Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH2:7][CH2:8][OH:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>[Ag].O>[C:1]1([CH2:7][CH:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OCCc1ccccc1
Agent: [Ag]
Solvent: O
Product: O=CCc1ccccc1
Reaction time: 0 h
Yield: 67 %

Procedure:
The same installation as in Example 1 is used. A catalyst comprising 82 parts of silver crystals of particle sizes from 0.1 to 2.5 mm is introduced, as a homogeneous bed, into the reactor. The height of the catalyst bed is 30 mm. Using a similar method to Example 1, a mixture of 150 parts of 2-phenylethanol and 60 parts of water with 210 parts of air is passed per hour over the catalyst at 540° C. and 1.1 bar. The residence time is 0.07 second and the throughput 0.2 tonne/m2.h. 99 parts of phenylacetaldehyde (in the form of a 73 percent strength by weight organic phase) are obtained per hour, corresponding to a yield of 67% of theory. The conversion is 78 percent and the space-time yield is 5 grams of phenylacetaldehyde per cm3 of catalyst volume per hour.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:12]=[C:11]([N+:13]([O-])=O)[CH:10]=[C:6]([C:7]([OH:9])=O)[CH:5]=1.Cl.[CH3:18][N:19](C)[CH2:20][CH2:21][CH2:22]N=C=NCC.ON1C2C=CC=CC=2N=N1.C(NC)CC.C(N(CC)CC)C>ClCCl.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:12]=[C:11]([NH2:13])[CH:10]=[C:6]([C:7]([N:19]([CH3:18])[CH2:20][CH2:21][CH3:22])=[O:9])[CH:5]=1
Reactant: COC(=O)c1cc(C(=O)O)cc([N+](=O)[O-])c1
Reactant: CCN=C=NCCCN(C)C
Agent: CCCNC
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CCCN(C)C(=O)c1cc(N)cc(C(=O)OC)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Mix 5-nitro-isophthalic acid monomethylester (3.0 g, 13.32 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (3.20 g, 16.65 mmol), and 1-hydroxybenzotriazole (2.25 g, 16.65 mmol) in dichloromethane (100 mL) at room temperature for 20 min. Add propylmethylamine (1.46 g, 16.65 mmol) and triethylamine (3.36 g, 33.3 mmol). Stir at room temperature for 1 h, dilute with ethyl acetate, wash with 10% aqueous potassium carbonate, 1 N citric acid, saturated aqueous sodium chloride and concentrate. Dissolve in ethanol (100 mL), add a slurry of 10% Pd/C (300 mg) in ethanol (10 mL) and place under a hydrogen atmosphere using a balloon and stir overnight. Flush with nitrogen, filter and concentrate to give the title-compound as an oil.
Reaction SMILES: [F:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]1([OH:18])[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:26][CH2:27][O:28][CH3:29].Cl>C(#N)C>[F:1][C:2]1[C:7]([C:8]([F:10])([F:11])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]1([OH:18])[CH2:17][CH2:16][N:15]([CH2:26][CH2:27][O:28][CH3:29])[CH2:14][CH2:13]1
Reactant: COCCBr
Reactant: OC1(c2cccc(C(F)(F)F)c2F)CCNCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COCCN1CCC(O)(c2cccc(C(F)(F)F)c2F)CC1

Procedure:
Preparation according to Example 2: 4-[2-fluoro-3-(trifluoromethyl)phenyl]piperidin-4-ol (0.31 g, 1.18 mmol), potassium carbonate (0.3 g, 2.17 mmol), acetonitrile (20 ml), 1-bromo-2-methoxy ethane (0.11 ml, 1.3 mmol). Yield: (0.29 g, 76%). The amine was converted to the hydrochloric acid salt and recrystallized from ethanol/diethyl ether: M.p. 159-160° C. MS m/z (relative intensity, 70 eV) 321 (M+, 3), 277 (13), 276 (bp), 258 (24) 191 (9).
Reaction SMILES: [CH2:1](N)[CH2:2]N.[C-]#[C-].[Li+].[Li+].Br[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:19]=[C:20]([C:24]([NH2:26])=[O:25])[CH:21]=[CH:22][CH:23]=1>CS(C)=O.Cl>[CH2:16]([O:17][C:18]1[CH:19]=[C:20]([C:24]([NH2:26])=[O:25])[CH:21]=[CH:22][CH:23]=1)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][C:1]#[CH:2]
Reactant: NC(=O)c1cccc(OCCCCCCCBr)c1
Reactant: NCCN
Agent: Cl
Agent: [C-]#[C-]
Agent: [Li+]
Solvent: CS(C)=O
Product: C#CCCCCCCCOc1cccc(C(N)=O)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 12.9 %

Procedure:
(Method F) Lithium acetylide ethylenediamine complex (305 mg, 3.3 mmol, 1.1 equiv.) was placed in a three-neck flask, degassed, flushed with N2 and suspended in DMSO (2 ml). To the stirred suspension a solution of 3-[(7-bromoheptyl)oxy]benzenecarboxamide (943 mg, 3 mmol, 1 equiv.) in DMSO (2 ml), was added, slowly, dropwise, at r.t., under N2. The reaction mixture was stirred at r.t. for 16 h. After that time it was diluted with 1N HCl solution and extracted with EtOAc (×3). The combined organic extracts were washed with brine, dried (Na2SO4) and evaporated to dryness under reduced pressure. The crude product was purified by column chromatography on silica eluting with EtOAc/hexane 20%, to give the desired compound as a white solid (100 mg, 13%), mp 82-83° C. HPLC-MS (method 1): m/z 260 [M+H]+, Rt=4.26 min.
Reaction SMILES: C(N(CC)CC)C.[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@:16]12[CH2:25][O:24][C@@H:23]([CH2:26][OH:27])[CH2:22][C@H:21]1[CH2:20][S:19][C:18]([NH:28][C:29](=[O:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[N:17]2.CS(C)=O>ClCCl.[Cl-].[Na+].O>[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@:16]12[CH2:25][O:24][C@@H:23]([CH:26]=[O:27])[CH2:22][C@H:21]1[CH2:20][S:19][C:18]([NH:28][C:29](=[O:36])[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[N:17]2
Reactant: O=C(NC1=N[C@@]2(c3ccc(F)cc3F)CO[C@@H](CO)C[C@H]2CS1)c1ccccc1
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C[C@H]1C[C@H]2CSC(NC(=O)c3ccccc3)=N[C@@]2(c2ccc(F)cc2F)CO1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
Triethylamine (75.9 mL, 545 mmol) was added to a solution of N-[(4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(hydroxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (P1) (19 g, 45 mmol) in dichloromethane (908 mL) in an ambient temperature water bath. After 5 minutes, dimethyl sulfoxide (45.2 mL, 636 mmol) was rapidly added, immediately followed by sulfur trioxide pyridine complex (98%, 59.0 g, 363 mmol) in a single portion. The resulting solution was stirred at room temperature for 4 hours, whereupon it was diluted with a 1:1 mixture of saturated aqueous sodium chloride solution and water, and stirred for 10 minutes. The aqueous layer was extracted twice with dichloromethane; the combined organic layers were washed with water until the pH of the aqueous extract was pH 6-7, then were washed twice with 0.2 N hydrochloric acid, and once with saturated aqueous sodium chloride solution. After being dried over sodium sulfate, the organic layer was filtered, and concentrated in vacuo. Silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane) provided the product as a pale yellow solid. Yield: 13.27 g, 31.86 mmol, 71%. 1H NMR (400 MHz, CDCl3) δ 9.71 (br s, 1H), 8.16-8.24 (m, 2H), 7.50-7.56 (m, 1H), 7.36-7.48 (m, 3H), 6.87-6.98 (m, 2H), 4.23 (dd, J=12.2, 1.6 Hz, 1H), 4.09-4.15 (m, 1H), 3.94 (d, J=12.1 Hz, 1H), 3.13-3.22 (m, 1H), 3.04 (dd, J=13.1, 4.0 Hz, 1H), 2.69 (dd, J=13.0, 2.9 Hz, 1H), 2.02-2.15 (m, 1H), 1.92-1.99 (m, 1H).
Reaction SMILES: [CH:1](=[O:7])[C:2]1[O:6][CH:5]=[CH:4][CH:3]=1.O1C[CH2:11][CH2:10][CH2:9]1>[Cl-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[OH:7][CH:1]([C:2]1[O:6][CH:5]=[CH:4][CH:3]=1)[CH2:11][C:10]#[CH:9]
Reactant: C1CCOC1
Reactant: O=Cc1ccco1
Agent: CCCCCCCCCCCCCCCC[N+](C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Solvent: Cc1ccccc1
Product: C#CCC(O)c1ccco1

Procedure:
Reaction and after-treatment were carried out in the same manner as in Example 18 except that an equimolar amount of furfural was used in place of 5-methylfurfural, and that cetyltrimethylammonium chloride and tetrahydrofuran were used in place of tetrabutylammonium bromide and toluene, respectively, in the same weights as those of the latter, to obtain 50.1 g of the fraction of 2-(1-hydroxy-3-butynyl)furan (content, 99.4%) (yield, 91.4%).
Reaction SMILES: [C:1]1(=[O:26])[N:5]([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:19]=[C:18]3[C:13]([CH2:14][CH2:15][CH2:16][C:17]3=O)=[CH:12][CH:11]=2)[C:4](=[O:21])[C:3]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:2]12.[CH3:27][NH:28][CH3:29]>C1(C)C=CC=CC=1.[Ti](Cl)(Cl)(Cl)Cl>[CH3:27][N:28]([CH3:29])[C:17]1[C:18]2[C:13](=[CH:12][CH:11]=[C:10]([O:9][CH2:8][CH2:7][CH2:6][N:5]3[C:4](=[O:21])[C:3]4=[CH:22][CH:23]=[CH:24][CH:25]=[C:2]4[C:1]3=[O:26])[CH:19]=2)[CH2:14][CH2:15][CH:16]=1
Reactant: O=C1CCCc2ccc(OCCCN3C(=O)c4ccccc4C3=O)cc21
Reactant: CNC
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: Cc1ccccc1
Product: CN(C)C1=CCCc2ccc(OCCCN3C(=O)c4ccccc4C3=O)cc21
Temperature: 1 °C
Reaction time: 2 h

Procedure:
A solution of titanium tetrachloride (5.4 g) in toluene (20 ml) is added over a period of 15 minutes to a stirred solution of 7-(3-phthalimido)propoxy-1-tetralone (19.9 g) suspended in a solution of anhydrous dimethyl amine (22 g) in dry toluene (200 ml) while maintaining a reaction temperature of about 1° C. under a N2 atmosphere. When the addition is complete, the reaction mixture is allowed to warm to RT and stirred at RT for 41/2 hours. The reaction mixture is filtered, the salts washed with dry toluene and the clear filtrate evaporated, affording a light yellow oil, which is stored under N2 and used in the next step without any further treatment.
Reaction SMILES: [H-].[Na+].[OH:3][CH2:4][CH2:5][N:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1.[CH3:11][O:12][C:13]1[CH:14]=[CH:15][C:16]2[C:20]([C:21]([C:23]3[CH:28]=[CH:27][C:26](F)=[C:25]([Br:30])[CH:24]=3)=[O:22])=[C:19]([C:31]3[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][N:40]4[CH2:44][CH2:43][CH2:42][CH2:41]4)=[CH:33][CH:32]=3)[S:18][C:17]=2[CH:45]=1.O>CN(C=O)C>[CH3:11][O:12][C:13]1[CH:14]=[CH:15][C:16]2[C:20]([C:21]([C:23]3[CH:28]=[CH:27][C:26]([O:3][CH2:4][CH2:5][N:6]4[CH2:10][CH2:9][CH2:8][CH2:7]4)=[C:25]([Br:30])[CH:24]=3)=[O:22])=[C:19]([C:31]3[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][N:40]4[CH2:41][CH2:42][CH2:43][CH2:44]4)=[CH:33][CH:32]=3)[S:18][C:17]=2[CH:45]=1
Reactant: COc1ccc2c(C(=O)c3ccc(F)c(Br)c3)c(-c3ccc(OCCN4CCCC4)cc3)sc2c1
Reactant: OCCN1CCCC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc2c(C(=O)c3ccc(OCCN4CCCC4)c(Br)c3)c(-c3ccc(OCCN4CCCC4)cc3)sc2c1
Reaction time: 0.08 h
Yield: 10 %

Procedure:
Sodium hydride (95 mg of a 60% suspension in mineral oil; 2.4 mmol) was suspended in 22 mL of DMF in a flame-dried, argon-filled flask and stirred for about 5 min. 1-(2-Hydroxyethyl)pyrrolidine (0.23 mL; 2.0 mmol) was added and the mixture was stirred for 15 min. 3-Bromo-4-fluorophenyl 6-methoxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl ketone in 3 mL of DMF was then added. The mixture was stirred for 4 h at room temperature, then poured into water (25 mL), and extracted with EtOAc (4×25 mL). The combined organics were washed with brine and dried over magnesium sulfate. The title compound (135 mg; 10% yield) was isolated by flash chromatography on silica gel eluting with a gradient of EtOAc(100-90%)/Et3N(0-5%)/MeOH(0-5%).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[S:7][CH:8]=[CH:9][N:10]=1.[CH3:11][N:12]=[C:13]=[S:14]>C(O)C.C(OCC)(=O)C>[CH3:11][NH:12][C:13]([NH:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[S:7][CH:8]=[CH:9][N:10]=1)=[S:14]
Reactant: CN=C=S
Reactant: NCCCCc1nccs1
Solvent: CCOC(C)=O
Solvent: CCO
Product: CNC(=S)NCCCCc1nccs1
Yield: 85.2 %

Procedure:
2-(4-Phthalimidobutyl)thiazole (5.0 g) is hydrolysed with hydrochloric acid in the usual way. The amine hydrochloride obtained is basified with potassium carbonate and extracted with ether-ethanol (3:1 ) to give 2-(4-amino-butyl)thiazole as a colourless oil. The reaction of the amine (2.0 g) and methyl isothiocyanate (0.98 g) in ethanol (10 ml) for 1 hour, followed by chromatography of the product on silica gel with ethyl acetate as eluent gives N-methyl-N'-(4-(2-thiazolyl)butyl)thiourea (2.5 g) as a colourless oil. Formation of the hydrobromide salt yields a crystalline solid, m.p. 130°-132°C.
Reaction SMILES: [C@@H:1]12[CH2:7][NH:6][C@@H:5]1[CH2:4][N:3]([C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9])[CH2:2]2.Br[C:19]1[CH:20]=[N:21][CH:22]=[C:23]([O:25][CH3:26])[CH:24]=1>>[CH3:26][O:25][C:23]1[CH:24]=[C:19]([N:6]2[CH2:7][C@@H:1]3[C@H:5]2[CH2:4][N:3]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:2]3)[CH:20]=[N:21][CH:22]=1
Reactant: COc1cncc(Br)c1
Reactant: O=C(OCc1ccccc1)N1C[C@@H]2CN[C@@H]2C1
Product: COc1cncc(N2C[C@H]3CN(C(=O)OCc4ccccc4)C[C@H]32)c1
Yield: 36.4 %

Procedure:
The product of Example 52D (940 mg, 4.05 mmol) and 3-bromo-5-methoxypyridine (1.13 g, 6.07 mmol) were processed according to the procedure described in Example 1E. The crude product was purified by chromatography (SiO2, ethyl acetate:hexane, 1:1) to provide the title compound (0.50 g, 37% yield). MS (DCI/NH3) m/z 340 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[CH3:13][N:14]1[CH:19]2[CH2:20][CH2:21][CH:15]1[CH2:16][C:17](=[O:22])[CH2:18]2>>[CH3:13][N:14]1[CH:19]2[CH2:20][CH2:21][CH:15]1[CH2:16][C:17]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)([OH:22])[CH2:18]2
Reactant: Brc1ccccc1
Reactant: CN1C2CCC1CC(=O)C2
Agent: [Li]CCCC
Product: CN1C2CCC1CC(O)(c1ccccc1)C2

Procedure:
The title compound was prepared from bromobenzene (42.1 mL, 0.4 mol), n-butyllithium in hexanes (156 mL, 2.5 M, 0.39 mol) and 8-methyl-8-azabicyclo[3.2.1]-octan-3-one (25 g, 0.18 mol). Yield 14 g (36%), m.p. 157-159° C.
Reaction SMILES: Cl.[Cl:2][CH2:3][C:4]1[N:5]=[CH:6][NH:7][CH:8]=1.[N+:9]([C:12]1[CH:17]=[C:16]([N+:18]([O-:20])=[O:19])[CH:15]=[CH:14][C:13]=1F)([O-:11])=[O:10].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[N+:9]([C:12]1[CH:17]=[C:16]([N+:18]([O-:20])=[O:19])[CH:15]=[CH:14][C:13]=1[N:7]1[CH:8]=[C:4]([CH2:3][Cl:2])[N:5]=[CH:6]1)([O-:11])=[O:10]
Reactant: O=[N+]([O-])c1ccc(F)c([N+](=O)[O-])c1
Reactant: ClCc1c[nH]cn1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: O=[N+]([O-])c1ccc(-n2cnc(CCl)c2)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4-(Chloromethyl)imidazole hydrochloride (790 mg) was dissolved in 20 ml of acetonitrile. To this solution was added 713 μL of 2,4-dinitrofluorobenzene and 2.14 g of potassium carbonate. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between ethyl acetate and water. The organic layer was dried (sodium sulfate) and concentrated. The crude reaction product was purified by flash silica gel chromatography (8:2 ethyl acetate-hexane elution) to give 745 mg of the title compound.
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:23][CH2:24][C:25]1[N:29]([C:30]2[S:31][C:32]([CH2:44][CH3:45])=[CH:33][C:34]=2[C:35](=[O:43])[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[Cl:42])[C:28]([CH3:46])=[N:27][N:26]=1.[C:47]1([N:53]=[C:54]=[O:55])[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.C(N(CC)CC)C>ClC(Cl)C>[Cl:42][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=1[C:35]([C:34]1[CH:33]=[C:32]([CH2:44][CH3:45])[S:31][C:30]=1[N:29]1[C:28]([CH3:46])=[N:27][N:26]=[C:25]1[CH2:24][NH:23][C:54]([NH:53][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:55])=[O:43]
Reactant: CCc1cc(C(=O)c2ccccc2Cl)c(-n2c(C)nnc2CN)s1
Reactant: O=C=Nc1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCN(CC)CC
Solvent: CC(Cl)Cl
Product: CCc1cc(C(=O)c2ccccc2Cl)c(-n2c(C)nnc2CNC(=O)Nc2ccccc2)s1
Reaction time: 4 h

Procedure:
3-Aminomethyl-4-(3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl)-5-methyl[1,2,4]triazole di-p-toluenesulfonate (5.0 g) was dissolved in dichloroethane (80 ml). Phenyl isocyanate (0.807 ml) and triethylamine (2.8 ml) were added at room temperature, and the mixture was stirred for 4 hours. Then, the reaction mixture was washed with water and dried over magnesium sulfate. The solvent was evaporated, and the residue was recrystallized from ethyl acetate to give 2.1 g of N-(4-(3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl)-5-methyl[1,2,4]triazol-3-ylmethyl)-N'-phenylurea.
Reaction SMILES: [CH3:1][C:2]([CH3:4])=O.[CH3:5][N:6]([CH3:14])[C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=1.C(O)(=O)C.C([BH3-])#N.[Na+].C1COCC1>CO>[CH:2]([NH:13][C:10]1[CH:11]=[CH:12][C:7]([N:6]([CH3:14])[CH3:5])=[CH:8][CH:9]=1)([CH3:4])[CH3:1]
Reactant: CN(C)c1ccc(N)cc1
Reactant: CC(C)=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CC(C)Nc1ccc(N(C)C)cc1
Reaction time: 8 h
Yield: 106.5 %

Procedure:
Acetone (30 mL, 408 mmol) is added to a mixture of N',N'-dimethyl-benzene-1,4-diamine (27.2 g, 200 mmol), acetic acid (glacial, 13.8 mL, 241 mmol), methanol (500 mL), and sodium cyanoborohydride in THF (1M, 440 mL, 440 mmol) and allowed to stir overnight under nitrogen. After concentrating in vacuo to a residue, the reaction mixture is partitioned between ethyl acetate and aqueous sodium carbonate. The layers are separated and the aqueous layer is extracted twice with ethyl acetate. The organic layers are combined, extracted with saturated brine, dried over anhydrous potassium carbonate, and concentrated in vacuo to afford the title compound as an oil (38.0 g, 213 mmol) of sufficient purity for the next step. 1H NMR (300 MHz, CDCl3) δ=1.18 (d, J=6.28 Hz, 6H); 2.82 (s, 6H); 3.04 (b, 1H), 3.47-3.59 (m, 1H); 6.59 (d, J=9.0 Hz, 2H); 6.73 (d, J=9.0 Hz, 2H). TLC Rf -0.3 (20:80 ethyl acetate: n-hexane).
Reaction SMILES: C([O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[CH:8]2)C=C.[CH3:14][C:15]1C=CC(C)=C(C)[C:16]=1C>>[CH2:16]([C:6]1[C:5]([OH:4])=[CH:13][CH:12]=[C:11]2[C:7]=1[CH:8]=[CH:9][NH:10]2)[CH:15]=[CH2:14]
Reactant: C=CCOc1ccc2[nH]ccc2c1
Reactant: Cc1ccc(C)c(C)c1C
Product: C=CCc1c(O)ccc2[nH]ccc12
Temperature: 190 °C
Yield: 70 %

Procedure:
5-(Allyloxy)-1H-indole (514 mg, 2.97 mmol) (Example 53) was dissolved in 1,2,3,4-tetramethylbenzene (2.5 mL), and the reaction mixture was heated at 190° C. for 2 h. The mixture was cooled to rt and sonicated for 30 min. The mixture was then purified by silica gel column chromatography (EtOAc/hexane (v/v)=1:9) to give 361 mg (70%) of the title compound as a white crystalline solid. 1H NMR (400 MHz, CDCl3): δ 3.68 (d, 2H), 5.13 (d, 1H), 5.18 (d, 1H), 6.07 (m, 1H), 6.45 (s, 1H), 6.79 (d, 1H), 7.12-7.18 (m, 2H), 8.06 (br, 1H).
Reaction SMILES: [CH:1]1[C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH2:7][NH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH3:15][C:16]1[CH:33]=[CH:32][CH:31]=[CH:30][C:17]=1[C:18]([NH:20][C:21]1[CH:29]=[CH:28][C:24]([C:25](Cl)=[O:26])=[CH:23][CH:22]=1)=[O:19].Cl>N1C=CC=CC=1>[CH3:15][C:16]1[CH:33]=[CH:32][CH:31]=[CH:30][C:17]=1[C:18]([NH:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([N:6]2[CH2:7][C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:14]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]2=3)=[O:26])=[CH:23][CH:22]=1)=[O:19]
Reactant: Cc1ccccc1C(=O)Nc1ccc(C(=O)Cl)cc1
Reactant: c1ccc2c(c1)CNc1ccccc1-2
Agent: Cl
Solvent: c1ccncc1
Product: Cc1ccccc1C(=O)Nc1ccc(C(=O)N2Cc3ccccc3-c3ccccc32)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 18.9 %

Procedure:
To a solution of 0.181 g (1.0 mmol) of 5,6-dihydrophenanthridine in 2 ml of warm pyridine is added 0.273 g (1.0 mmol) of 4-[(2-methylbenzoyl)amino]benzoyl chloride. The mixture is stirred overnight at room temperature, 1.2 ml of 2N HCl added. The solid which separates is filtered and washed with water. The solid is dissolved in dichloromethane and the solution washed with 2M sodium carbonate. The organic layer is concentrated and the residue chromatographed twice on silica gel with ethyl acetate-hexane as solvent to give 79 mg of crystals, m.p. 190°-194° C. Mass Spec-FAB 419 (M+H).
Reaction SMILES: [CH3:1][C:2]1[C:10]2[N:9]=[C:8]([CH2:11][CH2:12][CH3:13])[N:7]([CH2:14][C:15]3[CH:32]=[CH:31][C:18]4/[C:19](=[CH:28]\[C:29]#[N:30])/[C:20]5[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=5[O:22][CH2:23][C:17]=4[CH:16]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.N[OH:34].O>C(O)C>[CH3:1][C:2]1[C:10]2[N:9]=[C:8]([CH2:11][CH2:12][CH3:13])[N:7]([CH2:14][C:15]3[CH:32]=[CH:31][C:18]4[C:19](=[CH:28]/[CH:29]=[N:30]/[OH:34])[C:20]5[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=5[O:22][CH2:23][C:17]=4[CH:16]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: CCCc1nc2c(C)cccc2n1Cc1ccc2c(c1)COc1ccccc1/C2=C/C#N
Reactant: NO
Solvent: CCO
Solvent: O
Product: CCCc1nc2c(C)cccc2n1Cc1ccc2c(c1)COc1ccccc1C2=C/C=N/O
Yield: 93.9 %

Procedure:
[step 1] (E)-2-{8-(4-Methyl-2-propylbenzimidazol-1-yl)methyl-6,11-dihydrodibenzo[b,e]oxepin-11-ylidene}acetonitrile (310 mg, 0.74 mmol) obtained in Example 104, step 1 was dissolved in ethanol (3.7 mL), hydroxylamine (50% aqueous solution, 2.3 mL, 36.95 mmol) was added, and the mixture was stirred under reflux for 16 hr. Water was added to the mixture, and the precipitated solid was collected by filtration to give (E)-2-[8-(4-methyl-2-propylbenzimidazol-1-yl)methyl-6,11-dihydrodibenzo[b,e]oxepin-11-ylidene]acetaldoxime (304 mg, 91%). [step 2] Using (E)-2-[8-(4-methyl-2-propylbenzimidazol-1-yl)methyl-6,11-dihydrodibenzo[b,e]oxepin-11-ylidene]acetaldoxime (150 mg, 0.33 mmol) obtained in step 1 and in the same manner as in Example 107, the title compound (compound 108) (7.1 mg, 5%) was obtained.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:25](O)=[O:26])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(OCC)=O.S(C1C=CC(C)=CC=1)(O)(=O)=O.[CH2:45]([O:52][C:53](=[O:56])[CH2:54][NH2:55])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.ClCl.CC1C=C(C2C=CC(N)=C(C)C=2)C=CC=1N.II>O1CCCC1.CO.C(N(CC)CC)C>[CH2:45]([O:52][C:53](=[O:56])[CH2:54][NH:55][C:25](=[O:26])[C@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:15][CH:16]=1)[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(OCc2ccccc2)cc1)C(=O)O
Reactant: NCC(=O)OCc1ccccc1
Agent: CCOC(=O)Cl
Agent: Cc1cc(-c2ccc(N)c(C)c2)ccc1N
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(OCc2ccccc2)cc1)C(=O)NCC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 93 %

Procedure:
N-tert-Butyloxycarbonyl-O-benzyltyrosine (LV) (27.6 g) and dry tetrahydrofuran (100 ml) at 0° C. were treated successively with triethylamine (10.3 ml), ethyl chloroformate (7.1 ml) and, after an hr, glycine benzyl ester tosylate (XXXVI) (25 g) and triethylamine (10.3 ml) in dry tetrahydrofuran (100 ml). After being stirred at room temperature during 16 hr, the reaction mixture was evaporated to dryness. The residue was dissolved in ethyl acetate (400 ml) and the solution was washed with 5% citric acid (2×50 ml), 5% sodium bicarbonate solution (2×50 ml) and water 2×50 ml). The organic layer was dried (Na2SO4) and evaporated. The residue was crystallized from methanol-n-hexane to afford the (LVI); 35.7 g, yield 93%; m.p. 101°-4° C; [α]D22 + 1.2° (c 1.29, methanol); Rf4 0.91; single spot with chlorine/tolidine and iodine reagents. τCDCL3 2.65, d, 10H benzylic aromatic protons; 4.86, s,2H and 4.98,s,2H benzylic methylene protons and 8.64,s,9H butyloxy protons.
Reaction SMILES: [C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4])[OH:2].[O-]CCCC.[Hf+4:14].[O-]CCCC.[O-]CCCC.[O-]CCCC>C1(C)C=CC=CC=1>[C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[O-:4])[O-:2].[Hf+4:14].[C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[O-:4])[O-:2]
Reactant: Oc1ccccc1O
Agent: [Hf+4]
Agent: CCCC[O-]
Solvent: Cc1ccccc1
Product: [O-]c1ccccc1[O-]
Temperature: 100 °C

Procedure:
A solution of catechol (2.34 g, 2.12 mmol) and toluene (26 ml) was dehydrated by distilling 5 mL of the solution. Thereafter, 5.00 g (10.6 mmol) of hafnium(IV) butoxide was added to the solution while stirring. The mixed solution was refluxed for 1 hour, and then, while the distillation temperature was 100° C. or higher, distilled until the amount of the solution became half. After the distillation, solid content of the product was isolated by suction filtering using a membrane suction filter. The residual solid content was heated to 100° C. under vacuum using a vacuum dryer so that remaining volatile components were completely removed. The solid content (catechol-hafnium complex) was black in color. The yield amount was 4.18 g (10.6 mmol), and the yield percentage was 100%. Catechol-hafnium complex was dissolved into acetylacetone until saturated, and then filtered to be used as a coating liquid.