Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH:10]=[C:11]([Cl:13])[Cl:12])[CH:5]=[C:4]([Cl:14])[C:3]=1[OH:15].[Cl:16][C:17]([Cl:31])=[CH:18][CH2:19][O:20][N:21]=[CH:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29]O)=[CH:25][CH:24]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[Cl:16][C:17]([Cl:31])=[CH:18][CH2:19][O:20][N:21]=[CH:22][C:23]1[CH:24]=[CH:25][C:26]([CH2:29][O:15][C:3]2[C:2]([Cl:1])=[CH:7][C:6]([O:8][CH2:9][CH:10]=[C:11]([Cl:13])[Cl:12])=[CH:5][C:4]=2[Cl:14])=[CH:27][CH:28]=1
Reactant: Oc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Reactant: OCc1ccc(C=NOCC=C(Cl)Cl)cc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: ClC(Cl)=CCON=Cc1ccc(COc2c(Cl)cc(OCC=C(Cl)Cl)cc2Cl)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 66.7 %

Procedure:
To a mixture of 0.35 g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol, 0.32 g of 4-(hydroxymethyl)benzaldehyde O-(3,3-dichloro-2-propenyl)oxime, 0.32 g of triphenylphosphine, and 10 ml of dichloromethane was slowly added dropwise 0.25 g of diisopropyl azodicarboxylate. After stirring at room temperature for 12 hours, the reaction mixture was concentrated to give a residue. This residue was subjected to silica gel chromatography, which afforded 0.43 g (yield, 67%) of 4-((2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)methyl)benzaldehyde O-(3,3-dichloro-2-propenyl)oxime, m.p., 76.2° C.
Reaction SMILES: C(O)(=O)C.[N+:5]([C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:17]=1[N:16]=[CH:15][C:14]([S:18]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:20])=[O:19])=[CH:13]2)([O-])=O.C1(C)C=CC=CC=1.[CH3:34][S:35]([OH:38])(=[O:37])=[O:36]>C1COCC1.O.[Fe]>[CH3:34][S:35]([OH:38])(=[O:37])=[O:36].[NH2:5][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:17]=1[N:16]=[CH:15][C:14]([S:18]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)(=[O:20])=[O:19])=[CH:13]2
Reactant: O=[N+]([O-])c1cccc2cc(S(=O)(=O)c3ccccc3)cnc12
Agent: [Fe]
Agent: CS(=O)(=O)O
Solvent: O
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: Nc1cccc2cc(S(=O)(=O)c3ccccc3)cnc12
Temperature: 50 °C
Reaction time: 1 h

Procedure:
A suspension of iron powder (26.7 g, 5 eq, 325 mesh) in THF (300 ml, 10 vol), water (30 ml, 1 vol) and acetic acid (19.2 ml, 3.5 eq) was heated to 50° C. 8-Nitro-3-phenylsulfonylquinoline (D4) (30 g, 1 wt) was added portionwise to the mixture over 30 min, keeping the temperature below 60° C. The reaction mixture was stirred at 50 to 55° C. for 60 min. Toluene (240 ml, 8 vol) was added, followed by water (60 ml, 2 vol) before cooling to 40° C. and filtering the mixture through a silica gel plug. The silica plug was washed with toluene (2×60 ml, 2 vol). The layers of the combined filtrate were separated and the organic layer concentrated in vacuo to ca 10 volumes. The reaction mixture was warmed to 77° C. then treated with methanesulfonic acid (7.42 ml, 1.2 eq) added over 15 min maintaining the temperature at 75 to 80° C. The resulting orange suspension was cooled slowly to ambient, stirred at ambient temperature for ca 2 h, then the product filtered and washed with toluene (3×60 ml). The resulting pink solid (D35) was dried in vacuo at ca 45° C. to constant weight. Yield: 34.17 g, 94%.
Reaction SMILES: [C:1]([OH:4])(=[O:3])[CH3:2].O.[C:6]1([CH3:12])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>[Pd]>[C:1]([O:4][CH2:12][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)O
Reactant: Cc1ccccc1
Agent: [Pd]
Solvent: O
Product: CC(=O)OCc1ccccc1
Reaction time: 2 h

Procedure:
A mixture of 70.7 wt. % acetic acid, 23.2 wt. % toluene and 6.1 wt. % water was first, at the rate of 0.198 gm./min., vaporized and then fed into a 3/8" I.D. stainless-steel tubular reactor packed with about 4.7 gm. of palladium on alumina support, at 160°-170° C. and about 30 psig. The palladium content contained in the supported catalyst was about 2% by weight. After about two hours of continuously running the reaction, the gaseous reaction product was directly sent to an on-line G.C. analyzer. The G.C. analysis showed that about 15% of toluene was converted; and that no product other than benzyl acetate was formed from the vapor phase reaction. A check based on the feed/product material balance indicated that the yield of benzyl acetate was over 90 mole % of toluene reacted.
Reaction SMILES: [OH-:1].[K+].Cl[C:4]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[C:10]2[C:5]=1[CH:6]=[CH:7][CH:8]=[N:9]2>CCO.O>[N+:14]([C:11]1[C:10]2[N:9]=[CH:8][CH:7]=[CH:6][C:5]=2[C:4]([OH:1])=[CH:13][CH:12]=1)([O-:16])=[O:15]
Reactant: [OH-]
Reactant: O=[N+]([O-])c1ccc(Cl)c2cccnc12
Agent: [K+]
Solvent: O
Solvent: CCO
Product: O=[N+]([O-])c1ccc(O)c2cccnc12
Temperature: 100 °C
Yield: 67.6 %

Procedure:
KOH (2.69 g, 47.9 mmol) was added to a solution of 5-chloro-8-nitro-quinoline 27 (1.0 g, 4.79 mmol) in EtOH (20 ml) and water (30 ml) and the mixture was heated at 100° C. for 2 h. The reaction mixture was cooled in the fridge for 18 h and the resulting crystals were collected by filtration and dried to give the title compound (616 mg, 68%).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]3([CH2:22][O:23][P:24]([C:30]([CH3:33])([CH3:32])[CH3:31])([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])[CH2:20][O:19][C:18]([CH3:21])=[N:17]3)=[CH:10][CH:9]=2)=[C:4]([F:34])[CH:3]=1.[CH3:35][C:36]1[CH:37]=[C:38]([SH:42])[CH:39]=[CH:40][CH:41]=1.C(N(C(C)C)CC)(C)C.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd].O>[F:34][C:4]1[CH:3]=[C:2]([S:42][C:38]2[CH:39]=[CH:40][CH:41]=[C:36]([CH3:35])[CH:37]=2)[CH:7]=[CH:6][C:5]=1[C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]2([CH2:22][O:23][P:24]([C:30]([CH3:33])([CH3:32])[CH3:31])([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])[CH2:20][O:19][C:18]([CH3:21])=[N:17]2)=[CH:10][CH:9]=1
Reactant: CC1=NC(CCc2ccc(-c3ccc(Br)cc3F)cc2)(COP(=O)(C(C)(C)C)C(C)(C)C)CO1
Reactant: Cc1cccc(S)c1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClC(Cl)Cl
Solvent: C1COCCO1
Product: CC1=NC(CCc2ccc(-c3ccc(Sc4cccc(C)c4)cc3F)cc2)(COP(=O)(C(C)(C)C)C(C)(C)C)CO1
Yield: 65.4 %

Procedure:
A solution of 4-[2-(4′-bromo-2′-fluorobiphenyl-4-yl)ethyl]-4-di(tert-butyl)phosphoryloxymethyl-2-methyl-2-oxazoline (210 mg) of Example 23, (23-2), 3-methylbenzenethiol (49 mg), diisopropylethylamine (93 mg), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (18.6 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (21.4 mg) in 1,4-dioxane (2 mL) was heated under reflux for 9 hr under a nitrogen atmosphere. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound (148 mg) as a pale-yellow oil.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH:16]([O:23][C:24](=[O:26])[NH2:25])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:34](Cl)(=[O:36])[CH3:35]>O1CCCC1.O>[C:24]([O:23][CH:16]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:15][CH2:14][N:11]1[CH2:12][CH2:13][N:8]([C:5]2[CH:6]=[CH:7][C:2]([O:1][C:34](=[O:36])[CH3:35])=[CH:3][CH:4]=2)[CH2:9][CH2:10]1)(=[O:26])[NH2:25]
Reactant: CC(=O)Cl
Reactant: NC(=O)OC(CCN1CCN(c2ccc(O)cc2)CC1)c1ccccc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: O
Product: CC(=O)Oc1ccc(N2CCN(CCC(OC(N)=O)c3ccccc3)CC2)cc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
The compound ‘carbamic acid 3-[4-(4-hydroxy-phenyl)-piperazin-1-yl]-1-phenyl-propyl ester (2 mmol) prepared in Example 84 was dissolved in tetrahydrofuran (25 mL), and triethylamine (2.4 mmol) and acetylchloride (2.4 mmol) were added thereto, and the resulting mixture was stirred at a room temperature for 5 hours. The reaction mixture was diluted with water, and extracted several times with ethyl acetate to obtain an organic phase. The prepared organic phase was dried over magnesium sulfate, and concentrated under a reduced pressure. The resulting pellet was purified with column chromatography (hexane:ethyl acetate=1:1) to obtain a title compound.
Reaction SMILES: [Br-].C([N+]1C2C=CC=CC=2SC=1)C.[CH:13]([C:15]1[CH:32]=[CH:31][C:18]([CH:19]=[C:20]2[CH:28]3[CH2:29][CH:22]([CH:23]4[CH:27]3[CH2:26][CH2:25][CH2:24]4)[C:21]2=[O:30])=[CH:17][CH:16]=1)=[O:14].[O:33]=[C:34]1CC2CC1C1C2CCC1.C[O-].[Na+].C=O>C(O)C.C(N(CC)CC)C>[OH:33][CH2:34][C:13]([C:15]1[CH:16]=[CH:17][C:18]([CH:19]=[C:20]2[CH:28]3[CH2:29][CH:22]([CH:23]4[CH:27]3[CH2:26][CH2:25][CH2:24]4)[C:21]2=[O:30])=[CH:31][CH:32]=1)=[O:14]
Reactant: O=Cc1ccc(C=C2C(=O)C3CC2C2CCCC32)cc1
Reactant: O=C1CC2CC1C1CCCC21
Agent: C=O
Agent: CC[n+]1csc2ccccc21
Agent: C[O-]
Solvent: CCO
Solvent: CCN(CC)CC
Product: O=C(CO)c1ccc(C=C2C(=O)C3CC2C2CCCC32)cc1

Procedure:
0.8 g (3.5 mmol) of 3-ethylbenzothiazolium bromide and triethylamine are added to a mixture of 35 mmol of 9-(4'- formylbenzylidene)-8-ketotricyclo[5.2.1.02.6 ]decane (prepared from 8-ketotricyclo[5.2.1.02.6 ]decane and terephthaldehyde di ethyl acetal (sic) in the presence of sodium methylate and subsequent acetal cleavage) and 1.2 g of paraformaldehyde in 70 ml of ethanol, and the mixture is heated under reflux. After working up analogously to Example 1, 9-(4'-(2"-hydroxy1"-oxoethyl)-benzylidene)-8-ketotricyclo[5.2.1.02.6 ]decane is obtained. The spectra correspond to the expected compound.
Reaction SMILES: [I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[CH3:9][N:10]([CH:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25](=[O:27])[CH3:26])[CH2:20][CH2:19]1)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14].O>CS(C)=O>[CH3:9][N:10]([CH:18]1[CH2:19][CH2:20][N:21]([CH2:24][C:25]2([CH3:2])[CH2:26][O:27]2)[CH2:22][CH2:23]1)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:14])[CH3:15]
Reactant: C[S+](C)(C)=O
Reactant: CC(=O)CN1CCC(N(C)C(=O)OC(C)(C)C)CC1
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CN(C(=O)OC(C)(C)C)C1CCN(CC2(C)CO2)CC1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 86.9 %

Procedure:
Trimethylsulfoxonium iodide (1.96 g, 8.89 mmol) was gradually added to a suspension of sodium hydride (372 mg, 9.32 mmol) in dimethylsulfoxide (20 ml), and the mixture was stirred at room temperature for 1.5 hours. To which a solution of tert-butyl N-methyl-[1-(2-oxopropyl)piperidin-4-yl]carbamate (2.3 g, 8.5 mmol) in dimethylsulfoxide (20 ml) was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into iced water, and extracted with diethyl ether. The extract was washed with a saturated saline solution, dried over magnesium sulfate, and then filtered. The resultant filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1) to afford tert-butyl N-methyl-[1-(2-methyl-2-oxiranylmethyl)piperidin-4-yl]carbamate (2.1 g, yield 86%) as a light yellow oily material.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[C:5]([NH:11][CH2:12][CH2:13][O:14][CH3:15])=[C:4]([O:16][CH3:17])[CH:3]=1>C1COCC1.[Ni]>[Br:1][C:2]1[CH:7]=[C:6]([NH2:8])[C:5]([NH:11][CH2:12][CH2:13][O:14][CH3:15])=[C:4]([O:16][CH3:17])[CH:3]=1
Reactant: COCCNc1c(OC)cc(Br)cc1[N+](=O)[O-]
Agent: [Ni]
Solvent: C1CCOC1
Product: COCCNc1c(N)cc(Br)cc1OC

Procedure:
A solution of 6.19 (20 mmol) (4-bromo-2-methoxy-6-nitro-phenyl)-(2-methoxy-ethyl)-amine in 140 ml THF is hydrogenated in the presence of 1.4 g Raney-Nickel (B113W Degussa) at normal pressure for 25 h. The catalyst is filtered off and the filtrate is concentrated in vacuo. The residue is purified by flash-chromatography on silica gel (hexane:EtOAc=2:1) to afford 4.95 g of the title compound as a as a reddish oil.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5](O)=[O:6].S(Cl)([Cl:14])=O.CN(C=O)C>C1COCC1>[I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([Cl:14])=[O:6]
Reactant: Cc1ccc(C(=O)O)cc1I
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: Cc1ccc(C(=O)Cl)cc1I

Procedure:
3-Iodo-4-methylbenzoic acid (9.84 g) was dissolved in THF (50 ml) and thionyl chloride (4 ml) and DMF (0.05 ml) were added. The mixture was heated under ref lux for 3 hrs. The reaction mixture was concentrated under reduced pressure to give 3-iodo-4-methylbenzoyl chloride (10.18 g) as a brown powder. Then, by the reaction in the same manner as in Example 26-i), the title compound (3.47 g) was obtained from a solution of 3-iodo-4-methylbenzoyl chloride (4.00 g) and methylamine in THF (2M, 30 ml) as colorless powder crystals
Reaction SMILES: [Cl:1][C:2]1[N:6]([CH3:7])[C:5]([C:8]([OH:10])=O)=[CH:4][N:3]=1.[CH:11]([N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)([CH3:13])[CH3:12].[Cl-].ClC1N(C)CC[NH+]1C>C1(C)C=CC=CC=1.CCN(C(C)C)C(C)C.CCOC(C)=O>[Cl:1][C:2]1[N:6]([CH3:7])[C:5]([C:8]([N:17]2[CH2:18][CH2:19][N:14]([CH:11]([CH3:13])[CH3:12])[CH2:15][CH2:16]2)=[O:10])=[CH:4][N:3]=1
Reactant: CC(C)N1CCNCC1
Reactant: Cn1c(C(=O)O)cnc1Cl
Agent: CN1CC[NH+](C)C1Cl
Agent: [Cl-]
Solvent: Cc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Product: CC(C)N1CCN(C(=O)c2cnc(Cl)n2C)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Under nitrogen, 2-chloro-3-methyl-3H-imidazole-4-carboxylic acid (0.161 g, 1.0 mmol) is dissolved in toluene (5 mL, anhydrous) and DIEA (0.26 mL). N-isopropylpiperazine (0.2 M in toluene; 5.5 mL; 1.1 mmol) is added followed by the slow addition of 2-chloro-1,3-dimethylimidazolinium chloride (0.3 M in acetonitrile; 4.0 mL; 1.2 mmol). The reaction mixture is stirred at rt for 2 hr and is then diluted with EtOAc and washed with NaOH (1 N). The aqueous layer is drained and reextracted with EtOAc and the combined organic extracts are extracted twice with HCl (1 N). The combined acidic aqueous extracts are washed with EtOAc then basified with NaOH (2.5 M). The resulting basic aqueous solution is extracted three times with EtOAc and the combined organic extracts are washed with brine, then dried over Na2SO4, filtered and concentrated in vacuo.
Reaction SMILES: [CH3:1][N:2]1[N:6]=[N:5][C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([N+:13]([O-])=O)[CH:8]=2)=[N:3]1.[OH-].[Na+]>C(O)C>[CH3:1][N:2]1[N:6]=[N:5][C:4]([C:7]2[CH:8]=[C:9]([CH:10]=[CH:11][CH:12]=2)[NH2:13])=[N:3]1
Reactant: Cn1nnc(-c2cccc([N+](=O)[O-])c2)n1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Cn1nnc(-c2cccc(N)c2)n1
Temperature: 0 °C

Procedure:
2-Methyl-5-(3-nitrophenyl)-2H-tetrazole (2.12 g, 10 mmol) was added ethanol (50 mL) and heated to reflux. At reflux, the mixture was added SnCl2 dihydrate (11.6 g, 52 mmol) and the mixture was heated at reflux for 2 hours. After cooling, the mixture was poured into ice/water (200 mL) and neutralised (to pH 7) with 1 N sodium hydroxide. The mixture was filtered through celite, and the filter cake was washed with ethyl acetate. For the combined filtrate and washings the phases were separated and the aqueous phase was extracted with ethyl acetate (2×250 mL). The combined organic phases were dried (MgSO4) and evaporated in vacuo to afford 3-(2-methyl-2H-tetrazol-5-yl)aniline.
Reaction SMILES: Br[C:2]1[C:11]([O:12][CH3:13])=[C:10]2[C:5]([C:6](=[O:22])[C:7]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:8][N:9]2[CH:14]2[CH2:16][CH2:15]2)=[CH:4][CH:3]=1.[F:23][C:24]1[CH:32]=[C:31]2[C:27]([CH2:28][N:29]([S:33]([C:36]3[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][CH:37]=3)(=[O:35])=[O:34])[CH2:30]2)=[CH:26][C:25]=1[Sn](CCCC)(CCCC)CCCC>>[CH:14]1([N:9]2[C:10]3[C:5](=[CH:4][CH:3]=[C:2]([C:25]4[CH:26]=[C:27]5[C:31](=[CH:32][C:24]=4[F:23])[CH2:30][N:29]([S:33]([C:36]4[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][CH:37]=4)(=[O:34])=[O:35])[CH2:28]5)[C:11]=3[O:12][CH3:13])[C:6](=[O:22])[C:7]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:8]2)[CH2:16][CH2:15]1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cc2c(cc1F)CN(S(=O)(=O)c1ccc(C)cc1)C2
Reactant: CCOC(=O)c1cn(C2CC2)c2c(OC)c(Br)ccc2c1=O
Product: CCOC(=O)c1cn(C2CC2)c2c(OC)c(-c3cc4c(cc3F)CN(S(=O)(=O)c3ccc(C)cc3)C4)ccc2c1=O
Yield: 69 %

Procedure:
In the same manner as in Example 1, 0.23 g of ethyl 7-bromo-1-cyclopropyl-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylate was reacted with 0.63 g of 6-fluoro-2-(p-toluenesulfonyl)-5-tributylstannyliso-indoline to obtain 0.25 g of ethyl 1-cyclopropyl-7-[6-fluoro-2-(p-toluenesulfonyl)isoindolin-5-yl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylate.
Reaction SMILES: [F:1][CH:2]([F:20])[CH2:3][NH:4][C:5]1[CH:6]=[N:7][CH:8]=[CH:9][C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=1[O:18][CH3:19].[F:21][C:22]([F:37])([F:36])[C:23]1[CH:24]=[C:25]([CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[N:31]=1)[C:26](O)=[O:27]>>[F:20][CH:2]([F:1])[CH2:3][N:4]([C:5]1[CH:6]=[N:7][CH:8]=[CH:9][C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=1[O:18][CH3:19])[C:26](=[O:27])[C:25]1[CH:29]=[C:30]([C:32]([F:33])([F:34])[F:35])[N:31]=[C:23]([C:22]([F:37])([F:21])[F:36])[CH:24]=1
Reactant: O=C(O)c1cc(C(F)(F)F)nc(C(F)(F)F)c1
Reactant: COc1cc(F)ccc1-c1ccncc1NCC(F)F
Product: COc1cc(F)ccc1-c1ccncc1N(CC(F)F)C(=O)c1cc(C(F)(F)F)nc(C(F)(F)F)c1

Procedure:
The title compound was prepared in analogy to example 90, from (2,2-difluoro-ethyl)-[4-(4-fluoro-2-methoxy-phenyl)-pyridin-3-yl]amine and 2,6-bis(trifluoromethyl)isonicotinic acid (Key Organics Ltd.) after a reaction time of 68 hours. The compound was purified by silica gel chromatography on a 10 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 50:50). Light brown solid (57%). MS (ESI): m/z=524.10 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[OH:11].[F:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=1)[CH2:16]Br>>[F:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=1)[CH2:16][O:11][C:3]1[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[CH3:1]
Reactant: Fc1cccc(CBr)c1
Reactant: Cc1cc([N+](=O)[O-])ccc1O
Product: Cc1cc([N+](=O)[O-])ccc1OCc1cccc(F)c1
Yield: 62 %

Procedure:
Prepared in analogy to example 8 from 2-methyl-4-nitrophenol and 3-fluoro-benzylbromide. Colorless oil. Yield=62%. MS: m/e=261.1 (M+).
Reaction SMILES: [C:1]1([CH:11]=[CH:12][C:13](Cl)=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CC(C)=O>[C:1]1([CH:11]=[CH:12][CH:13]=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: O=C(Cl)C=Cc1cccc2ccccc12
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC(C)=O
Product: O=CC=Cc1cccc2ccccc12
Yield: 75.9 %

Procedure:
To a stirred solution of 3-(1-naphthalenyl)-2-propenoyl chloride (2.5 g, 0.012 mol) and 6.03 g (0.023 mol) of triphenyl phosphine in 50 ml of acetone was added 7.65 g (0.013 mol) of bis(triphenylphosphine)tetrahydroboratocopper in one portion. After an hour the solution was filtered and the filtrate was evaporated to dryness. The residue was dissolved in 20 ml of chloroform and treated with 6 g of cuprous chloride, allowed to stir for an hour and filtered. The solvent was evaporated to dryness to yield 1.66 g (79 percent) of solid.
Reaction SMILES: Cl.[CH:2]1([C:8]([CH:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][C:25]([C:27]3[CH:32]=[CH:31][C:30]([C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:29][CH:28]=3)=[O:26])[CH2:18][CH2:17]2)([OH:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.Cl.C(C1C=CC(C(C2CCN(CCCC(C3C=CC=CC=3)=O)CC2)(O)C2C=CC=CC=2)=CC=1)(C)(C)C>>[C:33]([C:30]1[CH:29]=[CH:28][C:27]([CH:25]([OH:26])[CH2:24][CH2:23][CH2:22][N:19]2[CH2:18][CH2:17][CH:16]([C:8]([CH:9]3[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]3)([OH:15])[C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH2:21][CH2:20]2)=[CH:32][CH:31]=1)([CH3:36])([CH3:34])[CH3:35]
Reactant: CC(C)(C)c1ccc(C(=O)CCCN2CCC(C(O)(c3ccccc3)C3CCCCC3)CC2)cc1
Agent: CC(C)(C)c1ccc(C(O)(c2ccccc2)C2CCN(CCCC(=O)c3ccccc3)CC2)cc1
Agent: Cl
Product: CC(C)(C)c1ccc(C(O)CCCN2CCC(C(O)(c3ccccc3)C3CCCCC3)CC2)cc1

Procedure:
When in the procedure of Example 1 an appropriate amount of 4-[4-(α-cyclohexyl-α-hydroxybenzyl)piperidino]4'-tert-butylbutyrophenone hydrochloride is substituted for 4-[4-[α-(p-tert-butylphenyl)-α-hydroxybenzyl]piperidino]butyrophenone hydrochloride and the reaction mixture is refluxed for three hours, α-(4-tert-butylphenyl)-4-(α-cyclohexyl-α-hydroxybenzyl)-1-piperidinebutanol is obtained, M.P. 75°-81°C. This compound was converted to the the hydrochloride salt, M.P. 240°-242.5°C. (dec.) by the usual methods.
Reaction SMILES: [CH:1]1[CH:6]=[C:5]2[C:7]([C:9](O)(O)[C:10](=[O:11])[C:4]2=[CH:3][CH:2]=1)=[O:8].Cl.[Cl:15][C:16]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=1[NH:23][C:24](=[O:27])[NH:25][NH2:26]>>[Cl:15][C:16]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=1[NH:23][C:24](=[O:27])[NH:25][N:26]=[C:9]1[C:10](=[O:11])[C:4]2[C:5](=[CH:6][CH:1]=[CH:2][CH:3]=2)[C:7]1=[O:8]
Reactant: O=C1c2ccccc2C(=O)C1(O)O
Reactant: NNC(=O)Nc1ccc(Cl)cc1Cl
Agent: Cl
Product: O=C(NN=c1c(=O)c2ccccc2c1=O)Nc1ccc(Cl)cc1Cl

Procedure:
ninhydrin, 4-(2,4-dichlorophenyl)-semicarbazide hydrochloride
Reaction SMILES: Br[C:2]1[S:6][C:5]([NH:7][C:8](=[O:23])[N:9]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[C@H:10]2[CH2:15][CH2:14][C@H:13]([CH3:16])[CH2:12][CH2:11]2)=[N:4][CH:3]=1.[CH3:24][O:25][C:26](=[O:38])[C@H:27]([CH2:36][SH:37])[NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30]>>[CH3:24][O:25][C:26](=[O:38])[C@H:27]([NH:28][C:29]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:30])[CH2:36][S:37][C:2]1[S:6][C:5]([NH:7][C:8]([N:9]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[C@H:10]2[CH2:15][CH2:14][C@H:13]([CH3:16])[CH2:12][CH2:11]2)=[O:23])=[N:4][CH:3]=1
Reactant: C[C@H]1CC[C@H](N(C(=O)Nc2ncc(Br)s2)C2CCCCC2)CC1
Reactant: COC(=O)[C@H](CS)NC(=O)OC(C)(C)C
Product: COC(=O)[C@@H](CSc1cnc(NC(=O)N(C2CCCCC2)[C@H]2CC[C@H](C)CC2)s1)NC(=O)OC(C)(C)C

Procedure:
Prepared in 60% (333 mg) yield as described in general procedure (D) using trans-3-(5-bromo-thiazol-2-yl)-1-cyclohexyl-1-(4-methyl-cyclohexyl)-urea (400 mg, 1.0 mmol) and N-(tert-butoxycarbonyl)-L-cysteine methyl ester (470 mg, 2.0 mmol).
Reaction SMILES: [CH:1]1([C:4]2[CH:5]=[C:6]([C:17]#[C:18][Si](C)(C)C)[CH:7]=[C:8]3[C:13]=2[C:12](=[O:14])[CH2:11][CH2:10][C:9]3([CH3:16])[CH3:15])[CH2:3][CH2:2]1.CO.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CCCCCC>[CH:1]1([C:4]2[CH:5]=[C:6]([C:17]#[CH:18])[CH:7]=[C:8]3[C:13]=2[C:12](=[O:14])[CH2:11][CH2:10][C:9]3([CH3:15])[CH3:16])[CH2:3][CH2:2]1
Reactant: CC1(C)CCC(=O)c2c(C3CC3)cc(C#C[Si](C)(C)C)cc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: CCCCCC
Product: C#Cc1cc(C2CC2)c2c(c1)C(C)(C)CCC2=O

Procedure:
Following General Procedure F and using 8-cyclopropyl-4,4-dimethyl-6-(trimethylsilanyl)ethynyl-1-tetralone (Intermediate 159, 1.05 g, 3.38 mmol), methanol (20 mL) and potassium carbonate (1 g, 14.5 mmol) followed by flash column chromatography using 7% ethyl acetate in hexane as the eluent, the title compound was obtained (0.57 g, 80%) as a pale yellow solid.