Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][CH:8](/[CH:11]=[N:12]/[S:13]([C:15]([CH3:18])([CH3:17])[CH3:16])=[O:14])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[Br-].[CH2:20]1[CH2:24]OC[CH2:21]1>>[O:1]1[C:5]2([CH2:6][CH2:7][CH:8]([CH:11]([NH:12][S:13]([C:15]([CH3:18])([CH3:17])[CH3:16])=[O:14])[CH2:24][CH:20]=[CH2:21])[CH2:9][CH2:10]2)[O:4][CH2:3][CH2:2]1
Reactant: CC(C)(C)S(=O)/N=C/C1CCC2(CC1)OCCO2
Reactant: C1CCOC1
Agent: [Br-]
Product: C=CCC(NS(=O)C(C)(C)C)C1CCC2(CC1)OCCO2
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution (E)-N-(1,4-dioxaspiro[4.5]decan-8-ylmethylene)-2-methylpropane-2-sulfinamide (1.91 g, 6.99 mmol), prepared in the previous step, in dry THF (48 mL) was treated with a solution of allylmagnesiumm bromide (10.5 mL, 21 mmol, 2N in THF) dropwise at ambient temperature under argon. After the complete addition, the reaction mixture was allowed to stir at room temperature and for 3 hours and then quenched at 0° C. by the cautious addition of saturated ammonium chloride solution. After extraction with ethyl acetate, the organic layer was concentrated in vacuo and the residue purified by flash chromatography (silica gel, 0-5% MeOH/Ethyl Acetate) to afford the product as a mixture of disatereomers.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:28])[NH:20][C:21]([CH3:27])=[CH:22][C:23]=2[CH2:24][O:25][CH3:26])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.[CH3:29][C:30]1([CH3:41])[CH2:35][C:34](B(O)O)=[CH:33][C:32]([CH3:40])([CH3:39])[NH:31]1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:11]([N:8]1[C:6]2[N:7]=[C:2]([C:34]3[CH2:33][C:32]([CH3:40])([CH3:39])[NH:31][C:30]([CH3:41])([CH3:29])[CH:35]=3)[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]3[C:19](=[O:28])[NH:20][C:21]([CH3:27])=[CH:22][C:23]=3[CH2:24][O:25][CH3:26])=[O:15])[C:5]=2[CH:10]=[N:9]1)([CH3:13])[CH3:12]
Reactant: COCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(Br)nc2c1cnn2C(C)C
Reactant: CC1(C)C=C(B(O)O)CC(C)(C)N1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: COCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(C2=CC(C)(C)NC(C)(C)C2)nc2c1cnn2C(C)C
Temperature: 100 °C
Yield: 44 %

Procedure:
To a stirred solution of 6-bromo-1-isopropyl-N-((4-(methoxymethyl)-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (0.06 g, 0.133 mmol) and (2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)boronic acid (0.043 g, 0.160 mmol) in dioxane/water mixture (1.5 mL+0.5 mL), Na2CO3 (0.5 g, 0.5 mmol) was added and solution purged with argon for 15 min. Then Pd(PPh3)4 (0.008 g, 0.007 mmol) was added and argon was purged again for 10 min. Reaction mass was heated at 100° C. for 2 h. On completion, reaction mixture was diluted with water and extracted with 10% MeOH/DCM. Combined organic layers were dried over Na2SO4 and solvent removed under reduced pressure to obtain crude material which was purified by column chromatography over silica gel to afford the desired product (44% yield). LCMS: 507.25 (M+1)+; HPLC: 99.64% (@ 254 nm) (Rt; 5.159); 1H NMR (DMSO-d6, 400 MHz) δ 11.68 (bs, 1H), 8.91 (t, 1H), 8.26 (s, 1H), 7.77 (s, 1H), 6.80 (s, 1H), 6.09 (s, 1H), 5.24-5.18 (m, 1H), 4.51 (s, 2H), 4.35 (d, 2H, J=4.4 Hz), 3.32 (3H merged in DMSO peak), 2.43 (s, 2H), 2.17 (s, 3H), 1.49 (d, 6H, J=6 Hz), 1.24 (s, 6H), 1.14 (s, 6H).
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[C:6]([CH3:7])=[CH:5][CH2:4][CH:3]1[CH2:8][CH:9]1[CH2:11][CH:10]1[C:12](=[O:14])[CH3:13].[BH4-].[Na+].Cl>C(O)C>[CH3:15][C:2]1([CH3:1])[C:6]([CH3:7])=[CH:5][CH2:4][CH:3]1[CH2:8][CH:9]1[CH2:11][CH:10]1[CH:12]([OH:14])[CH3:13]
Reactant: CC(=O)C1CC1CC1CC=C(C)C1(C)C
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: CC1=CCC(CC2CC2C(C)O)C1(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 85.5 %

Procedure:
1.5 g (7.3 mmol) of 1-[2-(2,2,3-trimethylcyclopent-3-enylmethyl)cyclopropyl]-ethanone dissolved in 5 ml of ethanol was added to a suspension of 0.50 g (13 mmol) of sodium borohydride in 30 ml of the same solvent under nitrogen at 15° C. The reaction mixture was stirred at room temperature for further 2 hours. After addition of 50 ml of 1N aqueous hydrochloric acid it was extracted with 200 ml of MTBE, the organic layer washed with 2×200 ml of brine, dried (MgSO4) evaporated in vacuo and bulb-to-bulb distilled to give 1.3 g of 1-[2-(2,2,3-trimethylcyclopent-3-enylmethyl)cyclopropyl]ethanol (87% yield).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([N:7]2[C:15]3[C:10](=[CH:11][C:12]([NH2:16])=[CH:13][CH:14]=3)[CH:9]=[CH:8]2)[CH:2]=1.I.[S:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[C:23](SC)=[NH:24].N>CCO.CO.C(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([N:7]2[C:15]3[C:10](=[CH:11][C:12]([NH:16][C:23]([C:19]4[S:18][CH:22]=[CH:21][CH:20]=4)=[NH:24])=[CH:13][CH:14]=3)[CH:9]=[CH:8]2)[CH:2]=1
Reactant: Nc1ccc2c(ccn2-c2cccnc2)c1
Reactant: CSC(=N)c1cccs1
Agent: I
Agent: N
Solvent: CCO
Solvent: ClCCl
Solvent: CO
Product: N=C(Nc1ccc2c(ccn2-c2cccnc2)c1)c1cccs1
Temperature: 25 °C
Reaction time: 8 h
Yield: 50 %

Procedure:
A solution of compound 73 (275 mg, 1.32 mmol) in 15 mL EtOH was treated with methyl thiophene-2-carbimidothioate hydroiodide (750 mg, 2.63 mmol) and stirred overnight at room temperature. Argon was bubbled through the mixture for 20 minutes then it was diluted with CH2Cl2 (50 mL) and treated with saturated sodium bicarbonate (20 mL). The organic layer was separated and the aqueous layer was extracted with an additional 50 mL CH2Cl2. The combined organic layers were dried over sodium sulfate and concentrated to give a yellow solid which was subjected to flash chromatography on silica gel using 5% MeOH/CH2Cl2 to 5% 2M NH3 in MeOH/CH2Cl2 to give an off-white residue, compound 74 (210 mg, 50%). HPLC analysis indicated that the product is >98% pure. 1H NMR (DMSO-d6) δ 8.85 (d, J=2.5 Hz, 1H), 8.58 (d, J=4.0 Hz, 1H), 8.08-8.05 (m, 1H), 7.75-7.53 (m, 5H), 7.12-7.09 (m, 2H), 6.78 (dd, J=1.5, 7.0 Hz, 1H), 6.67 (d, J=3.1 Hz, 1H), 6.35 (brs, 2H); ESI-MS (m/z, %): 319 (M+1, 100%); ESI-HRMS calculated for C18H15N4S (MH+): 319.1011, observed: 319.1015.
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:22])[C:12]3[S:19][C:18]([CH2:20]Cl)=[CH:17][C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1.[NH:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([CH:34]([OH:38])[CH2:35][NH:36][CH3:37])=[CH:26]1.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:22])[C:12]3[S:19][C:18]([CH2:20][N:36]([CH2:35][CH:34]([OH:38])[C:27]4[C:28]5[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=5)[NH:25][CH:26]=4)[CH3:37])=[CH:17][C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1
Reactant: Cn1cc(C(=O)NCc2ccc(Cl)cc2)c(=O)c2sc(CCl)cc21
Reactant: CNCC(O)c1c[nH]c2ccccc12
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: O
Product: CN(Cc1cc2c(s1)c(=O)c(C(=O)NCc1ccc(Cl)cc1)cn2C)CC(O)c1c[nH]c2ccccc12
Temperature: 60 °C
Reaction time: 5 h
Yield: 42.4 %

Procedure:
A mixture of N-(4-chlorobenzyl)-2-(chloromethyl)-4-methyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide (100 mg, 0.26 mmol), 1-(1H-indol-3-yl)-2-(methylamino)ethanol (Khim.-Farm. Zh. 1970, 4, 5-9)(75 mg, 0.39 mmol) and diisopropylethylamine (180 μL, 1.04 mmol) in dry DMF (5 mL) was heated to 60° C., becoming a solution. The reaction was stirred for 5 hours at that temperature. After cooling to room temperature, the solution was diluted with water (15 mL). The resulting milky suspension was stirred vigorously for 30 minutes, and then left standing overnight in the refrigerator. The mixture was filtered, and the collected solid was washed with water and dried in vacuo, leaving a white solid. Recrystallization from acetonitrile/water (dissolved with warming 5 mL of acetonitrile, then cooled to 0° C. and then diluted with 3 mL of water, left overnight) gave the title compound (59 mg) as a white solid.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[C:6]([C:10](=O)[CH3:11])[CH:7]=[CH:8][CH:9]=1)([CH3:3])[CH3:2].[CH3:13][C:14]([S@@:17]([NH2:19])=[O:18])([CH3:16])[CH3:15].O>C1COCC1.CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C>[CH:1]([C:4]1[CH:5]=[C:6](/[C:10](=[N:19]/[S@:17]([C:14]([CH3:16])([CH3:15])[CH3:13])=[O:18])/[CH3:11])[CH:7]=[CH:8][CH:9]=1)([CH3:3])[CH3:2]
Reactant: CC(=O)c1cccc(C(C)C)c1
Reactant: CC(C)(C)[S@@](N)=O
Agent: CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C
Solvent: O
Solvent: C1CCOC1
Product: C/C(=N\[S@@](=O)C(C)(C)C)c1cccc(C(C)C)c1
Temperature: 90 °C
Reaction time: 16 h

Procedure:
The mixture of 1-(3-isopropylphenyl)ethanone (5.8 g, 0.036 mol), (S)-2-methylpropane-2-sulfinamide (5.2 g, 0.043 mol) and Ti(OiPr)4 in THF was stirred at 90° C. for 16 hours. Then the mixture was poured to water and the solid was filtered, the filtrate was partitioned between EtOAc and water. The layers were separated and the organic layer was washed with water, brine, dried over Na2SO4, and concentrated. The residue was purified by column chromatography to give the titled compound.
Reaction SMILES: [CH2:1]([Li])CCC.CCCCCC.[CH3:12][C:13]([CH3:32])([CH3:31])[C:14]#[C:15]/[CH:16]=[CH:17]/[CH2:18][N:19]([CH2:21][C:22]1[CH:23]=[C:24]([C:28](=O)[CH3:29])[CH:25]=[CH:26][CH:27]=1)[CH3:20]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1>[CH3:12][C:13]([CH3:32])([CH3:31])[C:14]#[C:15]/[CH:16]=[CH:17]/[CH2:18][N:19]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([CH3:1])=[CH2:29])[CH:23]=1)[CH3:20]
Reactant: [Li]CCCC
Reactant: CC(=O)c1cccc(CN(C)C/C=C/C#CC(C)(C)C)c1
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: C=C(C)c1cccc(CN(C)C/C=C/C#CC(C)(C)C)c1
Temperature: 25 °C
Yield: 45.2 %

Procedure:
Methyl triphenylphosphonium bromide (2.33 g; 6.52 mmol) was suspended in tetrahydrofuran (15 ml). While the suspension was stirred under nitrogen atmosphere at room temperature, n-butyl lithium in n-hexane (1.68 M: 4.6 ml; 7.82 mmol) was added dropwise. After the reaction mixture turned deep red, the mixture was cooled in an ice bath, and Compound 1 (1.54 g; 5.43 mmol) in tetrahydrofuran (15 ml) was added dropwise thereto. After completion of the addition, the mixture was removed from the ice bath, and stirred for 30 minutes at room temperature. Reaction was stopped by pouring the mixture into ice/water, followed by extraction with ether (100 ml). The organic layer was washed with saturated aqueous sodium bicarbonate solution and with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=10:1), to thereby yield 0.69 g of the target compound (yield: 45.2%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([OH:17])[CH:5]=[CH:6][C:7]=1/[CH:8]=[CH:9]/[C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1.[C:18](OC(=O)C)(=[O:20])[CH3:19].CCN(CC)CC.C([O-])([O-])=O.[K+].[K+]>C1COCC1.CO.O>[OH:17][C:4]1[CH:5]=[CH:6][C:7](/[CH:8]=[CH:9]/[C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)=[C:2]([NH:1][C:18](=[O:20])[CH3:19])[CH:3]=1
Reactant: CC(=O)OC(C)=O
Reactant: Nc1cc(O)ccc1/C=C/c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(=O)Nc1cc(O)ccc1/C=C/c1ccc(O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 46.4 %

Procedure:
To the solution of 3-amino-4-[(E)-2-(4-hydroxy-phenyl)vinyl]phenol (100 mg) in anhydrous THF was added 225 mg of acetic anhydride and 223 mg of Et3N. The resulting solution was stirred at rt overnight. The reaction mixture was concentrated by vacuum evaporation. The residue, which was identified as mainly desired compound by 1H-NMR, was not further purified and used directly for the next step. The crude mixture from the previous reaction was dissolved in 30 mL of methanol. K2CO3 (197 mg, ˜12 eq.) was added as well as 20 mL of H2O. The resulting solution was vigorously stirred at rt for 1 h. All volatile solvents were evaporated and the residue was loaded on a silica gel column with 5% MeOH/dichloromethane as eluent to give N-{5-hydroxy-2-[(E)-2-(4-hydroxyphenyl)vinyl]phenyl}-acetamide (55 mg, 46.4% in two steps). MS (ES) m/z: 270.14 (M+1); Mp. 227-229° C.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][C:6]1[C:10]([CH2:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:9][NH:8][N:7]=1)[CH3:4].Cl[CH2:19][C:20]1[CH:25]=[CH:24][N:23]=[C:22]([O:26][CH2:27][C:28]2[N:29]=[C:30]([C:34]3[O:35][CH:36]=[CH:37][CH:38]=3)[O:31][C:32]=2[CH3:33])[CH:21]=1.O>CN(C)C=O>[CH2:3]([O:5][C:6]1[C:10]([CH2:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:9][N:8]([CH2:19][C:20]2[CH:25]=[CH:24][N:23]=[C:22]([O:26][CH2:27][C:28]3[N:29]=[C:30]([C:34]4[O:35][CH:36]=[CH:37][CH:38]=4)[O:31][C:32]=3[CH3:33])[CH:21]=2)[N:7]=1)[CH3:4]
Reactant: Cc1oc(-c2ccco2)nc1COc1cc(CCl)ccn1
Reactant: CCOC(=O)CCc1c[nH]nc1OCC
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCc1cn(Cc2ccnc(OCc3nc(-c4ccco4)oc3C)c2)nc1OCC
Temperature: 25 °C
Reaction time: 1 h
Yield: 89.3 %

Procedure:
Sodium hydride (60%, oily, 60.0 mg) was added to a solution of ethyl 3-(3-ethoxy-1H-pyrazol-4-yl)propionate (318 mg) and 4-chloromethyl-2-[2-(2-furyl)-5-methyl-4-oxazolylmethoxy]pyridine (457 mg) in N,N-dimethylformamide (10 ml) at 0° C., and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into water, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The residue was subjected to silica gel column chromatography to obtain ethyl 3-[3-ethoxy-1-[2-[2-(2-furyl)-5-methyl-4-oxazolylmethoxy]-4-pyridylmethyl]-1H-pyrazol-4-yl]propionate (643 mg, yield: 89%) as a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:1, volume ratio).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1.[Cl-].[Ca+2].[Cl-].[Cl-].[Al+3].[Cl-].[Cl-].[C:16]1([CH3:22])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1C2C(=CC=CC=2)CCC1>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:19]2[CH:20]=[CH:21][C:16]([CH3:22])=[CH:17][CH:18]=2)=[CH:3][CH:4]=1
Reactant: Cc1ccccc1
Reactant: Cc1ccc(N)cc1
Agent: [Al+3]
Agent: [Ca+2]
Agent: [Cl-]
Solvent: c1ccc2c(c1)CCCC2
Product: Cc1ccc(Nc2ccc(C)cc2)cc1
Temperature: 0 °C
Yield: 69.8 %

Procedure:
In a 500-ml four-necked flask were charged 56 ml of 1,2,3,4-tetrahydronaphthalene (boiling point: 207° C.) as a solvent and 91.1 g (0.83 mol) of p-toluidine, followed by the addition of 25.6 g (0.23 mol) of anhydrous calcium chloride and 30.8 g (0.23 mol) of anhydrous aluminum chloride under stirring. The resulting mixture was reacted at 210 to 220° C. for 3 hours under a nitrogen atmosphere. After cooling, the reaction mixture was added with 126 ml of toluene, followed by charging in 160 g of ice water. The resulting mixture was stirred and allowed to stand, and then the resulting water layer was separate out. The organic layer was washed successively with 150 ml of a 5% aqueous solution of hydrochloric acid, 100 ml of a 5% aqueous solution of sodium bicarbonate and 100 ml of water. After removal of the organic solvent by distillation under reduced pressure, 80 ml of methanol was added to the residue and the mixture was crystallized overnight at −3 to −8° C. The resulting crystals were collected by filtration, washed with 30 ml of methanol and then dried, whereby 57.1 g (yield: 69.8%) of the title compound was obtained as white crystals. As a result of HPLC. analysis (column: YMC-A-312, detection UV: 280 nm, flow rate: 1.0 ml/min, eluent: acetonitrile/water=8/2), the compound was found to have a purity of 99.8%.
Reaction SMILES: [OH:1][CH:2]([C:7]1[CH:17]=[CH:16][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:9][CH:8]=1)[CH2:3][CH:4]([CH3:6])[CH3:5].ClCCl.CS(C)=O.C(N(CC)CC)C>[Cl-].[Na+].O>[CH3:6][CH:4]([CH3:5])[CH2:3][C:2]([C:7]1[CH:8]=[CH:9][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:16][CH:17]=1)=[O:1]
Reactant: CCOC(=O)c1ccc(C(O)CC(C)C)cc1
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)c1ccc(C(=O)CC(C)C)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 81.3 %

Procedure:
A mixture of ethyl 4-(1-hydroxy-3-methylbutyl)benzoate (15 g, 63 mmol), dichloromethane (150 mL), dimethylsulfoxide (198 g, 2540 mmol), and triethylamine (32 g, 317 mmol) was cooled to 0° C. Sulfur trioxide pyridine complex (30 g, 190 mmol) was added in portions, maintaining the internal temperature below 50° C. The mixture was stirred at 0° C. for 1 hour. The reaction was then allowed to warm to room temperature and stir for 36 hours. The reaction was diluted with brine (300 mL) and extracted with methyl tert-butylether (2×500 mL). The combined organics were washed with 1 N aqueous hydrochloric acid (500 mL), dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography gave ethyl 4-(3-methylbutanoyl)benzoate (12 g, 80%) as a white solid. 1H NMR (400 MHz, CDCl3, δ): 8.11 (dd, J=1.6, 6.8 Hz, 2H), 7.98 (d, J=6.8 Hz, 2H), 4.40 (q, J=7.2 Hz, 2H), 2.85 (d, J=6.8 Hz, 2H), 2.24-2.34 (m, 1H), 1.39-1.43 (t, J=7.2 Hz, 3H), 1.50 (d, J=6.8 Hz, 6H).
Reaction SMILES: [CH3:1][N:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)[CH:5]=[C:4]([N+:14]([O-])=O)[C:3]1=[O:17].[N+](C1C(=O)NC=CC=1)([O-])=O>CN(C)C=O>[NH2:14][C:4]1[C:3](=[O:17])[N:2]([CH3:1])[CH:7]=[C:6]([C:8]2[CH:9]=[CH:10][N:11]=[CH:12][CH:13]=2)[CH:5]=1
Reactant: Cn1cc(-c2ccncc2)cc([N+](=O)[O-])c1=O
Agent: O=c1[nH]cccc1[N+](=O)[O-]
Solvent: CN(C)C=O
Product: Cn1cc(-c2ccncc2)cc(N)c1=O
Reaction time: 3 h

Procedure:
A mixture containing 10.7 g. of 1-methyl-3-nitro-5-(4-pyridinyl)-2(1H)-pyridinone and 200 ml. of dimethylformamide was warmed to dissolve the nitro-pyridinone and the solution was filtered through infusorial earth. The filtrate was charged into a 500 ml. Parr bottle with 1.2 g. of 10% palladium-on-charcoal catalyst and the mixture was shaken under 40 p.s.i. of hydrogen at room temperature for three hours, after which time no further hydrogen was taken up. The reaction mixture was filtered and the filtrate was concentrated to dryness under reduced pressure (0.1 mm.) on a water bath at 40° C. leaving 10.1 g. of brown crystalline solid. The solid was recrystallized three times from benzene-ethanol, the third time using decolorizing charcoal, to yield 4.5 g. of 3-amino-1-methyl-5-(4-pyridinyl)-2(1H)-pyridinone, m.p. 175°-176° C. after drying at room temperature in vacuo for twenty hours.
Reaction SMILES: [NH:1](C(OCC1C=CC=CC=1)=O)[C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[N:23]1([NH-:29])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1.[H][H]>CO.[Pd]>[NH2:1][C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[N:23]1([NH-:29])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1
Reactant: O=C(N[C@@H](Cc1ccccc1)C(=O)O)OCc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Agent: [NH-]N1CCOCC1
Solvent: CO
Product: N[C@@H](Cc1ccccc1)C(=O)O

Procedure:
A solution of 5.5 g of Z-(L)-Phe-morpholin-4-ylamide in 150 ml of methanol is converted into the title compound by hydrogenolysis with the calculated amount of hydrogen for 1 hour at room temperature in the presence of 1.5 g of 10% Pd/C. The catalyst is filtered off and the reaction mixture is concentrated, and after dilution with ethyl acetate the resulting solution is washed with a saturated sodium hydrogen carbonate solution, dried over sodium sulfate and concentrated under reduced pressure. After column chromatography (analogously to Example 1 g)) the title compound is obtained in pure form. TLC Rf (D)=0.3.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]2[S:10][CH2:9][CH:8]([CH2:11][N:12]3[CH2:17][CH2:16][CH:15]([CH2:18][OH:19])[CH2:14][CH2:13]3)[CH2:7][C:6]=2[CH:20]=1.C(N(CC)CC)C.[F:28][C:29]1[CH:37]=[CH:36][C:32]([C:33](Cl)=[O:34])=[CH:31][CH:30]=1>C(Cl)Cl>[F:28][C:29]1[CH:37]=[CH:36][C:32]([C:33]([O:19][CH2:18][CH:15]2[CH2:16][CH2:17][N:12]([CH2:11][CH:8]3[CH2:7][C:6]4[CH:20]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=4[S:10][CH2:9]3)[CH2:13][CH2:14]2)=[O:34])=[CH:31][CH:30]=1
Reactant: OCC1CCN(CC2CSc3ccc(F)cc3C2)CC1
Reactant: O=C(Cl)c1ccc(F)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(OCC1CCN(CC2CSc3ccc(F)cc3C2)CC1)c1ccc(F)cc1

Procedure:
To a solution of 400 mg 6-fluoro-3-(4-[hydroxymethyl]-piperidinomethyl)-3,4-dihydro-2H-1-benzothiopyran and 200 mg triethylamine in 10 ml methylene chloride is added 221 mg p-fluorobenzoyl chloride. After 30 minutes at room temperature the reaction mixture is washed with 1 N sodium hydroxide, dried over magnesium sulfate and the solvent is removed in vacuo. The residue is triturated with ether/hexane to afford the title compound, m.p. 113°-114° C.
Reaction SMILES: [C:1]1([N:7]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[C:28]4[C:24](=[N:25][NH:26][N:27]=4)[C:23]([C:29]4[CH:34]=[CH:33][C:32]([N:35]([C:42]5[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=5)[C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)=[CH:31][CH:30]=4)=[CH:22][CH:21]=3)=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:49]1[N:54]=[CH:53][CH:52]=[CH:51][N:50]=1.[H-].[Na+].CN(C)C=O>O>[C:8]1([N:7]([C:14]2[CH:15]=[CH:16][C:17]([C:20]3[C:28]4[C:24](=[N:25][N:26]([C:49]5[N:54]=[CH:53][CH:52]=[CH:51][N:50]=5)[N:27]=4)[C:23]([C:29]4[CH:34]=[CH:33][C:32]([N:35]([C:36]5[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=5)[C:42]5[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=5)=[CH:31][CH:30]=4)=[CH:22][CH:21]=3)=[CH:18][CH:19]=2)[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: c1ccc(N(c2ccccc2)c2ccc(-c3ccc(-c4ccc(N(c5ccccc5)c5ccccc5)cc4)c4n[nH]nc34)cc2)cc1
Reactant: Clc1ncccn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: c1ccc(N(c2ccccc2)c2ccc(-c3ccc(-c4ccc(N(c5ccccc5)c5ccccc5)cc4)c4nn(-c5ncccn5)nc34)cc2)cc1
Temperature: 120 °C

Procedure:
A mixture of Intermediate A (500 mg, 0.82 mmol), 2-chloropyrimidine (343 mg, 3.0 mmol), 60% NaH (60 mg, 1.5 mmol), and dimethylformamide (10 mL) was stirred under argon and heated at 120° C. for 20 hours. The reaction mixture was poured into water (100 mL) and extracted with dichloromethane (4×100 mL). The extract was dried over anhydrous sodium sulfate, the volatiles were removed under reduced pressure, and the residue was chromatographed using silica gel and dichloromethane/ethyl acetate (95:5) as an eluent. The obtained product was recrystallized from ethanol to give 4,7-bis(4-(N,N-diphenylamino)phenyl)-2-(pyrimidin-2-yl)-2H-benzo[d][1,2,3]triazole (Compound 1), orange crystals, 340 mg (61%). 1H NMR (400 MHz, CDCl3): δ 8.99 (d, J=5.1 Hz, 2H, pyrimidine), 8.02 (d, J=8.8 Hz, 4H, p-phenylene), 7.66 (s, 2H, benzotriazole), 7.47 (t, J=4.8 Hz, 1H, pyrimidine), 7.28 (m, 8H, Ph), 7.21 (d, J=8.4 Hz, 4H, p-phenylene), 7.18 (m, 8H, Ph), 7.05 (tt, J=7.3 and 1.1 Hz, 4H, Ph). UV-vis spectrum (dichloromethane): λmax=451 nm. Fluorimetry (dichloromethane): λmax=600 nm.