Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[CH:11][C:5]([CH:6]=[CH:7][C:8]([OH:10])=[O:9])=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14].[CH3:16][Si](C=[N+]=[N-])(C)C.CCCCCC.[N+](=C)=[N-]>CO.C(Cl)Cl>[Cl:1][C:2]1[CH:12]=[CH:11][C:5](/[CH:6]=[CH:7]/[C:8]([O:10][CH3:16])=[O:9])=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14]
Reactant: O=C(O)C=Cc1ccc(Cl)c([N+](=O)[O-])c1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Agent: C=[N+]=[N-]
Solvent: CO
Solvent: CCCCCC
Solvent: ClCCl
Product: COC(=O)/C=C/c1ccc(Cl)c([N+](=O)[O-])c1
Yield: 97 %

Procedure:
To a solution of 4-chloro-3-nitrocinnamic acid in a mixture of methanol/DCM (1:1, v/v, 0.09 M), a 2 M solution of trimethylsilyl diazomethane in hexane (4 eq) was slowly added until the yellow color persisted, indicating an excess of diazomethane. The resulting mixture was evaporated. PE was added to the residue and the resultant precipitate was filtered and dried under vacuo to afford the title compound (97%) as a solid. 1H NMR (400 MHz; DMSO-d6, 300 K) δ 3.75 (s, 3H), 6.86 (d, J 16, 1H), 7.73 (d, J 16, 1H), 7.84 (d, J 8.4, 1H), 8.08 (d, J 8.4, 1H), 8.48 (s, 1H); MS (ES+) m/z 242 (M+H)+.
Reaction SMILES: [C:1]1([OH:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[OH-:12].[K+].Cl[C:15]1[C:28]2[C:27](=[O:29])[C:26]3[C:21](=[C:22](Cl)[CH:23]=[CH:24][CH:25]=3)[C:20](=[O:31])[C:19]=2[CH:18]=[CH:17][CH:16]=1>C1(C)C=CC=CC=1.CN(C=O)C.[Cu]>[C:1]1([O:11][C:15]2[C:28]3[C:27](=[O:29])[C:26]4[C:21](=[C:22]([O:12][C:9]5[C:10]6[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=6)[CH:6]=[CH:7][CH:8]=5)[CH:23]=[CH:24][CH:25]=4)[C:20](=[O:31])[C:19]=3[CH:18]=[CH:17][CH:16]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: O=C1c2cccc(Cl)c2C(=O)c2cccc(Cl)c21
Reactant: [OH-]
Reactant: Oc1cccc2ccccc12
Agent: [Cu]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: O=C1c2cccc(Oc3cccc4ccccc34)c2C(=O)c2cccc(Oc3cccc4ccccc34)c21
Reaction time: 4 h

Procedure:
Under a nitrogen atmosphere, 50 parts of 1-naphthol and 17 parts of potassium hydroxide were dissolved in 500 parts of toluene, and the mixture was refluxed under heat. After stirred for 4 hours, the solution was allowed to cool, and the precipitated solid was filtered. Then, under a nitrogen stream, the precipitate obtained, 24 parts of 1,5-dichloroanthraquinone and 7.2 parts of copper powder were dissolved in 500 parts of DMF, and the mixture was refluxed under heat for 5 hours. The reaction solution poured into an aqueous potassium hydroxide solution, and the precipitated solid was filtered, washed, and dried. Then, after removal of inorganic materials with toluene, the solid obtained was recrystallized from 2-ethoxyethanol, filtered, washed, and dried, to give 21 parts of 1,5-bis(1-naphthyloxy)anthraquinone as an intermediate.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[N:5]([CH3:10])[C:4]([CH3:12])([CH3:11])[CH2:3]1.[Cl:13][C:14]1[N:19]=[CH:18][C:17]([F:20])=[C:16](Cl)[N:15]=1>CO>[ClH:13].[Cl:13][C:14]1[N:19]=[C:18]([NH:1][CH:2]2[CH2:3][C:4]([CH3:12])([CH3:11])[N:5]([CH3:10])[C:6]([CH3:8])([CH3:9])[CH2:7]2)[C:17]([F:20])=[CH:16][N:15]=1
Reactant: CN1C(C)(C)CC(N)CC1(C)C
Reactant: Fc1cnc(Cl)nc1Cl
Solvent: CO
Product: CN1C(C)(C)CC(Nc2nc(Cl)ncc2F)CC1(C)C
Product: Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 108.9 %

Procedure:
4-Amino-1,2,2,6,6-pentamethylpiperidine (1 g) and 2,6-dichloro-5-fluoropyrimidine (1.5 g) were dissolved in methanol (10 mL). The reaction solution was stirred at room temperature overnight. The reaction solution was evaporated and crystallized from ethyl acetate and hexanes to give 2-chloro-5-fluoro-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-4-pyrimidineamine HCl salt (1.65 g, 93%).
Reaction SMILES: [BH4-].[Li+].[C:3]([C:5]1[CH:14]=[CH:13][C:8]([C:9](OC)=[O:10])=[CH:7][C:6]=1[CH3:15])#[N:4]>C1COCC1.O>[OH:10][CH2:9][C:8]1[CH:13]=[CH:14][C:5]([C:3]#[N:4])=[C:6]([CH3:15])[CH:7]=1
Reactant: COC(=O)c1ccc(C#N)c(C)c1
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1cc(CO)ccc1C#N
Temperature: 25 °C
Reaction time: 4 h
Yield: 94.6 %

Procedure:
Lithium borohydride (33 mg, 1.54 mmol) was added into a solution of methyl 4-cyano-3-methylbenzoate (245 mg, 1.40 mmol) in THF (3 mL) and the resulting mixture was stirred at RT for 4 hours. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (4×20 mL). The combined organic fractions were dried (MgSO4) and concentrated under vacuum. The residue was purified by flash chromatography (silica, petrol ether/EtOAc) to give the title compound as a colorless gum (195 mg, 95%). 1H NMR (CDCl3, 400 MHz) δ 7.58 (1H, d, J=7.9 Hz), 7.33 (1H, s), 7.26 (1H, m), 4.74 (2H, s), 2.55 (3H, s), 1.95 (1H, s). LC/MS (Method A): 144 (M+H)+. HPLC (Method F) Rt 3.95 min (Purity: 95.3%).
Reaction SMILES: [F:1]C1C=CC=CC=1C(Cl)=O.[CH3:11][O:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:22]=1[O:23][CH3:24])[N:19]=[CH:18][CH:17]=[C:16]2[O:25][C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[C:28](F)[CH:27]=1.[F:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[C:41]([N:43]=[C:44]=[S:45])=[O:42]>C1(C)C=CC=CC=1.C(O)C>[F:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[C:41]([N:43]=[C:44]=[S:45])=[O:42].[CH3:11][O:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:22]=1[O:23][CH3:24])[N:19]=[CH:18][CH:17]=[C:16]2[O:25][C:26]1[CH:32]=[CH:31][C:29]([NH:30][C:44]([NH:43][C:41](=[O:42])[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=2[F:34])=[S:45])=[CH:28][C:27]=1[F:1]
Reactant: COc1cc2nccc(Oc3ccc(N)c(F)c3)c2cc1OC
Reactant: O=C(Cl)c1ccccc1F
Agent: O=C(N=C=S)c1ccccc1F
Solvent: CCO
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)c4ccccc4F)cc3F)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 86 %

Procedure:
2-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (68 mg, yield 86%).
Reaction SMILES: [Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[O:13]=[C:14]1[C:19]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[C:28]([C:33]#[N:34])=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:23][CH:22]=2)=[C:18]([CH2:35][CH2:36][CH3:37])[N:17]2[N:38]=[CH:39][N:40]=[C:16]2[N:15]1[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>C(OCC)(=O)C>[O:7]=[C:4]1[O:5][N:3]=[C:33]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[C:24]2[CH:23]=[CH:22][C:21]([CH2:20][C:19]3[C:14](=[O:13])[N:15]([C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)[C:16]4[N:17]([N:38]=[CH:39][N:40]=4)[C:18]=3[CH2:35][CH2:36][CH3:37])=[CH:26][CH:25]=2)[NH:34]1
Reactant: O=C([O-])O
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(-c2ccccc2)c2ncnn12
Reactant: [NH3+]O
Agent: [Cl-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: CCCc1c(Cc2ccc(-c3ccccc3-c3noc(=O)[nH]3)cc2)c(=O)n(-c2ccccc2)c2ncnn12
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 35 %

Procedure:
A mixture of hydroxylammonium chloride (1.4 g), sodium hydrogen carbonate (2.2 g) and dimethyl sulfoxide (15 mL) was stirred at 40° C. for 30 min, 4′-[(5-oxo-4-phenyl-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (0.58 g) was added, and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (15 mL). N,N′-Carbonyldiimidazole (0.25 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.21 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.23 g, 44%).
Reaction SMILES: Cl.O1CCOCC1.[CH2:8]([NH:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:33]C)[N:19]2[CH2:22][CH2:23][CH2:24][CH:25]2[CH2:30][CH2:29][O:28][C:27]([CH3:32])([CH3:31])[CH2:26]2)=[C:15]([NH2:35])[N:14]=1)[CH2:9][CH2:10][CH3:11]>CO.C(Cl)Cl.CO>[NH2:35][C:15]1[N:14]=[C:13]([NH:12][CH2:8][CH2:9][CH2:10][CH3:11])[N:21]=[C:20]2[C:16]=1[NH:17][C:18](=[O:33])[N:19]2[CH2:22][CH2:23][CH2:24][CH:25]1[CH2:30][CH2:29][O:28][C:27]([CH3:32])([CH3:31])[CH2:26]1
Reactant: CCCCNc1nc(N)c2nc(OC)n(CCCC3CCOC(C)(C)C3)c2n1
Agent: Cl
Solvent: ClCCl
Solvent: CO
Solvent: C1COCCO1
Product: CCCCNc1nc(N)c2[nH]c(=O)n(CCCC3CCOC(C)(C)C3)c2n1
Reaction time: 8 h
Yield: 36.5 %

Procedure:
4M HCl in 1,4-dioxane (3 ml, 12.00 mmol) was added in one portion to a stirred solution of N2-butyl-9-[3-(2,2-dimethyltetrahydro-2H-pyran-4-yl)propyl]-8-(methyloxy)-9H-purine-2,6-diamine (40 mg, 0.102 mmol) in methanol (3 ml) at room temperature and the mixture stirred under nitrogen overnight. The mixture was then concentrated and the residue dissolved in MeOH:DCM (1:15 ml) and loaded onto a 2 g aminopropyl SPE cartridge. The cartridge was washed with MeOH:DCM (1:1, 3 column volumes) and the desired fractions were concentrated in vacuo to give material of ca. 80% purity. This material was dissolved in DCM:MeOH (1:1), applied to a 2 g SCX column and eluted firstly with MeOH:DCM (3 column volumes) and the product then released by 2M ammonia in methanol: DCM (1:1, 3 column volumes). The solvent was removed to yield the title compound as a yellow solid (14 mg).
Reaction SMILES: C(OC(=O)C)(=O)C.[N+:8]1([O-:24])[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:9]=1[C:19]([O:21][CH2:22][CH3:23])=[O:20].[N+:25]([O-])([OH:27])=[O:26]>C(O)(=O)C>[N+:25]([C:12]1[CH:11]=[C:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:9]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[N+:8]([O-:24])[CH:13]=1)([O-:27])=[O:26]
Reactant: CCOC(=O)c1ccc[n+]([O-])c1C(=O)OCC
Reactant: O=[N+]([O-])O
Solvent: CC(=O)OC(C)=O
Solvent: CC(=O)O
Product: CCOC(=O)c1cc([N+](=O)[O-])c[n+]([O-])c1C(=O)OCC
Temperature: 0 °C
Yield: 78 %

Procedure:
255 ml of acetic anhydride were added to a mixture of 203.2 g (0.85 mol) of diethyl pyridine-2,3-dicarboxylate-N-oxide in 1.2 1 of glacial acetic acid. 68.3 g (1.06 mol) of 98% strength nitric acid were then added in the course of 40 minutes at from 20 to 28° C. with gentle cooling and stirring and the mixture was stirred at 30° C. for 12 hours. The reaction solution was poured into 3.5 l of ice-water and extracted with methylene chloride. The organic phase was extracted in succession with water, saturated sodium hydrogencarbonate solution and sodium chloride solution, dried over magnesium sulfate and filtered off with suction through silica gel. After concentration, 177.6 g (78% of theory) of diethyl 5-nitropyridine-2,3-dicarboxylate-N-oxide were obtained of nD25 =1.5290. A sample crystallized after relatively long standing; m.p. 84-86° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[C:4]([Cl:9])[N:3]=1.[NH2:10][CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:13]1>O1CCOCC1.C(N(C(C)C)CC)(C)C>[Cl:9][C:4]1[N:3]=[C:2]([NH:10][CH2:11][CH:12]2[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][CH2:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)=[O:19])[CH2:13]2)[CH:7]=[C:6]([I:8])[CH:5]=1
Reactant: NCC1CCCN(C(=O)OCc2ccccc2)C1
Reactant: Clc1cc(I)cc(Cl)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Product: O=C(OCc1ccccc1)N1CCCC(CNc2cc(I)cc(Cl)n2)C1
Temperature: 150 °C

Procedure:
To a mixture of 2,6-dichloro-4-iodopyridine (1.5 g, 5.5 mmol) and benzyl 3-(aminomethyl)piperidine-1-carboxylate (2.7 g, 11 mmol) in dioxane (10 mL) in a microwave tube was added ten drops of diisopropylethyl amine and sealed. The tube was heated at 150° C. for 72 hours. The reaction mixture was cooled to room temperature and concentrated, the residue was purified by flash chromatography eluting with EtOAc/hexane=1:3 to 1:2 to give the title compound. Yield: 1.0 g (38%). MS (DCI/NH3) m/z 486 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([Br:8])[CH:5]=[CH:4][N:3]=1.[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1B(O)O>>[Br:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[Cl:9])[CH:7]=1
Reactant: OB(O)c1ccccc1Cl
Reactant: Brc1ccnc(Br)c1
Product: Clc1ccccc1-c1cc(Br)ccn1

Procedure:
Prepared according to the procedure described in Example 1, Step 10, using 2,4-dibromo-pyridine and 2-chlorophenylboronic acid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[NH:14][CH2:15][C:16]2[O:17][CH:18]=[C:19]([CH3:21])[N:20]=2)=[C:4]([O:22][CH3:23])[CH:3]=1.[CH3:24][S:25]([C:28]1[CH:29]=[C:30]([CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1)[C:31](O)=[O:32])(=[O:27])=[O:26]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH2:15][C:16]2[O:17][CH:18]=[C:19]([CH3:21])[N:20]=2)[C:31](=[O:32])[C:30]2[CH:34]=[C:35]([C:37]([F:40])([F:38])[F:39])[CH:36]=[C:28]([S:25]([CH3:24])(=[O:27])=[O:26])[CH:29]=2)=[C:4]([O:22][CH3:23])[CH:3]=1
Reactant: CS(=O)(=O)c1cc(C(=O)O)cc(C(F)(F)F)c1
Reactant: COc1cc(F)ccc1-c1ccncc1NCc1nc(C)co1
Product: COc1cc(F)ccc1-c1ccncc1N(Cc1nc(C)co1)C(=O)c1cc(C(F)(F)F)cc(S(C)(=O)=O)c1

Procedure:
The title compound was prepared in analogy to example 90, from [4-(4-fluoro-2-methoxy-phenyl)-pyridin-3-yl]-(4-methyl-oxazol-2-ylmethyl)-amine and 3-(methylsulfonyl)-5-(trifluoromethyl)benzoic acid (example 114, intermediate a) after a reaction time of 90 hours at room temperature. The product was purified by preparative HPLC (Gemini NX) with a gradient of MeOH:water (containing 0.05% formic acid) (80:20 to 98:2). Colorless solid (34%). MS (ESI): m/z=564.121 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[N:9]=[C:10]=[S:11].[CH2:12]([NH:16][CH2:17][C:18](O)=[O:19])[CH2:13][CH2:14][CH3:15].C(N(CC)CC)C>C(Cl)Cl>[CH2:12]([N:16]1[CH2:17][C:18](=[O:19])[N:9]([C:3]2[C:4]([CH3:8])=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[C:10]1=[S:11])[CH2:13][CH2:14][CH3:15]
Reactant: Cc1cccc(Cl)c1N=C=S
Reactant: CCCCNCC(=O)O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCN1CC(=O)N(c2c(C)cccc2Cl)C1=S
Yield: 36.6 %

Procedure:
The title compound was prepared by the procedure described in Example 11 using 6.5 g of 2-chloro-6-methylphenyl-isothiocyanate, 8.5 g of N-butyl glycine, 10.0 g of triethyl amine, and 150 mL of methylene chloride. Purification was achieved by flash chromatography on silica gel (methylene chloride). Crystallization from ethanol afforded the title compound (3.85 g) as a light pink solid, m.p. 97°-100° C. Anal. Calcd. for. C14H17Cl N2O S : C, 56.65; H, 5.77; N, 9.44. Found: C, 56.45; H, 5.67; N, 9.33. Mass spectrum (+FAB, [M+H]+) m/z 297.
Reaction SMILES: [OH2:1].OO.[F:4][C:5]1[C:10]([F:11])=[CH:9][C:8](B2OC(C)(C)C(C)(C)O2)=[CH:7][N:6]=1>O1CCCC1.O>[F:11][C:10]1[CH:9]=[C:8]([OH:1])[CH:7]=[N:6][C:5]=1[F:4]
Reactant: O
Reactant: CC1(C)OB(c2cnc(F)c(F)c2)OC1(C)C
Agent: OO
Solvent: C1CCOC1
Product: Oc1cnc(F)c(F)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 29.6 %

Procedure:
A mixture of hydrogen peroxide water (1.50 mL, 13.2 mmol) and 2,3-difluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2.8 g) in tetrahydrofuran (15 mL) was stirred at room temperature for 2 h, then diluted with water and extracted with ethyl acetate. Combined organic portions were washed with aqueous 5% sodium thiosulfate solution and saturated saline water, dried over anhydrous sodium sulfate and concentrated. Purification via Biotage Spla HPFC system (C18, mobile phase: 0.01% NH4HCO3, CH3CN/water, 10˜95%) afforded the title product as a white solid (450 mg).
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([C:17]2[NH:25][C:20]3=[N:21][CH:22]=[CH:23][CH:24]=[C:19]3[CH:18]=2)[C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:16])=[O:15])=[CH:10][CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(C=C(C2NC3=NC=CC=C3C=2)C2C=CC(S(C)=[O:40])=CC=2)CCCC1.[Mn]([O-])(=O)(=O)=O.[K+]>CO.O>[CH:1]1([CH2:6][CH:7]([C:17]2[NH:25][C:20]3=[N:21][CH:22]=[CH:23][CH:24]=[C:19]3[CH:18]=2)[C:8]2[CH:9]=[CH:10][C:11]([S:14]([CH3:16])(=[O:40])=[O:15])=[CH:12][CH:13]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CS(=O)c1ccc(C(=CC2CCCC2)c2cc3cccnc3[nH]2)cc1
Reactant: CS(=O)c1ccc(C(CC2CCCC2)c2cc3cccnc3[nH]2)cc1
Agent: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: CS(=O)(=O)c1ccc(C(CC2CCCC2)c2cc3cccnc3[nH]2)cc1
Reaction time: 1.5 h
Yield: 23 %

Procedure:
A solution of the mixture of 2-[2-cyclopentyl-1-(4-methanesulfinyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridine and 2-[2-cyclopentyl-1-(4-methanesulfinyl-phenyl)-vinyl]-1H-pyrrolo[2,3-b]pyridine (1.7 g) in methanol (50 mL) at 0° C. was treated dropwise with a solution of potassium permanganate (800 mg, 5.09 mmol) in water (15 mL). The resulting mixture was stirred to 1.5 h. The mixture was then partitioned between water (100 mL) and chloroform (100 mL). The aqueous layer was then extracted with ethyl acetate (2×100 mL). The combined organic layers were then dried over magnesium sulfate, filtered and the filterate concentrated in vacuo. Purification using a Biotage flash chromatography system (40 M column, 50% ethyl acetate/hexanes) afforded 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridine (420 mg, 23%) as a yellow foam which still contained some impurities. After standing overnight, a white solid had formed and this was then collected by filtration and the solids lightly washed with 10% ethyl acetate/hexanes to afford 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridine (300 mg) as a white solid: 1H NMR (300 MHz, CDCl3) δ ppm 9.81 (br s, 1H), 8.18 (dd, J=4.8, 1.5 Hz, 1H), 7.86 (d, J=8.2 Hz, 2H), 7.81-7.90 (m, 1H), 7.48 (d, J=8.2 Hz, 2H), 7.05 (dd, J=7.7, 4.8 Hz, 1H), 6.37 (d, J=1.5 Hz, 1H), 4.25 (t, J=7.9 Hz, 1H), 3.02 (s, 3H), 2.19-2.31 (m, 1H), 2.05-2.17 (m, 1H), 1.61-1.88 (m, 5H), 1.41-1.54 (m, 2H), 1.08-1.24 (m, 2H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([N:8]([CH3:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:5]=[C:4]([C:16]2[N:20]=[C:19]([C:21]3[N:26]=[CH:25][C:24]([CH:27]([OH:29])[CH3:28])=[CH:23][CH:22]=3)[O:18][N:17]=2)[N:3]=1.[Cl:30][C:31]([Cl:35])([Cl:34])[C:32]#N.[N:36]1(C2CCCCCCCCCC2)CCCN=CCCCC[CH2:37]1.O>C(Cl)Cl>[Cl:30][C:31]([Cl:35])([Cl:34])[CH2:32][C:37](=[NH:36])[O:29][CH:27]([C:24]1[CH:25]=[N:26][C:21]([C:19]2[O:18][N:17]=[C:16]([C:4]3[N:3]=[C:2]([NH2:1])[N:7]=[C:6]([N:8]([CH3:15])[C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=4)[N:5]=3)[N:20]=2)=[CH:22][CH:23]=1)[CH3:28]
Reactant: C1=NCCCN(C2CCCCCCCCCC2)CCCCC1
Reactant: N#CC(Cl)(Cl)Cl
Reactant: CC(O)c1ccc(-c2nc(-c3nc(N)nc(N(C)c4ccccc4)n3)no2)nc1
Solvent: ClCCl
Solvent: O
Product: CC(OC(=N)CC(Cl)(Cl)Cl)c1ccc(-c2nc(-c3nc(N)nc(N(C)c4ccccc4)n3)no2)nc1
Temperature: 25 °C
Reaction time: 19 h
Yield: 91 %

Procedure:
1-[6-(3-{4-Amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl}-1,2,4-oxadiazol-5-yl)pyridin-3-yl]ethan-1-ol (Intermediate 140, 0.400 g, 1.02 mmol) was suspended in DCM. Trichloroacetonitrile (0.123 mL, 1.22 mmol) and 1,8-diazabicycloundec-7-ene (few drops) were added and the mixture was stirred at room temperature for 19 h. DCM (30 mL) and water (30 mL) were added, the organic layer was separated and washed with brine (30 mL), before being dried over sodium sulfate and concentrated under vacuum to afford the title compound as a golden-brown solid (0.497 g, 91%), which was used in the next step without further purification. Method C HPLC-MS: MH+ requires m/z=534 Found: m/z=534, Rt=1.55 min (57%).
Reaction SMILES: [C:1]1(=[O:19])[N:5]([CH2:6][C:7](=O)[CH2:8][CH2:9][C:10](=O)[CH3:11])[C:4](=[O:14])[C:3]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:2]12.Cl.[CH2:21]([O:23][C:24](=[O:28])[CH2:25][CH2:26][NH2:27])[CH3:22].C(N(CC)CC)C>C(O)(=O)C>[CH2:21]([O:23][C:24]([CH2:25][CH2:26][N:27]1[C:10]([CH3:11])=[CH:9][CH:8]=[C:7]1[CH2:6][N:5]1[C:4](=[O:14])[C:3]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:2]2[C:1]1=[O:19])=[O:28])[CH3:22]
Reactant: CC(=O)CCC(=O)CN1C(=O)c2ccccc2C1=O
Reactant: CCOC(=O)CCN
Agent: Cl
Solvent: CC(=O)O
Solvent: CCN(CC)CC
Product: CCOC(=O)CCn1c(C)ccc1CN1C(=O)c2ccccc2C1=O

Procedure:
3.9 g (0.015 mol) of 6-phthalimido-2,5-hexanedione, 3.1 g (0.02 mol) of β-alanine ethyl ester hydrochloride and 3 ml (0.02 mol) of triethylamine are stirred in 80 ml of glacial acetic acid at 50° C. for 8 hours and the mixture is worked up as in Example 27.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:8][C:9]1[CH:13]=[CH:12][N:11]([CH3:14])[N:10]=1.Cl[C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([OH:26])[CH:24]=2)[N:19]=[CH:18][N:17]=1>>[CH3:14][N:11]1[CH:12]=[CH:13][C:9]([NH:8][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([O:26][C:4]4[CH:5]=[CH:6][N:7]=[CH:2][N:3]=4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[N:10]1
Reactant: Oc1ccc2ncnc(Cl)c2c1
Reactant: Clc1ncccn1
Reactant: Cn1ccc(N)n1
Product: Cn1ccc(Nc2ncnc3ccc(Oc4ccncn4)cc23)n1

Procedure:
The compound of Example 110 was manufactured by the same method as in Example 95, by a similar method thereto or by a combination of such a method with a conventional method using 2-chloropyrimidine, 3-amino-1-methyl-1H-pyrazole and 4-chloro-6-hydroxyquinazoline.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([I:10])[C:3]=1[CH:4]=O.[C:11](Br)(Br)([Br:13])[Br:12].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>>[Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([I:10])[C:3]=1[CH:4]=[C:11]([Br:13])[Br:12]
Reactant: BrC(Br)(Br)Br
Reactant: O=Cc1c(Cl)cccc1I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: Clc1cccc(I)c1C=C(Br)Br

Procedure:
Chloro-2-(2,2-dibromo-vinyl)-3-iodo-benzene was prepared from 2-chloro-6-iodo-benzaldehyde, carbon tetrabromide and triphenylphosphine in analogy to Example 1d): colourless oil; MS (EI): 425.8 (5%), 423.8 (20%), 421.7 (46%) and 419.7 (18%) (M+), 344.9 (30%), 342.8 (100%) and 340.8 (90%) ([M-Br]+), 263.9 (5%) and 261.9 (25%) ([M-2Br]+), 218.0 (9%), 216.0 (50%) and 214.0 (35%) ([M-Br])+).
Reaction SMILES: [Si:1]([O:18][C@@H:19]1[CH2:36][CH2:35][C@@:34]2([CH3:37])[C@H:21]([CH2:22][CH2:23][C@@H:24]3[C@@H:33]2[CH2:32][C@H:31]([OH:38])[C@@:29]2([CH3:30])[C@H:25]3[CH2:26][CH2:27][C:28]2=[O:39])[CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([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.N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si:54]([CH3:57])([CH3:56])[CH3:55])(=O)=O>CCOCC>[Si:1]([O:18][C@@H:19]1[CH2:36][CH2:35][C@@:34]2([CH3:37])[C@H:21]([CH2:22][CH2:23][C@@H:24]3[C@@H:33]2[CH2:32][C@H:31]([O:38][Si:54]([CH3:57])([CH3:56])[CH3:55])[C@@:29]2([CH3:30])[C@H:25]3[CH2:26][CH2:27][C:28]2=[O:39])[CH2:20]1)([C:14]([CH3:16])([CH3:17])[CH3:15])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)[Si](O[C@@H]1CC[C@@]2(C)[C@H](CC[C@@H]3[C@@H]2C[C@H](O)[C@]2(C)C(=O)CC[C@@H]32)C1)(c1ccccc1)c1ccccc1
Reactant: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: CCOCC
Solvent: Cc1cccc(C)n1
Product: CC(C)(C)[Si](O[C@@H]1CC[C@@]2(C)[C@H](CC[C@@H]3[C@@H]2C[C@H](O[Si](C)(C)C)[C@]2(C)C(=O)CC[C@@H]32)C1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A solution of 3α-tert-butyldiphenylsilyloxy-12α-hydroxy-5β-androstan-17-one (14.6 g) in ether (75 ml) is cooled to 0° C. and 2,6-lutidine (4.2 ml), trimethylsilyl trifluoromethanesulfonate (4.6 ml) are added and the mixture allowed to warm to room temperature, stirred for about 15 minutes, then diluted with ether. The organic solution was washed with dilute aqueous sodium bicarbonate, water and brine, then dried over magnesium sulfate, filtered, concentrated in vacuo, and the crude product purified by flash chromatography in 15% ether in hexane to give the desired product.