Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([CH2:8][NH:9][C:10]2[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][N:13]=[C:12]([NH:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][C:28]([F:31])([F:30])[F:29])[N:11]=2)[CH2:4][CH2:3]1.[O:32]1[C:34]([CH3:36])([CH3:35])[CH:33]1O>C(O)C>[CH3:33][C:34]([OH:32])([CH3:36])[CH2:35][NH:1][C@H:2]1[CH2:3][CH2:4][C@H:5]([CH2:8][NH:9][C:10]2[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][N:13]=[C:12]([NH:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][C:28]([F:30])([F:31])[F:29])[N:11]=2)[CH2:6][CH2:7]1
Reactant: N[C@H]1CC[C@H](CNc2nc(NCc3ccccc3OC(F)(F)F)ncc2[N+](=O)[O-])CC1
Reactant: CC1(C)OC1O
Solvent: CCO
Product: CC(C)(O)CN[C@H]1CC[C@H](CNc2nc(NCc3ccccc3OC(F)(F)F)ncc2[N+](=O)[O-])CC1
Temperature: 100 °C

Procedure:
A reaction mixture of N4-[(trans-4-aminocyclohexyl)methyl]-5-nitro-N2-[2-(trifluoromethoxy)benzyl]pyrimidine-2,4-diamine (50 mg, 0.11 mmol) and 1,2-epoxy-2-methylpropanol (500 μL) in ethanol (1 mL) was heated to 100° C. for 1 h in a microwave. The reaction mixture was concentrated and the resulting residue was purified by silica gel preparative TLC using 10:1 CH2Cl2:MeOH as an eluent to afford 28 mg (47%) of the title compound as a white solid, m/z 513.5 [M+1]+
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[Br:16][C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=1.C(=O)([O-])O.[Na+]>>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH3:15])[N:5]=[CH:4][CH:3]=[C:2]2[O:23][C:20]1[CH:21]=[CH:22][C:17]([Br:16])=[CH:18][CH:19]=1
Reactant: COc1cc2nccc(Cl)c2cc1OC
Reactant: Oc1ccc(Br)cc1
Agent: O=C([O-])O
Agent: [Na+]
Product: COc1cc2nccc(Oc3ccc(Br)cc3)c2cc1OC
Temperature: 180 °C
Reaction time: 0.67 h
Yield: 501.2 %

Procedure:
4-Chloro-6,7-dimethoxyquinoline (1.00 g) and commercially available 4-bromophenol (115 mg) were mixed and stirred at 180° C. for 40 minutes. The reaction mixture was neutralized with saturated aqueous sodium hydrogen carbonate and then partitioned between water and chloroform, and the chloroform layer was washed with brine and dried with sodium sulfate. After removing the solvent by reduced-pressure distillation, the resulting residue was purified by column chromatography on silica gel, eluting in sequence with hexane/acetone, chloroform and chloroform/methanol, to obtain 1.20 g of the title compound (yield: 76%).
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[CH3:6][C:7]([N:9]([CH3:11])[CH3:10])=O.[C:12]([C:14]1[CH:20]=[C:19]([O:21][CH3:22])[C:18]([O:23][CH3:24])=[CH:17][C:15]=1[NH2:16])#[N:13]>C(Cl)(Cl)Cl>[CH3:10][N:9]([CH3:11])[C:7](=[N:16][C:15]1[CH:17]=[C:18]([O:23][CH3:24])[C:19]([O:21][CH3:22])=[CH:20][C:14]=1[C:12]#[N:13])[CH3:6]
Reactant: CC(=O)N(C)C
Reactant: COc1cc(N)c(C#N)cc1OC
Solvent: ClC(Cl)Cl
Solvent: O=P(Cl)(Cl)Cl
Product: COc1cc(C#N)c(N=C(C)N(C)C)cc1OC
Reaction time: 0.08 h

Procedure:
Phosphorous oxychloride (1.0 ml) was added to a stirred solution of dimethylacetamide (2.8 ml) in chloroform (10 ml) at room temperature. The mixture was stirred for 5 minutes, 2-cyano-4,5-dimethoxyaniline (1.78 g) added and the reaction stirred under reflux for 4 hours. The mixture was cooled, poured onto ice and extracted with chloroform and the organic phase discarded. The aqueous layer was basified (solid NaOH) extracted with chloroform, the combined extracts washed with water, dried (Na2SO4) and evaporated in vacuo. A sample of the brown oily residue (2 g) was crystallised from diisopropylether to give N,N-dimethyl-N'-(2-cyano-4,5-dimethoxyphenyl)acetamidine, m.p. 94°-96°.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:5]=[C:6]([CH3:16])[C:7]=1[C:8]1[C:9](=[O:15])[CH2:10][CH2:11][C:12]=1[O:13][CH3:14].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[O:33]1[CH2:37][CH2:36][CH:35]([CH:38]=[O:39])[CH2:34]1>O1CCCC1>[CH3:16][C:6]1[CH:5]=[C:4]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:3]=[C:2]([CH3:1])[C:7]=1[C:8]1[C:9](=[O:15])[CH:10]([CH:38]([OH:39])[CH:35]2[CH2:36][CH2:37][O:33][CH2:34]2)[CH2:11][C:12]=1[O:13][CH3:14]
Reactant: COC1=C(c2c(C)cc(-c3ccccc3)cc2C)C(=O)CC1
Reactant: O=CC1CCOC1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COC1=C(c2c(C)cc(-c3ccccc3)cc2C)C(=O)C(C(O)C2CCOC2)C1
Temperature: -75 °C
Reaction time: 0.67 h
Yield: 136.7 %

Procedure:
To a solution of 2-(3,5-Dimethylbiphenyl-4-yl)-3-methoxy cyclopent-2-enone (0.6 g, 2.05 mmol) in tetrahydrofuran (12 ml) is added 1 molar solution of lithium bis(trimethylsilyl)amide in THF (2.5 ml, 2.5 mmol) under nitrogen atmosphere at −75° C. The resulting solution is stirred at −75° C. for 40 minutes and to this mixture, a solution of 3-tetrahydrofurancarboxaldehyde (0.42 g, 4.1 mmol) in THF is added over 20 minutes. The resulting solution is stirred at −75° C. for 2 hours. The cooling bath is removed and the mixture is allowed to reach room temperature, then stirred for 2 hours. The reaction mixture is quenched with ice cold water (100 ml) and extracted with ethyl acetate (3×75 ml, dried over anhydrous sodium sulphate, filtered and the filtrate is concentrated in vacuo to give a residue (1.1 g) which is used as such for the next step.
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][N+:4]([O-:8])=[C:5]([SH:7])[CH:6]=1.[C:9]([O-:14])(=[O:13])[C:10]([CH3:12])=[CH2:11].[C:15](OC)(=O)C(C)=C.[C:22]1([CH3:28])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(Cl)Cl.CC(N=NC(C#N)(C)C)(C#N)C>[CH:1]1[CH:2]=[CH:3][N+:4]([O-:8])=[C:5]([SH:7])[CH:6]=1.[C:9]([O-:14])(=[O:13])[C:10]([CH3:12])=[CH2:11].[CH2:15]=[CH:28][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: C=C(C)C(=O)OC
Reactant: Cc1ccccc1
Agent: C=C(C)C(=O)[O-]
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: [O-][n+]1ccccc1S
Solvent: ClCCl
Product: C=Cc1ccccc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A 6-ml flask was charged with 0.489 g of pyrithione methacrylate (2.5 mmole), 2.6 ml of methyl methacrylate (22.5 mmole) and 0.083 g of AIBN (0.5 mmole), and 3 ml of toluene. The flask was sealed and placed in an oven at 80° C. for 16 hours. After cooling to room temperature, the product was diluted with 10 ml of methylene chloride and filtered. The solution was concentrated via roto-evaporation and 2.32 g of the desired product was isolated as a yellow polymeric material for a 79.6% yield. The structure was confirmed by NMR and IR. Similar results were obtained by employing either acetyl peroxide, benzoyl peroxide, or lauryl peroxide as the radical initiator.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([N:8]([CH3:10])[CH3:9])[CH:5]=[C:4]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:3]=1.CCCCCC.[Li]CCCC.[CH:33]([N:36]=[C:37]=[O:38])([CH3:35])[CH3:34]>C(OCC)C>[CH:33]([NH:36][C:37]([C:2]1[CH:7]=[C:6]([N:8]([CH3:10])[CH3:9])[CH:5]=[C:4]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:3]=1)=[O:38])([CH3:35])[CH3:34]
Reactant: CC(C)N=C=O
Reactant: CN(C)c1cc(Br)nc(Oc2cccc(C(F)(F)F)c2)c1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CCOCC
Product: CC(C)NC(=O)c1cc(N(C)C)cc(Oc2cccc(C(F)(F)F)c2)n1
Reaction time: 0.17 h

Procedure:
0.75 g (0.0021 mol) of 2-bromo-4-dimethylamino-6-{3-(trifluoromethyl)phenoxy} pyridine was suspended in about 15 ml of diethyl ether. While cooling the obtained suspension in a dry ice-acetone bath in an argon atmosphere, 1.4 ml of a 1.65M-hexane solution of BuLi (0.0021×1.1 mol) was added thereto, followed by stirring the suspension for about 10 minutes. After 0.35 g (0.0021×2.0 mol) of isopropyl isocyanate dissolved in about 10 ml of diethyl ether was added to the reaction solution, the obtained solution was removed from the bath and stirred at room temperature for about one hour. The reaction solution was mixed with about 5 ml of a 1N-hydrochloric acid aqueous solution, and then distributed in ethyl acetate-saturated sodium bicarbonate water, followed by washing with saturated brine. The organic phase of the obtained solution was dried with anhydrous sodium sulfate, concentrated and purified by silica gel column chromatography (eluting solution: ethyl acetate/hexane) and reversed phase column (Lobor LiCHroprep RP-10; eluting solution: acetonitrile/water), thereby obtaining an aimed product.
Reaction SMILES: [H-].[Na+].O1CCC[CH2:4]1.[CH3:8][CH:9]([C:13](=[O:15])[CH3:14])[C:10](=[O:12])[CH3:11].IC>O>[CH3:8][C:9]([CH3:4])([C:13](=[O:15])[CH3:14])[C:10](=[O:12])[CH3:11]
Reactant: CC(=O)C(C)C(C)=O
Reactant: C1CCOC1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CI
Product: CC(=O)C(C)(C)C(C)=O
Reaction time: 0.5 h
Yield: 98 %

Procedure:
To 0.1 mol sodium hydride was added 100 ml anhydrous tetrahydrofuran, and slowly added dropwise 0.12 mol 3-methyl-2,4-pentandione at room temperature. Upon completion, the mixture was stirred for 0.5 hours, then 0.12 mol iodomethane was slowly added dropwise. After stirred at room temperature for 10 hours, 20 ml water was added to dissolve solid. The mixture was extracted with ethyl acetate. The solvent was removed. Distillation was carried out under reduced pressure, and cut fraction 82-84° C./1 kPa was collected. The yield was 98%.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.Cl[C:12]1[CH:17]=[CH:16][N:15]2[N:18]=[C:19]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)[C:20]([C:21]([N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:22])=[C:14]2[C:13]=1[F:39].CC1C=CC(C(O)=O)=CC=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+]>O.O1CCOCC1>[C:26]([O:25][C:24]([N:23]([CH3:31])[C:21]([C:20]1[C:19]([C:32]2[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=2)=[N:18][N:15]2[CH:16]=[CH:17][C:12]([C:3]3[CH:4]=[C:5]([CH:9]=[CH:10][C:2]=3[CH3:1])[C:6]([OH:8])=[O:7])=[C:13]([F:39])[C:14]=12)=[O:22])=[O:30])([CH3:29])([CH3:28])[CH3:27]
Reactant: Cc1ccc(C(=O)O)cc1
Reactant: CN(C(=O)OC(C)(C)C)C(=O)c1c(-c2ccc(F)cc2)nn2ccc(Cl)c(F)c12
Agent: Cc1ccc(C(=O)O)cc1B1OC(C)(C)C(C)(C)O1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: Cc1ccc(C(=O)O)cc1-c1ccn2nc(-c3ccc(F)cc3)c(C(=O)N(C)C(=O)OC(C)(C)C)c2c1F
Temperature: 95 °C
Reaction time: 18 h

Procedure:
3-(3-(tert-butoxycarbonyl)methyl)carbamoyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid. To a degassed solution containing tert-butyl 5-chloro-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-3-carbonyl(methyl)carbamate (0.10 g, 0.24 mmol), 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (0.078 g, 0.30 mmol), sodium carbonate (0.075 g, 0.71 mmol), dioxane (2.0 mL) and water (0.40 mL) was added tetrakis(tiphenylphosphine)palladium(0) (0.008 g, 0.007 mmol). The mixture was stirred at 95° C. for 18 h. The solution was cooled to room temperature, filtered to remove solids and adjusted to below pH 4 with 1 N aqueous hydrochloric acid (2.0 mL). Water was added (10 mL) and the aqueous portion was extracted with ethyl acetate (2×15 mL). The combined organic portions were washed with brine (20 mL) and dried over magnesium sulfate. The mixture was filtered and concentrated to afford 3-(3-(tert-butoxycarbonyl(methyl)carbamoyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid as a residue which was used without further purification. LCMS retention time: 2.467 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Sunfire C18, 5 micron, C18, 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% CH3CN/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3CN/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 522 (MH+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[O:16][C:15]3[CH:14]=[CH:13][NH:12][C:11](=[O:17])[C:10]=3[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.F[C:19]1[CH:20]=[CH:21][C:22]([N+:26]([O-:28])=[O:27])=[C:23]([CH3:25])[CH:24]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[O:16][C:15]3[CH:14]=[CH:13][N:12]([C:19]4[CH:20]=[CH:21][C:22]([N+:26]([O-:28])=[O:27])=[C:23]([CH3:25])[CH:24]=4)[C:11](=[O:17])[C:10]=3[CH:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cc(F)ccc1[N+](=O)[O-]
Reactant: O=c1[nH]ccc2oc(-c3cccc(Cl)c3)cc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: Cc1cc(-n2ccc3oc(-c4cccc(Cl)c4)cc3c2=O)ccc1[N+](=O)[O-]
Temperature: 120 °C
Reaction time: 48 h
Yield: 78.5 %

Procedure:
To a solution of 2-(3-chlorophenyl)-5H-furo[3,2-c]pyridine-4-one (1.00 g, 4.08 mmol) in DMF (9.46 mL) was added 5-fluoro-2-nitrotoluene (0.57 mL, 4.7 mmol) and Cs2CO3 (1.32 g, 4.08 mmol). After stirring at 120° C. for 48 h, the reaction mixture was cooled and the solids were collected by filtration. The solids were washed with EtOAc (300 ml) to yield the title compound (1.22 g, 78%) as a golden yellow solid: 1H NMR (500 MHz, DMSO-d6) δ 8.14 (d, J=8.6 Hz, 1H), 7.97 (t, J=17 Hz, 1H), 7.86 (d, J=6.9 Hz, 1H), 7.74 (s, 1H), 7.73 (d, J=7.0 Hz, 1H), 7.68 (d, J=2 Hz, 1H), 7.60 (dd, J=8.0, 2.2 Hz, 1H), 7.53 (t, J=8.0 Hz, 1H), 7.46-7.44 (m, 1H), 6.97 (d, J=7.5 Hz, 1H), 2.58 (s, 3H).
Reaction SMILES: [BH4-].[Na+].CO.[CH3:5][O:6][C:7](=[O:32])[CH2:8][CH2:9][CH2:10][C:11]#[C:12][CH2:13][N:14]1[C@@H:19](/[CH:20]=[CH:21]/[C:22](=[O:30])[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:18][CH2:17][CH2:16][C:15]1=[O:31]>C(Cl)Cl>[CH3:5][O:6][C:7](=[O:32])[CH2:8][CH2:9][CH2:10][C:11]#[C:12][CH2:13][N:14]1[C:15](=[O:31])[CH2:16][CH2:17][CH2:18][C@@H:19]1/[CH:20]=[CH:21]/[CH:22]([OH:30])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: COC(=O)CCCC#CCN1C(=O)CCC[C@@H]1/C=C/C(=O)Cc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: COC(=O)CCCC#CCN1C(=O)CCC[C@@H]1/C=C/C(O)Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 77.5 %

Procedure:
Sodium borohydride (2 mg, 0.053 mmol), followed by MeOH (0.1 mL), was added to a solution of 7-[(R)-2-oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-hept-5-ynoic acid methyl ester (14 mg, 0.037 mmol) in CH2Cl2 (0.5 mL) at 0° C. The mixture was allowed to warm to rt. After 30 min at rt, the reaction was quenched with aqueous HCl (1.0 M, 1 mL) and extracted with EtOAc (3×5 mL). The combined organic phase was washed with brine (10 mL) then dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→2% MeOH/CH2Cl2, gradient) afforded 11 mg (78%) of the title compound.
Reaction SMILES: C(O[CH:4]=[C:5]1[C:16]2[C:8](=[CH:9][CH:10]=[C:11]3[C:15]=2[S:14][CH:13]=[N:12]3)[NH:7][C:6]1=[O:17])C.[CH:18]1[CH:19]=[CH:20][N:21]=[C:22]([NH:24][S:25]([C:28]2[CH:29]=[CH:30][C:31]([NH2:34])=[CH:32][CH:33]=2)(=[O:27])=[O:26])[CH:23]=1.C(O)C>O>[O:17]=[C:6]1[C:5](=[CH:4][NH:34][C:31]2[CH:30]=[CH:29][C:28]([S:25]([NH:24][C:22]3[CH:23]=[CH:18][CH:19]=[CH:20][N:21]=3)(=[O:27])=[O:26])=[CH:33][CH:32]=2)[C:16]2[C:8](=[CH:9][CH:10]=[C:11]3[C:15]=2[S:14][CH:13]=[N:12]3)[NH:7]1
Reactant: Nc1ccc(S(=O)(=O)Nc2ccccn2)cc1
Reactant: CCOC=C1C(=O)Nc2ccc3ncsc3c21
Solvent: CCO
Solvent: O
Product: O=C1Nc2ccc3ncsc3c2C1=CNc1ccc(S(=O)(=O)Nc2ccccn2)cc1
Reaction time: 18 h
Yield: 71 %

Procedure:
To a 25 ml round bottom flask was added a stir bar, 246 mg (1.00 mmol) of 8-ethoxymethylene-6,8-dihydro-1-thia-3,6-diaza-as-indacen-7-one. 249 (1.00 mmol) of sulfapyridine and 10 ml of ethanol. The flask was fitted with a water-cooled reflux condenser, and the mixture was heated to reflux using an oil bath with stirring for 18 h. The reaction was allowed to cool and was filtered. The precipitate was washed with excess ethanol and dried under vacuum to yield 321 mg (71%) of the title compound: 1H NMR (DMSO-d6): δ 11.9 (br s, 1H), 11.2 (d, 1H), 10.9 (s, 1H), 9.3 (s, 1H), 8.1 (d, 2H), 7.9 (m 3H) 7.8 (m, 1H), 7.6 (d, 2H), 7.2 (d, 1H), 7.2 (d, 1H), 6.9 (t, 1H); C21H15N5O3S2: APCI−MS m/z 450 (M+H)+.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]([CH3:36])=[C:9]([CH2:11][O:12][C:13]2[CH:33]=[CH:32][C:16]([CH2:17][O:18][C:19]3[C:23]([CH:24]=[O:25])=[CH:22][N:21]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[N:20]=3)=[CH:15][C:14]=2[O:34][CH3:35])[N:10]=1.C1(C)C=CC(S([CH2:46][N+:47]#[C-:48])(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].CO>O>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]([CH3:36])=[C:9]([CH2:11][O:12][C:13]2[CH:33]=[CH:32][C:16]([CH2:17][O:18][C:19]3[C:23]([C:24]4[O:25][CH:48]=[N:47][CH:46]=4)=[CH:22][N:21]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[N:20]=3)=[CH:15][C:14]=2[O:34][CH3:35])[N:10]=1
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Reactant: COc1cc(COc2nn(-c3ccccc3)cc2C=O)ccc1OCc1nc(-c2ccco2)oc1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CO
Product: COc1cc(COc2nn(-c3ccccc3)cc2-c2cnco2)ccc1OCc1nc(-c2ccco2)oc1C
Yield: 52.4 %

Procedure:
A mixture of 3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazole-4-carbaldehyde (0.60 g), p-toluenesulfonylmethylisocyanide (0.25 g), potassium carbonate (0.17 g) and methanol (30 mL) was heated under reflux for 3 hrs. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give 2-(2-furyl)-4-{[2-methoxy-4-({[4-(1,3-oxazol-5-yl)-1-phenyl-1H-pyrazol-3-yl]oxy}methyl)phenoxy]methyl}-5-methyl-1,3-oxazole as colorless crystals (0.34 g, yield 54%) from a fraction eluted with ethyl acetate-hexane (1:1, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 153-154° C.
Reaction SMILES: [Br:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([F:11])[CH:9]=2)[NH:4][N:3]=1.C([O-])([O-])=O.[K+].[K+].Cl[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[CH:25]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([F:11])[CH:9]=2)[N:4]([C:25]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:19]=2)([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[N:3]=1
Reactant: Fc1cnc2[nH]nc(Br)c2c1
Reactant: Clc1ccccc1C(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Fc1cnc2c(c1)c(Br)nn2C(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
A mixture of 3-bromo-5-fluoro-1H-pyrazolo[3,4-b]pyridine, 4, (0.97 g, 4.49 mmol) and K2CO3 (1.86 g, 13.47 mmol) in DMF (9.7 mL) was cooled to 0° C. Chlorodiphenylmethylbenzene (1.38 g, 4.94 mmol) was added. The mixture was stirred at room temperature overnight. The mixture was diluted with 40 mL of ethyl acetate and washed with 30 mL of water. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The product was purified by silica gel chromatography (40% ethyl acetate/hexanes) to afford 1.68 g of the desired product as a white solid: 1H NMR (300 MHz, d6-DMSO) δ 8.45-8.38 (m, 1H), 8.04 (dd, J=8.0, 2.7 Hz, 1H), 7.35-7.16 (m, 15H); LC/MS Gradient 10-90%, 0.1% formic 5 min, C18/ACN, Retention Time=3.03 min, (M+H) 459.46.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([NH:9][C:10](=[O:12])[CH3:11])=[C:4]([CH3:13])[CH:3]=1.[F:14][C:15]([F:25])([F:24])[C:16]1[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][CH:17]=1.O>C(O)C>[CH3:8][C:6]1[CH:7]=[C:2]([NH:1][CH2:20][C:19]2[CH:18]=[CH:17][C:16]([C:15]([F:14])([F:24])[F:25])=[CH:23][CH:22]=2)[CH:3]=[C:4]([CH3:13])[C:5]=1[NH:9][C:10](=[O:12])[CH3:11]
Reactant: O=Cc1ccc(C(F)(F)F)cc1
Reactant: CC(=O)Nc1c(C)cc(N)cc1C
Solvent: O
Solvent: CCO
Product: CC(=O)Nc1c(C)cc(NCc2ccc(C(F)(F)F)cc2)cc1C
Reaction time: 0.25 h
Yield: 30 %

Procedure:
N-(4-Amino-2,6-dimethyl-phenyl)-acetamide (1.2 g) and 4-trifluoromethyl-benzaldehyde (1.3 g) were dissolved in ethanol (100 mL) and refluxed for 16 h. The reaction mixture was poured into water (3 L) and the precipitate collected by filtration. Sodium cyanoborohydride (2 g) and acetic acid (2 mL) were added to the precipitate dispersed in methanol (50 mL) and stirred for 15 minutes. The reaction mixture was filtered, water (100 mL) was added and the organic solvent was removed in vacuo. The product was allowed to precipitate at 25° C. and collected by filtration and washed with water (200 mL) to furnish 0.68 g (30% yield) of the title compound as a pale yellow solid. LC-MS (m/z) 337 (MH+); tR=2.39, (UV, ELSD) 99%, 99%. 1H NMR (500 MHz, DMSO-d6): 1.95 (s, 3H), 1.96 (s, 6H), 4.34 (d, 2H), 6.18 (t, 1H), 6.25 (s, 2H), 7.55 (d, 2H), 7.69 (d, 2H), 8.81 (s, 1H).
Reaction SMILES: [C:1]1([CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1.O[N:24]1[C:28](=[O:29])[CH2:27][CH2:26][C:25]1=[O:30].ClC(N=C=N)CC(Cl)CCC>CS(C)=O>[C:25]1(=[O:30])[N:24]([C:2]2[CH:3]=[C:4]3[C:15]4=[C:16]5[C:11]([CH:10]=[CH:9][CH:8]=[C:7]5[CH:6]=[CH:5]3)=[CH:12][CH:13]=[C:14]4[C:1]=2[CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])[C:28](=[O:29])[CH2:27][CH2:26]1
Reactant: O=C1CCC(=O)N1O
Reactant: O=C(O)CCCc1ccc2ccc3cccc4ccc1c2c34
Agent: CCCC(Cl)CC(Cl)N=C=N
Solvent: CS(C)=O
Product: O=C(O)CCCc1c(N2C(=O)CCC2=O)cc2ccc3cccc4ccc1c2c34
Temperature: 0 °C
Yield: 62.5 %

Procedure:
SPB was prepared according to the synthesis scheme shown in FIG. 2. In 20 ml of dimethylsulfoxide (DMF), 2.25 g of 1-pyrenebutanoic acid (7.8 mmol: obtained from Molecular Probes, Inc.) and 1.2 g of N-hydroxy succinimide (10.4 mmol: obtained from Wako Pure Chemical Industries, Ltd.) were dissolved. After the mixed solution was cooled to 0° C., 2.69 g of 1,3-dichlorohexylcarbodiimide (13.1 mmol: DCC) was added thereto. Then, the mixture was reacted at 0° C. for 24 hours while stirring. After the reacted solution was filtered with a 0.45 μm filter, the filtrate was collected and dried using an evaporator. Then, the filtrate was recrystallized from 95% ethanol, thereby obtaining 1.88 g of succinimidyl-1-pyrenebutanoic acid (yield: 70%).
Reaction SMILES: [CH2:1]([NH:16][C:17]([O:19][CH2:20][C:21](=[CH2:24])[CH2:22][OH:23])=[O:18])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].[Br:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][C:33](O)=[O:34]>>[CH2:1]([NH:16][C:17]([O:19][CH2:20][C:21](=[CH2:24])[CH2:22][O:23][C:33](=[O:34])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][Br:25])=[O:18])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: O=C(O)CCCCCCCBr
Reactant: C=C(CO)COC(=O)NCCCCCCCCCCCCCCC
Product: C=C(COC(=O)CCCCCCCBr)COC(=O)NCCCCCCCCCCCCCCC

Procedure:
Following the procedure described in Preparation 9, but replacing 3-octadecylaminocarbonyloxy-2-methylenepropan-1-ol with 3-pentadecylaminocarbonyloxy-2-methylenepropan-1-ol (from Preparation 4), and replacing 6-bromohexanoic acid with 8-bromooctanoic acid, the desired product was obtained.