Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C@@H:2]([NH:10]C(=O)OCC1C=CC=CC=1)[C:3](=[O:9])[N:4]1[CH2:8][CH2:7][CH2:6][CH2:5]1>CO>[O:9]=[C:3]([N:4]1[CH2:8][CH2:7][CH2:6][CH2:5]1)[C@H:2]([NH2:10])[CH3:1]
Reactant: C[C@@H](NC(=O)OCc1ccccc1)C(=O)N1CCCC1
Solvent: CO
Product: C[C@@H](N)C(=O)N1CCCC1
Yield: 91.8 %

Procedure:
Phenylmethyl [(1R)-1-methyl-2-oxo-2-(1-pyrrolidinyl)ethyl]carbamate (496 mg, 1.8 mmol) was dissolved in 20 mL of MeOH, degassed and placed under argon. 10% Pd/C (125 mg) was added, and the contents were thoroughly degassed and placed under a hydrogen balloon overnight. The contents were then degassed and filtered through Celite, and the Celite pad was washed with DCM and MeOH. The resulting filtrate was concentrated in vacuo to provide the (2R)-1-oxo-1-(1-pyrrolidinyl)-2-propanamine (235 mg, 91%). LCMS: (M+H)+: 143.1.
Reaction SMILES: Br[CH2:2][CH:3]1[O:18][C:6]2=[C:7]3[C:12](=[C:13]([CH3:15])[CH:14]=[C:5]2[CH:4]1[CH2:19][CH3:20])[NH:11][C:10](=[O:16])[C:9]([CH3:17])=[CH:8]3.[N-:21]=[N+:22]=[N-:23].[Na+]>CN(C)C=O>[N:21]([CH2:2][CH:3]1[O:18][C:6]2=[C:7]3[C:12](=[C:13]([CH3:15])[CH:14]=[C:5]2[CH:4]1[CH2:19][CH3:20])[NH:11][C:10](=[O:16])[C:9]([CH3:17])=[CH:8]3)=[N+:22]=[N-:23]
Reactant: CCC1c2cc(C)c3[nH]c(=O)c(C)cc3c2OC1CBr
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCC1c2cc(C)c3[nH]c(=O)c(C)cc3c2OC1CN=[N+]=[N-]
Yield: 57.5 %

Procedure:
The title compound was prepared in a manner similar to that described in Example 274 using the compound obtained in Example 292 (46 mg, 0.14 mmol), sodium azide (53 mg, 0.82 mmol) and dimethylformamide (1.0 ml). 24 mg of the title compound was obtained as a pale yellow solid (58.8%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=1)/[C:6]([CH3:20])=[C:5]2[CH2:21][CH2:22][O:23][NH2:24].[O:25]([CH2:32][CH:33]=O)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=1)/[C:6]([CH3:20])=[C:5]2[CH2:21][CH2:22][O:23][N:24]=[CH:33][CH2:32][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: O=CCOc1ccccc1
Reactant: CSc1ccc(/C=C2/C(C)=C(CCON)c3cc(F)ccc32)cc1
Product: CSc1ccc(/C=C2/C(C)=C(CCON=CCOc3ccccc3)c3cc(F)ccc32)cc1

Procedure:
The title compound is prepared by reaction of O-2-[Z-5-fluoro-2-methyl-1-(4-methylthiophenyl)methylene-1H-inden-3-yl]ethyl hydroxylamine with phenoxyacetaldehyde by the method of Example 1.
Reaction SMILES: Cl[C:2]1[N:11]=[C:10]([CH3:12])[C:9]([N+:13]([O-])=O)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].C(N(CC)CC)C>CO.[Pd]>[NH2:13][C:9]1[C:10]([CH3:12])=[N:11][CH:2]=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)c1cc([N+](=O)[O-])c(C)nc1Cl
Agent: [Pd]
Solvent: CCN(CC)CC
Solvent: CO
Product: COC(=O)c1cnc(C)c(N)c1
Temperature: 25 °C
Reaction time: 48 h
Yield: 37.9 %

Procedure:
A round-bottom flask, containing a solution of methyl 2-chloro-6-methyl-5-nitronicotinate (12.8 g, 55.5 mmol, 1.00 equiv) in methanol (120 mL) was purged with nitrogen. Triethylamine (15.0 g, 149 mmol, 2.68 equiv) and palladium on carbon (1.30 g) were added. After further purging the flask with nitrogen, the atmosphere was changed to hydrogen and the resulting solution was stirred for 2 days at room temperature under atmospheric pressure. After purging the system with nitrogen, the solids were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:50-1:5) as eluent to furnish 3.50 g (38%) of the title compound as a yellow solid.
Reaction SMILES: [C:1]([N:20]1[CH:28]=[N:27][C:26]2[C:21]1=[N:22][CH:23]=[N:24][C:25]=2[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:40][C:41]1[O:42][C:43](=[O:57])[C:44]2[C:49]([C:50]=1[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)=[CH:48][CH:47]=[CH:46][CH:45]=2.O>CN(C=O)C>[O:57]=[C:43]1[C:44]2[C:49](=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:50]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)=[C:41]([CH2:40][N:29]([C:25]2[N:24]=[CH:23][N:22]=[C:21]3[C:26]=2[N:27]=[CH:28][N:20]3[C:1]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])[O:42]1
Reactant: O=c1oc(CBr)c(-c2ccccc2)c2ccccc12
Reactant: CC(C)(C)OC(=O)Nc1ncnc2c1ncn2C(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)N(Cc1oc(=O)c2ccccc2c1-c1ccccc1)c1ncnc2c1ncn2C(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C

Procedure:
tert-Butyl 9-trityl-9H-purin-6-ylcarbamate (63.6 mg, 0.133 mmol) in DMF (0.1 ml) was added to a suspension of 50% dispersion in mineral oil NaH (5.33 mg, 0.133 mmol) in DMF (0.1 ml) at 0° C. 3-(bromomethyl)-4-phenyl-1H-isochromen-1-one (intermediate C1, 35 mg, 0.111 mmol) in DMF (0.2 ml) was added and the resulting mixture was allowed to warm to RT. The reaction mixture was then poured into water and extracted with EtOAc. The collected organic phases were dried and concentrated under reduced pressure and the resulting crude (80 mg) was used in the next step without any further purification and characterization.
Reaction SMILES: [NH2:1][CH2:2][C:3]1([CH2:6][O:7][C:8]2[C:13]([O:14][CH3:15])=[C:12]([O:16][CH3:17])[CH:11]=[CH:10][C:9]=2[C:18]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:19]=2[CH2:20][CH2:21][C:22]3=[O:27])[CH2:5][CH2:4]1.C(N(C(C)C)CC)(C)C.[C:37](Cl)(=[O:41])[CH2:38][CH2:39][CH3:40]>ClCCl>[CH3:15][O:14][C:13]1[C:12]([O:16][CH3:17])=[CH:11][CH:10]=[C:9]([C:18]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:19]=2[CH2:20][CH2:21][C:22]3=[O:27])[C:8]=1[O:7][CH2:6][C:3]1([CH2:2][NH:1][C:37](=[O:41])[CH2:38][CH2:39][CH3:40])[CH2:4][CH2:5]1
Reactant: CCCC(=O)Cl
Reactant: COc1ccc(-c2cccc3c2CCC3=O)c(OCC2(CN)CC2)c1OC
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCCC(=O)NCC1(COc2c(-c3cccc4c3CCC4=O)ccc(OC)c2OC)CC1

Procedure:
To a stirring solution of 4-[2-(1-Aminomethyl-cyclopropylmethoxy)-3,4-dimethoxy-phenyl]-indan-1-one (Compound 182) (100 mg, 0.272 mmol) in dichloromethane (10 mL), were added diisopropylethylamine (0.034 g, 0.272 mmol) and butyryl chloride (29 mg, 0.272 mmol) and the resultant reaction mixture was subjected to the conditions used in the preparation of compound 183 to afford the title compound as a solid.
Reaction SMILES: C(O[C:5](=[O:7])[CH3:6])(=O)C.[CH2:8]([N:15]1[CH2:19][CH:18]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[CH:17]([NH2:28])[CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C1COCC1>[CH2:8]([N:15]1[CH2:19][C@@H:18]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[C@H:17]([NH:28][C:5](=[O:7])[CH3:6])[CH2:16]1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: NC1CN(Cc2ccccc2)CC1c1ccc(Cl)c(Cl)c1
Reactant: CC(=O)OC(C)=O
Solvent: C1CCOC1
Product: CC(=O)N[C@@H]1CN(Cc2ccccc2)C[C@H]1c1ccc(Cl)c(Cl)c1

Procedure:
To a stirred solution of acetic anhydride (0.75 ml, 7.97 mmol) in THF (10 ml) was added a solution of rac-(3S,4R)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-ylamine (described herein above) (2.00 g, 6.22 mmol) in THF (10 ml) dropwise over 30 minutes. The reaction mixture was stirred one additional hour, concentrated under vacuo, taken up in EtOAc, washed with aq. NaHCO3. and then the organic phase was dried over Na2SO4 to afford the intermediate N-[(3S,4R)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-acetamide. To this intermediate in THF (10 ml) at 0° C., was added portion wise LiAlH4 (0.49 g, 12.83 mmol). Stirring was continued over night at 65° C.). The reaction mixture was then heated at 65° C. over night, cooled to RT and carefully quenched with aq. NaHCO3. The product was extracted several times with EtOAc, the organic phases were then dried over Na2SO4 and the product purified by flash chromatography (SiO2, CH2Cl2/MeOH 9:1) to afford 1.03 g (46%) of rac-[(3S,4R)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethyl-amine as a colorless oil. ES-MS m/e: 349.10 (M+H+).
Reaction SMILES: [OH:1][C:2]1([CH2:11][NH:12][C:13]([C:15]2[C:16]3[CH:17]=[CH:18][C:19](Cl)=[N:20][C:21]=3[CH:22]=[CH:23][C:24]=2[Cl:25])=[O:14])[CH2:7][CH2:6][CH2:5][CH:4]([CH:8]2[CH2:10][CH2:9]2)[CH2:3]1.CCN(C(C)C)C(C)C.[CH3:36][N:37]([CH3:43])[C@H:38]1[CH2:42][CH2:41][NH:40][CH2:39]1>>[OH:1][C:2]1([CH2:11][NH:12][C:13]([C:15]2[C:16]3[CH:17]=[CH:18][C:19]([N:40]4[CH2:41][CH2:42][C@H:38]([N:37]([CH3:43])[CH3:36])[CH2:39]4)=[N:20][C:21]=3[CH:22]=[CH:23][C:24]=2[Cl:25])=[O:14])[CH2:7][CH2:6][CH2:5][CH:4]([CH:8]2[CH2:10][CH2:9]2)[CH2:3]1
Reactant: O=C(NCC1(O)CCCC(C2CC2)C1)c1c(Cl)ccc2nc(Cl)ccc12
Reactant: CN(C)[C@H]1CCNC1
Solvent: CCN(C(C)C)C(C)C
Product: CN(C)[C@H]1CCN(c2ccc3c(C(=O)NCC4(O)CCCC(C5CC5)C4)c(Cl)ccc3n2)C1

Procedure:
The title compound was synthesized according to the procedure described in example 1 using 2,6-dichloro-quinoline-5-carboxylic acid (1-hydroxy-3-cyclopropyl-cyclohexylmethyl)-amide, DIPEA and (S)-3-dimethylamino-pyrrolidine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.75 (1H), 7.85 (m, 1H), 7.58 (2H), 7.05 (1H), 4.26 (s, 1H), 3.87 (t, 1H), 3.75 (m, 2H), 3.56 (m, 1H), 3.49 (m, 1H), 3.36 (m, 2H), 3.24 (m, 2H), 2.84 (m, 1H), 2.22 (s, 6H), 1.85 (m, 1H), 1.67 (m, 2H), 1.44-1.38 (m, 4H), 1.27 (m, 2H), 0.30 (m, 2H), 0.23 (m, 2H). m/z: 458 [M+H]
Reaction SMILES: [O:1]1[CH:5]=[N:4][C:3]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]([C:13]3[C:18]([Cl:19])=[CH:17][N:16]=[C:15]([NH2:20])[C:14]=3[N+:21]([O-])=O)[CH2:9][CH2:8]2)=[N:2]1.[CH3:24][N:25]1[CH:29]=[C:28]([CH:30]=O)[C:27]([CH3:32])=[N:26]1.[O-]S(S([O-])=O)=O.[Na+].[Na+]>CCO>[Cl:19][C:18]1[C:13]([N:10]2[CH2:11][CH2:12][N:7]([CH2:6][C:3]3[N:4]=[CH:5][O:1][N:2]=3)[CH2:8][CH2:9]2)=[C:14]2[N:21]=[C:30]([C:28]3[C:27]([CH3:32])=[N:26][N:25]([CH3:24])[CH:29]=3)[NH:20][C:15]2=[N:16][CH:17]=1
Reactant: Cc1nn(C)cc1C=O
Reactant: Nc1ncc(Cl)c(N2CCN(Cc3ncon3)CC2)c1[N+](=O)[O-]
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: CCO
Product: Cc1nn(C)cc1-c1nc2c(N3CCN(Cc4ncon4)CC3)c(Cl)cnc2[nH]1
Temperature: 80 °C
Reaction time: 15 h
Yield: 42.7 %

Procedure:
To a solution of 4-(4-((1,2,4-oxadiazol-3-yl)methyl)piperazin-1-yl)-5-chloro-3-nitropyridin-2-amine (50.0 mg, 0.147 mmol) and 1,3-dimethyl-1H-pyrazole-4-carbaldehyde (19.2 mg, 0.155 mmol) in EtOH (3.4 mL) was added 1M Na2S2O4 (0.588 mL, 0.588 mmol, freshly prepared) and the solution was heated to 80° C. and stirred for 15 h whilst being open to air. Once cooled, the reaction was evaporated in vacuo and the residue dry loaded onto silica. Purification was accomplished by flash chromatography on silica gel (2×14) eluting with MeOH/CH2Cl2 (5-7.5%) to yield the title compound (26 mg, 43%) as a pale yellow solid.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[S:10])=[C:4]([F:11])[CH:3]=1.Cl[C:13]1[C:18]([CH2:19][C:20]#[N:21])=[CH:17][CH:16]=[CH:15][N:14]=1.[H-].[Na+]>CS(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[S:10][C:13]3=[N:14][CH:15]=[CH:16][CH:17]=[C:18]3[C:19]=2[C:20]#[N:21])=[C:4]([F:11])[CH:3]=1
Reactant: Fc1cc(Br)ccc1N=C=S
Reactant: N#CCc1cccnc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: N#Cc1c(Nc2ccc(Br)cc2F)sc2ncccc12
Temperature: 80 °C
Yield: 8 %

Procedure:
4-Bromo-2-fluoro-1-isothiocyanatobenzene (250 mg, 1.08 mmol) and (2-chloropyridin-3-yl)acetonitrile (D. H. Bremner et al., Synthesis, 1997, 949) (165 mg, 1.08 mmol) were stirred in DMSO (20 mL) and sodium hydride (52 mg, 1.3 mmol) added portionwise. After evolution of gases had finished the reaction mixture was heated for 4 h at 80° C. After this time the reaction mixture was added to ice (50 mL) and a precipitate formed. This was filtered and purified by preparative HPLC (pH 10, 2-3 min) to give the title compound as a white powder (30 mg, 9%). δH (DMSO-d6) 10.45 (1H, s), 8.31 (1H, d, J 3.9 Hz), 7.75 (2H, m), 7.51-7.38 (3H, m). LCMS (ES+) RT 3.49 minutes, 350 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[S:3][CH:4]=[C:5]([CH:7]=O)[N:6]=1.[CH3:9][O:10][C:11](=[O:32])[CH:12]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>O1CCCC1.O>[CH3:9][O:10][C:11](=[O:32])[CH:12]=[CH:7][C:5]1[N:6]=[C:2]([Br:1])[S:3][CH:4]=1
Reactant: COC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=Cc1csc(Br)n1
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)C=Cc1csc(Br)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 80.8 %

Procedure:
Dissolve 2-bromothiazole-4-carbaldehyde (3.00 g, 15.62 mmol) in tetrahydrofuran (52 mL) and add methyl(triphenylphosphoranylidene)acetate (5.33 g. 15.62 mmol). Stir the mixture overnight at room temperature. Dilute the mixture with water and extract twice using diethyl ether. Dry the combined organics over sodium sulfate, filter, and concentrate. Purify via silica gel chromatography using a 0-30% gradient of EtOAc/hexanes to give 3.13 g (81%) of the title compound as a white solid.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:10]([C:12]1[CH:16]=[CH:15][S:14][C:13]=1Br)=[O:11].[C:18](=O)([O-])[O-].[K+].[K+]>CS(C)=O>[CH3:18][C:15]1[S:14][C:13]2[O:1][C:2]3[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=3[NH:9][C:10](=[O:11])[C:12]=2[CH:16]=1
Reactant: O=C([O-])[O-]
Reactant: Cc1ccc(O)c(NC(=O)c2ccsc2Br)c1
Agent: [K+]
Solvent: CS(C)=O
Product: Cc1ccc2c(c1)NC(=O)c1cc(C)sc1O2
Temperature: 145 °C
Reaction time: 2 h
Yield: 43.9 %

Procedure:
To a solution of N-(2-hydroxy-5-methylphenyl)-2-bromo-3-thiophenecarboxamide (2.9 g) in dimethyl sulfoxide (24 ml) was added potassium carbonate (2.4 g) and the mixture was stirred at 140-150° C. for 2 hours. The reaction system was cooled to room temperature and the reaction mixture was poured into ice water. The precipitated crystals were collected by filtration. The filtrate was extracted twice with chloroform and the organic layer was dried over sodium sulfate. The solvent was evaporated under reduced pressure. The residue and the above-mentioned crystals were combined and purified by silica gel column chromatography (chloroform:methanol=20:1). The obtained solid was collected by filtration from hexane to give 2,7-dimethylthieno[2,3-b][1,5]benzoxazepin-4(5H)-one (1.0 g).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Cl:12])[CH:10]=2)[N:5]=[CH:4][N:3]=1.Cl.[Cl:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][NH2:20])=[CH:17][C:16]=1[N+:23]([O-:25])=[O:24]>C(O)(C)C.C(N(CC)CC)C>[Cl:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][NH:20][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([Cl:12])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:17][C:16]=1[N+:23]([O-:25])=[O:24]
Reactant: Clc1ccc2ncnc(Cl)c2c1
Reactant: NCc1ccc(Cl)c([N+](=O)[O-])c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CC(C)O
Product: O=[N+]([O-])c1cc(CNc2ncnc3ccc(Cl)cc23)ccc1Cl
Yield: 92.6 %

Procedure:
3.00 g (0.015 mol) of 4,6-dichloroquinazoline and 3.80 g (0.0170 mol) of 4-chloro-3-nitrobenzylamine hydrochloride were dissolved in a mixture comprising 100 ml of isopropyl alcohol and 15 ml of triethylamine. The obtained solution was heated under reflux for 24 hours and distilled under a reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (chloroform/ethyl acetate) and recrystallized from chloroform/n-hexane to give 4.85 g of the title compounds as a pale-yellow crystal.
Reaction SMILES: [C:1]([O:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15](=[O:17])[CH3:16])[C:6]=1[C:7]([OH:9])=[O:8])(=[O:3])[CH3:2].[C:18]1(C)C=CC=CC=1.CO.[Si](C=[N+]=[N-])(C)(C)C.CCCCCC>CCCCCC>[C:1]([O:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15](=[O:17])[CH3:16])[C:6]=1[C:7]([O:9][CH3:18])=[O:8])(=[O:3])[CH3:2]
Reactant: Cc1ccccc1
Reactant: CC(=O)Oc1cccc(OC(C)=O)c1C(=O)O
Agent: C[Si](C)(C)C=[N+]=[N-]
Solvent: CO
Solvent: CCCCCC
Product: COC(=O)c1c(OC(C)=O)cccc1OC(C)=O

Procedure:
To a stirred 4° solution of Part B 2,6-diacetoxybenzoic acid (5.8 g, mmol) in 4:1 PhMe/MeOH (25 mL) was added 17 mL of 2M TMSCHN2/hexane over 10 min. After tlc analysis (1:1 ETOAc/hexane) revealed complete conversion, the volatiles were removed using a rotary evaporator and the residue purified by silica gel chromatography. 1:1 CH2Cl2/hexane-CH2Cl2 eluted 4.5 g of methyl 2,6-diacetoxybenzoate.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[C:15](=[O:19])[CH2:14][CH2:13][CH2:12]3)[CH:5]=[CH:4][N:3]=[CH:2]1.[C:20]1([CH:30]=O)[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][CH:21]=1>[OH-].[K+].CCO>[N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[C:15](=[O:19])[C:14](=[CH:30][C:20]2[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=[CH:22][CH:21]=2)[CH2:13][CH2:12]3)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: O=C1CCCc2cc(OCCn3ccnc3)ccc21
Reactant: O=Cc1cccc2ccccc12
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: O=C1C(=Cc2cccc3ccccc23)CCc2cc(OCCn3ccnc3)ccc21
Yield: 87.6 %

Procedure:
According to the method of Example 6, 6-(2-imidazole-1-yl-ethoxy)-3,4-dihydro-2H-naphthalen-1-one (0.475 g, 1.85 mmol) was reacted with 1-naphthaldehyde (0.448 g, 2.87 mmol) in 3.0 mL of 4% KOH in EtOH for 6 hours at room temperature to afford 0.639 g (88%) of the title compound as a bright yellow solid, mp 147-148° C.: CL-MS m/e 494 (M+), 495 (M+ +1);
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH2:12][CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[C:18]3[C:22]=2[CH2:21][C:20]([CH3:23])=[CH:19]3)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[C:24]([O-])([O-])=O.[Cs+].[Cs+].CI>CN(C=O)C>[CH3:24][N:11]([CH2:12][CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:22]=1[CH2:21][C:20]([CH3:23])=[CH:19]2)[S:8]([C:5]1[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=1)(=[O:10])=[O:9]
Reactant: O=C([O-])[O-]
Reactant: CC1=Cc2cccc(CCNS(=O)(=O)c3ccc(C)cc3)c2C1
Agent: [Cs+]
Solvent: CI
Solvent: CN(C)C=O
Product: CC1=Cc2cccc(CCN(C)S(=O)(=O)c3ccc(C)cc3)c2C1
Temperature: 50 °C
Reaction time: 24 h

Procedure:
To a solution of 15.0 g (45.8 mmol) of 4-methyl-N-[2-(2-methyl-1H-inden-7-yl)ethyl]-benzenesulfonamide in 100 mL of dry DMF at room temperature, 22.4 g (68.7 mmol) of Cs2CO3 was added, followed by the dropwise addition of 10.0 g (70.4 mmol) of MeI over a 10 minute period. This mixture was stirred for 24 hours at 50° C. and then evaporated under vacuum. To the residue, 200 mL of water and 200 mL of dichloromethane were added. The organic layer was separated, and the aqueous layer was washed with 200 mL of dichloromethane. The combined organic extract was evaporated to dryness. The product was isolated by flash chromatography on silica gel 60 (40-63 um, eluent—dichloromethane). Yield, 14.1 g (90%) of white solid. This product was further used without an additional purification. 1H NMR (CDCl3): δ 7.50-7.55 (m, 2H, 2,6-H in p-tolyl), 7.15-7.20 (m, 2H, 3,5-H in p-tolyl), 7.04 (m, 1H, 5-H in indenyl), 7.01 (m, 1H, 6-H in indenyl), 6.78 (m, 1H, 4-H in indenyl), 6.36 (m, 1H, 3-H in indenyl), 3.08-3.18 (m, 6H, 1,1′-H in indenyl and CH2CH2), 2.69 (s, 3H, NMe), 2.67 (s, 3H, 4-Me in p-tolyl), 2.05 (s, 3H, 2-Me in indenyl). Anal. Calc. for C20H23NO2S: C, 70.35; H, 6.79; N, 4.10%. Found: C, 70.95; H, 7.13; N, 3.78%.
Reaction SMILES: [CH3:1][C:2]([CH3:31])([CH3:30])[CH2:3][C:4]([NH:6][C:7]1[C:8]([CH3:29])=[C:9](B(O)O)[C:10]2[O:14][CH2:13][CH:12]([C:15]3[CH:20]=[CH:19][C:18]([CH:21]([CH3:23])[CH3:22])=[CH:17][CH:16]=3)[C:11]=2[C:24]=1[CH3:25])=[O:5].Br[C:33]1[S:34][CH:35]=[CH:36][CH:37]=1>CCCCCC.C(OCC)(=O)C>[CH:21]([C:18]1[CH:19]=[CH:20][C:15]([CH:12]2[C:11]3[C:24]([CH3:25])=[C:7]([NH:6][C:4](=[O:5])[CH2:3][C:2]([CH3:31])([CH3:30])[CH3:1])[C:8]([CH3:29])=[C:9]([C:33]4[S:34][CH:35]=[CH:36][CH:37]=4)[C:10]=3[O:14][CH2:13]2)=[CH:16][CH:17]=1)([CH3:23])[CH3:22]
Reactant: Brc1cccs1
Reactant: Cc1c(NC(=O)CC(C)(C)C)c(C)c2c(c1B(O)O)OCC2c1ccc(C(C)C)cc1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: Cc1c(NC(=O)CC(C)(C)C)c(C)c2c(c1-c1cccs1)OCC2c1ccc(C(C)C)cc1
Yield: 58 %

Procedure:
Using (5-((3,3-dimethylbutanoyl)amino)-3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzofuran-7-yl) boronic acid obtained in Example 116 and 2-bromothiophene, the title compound was synthesized in the same manner as in Example 107. Yield: 58%. Melting point: 155-156° C. (hexane-ethyl acetate).
Reaction SMILES: [CH2:1]([CH:3]1[C:8]([C:9]2[CH:31]=[CH:30][C:12]3[N:13]=[C:14]([C:16]4[CH:21]=[CH:20][C:19]([CH:22]=[CH:23][C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)=[CH:18][CH:17]=4)[O:15][C:11]=3[CH:10]=2)=[N:7][NH:6][C:5](=[O:32])[CH2:4]1)[CH3:2].[H][H]>[Pd].CO>[CH2:1]([CH:3]1[C:8]([C:9]2[CH:31]=[CH:30][C:12]3[N:13]=[C:14]([C:16]4[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)=[CH:18][CH:17]=4)[O:15][C:11]=3[CH:10]=2)=[N:7][NH:6][C:5](=[O:32])[CH2:4]1)[CH3:2]
Reactant: [H][H]
Reactant: CCC1CC(=O)NN=C1c1ccc2nc(-c3ccc(C=Cc4ccccc4)cc3)oc2c1
Agent: [Pd]
Solvent: CO
Product: CCC1CC(=O)NN=C1c1ccc2nc(-c3ccc(CCc4ccccc4)cc3)oc2c1

Procedure:
9 mg (21 μmol) 5-ethyl-6-{2-[4-styryl-phenyl]-benzoxazol-6-yl}-4,5-dihydro-2H-pyridazin-3-one are hydrogenated together with 2 mg palladium on charcoal 10% and 10 ml of methanol at RT and 3.45 bar hydrogen pressure for 80 min, then the catalyst is filtered off and the filtrate is evaporated down completely i.V. The residue is purified through silica gel (eluant: DCM/methanol) and then stirred with cyclohexane/EA.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:15][CH3:16])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:17]#[N:18].[Cl:19][C:20]1[CH:21]=[C:22]([NH2:27])[CH:23]=[CH:24][C:25]=1[F:26]>CC(O)C>[Cl:19][C:20]1[CH:21]=[C:22]([NH:27][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:15][CH3:16])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=3)[N:5]=[CH:4][C:3]=2[C:17]#[N:18])[CH:23]=[CH:24][C:25]=1[F:26]
Reactant: COc1cc2ncc(C#N)c(Cl)c2cc1[N+](=O)[O-]
Reactant: Nc1ccc(F)c(Cl)c1
Solvent: CC(C)O
Product: COc1cc2ncc(C#N)c(Nc3ccc(F)c(Cl)c3)c2cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 20 h
Yield: 99.1 %

Procedure:
An amount of 4-chloro-7-methoxy-6-nitro-quinoline-3-carbonitrile (7.1 g, 26.9 mmol), and 3-chloro-4-fluoro-phenylamine (3.9 g, 26.8 mmol), were stirred in 2-propanol (70 mL), and heated at reflux for 2 hours. The mixture was cooled to room temperature and stirred for an additional 20 hours. The reaction mixture was evaporated to dryness, stirred with ethyl acetate and saturated sodium bicarbonate solution. After separation of the layers, the organic layer was washed with saturated brine solution and dried on magnesium sulfate, to give a dark green powder (9.9 g, 99%), which was used without further purification.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:13])[CH2:9][CH2:10][CH2:11][CH3:12])[CH:5]=[CH:6][CH:7]=1.O[C:15]1[CH:27]=[CH:26][C:18]([O:19][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:17]([CH3:28])[CH:16]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]([O:13][C:15]2[CH:27]=[CH:26][C:18]([O:19][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:17]([CH3:28])[CH:16]=2)[CH2:9][CH2:10][CH2:11][CH3:12])[CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)COc1ccc(O)cc1C
Reactant: CCCCC(O)c1cccc(Br)c1
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCCCC(Oc1ccc(OCC(=O)OCC)c(C)c1)c1cccc(Br)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 64.3 %

Procedure:
To a solution of 1-(3-bromophenyl)-1-pentanol (1.00 g, 4.11 mmol) in dry THF (40 mL) at 0° C. was added ethyl (4-hydroxy-2-methylphenoxy)acetate (865 mg, 4.11 mmol), PPh3 (1.30 g, 4.94 mmol) and ADDP (1.25 g, 4.94 mmol) and the reaction stirred for 30 minutes and then allowed to warm to rt overnight. The mixture was then reduced under vacuum and the residue partitioned between EtOAc and water and the layers separated. The organic layer was washed with water (2×) then brine, dried (Na2SO4) and reduced under vacuum to give a brown oil. Purification by Biotage™ chromatography (silica, 90 g cartridge) eluting with petroleum ether 40-60° C.:EtOAc (gradient 1:0 to 9:1) afforded the title compound as colourless oil (1.15 g).