Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[O:6][C:7]([CH3:16])=[CH:8][C:9](=[C:11]([C:14]#[N:15])[C:12]#[N:13])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[C:17]1([N:23]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:24]2[CH:29]=[CH:28][C:27]([C:30]3[S:34][C:33]([CH:35]=O)=[CH:32][CH:31]=3)=[CH:26][CH:25]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.N1CCCCC1>C(O)C>[C:1]([C:5]1[O:6][C:7]([CH:16]=[CH:35][C:33]2[S:34][C:30]([C:27]3[CH:28]=[CH:29][C:24]([N:23]([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:25][CH:26]=3)=[CH:31][CH:32]=2)=[CH:8][C:9](=[C:11]([C:14]#[N:15])[C:12]#[N:13])[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: O=Cc1ccc(-c2ccc(N(c3ccccc3)c3ccccc3)cc2)s1
Reactant: CC1=CC(=C(C#N)C#N)C=C(C(C)(C)C)O1
Solvent: CCO
Solvent: C1CCNCC1
Product: CC(C)(C)C1=CC(=C(C#N)C#N)C=C(C=Cc2ccc(-c3ccc(N(c4ccccc4)c4ccccc4)cc3)s2)O1
Yield: 50 %

Procedure:
As shown in the following reaction 3, 0.72 g (3.37 mmol) of (2-(2-tert-butyl-6-methyl-pyran-4-ylidene)-malononitrile and 1 g (2.81 mmol) of 5-(4-diphenylamino-phenyl)-thiophene-2-carbaldehyde were added into 50 ml of ethanol, and 0.28 g (3.37 mmol) of piperidine was added thereto. The reaction solution was heated for 24 hours while refluxing. After cooling the reaction solution, the precipitated red solid was filtered, and recrystallized with ethanol to obtain 0.79 g of the target compound (Yield 50%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([NH2:14])[S:12][CH:13]=2)=[CH:5][CH:4]=1.Br[CH2:16][C:17]1[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=1.C(N(CC)C(C)C)(C)C.C(OCC)(=O)C>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:10]=[C:11]([NH:14][CH2:16][C:17]3[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=3)[S:12][CH:13]=2)=[CH:7][CH:8]=1
Reactant: N#Cc1ccc(CBr)cc1
Reactant: COc1ccc(-c2csc(N)n2)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1ccc(-c2csc(NCc3ccc(C#N)cc3)n2)cc1
Temperature: 100 °C
Yield: 34.3 %

Procedure:
5.0 g 4-(4-Methoxyphenyl)-1,3-thiazol-2-amine, 4.29 g 4-bromomethyl-benzonitrile and 6.0 ml N,N-Diisopropylethylamine were suspended in 20 ml dimethylformamide. The reaction mixture was stirred under microwave irradiation at 100° C. for thirty minutes. The cooled reaction mixture was diluted by the addition of 100 ml ethyl acetate and washed 50 ml saturated NaHCO3 solution and the dried over MgSO4. The solvent was removed in vacuo and the resulting residue was purified by chromatography on silica gel with the eluent petroleum ether: ethyl acetate=3:2 to obtain 2.41 g 4-{[4-(4-Methoxy-phenyl)-thiazol-2-ylamino]-methyl}-benzonitrile.
Reaction SMILES: [OH:1][CH2:2][C:3]1[O:4][C:5]([CH3:18])=[CH:6][C:7](=[O:17])[C:8]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.O[CH:20](C1OC(C)=CC(=O)C=1O)C.C(Br)C1C=CC=CC=1>>[OH:1][CH:2]([C:3]1[O:4][C:5]([CH3:18])=[CH:6][C:7](=[O:17])[C:8]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:20]
Reactant: Cc1cc(=O)c(O)c(C(C)O)o1
Reactant: Cc1cc(=O)c(OCc2ccccc2)c(CO)o1
Agent: BrCc1ccccc1
Product: Cc1cc(=O)c(OCc2ccccc2)c(C(C)O)o1

Procedure:
The title compound was prepared by the method outlined for 2-hydroxymethyl-3-benzyloxy-6-methyl-pyran-4(1H)-one, using 8.5 g (50 mmol, 1 eq.) of 2-(1-hydroxyethyl)-3-hydroxy-6-methyl-pyran-4(1H)-one and 9.5 g benzyl bromide (55 mmol, 1.1 eq.) to yield the pure product 10.1 g (77.7%) after recrystallisation from CH2Cl2/Pet. ether 40/60, as a white crystalline solid. m.p 91-92° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH3:11])=[C:5]2[C:12]([OH:14])=O.[NH2:15][CH:16]1[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:18][CH2:17]1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH3:11])=[C:5]2[C:12]([NH:15][CH:16]1[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:18][CH2:17]1)=[O:14]
Reactant: Cc1[nH]c2ccc(O)cc2c1C(=O)O
Reactant: NC1CCN(CCCc2ccccc2)CC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: C1CCOC1
Product: Cc1[nH]c2ccc(O)cc2c1C(=O)NC1CCN(CCCc2ccccc2)CC1

Procedure:
To a mixture of 3.2 g of 5-hydroxy-2-methylindole-3-carboxylic acid and 3.7 g of 4-amino-1-(3-phenylpropyl)piperidine in 60 ml of tetrahydrofuran was added 3.8 g of dicyclohexylcarbodiimide, and the whole mixture was refluxed for 2 hours. After cooling, the precipitated dicyclohexylurea was filtered off and the filtrate was concentrated. The residue was crystallized from ethyl acetate. The crystals were filtered with suction, and recrystallized from a mixture of ethyl acetate and methanol to give 5-hydroxy-2-methyl-N-[1-(3-phenylpropyl)-4-piperidyl]indole-3-carboxamide, melting at 181°-184° C. The compound was precipitated as a monohydrate at first, but the water of crystallization was evaporated by vacuum drying over 3 hours at 90° C.
Reaction SMILES: [CH3:1][N:2]([CH3:25])[CH2:3][CH2:4][CH:5]1[CH:11]=[CH:10][N:9]([C:12](=[O:20])[C:13]2[CH:18]=[CH:17][C:16]([NH2:19])=[CH:15][CH:14]=2)[C:8]2[CH:21]=[CH:22][CH:23]=[CH:24][C:7]=2[S:6]1.[C:26]1([CH3:35])[C:27]([C:32](Cl)=[O:33])=[CH:28][CH:29]=[CH:30][CH:31]=1.C1(C2C=CC=CC=2C(Cl)=O)C=CC=CC=1>>[CH3:25][N:2]([CH3:1])[CH2:3][CH2:4][CH:5]1[CH:11]=[CH:10][N:9]([C:12](=[O:20])[C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:32](=[O:33])[C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=3[CH3:35])=[CH:15][CH:14]=2)[C:8]2[CH:21]=[CH:22][CH:23]=[CH:24][C:7]=2[S:6]1
Reactant: CN(C)CCC1C=CN(C(=O)c2ccc(N)cc2)c2ccccc2S1
Reactant: Cc1ccccc1C(=O)Cl
Agent: O=C(Cl)c1ccccc1-c1ccccc1
Product: Cc1ccccc1C(=O)Nc1ccc(C(=O)N2C=CC(CCN(C)C)Sc3ccccc32)cc1

Procedure:
Compound 12 as prepared in Example 7 (0.118 mg, 0.37 mM) was treated following the procedure of Example 8, with 2-toluoyl chloride (0.04 ml, 0.33 mM) substituted for 2-phenylbenzoyl chloride, to give a white solid product. m/z (MH+) 474.
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]([C:8]([OH:10])=O)=[C:5]([CH3:7])[N:6]=1.CN(C)C=O.C(Cl)(=O)C(Cl)=O.[NH2:22][C:23]1[CH:24]=[C:25]([CH:42]=[CH:43][C:44]=1[Cl:45])[O:26][C:27]1[CH:28]=[CH:29][C:30]2[N:31]([CH:33]=[C:34]([NH:36][C:37]([CH:39]3[CH2:41][CH2:40]3)=[O:38])[N:35]=2)[N:32]=1>CN(C)C(=O)C.O1CCCC1>[Cl:45][C:44]1[CH:43]=[CH:42][C:25]([O:26][C:27]2[CH:28]=[CH:29][C:30]3[N:31]([CH:33]=[C:34]([NH:36][C:37]([CH:39]4[CH2:41][CH2:40]4)=[O:38])[N:35]=3)[N:32]=2)=[CH:24][C:23]=1[NH:22][C:8]([C:4]1[S:3][C:2]([CH3:1])=[N:6][C:5]=1[CH3:7])=[O:10]
Reactant: Nc1cc(Oc2ccc3nc(NC(=O)C4CC4)cn3n2)ccc1Cl
Reactant: Cc1nc(C)c(C(=O)O)s1
Agent: O=C(Cl)C(=O)Cl
Solvent: CC(=O)N(C)C
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: Cc1nc(C)c(C(=O)Nc2cc(Oc3ccc4nc(NC(=O)C5CC5)cn4n3)ccc2Cl)s1
Yield: 49 %

Procedure:
Using 2,4-dimethyl-1,3-thiazole-5-carboxylic acid (192 mg, 1.22 mmol), tetrahydrofuran (4.5 mL), N,N-dimethylformamide (30 μL, 0.39 mmol), oxalyl chloride (107 μL, 1.22 mmol), N-[6-(3-amino-4-chlorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (300 mg, 0.87 mmol) and N,N-dimethylacetamide (6.0 mL), and in the same manner as in Example 249, the title compound (206 mg, 49%) was obtained as a white powder.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@:32]2([CH3:33])[C:9](=[CH:10][CH2:11][C@@H:12]3[C@@H:31]2[CH2:30][CH2:29][C@@:28]2([CH3:34])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[C@H:17]([CH3:27])[CH2:18][CH2:19][C:20]([F:26])([F:25])[C:21]([OH:24])([CH3:23])[CH3:22])[CH2:8][C@@H:7]([O:35][C:36](=[O:38])[CH3:37])[CH2:6]1)(=[O:3])[CH3:2].C(=O)(O)[O-].[Na+].[Br:44]N1C(C)(C)C(=O)N(Br)C1=O>CCCCCC>[C:1]([O:4][C@@H:5]1[C@@:32]2([CH3:33])[C:9](=[CH:10][CH:11]([Br:44])[C@@H:12]3[C@@H:31]2[CH2:30][CH2:29][C@@:28]2([CH3:34])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[C@H:17]([CH3:27])[CH2:18][CH2:19][C:20]([F:26])([F:25])[C:21]([OH:24])([CH3:23])[CH3:22])[CH2:8][C@@H:7]([O:35][C:36](=[O:38])[CH3:37])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@@H]1CC2=CC[C@H]3[C@@H]4CC[C@H]([C@H](C)CCC(F)(F)C(C)(C)O)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(C)=O)C1
Reactant: CC1(C)C(=O)N(Br)C(=O)N1Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCCCCC
Product: CC(=O)O[C@@H]1CC2=CC(Br)[C@H]3[C@@H]4CC[C@H]([C@H](C)CCC(F)(F)C(C)(C)O)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(C)=O)C1
Temperature: 80 °C

Procedure:
A mixture of 1.05 g (0.0019 mol) of [1α,3β]-24,24-difluorocholest-5-en-1,3,25-triol 1,3-diacetate, 0.84 g of sodium bicarbonate, 0.357 g (0.0012 mol) of 1,3-dibromo-5,5-dimethylhydantoin and 40 mL of hexane was heated at reflux (80° C.) for 1 hr and cooled. The mixture was filtered and the solids were triturated with hexane and filtered. The filtrates were evaporated to dryness to yield [1α,3β,7ξ]-7-bromo-24,24-difluorocholest-5-en-1,3,25-triol 1,3-diacetate.
Reaction SMILES: Cl[C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[C:5]2=[N:12][N:13]=[N:14][N:4]2[N:3]=1.[NH:15]1[CH2:19][CH2:18][CH2:17][C:16]1=O>CO>[N:15]1([C:2]2[C:11]3[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=3[C:5]3=[N:12][N:13]=[N:14][N:4]3[N:3]=2)[CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: Clc1nn2nnnc2c2c1CCCC2
Reactant: O=C1CCCN1
Solvent: CO
Product: C1CCc2c(c(N3CCCC3)nn3nnnc23)C1

Procedure:
A mixture of 6 g of 6-chloro-7,8,9,10-tetrahydrotetrazolo[5,1-a]phthalazine, 150 ml of methanol and excess pyrrolidone was heated on a boiling-water steam bath for 10 minutes and cooled. The solid which formed was separated by filtration, washed with water and recrystallized from a mixture of dimethylsulfoxide and water to give 6-(1-pyrrolidinyl)-7,8,9,10-tetrahydrotetrazolo[5,1-a]phthalazine melting at about 272°-273° C.
Reaction SMILES: [C:1](Cl)(=[O:7])[CH2:2][CH2:3][C:4]([OH:6])=[O:5].[NH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.S(=O)(=O)(O)O>C(#N)C>[C:10]1([NH:9][C:1](=[O:7])[CH2:2][CH2:3][C:4]([OH:6])=[O:5])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: Nc1ccccc1
Reactant: O=C(O)CCC(=O)Cl
Agent: O=S(=O)(O)O
Solvent: CC#N
Product: O=C(O)CCC(=O)Nc1ccccc1
Reaction time: 0.5 h
Yield: 63.6 %

Procedure:
100 mg of succinic acid monochloride are dissolved in 2 ml of anhydrous acetonitrile. 1.5 equivalents of aniline (102 mg) are added at room temperature and the reaction mixture is kept stirred for 30 minutes. 100 ml of 0.005M sulfuric acid are then added and the solution is extracted with ethyl ether (3×3 ml). The ether phases are combined and washed with water to neutrality and then dried over anhydrous MgSO4. The ether is then filtered and evaporated under reduced pressure to give 90 mg of N-phenylsuccinamic acid.
Reaction SMILES: Cl.[CH3:2][CH:3]1[CH2:8][CH2:7][NH:6][CH:5]([C:9]([OH:11])=[O:10])[CH2:4]1.[CH2:12](O)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.O.[C:21]1([CH3:31])[CH:26]=[CH:25][C:24]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:23][CH:22]=1.O>C1C=CC=CC=1>[C:21]1([CH3:31])[CH:22]=[CH:23][C:24]([S:27]([OH:30])(=[O:28])=[O:29])=[CH:25][CH:26]=1.[CH2:12]([N:6]1[CH2:7][CH2:8][CH:3]([CH3:2])[CH2:4][CH:5]1[C:9]([OH:11])=[O:10])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: OCc1ccccc1
Reactant: CC1CCNC(C(=O)O)C1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: Cl
Solvent: c1ccccc1
Solvent: O
Product: CC1CCN(Cc2ccccc2)C(C(=O)O)C1
Yield: 22 %

Procedure:
A solution of 20 g (0.112 mole) of 4-methyl-2-piperidinecarboxylic acid hydrochloride, 24 g (0.224 mole) of benzyl alcohol and 25.6 g (0.134 mole) of p-toluenesulfonic acid monohydrate in 100 ml of benzene was refluxed for 5 hours with the continuous removal of water through a Dean-Stark water trap. At the end of this period, the solvent was distilled off, and the residue was washed with ether-n-hexane and recrystallized to give 10 g (22%) of benzyl 4-methyl-2-piperidinecarboxylic p-toluenesulfonate, M.P. 160°-163° C.
Reaction SMILES: [C:1]1([C:13](Cl)=[O:14])[CH:6]=[C:5]([C:7](Cl)=[O:8])[CH:4]=[C:3](C(Cl)=O)[CH:2]=1.C1(N)C=CC=C(N)C=1.NC1C=CC=CC=1.O.CN1[C:37](=[O:38])CCC1>>[C:13](=[C:1]1[CH2:2][CH:3]=[CH:4][C:5](=[C:7]=[O:8])[C:6]1=[C:37]=[O:38])=[O:14]
Reactant: CN1CCCC1=O
Reactant: O=C(Cl)c1cc(C(=O)Cl)cc(C(=O)Cl)c1
Agent: Nc1cccc(N)c1
Solvent: Nc1ccccc1
Solvent: O
Product: O=C=C1C=CCC(=C=O)C1=C=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
In a nitrogen atmosphere, a 50 mL four-neck flask was charged with 3 g (11.3 mmol) of 1,3,5-benzenetricarbonyl trichloride (Tokyo Chemical Industry) and 13.3 g of NMP (Junsei Chemical Co., Ltd.), following which a solution of 0.92 g (8.48 mmol) of 1,3-phenylenediamine (DuPont K.K.) and 0.79 g (8.48 mmol) of aniline (Junsei Chemical Co., Ltd.) in 13.3 g of NMP (Junsei Chemical Co., Ltd.) was added dropwise over a period of 30 minutes at an internal temperature of 12° C. and polymerization was carried out. Following the completion of dropwise addition, the flask contents were stirred for 30 minutes at room temperature, pure water (3 g) was added dropwise, followed by another 30 minutes of stirring, after which the reaction mixture was added to 450 g of pure water, thereby effecting re-precipitation. The resulting precipitate was collected by filtration, then again dissolved in a mixed solvent of 24 g of THF (Kanto Chemical Co., Ltd.) and 1.8 g of pure water, after which the solution was added to 450 g of pure water, thereby effecting re-precipitation. The resulting precipitate was collected by filtration and dried at 150° C. for 2 hours in a vacuum desiccator, thereby giving 3.3 g of the target tricarbonylbenzene-based hyperbranched polymer (abbreviated below as “TmPDA-An”). FIG. 2 shows the 1H-NMR spectrum obtained for TmPDA-An.
Reaction SMILES: C(OC([N:11]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:12]1[C:17]([O:19][CH3:20])=[O:18])=O)C1C=CC=CC=1.C(O)(=O)C.[H][H]>C(O)C.[C].[Pd]>[C:17]([OH:19])(=[O:18])[CH3:12].[CH3:20][O:19][C:17]([C@@H:12]1[CH2:13][C@@H:14]([OH:16])[CH2:15][NH:11]1)=[O:18]
Reactant: [H][H]
Reactant: COC(=O)[C@@H]1C[C@@H](O)CN1C(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CCO
Product: COC(=O)[C@@H]1C[C@@H](O)CN1

Procedure:
To a solution of (2S,4R)-1-benzyloxycarbonyl-2-methoxycarbonyl-4-hydroxypyrrolidine (4.34 g) in 95% ethanol (44 ml), 10% palladium-carbon (419 mg) and acetic acid (0.89 ml) were added. The mixture was vigorously stirred at room temperature for 1.5 hours under an atmospheric pressure of hydrogen. Removal of the catalyst gave (2S,4R)-2-methoxycarbonyl-4-hydroxypyrrolidine acetate.
Reaction SMILES: C([O:3][C:4](=[O:29])[CH2:5][NH:6][CH2:7][C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH:19]3[CH2:24][CH2:23][CH:22]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:21][CH2:20]3)[CH:14]=2)[CH:9]=1)C.[OH-].[Li+].Cl>CO>[C:25]([C@H:22]1[CH2:21][CH2:20][C@H:19]([O:18][C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][CH:12]=2)[CH:9]=[C:8]([CH2:7][NH:6][CH2:5][C:4]([OH:29])=[O:3])[CH:17]=[CH:16]3)[CH2:24][CH2:23]1)([CH3:28])([CH3:26])[CH3:27]
Reactant: CCOC(=O)CNCc1ccc2cc(OC3CCC(C(C)(C)C)CC3)ccc2c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)[C@H]1CC[C@H](Oc2ccc3cc(CNCC(=O)O)ccc3c2)CC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of {[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-amino}-acetic acid ethyl ester (60 mg, 0.15 mmol) in methanol (1 mL) was added aqueous lithium hydroxide (4.2 M, 0.5 mL, 2 mmol) to form a white precipitate. The mixture slurry was stirred at room temperature for 3 hrs then at 50° C. for 2 hrs. The slurry was neutralized with 1 N HCl to pH 6 and the white precipitate was filtered and dried under vacuum to give white precipitate (48 mg, yield: 86%). ESI-MS: 392.3 (M+23)+; 1H NMR (400 MHz, DMSO) δ=7.77-7.82 (m, 3H), 7.48 (dd, 1H), 7.37 (d, 1H) 7.15 (dd, 1H), 4.38 (m, 1H), 4.07 (s, 2H), 3.16 (s, 2H), 2.20 (d, 2H), 1.82 (d, 2H), 1.35 (m, 2H), 1.10-1.25 (m, 3H), 0.89 (s, 9H).
Reaction SMILES: [F:1][C:2]([F:16])([F:15])[C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[C:6]#[N:7].N.[H][H]>[Pd].CO>[F:1][C:2]([F:15])([F:16])[C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([C:11]([F:14])([F:12])[F:13])[CH:10]=1)[CH2:6][NH2:7]
Reactant: N#Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: [H][H]
Agent: [Pd]
Agent: N
Solvent: CO
Product: NCc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Yield: 85.1 %

Procedure:
At first, a 1-liter autoclave equipped with a mechanical stirrer was charged with 200 g (0.84 mol) of 3,5-bis(trifluoromethyl)benzonitrile, 200 ml of methanol, and 6 g of a catalyst (i.e., a carbon powder (50% wet) carrying thereon 5% palladium), followed by introduction of 14 g of liquid ammonia and then introduction of hydrogen to have a pressure of 1 MPa. Then, the reaction mixture was stirred, while the reaction temperature was maintained at 20° C. and while hydrogen was gradually introduced into the autoclave in a manner to maintain the total pressure at 1 MPa. After conducting the reaction for 3 hr, the reaction was stopped, followed by removing the catalyst by filtration. As a result of analyzing the obtained reaction liquid by gas chromatography, 3,5-bis(trifluoromethyl)benzylamine was formed at a yield of 85.1%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH3:10].[C:11]1(=[O:17])[O:16][C:14](=[O:15])[CH2:13][CH2:12]1.[Cl-].[Al+3].[Cl-].[Cl-]>>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:11](=[O:17])[CH2:12][CH2:13][C:14]([OH:16])=[O:15])[CH:6]=[CH:5][C:4]=1[O:9][CH3:10]
Reactant: O=C1CCC(=O)O1
Reactant: COc1ccccc1OC
Agent: [Al+3]
Agent: [Cl-]
Product: COc1ccc(C(=O)CCC(=O)O)cc1OC

Procedure:
The naphthalenes of formulas A and B are known to the art. Moreover, they can be prepared by conventional means. For example, 1,2-dimethoxybenzene is treated with succinic anhydride and aluminum chloride in a hydrocarbon solvent to afford 4-(3', 4'-dimethoxyphenyl)-4-oxobutanoic acid. This is reduced by treatment with sodium borohydride, hydrogenolyzed by treating with palladium charcoal catalyst and hydrogen to furnish 4-(3', 4'-dimethoxyphenyl) butanoic acid. The corresponding acid chloride is prepared such as by treatment with thionyl chloride, and the acid chloride is treated with aluminum chloride to afford 6,7-dimethoxy-1-tetralone. The tetralone is reduced and hydrogenolyzed by the means described above to furnish 6,7-dimethoxytetralin which is dehydrogenated by treating with palladium charcoal catalyst to afford 2,3-dimethoxy naphthalene. By utilizing 1-methyl-3-fluorobenzene in the above process, 6-methyl-8-fluoro-4-tetralone and 6-fluoro-8-methyl-4-tetralone (as intermediates) and 1-methyl-3-fluoro naphthalene and 1-fluoro-3-methyl naphthalene are prepared. The mixture of naphthalenes are separated by conventional means, such as vacuum distillation.
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:23])[CH:10]([O:20][CH2:21][CH3:22])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[C:14]([CH3:19])[CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:24]([O:28][C:29]([NH:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][C:39](O)=[O:40])=[CH:34][CH:33]=1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C(OC(=O)C(OCC)CC1C=CC(OC(=O)CC2N=C(C3C=CC=CC=3)OC=2C)=C(CC2C=CC=CC=2)C=1)C1C=CC=CC=1>>[CH2:1]([O:8][C:9](=[O:23])[CH:10]([O:20][CH2:21][CH3:22])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][C:39](=[O:40])[CH2:38][C:35]2[CH:34]=[CH:33][C:32]([NH:31][C:29]([O:28][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:30])=[CH:37][CH:36]=2)=[C:14]([CH3:19])[CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(Cc1ccc(O)c(C)c1)C(=O)OCc1ccccc1
Reactant: CC(C)(C)OC(=O)Nc1ccc(CC(=O)O)cc1
Agent: CCOC(Cc1ccc(OC(=O)Cc2nc(-c3ccccc3)oc2C)c(Cc2ccccc2)c1)C(=O)OCc1ccccc1
Product: CCOC(Cc1ccc(OC(=O)Cc2ccc(NC(=O)OC(C)(C)C)cc2)c(C)c1)C(=O)OCc1ccccc1

Procedure:
The title compound was prepared from 2-ethoxy-3-(4-hydroxy-3-methyl-phenyl)-propionic acid benzyl ester (38 mg, 0.15 mmol) and (4-tert-butoxycarbonylamino-phenyl)-acetic acid (47 mg, 0.15 mmol) in the same manner as described for 3-{3-benzyl-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-acetoxy]-phenyl}-2-ethoxy-propionic acid benzyl ester. The crude product was purified by column chromatography using n-heptane/EtOAc (2:3) as the eluent to afford the product as a solid (32 mg, 85%). 1H NMR (400 MHz, CDCl3): δ 7.26-7.38 (m, 9H), 6.99-7.02 (m, 2H), 6.83-6.86 (d, 1H), 6.49 (br s, 1H), 5.12 (s, 2H), 4.00-4.05 (t, 1H), 3.80 (s, 2H), 3.58-3.61 (m, 1H), 3.31-3.36 (m, 1H), 2.94-2.96 (d, 2H), 1.98 (s, 3H), 1.52 (s, 9H), 1.12-1.16 (t, 3H).
Reaction SMILES: [S:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[CH2:3][CH2:2]1.C(O[CH:15](OCC)[N:16]([CH3:18])[CH3:17])C>>[CH3:15][N:16]([CH:18]=[C:3]1[CH2:2][S:1][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]1=[O:11])[CH3:17]
Reactant: O=C1CCSc2ccccc21
Reactant: CCOC(OCC)N(C)C
Product: CN(C)C=C1CSc2ccccc2C1=O

Procedure:
The 3,4-dihydro-2-(dimethylaminomethylene)-4-thia-1(2H)-naphthalenone starting material was prepared from thiochroman-4-one (4.93 g, 26.8 mmol) and N,N-dimethylformamide diethyl acetal (23 ml, 133.8 mmol) to give the desired product as golden yellow crystals (5.15 g) m.p. 96-97°. MS (ES+) 220 (MH+, 100%).
Reaction SMILES: [CH:1]1[C:18]2[C:19]3[C:4]([C:5]4[CH:6]=[CH:7][CH:8]=[C:9]5[C:24]=4[C:13]([C:14]=3[C:15]3[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=3[CH:17]=2)=[C:12]2[CH:25]=[CH:26][CH:27]=[CH:28][C:11]2=[CH:10]5)=[CH:3][CH:2]=1.[Br:29]Br>C(Cl)(Cl)(Cl)Cl>[Br:29][C:10]1[C:9]2[C:24]3[C:13]([C:14]4[C:15]5[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=5[CH:17]=[C:18]5[C:19]=4[C:4]([C:5]=3[CH:6]=[CH:7][CH:8]=2)=[CH:3][CH:2]=[CH:1]5)=[C:12]2[CH:25]=[CH:26][CH:27]=[CH:28][C:11]=12
Reactant: c1ccc2c(c1)cc1cccc3c4cccc5cc6ccccc6c(c54)c2c13
Reactant: BrBr
Solvent: ClC(Cl)(Cl)Cl
Product: Brc1c2ccccc2c2c3c1cccc3c1cccc3cc4ccccc4c2c31

Procedure:
After dibenzo[a,o]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 7-bromodibenzo-[a,o]perylene. Di-p-tolylamine, potassium carbonate and copper powder were added to the thus obtained 7-bromodibenzo[a,o]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 32.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[CH:12][CH:11]=2)=[O:9])=[CH:4][CH:3]=1.CN1C(C(C2C=CC([N+]([O-])=O)=CC=2)=O)=CN=C1>>[NH2:16][C:13]1[CH:14]=[CH:15][C:10]([C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[O:9])=[CH:11][CH:12]=1
Reactant: O=C(c1ccc(Cl)cc1)c1ccc([N+](=O)[O-])cc1
Agent: Cn1cncc1C(=O)c1ccc([N+](=O)[O-])cc1
Product: Nc1ccc(C(=O)c2ccc(Cl)cc2)cc1

Procedure:
The title compound was prepared by using (4-chlorophenyl)(4-nitrophenyl)methanone (Intermediate 16: step a) in place of (1-methyl-1H-imidazol-5-yl)(4-nitrophenyl)methanone (Intermediate 15: step b) then following the procedure described for the preparation of (4-aminophenyl)(1-methyl-1H-imidazol-5-yl)methanone (Intermediate 15: step c).
Reaction SMILES: [F:1][CH:2]1[C:8](=[O:9])[CH2:7][CH2:6][N:5]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:4][CH2:3]1.[BH4-].[Na+]>CO>[F:1][CH:2]1[CH:8]([OH:9])[CH2:7][CH2:6][N:5]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:4][CH2:3]1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)C(F)CC1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC(O)C(F)CC1
Temperature: 0 °C
Reaction time: 3 h
Yield: 97.2 %

Procedure:
To a 50 mL flask containing the product from Step B (1.0 g, 4.32 mmol) was added MeOH (20 mL), and the resulting solution was cooled to 0° C. NaBH4 (0.409 g, 10.8 mmol) was carefully added and the mixture stirred at 0° C. for 3.0 hours. The mixture was concentrated to remove the solvent and the residue was taken up in EtOAc (50 mL) and a saturated aqueous NH4Cl solution (20 mL) was added followed by water (20 mL). The layers were mixed and separated and the aqueous phase extracted with EtOAc (2×20 mL). The combined organic extracts were washed with brine and dried over Na2SO4, then filtered and concentrated. The crude product was purified by column chromatography (10% to 60% EtOAc/hexanes gradient) to provide 0.980 g (97%) of the product as a thick colorless oil that solidified to a white solid while standing overnight. The product contained of a mixture of cis and trans isomers.