Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[C:13]([C:21]([F:24])([F:23])[F:22])[CH:12]=2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[NH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=1>C(Cl)Cl.N1C=CC=CC=1>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:18])=[O:19])=[C:13]([C:21]([F:22])([F:23])[F:24])[CH:12]=2)[C:8]([NH:52][C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: Nc1ccccn1
Reactant: CS(=O)(=O)c1ccc(C(CC2CCCC2)C(=O)O)cc1C(F)(F)F
Agent: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CS(=O)(=O)c1ccc(C(CC2CCCC2)C(=O)Nc2ccccn2)cc1C(F)(F)F
Temperature: 25 °C
Reaction time: 48 h
Yield: 61.5 %

Procedure:
A solution of 3-cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-propionic acid (73 mg, 0.2 mmol) and triphenylphosphine (79 mg, 0.3 mmol) in methylene chloride (5.0 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (60.5 mg, 0.34 mmol). After the complete addition of N-bromosuccinimide, the reaction mixture was allowed to warm to 25° C. over 30 min. The reaction mixture was then treated with 2-aminopyridine (28.2 mg, 0.3 mmol) and pyridine (1 drop). The resulting reaction mixture was stirred at 25° C. for 48 h. The reaction mixture was then diluted with methylene chloride (50 mL). The organic layer was washed with water (1×50 mL) and a saturated aqueous sodium chloride solution (2×25 mL), dried over magnesium sulfate and sodium sulfate, filtered, and concentrated in vacuo. High pressure liquid chromatography (Chromegasphere SI-60, 10 μM, 60 Å, 25 cm×23 cm ID, 50/50 heptane/ethyl acetate) afforded 3-cyclopentyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-N-pyridin-2-yl-propionamide (54.2 mg, 61.5%) as a white solid: mp 86–89° C.; EI-HRMS m/e calcd for C21H23F3N2O3S (M+) 440.1383, found 440.1381.
Reaction SMILES: [CH2:1]1[CH2:7][CH2:6][C:5]2[N:8]=[CH:9][CH:10]=[CH:11][C:4]=2[CH2:3][CH2:2]1.[OH:12]O>C(O)(=O)C>[N+:8]1([O-:12])[CH:9]=[CH:10][CH:11]=[C:4]2[CH2:3][CH2:2][CH2:1][CH2:7][CH2:6][C:5]=12
Reactant: c1cnc2c(c1)CCCCC2
Reactant: OO
Solvent: CC(=O)O
Product: [O-][n+]1cccc2c1CCCCC2
Temperature: 25 °C
Reaction time: 6 h

Procedure:
To a stirred solution of 2,3-cycloheptenopyridine (42.94 g, 0.292 mol) in glacial acetic acid (160 mL) at room temperature was added 30% H2O2 (30 mL) and the resultant solution was heated to 70° C. After 6 hours, the reaction mixture was cooled to room temperature, additional H2O2 (30 mL) was added, and the solution was heated at 70° C. overnight. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in CHCl3 (200 mL) and treated with solid Na2CO3 (100 g). After 1 hour, the supernatant was decanted and the residue was washed with warm CHCl3 (3×200 mL). The combined supernatants were filtered and concentrated to provide 60 g of 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine 1-oxide as a yellow oil. 1H NMR (CDCl3) δ 1.63-1.73 (m, 4H), 1.82-1.91 (m, 2H), 2.77-2.83 (m, 2H), 3.36-3.42 (m, 2H), 6.94-7.05 (m, 2H), 8.17,(d, 1H, J=6.1 Hz).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[CH2:13][CH2:14][CH2:15][C@@H:16]1[CH2:21][CH2:20][N:19]([CH2:22][C:23]#[CH:24])[CH2:18][C@@H:17]1[C:25]([O:27][CH3:28])=[O:26].[F:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1I.C(N(CC)CC)C>C(#N)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[CH2:13][CH2:14][CH2:15][C@@H:16]1[CH2:21][CH2:20][N:19]([CH2:22][C:23]#[C:24][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[F:29])[CH2:18][C@@H:17]1[C:25]([O:27][CH3:28])=[O:26]
Reactant: C#CCN1CC[C@@H](CCCc2ccnc3ccc(OC)cc23)[C@@H](C(=O)OC)C1
Reactant: Fc1ccccc1I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: COC(=O)[C@H]1CN(CC#Cc2ccccc2F)CC[C@H]1CCCc1ccnc2ccc(OC)cc12
Temperature: 20 °C
Reaction time: 20 h

Procedure:
0.041 g of tetrakis(triphenylphosphine)palladium and 0.070 g of cuprous iodide were added, at a temperature in the region of 20° C. and under an inert atmosphere, to a stirred solution of 0.7 g of methyl (3R,4R)-4-[3-(6-methoxyquinolin-4-yl)propyl]-1-(prop-2-ynyl)piperidine-3-carboxylate in 14 cm3 of acetonitrile. 0.32 cm3 of 1-fluoro-2-iodobenzene and 0.51 cm3 of triethylamine were subsequently added. The mixture was stirred at a temperature in the region of 20° C. for 20 hours. The reaction mixture was filtered and the cake was washed with 3 times 10 cm3 of acetonitrile. The combined filtrates were taken up with stirring in a mixture of 100 cm3 of dichloromethane and 100 cm3 of water. The organic phase was separated by settling, washed with 3 times 50 cm3 of a saturated sodium chloride solution, dried over magnesium sulfate, and then, after filtration, concentrated under reduced pressure (2 kPa) at a temperature in the region of 35° C. The residue obtained was purified by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 40-63 μm; diameter 4 cm; height 14 cm), elution was carried out with ethyl acetate, and 2-cm3 fractions were collected. Fractions 33 to 160 were combined and then evaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.56 g of methyl (3R,4R)-4-(3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(2-fluorophenyl)prop-2-ynyl]piperidine-3-carboxylate was obtained in the form of an oil with a light brown color.
Reaction SMILES: [OH-].[Li+].[CH3:3][C:4]1[N:8]=[C:7]([C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][N:18]=2)[C:12]([O:14]C)=[O:13])[O:6][N:5]=1>C(O)C>[CH3:3][C:4]1[N:8]=[C:7]([C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][N:18]=2)[C:12]([OH:14])=[O:13])[O:6][N:5]=1
Reactant: COC(=O)c1ccnc(-c2nc(C)no2)c1
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Product: Cc1noc(-c2cc(C(=O)O)ccn2)n1
Temperature: 25 °C
Reaction time: 5 h
Yield: 89 %

Procedure:
A mixture of lithium hydroxide (15 g, 0.25 mol), ethanol (500 mL) and methyl 2-(3-methyl-1,2,4-oxadiazol-5-yl)isonicotinate (52 g, 0.23 mol) were stirred at room temperature for 5 hours, then mixture was concentrated in vacuo. Water was added then extracted with ethyl acetate. The water layer was brought to pH 1.5 with aqueous 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was concentrated in vacuo to afford the title compound as a white solid (42 g). 1H NMR (300 MHz, DMSO-d6) δ ppm 14.08 (Or s, 1H) 9.00-8.98 (m, 1H) 8.50 (s, 1H) 8.09-8.07 (m, 1H), 2.46 (s, 3H).
Reaction SMILES: [CH2:1]([C:3]1[O:7][C:6]([C:8]2([N:14]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:15](=[O:18])[CH2:16][CH3:17])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[N:5][N:4]=1)[CH3:2].[S:25]1[CH:29]=[CH:28][CH:27]=[C:26]1[CH2:30][CH2:31]Cl.[Na+].[I-].C([O-])([O-])=O.[Na+].[Na+]>C(#N)C>[S:25]1[CH:29]=[CH:28][CH:27]=[C:26]1[CH2:30][CH2:31][N:11]1[CH2:10][CH2:9][C:8]([C:6]2[O:7][C:3]([CH2:1][CH3:2])=[N:4][N:5]=2)([N:14]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:15](=[O:18])[CH2:16][CH3:17])[CH2:13][CH2:12]1
Reactant: CCC(=O)N(c1ccccc1)C1(c2nnc(CC)o2)CCNCC1
Reactant: ClCCc1cccs1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [Na+]
Solvent: CC#N
Product: CCC(=O)N(c1ccccc1)C1(c2nnc(CC)o2)CCN(CCc2cccs2)CC1
Temperature: 25 °C
Yield: 81.4 %

Procedure:
A mixture of 4-(ethyl-1,3,4-oxadiazolyl)-4-(N-phenylpropionamido)piperidine (880 mg, 2.68 mmol), 2-(2-thienyl)ethyl chloride (385 mg, 2.63 mmol), NaI (470 mg, 3.1 mmol) and Na2CO3 (2.0 g) in acetonitrile (50 ml) was refluxed for 72 hours. It was cooled down to room temperature and filtered. The filtrate was concentrated in vacuo and the residue was treated with CH2Cl2 (100 ml). The resulting mixture was filtered and the filtrate was concentrated in vacuo. The residue was chromatographed to give the product (940 mg, 2.14 mmol) as an amber oil: IR (neat) 1660 cm-1 ; NMR (60 MHz, CDCl3) δ0.88 (t, 3H, CH3CH2CO), 1.39 (t, 3H, oxadiazolyl CH3), 1.60 to 3.20 (m, 16H), 6.70 to 7.40 (m, 3H, thienyl H's) 7.44 (s, 5 H, phenyl H's). ##STR33##
Reaction SMILES: [OH:1][C:2]1[C:3]([OH:20])=[CH:4][C:5]2[O:10][CH:9]=[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=3)[C:7](=[O:18])[C:6]=2[CH:19]=1.[C:21](OC(=O)C)(=[O:23])[CH3:22].[CH2:28]([OH:30])[CH3:29]>>[C:21]([O:20][C:3]1[C:2]([OH:1])=[CH:19][C:6]2[C:7](=[O:18])[C:8]([C:11]3[CH:12]=[CH:13][C:14]([NH:17][C:28](=[O:30])[CH3:29])=[CH:15][CH:16]=3)=[CH:9][O:10][C:5]=2[CH:4]=1)(=[O:23])[CH3:22]
Reactant: CC(=O)OC(C)=O
Reactant: Nc1ccc(-c2coc3cc(O)c(O)cc3c2=O)cc1
Reactant: CCO
Product: CC(=O)Nc1ccc(-c2coc3cc(OC(C)=O)c(O)cc3c2=O)cc1
Reaction time: 8 h

Procedure:
6,7-Dihydroxy-3-(4-aminophenyl)-4H-1-benzopyran-4-one [see Example 51a] (269 mg) is dissolved in ethanol (3 ml). Acetic anhydride (4 ml) is added and the solution heated to 70° for 2.5 h, then left overnight at room temperature. The resulting precipitate is filtered, washed with water and dried to give 7-acetyloxy-6-hydroxy-3-(4-acetylaminophenyl)-4H-1-benzopyran-4-one, m.p. 265°-266°.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:13])([CH3:12])[C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.C([Li])CCC.CCCCCC.[B:25](OC(C)C)([O:30]C(C)C)[O:26]C(C)C>C1COCC1>[B:25]([C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:13])([CH3:12])[C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1)([OH:30])[OH:26]
Reactant: CC(C)(C(=O)O)c1ccc(Br)cc1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC(C)(C(=O)O)c1ccc(B(O)O)cc1
Temperature: -50 °C
Reaction time: 2 h
Yield: 101.3 %

Procedure:
To a solution of 2-(4-bromophenyl)-2-methylpropanoic acid (15 g, 61.7 mmol) in anhydrous THF (150 mL) was added at −78° C. under argon a 2.5 M solution of n-butyllithium in hexane (37 ml, 92.6 mmol) dropwise, followed by triisopropyl borate (43 ml, 185.1 mmol). After the addition, the reaction mixture was stirred at −50° C. for 2 hrs and allowed to warm up to room temperature and stirred over night. The reaction mixture was quenched with 1 N HCl then extracted with EtOAc and washed successively with water and brine, dried over MgSO4, filtered and evaporated to give 13 g of product as a white solid in 99% yield. 1H NMR (400 MHz, DMSO): δ 1.41 (s, 6H), 7.25-7.27 (d, 2H), 7.29-7.47 (dd, 1H), 7.68-7.70 (d, 1H), 12.31 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[S:10][C:11]2[CH:12]=[N+:13]([O-])[CH:14]=[C:15]([F:18])[C:16]=2[N:17]=1.P(Cl)(Cl)([Cl:22])=O>>[Cl:22][C:12]1[C:11]2[S:10][C:9]([C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=3[Cl:8])=[N:17][C:16]=2[C:15]([F:18])=[CH:14][N:13]=1
Reactant: [O-][n+]1cc(F)c2nc(-c3c(Cl)cccc3Cl)sc2c1
Reactant: O=P(Cl)(Cl)Cl
Product: Fc1cnc(Cl)c2sc(-c3c(Cl)cccc3Cl)nc12
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 49 %

Procedure:
A stirred solution of 2-(2,6-dichlorophenyl)-7-fluorothiazolo[5,4-c]pyridine 5-oxide (0.095 g, 0.30 mmol) in phosphoryl chloride (3 mL) was heated under reflux for 0.5 hour and then at 110° C. for 15 minutes. The reaction was repeated on a larger scale by reacting 2-(2,6-dichlorophenyl)-7-fluorothiazolo[5,4-c]pyridine 5-oxide (6.4 g, 17.0 mmol) with phosphoryl chloride (100 mL) and by heating the mixture under reflux for 30 minutes. After cooling to room temperature, the mixture was left standing at room temperature for 18 hours and then heated at reflux temperature for 15 minutes. The two crude reaction mixtures were combined and the volatiles were removed under reduced pressure. The crude residue was dissolved in EtOAc (200 mL) and washed with a saturated solution of potassium carbonate, followed by water, then dried (Na2SO4) and concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel eluting with 0-20% EtOAc in pentane to afford the title compound as a white solid (3.42 g, 49% yield). 1H NMR (400 MHz, CDCl3): δ 8.39 (d, J=1.9 Hz, 1H), 7.53-7.41 (m, 3H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]([C:8]2[CH:16]=[CH:15][C:14]3[C:10](=[C:11]([CH3:19])[N:12]([CH2:17][CH3:18])[N:13]=3)[CH:9]=2)[C:4](=[O:20])[CH:3]=1.[F:21][C:22]([F:31])([F:30])[C:23]1[N:24]=[C:25]([CH2:28][OH:29])[S:26][CH:27]=1.CC(C)([O-])C.[K+].O>C1(C)C=CC=CC=1>[CH2:17]([N:12]1[C:11]([CH3:19])=[C:10]2[C:14]([CH:15]=[CH:16][C:8]([N:5]3[CH:6]=[CH:7][C:2]([O:29][CH2:28][C:25]4[S:26][CH:27]=[C:23]([C:22]([F:31])([F:30])[F:21])[N:24]=4)=[CH:3][C:4]3=[O:20])=[CH:9]2)=[N:13]1)[CH3:18]
Reactant: OCc1nc(C(F)(F)F)cs1
Reactant: CCn1nc2ccc(-n3ccc(Br)cc3=O)cc2c1C
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: O
Product: CCn1nc2ccc(-n3ccc(OCc4nc(C(F)(F)F)cs4)cc3=O)cc2c1C
Temperature: 100 °C
Reaction time: 2 h
Yield: 16.4 %

Procedure:
To a solution of 4-bromo-1-(2-ethyl-3-methyl-2H-indazol-5-yl)pyridin-2(1H)-one (350 mg) and [4-(trifluoromethyl)-1,3-thiazol-2-yl]methanol (289 mg) in toluene (5 ml) was added potassium tert-butoxide (355 mg) at room temperature, and the mixture was stirred at 100° C. for 2 hr. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate) and recrystallized from ethanol-water to give the title compound (75 mg).
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1[N:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[CH3:11]I.O>CS(C)=O.CCOCC>[CH3:11][O:10][C:7]1[CH:6]=[CH:5][C:4]([CH3:3])=[N:9][CH:8]=1
Reactant: CI
Reactant: Cc1ccc(O)cn1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOCC
Solvent: O
Product: COc1ccc(C)nc1
Temperature: 0 °C
Reaction time: 0.67 h

Procedure:
To a stirred solution of 60% NaH (in mineral oil) (18.27 g, 0.458 mol, Aldrich, India) in DMSO (66 mL, Spectrochem., India) at 0° C., was added 6-methylpyridin-3-ol (25.0 g, 0.229 mol) dissolved in DMSO (100 mL) drop wise over a period of 15 min. After complete addition, the reaction mixture was stirred at 0° C. for 40 min. Methyl iodide (29.5 mL, 0.458 mol, Spectrochem, India) was added and the reaction mixture was stirred at rt for 2 h. The reaction with water and Et2O (1:1, 200 mL). The organic layer was separated and aqueous layer was back extracted with Et2O (75 mL×3). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated to give the title compound as a dark brown gummy oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.19 (d, J=2.8 Hz, 1H), 7.12-7.05 (m, 2H), 3.83 (s, 3H), 2.49 (s, 3H). MS (ESI, positive ion) m/z: 124.0 (M+H).
Reaction SMILES: [OH-].[Na+].[O:3]=[C:4]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[CH:14]4[CH:19]([N:7]([C:8]=23)[CH:6]=[C:5]1[C:20]([O:22]CC)=[O:21])[CH2:18][CH2:17][CH2:16][CH2:15]4>O>[O:3]=[C:4]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[CH:14]4[CH:19]([N:7]([C:8]=23)[CH:6]=[C:5]1[C:20]([OH:22])=[O:21])[CH2:18][CH2:17][CH2:16][CH2:15]4
Reactant: CCOC(=O)c1cn2c3c(cccc3c1=O)C1CCCCC12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)c1cn2c3c(cccc3c1=O)C1CCCCC12
Yield: 63.1 %

Procedure:
250 ml of a 10% aqueous sodium hydroxide solution was added to 28 g of ethyl 7a,8,9,10,11,11a-hexahydro-4-oxo-4H-pyrido[3,2,1-jk]carbazol-5-carboxylate, followed by heat-refluxing for 2 hours. The reaction system changed from a suspension state to a uniform solution as the reaction proceeded. 200 ml of water was added to the reaction mixture which was then filtered, and the filtrate was rendered acidic with concentrated hydrochloric acid to precipitate light yellow crystals. The crystals were separated by filtration, washed successively with water and a small amount of ethanol, dried and recrystallized from chloroform-hexane (1:1 by volume) to obtain 16 g of 7a,8,9,10,11,11a -hexahydro-4-oxo-4H-pyrido[3,2,1-jk]carbazol-5-carboxylic acid as light yellow amorphous crystals having a melting point of 238°-241° C.
Reaction SMILES: [Br:1][CH2:2][C:3](Br)=[O:4].C(=O)(O)[O-].[Na+].[CH2:11]([C:13]1[CH:25]=[CH:24][C:16]([O:17][CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)=[CH:15][CH:14]=1)[CH3:12].O>ClCCl>[Br:1][CH2:2][C:3]([N:21]1[CH2:22][CH2:23][CH:18]([O:17][C:16]2[CH:24]=[CH:25][C:13]([CH2:11][CH3:12])=[CH:14][CH:15]=2)[CH2:19][CH2:20]1)=[O:4]
Reactant: O=C(Br)CBr
Reactant: CCc1ccc(OC2CCNCC2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: CCc1ccc(OC2CCN(C(=O)CBr)CC2)cc1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 96.7 %

Procedure:
To a stirred suspension of 6.03 ml (69.3 mmol) of bromoacetyl bromide, 13.0 g (155 mmol) of sodium bicarbonate and 160 ml of dry dichloromethane in an ice bath was added dropwise a solution of 13.0 g (63.4 mmol) of 4-(4-ethylphenoxy)piperidine in 140 ml of dry dichloromethane. The mixture was stirred 1 hour at 0° and 45 minutes at room temperature. The mixture was subsequently poured into water, extracted twice with dichloromethane, washed with saturated sodium chloride and dried over potassium carbonate. Filtration followed by evaporation of the solvent provided 20.0 g (61.3 mmol) of 1-(2-bromoacetyl)-4-(4-ethylphenoxy)piperidine as an oil.
Reaction SMILES: [C:1]([O-:4])(=[O:3])C.C([O-])(=O)C.[B+3].ClC1C=[C:19]2[C:14]([C:15](=O)C(C([O-])=O)=CN2C2CC2)=[CH:13]C=1F.FC1C=C(N2C[C@H](CNC(=O)C)OC2=O)C=CC=1[S:36][CH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1>>[C:14]([O:4][C:1]([N:40]1[CH2:39][CH2:38][CH:37]([SH:36])[CH2:42][CH2:41]1)=[O:3])([CH3:19])([CH3:15])[CH3:13]
Reactant: O=C([O-])c1cn(C2CC2)c2cc(Cl)c(F)cc2c1=O
Reactant: CC(=O)[O-]
Reactant: CC(=O)NC[C@H]1CN(c2ccc(SC3CCNCC3)c(F)c2)C(=O)O1
Agent: [B+3]
Product: CC(C)(C)OC(=O)N1CCC(S)CC1

Procedure:
Was prepared in analogy to example 28 starting from 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylate boron diacetate and (S)—N-[[3-(3-fluoro-4-(4-piperidinylsulfanyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]-acetamide. The later being obtained from 4-mercapto-piperidine-1-carboxylic acid tert-butyl ester (J. Antibiotics, 1995, 48, 408-16).
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[CH2:4][N:5]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH3:16])=[CH:12][CH:13]=2)[C:8]([CH3:17])=[CH:7][C:6]1=[O:18].[H-].[Na+].[C:25](=O)([O:29]CC)[O:26]CC.[CH3:33]O>>[Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[CH2:4][N:5]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH3:16])=[CH:12][CH:13]=2)[C:8]([CH:17]([CH3:33])[C:25]([OH:29])=[O:26])=[CH:7][C:6]1=[O:18]
Reactant: COc1ccc2c(c1)c(C)cc(=O)n2Cc1ccccc1Cl
Reactant: CO
Reactant: CCOC(=O)OCC
Agent: [H-]
Agent: [Na+]
Product: COc1ccc2c(c1)c(C(C)C(=O)O)cc(=O)n2Cc1ccccc1Cl
Reaction time: 24 h
Yield: 48 %

Procedure:
A mixture of 1-o-chlorobenzyl-4-methyl-6-methoxy-2-oxo-1,2-dihydroquinoline (2.5 g.), oil-free sodium hydride (obtained from 2.5 g. of a 50% w/w suspension as described in Example 1) and diethyl carbonate (50 ml.) was heated over 1 hour to reflux and the reflux maintained for 3 hours. The mixture was cooled and treated with methanol (2 ml.) to destroy excess sodium hydride. Ether (200 ml.) was added and the yellow precipitate was filtered off, washed with ether (50 ml.), and dried, and was then suspended in dimethylformamide (100 ml.) containing methyl iodide (4 ml.). After 24 hours standing at room temperature, the mixture was diluted with water (200 ml.) and the aqueous mixture extracted with ether (3×100 ml.). The combined ethereal extracts were washed with water (2×100 ml.), and dried with magnesium sulphate, and the ether was evaporated. The residue, which comprised diethyl α-(1-o-chlorobenzyl-6-methoxy-2-oxo-1,2-dihydroquinol-4-yl)-α-methylmalonate, was dissolved in a solution of potassium hydroxide (3.6 g.) in water (4 ml.) and ethanol (100 ml.). The mixture was refluxed for 1 hour, cooled, and diluted with N-hydrochloric acid (100 ml.). The resulting mixture was filtered, and the solid residue washed with water and crystallised from methanol (100 ml.) to give α-(1-o-chlorobenzyl-6-methoxy-2-oxo-1,2-dihydroquinol-4-yl)propionic acid, m.p. 187°-188° C. in 48% yield.
Reaction SMILES: [Br:1][CH:2]([CH3:6])[C:3](Cl)=[O:4].[CH2:7]([OH:10])[CH2:8][OH:9].N1C=CC=CC=1.Cl>C1COCC1.C(OCC)(=O)C>[Br:1][CH:2]([CH3:6])[C:3]([O:9][CH2:8][CH2:7][OH:10])=[O:4]
Reactant: CC(Br)C(=O)Cl
Reactant: OCCO
Agent: Cl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CC(Br)C(=O)OCCO
Reaction time: 2 h

Procedure:
In a nitrogen atmosphere, 2-bromopropionyl chloride (2 mL, 3.35 g, 19.5 mmol) was slowly added dropwise to a solution of ethylene glycol (10.9 mL, 195 mmol) and pyridine (3 g, 39 mmol) in THF (10 mL) at 0° C. The resulting solution was then stirred at that temperature for 2 hours. Diluted hydrochloric acid (20 mL) and ethyl acetate (30 mL) were added and the mixture was allowed to separate into two layers. The organic layer was separated, washed with diluted hydrochloric acid and brine and dried over sodium sulfate, and the volatile matter was distilled off under reduced pressure, to give a crude product (3.07 g). Distillation of this crude product under reduced pressure (70-73° C., 0.5 mmHg) gave 2-hydoxyethyl 2-bromopropionate of the formula shown below (2.14 g, 56%).
Reaction SMILES: [ClH:1].Cl.[NH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:15][CH:14]([C:16]([N:18]3[CH2:23][CH2:22][N:21]([CH2:24][C:25]([O:27]CC4C=CC=CC=4)=[O:26])[CH2:20][CH2:19]3)=[O:17])[O:13][C:12]2=[O:35])=[CH:7][CH:6]=1.O.C(O)(=O)C>CO.[Pd].C>[ClH:1].[ClH:1].[NH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:15][CH:14]([C:16]([N:18]3[CH2:19][CH2:20][N:21]([CH2:24][C:25]([OH:27])=[O:26])[CH2:22][CH2:23]3)=[O:17])[O:13][C:12]2=[O:35])=[CH:7][CH:6]=1
Reactant: NCc1ccc(N2CC(C(=O)N3CCN(CC(=O)OCc4ccccc4)CC3)OC2=O)cc1
Agent: [Pd]
Agent: Cl
Solvent: CC(=O)O
Solvent: CO
Solvent: O
Product: NCc1ccc(N2CC(C(=O)N3CCN(CC(=O)O)CC3)OC2=O)cc1

Procedure:
0.6 g of benzyl 2-{1-[3-(4-aminomethylphenyl)-2-oxo-5-oxazolidinylcarbonyl]-4-piperazinyl}acetate, dihydrochloride, is hydrogenated over Pd/charcoal, in a mixture of 30 ml of methanol, 5 ml of water and 5 ml of glacial acetic acid. The reaction mixture is filtered and the filtrate is concentrated in vacuo. Trituration of the crude product with ethyl acetate gives 2-{1-[3-(4-aminomethylphenyl)-2-oxo-5-oxazolidinylcarbonyl]-4-piperazinyl}acetic acid, dihydrochloride, m.p. 91° (decomposition).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][CH:3]=1.[C:9]1(B(O)O)[C:22]2[C:23]3=[C:24]4[C:19](=[CH:20][CH:21]=2)[CH:18]=[CH:17][CH:16]=[C:15]4[CH:14]=[CH:13][C:12]3=[CH:11][CH:10]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:16]2[C:15]3[C:24]4=[C:23]5[C:12](=[CH:13][CH:14]=3)[CH:11]=[CH:10][CH:9]=[C:22]5[CH:21]=[CH:20][C:19]4=[CH:18][CH:17]=2)=[CH:4][CH:3]=1
Reactant: Brc1ccc(I)cc1
Reactant: OB(O)c1ccc2ccc3cccc4ccc1c2c34
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: Brc1ccc(-c2ccc3ccc4cccc5ccc2c3c45)cc1
Yield: 80.3 %

Procedure:
Under an atmosphere of argon, 4-bromoiodobenzene (7.0 g, 25 mmole), 1-pyreneboronic acid (5.7 g, 23 mmole) and tetrakis(triphenylphosphine)palladium(0) (0.5 g, 0.43 mmole, 1.7% Pd) were dissolved into toluene (50 ml). To the obtained solution, an aqueous solution of sodium carbonate (7.3 g, 69 mmole, 3 eq/35 ml) was added. The resultant solution was heated under refluxing for 10 hours and left standing for one night. The formed organic layer was separated, washed with a saturated aqueous solution of sodium chloride (50 ml) and dried with anhydrous magnesium sulfate. Then, the solvent was removed by distillation and a yellow oil was obtained. The obtained oil was purified by the column chromatography (silica gel/hexane, hexane+3% dichloromethane and hexane+10% dichloromethane, successively) and white needle crystals (6.6 g, 80%) were obtained.