Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:32][CH2:33][CH:34]4[CH2:36][CH2:35]4)=[C:17]([NH:20][C:21](=[O:31])[CH:22]=[CH:23][CH2:24][N:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].[C:37]([O:41][CH2:42][CH3:43])(=[O:40])[CH:38]=[CH2:39]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:32][CH2:33][CH:34]4[CH2:35][CH2:36]4)=[C:17]([NH:20][C:21](=[O:31])[CH:22]=[CH:23][CH2:24][N:25]4[CH2:30][CH2:29][N:28]([CH2:39][CH2:38][C:37]([O:41][CH2:42][CH3:43])=[O:40])[CH2:27][CH2:26]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: C=CC(=O)OCC
Reactant: O=C(C=CCN1CCNCC1)Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC1CC1
Solvent: CCO
Product: CCOC(=O)CCN1CCN(CC=CC(=O)Nc2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3cc2OCC2CC2)CC1

Procedure:
A mixture of 200 mg of 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{[4-(piperazin-1-yl)-1-oxo-2-buten-1-yl]amino}-7-cyclopropylmethoxy-quinazoline and 0.11 ml of ethyl acrylate in 2 ml of ethanol is heated under reflux for one hour. The solvent is evaporated in vacuo and the crude product is purified by column chromatography on silica gel with methylene chloride/methanol (95:5 to 90:10) followed by recrystallization from diethyl ether. Yield: 164 mg (69% of theory), Melting point: 183-185° C. Mass spectrum (ESI−): m/z=609, 611 [M−H]−
Reaction SMILES: Br.[Br:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]Br.[OH2:20]>C1CCCCC1>[Br:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][OH:20]
Reactant: O
Reactant: BrCCCCCCCCCCCCCCCCBr
Agent: Br
Solvent: C1CCCCC1
Product: OCCCCCCCCCCCCCCCCBr

Procedure:
The diol 14 (1.047 g, 4.05 mmol) was dissolved in cyclohexane (30 mL) and vigorously stirred with 48% HBr (0.5 mL, 4.46 mmol, 1.1 eq.). The mixture was refluxed for 6 h, diluted with water (50 mL) and the phases were separated. The aqueous phase was extracted with a mixture of dichloromethane and methanol (v/v, 4:1 3×20 mL). The combined organic layer was dried over MgSO4. The product was purified by column chromatography with silica gel (6×6 cm, cyclohexane/ethyl acetate, 8:1) and isolated as a white solid. Yield: 4.598 g (96%). Traces of 1,16-dibromohexadecane were also found.
Reaction SMILES: [CH2:1](OS(C1C=CC(C)=CC=1)(=O)=O)[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:20]([O:22][C:23]([C:25]1[NH:26][C:27]2[C:32]([C:33]=1[OH:34])=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:35])=[O:24])[CH3:21]>CN(C)C=O>[CH2:20]([O:22][C:23]([C:25]1[NH:26][C:27]2[C:32]([C:33]=1[O:34][CH2:1][CH3:2])=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:35])=[O:24])[CH3:21]
Reactant: CCOS(=O)(=O)c1ccc(C)cc1
Reactant: CCOC(=O)c1[nH]c2c(C)cccc2c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1[nH]c2c(C)cccc2c1OCC
Temperature: 50 °C
Reaction time: 16 h
Yield: 73.8 %

Procedure:
Toluene-4-sulfonic acid ethyl ester (274 mg, 1.37 mmol) and potassium carbonate (378 mg, 2.74 mmol) were added to a solution of 3-hydroxy-7-methyl-1H-indole-2-carboxylic acid ethyl ester (300 mg, 1.37 mmol) in N,N-dimethylformamide (3 mL). The mixture was stirred at 50° C. for 16 h, then cooled to room temperature and partitioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried (MgSO4), and evaporated. Chromatography (SiO2, hexane/ethyl acetate 6:1) afforded the title compound (250 mg, 74%). White solid, ISP-MS: m/e=248.2 ([M+H+]).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH2:18][CH:19]=[CH:20][CH2:21]Br)=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:23]([CH2:26][NH2:27])[CH:24]=C.[CH3:28]N(C=O)C>>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH2:18][CH:19]=[CH:20][CH2:21][N:27]([CH2:26][CH:23]=[CH2:24])[CH3:28])=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C=CCCN
Reactant: CN(C)C=O
Reactant: CC(C)(C)OC(=O)N1CCc2cc(OCC=CCBr)ccc21
Product: C=CCN(C)CC=CCOc1ccc2c(c1)CCN2C(=O)OC(C)(C)C
Yield: 83 %

Procedure:
214 mg (0.6 mmol) 5-(4-Bromo-but-2-enyloxy)-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester in 3 ml DMF were treated with 213 mg (3 mmol) N-allylmethylamine at 50° C. for 0.5 h. The mixture was extracted with ether and water. The organic phase was washed with water and dried over Na2SO4 and evaporated to yield 180 mg (83%) 5-[4-(Allyl-methyl-amino)-but-2-enyloxy]-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester as yellow oil, MS: 359 (MH+).
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[S:15][CH2:16][C:17]1[C:22]([CH3:23])=[C:21]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:20]=[CH:19][N:18]=1)=[O:5])[CH3:2].ClC1C=CC=C(C(OO)=[O:38])C=1.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>ClCCl>[CH2:1]([O:3][C:4]([N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[S:15]([CH2:16][C:17]1[C:22]([CH3:23])=[C:21]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:20]=[CH:19][N:18]=1)=[O:38])=[O:5])[CH3:2]
Reactant: CCOC(=O)n1c(SCc2nccc(OCCCOC)c2C)nc2ccccc21
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)n1c(S(=O)Cc2nccc(OCCCOC)c2C)nc2ccccc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 33.7 %

Procedure:
0.6 g of 1-ethoxycarbonyl-2-{4-(3-methoxypropoxy)-3-methylpyridine-2-yl}methylthiobenzimidazole was dissolved in 20 ml of dichloromethane to obtain a solution. 0.4 g of m-chloroperbenzoic acid was added to the solution at -45° C. After one hour, 0.3 g of triethylamine and 20 ml of a saturated aqueous solution of sodium hydrogencarbonate were added to the resulting mixture. The obtained mixture was stirred at a room temperature for 30 minutes. The dichloromethane layer was separated, washed with a saturated aqueous solution of sodium hydrogencarbonate twice, dried over magnesium sulfate and filtered. The filtrate was concentrated to obtain a residue. This residue was purified by silica gel column chromatography to obtain 0.21 g of the title compound as a yellow oil.
Reaction SMILES: CO[C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[N:14][O:15][C:16]=2[C:17]([F:20])([F:19])[F:18])=[N:6][CH:5]=1.COC(=O)C1C=CC(OCC2C(C3C=CC=C(F)C=3)=NOC=2C)=NC=1.[CH:54]1([NH2:57])[CH2:56][CH2:55]1>>[CH:54]1([NH:57][C:3](=[O:28])[C:4]2[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]3[C:13]([C:21]4[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=4)=[N:14][O:15][C:16]=3[C:17]([F:20])([F:18])[F:19])=[N:6][CH:5]=2)[CH2:56][CH2:55]1
Reactant: COC(=O)c1ccc(OCc2c(-c3ccc(F)cc3)noc2C(F)(F)F)nc1
Reactant: NC1CC1
Agent: COC(=O)c1ccc(OCc2c(-c3cccc(F)c3)noc2C)nc1
Product: O=C(NC1CC1)c1ccc(OCc2c(-c3ccc(F)cc3)noc2C(F)(F)F)nc1
Yield: 54 %

Procedure:
As described for example 89, 6-[3-(4-fluoro-phenyl)-5-trifluoromethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (100 mg, 0.25 mmol), instead of 6-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester, was converted, using cylopropylamine instead of 2,2,2-trifluoroethylamine, to the title compound (90 mg, 54%) which was obtained as a white solid. MS: m/e=422.1 [M+H]+.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH:6]=[O:7].S(S([O-])=O)([O-])(=O)=[O:14].[Na+].[Na+].CC[O:24][CH2:25]C>O>[OH:7][CH:6]([C:5]1[CH:8]=[CH:9][CH:10]=[C:3]([C:2]([F:11])([F:12])[F:1])[CH:4]=1)[C:25]([OH:24])=[O:14]
Reactant: O=Cc1cccc(C(F)(F)F)c1
Reactant: CCOCC
Reactant: O=S([O-])S(=O)(=O)[O-]
Agent: [Na+]
Solvent: O
Product: O=C(O)C(O)c1cccc(C(F)(F)F)c1

Procedure:
A solution of 3-trifluoromethylbenzaldehyde (69.2 g) in ether (250 ml) was shaken with a solution of sodium metabisulphite (84.5 g) in water (85 ml). The mixture was cooled in the refrigerator overnight, the solid was collected, washed with a little propan-2-ol and dried (120 g). The bisulphite addition complex was suspended in a mixture of water (70 ml) and ether (250 ml) with rapid stirring during the addition of a solution of potassium cyanide (28.5 g) in water (85 ml). The mixture was stirred until all the solid was dissolved and the two layers were clear (ca 2 h). The ethereal layer was separated, evaporated and hydrochloric acid (400 ml) was added. The mixture was stirred on the steam bath for 5 h, cooled. The residue was taken up in the minimum amount of 4N sodium hydroxide solution, washed with ether, acidified with hydrochloric acid and extracted into chloroform. The chloroform extracts were dried and evaporated to an oil (61.8 g) which crystallised on standing.
Reaction SMILES: [CH3:1][NH:2][C:3]1[C:16]2[C:15](=[O:17])[N:14]([C:18]3[CH:19]=[C:20]([C:24]4[O:28][C:27](=[O:29])[N:26]([CH3:30])[N:25]=4)[CH:21]=[CH:22][CH:23]=3)[CH2:13][C@H:12]3[N:8]([CH2:9][CH2:10][CH2:11]3)[C:7]=2[N:6]=[C:5](SC)[N:4]=1.ClC1C=CC=C(C(OO)=O)C=1.C(=O)(O)[O-].[Na+].[CH3:49][NH2:50].C1COCC1>ClCCl.C(Cl)(Cl)Cl>[CH3:1][NH:2][C:3]1[C:16]2[C:15](=[O:17])[N:14]([C:18]3[CH:19]=[C:20]([C:24]4[O:28][C:27](=[O:29])[N:26]([CH3:30])[N:25]=4)[CH:21]=[CH:22][CH:23]=3)[CH2:13][C@H:12]3[N:8]([CH2:9][CH2:10][CH2:11]3)[C:7]=2[N:6]=[C:5]([NH:50][CH3:49])[N:4]=1
Reactant: CN
Reactant: CNc1nc(SC)nc2c1C(=O)N(c1cccc(-c3nn(C)c(=O)o3)c1)C[C@@H]1CCCN21
Agent: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Solvent: C1CCOC1
Product: CNc1nc(NC)c2c(n1)N1CCC[C@H]1CN(c1cccc(-c3nn(C)c(=O)o3)c1)C2=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 47.2 %

Procedure:
(S)-5-[3-(7-Methylamino-9-methylthio-6-oxo-2,3,3a,4-tetrahydro-1H,6H-5,8,10,10b-tetraazabenzo[e]azulen-5-yl)phenyl]-3-methyl-1,3,4-oxadiazol-2(3H)-one (17.6 mg, 0.0388 mmol) obtained in Step 9 was dissolved in dichloromethane (2.5 mL), and the mixture was stirred at room temperature for 30 minutes after adding 3-chloroperbenzoic acid (20.5 mg, 0.0582 mmol). A saturated aqueous sodium bicarbonate solution and chloroform were added to the mixture to separate the organic layer. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was dissolved in THF (2.0 mL), and the mixture was stirred at 90° C. for 30 minutes under microwave (CEM; Discover; 250 watts) irradiation after adding a 2.0 mol/L methylamine/THF solution (1.0 mL, 2.00 mmol). The mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound (Compound 156) (8.0 mg, 47%).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)=[CH:13][C:14]([NH:16][CH3:17])=[O:15])=[CH:9][CH:10]=2)[NH:5][N:4]=1.N1C2C(=CC=CC=2C(C2C=CC=CC=2)CC(NC)=O)C=C1>>[CH3:1][O:2][C:3]1[C:11]2[C:6](=[CH:7][C:8]([CH:12]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[CH2:13][C:14]([NH:16][CH3:17])=[O:15])=[CH:9][CH:10]=2)[NH:5][N:4]=1
Reactant: CNC(=O)C=C(c1ccc2c(OC)n[nH]c2c1)c1ccccn1
Agent: CNC(=O)CC(c1ccccc1)c1cccc2cc[nH]c12
Product: CNC(=O)CC(c1ccc2c(OC)n[nH]c2c1)c1ccccn1

Procedure:
3-(3-Methoxy-1H-indazol-6-yl)-N-methyl-3-pyridin-2yl-propionamide CCXLVI was prepared from 3-(3-methoxy-1H-indazol-6-yl)-N-methyl-3-pyridin-2yl-acrylamide using the procedure described for preparation of 3-(1H-Indol-7-yl)-N-methyl-3-phenyl-propionamide XIX (Example 4). The crude product (90% yield) was purified via chiral preparative HPLC by multiple injections onto 20×250 mm Chiralpak AD preparative column using a mixture of 60/40 hexane/isopropanol at 7 ml/min affording the enantiomer CCXLVI-A (αD=−0.269°) and the enantiomer CCXLVI-B (αD=+0.209°).
Reaction SMILES: [C:1]1([CH2:6][SH:7])[S:5][CH:4]=[CH:3][CH:2]=1.C(N1C(=O)C2=CC=CC=[C:12]2[C:11]1=[S:20])C>>[CH2:11]([S:20][S:7][CH2:6][C:1]1[S:5][CH:4]=[CH:3][CH:2]=1)[CH3:12]
Reactant: CCN1C(=O)c2ccccc2C1=S
Reactant: SCc1cccs1
Product: CCSSCc1cccs1

Procedure:
Starting from thenylmercaptan and N-ethylthiophthalimide there is obtained ethyl-thenyl-disulphide. nD20 = 1.6044. IR (liq.): bands inter alia at 3000, 1450, 1250, 1035, 850, 700 cm-1.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][C:5]1[N:6]([CH2:18][CH2:19][O:20][CH2:21][CH2:22][N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:17]=1.C1C=C(Cl)C=C(C(OO)=[O:40])C=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:1][O:2][CH2:3][CH2:4][C:5]1[N:6]([CH2:18][CH2:19][O:20][CH2:21][CH2:22][N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N+:10]([O-:40])=[CH:9][C:8]=2[N:17]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COCCc1nc2cnc3ccccc3c2n1CCOCCN(C)C(=O)OC(C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: COCCc1nc2c[n+]([O-])c3ccccc3c2n1CCOCCN(C)C(=O)OC(C)(C)C
Reaction time: 6 h
Yield: 94.4 %

Procedure:
A solution of tert-butyl 2-{2-[2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]ethoxy}ethyl(methyl)carbamate (7.20 g, 16.8 mmol) in 200 mL of CH2Cl2 was treated with MCPBA (77%, 4.32 g, 19.3 mmol). After stirring 6 h, the reaction mixture was treated with saturated NaHCO3 solution and the layers were separated. The organic portion was washed with H2O and brine then dried over Na2SO4and concentrated to give 7.05 g of tert-butyl 2-{2-[2-(2-methoxyethyl)-5-oxido-1H-imidazo[4,5-c]quinolin-1-yl]ethoxy}ethyl(methyl)carbamate as a light brown solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[CH2:18][C:17](=[O:19])[N:16]([CH3:20])[C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8].[CH3:21][C:22]1[CH:26]=[C:25]([C:27]([N:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)=[O:28])[NH:24][C:23]=1[CH:36]=O>N1CCCCC1.C(O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[C:18](=[CH:36][C:23]4[NH:24][C:25]([C:27]([N:29]5[CH2:30][CH2:31][N:32]([CH3:35])[CH2:33][CH2:34]5)=[O:28])=[CH:26][C:22]=4[CH3:21])[C:17](=[O:19])[N:16]([CH3:20])[C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: Cc1cc(C(=O)N2CCN(C)CC2)[nH]c1C=O
Reactant: CN1C(=O)Cc2c(Nc3ccc(F)c(Cl)c3)ncnc21
Solvent: O
Solvent: C1CCNCC1
Solvent: CCO
Product: Cc1cc(C(=O)N2CCN(C)CC2)[nH]c1C=C1C(=O)N(C)c2ncnc(Nc3ccc(F)c(Cl)c3)c21
Temperature: 90 °C
Reaction time: 2 h
Yield: 72 %

Procedure:
A mixture of 4-(3-chloro-4-fluoro-phenylamino)-7-methyl-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-one (80 mg, 0.27 mmol), 3-methyl-5-(4-methyl-piperazine-1-carbonyl)-1H-pyrrole-2-carbaldehyde (1.2 equiv.) and piperidine (1 drop) in ethanol (2 mL) was stirred at 90° C. for 2 hours. The reaction was diluted with water and the precipitate was collected by vacuum filtration, washed with water, ethyl acetate and hexane and dried to give 120.5 mg (72%) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ 13.42 (br s, 1H, NH), 9.32 (br s, 1H), 8.40 (s, 1H), 7.71 (m, 1H), 7.35-7.41 (m, 3H), 6.60 (s, 1H), 3.69 (m, 4H, 2×CH2), 3.30 (s, 3H, CH3), 2.35 (m, 4H, 2×CH2), 2.21 (s, 3H, CH3),2.20 (s, 3H, CH3). MS 510 [M+1].
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:15]=[CH:14][C:12]([NH2:13])=[C:11]([NH2:16])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[NH2:8].[CH3:17][N:18]([CH3:29])[C:19]1[CH:24]=[CH:23][C:22]([CH:25]=[CH:26][CH:27]=O)=[CH:21][CH:20]=1>>[NH:8]1[C:7]2[CH:6]=[CH:5][C:4]([C:9]3[CH:15]=[CH:14][C:12]4[N:13]=[C:27](/[CH:26]=[CH:25]/[C:22]5[CH:23]=[CH:24][C:19]([N:18]([CH3:29])[CH3:17])=[CH:20][CH:21]=5)[NH:16][C:11]=4[CH:10]=3)=[CH:3][C:2]=2[N:1]=[C:27]1/[CH:26]=[CH:25]/[C:22]1[CH:21]=[CH:20][C:19]([N:18]([CH3:17])[CH3:29])=[CH:24][CH:23]=1
Reactant: CN(C)c1ccc(C=CC=O)cc1
Reactant: Nc1ccc(-c2ccc(N)c(N)c2)cc1N
Product: CN(C)c1ccc(/C=C/c2nc3cc(-c4ccc5nc(/C=C/c6ccc(N(C)C)cc6)[nH]c5c4)ccc3[nH]2)cc1

Procedure:
Compound 264 was prepared according to the procedure similar to that described in Scheme III from 3,3′-diaminobenzidine and 3-(4-dimethylaminophenyl)acrylaldehyde. [M+H]+ calcd for C34H32N6: 525.27; found: 525.59.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][S:5]([O:8][CH2:9][C:10]([CH3:35])([CH3:34])[CH:11]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:12]([O:14][CH2:15][CH2:16][O:17][C:18](=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:13])(=[O:7])=[O:6].[N-:36]=[N+:37]=[N-:38].[Na+]>CS(C)=O>[N:36]([CH2:2][CH2:3][CH2:4][S:5]([O:8][CH2:9][C:10]([CH3:35])([CH3:34])[CH:11]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:12]([O:14][CH2:15][CH2:16][O:17][C:18](=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:13])(=[O:7])=[O:6])=[N+:37]=[N-:38]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(COS(=O)(=O)CCCCl)C(OCc1ccccc1)C(=O)OCCOC(=O)c1ccccc1
Agent: [Na+]
Solvent: CS(C)=O
Product: CC(C)(COS(=O)(=O)CCCN=[N+]=[N-])C(OCc1ccccc1)C(=O)OCCOC(=O)c1ccccc1

Procedure:
Following the general procedure for the preparation of azides of Description 16, benzoyloxyethyl (2R/S)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoate (39a) (3.2 g max.) dissolved in 30 mL of anhydrous dimethyl sulfoxide (DMSO) was reacted with 0.51 g (8.0 mmol) of sodium azide (NaN3). After work-up, the crude title compound (39b) was obtained and used in the next step without further purification. MS (ESI) m/z 555.83 (M+Na)+.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11]([C:13]([CH2:26][CH3:27])(C3C=CC(O)=C(C(C)C)C=3)[CH2:14][CH3:15])=[CH:10][C:9]=2[CH:28]=1)=[O:4].Br[CH2:30][C:31](=[O:36])[C:32]([CH3:35])([CH3:34])[CH3:33].[C:37]([O-:40])([O-])=O.[K+].[K+]>>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11]([CH:13]([CH:26]([C:6]3[CH:5]=[CH:3][C:37]([O:40][CH2:30][C:31](=[O:36])[C:32]([CH3:35])([CH3:34])[CH3:33])=[C:8]([CH:9]([CH3:28])[CH3:10])[CH:7]=3)[CH3:27])[CH2:14][CH3:15])=[CH:10][C:9]=2[CH:28]=1)=[O:4]
Reactant: O=C([O-])[O-]
Reactant: CCC(CC)(c1ccc(O)c(C(C)C)c1)c1cc2cc(C(=O)OC)ccc2o1
Reactant: CC(C)(C)C(=O)CBr
Agent: [K+]
Product: CCC(c1cc2cc(C(=O)OC)ccc2o1)C(C)c1ccc(OCC(=O)C(C)(C)C)c(C(C)C)c1
Yield: 197.5 %

Procedure:
2-[1-Ethyl-1-(4-hydroxy-3-isopropyl-phenyl)-propyl]-benzofuran-5-carboxylic acid methyl ester (1.25 g, 3.28 mmol) and 1-bromopinacolone (0.882 g, 4.93 mmol) and K2CO3 (0.91 g, 6.57 mmol) are reacted analogous to Example 1E to give the title compound (1.55 g, 99%).
Reaction SMILES: [CH3:1][CH:2]([C:11](=[O:21])[CH2:12][C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=O)[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=O.[F:22][C:23]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:24]=1[NH2:25].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C(C)=CC=CC=1>[F:22][C:23]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:24]=1[N:25]1[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:12][C:11](=[O:21])[C:2]([CH3:1])=[C:3]1[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: Nc1c(F)cccc1F
Reactant: CC(C(=O)CC(=O)c1ccccc1)C(=O)c1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1C
Product: Cc1c(-c2ccccc2)n(-c2c(F)cccc2F)c(-c2ccccc2)cc1=O
Yield: 18.7 %

Procedure:
To 150 ml of xylene were added 2.8 g (0.010 mole) of 2-methyl-1,5-diphenyl-1,3,5-pentanetrione, 12.9 g (0.010 mole) of 2,6-diflouroaniline, 3.0 g (0.016 mole) of para-toluenesulfonic acid and 30.0 g of Molecular Sieves 5A, followed by refluxing the resulting mixture for 3 hours. After cooling the reaction mixture, solid matter was filtered off and the filtrate was washed successively with 50 ml of 10% hydrochloric acid, 50 ml of 10% aqueous solution of sodium hydroxide and water. The filtrate was then dried over anhydrous sodium sulfate. Subsequent to removal of the sodium sulfate by filtration, the solvent was distilled off and the residue was crystallized from a 2:1 mixed solvent of acetone and hexane to give 0.7 g of 1-(2,6-diflourophenyl)-3-methyl-2,6-diphenyl-4(1H)-pyridinone having a melting point of 219°-221° C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[CH:11]=[C:10]([C:24]([F:27])([F:26])[F:25])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[S:28]([C:32]1[CH:33]=[N:34][CH:35]=[C:36](B(O)O)[CH:37]=1)(=[O:31])(=[O:30])[NH2:29]>>[F:25][C:24]([F:27])([F:26])[C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2]([C:36]3[CH:37]=[C:32]([S:28]([NH2:29])(=[O:31])=[O:30])[CH:33]=[N:34][CH:35]=3)[CH:7]=[CH:6][CH:5]=2)[CH:13]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[CH:11]=1
Reactant: NS(=O)(=O)c1cncc(B(O)O)c1
Reactant: FC(F)(F)c1ccc(-c2cc(-c3cccc(Br)c3)nc(C(F)(F)F)c2)cc1
Product: NS(=O)(=O)c1cncc(-c2cccc(-c3cc(-c4ccc(C(F)(F)F)cc4)cc(C(F)(F)F)n3)c2)c1

Procedure:
The title compound was prepared 2-(3-bromo-phenyl)-6-trifluoromethyl-4-(4-trifluoromethyl-phenyl)-pyridine (example E.81) (0.20 g, 0.448 mmol) and 3-sulfamoyl-pyridine-5-boronic acid (example F.3) (0.100 g, 0.488 mmol) according to the general procedure VI. Obtained as a white solid (0.035 g, 15%). MS (ISP) 522.2 [(M+H)+]; mp 240° C.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].[Na].Cl[C:9]1[C:14]([N+:15]([O-:17])=[O:16])=[C:13]([N:18]([CH2:21][CH3:22])[CH2:19][CH3:20])[C:12]([N+:23]([O-:25])=[O:24])=[CH:11][C:10]=1[C:26]([F:29])([F:28])[F:27]>CN(C=O)C>[CH2:21]([N:18]([CH2:19][CH3:20])[C:13]1[C:12]([N+:23]([O-:25])=[O:24])=[C:11]([N:1]2[CH2:5][CH2:4][CH2:3][C:2]2=[O:6])[C:10]([C:26]([F:29])([F:28])[F:27])=[CH:9][C:14]=1[N+:15]([O-:17])=[O:16])[CH3:22]
Reactant: O=C1CCCN1
Reactant: CCN(CC)c1c([N+](=O)[O-])cc(C(F)(F)F)c(Cl)c1[N+](=O)[O-]
Agent: [Na]
Solvent: CN(C)C=O
Product: CCN(CC)c1c([N+](=O)[O-])cc(C(F)(F)F)c(N2CCCC2=O)c1[N+](=O)[O-]
Yield: 5 %

Procedure:
The residue, which contained sodium pyrrolidone, was cooled to 40°, and a solution of 34.2 g of 2-chloro-4-diethylamino-3,5-dinitrobenzotrifluoride (0.1 m) in 50 cc of DMF was added in 0.5 hr. at 40°-46°. The reaction mixture was heated at 112°-115° for 21.5 hr., cooled, and partitioned between 100 cc of tolune and 200 cc of water. The toluene phase was given 5 × 100 cc water washes, and the toluene was removed by rotary evaporation, leaving 21.0 g of residue. The residue then was vacuum distilled using a micro short-path distillation apparatus. The product (5.5 g) distilled at 170°-180° (0.1-0.2 mm). The yellow distillate was recrystallized twice from 1 part of methanol to yield 2.2 g, 5.0% yield; mp 94°-95°; IR(KBr) 3080 (CH aromatic), 2990 (CH aliphatic), 1710 (C=O), 1530 and 1340 cm-1 (NO2); NMR (CDCl3) δ 8.1 (1, s, CH aromatic), 3.6 (2, t, CH2NCO), 3.1 (4, q NCH2 -CH3), 2.6-2.1 (4, m, CH2CH2C=O), 1.1 (6, t, CH3).
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Br:12])[CH:8]=2)[CH:3]=1.S(OC)(O[CH3:17])(=O)=O.C(OCC)(=O)C.[OH-].[Na+]>O1CCOCC1>[Br:12][C:7]1[CH:6]=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([NH:1][CH3:17])[CH:3]=2)[CH:8]=1
Reactant: Nc1ccc2cc(Br)ccc2c1
Reactant: COS(=O)(=O)OC
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CNc1ccc2cc(Br)ccc2c1
Temperature: 25 °C
Reaction time: 46 h

Procedure:
A solution of 2-amino-6-bromonaphthalene (2.0 g) in 1,4-dioxane (30 ml) was added dropwise with dimethyl sulfate (1300 μl) and stirred at room temperature for 46 hours. The reaction mixture was added with ethyl acetate (90 ml) and then added with 1 N aqueous sodium hydroxide (5 ml). This mixture was extracted with ethyl acetate (150 ml×3). The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane:ethyl acetate=15:1) to obtain the title compound (Intermediate 27, 152 mg).