Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:4][CH2:5][CH:6]([O:9][CH2:10][N:11]1[CH:15]=[CH:14][N:13]=[C:12]1[N+:16]([O-:18])=[O:17])[CH2:7]O)(=[O:3])[CH3:2].C1(C)[C:20]([S:25](Cl)(=[O:27])=[O:26])=CC=CC=1>N1C=CC=CC=1>[C:1]([O:4][CH2:5][CH:6]([O:9][CH2:10][N:11]1[CH:15]=[CH:14][N:13]=[C:12]1[N+:16]([O-:18])=[O:17])[CH2:7][S:25]([CH3:20])(=[O:27])=[O:26])(=[O:3])[CH3:2]
Reactant: Cc1ccccc1S(=O)(=O)Cl
Reactant: CC(=O)OCC(CO)OCn1ccnc1[N+](=O)[O-]
Solvent: c1ccncc1
Product: CC(=O)OCC(CS(C)(=O)=O)OCn1ccnc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 5 h

Procedure:
117 mg of the thus-obtained 1-[1-acetoxymethyl-2-(hydroxy)ethoxy]methyl-2-nitroimidazole was placed in a flask together with dry pyridine, and 252 mg of toluenesulfonyl chloride was added. The mixture was stirred for 5 hours at room temperature. The reaction mixture was extracted with 30 ml of added ethyl acetate, and the obtained extract was subjected to partition and water washing, two times with 30 ml of water. The organic phase was dried over sodium sulfate, subsequently concentrated under reduced pressure, and purified by silica gel column chromatography, to obtain 1-[1-acetoxymethyl-2-mesylethoxy]methyl-2-nitroimidazole. 10 ml of dry DMF was added to dissolve the product, and the solution was added to a mixture which had been prepared by mixing 10 ml of acetonitrile and 1 ml of water in advance, adding 33.8 mg of potassium fluoride and 80 mg of 18-crown-6, and drying under reduced pressure. The resulting mixture was heated at 110° C. for 8 hours. To the obtained reaction mixture, 20 ml of ethyl acetate was added, and the mixture was washed with 20 ml of water. The aqueous phase was extracted two times with 20 ml of ethyl acetate, and the obtained extract was combined with the organic phase and dried to solid under reduced pressure. The dried product was purified by preparative high performance chromatography, to obtain 15.4 mg of 1-(1-hydroxymethyl-2-fluoro)ethoxymethyl-2-nitroimidazole. From the mass analysis results for this product, M+1(219) was recognized, and thus the structure was confirmed. Also, the elemental analysis values resulted in 38.55% of carbon, 4.11% of hydrogen, 19.28% of nitrogen, and 8.70% of fluorine, thus supporting the structure.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)=[CH:14][CH:15]=2)[C:10]([C:28](=[O:34])[C:29]([O:31]CC)=[O:30])=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+].Cl>C1COCC1.O>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:25])[F:26])=[CH:19][CH:18]=3)=[CH:14][CH:15]=2)[C:10]([C:28](=[O:34])[C:29]([OH:31])=[O:30])=[CH:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)C(=O)c1cn(Cc2ccccc2)c2ccc(-c3ccc(OC(F)(F)F)cc3)cc12
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)C(=O)c1cn(Cc2ccccc2)c2ccc(-c3ccc(OC(F)(F)F)cc3)cc12
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 72.1 %

Procedure:
A mixture of ethyl 2-{1-benzyl-5-[4-(trifluoromethoxy)phenyl]-1H-indol-3-yl}-2-oxoacetate (0.463 g, 0.991 mmol), potassium hydroxide (0.224 g, 3.99 mmol) in THF (5 mL) and water (5 mL) was stirred for 40 minutes at room temperature then poured into excess water, acidified with 2N hydrochloric acid and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over anhydrous magnesium sulfate, and evaporated to dryness. The residue was dried for 15 hours at 80° C. to yield the title compound as a light yellow solid (0.314 g, 78%), mp 169–171° C. A sample was crystallized from acetonitrile for analysis. Mass spectrum (+APCI, [M+H]+) m/z 440; 1HNMR (400 MHz, DMSO-d6): δ13.8–14.2 (br, 1H), 8.75 (s, 1H), 8.45 (d, 1H, J=1.5 Hz), 7.75–7.8 (m, 2H), 7.7 (d, 1H, J=8.5 Hz), 7.6 (dd, 1H, J=8.7 Hz), 7.45 (d, 2H, J=8.8 Hz), 7.25–7.35 (m, 5H), and 5.65 ppm (s, 2H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH:9]([NH2:15])[CH2:8][CH2:7][CH2:6][C:5]2=1.[C:16](Cl)(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(N(C(C)C)CC)(C)C>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH:9]([NH:15][C:16](=[O:23])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:8][CH2:7][CH2:6][C:5]2=1
Reactant: O=C(Cl)c1ccccc1
Reactant: NC1CCCc2c1[nH]c1ccc(Br)cc21
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NC1CCCc2c1[nH]c1ccc(Br)cc21)c1ccccc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 25.7 %

Procedure:
To a solution of 6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-amine (50 mg, 0.19 mmol) and benzoyl chloride (24 μL, 0.21 mmol) in dichloromethane (1 mL) at 0° C. was added diisopropylethylamine (66 μL, 0.38 mmol). The mixture was stirred at room temperature 15 hours, the solvent removed, and the residue purified by flash chromatography (0-30% ethyl acetate-hexanes) to give 18 mg (26% yield) of a yellow solid. 1H-NMR (CDCl3): δ 8.97 (s, 1H), 7.78 (d, 2H), 7.61 (m, 1H), 7.52 (m, 1H), 7.44 (t, 2H), 7.23 (m, 1H), 7.17 (d, 1H), 6.42 (d, 1H), 5.34 (m, 1H), 2.72 (m, 2H), 2.32 (m, 1H), 2.02-1.93 (m, 3H); MS m/z 369 (M−1).
Reaction SMILES: [N:1]1[O:2][N:3]=[C:4]2[CH:9]=[C:8]([C:10](=[O:17])[C:11]#[C:12][C:13](O)([CH3:15])[CH3:14])[CH:7]=[CH:6][C:5]=12.C(NCC)C.C([OH:25])C>>[N:1]1[O:2][N:3]=[C:4]2[CH:9]=[C:8]([C:10]3[O:17][C:13]([CH3:14])([CH3:15])[C:12](=[O:25])[CH:11]=3)[CH:7]=[CH:6][C:5]=12
Reactant: CC(C)(O)C#CC(=O)c1ccc2nonc2c1
Reactant: CCO
Solvent: CCNCC
Product: CC1(C)OC(c2ccc3nonc3c2)=CC1=O
Reaction time: 2 h
Yield: 83 %

Procedure:
To a stirred solution of 1-(benzo[c][1,2,5]oxadiazol-5-yl)-4-hydroxy-4-methylpent-2-yn-1-one (0.3 g, 1.304 mmol) in ethanol (15 mL), a solution of diethyl amine (0.095 g, 1.304 mmol) in EtOH (5 mL) was added dropwise at RT. The reaction mixture was then stirred for 2 h. The ethanol was then removed, and the mixture was diluted with EtOAc (10 mL). The combined organic layers were washed with water (5 mL) and brine (10 mL), dried over Na2SO4, filtered, and concentrated in vacuo to afford 5-(benzo[c][1,2,5]oxadiazol-5-yl)-2,2-dimethylfuran-3(2H)-one (0.25 g, 83%) as a black oil.
Reaction SMILES: [CH3:1][CH:2]([C:8]([O:10]CC)=O)[C:3]([O:5][CH2:6][CH3:7])=[O:4].N1C=CC=CC=1.[Cl:19][C:20]1[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:21]=1[NH2:22]>>[Cl:19][C:20]1[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:21]=1[NH:22][C:8](=[O:10])[CH:2]([CH3:1])[C:3]([O:5][CH2:6][CH3:7])=[O:4]
Reactant: CCOC(=O)C(C)C(=O)OCC
Reactant: Nc1cccc(F)c1Cl
Solvent: c1ccncc1
Product: CCOC(=O)C(C)C(=O)Nc1cccc(F)c1Cl

Procedure:
The ester was prepared according to Procedure A using diethyl 2-methylmalonate (5.32 mL, 30.9 mmol), pyridine (3.33 mL, 41.2 mmol) and 2-chloro-3-fluoroaniline (3.00 g, 20.61 mmol) over 7 days. The residue was purified by column chromatography on silica gel (0-30% EtOAc/hexanes) to give ethyl 3-(2-chloro-3-fluorophenylamino)-2-methyl-3-oxopropanoate as a red oil. Mass Spectrum (ESI) m/e=274.0 (M+1).
Reaction SMILES: [C:1]([C:9]1[S:13][C:12]2[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=2[C:10]=1[OH:18])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=O)C.[NH4+:23]>CS(C)=O>[NH2:23]/[C:1](/[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[C:9]1\[C:10](=[O:18])[C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=2[S:13]\1
Reactant: [NH4+]
Reactant: O=C(c1ccccc1)c1sc2ccccc2c1O
Agent: CC(=O)[O-]
Solvent: CS(C)=O
Product: N/C(=C1/Sc2ccccc2C1=O)c1ccccc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A mixture of 35.0 gm (0.138 mol) of 2-benzoylbenzo[b]-thiophen-3-ol, 24.0 gm (0.311 mol) of ammonium acetate and 25 cc of dimethylsulfoxide was stirrd for one hour at a reaction temperature of 125° C. The cooled reaction mixture was stirred into a mixture of 150 cc of petroleum ether and 300 cc of ice water. The resulting suspension was filtered with suction, and the filter residue was thoroughly washed with water. For purification purposes, the dried crude product was taken up in 40 cc of ethyl acetate, and just enough petroleum ether was added to ensure that no further precipitate formed (about 20 cc). 5 gm of activated carbon were added, followed by boiling and filtering while hot. The pure product was obtained from the crude filtrate by adding 60 cc of petroleum ether and cooling to +10° C. Further product of the same quality was obtained by concentrating the mother liquor to approximately 30 cc total volume. The combined crystalline product was washed with petroleum ether and dried in vacuo, yielding 25.2 gm (72% of theory) of the desired product, m.p. 121.6°-122.5° C., which was found to be identical with that of Example 1 based on its thin-layer chromatogram, mixed melting point and IR spectrum.
Reaction SMILES: COC1C=C(OC)C=CC=1C[N:6]1[C:11](=[O:12])[C:10]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]3[NH:30][C:29](=[O:31])[O:28][N:27]=3)=[CH:16][C:15]=2[F:32])=[C:9]([CH2:33][CH2:34][CH3:35])[N:8]2[N:36]=[CH:37][N:38]=[C:7]12.FC(F)(F)C(O)=O>C1(C)C=CC=CC=1>[F:32][C:15]1[CH:16]=[C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[C:26]2[NH:30][C:29](=[O:31])[O:28][N:27]=2)[CH:18]=[CH:19][C:14]=1[CH2:13][C:10]1[C:11](=[O:12])[NH:6][C:7]2[N:8]([N:36]=[CH:37][N:38]=2)[C:9]=1[CH2:33][CH2:34][CH3:35]
Reactant: CCCc1c(Cc2ccc(-c3ccccc3-c3noc(=O)[nH]3)cc2F)c(=O)n(Cc2ccc(OC)cc2OC)c2ncnn12
Solvent: Cc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: CCCc1c(Cc2ccc(-c3ccccc3-c3noc(=O)[nH]3)cc2F)c(=O)[nH]c2ncnn12
Temperature: 25 °C
Reaction time: 16 h
Yield: 9.8 %

Procedure:
A mixture of 4-(2,4-dimethoxybenzyl)-6-{[3-fluoro-2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one (0.3 g), trifluoroacetic acid (5 mL) and toluene (5 mL) was stirred at room temperature for 16 hr. The reaction mixture was concentrated, and the residue was purified by silica gel column chromatography to give the title compound as a colorless amorphous solid (0.022 g, 10%).
Reaction SMILES: [NH2:1][CH2:2][C:3]1([O:10][CH3:11])[CH2:7][CH2:6][CH:5]([O:8][CH3:9])[O:4]1.C(N(CC)CC)C.[C:19](Cl)(=[O:21])[CH3:20]>O1CCCC1>[CH3:11][O:10][C:3]1([CH2:2][NH:1][C:19](=[O:21])[CH3:20])[CH2:7][CH2:6][CH:5]([O:8][CH3:9])[O:4]1
Reactant: CC(=O)Cl
Reactant: COC1CCC(CN)(OC)O1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COC1CCC(CNC(C)=O)(OC)O1
Reaction time: 1 h
Yield: 82.8 %

Procedure:
11.5 [lacuna] (71.3 mmol) of 2-aminomethyl-2,5-dimethoxytetrahydrofuran and 20 ml (143 mmol) of triethylamine were dissolved in 150 ml of anhydrous tetrahydrofuran. At 0° C., a solution of 5 ml (71.3 mmol) of acetyl chloride in 50 ml of tetrahydrofuran was added dropwise, and the mixture was stirred for 1 h. The precipitate was filtered off and the filtrate was concentrated under reduced pressure. 12 g of crude product were obtained and were reacted further without purification.
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H][H]>C(O)C.[Ni]>[C:1]1([C@H:7]2[CH2:8][CH2:9][C@H:10]([OH:13])[CH2:11][CH2:12]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: [H][H]
Reactant: Oc1ccc(-c2ccccc2)cc1
Agent: [Ni]
Solvent: CCO
Product: O[C@H]1CC[C@H](c2ccccc2)CC1

Procedure:
p-Phenylphenol (VI) (1 kg, 5.88 mols) dissolved in ethanol (2 l) was fed into a 5 l autoclave, and hydrogenation reaction was carried out at a reaction temperature of 150° to 160° C. under a hydrogen pressure of 30 to 40 kg/cm2 using a developed Raney nickel (100 g) as catalyst. When 17.6 mols of hydrogen were absorbed, the reaction was stopped. After cooling, the catalyst was filtered off, and the filtrate was concentrated to remove ethanol. The resulting residue was dissolved in toluene. The toluene solution was washed a few times with 2 N--NaOH aqueous solution and further with water, and toluene was then removed by concentration of the solution. The resulting raw crystals were recrystallized from ethanol to obtain trans-4-phenylcyclohexanol (VII) (200 g) having a melting point of 118.4°-119.2° C.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[O:17]COCC[Si](C)(C)C)[OH:10])=[CH:5][CH:4]=1)[CH3:2].O1CCCC1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>O>[CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([CH:9]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[OH:17])[OH:10])=[CH:7][CH:8]=1)[CH3:2]
Reactant: CCc1ccc(C(O)c2ccncc2OCOCC[Si](C)(C)C)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCc1ccc(C(O)c2ccncc2O)cc1
Temperature: 50 °C
Reaction time: 3 h
Yield: 85.5 %

Procedure:
Next, to a mixture of (4-ethylphenyl)-[3-[2-(trimethylsilyl)ethoxymethoxy]pyridin-4-yl]-methanol (20 g, 55.6 mmol), tetrahydrofuran (500 ml) and water (20 ml), p-toluenesulfonic acid monohydrate (26.3 g, 138 mmol) was added. After stirring at 50° C. for 4 hours, at room temperature for 15.5 hours and at 50° C. for 3 hours, the reaction mixture was neutralized with saturated aqueous sodium bicarbonate and extracted three times with chloroform. The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=10:1) to give (4-ethylphenyl)-(3-hydroxypyridin-4-yl)-methanol (10.9 g, 86%) as a light-yellow amorphous substance.
Reaction SMILES: [C:1]1(S(OCC#C)(=O)=O)[CH:6]=CC=C[CH:2]=1.[NH2:14][CH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][CH2:16]1.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH:2]#[C:1][CH2:6][NH:14][C@H:15]1[C:23]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH2:17][CH2:16]1
Reactant: C#CCOS(=O)(=O)c1ccccc1
Reactant: NC1CCc2ccccc21
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: C#CCN[C@@H]1CCc2ccccc21

Procedure:
U.S. Pat. No. 5,532,415 discloses process for preparation of R(+)-Rasagiline mesylate which comprises treating a solution of propargyl benzenesulfonate (3) and racemic aminoindan (2) in toluene with aqueous solution of 15% sodium hydroxide to get racemic Rasagiline base (4). The obtained crude racemic Rasagiline is treated with L-tartaric acid in isopropanol (IPA) to get di(R-(+)-N-propargyl-1-aminoindan)-L-tartrate (5) which is recrystallized from 1:1 methanol/isopropanol. The obtained tartrate salt is reacted with methanesulphonic acid in isopropanol at reflux to obtain R(+)-Rasagiline mesylate. The disadvantage of this process is that the scheme consists of low atom efficiency and involves several steps to obtain the final product.
Reaction SMILES: [C:1](Cl)(=O)[CH:2]=[CH2:3].C(N([CH2:11][CH3:12])CC)C>C1COCC1>[CH3:3][CH2:2][CH2:1][CH2:3][CH2:2][CH2:1][CH2:11][CH2:12][CH2:11][CH3:12]
Reactant: C=CC(=O)Cl
Reactant: CCN(CC)CC
Solvent: C1CCOC1
Product: CCCCCCCCCC
Temperature: 60 °C
Reaction time: 3 h
Yield: 52 %

Procedure:
A mixture of 1 mmol of α,α-dimethyl-2-endotricyclo[5.2.1.02,6]decanemethanol obtained according to Example 9, 1.5 mmol of acrylic chloride, 1.5 mmol of triethylamine, and 3 ml of THF was stirred at 60° C. for 3 hours. The resulting reaction mixture was subjected to column chromatography on a silica gel to yield 4a-(1-acryloyloxy-1-methylethyl)-endotricyclo[5.2.1.02,6]decane represented by the following formula (yield: 52%).
Reaction SMILES: [C:1]1([N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:9][C:8]2=[S:16])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:24][C:25]#[C:26][CH2:27][OH:28]>CC(C)=O.C1C=CC=CC=1>[C:1]1([N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[C:8]2[S:16][CH2:24][CH:25]=[CH:26][CH2:27][OH:28])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: S=C1Cc2ccccc2N1c1ccccc1
Reactant: OCC#CCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: c1ccccc1
Product: OCC=CCSc1cc2ccccc2n1-c1ccccc1
Reaction time: 4 h
Yield: 107.5 %

Procedure:
To a solution of the product of the above (1)(2.2 g) in acetone (20 ml) are added potassium carbonate (1.54 g) and 4-chloro-2-butyn-1-ol (1.03 g). The mixture is stirred for 4 hours and filtered. The filtrate is condensed at below the room temperature. The oily residue is dissolved in benzene and evaporated at below the room temperature. Ether is added to the residue and then a 30% solution (1.5 ml) in methylamine in methanol on ice bath. The mixture is stirred for 30 minutes and after addition of ether, washed with ice-cooled 3 N-hydrochloric acid, water, an aqueous solution of sodium bicarbonate and water successively. The ether layer is dried and evaporated to give the title compound as an oil (3.1 g). The oil is chromatographed on a column of silica gel and eluted with hexane-benzene (1:10) benzene and ether-benzene (1:100) successively. The title compound is obtained as colorless oil.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[C:6]([NH:11][C:12](=[O:27])[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][N:20]([CH2:24][CH2:25][CH3:26])[CH2:21][CH2:22][CH3:23])[CH:14]=2)[CH:5]=1.[H-].[Na+].[CH3:31]I>CN(C=O)C>[CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[C:6]([N:11]([C:12](=[O:27])[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][N:20]([CH2:24][CH2:25][CH3:26])[CH2:21][CH2:22][CH3:23])[CH:14]=2)[CH3:31])[CH:5]=1
Reactant: CI
Reactant: CCCN(CCC)Cc1cccc(C(=O)Nc2cc(C(=O)OC)ccc2N)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCN(CCC)Cc1cccc(C(=O)N(C)c2cc(C(=O)OC)ccc2N)c1
Reaction time: 1 h
Yield: 21.1 %

Procedure:
The compound (380 mg) obtained in Example 18-3 was dissolved in DMF (7.6 ml) and 60% sodium hydride (60.0 mg) was added thereto, and the whole was stirred for 1 hour. After that, methyl iodide (213 mg) was gradually added thereto and the whole was stirred at room temperature for 2 hours. After completion of the reaction, the solvent was distilled off under reduced pressure. The residue was dissolved in chloroform and washed with a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with chloroform. The organic layer was washed with a saturated saline solution and dried with anhydrous sodium sulfate. After filtration, the solvent was distilled off under reduced pressure. The residue was purified through silica gel column chromatography (chloroform/methanol/water), thereby obtaining the subject compound (83.0 mg) as a brown solid.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[CH:10][C:9]=2[C:13]([OH:15])=O)=[CH:4][CH:3]=1.[CH2:16]([NH:18][CH2:19][CH3:20])[CH3:17]>>[CH2:16]([N:18]([CH2:19][CH3:20])[C:13]([C:9]1[CH:10]=[N:11][O:12][C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=1)=[O:15])[CH3:17]
Reactant: Cc1ccc(-c2oncc2C(=O)O)cc1
Reactant: CCNCC
Product: CCN(CC)C(=O)c1cnoc1-c1ccc(C)cc1

Procedure:
The title compound was prepared from 5-(4-methylphenyl)isoxazole-4-carboxylic acid (10.2 mg, 0.050 mmol) and diethylamine (4.4 mg, 0.060 mmol) as described in synthetic method A and thereafter purified by preparative HPLC method A to give a solid (7.0 mg). MS (pos) m/z 259.1 (M+1).
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8](/[C:11](/[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[C:12](\[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)/[C:13]([F:16])([F:15])[F:14])=[CH:7][CH:6]=1.[N-:29]=[N+:30]=[N-:31].[Na+]>COCCO.O>[N:29]([CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8](/[C:11](/[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[C:12](\[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)/[C:13]([F:16])([F:15])[F:14])=[CH:7][CH:6]=1)=[N+:30]=[N-:31]
Reactant: FC(F)(F)/C(=C(\c1ccccc1)c1ccc(OCCBr)cc1)c1ccccc1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: COCCO
Solvent: O
Product: [N-]=[N+]=NCCOc1ccc(/C(=C(\c2ccccc2)C(F)(F)F)c2ccccc2)cc1
Reaction time: 1 h
Yield: 82.2 %

Procedure:
9.83 g (22 mmoles) of (E)-1-[4-(2-bromoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propene are dissolved in 100 ml of 2-methoxyethanol, a solution of 2.86 g (44 mmoles) of sodium azide in 10 ml of water is added, and the mixture is boiled for one hour. The reaction mixture is processed as described in Example 5, and the product is recrystallized twice from ethanol. 7.40 g (82%) of the aimed compound are obtained; m.p.: 73°-75° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([Cl:24])=[CH:21][CH:22]=3)[NH:17][C:16](=O)[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:28]([CH2:30][NH2:31])[OH:29]>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([Cl:24])=[CH:21][CH:22]=3)[N:17]=[C:16]([NH:31][CH2:30][CH2:28][OH:29])[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]
Reactant: NCCO
Reactant: CC(C)(C)OC(=O)N1CCN(c2cc(=O)[nH]c3cc(Cl)ccc23)CC1
Agent: [H-]
Agent: [Na+]
Product: CC(C)(C)OC(=O)N1CCN(c2cc(NCCO)nc3cc(Cl)ccc23)CC1

Procedure:
4-[4-(tert-Butoxycarbonyl)piperazin-1-yl]-7-chloroquinol-2-one (150 mg, 0.4 mmol), sodium hydride (15 mg, 0.6 mmol), N-phenyl(trifluoromethylsulfon)imide (208 mg, 0.56 mmol), and ethanolamine (100 μL, 1.65 mmol) are treated according to method E yielding the title product.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]([CH3:21])[C@H:9]2[C@@H:13]3[O:14][C:15]([CH3:18])([CH3:17])[O:16][C@@H:12]3[C@@H:11]([CH2:19][OH:20])[CH2:10]2)[CH:3]=1.C(N(CC)C(C)C)(C)C.[NH2:31][C@@H:32]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][CH2:33]1>C(O)CCC>[C@@H:32]1([NH:31][C:2]2[N:7]=[CH:6][N:5]=[C:4]([N:8]([CH3:21])[C@H:9]3[C@@H:13]4[O:14][C:15]([CH3:18])([CH3:17])[O:16][C@@H:12]4[C@@H:11]([CH2:19][OH:20])[CH2:10]3)[CH:3]=2)[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][CH2:33]1
Reactant: N[C@H]1CCc2ccccc21
Reactant: CN(c1cc(Cl)ncn1)[C@@H]1C[C@H](CO)[C@H]2OC(C)(C)O[C@H]21
Solvent: CCCCO
Solvent: CCN(C(C)C)C(C)C
Product: CN(c1cc(N[C@H]2CCc3ccccc32)ncn1)[C@@H]1C[C@H](CO)[C@H]2OC(C)(C)O[C@H]21
Temperature: 200 °C
Yield: 24.1 %

Procedure:
{(3aR,4R,6R,6aS)-6-[(6-chloropyrimidin-4-yl)(methyl)amino]-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl}methanol (130 mg, 0.41 mmol) was weighed into a microwave reaction tube and dissolved in 1-butanol (1.50 mL). To this solution was added N,N-diisopropylethylamine (0.22 mL, 1.24 mmol) and (S)-(+)-1-aminoindan (0.16 mL, 1.24 mmol) and the mixture was heated in a sealed tube under microwave irradiation at 200° C. for 4 h. The reaction mixture was concentrated under vacuum, and the residue was purified via silica gel column chromatography eluting with a gradient of 2 to 5% methanol in DCM to afford the title compound (40.5 mg, 24%) as a colorless oil. LC/MS: Rt=1.49 min, ES+ 411.5 (AA standard).
Reaction SMILES: [Cl-].[Cl-].[Cl-].[Al+3].[C:5](Cl)(=[O:15])[C:6]1[CH:14]=[CH:13][C:9]([C:10](Cl)=[O:11])=[CH:8][CH:7]=1.Cl.[CH:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>ClCCl>[C:5]([C:6]1[CH:14]=[CH:13][C:9]([C:10](=[O:11])[C:6]2[CH:14]=[CH:13][CH:9]=[CH:8][CH:7]=2)=[CH:8][CH:7]=1)(=[O:15])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: c1ccccc1
Reactant: O=C(Cl)c1ccc(C(=O)Cl)cc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: O=C(c1ccccc1)c1ccc(C(=O)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 32 %

Procedure:
Aluminum trichloride (1.37 g, 10.33 mmol) was added to a solution of terephthaloyl dichloride (1.0 g, 4.42 mmol) in anhydrous dichloromethane and excess benzene. After stirring for 12 h at room temperature under an inert atmosphere of nitrogen gas, the reaction mixture treated with 10% HCl (50 mL) and the products were extracted with ethyl acetate (3×20 mL). The combined organic phases were washed with brine and dried over sodium sulfate. After the organic layer was concentrated under reduced pressure, purification using flash chromatography (silica gel, hexanes:ethyl acetate, 80:20) afforded 1,4-dibenzoyl benzene 1 (0.405 g, 1.41 mmol) in a 32% yield.