Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]=[C:2]1[N:6]2[CH2:7][CH2:8][NH:9][CH2:10][C@H:5]2[CH2:4][N:3]1[CH2:11][C:12]([CH3:17])(C)[C:13]([OH:15])=[O:14].F[C:19](F)(F)[C:20](O)=O.N[C@@H]1CCC[C@@H]1C(OCC)=O>>[O:1]=[C:2]1[N:6]2[CH2:7][CH2:8][NH:9][CH2:10][C@H:5]2[CH2:4][N:3]1[C@@H:11]1[CH2:20][CH2:19][CH2:17][C@@H:12]1[C:13]([OH:15])=[O:14]
Reactant: O=C(O)C(F)(F)F
Reactant: CC(C)(CN1C[C@@H]2CNCCN2C1=O)C(=O)O
Agent: CCOC(=O)[C@H]1CCC[C@H]1N
Product: O=C(O)[C@H]1CCC[C@H]1N1C[C@@H]2CNCCN2C1=O

Procedure:
Compound 50-A was prepared in analogy to compound Q in Example 19 by using ethyl (1S,2R)-2-aminocyclopentanecarboxylate trifluoroacetic acid salt (compound 50-B) instead of ethyl 3-amino-2,2-dimethyl-propanoate hydrochloride salt.
Reaction SMILES: [Cl-].[Cl-].[Cl:3][CH2:4][SiH:5]=[Zr+2:6]([CH:12]1[CH:16]=[CH:15][CH:14]=[CH:13]1)[CH:7]1[CH:11]=[CH:10][CH:9]=[CH:8]1>C1(C)C=CC=CC=1>[Cl:3][CH2:4][SiH:5]=[Zr:6]([CH:7]1[CH:8]=[CH:9][CH:10]=[CH:11]1)[CH:12]1[CH:16]=[CH:15][CH:14]=[CH:13]1
Reactant: ClC[SiH]=[Zr+2](C1C=CC=C1)C1C=CC=C1
Agent: [Cl-]
Solvent: Cc1ccccc1
Product: ClC[SiH]=[Zr](C1C=CC=C1)C1C=CC=C1
Temperature: 25 °C

Procedure:
In a flask of 250 ml of capacity it was weighed 5 g of silica modified with MAO commercialized by Witco with a 24.7% weight of Al and it was added 120 ml of toluene. Then, it was added a solution in toluene of (chloromethylsilandiyl)bis(cyclopentadienyl) zirconium dichloride (0.255 mmol of Zr). The reaction mixture was maintained under mechanic stirring at room temperature. After 2 hours of reaction the resulting solid was isolated by filtration and washed with consecutive fractions of toluene at 700° C. up to a total volume of 500 ml. The solid was finally dried under vacuum for 24 hours. The Zr and Al content in the catalyst was determined by ICP and it was 0.36% and 18.1% by weight respectively.
Reaction SMILES: N1C(C)=CC(C)=CC=1C.[CH3:10][N:11]1[CH:15]=[CH:14][C:13]([NH:16][C:17]([C:19]2[CH:29]=[C:28]([O:30][C:31]3[CH:36]=[CH:35][C:34]([S:37]([CH3:40])(=[O:39])=[O:38])=[CH:33][CH:32]=3)[C:22]3[CH2:23][CH:24]([CH2:26]O)[O:25][C:21]=3[CH:20]=2)=[O:18])=[N:12]1.CCN(S(F)(F)[F:47])CC>C(Cl)Cl>[CH3:10][N:11]1[CH:15]=[CH:14][C:13]([NH:16][C:17]([C:19]2[CH:29]=[C:28]([O:30][C:31]3[CH:36]=[CH:35][C:34]([S:37]([CH3:40])(=[O:39])=[O:38])=[CH:33][CH:32]=3)[C:22]3[CH2:23][CH:24]([CH2:26][F:47])[O:25][C:21]=3[CH:20]=2)=[O:18])=[N:12]1
Reactant: CCN(CC)S(F)(F)F
Reactant: Cn1ccc(NC(=O)c2cc(Oc3ccc(S(C)(=O)=O)cc3)c3c(c2)OC(CO)C3)n1
Solvent: Cc1cc(C)nc(C)c1
Solvent: ClCCl
Product: Cn1ccc(NC(=O)c2cc(Oc3ccc(S(C)(=O)=O)cc3)c3c(c2)OC(CF)C3)n1
Reaction time: 8 h
Yield: 18.4 %

Procedure:
A solution of 2,4,6-collidine (0.0311 mL, 0.235 mmol) and 2-hydroxymethyl-4-(4-methanesulfonyl-phenoxy)-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (200) (50 mg, 0.11 mmol) in CH2Cl2 (3 mL) was cooled to −15° C. DAST (0.0307 mL, 0.235 mmol) was added drop wise. The mixture was stirred at −15° C. to room temperature overnight, then quenched with MeOH at 0° C., concentrated, and purified by column chromatography eluting with 25-75% EtOAc in hexanes to give a white solid (9 mg, 18% yield). 1H NMR (400 MHz, CDCl3) δ 8.48 (s, 1 H) 7.78-8.03 (m, 2 H) 7.20-7.34 (m, 2 H) 7.02-7.20 (m, 3 H) 6.77 (d, J=2.27 Hz, 1 H) 5.01-5.19 (m, 1 H) 4.42-4.78 (m, 2 H) 3.79 (s, 3 H) 3.25 (dd, J=16.55, 9.73 Hz, 1 H) 3.08 (s, 3 H) 2.99-3.06 (m, 1 H); LCMS for C21H20FN3O5S m/z 446.00 (M+H+).
Reaction SMILES: [NH2:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([OH:12])=[C:4]([C:13]2[NH:18][C:17]3[CH:19]=[CH:20][C:21]([O:23][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:22][C:16]=3[S:15](=[O:32])(=[O:31])[N:14]=2)[C:3]1=[O:33].[CH:34]1([CH:37]=O)[CH2:36][CH2:35]1>CN(C)C(=O)C>[CH2:24]([O:23][C:21]1[CH:20]=[CH:19][C:17]2[NH:18][C:13]([C:4]3[C:3](=[O:33])[N:2]([N:1]=[CH:37][CH:34]4[CH2:36][CH2:35]4)[C:11]4[C:6]([C:5]=3[OH:12])=[CH:7][CH:8]=[CH:9][CH:10]=4)=[N:14][S:15](=[O:32])(=[O:31])[C:16]=2[CH:22]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: Nn1c(=O)c(C2=NS(=O)(=O)c3cc(OCc4ccccc4)ccc3N2)c(O)c2ccccc21
Reactant: O=CC1CC1
Solvent: CC(=O)N(C)C
Product: O=c1c(C2=NS(=O)(=O)c3cc(OCc4ccccc4)ccc3N2)c(O)c2ccccc2n1N=CC1CC1
Temperature: 165 °C
Yield: 84.3 %

Procedure:
The product of Example 304F (0.800 g, 1.73 mmol) and cyclopropane carboxaldehyde (1.60 mL, 20.76 mmol) in N,N-dimethylacetamide (2 mL) were reacted at 120° C. for 60 minutes in a microwave reactor in a sealed tube. The reaction was concentrated under a stream of nitrogen warmed through a manifold heated to 165° C. The resulting residue was triturated with diethyl ether and filtered to give the title compound (0.750 g, 84%).
Reaction SMILES: CC(CCCC(C)CCCC(C)CCCC(C)C)=CCC1C(C)=C([N:16]=[N:17][C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=2)C2C(=CC=CC=2)C=1O.C1(C)C=CC=CC=1.CO>[N+](C1C=CC=CC=1CCCCCCCCOCCCCCCCCC1C=CC=CC=1[N+]([O-])=O)([O-])=O>[N+:24]([C:21]1[CH:20]=[CH:19][C:18]([NH:17][NH2:16])=[CH:23][CH:22]=1)([O-:26])=[O:25]
Reactant: CC(=CCc1c(C)c(N=Nc2ccc([N+](=O)[O-])cc2)c2ccccc2c1O)CCCC(C)CCCC(C)CCCC(C)C
Agent: O=[N+]([O-])c1ccccc1CCCCCCCCOCCCCCCCCc1ccccc1[N+](=O)[O-]
Solvent: Cc1ccccc1
Solvent: CO
Product: NNc1ccc([N+](=O)[O-])cc1

Procedure:
2-(3,7,11,15-tetramethyl-2-hexadecenyl)-3-methyl-4-[(4-nitrophenyl)azo]-1-naphthol, TLC, silica gel 60 (Merck), mobile solvent: toluol/methanol=50:1; Rf =0.22, from 4-nitrophenylhydrazine, Transmission spectra at an acid or alkaline pH in o-nitrophenyloctyl ether yield λmax values of 455 or 637 nm.
Reaction SMILES: [CH:1]([N:3]=[C:4]=[O:5])=[CH2:2].C(OCC)(=O)C.[C:12]([OH:16])([CH3:15])([CH3:14])[CH3:13].C([O-])(=O)CCCCCCCCCCC.C([O-])(=O)CCCCCCCCCCC.C([Sn+2]CCCC)CCC>[Cl-].[Na+].O>[CH:1]([NH:3][C:4](=[O:5])[O:16][C:12]([CH3:15])([CH3:14])[CH3:13])=[CH2:2]
Reactant: C=CN=C=O
Reactant: CC(C)(C)O
Agent: CCCCCCCCCCCC(=O)[O-]
Agent: CCCC[Sn+2]CCCC
Agent: [Cl-]
Solvent: O
Solvent: CCOC(C)=O
Product: C=CNC(=O)OC(C)(C)C

Procedure:
69 parts of vinyl isocyanate and 70 parts of ethyl acetate are initially taken in a reaction vessel equipped with a high-efficiency condenser (with cooling brine), a stirrer, a thermometer and a feed Vessel. 74 parts of tert.-butanol, 73 parts of ethyl acetate and 0.01% of dibutyl-tin dilaurate are added in the course of 1 hour at 40° C., after which the mixture is allowed to react for a further 10 hours at this temperature. A pale yellow clear solution is formed. Content of blocked isocyanate groups: 14.7%.
Reaction SMILES: I[C:2]1[CH:11]=[CH:10][C:5]([O:6][CH2:7][CH2:8][OH:9])=[C:4]([CH3:12])[CH:3]=1.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:21]=[CH:22][C:23]([C:26]#[CH:27])=[N:24][CH:25]=2)=[CH:16][CH:15]=1>N1CCCCC1>[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2[CH:21]=[CH:22][C:23]([C:26]#[C:27][C:2]3[CH:11]=[CH:10][C:5]([O:6][CH2:7][CH2:8][OH:9])=[C:4]([CH3:12])[CH:3]=3)=[N:24][CH:25]=2)=[CH:18][CH:19]=1
Reactant: Cc1cc(I)ccc1OCCO
Reactant: C#Cc1ccc(-c2ccc(Cl)cc2)cn1
Solvent: C1CCNCC1
Product: Cc1cc(C#Cc2ccc(-c3ccc(Cl)cc3)cn2)ccc1OCCO

Procedure:
Prepared analogously to Example 4b from 380 mg (1.37 mmol) 2-(4-iodo-2-methyl-phenoxy)-ethanol and 292 mg (1.37 mmol) 5-(4-chloro-phenyl)-2-ethynyl-pyridine in 38 mL piperidine.
Reaction SMILES: C(O[C:9](=O)[N:10]([CH2:12][CH2:13][N:14]1[CH:18]=[C:17]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:20]=2)[N:16]=[C:15]1[CH:30]1[CH2:35][CH2:34][N:33]([C:36]2[C:37]3[CH2:44][C:43](=[O:45])[NH:42][C:38]=3[N:39]=[CH:40][N:41]=2)[CH2:32][CH2:31]1)C)C1C=CC=CC=1.[ClH:47]>>[ClH:47].[ClH:47].[ClH:47].[F:25][C:22]1[CH:23]=[CH:24][C:19]([C:17]2[N:16]=[C:15]([CH:30]3[CH2:31][CH2:32][N:33]([C:36]4[C:37]5[CH2:44][C:43](=[O:45])[NH:42][C:38]=5[N:39]=[CH:40][N:41]=4)[CH2:34][CH2:35]3)[N:14]([CH2:13][CH2:12][NH:10][CH3:9])[CH:18]=2)=[CH:20][C:21]=1[C:26]([F:27])([F:28])[F:29]
Reactant: CN(CCn1cc(-c2ccc(F)c(C(F)(F)F)c2)nc1C1CCN(c2ncnc3c2CC(=O)N3)CC1)C(=O)OCc1ccccc1
Agent: Cl
Product: CNCCn1cc(-c2ccc(F)c(C(F)(F)F)c2)nc1C1CCN(c2ncnc3c2CC(=O)N3)CC1
Temperature: 50 °C

Procedure:
Dissolve (2-{4-(4-fluoro-3-trifluoromethyl-phenyl)-2-[1-(6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidin-4-yl]-imidazol-1-yl}-ethyl)-methyl-carbamic acid benzyl ester (213 μmol; 136 mg) in conc. HCl (8 mL) and heat to 50° C. for 60 min. Cool to RT, extract 2 times with ether, evaporate the organic layer, co-evaporate the residue 2 times with MeOH, co-evaporate the residue 2 times with DCM/MeOH to provide 129.6 mg (0.21 mmol; 99%) of the title compound. MS (ES+): m/z=504 (M+H).
Reaction SMILES: [C:1]([NH:4][C:5]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=1)(C(OCC)=O)[C:6]([O:8]CC)=[O:7])(=[O:3])[CH3:2].[OH-].[Na+]>CC(C)=O>[C:1]([NH:4][CH:5]([CH2:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]([F:24])([F:25])[F:26])=[CH:21][CH:22]=1)[C:6]([OH:8])=[O:7])(=[O:3])[CH3:2]
Reactant: CCOC(=O)C(Cc1ccc(C(F)(F)F)cc1)(NC(C)=O)C(=O)OCC
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Product: CC(=O)NC(Cc1ccc(C(F)(F)F)cc1)C(=O)O
Yield: 75 %

Procedure:
To a solution of diethyl 2-acetamido-2-(4-(trifluoromethyl)benzyl)malonate (LXII) (theoretical 0.125 mole) in acetone (400 mL) was added aq. 2 M NaOH (400 mL). The mixture was refluxed overnight before the solvent was removed under reduced pressure. The residue was taken up in water, washed with hexane (3×), acidified to pH=1 and filtered to produce 2-acetamido-3-(4-(trifluoromethyl)phenyl)propanoic acid (LXIII) as a white solid (25.8 g, 93.7 mmol, 75% yield after two steps).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([CH3:11])=[CH:7]2.[OH-].[K+].Br[CH2:15][CH2:16][CH2:17][S:18][CH3:19]>COCCOCCN(CCOCCOC)CCOCCOC>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:15][CH2:16][CH2:17][S:18][CH3:19])[C:8]([CH3:11])=[CH:7]2
Reactant: CSCCCBr
Reactant: Cc1cc2cccc(Cl)c2[nH]1
Agent: COCCOCCN(CCOCCOC)CCOCCOC
Agent: [K+]
Agent: [OH-]
Product: CSCCCn1c(C)cc2cccc(Cl)c21
Reaction time: 2 h
Yield: 81.4 %

Procedure:
1.5 g of 7-chloro-2-methyl-1H-indole are mixed with stirring with 1.1 g of ground potassium hydroxide and 0.2 g of TDA-1. The mixture is left stirring for 2 hours at AT, then 3.1 g of 1-bromo-3-methylsulphanylpropane are added dropwise and the mixture is heated at reflux for 24 hours. Ground potassium hydroxide (0.5 g), TDA-1 (0.1 g) and 1.6 g of 1-bromo-3-methylsulphanylpropane are again added. After heating at reflux for 9 hours, 1.6 g of 1-bromo-3-methylsulphanylpropane are again added and the mixture is heated at reflux for 24 hours. The mixture is allowed to return to AT and is then extracted with toluene. The organic phase is washed with a 10% HCl solution, with water and then a saturated NaCl solution. It is dried and evaporated and then the residue is chromatographed on silica while eluting with a cyclohexane/toluene (50/50, v/v) mixture. 1.87 g of the expected compound are obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[NH:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[C:22]([C:26]([O:28]C)=[O:27])=[CH:21][CH:20]=[CH:19]2.[OH-].[Na+]>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[NH:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[C:22]([C:26]([OH:28])=[O:27])=[CH:21][CH:20]=[CH:19]2
Reactant: COC(=O)c1cccc2cc(Nc3ncnc4cc(OC)c(OC)cc34)ccc12
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: COc1cc2ncnc(Nc3ccc4c(C(=O)O)cccc4c3)c2cc1OC

Procedure:
Methyl 6-(6,7-dimethoxyquinazolin-4-ylamino)-1-naphthoate (500 mg, 1.28 mmol) was stirred with 6N NaOH (10 mL) and MeOH (10 mL) at 70° C. for 3 h. The mixture was poured into 6N HCl/ice and the pH adjusted to 7. The solid was collected and rinsed with water, stirred with MeOH (5 mL) and filtered again. The title compound was obtained (crude) as a yellow solid.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([NH2:7])[CH2:3][CH2:2]1.[N-:8]=[C:9]=[O:10].[K+].[Na+].[Cl-]>O>[O:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:9]([NH2:8])=[O:10])[CH2:3][CH2:2]1
Reactant: NC1CCOCC1
Reactant: [N-]=C=O
Agent: [Cl-]
Agent: [K+]
Agent: [Na+]
Solvent: O
Product: NC(=O)NC1CCOCC1
Temperature: 25 °C
Yield: 18 %

Procedure:
A mixture of tetrahydro-2H-pyran-4-amine (5.0 g, 49.4 mmol, 1 equiv.) and potassium isocyanate (4.0 g, 49.5 mmol, 1.0 equiv.) was refluxed in H2O (50 mL) overnight. The reaction was cooled to room temperature and excess NaCl was added to help saturate the aqueous layer. The precipitate was isolated by filtration to provide the desired product (1.28 g, 8.88 mmol). The aqueous layer was washed with EtOAc (3×15 mL) and then was concentrated and azeotroped with toluene (3×100 mL). The resulting solid was suspended in 1:4 MeOH:EtOAc (100 mL) and filtered a total of four times. The combined organics were concentrated under reduced pressure and combined with the isolated precipitate to provide 5.01 g (70%) of the title compound. LC/MS: m/z (ES+) 145 (M+H)+. 1H NMR (400 MHz, DMSO-d6): δ ppm 6.14 (d, J=7.5 Hz, 1H), 5.47 (s, 2H), 3.85 (dt, J=11.6, 3.6 Hz, 2H), 3.65-3.52 (m, 1H), 3.38 (td, J=11.4, 2.2 Hz, 2H), 1.80-1.72 (m, 2H), 1.42-1.27 (m, 2H).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8](=[O:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:6][CH:5]=[CH:4][C:3]=1[CH:16](SC)[C:17]([NH:19][CH3:20])=[O:18]>O1CCCC1.[Ni]>[NH2:1][C:2]1[C:7]([C:8](=[O:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:16][C:17]([NH:19][CH3:20])=[O:18]
Reactant: CNC(=O)C(SC)c1cccc(C(=O)c2ccccc2)c1N
Agent: [Ni]
Solvent: C1CCOC1
Product: CNC(=O)Cc1cccc(C(=O)c2ccccc2)c1N
Yield: 89 %

Procedure:
A solution of 22.5 g (0.072 mol) of 2-amino-3-benzoyl-α-(methylthio)-N-methylphenylacetamide in 400 ml of tetrahydrofuran was treated with 160 g of wet Raney nickel (washed 3 times with water and 3 times with tetrahydrofuran) for 10 minutes. The mixture was filtered and the filtrate was concentrated. The residue was crystallized from isopropyl alcohol to give 17.2 g (89%) of yellow needles, m.p. 145°-146° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[N:5]=[C:4]([N:15]2[CH2:19][CH2:18][CH2:17][C@@H:16]2[CH3:20])[N:3]=1.[Br:21][C:22]1[CH:23]=[C:24]([Cl:35])[C:25]([N:28]2[CH2:33][CH2:32][NH:31][C@H:30]([CH3:34])[CH2:29]2)=[N:26][CH:27]=1.C([O-])(O)=O.[Na+]>CCO>[Br:21][C:22]1[CH:23]=[C:24]([Cl:35])[C:25]([N:28]2[CH2:33][CH2:32][N:31]([C:2]3[CH:7]=[C:6]([C:8]4[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=4)[N:5]=[C:4]([N:15]4[CH2:19][CH2:18][CH2:17][C@@H:16]4[CH3:20])[N:3]=3)[C@H:30]([CH3:34])[CH2:29]2)=[N:26][CH:27]=1
Reactant: C[C@@H]1CN(c2ncc(Br)cc2Cl)CCN1
Reactant: C[C@H]1CCCN1c1nc(Cl)cc(-c2ccc(F)cc2)n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: C[C@@H]1CN(c2ncc(Br)cc2Cl)CCN1c1cc(-c2ccc(F)cc2)nc(N2CCC[C@@H]2C)n1

Procedure:
Heat a mixture of 4-chloro-6-(4-fluoro-phenyl)-2-(2-(S)-methyl-pyrrolidin-1-yl)-pyrimidine (1.30 g, 4.44 mmol), 1-(5-bromo-3-chloro-pyridin-2-yl)-3-(R)-methyl-piperazine (1.2 g), and NaHCO3 (0.71 g, 8.46 mmol) in EtOH at 50° C. for 20 h. Concentrate under reduced pressure and partition between EtOAc and brine. Dry the organic layer (Na2SO4) and concentrate under reduced pressure. Purify the residue by flash column eluting with EtOAc-Hexanes (1:4) to afford the title compound as a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[F:8].C(N(CC)CC)C.[CH3:17][N:18]1[C:22]([C:23](Cl)=[O:24])=[CH:21][C:20]([CH3:26])=[N:19]1>O1CCCC1.O>[F:8][C:7]1[CH:6]=[CH:5][C:4]([OH:9])=[CH:3][C:2]=1[NH:1][C:23]([C:22]1[N:18]([CH3:17])[N:19]=[C:20]([CH3:26])[CH:21]=1)=[O:24]
Reactant: Nc1cc(O)ccc1F
Reactant: Cc1cc(C(=O)Cl)n(C)n1
Solvent: O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1cc(C(=O)Nc2cc(O)ccc2F)n(C)n1
Yield: 100 %

Procedure:
To a solution of 3-amino-4-fluorophenol (5.05 g, 39.7 mmol) and triethylamine (5.77 mL, 41.7 mmol) in tetrahydrofuran (30 mL) was added dropwise with stirring under ice-cooling a solution of 1,3-dimethyl-1H-pyrazole-5-carbonyl chloride (6.61 g, 41.7 mmol) in tetrahydrofuran (10 mL), and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with water and extracted with ethyl acetate (×3). The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was collected by filtration and washed with ethyl acetate-hexane to give the title compound (9.89 g, 99%) as a white solid.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[C:12](=[O:24])[N:13]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[N:14]([CH3:17])[C:15]=2[CH3:16])=[O:10])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].Cl[C:32]1[CH:37]=[CH:36][N:35]=[C:34]([C:38]([NH2:40])=[O:39])[CH:33]=1>CN(C=O)C>[CH3:17][N:14]1[C:15]([CH3:16])=[C:11]([C:9]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([O:1][C:32]3[CH:37]=[CH:36][N:35]=[C:34]([C:38]([NH2:40])=[O:39])[CH:33]=3)=[CH:3][CH:4]=2)=[O:10])[C:12](=[O:24])[N:13]1[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: NC(=O)c1cc(Cl)ccn1
Reactant: Cc1c(C(=O)Nc2ccc(O)cc2)c(=O)n(-c2ccccc2)n1C
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1c(C(=O)Nc2ccc(Oc3ccnc(C(N)=O)c3)cc2)c(=O)n(-c2ccccc2)n1C
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 72.9 %

Procedure:
To a solution of N-(4-hydroxyphenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (1.80 g, 5.57 mmol) in DMF (35 mL) was added potassium tert-butoxide (1.87 g, 16.7 mmol). The solution was stirred at rt for 20 minutes, followed by the addition of 4-chloropicolinamide (1.046 g, 6.68 mmol). The reaction was heated at 120° C. for 3 hours, then concentrated to 2 mL in vacuo, and diluted with water (60 mL). The precipitate was obtained by filtration, washed with water (5 mL) and dried. The crude product was washed with DCM (20 mL) to give the title compound as a brown solid (1.8 g, 73%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-])=O)=[C:6]([CH3:11])[CH:5]=[C:4]([Cl:12])[N:3]=1.O.O.[Sn](Cl)Cl.[OH-].[Na+].[C:20](O)(=O)[CH3:21].C(=O)([O-])[O-].[Na+].[Na+].N>C(O)C.C(OCC)(=O)C>[Cl:12][C:4]1[N:3]=[C:2]2[N:1]=[C:20]([CH3:21])[NH:8][C:7]2=[C:6]([CH3:11])[CH:5]=1
Reactant: Cc1cc(Cl)nc(N)c1[N+](=O)[O-]
Reactant: CC(=O)O
Agent: Cl[Sn]Cl
Agent: N
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CCO
Product: Cc1nc2nc(Cl)cc(C)c2[nH]1
Temperature: 75 °C
Reaction time: 2 h

Procedure:
2-Amino-6-chloro-4-methyl-3-nitropiridine (1.2 g, 6.40 mmol) synthesized according to the method described in WO98/02442 was dissolved in ethanol (65 mL), and tin(II) chloride dihydrate (4.33 g, 19.2 mmol) was added, followed by stirring at 75° C. for 2 hours. The reaction mixture was diluted with ethyl acetate and was added with 3 mol/L aqueous sodium hydroxide solution. The unsoluble material was filtered out through Celite, and washed with ethyl acetate. The filtrate was sequentially washed with water, saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Next, polyphosphoric acid (15.3 g) and acetic acid (1.72 mL, 30.0 mmol) was added to the residue, and was stirred for 80° C. for 3 hours. The reaction mixture was moved to ice water and sodium carbonate (11.4 g, 0.108 mol) was added in a little portion while stirring. Then, 28% aqueous ammonia solution was added to the residue to control the pH to 9 and the mixture was stirred for 1 hour. Precipitated crude crystals were collected by filtration, and were washed with water, and the obtained crystals were dried in vacuo at 40° C. overnight to obtain Compound P38 (395 mg, 34%).
Reaction SMILES: Br[C:2]1[CH:15]=[CH:14][C:13]2[C:4](=[C:5]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:6]3[C:11]([C:12]=2[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH:3]=1.[C:28]1([NH:38][C:39]2[CH:40]=[CH:41][C:42]3[N:43]([C:52]4[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=4)[C:44]4[C:49]([C:50]=3[CH:51]=2)=[CH:48][CH:47]=[CH:46][CH:45]=4)[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=[CH:30][CH:29]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1(C)C=CC=CC=1>[C:28]1([N:38]([C:2]2[CH:15]=[CH:14][C:13]3[C:4](=[C:5]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:6]4[C:11]([C:12]=3[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:10][CH:9]=[CH:8][CH:7]=4)[CH:3]=2)[C:39]2[CH:40]=[CH:41][C:42]3[N:43]([C:52]4[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=4)[C:44]4[C:49]([C:50]=3[CH:51]=2)=[CH:48][CH:47]=[CH:46][CH:45]=4)[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=[CH:30][CH:29]=1
Reactant: Brc1ccc2c(-c3ccccc3)c3ccccc3c(-c3ccccc3)c2c1
Reactant: c1ccc(-n2c3ccccc3c3cc(Nc4cccc5ccccc45)ccc32)cc1
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: c1ccc(-c2c3ccccc3c(-c3ccccc3)c3cc(N(c4ccc5c(c4)c4ccccc4n5-c4ccccc4)c4cccc5ccccc45)ccc23)cc1
Temperature: 80 °C
Reaction time: 5 h
Yield: 42.4 %

Procedure:
3.5 g (8.6 mmol) of 2-bromo-9,10-diphenylanthracene synthesized in Step 1 of Embodiment 1, 3.2 g (9.4 mmol) of N-(1-naphthyl)-N-(9-phenylcarbazol-3-yl)amine (abbreviation: PCN), 0.25 g (0.43 mmol) of bis(benzylideneacetone)palladium (0), and 2.1 g (21 mmol) of sodium tert-butoxide were put in a 200 mL three-neck flask, and the atmosphere of the flask was substituted with nitrogen. Thereafter, 50 mL of toluene and 0.86 g (0.43 mmol) of tri(tert-butyl)phosphine (10% hexane solution) were added to the mixture, and this reaction mixture was stirred for 5 hours at 80° C. After the reaction was completed, the reaction solution was washed with water, and the aqueous layer was extracted with ethyl acetate. The extracted solution was combined with the organic layer, and then dried with magnesium sulfate. After drying, this mixture was subjected to suction filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography (eluent:toluene). The obtained solid was recrystallized with a mixed solvent of chloroform and hexane, giving 2.6 g of 2-[N-(1-naphthyl)-N-(9-phenylcarbazol-3-yl)-amino]-9,10-diphenylanthracene (abbreviation: 2PCNPA) as yellow powder in 42% yield. It was confirmed by a nuclear magnetic resonance measurement (NMR) that this compound was 2-[N-(1-naphthyl)-N-(9-phenylcarbazol-3-yl)-amino]-9,10-diphenylanthracene (abbreviation: 2PCNPA).
Reaction SMILES: C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([NH:19][C:20]3[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[CH:22][C:21]=3[Cl:28])=[N:14][CH:15]=[N:16]2)=[C:11]([O:29][CH:30]2[CH2:34][CH2:33][O:32][CH2:31]2)[CH:10]=1)C1C=CC=CC=1.FC(F)(F)C(O)=O.N>C(Cl)Cl>[Cl:28][C:21]1[CH:22]=[CH:23][C:24]([O:26][CH3:27])=[CH:25][C:20]=1[NH:19][C:13]1[C:12]2[C:17](=[CH:18][C:9]([OH:8])=[CH:10][C:11]=2[O:29][CH:30]2[CH2:34][CH2:33][O:32][CH2:31]2)[N:16]=[CH:15][N:14]=1
Reactant: COc1ccc(Cl)c(Nc2ncnc3cc(OCc4ccccc4)cc(OC4CCOC4)c23)c1
Agent: N
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(Cl)c(Nc2ncnc3cc(O)cc(OC4CCOC4)c23)c1
Yield: 148.5 %

Procedure:
Using an analogous procedure to that described in Example 20, 7-benzyloxy-4-(2-chloro-5-methoxyanilino)-5-tetrahydrofuran-3-yloxyquinazoline (0.39 g) was reacted with trifluoroacetic acid (2.5 ml). The reaction mixture was evaporated and the residue was triturated under diethyl ether. The precipitate was isolated and the solid was dissolved in a mixture of methylene chloride and a saturated methanolic ammonia solution. The mixture was evaporated and the residue was purified by column chromatography on silica using a 97:3 mixture of methylene chloride and methanol as eluent. There was thus obtained the title compound (0.47 g); NMR Spectrum: (DMSOd6 and CF3CO2D) 2.2-2.3 (m, 1M, 2.3-2.5 (m, 1H), 3.8 (s, 3H), 3.75-3.9 (m, 1H), 3.9-4.0 (m, 2H), 4.2 (d, 1H), 5.5 (m, 1H), 6.8 (s, 1H), 6.92 (s, 1H), 7.02 (m, 1H), 7.55 (d, 1H), 7.6 (d, 1H), 8.85 (s, 1H); Mass Spectrum: M+H+ 388 and 390.