Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15]OS(C)(=O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:21]1(=[O:31])[NH:25][C:24](=[O:26])[C:23]2=[CH:27][CH:28]=[CH:29][CH:30]=[C:22]12.[K].O>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([CH2:14][CH2:15][N:25]2[C:24](=[O:26])[C:23]3=[CH:27][CH:28]=[CH:29][CH:30]=[C:22]3[C:21]2=[O:31])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: CC(C)(C)OC(=O)N1CCC(CCOS(C)(=O)=O)CC1
Agent: [K]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(CCN2C(=O)c3ccccc3C2=O)CC1
Temperature: 40 °C
Reaction time: 2 h
Yield: 80 %

Procedure:
A mixture of 1-tert-butoxycarbonyl-4-(2-mesyloxyethyl)piperidine (1.20 g) and potassium phthalimide (0.80 g) in N,N-dimethylformamide (15 ml) was stirred at 40° C. for 2 hours. The mixture was poured into water and extracted with ethyl acetate. The extract was washed with water, and dried over magnesium sulfate and evaporated in vacuo to give N-[2-[1-tert-butoxycarbonylpiperidin-4-yl]ethyl]phthalimide (1.12 g).
Reaction SMILES: [C:1]([NH:4][CH:5]1[CH:10]([CH:11]([O:22][C:23](=[O:25])[CH3:24])[CH:12]([O:18][C:19](=[O:21])[CH3:20])[CH2:13][O:14][C:15](=[O:17])[CH3:16])[O:9][C:8]([C:26]([O:28][CH3:29])=[O:27])=[CH:7][CH:6]1[N:30]=[N+]=[N-])(=[O:3])[CH3:2].O.[Cl-].[NH4+]>C(Cl)Cl.[Zn]>[C:1]([NH:4][CH:5]1[CH:10]([CH:11]([O:22][C:23](=[O:25])[CH3:24])[CH:12]([O:18][C:19](=[O:21])[CH3:20])[CH2:13][O:14][C:15](=[O:17])[CH3:16])[O:9][C:8]([C:26]([O:28][CH3:29])=[O:27])=[CH:7][CH:6]1[NH2:30])(=[O:3])[CH3:2]
Reactant: COC(=O)C1=CC(N=[N+]=[N-])C(NC(C)=O)C(C(OC(C)=O)C(COC(C)=O)OC(C)=O)O1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: O
Solvent: ClCCl
Product: COC(=O)C1=CC(N)C(NC(C)=O)C(C(OC(C)=O)C(COC(C)=O)OC(C)=O)O1
Temperature: 25 °C
Yield: 100.3 %

Procedure:
To a reaction vessel, 55 g of methyl 5-acetamido-4-azido-6-(1,2,3-triacetoxypropyl)-5,6-dihydro-4H-pyran-2-carboxylate, 500 ml of denatured alcohol and 100 ml of water was added under stirring at room temperature. To the reaction mass 14 g ammonium chloride and 18 g zinc dust was added. The reaction mixture was stirred at 20° C.-30° C. for 30 minutes. On completion of reaction, the reaction mass was cooled to 10° C. and then filtered through hyflo. The filtrate was concentrated under vacuum to obtain a solid product which was then dissolved in about 200 ml of methylene dichloride. The organic layer was filtered and concentrated to yield 52 g of solid title compound, dried under vacuum (yield—94%, HPLC purity—96%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13](=[O:29])[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8](OS(C(F)(F)F)(=O)=O)[CH:7]=[CH:6]2.Br[C:39]1[C:44]([F:45])=[C:43]([F:46])[CH:42]=[CH:41][C:40]=1[F:47].OC1C=C2C(=CC=1)C(C(C1C=CC(OCCN3CCCCC3)=CC=1)=O)=C(C1C=C(F)C=C(F)C=1F)C=C2>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]3)=[CH:16][CH:15]=1)=[O:29])=[C:8]([C:39]1[C:40]([F:47])=[CH:41][CH:42]=[C:43]([F:46])[C:44]=1[F:45])[CH:7]=[CH:6]2
Reactant: Fc1ccc(F)c(Br)c1F
Reactant: COc1ccc2c(C(=O)c3ccc(OCCN4CCCCC4)cc3)c(OS(=O)(=O)C(F)(F)F)ccc2c1
Agent: O=C(c1ccc(OCCN2CCCCC2)cc1)c1c(-c2cc(F)cc(F)c2F)ccc2cc(O)ccc12
Product: COc1ccc2c(C(=O)c3ccc(OCCN4CCCCC4)cc3)c(-c3c(F)ccc(F)c3F)ccc2c1
Yield: 45.1 %

Procedure:
Couple trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (1.81 g, 3.37 mmol) with 2-bromo-1,3,4-trifluoro-benzene (1.42 g, 6.75 mmol) in a procedure similar to the preparation of [6-hydroxy-2-(2,3,5-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone to give 0.79 g (45%) of the title compound: mass spectrum (ion spray): m/z=520.3 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[C:6](I)[CH:5]=1.[Cu][C:14]#[N:15].[C-]#N.[Na+]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[C:6]([C:14]#[N:15])[CH:5]=1
Reactant: COC(=O)c1ccc(O)c(I)c1
Reactant: N#C[Cu]
Agent: [C-]#N
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(O)c(C#N)c1
Temperature: 105 °C
Reaction time: 8 h

Procedure:
Methyl-4-hydroxy-3-iodobenzoate (2.00 g, 7.2 mmol) was dissolved into 5 mL of dry DMF. Copper(I) cyanide (0.72 g, 8.0 mmol) and a small crystal of sodium cyanide was added. The mixture was flushed with nitrogen, placed in an oil heating bath (100-110° C.), and stirred overnight. TLC indicated nearly complete reaction. The mixture was cooled and the solids removed by filtration. The solids were extracted with DMF (3 mL). The filtrate and washings were taken up in 100 mL of ethyl acetate, then washed with 3 portions of saturated sodium chloride solution. The solids and aqueous washings were combined, and shaken with a mixture of 50 mL of ethyl acetate and a ferric chloride solution (4 g of hydrated ferric chloride in 7 mL of conc. hydrochloric acid). The ethyl acetate layers were combined, washed with brine containing sodium metabisulfite, dried over sodium sulfate, filtered, and the solvent removed in vacuo. The resulting solids were purified by flash chromatography on silica gel (20% ethyl acetate/hexane) to afford methyl-3-cyano-4-hydroxybenzoate, 0.93g (73%).
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[N:15]=[C:14]3[C:17](=[O:26])[C:18]4[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=4[CH2:20][CH2:21][C:13]3=[C:12](Br)[C:11]=2[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28][NH:29][CH3:30].CN>>[CH2:1]([N:8]1[C:16]2[N:15]=[C:14]3[C:17](=[O:26])[C:18]4[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=4[CH2:20][CH2:21][C:13]3=[C:12]([N:29]([CH3:30])[CH3:28])[C:11]=2[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1c2ccccc2CCc2c1nc1c(cnn1Cc1ccccc1)c2Br
Reactant: CNC
Agent: CN
Product: CN(C)c1c2c(nc3c1cnn3Cc1ccccc1)C(=O)c1ccccc1CC2

Procedure:
By substituting the product of Example 11 in the procedure of Example 5 and substituting dimethylamine for the methylamine, 1-benzyl-4-(dimethylamino)-5,6-dihydrobenzo[5,6]cyclohepta[1,2-b]pyrazolo[4,3-e]pyridin-11(1H)-one is obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7](Cl)[C:6]=2[C:13]#[N:14].O.[CH3:16][N:17](C)[CH:18]=O>>[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([N:17]([CH3:18])[CH3:16])[C:6]=2[C:13]#[N:14]
Reactant: CN(C)C=O
Reactant: N#Cc1c(Cl)ccc2cc(Cl)cnc12
Solvent: O
Product: CN(C)c1ccc2cc(Cl)cnc2c1C#N
Yield: 87 %

Procedure:
110 g of 3,7-dichloro-8-cyanoquinoline in 500 ml of dimethylformamide were refluxed for 20 hours, the solution was cooled, an amount of water corresponding to half the volume of the solution was added, and the precipitated solid was filtered off under suction. 100 g of 3-chloro-8-cyano-7-dimethylaminoquinoline of melting point 174° C. were obtained. Yield: 87% of theory.
Reaction SMILES: Br[C:2]1[C:6]2[CH:7]([O:13][CH3:14])[NH:8][CH:9]=[C:10]([C:11]#[N:12])[C:5]=2[N:4]([CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[CH:3]=1.[NH2:20][C:21]1[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=1)[C:24]([O:26][CH3:27])=[O:25].CC(C)([O-])C.[Na+].O>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:11]([C:10]1[C:5]2[N:4]([CH:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[CH:3]=[C:2]([NH:20][C:21]3[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=3)[C:24]([O:26][CH3:27])=[O:25])[C:6]=2[C:7]([O:13][CH3:14])=[N:8][CH:9]=1)#[N:12]
Reactant: COC1NC=C(C#N)c2c1c(Br)cn2C1CCCC1
Reactant: COC(=O)c1cccc(N)c1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: O
Solvent: Cc1ccccc1
Product: COC(=O)c1cccc(Nc2cn(C3CCCC3)c3c(C#N)cnc(OC)c23)c1
Temperature: 110 °C
Reaction time: 4 h
Yield: 10.5 %

Procedure:
To a solution of 3-bromo-1-cyclopentyl-4-methoxy-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-7-carbonitrile (1.5 g) obtained in Step H of Example 33, methyl 3-aminobenzoate (0.85 g), 4,5′-bis(diphenylphosphino)-9,9′-dimethylxanthene (0.54 g) and tris(dibenzylideneacetone)dipalladium(0) (0.43 g) in toluene (10 mL) was added sodium tert-butoxide (0.90 g), and the mixture was stirred at 110° C. for 4 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (190 mg).
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][N:3]=[C:2]1[CH2:6][C:7]1[C:12]2[CH:13]=[CH:14][O:15][C:11]=2[C:10]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])=[CH:9][CH:8]=1.[H][H]>CO.[Pd]>[NH:3]1[CH2:4][CH2:5][N:1]=[C:2]1[CH2:6][C:7]1[C:12]2[CH2:13][CH2:14][O:15][C:11]=2[C:10]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])=[CH:9][CH:8]=1
Reactant: [H][H]
Reactant: CS(=O)(=O)Nc1ccc(CC2=NCCN2)c2ccoc12
Agent: [Pd]
Solvent: CO
Product: CS(=O)(=O)Nc1ccc(CC2=NCCN2)c2c1OCC2

Procedure:
A mixture of N-[4-(4,5-dihydro-1H-imidazol-2-ylmethyl)-benzofuran-7-yl]-methanesulfonamide (44 mg, 0.13 mmoles) and 10% Pd-C (pinch) in methanol (5 mL) was stirred under hydrogen which was supplied by a hydrogen filled balloon, at room temperature for 17 days. The catalyst was removed by filtration through celite. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography over silica gel eluting with 10% to 12% methanol in dichloromethane with 0.1% ammonium hydroxide to give N-[4-(4,5-dihydro-1H-imidazol-2-ylmethyl)-2,3-dihydro-benzofuran-7-yl]-methanesulfonamide as a solid which was further purified by preparative RPHPLC (YMC Combiprep ODS-A column, 10-90% acetonitrile: water (0.1% TFA)) M+H 296. The following representative compounds were synthesized similarly as shown above. Additional compounds prepared according to the procedure of Example 1 are shown in Table 1.
Reaction SMILES: C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[O:35]1[CH2:40][CH2:39][N:38]([C:41]2[C:46]([NH2:47])=[CH:45][C:44]([N:48]3[CH2:53][CH2:52][O:51][CH2:50][CH2:49]3)=[CH:43][N:42]=2)[CH2:37][CH2:36]1.Cl[C:55]1[C:64]2[C:59](=[CH:60][C:61]([F:66])=[CH:62][C:63]=2[F:65])[N:58]=[C:57]([C:67]2[CH:68]=[C:69]3[C:73](=[CH:74][CH:75]=2)[N:72]([CH3:76])[CH:71]=[CH:70]3)[C:56]=1[CH3:77].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.O.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.[Pd].[Pd]>[N:38]1([C:41]2[C:46]([NH:47][C:55]3[C:64]4[C:59](=[CH:60][C:61]([F:66])=[CH:62][C:63]=4[F:65])[N:58]=[C:57]([C:67]4[CH:68]=[C:69]5[C:73](=[CH:74][CH:75]=4)[N:72]([CH3:76])[CH:71]=[CH:70]5)[C:56]=3[CH3:77])=[CH:45][C:44]([N:48]3[CH2:49][CH2:50][O:51][CH2:52][CH2:53]3)=[CH:43][N:42]=2)[CH2:39][CH2:40][O:35][CH2:36][CH2:37]1
Reactant: Nc1cc(N2CCOCC2)cnc1N1CCOCC1
Reactant: Cc1c(-c2ccc3c(ccn3C)c2)nc2cc(F)cc(F)c2c1Cl
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Solvent: O
Solvent: Cc1ccccc1
Product: Cc1c(-c2ccc3c(ccn3C)c2)nc2cc(F)cc(F)c2c1Nc1cc(N2CCOCC2)cnc1N1CCOCC1
Temperature: 120 °C
Reaction time: 2 h

Procedure:
To a stirred solution of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.022 g, 0.047 mmol), 2,5-dimorpholinopyridin-3-amine (0.093 g, 0.350 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(1-methyl-1H-indol-5-yl)quinoline (0.1 g, 0.292 mmol) and Pd2dba3 (10.7 mg, 0.012 mmol) in toluene (2.92 mL) was added sodium t-butoxide (0.070 g, 0.73 mmol). The reaction mixture was heated to 120° C. and stirring continued for 2 h. The reaction was cooled to rt and diluted with water (15 mL). The mixture was extracted with EtOAc (2×15 mL) and DCM (1×15 mL). The organic layers were combined and washed with brine (1×20 mL) and dried over magnesium sulfate. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product N-(2,5-di(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(1-methyl-1H-indol-5-yl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 7.87 (1H, s), 7.66 (3H, m), 7.46 (2H, s), 7.15 (1H, d, J=3.1 Hz), 6.94-7.04 (1H, m), 6.57 (1H, d, J=2.9 Hz), 6.43 (1H, br. s.), 3.89-3.96 (4H, m), 3.88 (3H, s), 3.83-3.87 (4H, m), 3.30 (4H, br s), 3.03-3.14 (4H, m), 2.20 (3H, s). Mass Spectrum (ESI) m/e=571.3 (M+1).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:23]([CH:24]3O[CH:27]=[N:26][CH:25]3S(C3C=CC(C)=CC=3)(=O)=O)=[CH:22][C:12]3[N:13](CCS(C)(=O)=O)[CH:14]=[N:15][C:11]=3[C:10]=2[F:39])=[C:4]([Cl:40])[CH:3]=1.[NH3:41]>CO>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:23]([C:24]3[NH:41][CH:27]=[N:26][CH:25]=3)=[CH:22][C:12]3[NH:13][CH:14]=[N:15][C:11]=3[C:10]=2[F:39])=[C:4]([Cl:40])[CH:3]=1
Reactant: Cc1ccc(S(=O)(=O)C2N=COC2c2cc3c(ncn3CCS(C)(=O)=O)c(F)c2Nc2ccc(Br)cc2Cl)cc1
Reactant: N
Solvent: CO
Product: Fc1c(Nc2ccc(Br)cc2Cl)c(-c2cnc[nH]2)cc2[nH]cnc12
Temperature: 90 °C
Reaction time: 20 h
Yield: 7 %

Procedure:
(4-Bromo-2-chloro-phenyl)-{4-fluoro-1-(2-methanesulfonyl-ethyl)-6-[4-(toluene-4-sulfonyl)-4,5-dihydro-oxazol-5-yl]-1H-benzoimidazol-5-yl}-amine 10bb (0.072 g, 0.107 mmol) is treated with 2.4 mL of a 2.0 M NH3 in MeOH solution in a sealed pressure tube. The reaction mixture is then heated to 90° C. with stirring for 20 hours and furthered stirred at room temperature for 3 days. The reaction mixture is transferred to a round bottom flask and concentrated under reduced pressure. Purification by flash column chromatography, twice, eluted with 10:1 methylene chloride:MeOH, followed by successive triturations with methylene chloride and then diethyl ether provides 3 mg (7%) desired product: LC/MS ESI (+) m/z 408, 406 (M+ Br pattern) detected; 1H NMR (400 MHz, MeOH-d4) δ 8.23 (s, 1H), 7.87 (s, 1H), 7.74 (s, 1H), 7.46 (m, 1H), 7.32 (d, 1H), 7.05 (m, 1H), 6.20 (dd, 1H).
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:9]([OH:14])(=[O:13])[C:10]([CH3:12])=[CH2:11].C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C1C=CC=CC=1>[CH:1]([CH2:12][C:10](=[CH2:11])[C:9]([OH:14])=[O:13])=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Reactant: C=C(C)C(=O)O
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: c1ccccc1
Product: C=C(CC=Cc1ccccc1)C(=O)O
Reaction time: 3 h

Procedure:
First, 100 g of styrene, 0.033 g of methacrylic acid, and 0.5 g of BPO (benzoyl peroxide) were dissolved in benzene (solvent), and the resulting solution was kept at 80° C. for 3 hours. Then, benzene as solvent was removed, and the styrene-methacrylic acid copolymer was obtained. This copolymer is hereinafter referred to as SMCPa. The content of methacrylic acid as a functional monomer in SMCPa was 0.05 mol %.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10].[CH3:24][S:25](Cl)(=[O:27])=[O:26].C(N(CC)CC)C>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:13][CH2:14][CH:15]([N:18]3[CH2:19][CH2:20][N:21]([S:25]([CH3:24])(=[O:27])=[O:26])[CH2:22][CH2:23]3)[CH2:16][CH2:17]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10]
Reactant: COc1cc(N2CCC(N3CCNCC3)CC2)ccc1[N+](=O)[O-]
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1cc(N2CCC(N3CCN(S(C)(=O)=O)CC3)CC2)ccc1[N+](=O)[O-]
Temperature: 25 °C
Yield: 76.6 %

Procedure:
To a suspension of 1-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}piperazine (5.0 g, 11.6 mmol), methane sulfonyl chloride (1.4 mL, 17.5 mmol) and dichloromethane (200 mL) was added triethylamine (8.1 mL, 58.2 mmol). The reaction was stirred at room temperature and monitored by TLC. After complete consumption of the starting material the clear yellow solution was concentrated onto silica gel and purified by chromatography to afford 1-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)piperazine as a yellow solid (3.54 g, 76%). 1H NMR (400 MHz, DMSO-d6) δ 7.85 (d, J=9.5 Hz, 1H), 6.57 (dd, J=9.2, 2.6 Hz, 1H), 6.48 (d, J=2.6 Hz, 1H), 4.09-4.00 (m, 2H), 3.89 (s, 3H), 3.10-3.03 (m, 4H), 2.99-2.90 (m, 2H), 2.84 (s, 3H), 2.61-2.52 (m, 5H), 1.85-1.77 (m, 2H), 1.50-1.37 (m, 2H).
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[Al+3].[Cl-].[Cl-].[F:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]2[C:25]([C:26]3[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][CH:27]=3)=[CH:24][CH:23]=[C:22]2[CH3:36])=[CH:17][CH:16]=1>C(Cl)Cl>[F:14][C:15]1[CH:16]=[CH:17][C:18]([N:21]2[C:25]([C:26]3[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][CH:27]=3)=[CH:24][C:23]([C:1]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:8])=[C:22]2[CH3:36])=[CH:19][CH:20]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Cc1ccc(-c2ccc(S(C)(=O)=O)cc2)n1-c1ccc(F)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: Cc1c(C(=O)c2ccccc2)cc(-c2ccc(S(C)(=O)=O)cc2)n1-c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 8.2 %

Procedure:
Benzoyl chloride (180 μl, 1.52 mmol) was slowly added to a stirred slurry of aluminum chloride (223 mg, 1.67 mmol) in methylene chloride (15 ml) at -10° C. After 30 minutes, a solution of 1-(4-fluorophenyl)-2-methyl-5-[4-(methylsulfonyl)phenyl]-1H-pyrrole (Example 1) (500 mg, 1.52 mmol) in methylene chloride (10 ml) was added. The reaction mixture was warmed to room temperature and stirred for 20 hours. The reaction mixture was poured over ice-water and extracted with methylene chloride. The organic fraction was washed with brine, dried (MgSO4), filtered and concentrated. The crude yellowish solid (570 mg) was purified by chromatography (silica gel, hexane/ethyl acetate, 6/4) to give [1-(4-fluorophenyl)-2-methyl-5-[4-(methylsulfonyl)phenyl]-1H-pyrrol-3-yl]-phenylmethanone (54 mg, 8%) as a white solid: Anal Calc'd. for C25H20NSFO3 ·0.5 H2O: C, 67.86; H, 4.78; N, 3.17. Found: C, 67.59; H, 4.70; N. 3.07.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[S:9][C:8]2[CH:10]=[CH:11][C:12]([N+:14]([O-])=O)=[CH:13][C:7]=2[CH:6]=1)=[O:4]>CO.[Pd]>[CH3:1][O:2][C:3]([C:5]1[S:9][C:8]2[CH:10]=[CH:11][C:12]([NH2:14])=[CH:13][C:7]=2[CH:6]=1)=[O:4]
Reactant: COC(=O)c1cc2cc([N+](=O)[O-])ccc2s1
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1cc2cc(N)ccc2s1
Reaction time: 2 h
Yield: 82.8 %

Procedure:
To a solution of 5-nitro-benzo[b]thiophene-2-carboxylic acid methyl ester [15] (130 mg, 0.548 mmol) in methanol (30 mL) was added 5% palladium on carbon (20 mg) and the mixture was stirred under 1 atm H2 for 2 h. The mixture was filtered through celite and the filtrate evaporated. The residue was passed through a silica column to afford 5-amino-benzo[b]thiophene-2-carboxylic acid methyl ester as a pale yellow solid (94 mg, 83%), single spot at Rf 0.75 (95:5 dichloromethane:methanol). 1H NMR (CDCl3): δ 7.86 (1H, s), 7.61 (1H, d, J=8.7 Hz), 7.11 (1H, d, J=2.2 Hz), 6.88(1H, dd, J=8.7, 2.5 Hz), 3.91 (3H, s), 3.76 (2H, s, N—H2) [16].
Reaction SMILES: [CH3:1][C@@:2]1([C:18]([F:21])([F:20])[F:19])[CH2:17][N:5]2[C:6](=[O:16])[CH:7]=[C:8]([N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[N:9]=[C:4]2[NH:3]1.[H-].[Na+].[CH3:24][C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27](Cl)=[O:28]>O1CCCC1>[CH3:1][C@@:2]1([C:18]([F:21])([F:19])[F:20])[CH2:17][N:5]2[C:6](=[O:16])[CH:7]=[C:8]([N:10]3[CH2:11][CH2:12][O:13][CH2:14][CH2:15]3)[N:9]=[C:4]2[N:3]1[C:27]([C:26]1[CH:30]=[CH:31][CH:32]=[CH:33][C:25]=1[CH3:24])=[O:28]
Reactant: C[C@@]1(C(F)(F)F)Cn2c(nc(N3CCOCC3)cc2=O)N1
Reactant: Cc1ccccc1C(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1ccccc1C(=O)N1c2nc(N3CCOCC3)cc(=O)n2C[C@@]1(C)C(F)(F)F

Procedure:
The product can be prepared as described in Example 21, but using 200 mg of (2S)-2-methyl-7-(morpholin-4-yl)-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one, 31 mg of sodium hydride at 60% in oil and 101 mg of 2-methylbenzoyl chloride in 4 ml of tetrahydrofuran. After purification by silica column chromatography (eluent: CH2Cl2/MeOH; gradient from 100/0 to 97/03), 44 mg of (2S)-2-methyl-1-[(2-methylphenyl)carbonyl]-7-(morpholin-4-yl)-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)one are obtained in the form of an ivory-coloured foam, the characteristics of which are the following:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:14]([O:16][CH:17]([CH3:19])[CH3:18])=[O:15])=[C:6]([S:8]([N:11]=[C:12]=[O:13])(=[O:10])=[O:9])[CH:7]=1.[NH2:20][C:21]1[N:26]=[C:25]([O:27][CH3:28])[N:24]=[C:23]([C:29]([F:32])([F:31])[F:30])[N:22]=1>ClCCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:14]([O:16][CH:17]([CH3:19])[CH3:18])=[O:15])=[C:6]([S:8]([NH:11][C:12]([NH:20][C:21]2[N:26]=[C:25]([O:27][CH3:28])[N:24]=[C:23]([C:29]([F:32])([F:31])[F:30])[N:22]=2)=[O:13])(=[O:9])=[O:10])[CH:7]=1
Reactant: CC(C)OC(=O)c1ccc(Cl)cc1S(=O)(=O)N=C=O
Reactant: COc1nc(N)nc(C(F)(F)F)n1
Solvent: ClCCCl
Product: COc1nc(NC(=O)NS(=O)(=O)c2cc(Cl)ccc2C(=O)OC(C)C)nc(C(F)(F)F)n1
Temperature: 25 °C
Reaction time: 16 h
Yield: 70 %

Procedure:
19.6 g of a solution of 6.1 g of 5-chloro-2-(i-propoxycarbonyl)benzenesulfonyl isocyanate (20 mmol) in 1,2-dichloroethane are added dropwise to a solution of 3.9 g of 2-amino-4-methoxy-6-trifluoromethyl-1, 3,5-triazine (20 mmol) in 150 ml of 1,2-dichloroethane at 25° C. The mixture is stirred at 25° C. for 16 h and then at 50° C. for 3 h. After removal of volatiles under waterpump vacuum at 60° C., the residue is extracted with 200 ml of a mixture of tert-butyl methyl ether and diethyl ether. The solvents are removed under waterpump vacuum at 50° C. and the residue is stirred in a little i-propanol. The solid product is filtered off with suction and dried under waterpump vacuum at 40° C. This results in 7.2 g of the title compound (14 mmol; 70% of theory) of melting point 160°-163° C.