Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[C:9]([C:11]([NH:13][C@@H:14]([C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)[CH3:15])=[O:12])[CH:8]=[C:7]([CH3:26])[C:3]=1[C:4](O)=[O:5].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Cl.[CH3:55][O:56][C:57](=[O:69])[C@H:58]([CH2:60][NH:61][C:62]([C:64]1[S:65][CH:66]=[CH:67][CH:68]=1)=[O:63])[NH2:59].C(N(C(C)C)CC)(C)C>ClCCl.C(OCC)(=O)C>[CH3:55][O:56][C:57](=[O:69])[C@H:58]([CH2:60][NH:61][C:62]([C:64]1[S:65][CH:66]=[CH:67][CH:68]=1)=[O:63])[NH:59][C:4](=[O:5])[C:3]1[C:2]([CH3:1])=[CH:10][C:9]([C:11]([NH:13][C@@H:14]([C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)[CH3:15])=[O:12])=[CH:8][C:7]=1[CH3:26]
Reactant: Cc1cc(C(=O)N[C@H](C)c2cccc3ccccc23)cc(C)c1C(=O)O
Reactant: COC(=O)[C@@H](N)CNC(=O)c1cccs1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: COC(=O)[C@H](CNC(=O)c1cccs1)NC(=O)c1c(C)cc(C(=O)N[C@H](C)c2cccc3ccccc23)cc1C
Reaction time: 2 h
Yield: 54.4 %

Procedure:
To a solution of 2,6-dimethyl-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoic acid (Example 31; 100 mg, 0.29 mmol) in dichloromethane (1 mL) at 25° C. was added benzotriazol-1-yloxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent, 140 mg, 0.32 mmol), 3-(thiophene-2-carbonyl)amino-L-alanine methyl ester HCl salt (Example 301; 114 mg, 0.43 mmol), followed by diisopropylethylamine (250 μL, 1.4 mmol) slowly dropwise. After stirring for 2 h, the reaction was diluted with ethyl acetate (50 mL) and washed with 1N HCl (10 mL), saturated aqueous sodium bicarbonate (10 mL) and brine (15 mL). The organic layer was dried (MgSO4), filtered, evaporated and flash chromatographed (silica, 50% ethyl acetate in petroleum ether) to give N-[2,6-dimethyl-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine methyl ester (88 mg, 54%) as an off-white solid.
Reaction SMILES: [C:1](Cl)(=[O:4])[CH:2]=[CH2:3].Cl.[NH2:7][C@H:8]([C:14]([NH2:16])=[O:15])[CH2:9][CH2:10][C:11](=[O:13])[NH2:12].C(=O)([O-])[O-].[K+].[K+].N[C@H](C(N)=O)CCC(=O)N>O.C(OCC)C>[C:1]([NH:16][C:14](=[O:15])[C@H:8]([CH2:9][CH2:10][C:11](=[O:13])[NH2:12])[NH2:7])(=[O:4])[CH:2]=[CH2:3]
Reactant: NC(=O)CC[C@H](N)C(N)=O
Reactant: C=CC(=O)Cl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOCC
Product: C=CC(=O)NC(=O)[C@@H](N)CCC(N)=O
Reaction time: 0.17 h

Procedure:
A 5 ml portion of acrylic acid chloride and 200 ml of diethyl ether were put into a 500 ml capacity eggplant type flask and stirred on an ice bath. Next, 2 g of glutamineamide hydrochloride (mfd. by Kokusan Kagaku) was dissolved in 25 ml of deionized water, and 3 g of potassium carbonate was dissolved in 25 ml of deionized water. The glutamineamide aqueous solution was mixed with the potassium carbonate aqueous solution. The mixed liquid was added dropwise into the eggplant type flask spending 10 minutes while stirring constantly, and the mixture after completion of the dropwise addition was stirred for 24 hours. Diethyl ether layer in the thus obtained reaction liquid was discarded, and the water layer was concentrated at 25° C. under a reduced pressure. A 500 ml portion of acetone was added to the thus obtained residue and stirred for 1 hour. The insoluble solids were removed by suction filtration. By recrystallizing from the acetone layer, 0.25 g of colorless crystals were obtained.
Reaction SMILES: [CH2:1]([C:5]1[N:6]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[C:29]#[N:30])=[CH:19][CH:18]=2)[CH:7]=[C:8]([CH:10]=[CH:11][C:12]([O:14][CH3:15])=[O:13])[CH:9]=1)[CH2:2][CH2:3][CH3:4]>C(Cl)Cl.[Pd]>[CH2:1]([C:5]1[N:6]([CH2:16][C:17]2[CH:18]=[CH:19][C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[C:29]#[N:30])=[CH:21][CH:22]=2)[CH:7]=[C:8]([CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH:9]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1cc(C=CC(=O)OC)cn1Cc1ccc(-c2ccccc2C#N)cc1
Agent: [Pd]
Solvent: ClCCl
Product: CCCCc1cc(CCC(=O)OC)cn1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 99.5 %

Procedure:
To a solution of methyl 3-[2-(n-butyl)-1-(2"-cyanobiphenyl-4'-ylmethyl)pyrrol-4-yl]acrylate (AF) (6.0 g) (prepared, e.g., as described in Preparation 22), in methylene chloride (200 ml) was added 5% palladium on carbon (1 g), and the resulting mixture was stirred under hydrogen at room temperature at atmospheric pressure for 4 hours. The reaction mixture was filtered through a Celite pad to remove catalyst, and evaporation of the filtrate gave methyl 3-[2-(n-butyl)-1-(2"-cyanobiphenyl-4'-ylmethyl)pyrrol-4-yl]propionate (6.0 g), a compound of Formula (AG), as an oil.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH:10]([N:15]=[N+:16]=[N-:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH:10]([N:15]=[N+:16]=[N-:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC(O)C(N=[N+]=[N-])C1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(=O)C(N=[N+]=[N-])C1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
To a solution of (±)-trans[3-azido-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (Example 112, 1.24 mmol, 0.3 g) in DCM (4 mL) at 0° C. was added Dess-Martin periodinane (1.48 mmol, 0.63 g) portion wise, and the reaction was stirred for 8 h. The reaction was diluted with DCM (5 mL), cooled to 0° C., and quenched with Na2S2O3 solution, organic layer was separated and washed with saturated NaHCO3 solution, water, brine and dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on a SiO2 cartridge with 5% ethyl acetate in hexanes −30% ethylacetate in hexanes to provide 3-azido-4-oxo-piperidine-1-carboxylic acid tert-butyl ester.
Reaction SMILES: C([Si](C1C=CC=CC=1)(C1C=CC=CC=1)[O:6][C:7]1[CH:8]=[C:9]([C:13]2[CH:18]([CH2:19][N:20]([CH3:22])[CH3:21])[CH2:17][CH2:16][C:15](=[O:23])[CH:14]=2)[CH:10]=[CH:11][CH:12]=1)(C)(C)C>CO.[Pd]>[CH3:22][N:20]([CH2:19][CH:18]1[CH2:17][CH2:16][C:15](=[O:23])[CH2:14][CH:13]1[C:9]1[CH:10]=[CH:11][CH:12]=[C:7]([OH:6])[CH:8]=1)[CH3:21]
Reactant: CN(C)CC1CCC(=O)C=C1c1cccc(O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c1
Agent: [Pd]
Solvent: CO
Product: CN(C)CC1CCC(=O)CC1c1cccc(O)c1
Reaction time: 5 h
Yield: 39.1 %

Procedure:
25 g 3-[3-(tert-butyl-diphenyl-silanyloxy)-phenyl]-4-dimethylaminomethyl-cyclohex-2-enone were dissolved in 110 ml absolute methanol. 2,8 g palladium-on-charcoal (10%) were added as a catalyst, while stirring and passing dry nitrogen over. Hydrogenation was then carried out for five hours under a pressure of 0.2 bar and at a temperature of 20° C. After filtration the solvent was evaporated off in vacuo and the residue was dissolved in 60 ml tetrahydrofuran. 15 ml tetrabutylammonium fluoride were then added at room temperature. When the reaction had ended the mixture was quenched with water and then extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution. The organic phase was then dried over magnesium sulfate and the solvent was evaporated in vacuo. The residue was purified by column chromatography on silica gel with ethyl acetate/methanol/diisopropyl ether=4/1/5 as the eluting agent. 5 g rac-cis-[4-dimethylaminomethyl-3-(3-hydroxy-phenyl)-cyclohexanone in the form of an oil were obtained as the first product fraction. To prepare the hydrochloride, the base was dissolved in acetone, and an equimolar amount of water and trimethylchlorosilane was added. The hydrochloride which had precipitated out was filtered off with suction and dried in vacuo. 4.8 g (32.9% of theory) rac-cis-[4-dimethylaminomethyl-3-(3-hydroxy-phenyl)-cyclohexanone hydrochloride were obtained in this way. The second product fraction gave 3.5 g rac-trans-[4-dimethylaminomethyl-3-(3-hydroxy-phenyl)-cyclohexanone, likewise as an oil. To prepare the hydrochloride, the base was dissolved in acetone, and an equimolar amount of water and trimethylchlorosilane was added. The hydrochloride which had precipitated out was filtered off with suction and dried in vacuo. 3.2 g (21.9% of theory) rac-trans-[4-dimethylaminomethyl-3-(3-hydroxy-phenyl)-cyclohexanone hydrochloride were obtained in this way.
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]1[N:12]1[C:16]([C:17]#[N:18])=[CH:15][N:14]=[CH:13]1.N.[H][H]>[Ni].CO>[CH3:1][C:2]1([CH3:19])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]1[N:12]1[C:16]([CH2:17][NH2:18])=[CH:15][N:14]=[CH:13]1
Reactant: CC1(C)CCc2ccccc2C1n1cncc1C#N
Reactant: [H][H]
Agent: [Ni]
Agent: N
Solvent: CO
Product: CC1(C)CCc2ccccc2C1n1cncc1CN
Yield: 90 %

Procedure:
A mixture of 25 parts of 1-(1,2,3,4-tetrahydro-2,2-dimethyl-1-naphthalenyl)-1H-imidazole-5-carbonitrile and 360 parts of methanol, saturated with ammonia was hydrogenated at normal pressure and at room temperature with 2 parts of Raney nickel catalyst. After the calculated amount of hydrogen was taken up, the catalyst was filtered off and the filtrate was evaporated. The residue was dried at 100° C., yielding 23 parts (90.0%) of 1-(1,2,3,4-tetrahydro-2,2-dimethyl-1-naphthalenyl)-1H-imidazole-5-methanamine as an oily residue (compound 2.37).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]2)=[CH:4][CH:3]=1.C([Li])CCC.CN(C)[CH:24]=[O:25]>C1COCC1.CCCCCC>[CH3:16][N:13]1[CH2:14][CH2:15][N:10]([CH2:9][CH2:8][C:5]2[CH:6]=[CH:7][C:2]([CH:24]=[O:25])=[CH:3][CH:4]=2)[CH2:11][CH2:12]1
Reactant: CN(C)C=O
Reactant: CN1CCN(CCc2ccc(Br)cc2)CC1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CN1CCN(CCc2ccc(C=O)cc2)CC1
Temperature: -10 °C
Reaction time: 0.5 h
Yield: 98 %

Procedure:
To 87 mL of a solution of 8.7 g of 1-[2-(4-bromophenyl)ethyl]-4-methylpiperazine in THF cooled to −70° C. was added dropwise 21.1 mL of a solution of n-butyllithium (1.6 mol/L) in hexane, and the mixture was stirred at the same temperature for 30 minutes. While the reaction mixture was stirred at the same temperature, 3.6 mL of N,N-dimethylformamide was added dropwise. The mixture was stirred at the same temperature for 30 minutes. The cooling bath was removed, and the mixture was allowed to warm to −10° C., poured into a mixture of 12 mL of 1 N hydrochloric acid and 100 mL of cold water, and subjected to extraction with CHCl3. The obtained extract was dried over MgSO4 and concentrated to give 7.04 g of the title compound (98%).
Reaction SMILES: [C:1]([C:3](=[CH:9][NH:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1)[C:4]([O:6]CC)=O)#[N:2].C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1>CCCCCC>[CH3:18][O:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][C:13]=1[O:19][CH3:20])[NH:10][CH:9]=[C:3]([C:1]#[N:2])[C:4]2=[O:6]
Reactant: CCOC(=O)C(C#N)=CNc1ccc(OC)c(OC)c1
Solvent: c1ccc(Oc2ccccc2)cc1
Solvent: CCCCCC
Solvent: c1ccc(-c2ccccc2)cc1
Product: COc1cc2[nH]cc(C#N)c(=O)c2cc1OC

Procedure:
A mixture of 40 g of ethyl 2-cyano-3-(3,4-dimethoxyphenylamino)acrylate and 1.2 L of Dowtherm® A was refluxed for 10 h, cooled, and diluted with hexane. The resulting solid was filtered, washed with hexane followed by dichloromethane, and dried; mp 330-350° C. (dec).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[C:12]([NH:14][CH3:15])=[O:13])[C:5]([O:7]C)=[O:6].[OH-].[Na+].Cl>C(O)(=O)C>[NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[C:12]([NH:14][CH3:15])=[O:13])[C:5]([OH:7])=[O:6]
Reactant: CNC(=O)c1ccc(C(=O)OC)cc1N
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Product: CNC(=O)c1ccc(C(=O)O)cc1N
Temperature: 25 °C
Reaction time: 4 h
Yield: 68.7 %

Procedure:
A mixture of methyl 3-amino-4-(methylamino)carbonylbenzoate (0.624 g, 0.003 mol) and 1N sodium hydroxide (4.5 mol, 0.0045 mol) was stirred at room temperature for 4 h. The mixture was neutralized with concentrated hydrochloric acid and then acetic acid was added to bring the pH close to 3. The precipitate obtained was collected by filtration, washed with water, and dried under vacuum over acetone for 24 h to give 0.4 g (69%) of 3-amino-4-(methylamino)carbonylbenzoic acid as a pale yellow powder, mp 215°-217° C.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][NH:8][C:9]2=[O:14])([O-])=O.Cl>CC(O)=O.C(O)C.[Pd]>[NH2:1][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][NH:8][C:9]2=[O:14]
Reactant: O=c1[nH]ccc2c([N+](=O)[O-])cccc12
Agent: [Pd]
Agent: Cl
Solvent: CC(=O)O
Solvent: CCO
Product: Nc1cccc2c(=O)[nH]ccc12
Reaction time: 18 h

Procedure:
A mixture of 4.0 g (21 mmol) of 5-nitroisoquinolinone in 100 ml HOAc and 0.5 g 5% Pd-C was hydrogenated at room temperature for 18 hours (three atmospheres). The mixture was filtered and concentrated to give a solid. The solid was dissolved in ethanol (50 ml) and 10 ml of saturated ethanolic HCl was added. The solution was cooled and the resulting solid was collected. It was dissolved in water and the solution was neutralized with 100 ml concentrated NH4OH. The precipitate was collected, dissolved in 150 ml of hot methanol, treated with charcoal, filtered, and diluted with water. Upon cooling, 1.10 g (32%) of the desired product was collected; mp 258°-259°.
Reaction SMILES: [Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C([Li])CCC.[CH3:29][C:30]1[CH:37]=[CH:36][C:33]([CH:34]=O)=[CH:32][CH:31]=1.[Cl-].[Na+]>C(OCC)C>[CH3:2][O:3][CH:4]=[CH:34][C:33]1[CH:36]=[CH:37][C:30]([CH3:29])=[CH:31][CH:32]=1
Reactant: COC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Cc1ccc(C=O)cc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CCOCC
Product: COC=Cc1ccc(C)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 63.3 %

Procedure:
28.5 g of methoxymethyltriphenylphosphonium chloride is introduced into 350 ml of diethyl ether under nitrogen. At 0° C., 39.95 ml of n-butyllithium solution (1.6 M in hexane) is added in drops, and it is stirred for one hour at room temperature. 10 g of 4-methylbenzaldehyde in 50 ml of diethyl ether is now added, and it is stirred for one more hour. Sodium chloride solution is added to the reaction mixture, extracted with ethyl acetate, dried on sodium sulfate and concentrated by evaporation. After chromatography on silica gel with ethyl acetate/hexane, 7.8 g of 1-methoxy-2-(4-methylphenyl)-ethene 36 (E,Z-mixture) is obtained as a colorless oil, which is dissolved in 200 ml of acetone and is stirred overnight under nitrogen with 10 ml of 2N hydrochloric acid. Sodium chloride solution is added, extracted with ethyl acetate, dried on sodium sulfate and concentrated by evaporation. Chromatographic purification on silica gel with ethyl acetate/hexane yields 4.5 g of title compound 37 as a colorless oil.
Reaction SMILES: [CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].ClCCl.[OH:14]O>O.[O-2].[O-2].[Mn+4]>[CH2:1]1[O:14][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: OO
Reactant: C=CCCCCCCCC
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Solvent: O
Product: CCCCCCCCC1CO1
Temperature: 25 °C
Reaction time: 14 h
Yield: 94 %

Procedure:
In a 25 mL scintillation vial equipped with a magnetic stirrer, 1-decene (1.41 g, 10 mmol) was placed followed by addition of 4 mL dichloromethane. To this solution was added BTSP (2.8 g, 15 mmol). The vial was immersed into ice/water bath. After 5 minutes Re2O7 (24 mg, 0.05 mmol)5 was added followed by 10 μL of water. The reaction turned bright yellow and was allowed to warm up to room temperature and stirred for 14 h. Upon completion, water (3 drops) was added followed by manganese dioxide (ca. 5 mg) in order to decompose the remaining H2O2. The destruction of H2O2 was evident by the disappearance of yellow color. The mixture was then dried over Na2SO4. Concentration afforded 1-decene oxide (1.48 g, 94% yield) of a colorless oil.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:26])[C@@H:4]([O:23][CH2:24][CH3:25])[C@@H:5]([C:7]1[C:12]([CH3:13])=[CH:11][C:10]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:9][C:8]=1[CH3:22])O.C([SiH](CC)CC)C>FC(F)(F)C(O)=O>[CH3:1][O:2][C:3](=[O:26])[C@@H:4]([O:23][CH2:24][CH3:25])[CH2:5][C:7]1[C:8]([CH3:22])=[CH:9][C:10]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:11][C:12]=1[CH3:13]
Reactant: CCO[C@H](C(=O)OC)[C@H](O)c1c(C)cc(OCc2ccccc2)cc1C
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: CCO[C@@H](Cc1c(C)cc(OCc2ccccc2)cc1C)C(=O)OC

Procedure:
In analogy to the procedure described in example 17 c], (2S,3R)-3-(4-benzyloxy-2,6-dimethyl-phenyl)-2-ethoxy-3-hydroxy-propionic acid methyl ester was treated with triethylsilane in trifluoroacetic acid to yield (2S)-3-(4-benzyloxy-2,6-dimethyl-phenyl)-2-ethoxy-propionic acid methyl ester as colorless liquid.
Reaction SMILES: CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].I[C:13]1[C:18]([O:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:32][CH3:33])=[C:27]([O:30][CH3:31])[CH:28]=3)[N:23]=[CH:22][CH:21]=2)=[CH:17][CH:16]=[C:15]([CH3:34])[N:14]=1.[F:35][C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[C:40]([F:42])[CH:41]=1>O>[F:35][C:36]1[CH:37]=[C:38]([C:13]2[C:18]([O:19][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:32][CH3:33])=[C:27]([O:30][CH3:31])[CH:28]=4)[N:23]=[CH:22][CH:21]=3)=[CH:17][CH:16]=[C:15]([CH3:34])[N:14]=2)[CH:39]=[C:40]([F:42])[CH:41]=1
Reactant: OB(O)c1cc(F)cc(F)c1
Reactant: COc1cc2nccc(Oc3ccc(C)nc3I)c2cc1OC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc2nccc(Oc3ccc(C)nc3-c3cc(F)cc(F)c3)c2cc1OC
Temperature: 70 °C
Reaction time: 5 h
Yield: 47.6 %

Procedure:
N,N-Dimethylformamide (1 ml) and a 2 M aqueous potassium carbonate solution (1 ml) were added to 4-(2-iodo-6-methyl-pyridin-3-yloxy)-6,7-dimethoxy-quinoline (compound 116) (50 mg), tetrakistriphenylphosphine palladium (14 mg), and 3,5-difluorophenylboronic acid (56 mg) under an argon atmosphere, and the mixture was stirred at 70° C. for 5 hr. The reaction solution was cooled to room temperature, water was then added thereto, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using chloroform-methanol to give the title compound (23 mg, yield 47%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:30][CH3:31])=[C:6]([S:8]([NH:11][C:12]2[CH:13]=[C:14]([CH:27]=[CH:28][CH:29]=2)[C:15]([NH:17][C:18]2[CH:26]=[CH:25][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=2)=[O:16])(=[O:10])=[O:9])[CH:7]=1.Cl[C:33]1C=CC(OC)=C(S(Cl)(=O)=O)[CH:38]=1>>[CH2:33]([O:23][C:22](=[O:24])[C:21]1[CH:25]=[CH:26][C:18]([NH:17][C:15](=[O:16])[C:14]2[CH:27]=[CH:28][CH:29]=[C:12]([NH:11][S:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[O:30][CH3:31])(=[O:9])=[O:10])[CH:13]=2)=[CH:19][CH:20]=1)[CH3:38]
Reactant: COc1ccc(Cl)cc1S(=O)(=O)Cl
Reactant: COc1ccc(Cl)cc1S(=O)(=O)Nc1cccc(C(=O)Nc2ccc(C(=O)O)cc2)c1
Product: CCOC(=O)c1ccc(NC(=O)c2cccc(NS(=O)(=O)c3cc(Cl)ccc3OC)c2)cc1

Procedure:
4-[3-(5-Chloro-2-methoxy-benzenesulfonylamino)-benzoylamino]-benzoic acid, MS (ISP): m/e=459.0 (M−H), was prepared in analogy to example 1, steps A to D. Step C was performed using 5-chloro-2-methoxy-benzenesulfonyl chloride and yielded 4-[3-(5-chloro-2-methoxy-benzenesulfonylamino)-benzoylamino]-benzoic acid ethyl ester, which was hydrolyzed in step D.
Reaction SMILES: N[C@H](C(O)=O)C[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C1C=CC([CH2:19][C@H:20]([OH:24])[C:21]([OH:23])=[O:22])=CC=1>>[C:4]1([O:23][C:21](=[O:22])[CH:20]([CH3:19])[OH:24])[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: O=C(O)[C@@H](O)Cc1ccccc1
Reactant: N[C@@H](Cc1ccccc1)C(=O)O
Product: CC(O)C(=O)Oc1ccccc1
Reaction time: 24 h

Procedure:
In a case in which 5 mM of L-phenylalanine was added to the culture medium, L-phenylalanine ceased to be detected after 24 hours of culture, and instead an equal level (5.7 mM) of D-3-phenyllactate had accumulated. This led to the conclusion that the present strain converts L-phenylalanine to D-3-phenyllactate. Specifically, it is thought that the present strain has an enzyme that produces optically active phenyllactate.
Reaction SMILES: Cl[CH2:2][C:3]1[O:7][N:6]=[C:5]([O:8][CH2:9][C:10]2[N:11]=[C:12]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[O:13][C:14]=2[CH3:15])[CH:4]=1.[OH:22][C:23]1[CH:24]=[C:25]([CH2:29][C:30]([O:32][CH3:33])=[O:31])[CH:26]=[CH:27][CH:28]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH3:15][C:14]1[O:13][C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:11][C:10]=1[CH2:9][O:8][C:5]1[CH:4]=[C:3]([CH2:2][O:22][C:23]2[CH:24]=[C:25]([CH2:29][C:30]([O:32][CH3:33])=[O:31])[CH:26]=[CH:27][CH:28]=2)[O:7][N:6]=1
Reactant: Cc1oc(-c2ccccc2)nc1COc1cc(CCl)on1
Reactant: COC(=O)Cc1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)Cc1cccc(OCc2cc(OCc3nc(-c4ccccc4)oc3C)no2)c1
Temperature: 60 °C
Reaction time: 3 h
Yield: 92.8 %

Procedure:
A mixture of 5-chloromethyl-3-(5-methyl-2-phenyl-4-oxazolylmethoxy)isoxazole (457 mg), methyl 2-(3-hydroxyphenyl)acetate (249 mg), anhydrous potassium carbonate (415 mg) and N,N-dimethylformamide (10 mL) was stirred at 60° C. for 3 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The obtained residue was subjected to silica gel column chromatography to give methyl 2-[3-[3-(5-methyl-2-phenyl-4-oxazolylmethoxy)-5-isoxazolylmethoxy]phenyl]acetate as a colorless oil (604 mg, 93%) from a fraction eluted with ethyl acetate-hexane (1:1, v/v).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:4]=1[CH:5]=O.[C:13]([O:19][CH2:20][CH3:21])(=[O:18])[CH2:14][C:15]([CH3:17])=[O:16].N1CCCCC1.C(O)(=O)C>C1(C)C=CC=CC=1>[O:16]=[C:15]([CH3:17])[C:14](=[CH:5][C:4]1[CH:7]=[C:8]([O:11][CH3:12])[CH:9]=[CH:10][C:3]=1[O:2][CH3:1])[C:13]([O:19][CH2:20][CH3:21])=[O:18]
Reactant: COc1ccc(OC)c(C=O)c1
Reactant: CCOC(=O)CC(C)=O
Solvent: CC(=O)O
Solvent: Cc1ccccc1
Solvent: C1CCNCC1
Product: CCOC(=O)C(=Cc1cc(OC)ccc1OC)C(C)=O
Yield: 76.7 %

Procedure:
A stirred solution of 25.0 grams (0.15 mole) of 2,5-dimethoxybenzaldehyde, 22.0 grams (0.17 mole) of ethyl acetoacetate, 2 mL of piperidine, and 3 mL of glacial acetic acid in about 250 mL of toluene is placed in a reaction vessel equipped with a Dean-Stark trap, and heated at reflux for about 12 hours. After this time, the reaction mixture is cooled and washed in turn with water, a cold solution of aqueous 10% hydrochloric acid, aqueous 5% sodium bicarbonate, and aqueous 1% acetic acid. The organic layer is dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure to a residue. The residue is subjected to column chromatography on silica gel. Elution is accomplished using methylene chloride. The column chromatography does not provide product purification as expected. The fractions are recombined and concentrated under reduced pressure to a residual oil. The oil is distilled under vacuum, yielding 32 grams of impure ethyl 3-oxo-2-(2,5-dimethoxyphenylmethylidene)butanoate. The NMR spectrum is consistent with the proposed structure.