O=C1CCC(=O)N1Cc1ccc(F)cc1
Yield: 85.1 %

Procedure:
Freshly ground potassium carbonate, K2CO3 (31 g, 225 mmol) was added to dry acetone (200 ml) in a 3-necked flask equipped with drying tube, condenser, and mechanical stirrer. Succinimide (7.43 g, 75 mmol) and 4-fluorobenzylbromide (11.21 mL, 90 mmol) were added. The mixture was refluxed for 19 hours and filtered through Celite. Acetone was removed under vacuum, diluted with EtOAc, washed with saturated aqueous sodium bicarbonate and also with brine, dried (MgSO4), filtered and concentrated to give crude. Crude product was chromatographed (EtOAc/Hexane) on silica gel to give N-4-fluorobenzyl-succinimide 1 as white solid (13.22 g, 85%). 1H NMR (CDCl3) δ 7.4 (dd, 2H), 7.0 (t, 2H), 4.6 (s, 1H), 2.7 (s, 4 H).
Reaction SMILES: [CH2:1]([NH:3][CH2:4][CH3:5])[CH3:2].C(N(CC)CC)C.[F:13][C:14]([F:35])([F:34])[C:15]1[CH:16]=[CH:17][C:18]([O:21][C:22]2[CH:33]=[CH:32][C:25]([O:26][CH:27]([CH3:31])[C:28](Cl)=[O:29])=[CH:24][CH:23]=2)=[N:19][CH:20]=1>C1C=CC=CC=1>[CH2:1]([N:3]([CH2:4][CH3:5])[C:28](=[O:29])[CH:27]([O:26][C:25]1[CH:32]=[CH:33][C:22]([O:21][C:18]2[CH:17]=[CH:16][C:15]([C:14]([F:35])([F:34])[F:13])=[CH:20][N:19]=2)=[CH:23][CH:24]=1)[CH3:31])[CH3:2]
Reactant: CCNCC
Reactant: CC(Oc1ccc(Oc2ccc(C(F)(F)F)cn2)cc1)C(=O)Cl
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: CCN(CC)C(=O)C(C)Oc1ccc(Oc2ccc(C(F)(F)F)cn2)cc1
Temperature: 25 °C

Procedure:
3.4 g (0.046 mol) of diethylamine and 4.8 g (0.47 mol) of triethylamine dissolved in 10 ml of benzene are dropped into the solution of 15.6 g (0.045 mol) of 2-[4-(5-trifluoromethyl-2-pyridyloxy)phenoxy]propionyl chloride in 40 ml of anhydrous benzene at 0°-5° C. under stirring. After termination of the portionwise addition, the reaction mixture is stirred for additional 2 hours whilst it is allowed to warm to room temperature. The mixture is filtered off, the precipitate is washed with a little volume of ether, the filtrate is washed first with 5% hydrochloric acid and then with saturated sodium chloride solution, then dried over anhydrous magnesium sulfate and finally evaporated to dryness. The crude product is purified by chromatography on a column filled with silica gel of 0.063-0.2 mm particle size by using a 4:1 mixture of n-hexane/acetone for elution.
Reaction SMILES: S(=O)(=O)(O)O.[C:6]1([OH:14])[C:7]([CH3:13])=[CH:8][CH:9]=[C:10]([CH3:12])[CH:11]=1.C1(O)C=CC=CC=1.[N:22]([O-])=[O:23].[Na+]>O.C(O)(=O)C>[N:22]([C:9]1[CH:8]=[C:7]([CH3:13])[C:6]([OH:14])=[CH:11][C:10]=1[CH3:12])=[O:23]
Reactant: Cc1ccc(C)c(O)c1
Reactant: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Solvent: Oc1ccccc1
Product: Cc1cc(N=O)c(C)cc1O
Reaction time: 0.21 h

Procedure:
A solution of 20 mL of 36N sulfuric acid solution in 40 mL of water (60 mL of 12N sulfuric acid) is added to a mixture of 6I g (500 mmol) of 2,5-xylenol and 200 mL of glacial acetic acid. A homogeneous solution is produced initially, but on continued stirring some of the phenol crystallizes. A solution of 35 g (500 mmol) of sodium nitrite in 60 mL of water is added dropwise to the previous mixture over 60 minutes at 5° to 10° C. Stirring is continued for 10 to 15 minutes and the heterogeneous mixture is poured into 1 L of water. The reaction flask is rinsed with water and the solid nitroso derivative collected, washed with water, and dried to a moist cake.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:14])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][CH:7]=1)[CH3:2].[CH2:15](OC(=O)C(OCC)=O)C.[H-].[Na+]>>[CH3:13][O:12][C:9]1[CH:10]=[CH:11][C:6]([C:5](=[CH2:15])[C:4]([O:3][CH2:1][CH3:2])=[O:14])=[CH:7][CH:8]=1
Reactant: CCOC(=O)Cc1ccc(OC)cc1
Reactant: CCOC(=O)C(=O)OCC
Agent: [H-]
Agent: [Na+]
Product: C=C(C(=O)OCC)c1ccc(OC)cc1

Procedure:
A process for preparing a compound of formula (6): ##STR120## characterized in that a compound of formula (1): ##STR121## is reacted with oxalic acid diethyl ester and sodium hydride to produce a compound of formula (2): ##STR122## the resulting compound of formula (2) is reacted with 3-methoxybenzenethiol represented by the formula: ##STR123## to produce a compound of formula (3): ##STR124## the resulting compound of formula (3) is reacted with hydrochloric acid to produce a compound of formula (4): ##STR125## the compound of formula formula (4) is then cyclized to produce a compound of formula (5): ##STR126## and the compound of formula (5) is reacted with methyl iodide in the presence of lithium diisopropylamide to produce the compound of formula (6).
Reaction SMILES: [C:1]12[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=1)[NH:6][C:5](=[O:12])[O:4][C:2]2=[O:3].O[CH2:14][CH2:15][N:16]1[CH:20]=[CH:19][N:18]=[CH:17]1>>[N:16]1([CH2:15][CH2:14][N:6]2[C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:1]=3[C:2](=[O:3])[O:4][C:5]2=[O:12])[CH:20]=[CH:19][N:18]=[CH:17]1
Reactant: O=c1[nH]c2ccccc2c(=O)o1
Reactant: OCCn1ccnc1
Product: O=c1oc(=O)n(CCn2ccnc2)c2ccccc12

Procedure:
Prepared by a similar procedure as described for preparation 7B, starting from isatoic anhydride and 1-(2-hydroxyethyl)-imidazole (Fluorochem). 13C-NMR (DMSO-d6) δ 158.7, 147.5, 141.3, 137.6, 136.9, 129.4, 128.5, 123.6, 119.7, 114.0, 111.3, 45.1, 43.3.
Reaction SMILES: S(=O)(=O)(O)O.[OH:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[C:17](=[O:18])[CH2:16][CH:15]([C:19]([OH:21])=[O:20])[CH2:14]2)=[CH:9][CH:8]=1.[CH3:22]O>>[OH:6][C:7]1[CH:8]=[CH:9][C:10]([N:13]2[C:17](=[O:18])[CH2:16][CH:15]([C:19]([O:21][CH3:22])=[O:20])[CH2:14]2)=[CH:11][CH:12]=1
Reactant: CO
Reactant: O=C(O)C1CC(=O)N(c2ccc(O)cc2)C1
Agent: O=S(=O)(O)O
Product: COC(=O)C1CC(=O)N(c2ccc(O)cc2)C1
Yield: 89 %

Procedure:
A catalytic amount of concentrated sulfuric acid is added to a solution of 1-(4-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid a50 (3.7 g, 16.7 mmol, 1 eq) in methanol (100 ml) and the mixture is heated at reflux overnight. The solvent is then removed under vacuum, and the residue is dissolved into ethyl acetate. The organic layer is washed with a saturated solution of aqueous sodium hydrogenocarbonate, dried over magnesium sulfate and concentrated under vacuum to afford 3.5 g of methyl 1-(4-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylate a51.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1.N1CCC[C@H]1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH:33]=[C:34]([C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[CH:37]=1)[CH3:35]>CN(C=O)C.[Cu]I>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:33]=[C:34](\[C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[CH:37]=3)/[CH3:35])[C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1
Reactant: CN1CCc2[nH]c3ccc(Cl)cc3c2C1
Reactant: CC(=CBr)c1cccc(F)c1
Agent: [Cu]I
Agent: O=C(O)[C@@H]1CCCN1
Agent: O=P([O-])([O-])[O-]
Solvent: CN(C)C=O
Product: C/C(=C/n1c2c(c3cc(Cl)ccc31)CN(C)CC2)c1cccc(F)c1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
8-Chloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (220 mg, 1 mmol) was dissolved in DMF. Copper (I) iodide (19 mg, 0.1 mmol), L-proline (23 mg, 0.2 mmol) and potassium phosphate (424 mg, 2 mmol) were added and the reaction mixture was stirred for 10 min. at RT. 1-(1-Bromoprop-1-en-2-yl)-3-fluorobenzene (258 mg, 1.2 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated overnight at 85° C. (prolonged heating in some cases was required). DMF was evaporated under reduced pressure, the residue was diluted with water and the solid was filtered. The solid material was purified by silica gel chromatography (100-200 mesh) eluting with 0-5% MeOH-DCM. The product was further purified by HPLC. Yield: 85 mg. 1H NMR (CD3OD, TFA salt) δ (ppm): 7.42 (s, 1H), 7.20 (d, 1H), 7.12 (m, 2H), 6.90 (t, 1H), 7.82 (d, 2H), 6.78 (dd, 1H), 4.60 (d, 1H), 4.30 (d, 1H), 3.70 (m, 1H), 3.40 (m, 1H), 3.0 (s, 3H), 2.80 (m, 2H), 2.30 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[C:8]2[CH:9]=[CH:10][C:11]([O:13][C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)=[CH:12][C:7]=2[O:6][C:4](=[O:5])[CH:3]=1.P(O)(O)(O)=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.CCC(COC(C(N(CC[NH+](C)C)C)=O)(C1C=CC=CC=1)C1C=CC=CC=1)CC.[Cl-].C[C@@H]([C@@H]1[C@@]2(C)[C@@H](O)C[C@@H]3[C@@]4(C)CC[C@@H](O)C[C@H]4C[C@@H](O)[C@H]3[C@@H]2CC1)CCC(NCCS([O-])(=O)=O)=O.[Na+]>>[CH3:1][C:2]1[C:8]2[CH:9]=[CH:10][C:11]([OH:13])=[CH:12][C:7]=2[O:6][C:4](=[O:5])[CH:3]=1
Reactant: Cc1cc(=O)oc2cc(O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)ccc12
Agent: CCC(CC)COC(C(=O)N(C)CC[NH+](C)C)(c1ccccc1)c1ccccc1
Agent: C[C@H](CCC(=O)NCCS(=O)(=O)[O-])[C@H]1CC[C@H]2[C@@H]3[C@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3C[C@H](O)[C@]12C
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Product: Cc1cc(=O)oc2cc(O)ccc12
Reaction time: 0.5 h

Procedure:
GC enzymatic activity was measured by the method of Ohashi, T., et al., J. Biol Chem. 266:3661 (1991), the disclosure of which is incorporated herein by reference, with the synthetic fluorogenic substrate 4-methylumbelliferyl-β-D-glucopyranoside (4MU-glc) (Sigma, St. Louis, Mo.). The reaction mixture (200 μl) contained 5 mM 4MU-glc, 0.1M citrate phosphate buffer (pH 5.4), 2.1 mM Triton X-100, 0.1% bovine serum albumin, and 3.5 mM sodium taurocholate. After incubation of each cell lysate with the substrate for 30 minutes at 37° C., reactions were terminated by the addition of 3.8 ml of 0.17M glycine carbonate buffer (pH 10.4). The 4-methylumbelliferone (4MU) that had formed was measured fluorometrically. Units of GC activity were expressed as nanomoles of 4MU substrate produced/hour/mg protein. All values represent the average of duplicate measurements.
Reaction SMILES: Cl[C:2]1[C:11]([CH3:12])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[NH:13]1[CH:17]=[N:16][CH:15]=[N:14]1.O.[OH-].[NH4+]>C(O)C>[N:13]1([C:2]2[C:11]([CH3:12])=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH:17]=[N:16][CH:15]=[N:14]1
Reactant: Cc1cc2ccccc2nc1Cl
Reactant: c1nc[nH]n1
Agent: [NH4+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: Cc1cc2ccccc2nc1-n1cncn1
Reaction time: 4 h
Yield: 70.9 %

Procedure:
A mixture of 1.78 g of 2-chloro-3-methyl-quinoline and 0.69 g of 1,2,4-triazole is melt and allowed to stand at 120° C. for 4 hours. The melt is cooled, then dissolved in 10 ml of ethanol, poured into 20 ml of water and neutralized with 1 ml of concentrated ammonium hydroxide. The precipitated product is filtered. Thus 1.49 g of the desired compound are obtained, yield 71%. Mp.: 80°-81° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[OH:9].IC.[C:12](=O)([O-])[O-].[K+].[K+].O>CC(C)=O>[Br:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[O:9][CH3:12]
Reactant: O=C([O-])[O-]
Reactant: Oc1ccc(Cl)cc1Br
Agent: [K+]
Solvent: O
Solvent: CI
Solvent: CC(C)=O
Product: COc1ccc(Cl)cc1Br
Temperature: 25 °C
Yield: 98.2 %

Procedure:
In a 250 mL r.b. flask, a solution of 2-bromo-4-chlorophenol (Lancaster: 16.94 g, 81.6 mmol, 1.0 equivuiv) in acetone (160 mL) was treated sequivuentially with iodomethane (6.10 mL, 98 mmol, 1.2 equivuiv), potassium carbonate (12 g), and water (4 mL). The reaction mixture was heated at reflux for 3 h, cooled to rt, and the bulk of the volatiles was removed under reduced pressure. The residue was poured into water (140 mL) and extracted with EtOAc (3×150 mL). The extracts were washed with brine (1×100 mL, combined, dried (K2CO3), filtered through a pad of Celite™, and concentrated to a clear oil. Short-path distillation (80°-85° C., 1 Torr) afforded 17.74 g (98%) of 2-bromo-4-chloroanisole as a clear liquid. Data for 2-bromo-4-chloroanisole: 1H NMR (400 MHz, acetone-d6) 7.53 (d, J=2.5, 1 H); 7.24 (dd, J=9.7, 2.5, 1 H); 6.81 (d, J=9.7, 1 H); 3.88 (s, 3 H).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=1)=[O:6].[NH:14]1[CH2:19][CH2:18][CH:17]([C:20]2[CH:21]=[C:22]([NH:26][C:27](=[O:30])[CH2:28][CH3:29])[CH:23]=[CH:24][CH:25]=2)[CH2:16][CH2:15]1>>[CH3:13][C:10]1[CH:11]=[CH:12][C:7]([C:5](=[O:6])[CH2:4][CH2:3][CH2:2][N:14]2[CH2:19][CH2:18][CH:17]([C:20]3[CH:21]=[C:22]([NH:26][C:27](=[O:30])[CH2:28][CH3:29])[CH:23]=[CH:24][CH:25]=3)[CH2:16][CH2:15]2)=[CH:8][CH:9]=1
Reactant: Cc1ccc(C(=O)CCCCl)cc1
Reactant: CCC(=O)Nc1cccc(C2CCNCC2)c1
Product: CCC(=O)Nc1cccc(C2CCN(CCCC(=O)c3ccc(C)cc3)CC2)c1

Procedure:
Prepared by Procedure K and Scheme B1 using 4-chloro-1-(4-methylphenyl)-1-butanone and N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 393.2 (M+H)+.
Reaction SMILES: [C:1]1([C:7]([OH:20])([CH2:10][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([CH3:13])[CH3:12])[CH2:8][OH:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CS(C)=O>C(N(CC)CC)C>[C:1]1([C:7]([OH:20])([CH2:10][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([CH3:13])[CH3:12])[CH:8]=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)(CC(O)(CO)c1ccccc1)c1ccccc1
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: CC(C)(CC(O)(C=O)c1ccccc1)c1ccccc1

Procedure:
Analogously to Example 1, 445 mg of 2,4-diphenyl-4-methyl-1,2-pentanediol is converted with 1.02 g of pyridine-sulfur trioxide complex, 5.85 ml of DMSO and 1.16 ml of triethylamine into 390 mg of aldehyde.
Reaction SMILES: [CH3:1][C:2]1[C:10]([C:11](=[O:19])[C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].S([O-])([O-])(=O)=O.[Ba+2].CCCCC1N=C(OCCN(C)C)C2C(=CC=CC=2)C=1.[S].[H][H].Cl>C1(C)C(C)=CC=CC=1>[CH3:1][C:2]1[C:10]([C:11](=[O:19])[C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[CH:9][CH:8]=[CH:7][C:3]=1[CH:4]=[O:5]
Reactant: [H][H]
Reactant: Cc1c(C(=O)Cl)cccc1C(=O)c1ccc(Cl)cc1
Agent: CCCCc1cc2ccccc2c(OCCN(C)C)n1
Agent: Cl
Agent: O=S(=O)([O-])[O-]
Solvent: Cc1ccccc1C
Product: Cc1c(C=O)cccc1C(=O)c1ccc(Cl)cc1
Temperature: 130 °C
Reaction time: 0.75 h
Yield: 62.7 %

Procedure:
A mixture of 43.92 g of 2-methyl-3-(p-chlorobenzoyl)-benzoic acid chloride, 450 ml of xylene, 4.5 g of barium sulfate containing 10% palladium and 0.4 ml of a solution obtaining by refluxing 6 g of quinolein and 1 g of sulfur for 5 hours was cooled and then was diluted with 70 ml of xylene. The mixture was stirred at 130° C. while passing hydrogen therethrough for 45 minutes and the said temperature was held until evolution of hydrochloric acid ceased. An inert gas was passed therethrough at 130° C. and the mixture was then cooled to 30° C. and filtered to remove the catalyst. The solvent was distilled off and the residual oil was dissolved in isopropyl ether. Sodium bisulfite was added to the resulting solution and the mixture was stirred for 18 hours. The bisulfitic compound which precipitated was recovered by vacuum filtration, was washed and was then decomposed by stirring for 21/2 hours in the presence of dilute sulfuric acid and ether under an inert gas. The ether was decanted and the aqueous phase was extracted with ether. The combined ether phases were washed with water, dried and evaporated to dryness under reduced pressure. The residue was crystallized from isopropyl ether to obtain 24.3 g of 2-methyl-3-(p-chlorobenzoyl)-benzaldehyde melting at 68° C.
Reaction SMILES: [N+:1](=[CH:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])=[N-:2].[CH3:9][CH:10]1[CH2:15][C:14](=O)[CH:13]=[CH:12][C:11]1([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.C(NC(C)C)(C)C>O1CCCC1.C(OCC)C.C(O)(=O)C>[CH3:9][CH:10]1[C:15]2[NH:2][N:1]=[C:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:14]=2[CH:13]=[CH:12][C:11]1([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: CCOC(=O)C=[N+]=[N-]
Reactant: CC1CC(=O)C=CC1(c1ccccc1)c1ccccc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Solvent: CCOCC
Product: CCOC(=O)c1n[nH]c2c1C=CC(c1ccccc1)(c1ccccc1)C2C
Temperature: -70 °C
Reaction time: 2 h

Procedure:
0.41 cm3 of ethyl diazoacetate is added dropwise to a solution, cooled to −78° C., of 0.8 g of 5-methyl-4,4-diphenylcyclohex-2-enone, which may be obtained according to J. Amer. Chem. Soc. 1995, 107, 5245–61, in 30 cm3 of tetrahydrofuran, followed by slow addition of 11.67 cm3 of lithium diisopropylamide solution prepared from 3 cm3 of 1.6M n-butyllithium and 0.67 cm3 of diisopropylamine in solution in 8 cm3 of tetrahydrofuran. After stirring the reaction mixture at a temperature in the region of −70° C. for 2 hours, 0.34 cm3 of glacial acetic acid is added and the temperature is allowed to rise to the region of 20° C. 100 cm3 of ethyl ether are added and the organic phases are then washed with five times 70 cm3 of distilled water, dried over sodium sulphate and concentrated to dryness under reduced pressure. The residue is dissolved in 25 cm3 of toluene, heated at a temperature in the region of 110° C. for 4 hours and then concentrated to dryness under reduced pressure. The residue obtained is purified by flash chromatography on silica gel (35–70 μm), eluting with a cyclohexane/ethyl acetate (80/20) mixture; 0.133 g of ethyl 7-methyl-6,6-diphenyl-6,7-dihydro-1H-indazole-3-carboxylate is obtained in the form of an off-white solid, the characteristics of which are as follows: