Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]=O)[C:3]=1[NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14].[NH2:18][CH:19]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:21][CH2:20]1.[BH4-].[Na+]>C(O)C>[CH2:25]([N:22]1[CH2:23][CH2:24][CH:19]([NH:18][CH2:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=2[NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:20][CH2:21]1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: CC(C)(C)OC(=O)Nc1c(F)cccc1C=O
Reactant: NC1CCN(Cc2ccccc2)CC1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: CC(C)(C)OC(=O)Nc1c(F)cccc1CNC1CCN(Cc2ccccc2)CC1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
To a solution of tert-butyl 2-fluoro-6-formylphenylcarbamate (48.0 g, 201 mmol) in ethanol (100 mL) was added 4-amino-1-benzylpiperidine (41.0 mL, 201 mmol). The solution was concentrated in vacuo, and then water was removed by twice dissolving the residue in toluene and concentrating the solution in vacuo. The resulting oil was dissolved in tetrahydrofuran (250 mL), cooled to 0° C., and treated with sodium borohydride (3.80 g, 100 mmol). The ice bath was removed and stirring continued overnight. The reaction was treated with ethanol (250 mL), an additional portion of sodium borohydride (2.00 g, 53 mmol), and an additional portion of 4-amino-1-benzylpiperidine (2.0 mL, 9.8 mmol). The resulting solution was stirred for 4 h at room temperature. The reaction was cooled to 0° C., quenched by addition of saturated ammonium chloride, filtered to remove solids, and concentrated to remove most (but not all) of the tetrahydrofuran. The reaction was extracted with diethyl ether (2×). The ethereal layer was washed with water (3×), then brine, dried over magnesium sulfate, and concentrated to give 83 g (100%) as a viscous yellow oil which was pure enough to use in the following step. Mass spec.: 414.51 (MH)+.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11](=O)[C:12]([O:14]C2C(F)=C(F)C(F)=C(F)C=2F)=O)=[CH:3]1.Cl.[CH3:28][N:29]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]([CH2:38][C:39](=[NH:44])[O:40]C(C)C)=[CH:30]1.C(N(CC)CC)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCl>[CH3:28][N:29]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]([C:38]2[C:39](=[O:40])[NH:44][C:12](=[O:14])[C:11]=2[C:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[N:2]([CH3:1])[CH:3]=2)=[CH:30]1
Reactant: CC(C)OC(=N)Cc1cn(C)c2ccccc12
Reactant: Cn1cc(C(=O)C(=O)Oc2c(F)c(F)c(F)c(F)c2F)c2ccccc21
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cn1cc(C2=C(c3cn(C)c4ccccc34)C(=O)NC2=O)c2ccccc21
Reaction time: 1 h
Yield: 44.7 %

Procedure:
A solution of 369 mg (1 mmol) of pentafluorophenyl 1-methylindole-3-glyoxylate in 20 ml of dichloromethane was added to a stirred solution of 266 mg (1 mmol) of isopropyl 1-methyl-3-indoleacetimidate hydrochloride and 404 mg (4 mmol) of triethylamine in 25 ml of dichloromethane. The solution obtained was heated to reflux under nitrogen for 18 hours, cooled and treated with 950 mg (5 mmol) of p-toluenesulfonic acid. After 1 hour, the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel using dichloromethane/ethyl acetate (8:1) for the elution to give 159mg (45%) of 3,4-bis-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione in the form of an orange colored solid of melting point >310° C.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[C:6]([C:11]3[CH:20]=[CH:19][C:14]([O:15][CH2:16][C:17]#[N:18])=[CH:13][CH:12]=3)[CH:7]=[CH:8][CH:9]=2)[C:4]([CH3:21])=[C:3]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[N-:28]=[N+:29]=[N-:30].[Na+].[NH4+].[Cl-]>CN(C=O)C>[CH3:1][N:2]1[C:10]2[C:5](=[C:6]([C:11]3[CH:20]=[CH:19][C:14]([O:15][CH2:16][C:17]4[NH:30][N:29]=[N:28][N:18]=4)=[CH:13][CH:12]=3)[CH:7]=[CH:8][CH:9]=2)[C:4]([CH3:21])=[C:3]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: [N-]=[N+]=[N-]
Reactant: Cc1c(-c2ccccc2)n(C)c2cccc(-c3ccc(OCC#N)cc3)c12
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1c(-c2ccccc2)n(C)c2cccc(-c3ccc(OCc4nnn[nH]4)cc3)c12

Procedure:
The desired product was prepared using a procedure similar to step 6 of example 3. Thus, [4-(1,3-dimethyl-2-phenyl-1H-indol-4-yl)-phenoxy]-acetonitrile (0.311 g, 0.882 mmol) was reacted with NaN3 (0.287 g, 4.412 mmol) and NH4Cl (0.236 g, 4.412 mmol) in DMF (5 ml) to give the product (0.246 g, 0.622 mmol, 71%) as a white solid, dec. 208-210° C.
Reaction SMILES: F[C:2]1[C:7]([CH:8]2[CH2:13][CH2:12][N:11]([CH3:14])[C:10](=[O:15])[CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[N:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[NH:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN1CCCC1=O>CCOC(C)=O>[CH3:14][N:11]1[CH2:12][CH2:13][CH:8]([C:7]2[C:2]([O:29][C:26]3[CH:25]=[CH:24][C:23]([NH:22][C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][N:16]=4)=[CH:28][CH:27]=3)=[N:3][CH:4]=[CH:5][CH:6]=2)[CH2:9][C:10]1=[O:15]
Reactant: CN1CCC(c2cccnc2F)CC1=O
Reactant: Oc1ccc(Nc2ccccn2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN1CCCC1=O
Solvent: CCOC(C)=O
Product: CN1CCC(c2cccnc2Oc2ccc(Nc3ccccn3)cc2)CC1=O
Temperature: 100 °C
Yield: 42.9 %

Procedure:
4-(2-Fluoropyridin-3-yl)-1-methylpiperidin-2-one (0.07 g, 0.33 mmol), 4-(pyridin-2-ylamino)phenol (0.144 g, 0.77 mmol), cesium carbonate (0.274 g, 0.84 mmol), and 1-methyl-2-pyrrolidinone (1 mL) were combined in a sealed tube and heated at 100° C. for 18 h. The cooled mixture was diluted with EtOAc and washed with water; the aqueous layer was back-washed with EtOAc (1×). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo. ISCO purification with 20% to 80% EtOAc (10% MeOH)/Hexanes afforded 1-methyl-4-(2-(4-(pyridin-2-ylamino)phenoxy)pyridin-3-yl)piperidin-2-one (0.053 g, 42.1% yield) as a tan amorphous solid. MS (ESI, pos. ion) m/z: 375.0 (M+1). IC50 (uM) 0.005.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:15]=[C:16]([F:18])[CH:17]=1)[CH2:5][N:6]1[C:10]([C:11]([OH:13])=O)=[CH:9][N:8]=[C:7]1[SH:14].ON1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1.[CH3:42][N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1>O1CCCC1>[F:18][C:16]1[CH:15]=[C:4]([CH:3]=[C:2]([F:1])[CH:17]=1)[CH2:5][N:6]1[C:10]([C:11]([N:46]2[CH2:47][CH2:48][N:43]([CH3:42])[CH2:44][CH2:45]2)=[O:13])=[CH:9][N:8]=[C:7]1[SH:14]
Reactant: CN1CCNCC1
Reactant: O=C(O)c1cnc(S)n1Cc1cc(F)cc(F)c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: O=C1CCC(=O)N1O
Solvent: C1CCOC1
Product: CN1CCN(C(=O)c2cnc(S)n2Cc2cc(F)cc(F)c2)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 1-(3,5-difluorobenzyl)-2-mercaptoimidazole-5-carboxylic acid (2.70 g, 0.01 moles) in tetrahydrofuran (25 ml) was added N-hydroxysuccinimide (1.27 g, 0.011 mole) followed by dropwise addition of dicyclohexylcarbodiimide (2.06 g, 0.01 mole) in tetrahydrofuran (30 ml). A solution of N-methylpiperazine (1.22 ml, 0.011 mole) in tetrahydrofuran (10 ml) was added and the mixture stirred at 25° C. for 2 hours and then at 40° C. for 16 hours. Additional N-methylpiperazine (1.0 ml, 0.009 mole) was added and the reaction mixture was stirred at 40° C. for 1.5 hours. The reaction mixture was filtered and the solvent removed under vacuum. The residue was dissolved in ethyl acetate and was washed with dilute sodium carbonate, water, and brine. The solution was dried and the solvent removed under vacuum. The resulting solid was triturated with ether and the product was filtered and dried to give a solid, m.p.: 243°-244° C. (2.10 g, 60%).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([N+:13]([O-:15])=[O:14])[CH:12]=1)[C:7]([OH:9])=[O:8])([O-:3])=[O:2].C(=O)([O-])O.[Na+].[I-].[Na+].Cl[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][OH:30]>CN1CCCC1=O.O>[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([N+:13]([O-:15])=[O:14])[CH:12]=1)[C:7]([O:9][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][OH:30])=[O:8])([O-:3])=[O:2]
Reactant: O=C(O)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Reactant: OCCCCCCCl
Agent: O=C([O-])O
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CN1CCCC1=O
Product: O=C(OCCCCCCO)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Temperature: 50 °C
Yield: 88.8 %

Procedure:
357.70 g (1.686 Mol) of 3,5-dinitrobenzoic acid are suspended in 750 ml of 1-methyl-2-pyrrolidone. The suspension is stirred up to 50° C. 386.36 g (4.599 Mol) of sodium hydrogen carbonate are added and the mixture was heated up to 90° C. 22.50 g (0.150 Mol) of sodium iodide and 204.0 ml (1.533 Mol) of 6-chlorohexanol are added to the reaction mixture which is heated to 100° C. for 1 h. After 1 h of reaction, the reaction is complete and the orange suspension is thrown on 2 l of ice and 1 l of water. The product is filtrated, washed water and dried at 50° C. under vacuum for 24 h to give 425.0 g (91%) of 6-hydroxyhexyl 3,5-dinitrobenzoate as a rose powder.
Reaction SMILES: [CH:1]([N:4]1[C:8]2[CH:9]=[C:10]([C:13](=O)[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=[CH:12][C:7]=2[N:6]=[C:5]1[NH2:21])([CH3:3])[CH3:2].[CH2:22]([Mg]Br)[CH3:23]>>[CH:1]([N:4]1[C:8]2[CH:9]=[C:10]([C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:22][CH3:23])[CH:11]=[CH:12][C:7]=2[N:6]=[C:5]1[NH2:21])([CH3:3])[CH3:2]
Reactant: CC[Mg]Br
Reactant: CC(C)n1c(N)nc2ccc(C(=O)c3ccccc3)cc21
Product: CC=C(c1ccccc1)c1ccc2nc(N)n(C(C)C)c2c1

Procedure:
Following the procedure of Example 69, 1-isopropyl-2-amino-6-benzoylbenzimidazole and ethyl magnesium bromide were reacted to give the title product as both the cis and trans alkylene isomers, M+ =291.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[CH3:5][O:6][P:7]([O:10]C)[O:8][CH3:9]>>[C:1]([P:7](=[O:10])([O:8][CH3:9])[O:6][CH3:5])(=[O:3])[CH3:2]
Reactant: CC(=O)Cl
Reactant: COP(OC)OC
Product: COP(=O)(OC)C(C)=O
Temperature: 80 °C

Procedure:
Acetyl chloride (7.85 ml, 110 mmol) was cooled to 0° C. and stirred. Trimethylphosphite (11.8 ml, 100 mmol) was added drop-wise over one hour while the cooling was maintained. The mixture was then heated to 80° C. for 5 minute to remove un-reacted acetyl chloride (the flow of argon accelerates the process). The crude product was used in the next step without additional purification (theoretical yield is 15.2 g).
Reaction SMILES: [NH4+].[OH-].S[C:4]1[N:5]=[C:6]([OH:14])[C:7]2[C@H:12]([CH3:13])[CH2:11][CH2:10][C:8]=2[N:9]=1>[Ni].O>[CH3:13][C@H:12]1[C:7]2[C:6]([OH:14])=[N:5][CH:4]=[N:9][C:8]=2[CH2:10][CH2:11]1
Reactant: C[C@@H]1CCc2nc(S)nc(O)c21
Agent: [Ni]
Agent: [NH4+]
Agent: [OH-]
Solvent: O
Product: C[C@@H]1CCc2ncnc(O)c21
Yield: 100.1 %

Procedure:
Raney Nickel (15 g) and NH4OH (20 mL) were added to a suspension of (R)-2-mercapto-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ol (12 g, 65.8 mmol) in distilled water (100 mL). The mixture was refluxed for 3 hours and then filtered. The filtrate was concentrated to afford (R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ol (9.89 g, 99%). MS (APCI+) [M+H]+151.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[CH:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[CH:15][CH:14]=1.[S:23](Cl)([CH3:26])(=[O:25])=[O:24]>N1C=CC=CC=1>[S:23]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[CH:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[CH:15][CH:14]=1)([CH3:26])(=[O:25])=[O:24]
Reactant: CS(=O)(=O)Cl
Reactant: Nc1ccc2c(c1)C(=Cc1ccnc3ccccc13)C(=O)N2
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1ccc2c(c1)C(=Cc1ccnc3ccccc13)C(=O)N2
Temperature: 0 °C
Reaction time: 5 h
Yield: 70 %

Procedure:
To a stirred solution of 5-amino-3-(quinol-4-ylmethylene)-2-oxindole (2.873 g, 10 mmol) in pyridine (10 ml) was added gradually mesylchloride (1.146 g, 10 mmol) at 0°-5° C. under cooling. The reaction mixture was stirred for about 5 h at 0°-5° C. and then for 15 hours at room temperature. The mixture was poured onto an ice-water mixture, the precipitate filtered off, the residue washed thoroughly with water and then chromatographed on silica gel using CHCl3 --MeOH mixtures as eluant. Thus pure title compound was obtained in about 70% yield.
Reaction SMILES: Cl[CH2:2][C:3]([N:5]1[CH2:10][CH2:9][CH:8]([N:11]2[C:15](=[O:16])[C:14]([CH3:18])([CH3:17])[C:13]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=3)=[N:12]2)[CH2:7][CH2:6]1)=[O:4].[C:29]1(=[O:35])[NH:33][C:32](=[O:34])[CH2:31][CH2:30]1.C(=O)([O-])[O-].[K+].[K+].O>CC(O)C>[CH3:28][O:27][C:21]1[CH:20]=[C:19]([C:13]2[C:14]([CH3:17])([CH3:18])[C:15](=[O:16])[N:11]([CH:8]3[CH2:9][CH2:10][N:5]([C:3](=[O:4])[CH2:2][N:33]4[C:29](=[O:35])[CH2:30][CH2:31][C:32]4=[O:34])[CH2:6][CH2:7]3)[N:12]=2)[CH:24]=[CH:23][C:22]=1[O:25][CH3:26]
Reactant: COc1ccc(C2=NN(C3CCN(C(=O)CCl)CC3)C(=O)C2(C)C)cc1OC
Reactant: O=C1CCC(=O)N1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Solvent: O
Product: COc1ccc(C2=NN(C3CCN(C(=O)CN4C(=O)CCC4=O)CC3)C(=O)C2(C)C)cc1OC
Temperature: 50 °C
Reaction time: 0.5 h

Procedure:
7.4 g 2-[1-(chloroacetyl)piperidin-4-yl]-5-(3,4-dimethoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (compound A1) and 3.6 g succinimide are suspended in 50 ml of 2-propanol and heated to 50° C. 5.1 g potassium carbonate are added in portions during 1 h. After adding potassium carbonate the reaction mixture is stirred for 30 min at 50° C., then 3-4 h at 75° C. until the reaction is complete. After stirring for 3-4 h at 75° C., the heating is turned off and the mixture is allowed to cool down slowly to RT. 100 ml of water is added, the mixture is stirred for 0.5 h at RT and the crystallized product is filtered. The product is dried at 50° C. in a vacuum dryer.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][CH:25]=1)[O:5][CH:6]1[CH2:9][N:8]([C:10]2[N:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:11]=2[C:12](O)=[O:13])[CH2:7]1.Cl.[NH2:27][C:28]1([C:31]2[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=2)[CH2:30][CH2:29]1>>[F:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][CH:25]=1)[O:5][CH:6]1[CH2:9][N:8]([C:10]2[N:18]=[CH:17][C:16]([C:19]([F:20])([F:21])[F:22])=[CH:15][C:11]=2[C:12]([NH:27][C:28]2([C:31]3[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=3)[CH2:30][CH2:29]2)=[O:13])[CH2:7]1
Reactant: COC(=O)c1ccc(C2(N)CC2)cc1
Reactant: O=C(O)c1cc(C(F)(F)F)cnc1N1CC(Oc2cccc(F)c2)C1
Agent: Cl
Product: COC(=O)c1ccc(C2(NC(=O)c3cc(C(F)(F)F)cnc3N3CC(Oc4cccc(F)c4)C3)CC2)cc1
Yield: 80.9 %

Procedure:
The title compound (D172) (60 mg) was prepared according to the experimental procedure described in Description 146 starting from 2-(3-(3-fluorophenoxy)azetidin-1-yl)-5-(trifluoromethyl)nicotinic acid (D121) (50 mg, 0.14 mmol) and methyl 4-(1-aminocyclopropyl)benzoate (D7) (31.95 mg, 0.14 mmol).
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:14]3[C:9](=[CH:10][C:11]([Cl:15])=[CH:12][CH:13]=3)[CH:8]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[NH:7][C:6]2=[O:22])[CH2:3][CH2:2]1.[H-].[Na+].[CH2:25]([N:27]([CH2:31][CH3:32])[CH2:28][CH2:29]Cl)[CH3:26].O.N>O.CN(C)C=O>[CH:1]1([CH2:4][N:5]2[C:14]3[C:9](=[CH:10][C:11]([Cl:15])=[CH:12][CH:13]=3)[CH:8]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:7]([CH2:26][CH2:25][N:27]([CH2:31][CH3:32])[CH2:28][CH3:29])[C:6]2=[O:22])[CH2:2][CH2:3]1
Reactant: CCN(CC)CCCl
Reactant: O=C1NC(c2ccccc2)c2cc(Cl)ccc2N1CC1CC1
Agent: N
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCN(CC)CCN1C(=O)N(CC2CC2)c2ccc(Cl)cc2C1c1ccccc1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
To a solution of 3.1 g. of 1-cyclopropylmethyl-4-phenyl-6-chloro-3,4-dihydro-2(1H)-quinazolinone in 50 ml. of dimethylformamide was added 0.42 g. of 63% sodium hydride, and the resulting mixture was stirred at 50° C. for 30 minutes. Thereafter, 2.7 g. of β-diethylaminoethyl chloride was added, and the mixture was stirred at 100° C. for 8 hours. After cooling, the reaction mixture was poured into 300 ml. of water, and ammonia water was added thereto to make alkaline. The resulting mixture was extracted with benzene. The benzene layer was washed with water and dried, and then the solvent was removed under reduced pressure. The residue was dissolved in 50 ml. of ether, and the insoluble material were separated by filtration. The filtrate was extracted with 50 ml. of 5% hydrochloric acid, and the water layer was further washed with ether, made alkaline by addition of ammonia water and then extracted with ether. The ether layer was washed with water and dried over anhydrous sodium sulfate, and then the solvent was removed to obtain oily 1-cyclopropylmethyl-3-(β-diethylaminoethyl)-3,4-dihydro-4-phenyl-6-chloro-2(1H)-quinazolinone.
Reaction SMILES: [CH3:1][C:2]([O:4][C@H:5]1[C:14]2[C@@:15]3([CH3:30])[C@@H:26]([CH2:27][O:28][CH3:29])[O:25][C:23](=[O:24])[C:17]4=[CH:18][O:19][C:20]([C:21](=[O:22])[C:13]=2[C@@H:8]2[CH2:9][CH2:10][C@H:11]([OH:12])[C@@:7]2([CH3:31])[CH2:6]1)=[C:16]34)=[O:3].[CH3:32][N:33]([CH3:44])[CH2:34][CH2:35][NH:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C(Cl)Cl>[CH2:37]([N:36]([CH:18]=[C:17]1[C:16]2[C:15]([CH3:30])([C:14]3[CH:5]([O:4][C:2](=[O:3])[CH3:1])[CH2:6][C:7]4([CH3:31])[CH:8]([C:13]=3[C:21](=[O:22])[C:20]=2[OH:19])[CH2:9][CH2:10][CH:11]4[OH:12])[CH:26]([CH2:27][O:28][CH3:29])[O:25][C:23]1=[O:24])[CH2:35][CH2:34][N:33]([CH3:44])[CH3:32])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1
Reactant: CN(C)CCNCc1ccccc1
Reactant: COC[C@H]1OC(=O)c2coc3c2[C@@]1(C)C1=C(C3=O)[C@@H]2CC[C@H](O)[C@@]2(C)C[C@H]1OC(C)=O
Solvent: ClCCl
Product: COCC1OC(=O)C(=CN(CCN(C)C)Cc2ccccc2)C2=C(O)C(=O)C3=C(C(OC(C)=O)CC4(C)C(O)CCC34)C21C
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 100 mg (0.23 mmol) 17-hydroxywortmannin in 2 mL CH2Cl2 is added N,N-Dimethyl-N′-benzyl-ethane-1,2-diamine (62 μL). The reaction mixture is stirred at room temperature for 12 hours and then concentrated in vacuo. The residue is dissolved in EtOAc and precipitated with hexane. The precipitate is washed two times with hexane to give the product as a yellow solid. MS (ESI) m/z 609 (M+H).
Reaction SMILES: [C:1]([C:4]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:5]=1[CH:6]=[O:7])([OH:3])=[O:2].S(OC)(O[CH3:17])(=O)=O>C(Cl)Cl>[C:1]([C:4]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:5]=1[CH:6]=[O:7])([O:3][CH3:17])=[O:2]
Reactant: O=Cc1cc(F)ccc1C(=O)O
Reactant: COS(=O)(=O)OC
Solvent: ClCCl
Product: COC(=O)c1ccc(F)cc1C=O
Temperature: 25 °C
Yield: 68.6 %

Procedure:
A stirred mixture of 3.4 g (0.02 mole) 2-carboxy-5-fluorobenzaldehyde (the product of Example 6) and 5.0 g [3.75 ml (0.04 mole)] dimethyl sulfate in methylene chloride was heated to reflux. The heating mantle was removed; and triethylamine, 4.15 g [5.7 ml (0.04 mole)] was added dropwise at a rate which maintained a brisk reflux. After the addition was complete, the reaction mixture was allowed to cool and was stirred at room temperature over the weekend. The reaction mixture was poured into water; the layers were separated. The methylene chloride layer was washed with a sodium bicarbonate solution, dried and evaporated to give 2.5 g of the above-identified product as a yellow oil.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:32])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:19]=[C:18]([O:20][CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)[CH:17]=[C:16](Br)[CH:15]=2)=[CH:9][C:8]=1[CH3:31])[CH3:2].[CH2:33]([N:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1)[C:34]#[CH:35]>C(N(CC)CC)C.CN(C=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu](I)I>[CH2:1]([O:3][C:4](=[O:32])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:15]=[C:16]([C:35]#[C:34][CH2:33][N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)[CH:17]=[C:18]([O:20][CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)[CH:19]=2)=[CH:9][C:8]=1[CH3:31])[CH3:2]
Reactant: CCOC(=O)COc1ccc(Sc2cc(Br)cc(OCCc3ccc(Cl)cc3)c2)cc1C
Reactant: C#CCN1CCOCC1
Agent: Cl[Pd]Cl
Agent: I[Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCOC(=O)COc1ccc(Sc2cc(C#CCN3CCOCC3)cc(OCCc3ccc(Cl)cc3)c2)cc1C

Procedure:
(4-{3-Bromo-5-[2-(4-chloro-phenyl)-ethoxy]-phenylsulfanyl}-2-methyl-phenoxy)acetic acid ethyl ester (300 mg; 0.56 mmol), 4-prop-2-ynyl-morpholine (280.4 mg; 2.2 mmol), bis(triphenylphosphine) palladium (II) chloride (31.4 mg; 0.045 mmol) and copper iodide (6.4 mg; 0.034 mmol) were dissolved in a mixture of triethylamine (2 mL) and DMF (2 mL) under an atmosphere of nitrogen. The reaction mixture was reacted in a microwave oven at 110° C. for 1.5 h. The reaction mixture was evaporated to dryness, and 5% aqueous citric acid (30 mL) and ethyl acetate (30 mL) was added. The two phases were separated and the aqueous phase was extracted with ethyl acetate (30 mL). The combined organic phases were dried and evaporated to dryness and purified by preparative HPLC (method B). Yield: 300 mg; 92%. HPLC-MS: m/z: 580.7 (M+H)+; Rt: 2.16 min.
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH:32][CH2:33][CH2:34][C:35]1[CH:43]=[CH:42][CH:41]=[C:40]2[C:36]=1[CH2:37][C:38](=[O:44])[NH:39]2.[CH:45]([C:48]1[CH:53]=[CH:52][C:51](O)=[CH:50][CH:49]=1)([CH3:47])[CH3:46]>O1CCCC1>[CH:45]([C:48]1[CH:53]=[CH:52][C:51]([O:32][CH2:33][CH2:34][C:35]2[CH:43]=[CH:42][CH:41]=[C:40]3[C:36]=2[CH2:37][C:38](=[O:44])[NH:39]3)=[CH:50][CH:49]=1)([CH3:47])[CH3:46]
Reactant: CC(C)c1ccc(O)cc1
Reactant: O=C1Cc2c(CCO)cccc2N1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)c1ccc(OCCc2cccc3c2CC(=O)N3)cc1
Reaction time: 0.25 h
Yield: 37.2 %

Procedure:
Diethyl azodicarboxylate (1.58 mL, 10 mmol) was added to a solution of triphenylphosphine (2.62 g, 10 mmol) in tetrahydrofuran (20 mL) under nitrogen atmosphere. The mixture was stirred for 15 minutes. To it was then added 4-(2-hydroxy-ethyl)-1,3-dihydro-indol-2-one (1.77 g, 10 mmol) followed by 4-isopropylphenol (1.36 g, 10 mmol). The mixture was stirred at room temperature for one day and the solvent was evaporated. The residue was chromatographed on silica gel eluting with ethyl acetate:hexane 2:8 to give 1.1 g (37%) of 4-[2-(4-isopropyl-phenoxy)-ethyl]-1,3-dihydro-indol-2-one as a light yellow solid.
Reaction SMILES: [CH:1]1[C:6]2=[CH:7][C:8]3[C:23]4[C:22]([C:21]5=[C:24]6[C:17](=[CH:18][CH:19]=[CH:20]5)[CH:16]=[C:15]5[CH:25]=[CH:26][CH:27]=[CH:28][C:14]5=[C:13]6[C:12]=4[CH:11]=[CH:10][CH:9]=3)=[C:5]2[CH:4]=[CH:3][CH:2]=1.[Br:29]Br>C(Cl)(Cl)(Cl)Cl>[Br:29][C:16]1[C:17]2[C:24]3[C:13]([C:12]4[CH:11]=[CH:10][CH:9]=[C:8]5[C:23]=4[C:22]([C:21]=3[CH:20]=[CH:19][CH:18]=2)=[C:5]2[CH:4]=[CH:3][CH:2]=[CH:1][C:6]2=[CH:7]5)=[C:14]2[CH:28]=[CH:27][CH:26]=[CH:25][C:15]=12
Reactant: c1ccc2c(c1)cc1cccc3c1c2c1cccc2cc4ccccc4c3c21
Reactant: BrBr
Solvent: ClC(Cl)(Cl)Cl
Product: Brc1c2ccccc2c2c3cccc4cc5ccccc5c(c5cccc1c52)c43

Procedure:
After dibenzo[a,j]perylene dissolved in carbon tetrachloride was brominated with cooling for four hours by adding one molar equivalent of bromine, the reaction product was refined in accordance with an ordinary method to obtain 8-bromodibenzo-[a,j]perylene. Di-p-tolylamine, potassium carbonate and copper powder were added to the thus obtained 8-bromodibenzo[a,j]perylene and were allowed to react for 30 hours at 200° C. After the reaction solution was diluted with water, the reaction product was extracted with chloroform. Thereafter, it was refined in accordance with an ordinary method to obtain a target compound expressed in Formula 26.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=1.Cl.[NH:11]1[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[OH:16][CH:13]1[CH2:14][CH2:15][N:11]([C:2]2[CH:3]=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=2)[CH2:12]1
Reactant: OC1CCNC1
Reactant: N#Cc1ccc(Cl)cn1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: N#Cc1ccc(N2CCC(O)C2)cn1
Reaction time: 16 h
Yield: 73.4 %

Procedure:
A mixture of 5-chloropicolinonitrile (2 g, 14.4 mmol), pyrrolidin-3-ol hydrochloride (2 g, 25.9 mmol) and K2CO3 (4 g, 28.9 mmol) in DMF (15 mL) was stirred at 140□ for 16 h. The organic solvent was removed under vacuum and the residue was taken into DCM (200 mL). Solid was removed by filtration and the filtrate was concentrated to give crude product (2.0 g yield 73%) as a yellow solid. [LCMS: RtA=1.19 min, m/z 190.2 [M+H]+].