Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.C(O[CH:15]=[C:16]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:17]([O:19][CH2:20][CH3:21])=[O:18])C.O>CN(C)C=O>[CH2:20]([O:19][C:17](=[O:18])[C:16](=[CH:15][NH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1)[C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH3:21]
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Reactant: Nc1ncnc2ccccc12
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)C(=CNc1ncnc2ccccc12)C(=O)OCC
Temperature: 160 °C
Reaction time: 0.33 h
Yield: 90.1 %

Procedure:
A mixture of 4-aminoquinazoline (11.6 g) and diethyl ethoxymethylenepropanedioate (19.0 g) in N,N-dimethylformamide (40 ml) was stirred for 1 hour and 20 minutes at 160° C. and then cooled to 0° C. to precipirate crystals. To the mixture was added small volume of water with stirring. The crystals were separated by filtration, washed with water, dried overnight under reduced pressure and dissolved in ethyl acetate. The resultant solution was dried over anhydrous magnesium sulfate and recrystallized from a mixture of ethyl acetate and hexane to give crystalline diethyl[(4-quinazolinylamino)methylene]propanedioate (22.7 g).
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Br)=[CH:4][CH:3]=1.[O:10]1[CH2:14][C:13](=[O:15])[NH:12][C:11]1=[O:16].CN(C)C(N(C)C)=N.C(OCC)(=O)C>O1CCCC1>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:12]2[C:13](=[O:15])[CH2:14][O:10][C:11]2=[O:16])=[CH:4][CH:3]=1
Reactant: BrCc1ccc(Br)cc1
Reactant: O=C1COC(=O)N1
Agent: CN(C)C(=N)N(C)C
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=C1COC(=O)N1Cc1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 70.3 %

Procedure:
A solution of 1.50 g (6 mmol) of 4-bromobenzyl bromide and 0.73 g (7.2 mmol) of 1,3-oxazolidine-2,4-dione in 6 ml of tetrahydrofuran is admixed dropwise with a solution of 1.39 g (12 mmol) of 1,1,3,3-tetramethylguanidine in 6 ml of tetrahydrofuran. The mixture is stirred at ambient temperature overnight. 50 ml of ice-cold aqueous hydrochloric acid (1N) and 100 ml of ethyl acetate are added. The organic phase is separated after settling out and washed successively with 25 ml of water and 25 ml of saturated aqueous sodium chloride solution. It is dried over sodium sulphate and the filtrate is concentrated under reduced pressure. The residue is purified by chromatography on silica gel, eluting with an 80/20 mixture of cyclohexane and ethyl acetate. 1.14 g of product are obtained in the form of white crystals.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9]([O-:11])=[O:10].[Na+].[Cl:15][C:16]1[N:21]=[C:20]([CH2:22]I)[CH:19]=[C:18]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][C@@H:25]2[CH3:30])[N:17]=1>C(#N)C>[Cl:15][C:16]1[N:17]=[C:18]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][C@@H:25]2[CH3:30])[CH:19]=[C:20]([CH2:22][S:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[C:2]([F:1])([F:12])[F:13])(=[O:11])=[O:10])[N:21]=1
Reactant: C[C@H]1COCCN1c1cc(CI)nc(Cl)n1
Reactant: O=S([O-])c1ccccc1C(F)(F)F
Agent: [Na+]
Solvent: CC#N
Product: C[C@H]1COCCN1c1cc(CS(=O)(=O)c2ccccc2C(F)(F)F)nc(Cl)n1
Temperature: 80 °C
Reaction time: 3 h
Yield: 59.2 %

Procedure:
Sodium 2-(trifluoromethyl)benzenesulfinate (10.24 g, 44 mmol) was added to 2-chloro-4-(iodomethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine (13 g, 36.77 mmol), in acetonitrile (500 mL) at RT under nitrogen. The resulting mixture was stirred at 80° C. for 3 hours. Additional sodium 2-(trifluoromethyl)benzenesulfinate (10.2 g, 44 mmol) was added and reaction heated at 80° C. for 1 hour. The reaction mixture allowed to cool and concentrated in vacuo. The material was dissolved in ethyl acetate (500 mL), and washed with water (200 mL). The organic layer was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 40% ethyl acetate in isohexane, to give the desired material as an orange/cream solid (9.48 g).
Reaction SMILES: [Br:1][C:2]1[CH:28]=[N:27][C:5]2[O:6][CH2:7][C:8](=[O:26])[N:9]([CH2:10][CH2:11][N:12]3[CH2:17][CH2:16][CH:15]([NH:18]C(=O)OC(C)(C)C)[CH2:14][CH2:13]3)[C:4]=2[CH:3]=1.NC1CCN(CCN2C3C(=CC=C(C#N)C=3)C=CC2=O)CC1>>[NH2:18][CH:15]1[CH2:14][CH2:13][N:12]([CH2:11][CH2:10][N:9]2[C:8](=[O:26])[CH2:7][O:6][C:5]3[N:27]=[CH:28][C:2]([Br:1])=[CH:3][C:4]2=3)[CH2:17][CH2:16]1
Reactant: CC(C)(C)OC(=O)NC1CCN(CCN2C(=O)COc3ncc(Br)cc32)CC1
Agent: N#Cc1ccc2ccc(=O)n(CCN3CCC(N)CC3)c2c1
Product: NC1CCN(CCN2C(=O)COc3ncc(Br)cc32)CC1

Procedure:
tert-Butyl {1-[2-(7-bromo-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-1-yl)ethyl]piperidin-4-yl}carbamate (Intermediate 210) (0.85 g) was reacted as described for Intermediate 14. The crude trifluoro acetate of the title compound was used without further purification for the next step (quantitative yield).
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-])=O)=[C:6]([O:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:5]=[CH:4][N:3]=1.O.NN>[Ni].CO>[NH2:1][C:2]1[C:7]([NH2:8])=[C:6]([O:11][CH2:12][CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:5]=[CH:4][N:3]=1
Reactant: Nc1nccc(OCCc2ccccc2)c1[N+](=O)[O-]
Agent: [Ni]
Agent: NN
Solvent: CO
Solvent: O
Product: Nc1nccc(OCCc2ccccc2)c1N
Yield: 69.3 %

Procedure:
A mixture of 1.11 g of 2-amino-4-(2-phenylethoxy)-3-nitropyridine (starting material K2), 1.0 ml of hydrazine hydrate and 0.130 g of Raney nickel in 30 ml of methanol is heated under reflux until no starting material is detectable by TLC. After filtration and evaporation of the solvent the residue is chromatographed on silica gel (dichloromethane/methanol 20:1+1% triethylamine). Concentration of the pure fractions and drying in vacuo gives 0.68 g of the title compound as an oil, which crystallizes on standing (m.p. 86–87° C.). The mass spectrum shows the molecular peak MH+ at 230.2 Da.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][C@H:6]([NH:11][S:12]([CH:15]([CH3:17])[CH3:16])(=[O:14])=[O:13])[CH2:5]2.[N:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][CH2:25][CH2:26]O)[CH:19]=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[N:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][CH2:25][CH2:26][O:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[CH2:7][C@H:6]([NH:11][S:12]([CH:15]([CH3:17])[CH3:16])(=[O:14])=[O:13])[CH2:5]3)[CH:19]=1
Reactant: CC(C)S(=O)(=O)N[C@H]1Cc2ccc(O)cc2C1
Reactant: OCCCc1cccnc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CC(C)S(=O)(=O)N[C@H]1Cc2ccc(OCCCc3cccnc3)cc2C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 46.3 %

Procedure:
To a solution of N-[(2S)-5-hydroxy-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide (50 mg, 0.196 mmol, Description 3) and 3-pyridinepropanol (0.028 ml, 0.215 mmol) in dichloromethane (1 ml) was added diisopropyl azodicarboxylate (0.038 ml, 0.196 mmol) followed by triphenylphosphine (51.4 mg, 0.196 mmol). The reaction mixture was stirred at 25° C. overnight. Solvent was removed under vacuum and the crude product was purified by reverse phase chromatography using the MDAP. Relevant fractions were combined and concentrated to give 34 mg of material which was dried in the vacuum oven overnight. This solid was then dissolved in DCM (10 ml) and washed with water (2*10 ml). The organic phase was dried over MgSO4 and concentrated. This product was purified by MDAP a second time. This material was dissolved in MeOH and loaded on to a SCX cartridge, washed with MeOH and eluted with methanolic ammonia. Relevant fractions were combined and concentrated to give the title compound as a white solid (2 mg).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][N:11]3[CH:18]=2)=[CH:4][CH:3]=1.Cl.[NH2:20][OH:21].C(N(CC)CC)C>C(O)(C)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([C:16]([NH:20][OH:21])=[NH:17])=[CH:12][N:11]3[CH:18]=2)=[CH:6][CH:7]=1
Reactant: NO
Reactant: N#Cc1ccc2nc(-c3ccc(F)cc3)cn2c1
Agent: Cl
Solvent: CC(C)O
Solvent: CCN(CC)CC
Product: N=C(NO)c1ccc2nc(-c3ccc(F)cc3)cn2c1

Procedure:
2-(4-Fluoro-phenyl)-imidazo[1,2-a]pyridine-6-carbonitrile (example 52, 537 mg, 2.26 mmol), hydroxylamine hydrochloride (943.8 mg, 13.58 mmol) and triethylamine (2.19 ml, 15.84 mmol) were stirred in 40 ml of isopropanol at 90° C. for 5 hours. The solvent was removed in vacuo and water was added. The solid was filtered, washed with diluted hydrochloric acid, water and was dried. Yield: 610 mg, 99%. MS: M+H+=271.03.
Reaction SMILES: C([O-])=O.[K+].C(O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([C:15](=[O:17])[CH3:16])[CH:12]=[CH:13][CH:14]=1>[Ru].CO>[Cl:8][C:9]1[CH:10]=[C:11]([C@@H:15]([OH:17])[CH3:16])[CH:12]=[CH:13][CH:14]=1
Reactant: CC(=O)c1cccc(Cl)c1
Agent: [Ru]
Agent: O=C[O-]
Agent: [K+]
Solvent: CO
Solvent: O=CO
Product: C[C@H](O)c1cccc(Cl)c1
Temperature: 50 °C
Reaction time: 24 h
Yield: 85 %

Procedure:
A ruthenium complex RuCl[(S,S)-BnSO2dpen] (mesitylene) (1.2 mg, 0.002 mmol), potassium formate (1.0 g, 12 mmol), formic acid (138 mg, 3 mmol) and 3′-chloroacetophenone (1.55 g, 10 mmol, substrate/catalyst ratio=5000) were set in a 20 mL glass Schlenk-type reaction tube under an argon atmosphere. Methanol (6 mL) was added thereto and stirred at 50° C. for 24 hours to give (S)-1-(3′-chlorophenyl)ethanol at 85% yield and 96.5% ee optical purity.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[C:6](=[CH:12][CH2:13][CH2:14][CH2:15][O:16][Si:17]([C:30]([CH3:33])([CH3:32])[CH3:31])([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:5]2.CCC(C)[BH-](C(C)CC)C(C)CC.[K+].[Cl-].[NH4+]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[CH:6]([CH2:12][CH2:13][CH2:14][CH2:15][O:16][Si:17]([C:30]([CH3:33])([CH3:32])[CH3:31])([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[CH2:5]2
Reactant: CC(C)(C)[Si](OCCCC=C1Cc2cc(Br)ccc2C1=O)(c1ccccc1)c1ccccc1
Agent: CCC(C)[BH-](C(C)CC)C(C)CC
Agent: [Cl-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](OCCCCC1Cc2cc(Br)ccc2C1=O)(c1ccccc1)c1ccccc1
Temperature: -78 °C
Yield: 44.3 %

Procedure:
The compound (4.56 g) obtained in Example 127-3 was dissolved in THF (136.8 ml). Then, the solution was added with a 1 mol/l K-Selectride® (manufactured by Aldrich Corporation)-THF solution (8.76 ml) while being stirred at −78° C., followed by stirring at the same temperature for 1 hour. The reaction solution was added with a saturated aqueous ammonium chloride solution and then subjected to separation/extraction with chloroform. The organic layer was washed with saturated saline solution and dried with anhydrous sodium sulfate, followed by concentration under reduced pressure. The residue was purified through silica gel column chromatography (hexane/diethyl ether), thereby obtaining the subject compound (2.03 g) as a yellow oily substance.
Reaction SMILES: C(N)C([NH2:4])C.[C:6]([O:15][CH3:16])(=[O:14])[C:7]([CH2:9][C:10](OC)=[O:11])=[CH2:8]>>[C:6]([CH:7]1[CH2:8][NH:4][C:10](=[O:11])[CH2:9]1)([O:15][CH3:16])=[O:14]
Reactant: C=C(CC(=O)OC)C(=O)OC
Reactant: CC(N)CN
Product: COC(=O)C1CNC(=O)C1
Temperature: 140 °C

Procedure:
Equimolar amounts of N-allyl, N-methyl, propylene diamine prepared as described above and Dimethyl Itaconate are charged to a reaction vessel and heated slowly with agitation to 130°-150° C. After the exotherm subsides, the reaction mixture is maintained at 140° C. for 3 hours. The reaction product 1-(N-allyl, N-methyl aminopropyl)-4-carbomethoxy pyrrolidone is isolated by distillation.
Reaction SMILES: [F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][S:7][C:8]2[C:9](=[O:16])[O:10][C:11]([CH3:15])=[CH:12][C:13]=2[OH:14])=[CH:4][CH:3]=1.[OH:19]O>C(O)(=O)C.O>[F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][S:7]([C:8]2[C:9](=[O:16])[O:10][C:11]([CH3:15])=[CH:12][C:13]=2[OH:14])=[O:19])=[CH:4][CH:3]=1
Reactant: OO
Reactant: Cc1cc(O)c(SCc2ccc(F)cc2)c(=O)o1
Solvent: O
Solvent: CC(=O)O
Product: Cc1cc(O)c(S(=O)Cc2ccc(F)cc2)c(=O)o1
Yield: 60 %

Procedure:
To a solution of 3-(p-fluorobenzylthio)-4-hydroxy-6-methyl-2-pyrone (10.0 g., 0.0376 mole) in glacial acetic acid (50 ml.) was added 30% hydrogen peroxide (4.3 g., 0.0376 mole). After standing for several days the solution was diluted with water, filtered and dried, yielding 6.4 g. (60 percent) of the desired product. Recrystallization from benzene yielded the pure product as a white solid, m.p. 127°-128°C.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[Cl:9][C:10]1[C:11]2[CH:18]=[CH:17][N:16]([Si:19]([CH:26]([CH3:28])[CH3:27])([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:22])[CH3:21])[C:12]=2[N:13]=[CH:14][N:15]=1>C(Cl)Cl>[Br:1][C:18]1[C:11]2[C:10]([Cl:9])=[N:15][CH:14]=[N:13][C:12]=2[N:16]([Si:19]([CH:23]([CH3:25])[CH3:24])([CH:26]([CH3:28])[CH3:27])[CH:20]([CH3:21])[CH3:22])[CH:17]=1
Reactant: CC(C)[Si](C(C)C)(C(C)C)n1ccc2c(Cl)ncnc21
Reactant: O=C1CCC(=O)N1Br
Solvent: ClCCl
Product: CC(C)[Si](C(C)C)(C(C)C)n1cc(Br)c2c(Cl)ncnc21
Yield: 71.3 %

Procedure:
N-Bromosuccinimide (60.3 g, 338 mmol) was added to a solution of 4-Chloro-7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidine (100 g, 323 mmol) in CH2Cl2 (1 L). After 12 h 15 the reaction was quenched with saturated aqueous NaHCO3 (500 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (4×500 mL). The combined organic layers were filtered through silica gel and concentrated in vacuo. Purification by flash column chromatography (ethyl acetate/hexanes 1:99) afforded the title compound as a clear solid (89.5 g, 72%). MS: 388.8/390.8 (MH+); HPLC Rf: 9.84 min. (HPLC method 4).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11](Cl)(=[O:13])=[O:12])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[NH2:15][C:16]1[S:20][C:19]([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])=[N:18][N:17]=1.Cl>N1C=CC=CC=1>[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:15][C:16]2[S:20][C:19]([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])=[N:18][N:17]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Cl)cc1
Reactant: CCOC(=O)Cc1nnc(N)s1
Agent: Cl
Solvent: c1ccncc1
Product: CCOC(=O)Cc1nnc(NS(=O)(=O)c2ccc(NC(C)=O)cc2)s1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 76 %

Procedure:
To a solution of p-acetamidobenzenesulfonyl chloride (275 mg, 1.18 mmol) in pyridine (5 mL) was added ethyl 2-(5-amino-1,3,4-thiadiazol-2-yl)acetate (200 mg, 1.07 mmol). The reaction mixture was stirred at room temperature for 4.5 h, then 2 M HCl (10 mL) was added to quench the reaction. The mixture was extracted with ethyl acetate (3×50 mL). The organic extracts were washed with water (20 mL), brine (20 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by chromatography over silica gel (70-230 mesh) eluted with CH2Cl2:methanol 19:1 to give the product as a solid, mp 156-157° C., in 76% yield (312 mg, 0.81 mmol); 1H NMR (300 MHz, DMSO-d6) δ 1.20 (t, 3H, J=7.0 Hz), 2.07 (s, 3H), 4.06 (s, 2H), 4.15 (q, 2H, J=7.0 Hz), 7.72 (m, 4H), 10.29 (s, 1H); 13C NMR (75 MHz, DMSO-d6) δ 14.0, 24.1, 35.7, 61.3, 118.6, 127.0, 135.5, 142.9, 151.6, 167.8, 168.1, 169.0; MS (LCQ, ESI+) Calcd for C14H17N4O5S2 385.1, found 385.1 (M+H)'; HRMS (ESI+, m/z) Calcd for C14H17N4O5S2 385.0640, found 385.0638 (M+H)+.
Reaction SMILES: CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:50]1[N:55]=[CH:54][C:53]([N:56]2[CH2:61][CH2:60][CH:59]([CH2:62][C:63]#[N:64])[CH2:58][CH2:57]2)=[CH:52][CH:51]=1.[CH:65]1([N:70]2[C:74]3[N:75]=[C:76]([NH2:79])[N:77]=[CH:78][C:73]=3[C:72]3[CH:80]=[CH:81][N:82]=[C:83]([F:84])[C:71]2=3)[CH2:69][CH2:68][CH2:67][CH2:66]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:65]1([N:70]2[C:74]3[N:75]=[C:76]([NH:79][C:50]4[N:55]=[CH:54][C:53]([N:56]5[CH2:61][CH2:60][CH:59]([CH2:62][C:63]#[N:64])[CH2:58][CH2:57]5)=[CH:52][CH:51]=4)[N:77]=[CH:78][C:73]=3[C:72]3[CH:80]=[CH:81][N:82]=[C:83]([F:84])[C:71]2=3)[CH2:66][CH2:67][CH2:68][CH2:69]1
Reactant: Nc1ncc2c3ccnc(F)c3n(C3CCCC3)c2n1
Reactant: N#CCC1CCN(c2ccc(Cl)nc2)CC1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Product: N#CCC1CCN(c2ccc(Nc3ncc4c5ccnc(F)c5n(C5CCCC5)c4n3)nc2)CC1
Temperature: 105 °C
Reaction time: 8 h
Yield: 54.6 %

Procedure:
To tris(dibenzylideneacetone)dipalladium (0) (0.0147 g, 0.0160 mmol), xantphos (0.0186 g, 0.0321 mmol), Cs2CO3 (0.0975 g, 0.299 mmol), 2-(1-(6-chloropyridin-3-yl)piperidin-4-yl)acetonitrile (0.0504 g, 0.214 mmol), and compound 245 (0.0580 g, 0.214 mmol) was added degassed (Ar) dioxane (1.0 mL). The reaction was stirred at 105° C. overnight. After 16 h, the reaction was cooled to room temperature and loaded directly onto silica gel. Crystallization from THF and HCl salt formation provided compound 252 (55 mg). 1H NMR (400 MHz, DMSO-d6) δ 1.43 (d, J=10.56 Hz, 2 H) 1.66-1.81 (m, 2 H) 1.86 (d, J=11.35 Hz, 3 H) 2.05 (d, J=6.26 Hz, 2 H) 2.15 (br. s., 2 H) 2.19-2.31 (m, 2 H) 2.59 (d, J=5.87 Hz, 2 H) 2.85 (t, J=11.74 Hz, 2 H) 3.75 (d, J=12.13 Hz, 2 H) 5.53 (quin, J=9.10 Hz, 1 H) 7.68 (d, J=9.39 Hz, 1 H) 8.00 (br. s., 1 H) 8.15 (d, J=5.09 Hz, 1 H) 8.20 (dd, J=9.39, 2.74 Hz, 1 H) 8.30 (dd, J=4.89, 2.93 Hz, 1 H) 9.55 (s, 1 H) 11.80 (br. s., 1 H) ppm.
Reaction SMILES: CS(O)(=O)=O.[C:6]1([CH3:16])[C:7](S(O)(=O)=O)=[CH:8][CH:9]=[CH:10][CH:11]=1.S(=O)(=O)(O)O.[C:22]([OH:25])(=O)[CH3:23]>>[CH:11]1[C:6]2[CH2:16][C:23]3[C:22](=[CH:7][CH:6]=[CH:11][CH:10]=3)[O:25][C:7]=2[CH:8]=[CH:9][CH:10]=1
Reactant: Cc1ccccc1S(=O)(=O)O
Reactant: CC(=O)O
Agent: CS(=O)(=O)O
Agent: O=S(=O)(O)O
Product: c1ccc2c(c1)Cc1ccccc1O2

Procedure:
The compounds according to the present invention can be synthesized by reference to the methods described in Journal of the American Chemical Society, Vol. 72, pages 3651 to 3655 or similar methods. A nuclear-substituted hydroquinone, as a starting material, is dissolved in a weak acidic carboxylic acid solvent such as acetic acid in an amount of about 10-2 mol/l to 5 mol/l and, a strong acidic compound such as hydrochloric acid is added to the solution in an amount of about 0.1 to 5 times w/w (weight ratio) based on the starting material. A condensing agent such as formalin, acetone or aldehydes is added to the solution in an amount of about 0.5 to 5 moles based on the starting material and the resulting solution is stirred at about 10° to 100° C. to obtain a diarylmethane compound. The resulting diarylmethane compound is dissolved in a solvent such as a hydrocarbon solvent (for example, benzene, toluene), an alcohol solvent (for example, ethanol, propanol), or an organic acid (for example, acetic acid) and, the solution is heated with refluxing in the presence or non-presence of a strong acid (for example, methane sulfonic acid, toluene sulfonic acid, sulfuric acid) in an amount of about 0.1 to 1.0 mole based on the starting material to obtain an objective compound of a xanthene compound. Specific synthesis examples are illustrated below for reference.
Reaction SMILES: [NH2:1][S:2]([C:5]1[CH:6]=[C:7]([CH:18]=[CH:19][C:20]=1[N:21]1[CH2:25][CH2:24][CH2:23][C:22]1=O)[O:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([OH:14])=[O:13])(=[O:4])=[O:3].C1CCN2C(=NCCC2)CC1.Cl>C1COCC1>[O:3]=[S:2]1(=[O:4])[C:5]2[CH:6]=[C:7]([O:8][C:9]3[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=3)[C:12]([OH:14])=[O:13])[CH:18]=[CH:19][C:20]=2[N:21]2[CH2:25][CH2:24][CH2:23][C:22]2=[N:1]1
Reactant: NS(=O)(=O)c1cc(Oc2cccc(C(=O)O)c2)ccc1N1CCCC1=O
Agent: Cl
Solvent: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Product: O=C(O)c1cccc(Oc2ccc3c(c2)S(=O)(=O)N=C2CCCN23)c1

Procedure:
A suspension of the product obtained in Step B (850 mg, 2.26 mmol) in 25 ml of THF in the presence of 675 μl (4.52 mmol) of DBU is refluxed for 1 hour. It is allowed to return to ambient temperature and is acidified with 1N HCl, and the white precipitate corresponding to the title product is filtered off.
Reaction SMILES: [OH-].[K+].[CH3:3][SH-:4][C:5](=[N:7][OH:8])[CH3:6].[CH3:9][N:10]([S:14][N:15]([CH3:17])[CH3:16])[C:11](F)=[O:12]>C1CC2OCCOCCOC3C(OCCOCCOC2CC1)CCCC3.C1C=CC=CC=1>[CH3:9][N:10]([S:14][N:15]([CH3:17])[CH3:16])[C:11]([O:8][N:7]=[C:5]([S:4][CH3:3])[CH3:6])=[O:12]
Reactant: CN(C)SN(C)C(=O)F
Reactant: C[SH-]C(C)=NO
Agent: C1CCC2OCCOCCOC3CCCCC3OCCOCCOC2C1
Agent: [K+]
Agent: [OH-]
Solvent: c1ccccc1
Product: CSC(C)=NOC(=O)N(C)SN(C)C
Reaction time: 1 h
Yield: 77.4 %

Procedure:
Powdered potassium hydroxide (3.3 g), 5.2 g of S-methyl-N-hydroxythioacetimidate, 0.1 g dicyclohexyl-18-crown-6, and 200 ml of benzene were stirred at room temperature for 0.5 hr. Then 8.0 g of N-methyl-N-(dimethylaminosulfenyl)carbamoyl fluoride was added slowly at 28° C. The reaction temperature was held at 28°-32° C. with external cooling. The mixture was stirred for 1 hr., and then was washed with water until neutral. After drying (MgSO4), the solution was concentrated in vacuo, and the residue was recrystallized from diisopropyl ether to give 9.0 g (76 percent yield) of S-methyl N-[N'-methyl-N'-(dimethylaminosulfenyl)carbamoyloxy]Thioacetimidate, m.p. 68°-70° C.
Reaction SMILES: [C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[K].Br[CH:14]([OH:16])[CH3:15].CN(C)C=O>>[C:1]1(=[O:11])[N:5]([CH2:15][CH2:14][OH:16])[C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12
Reactant: CC(O)Br
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CCO
Temperature: 70 °C
Reaction time: 12 h
Yield: 44.12 %

Procedure:
Potassium phthalimide 2 (2.7 g, 14.6 mmol) was added to a solution of bromoethanol 1 in N,N-dimethylformamide (12 mL, 14.1 mmol). After stirring for 12 h at 70° C., the mixture was concentrated and then diluted with dichloromethane (100 mL). After removal of solids by filtration, the organic layer was washed with water, dried, and concentrated. The concentrate was purified by flash column chromatography (3:2 to 2:3 hexane-ethyl acetate) to give compound 3 as a white solid (1.19 g, 44.12%) having a RF of 0.22 (3:2 hexane-ethyl acetate). See FIG. 2.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]3[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=3)=[CH:7][C:6]=2[CH:17]=1.[C:18]([OH:28])(=[O:27])[C:19]1[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=1.CC(C)([O-])C.[K+]>CN(C)C=O>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]3[CH:15]=[CH:14][C:13]([CH:16]=[CH:23][C:22]4[CH:25]=[CH:26][C:19]([C:18]([OH:28])=[O:27])=[CH:20][CH:21]=4)=[CH:12][CH:11]=3)=[CH:7][C:6]=2[CH:17]=1
Reactant: O=Cc1ccc(C(=O)O)cc1
Reactant: Cc1ccc(-c2cc3cc(C)ccc3o2)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1ccc2oc(-c3ccc(C=Cc4ccc(C(=O)O)cc4)cc3)cc2c1

Procedure:
Proceeding in a manner similar to that used in Example 1, 5-methyl-2-(p-tolyl)benzofuran (2.22 g; 0.01 mole) was interacted with 2.25 g (0.01 mole) of the anil derivative of terephthalaldehydic acid in the presence of 6.72 g (0.06 mole) of potassium tert-butoxide in 150 ml of dimethylformamide. The product thus produced was sublimed to obtain 5-methyl-2-[4-(4-carboxystyryl)phenyl ]benzofuran, melting at 355°-358°C. The wavelength of maximum excitation of this compound was 374 nm and the wavelength of maximum emission was 437 nm.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[NH:10]1[C:18](=[O:19])[C:16](=[O:17])[C:14](=[O:15])[NH:13][C:11]1=[O:12]>>[OH:17][C:16]1([C:2]2[S:1][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=2)[C:14](=[O:15])[NH:13][C:11](=[O:12])[NH:10][C:18]1=[O:19]
Reactant: c1ccc2scnc2c1
Reactant: O=C1NC(=O)C(=O)C(=O)N1
Product: O=C1NC(=O)C(O)(c2nc3ccccc3s2)C(=O)N1

Procedure:
By the procedure of Example 38, benzthiazole (2.7 g., 0.02 moles) was converted to its 2-lithio derivative and then reacted with anhydrous alloxan to yield title product, initially isolated as an oil. The latter was crystallized from ether-hexane [2.2 g.; Rf 0.55 (1:1 ethyl acetate:hexane/5% acetic acid)].