Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[C:10]2[C:5](=[CH:6][C:7]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:8][CH:9]=2)[NH:4][CH2:3]1.Cl[C:19]1[C:28]2[C:23](=[C:24]([CH3:29])[CH:25]=[CH:26][CH:27]=2)[N:22]=[C:21]([CH3:30])[C:20]=1[CH3:31].C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][C:2]1([CH3:17])[C:10]2[C:5](=[CH:6][C:7]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:8][CH:9]=2)[N:4]([C:19]2[C:28]3[C:23](=[C:24]([CH3:29])[CH:25]=[CH:26][CH:27]=3)[N:22]=[C:21]([CH3:30])[C:20]=2[CH3:31])[CH2:3]1
Reactant: CC1(C)CNc2cc(N3CCOCC3)ccc21
Reactant: Cc1nc2c(C)cccc2c(Cl)c1C
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: Cc1nc2c(C)cccc2c(N2CC(C)(C)c3ccc(N4CCOCC4)cc32)c1C

Procedure:
Prepared according to procedure T using 4-(3,3-dimethylindolin-6-yl)morpholine (0.151 g, 0.65 mmol), 4-chloro-2,3,8-trimethylquinoline (0.267 g, 1.3 mmol), cesium carbonate (0.424 g, 1.3 mmol), Pd2(dba)3 (0.060 g, 0.065 mmol) and (±) BINAP (0.061 g, 0.098 mmol) were added together in 1,4-dioxane (2 mL). Crude residue was purified via HPLC to give 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)-2,3,8-trimethylquinoline. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.40 (1H, d, J=7.8 Hz), 7.34 (1H, d, J=7.0 Hz), 7.17 (1H, m), 6.85 (1H, d, J=8.2 Hz), 6.04 (1H, dd, J=8.0, 2.2 Hz), 5.20 (1H, d, J=2.3 Hz), 3.50 (1H, d, J=9.0 Hz), 3.39 (5H, m), 2.63 (4H, dd, J=5.9, 3.9 Hz), 2.54 (3H, s), 2.52 (3H, s), 2.04 (3H, s), 1.26 (3H, s), 1.21 (3H, s). Mass Spectrum (ESI) m/e=407 (M+1).
Reaction SMILES: C(O[C:6]1[C:11]([F:12])=[CH:10][N:9]=[C:8]([CH:13]2[CH2:15][CH:14]2[CH2:16][C:17]#[N:18])[C:7]=1[CH3:19])(C)(C)C.O=P(Cl)(Cl)[Cl:22]>FC(F)(F)C(O)=O>[Cl:22][C:6]1[C:11]([F:12])=[CH:10][N:9]=[C:8]([CH:13]2[CH2:15][CH:14]2[CH2:16][C:17]#[N:18])[C:7]=1[CH3:19]
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1c(C2CC2CC#N)ncc(F)c1OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Product: Cc1c(C2CC2CC#N)ncc(F)c1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 73.1 %

Procedure:
A sample of 2-(4-t-butoxy-5-fluoro-3-methyl-2-pyridinyl)cyclopropaneacetonitrile (5.21 g, 19.86 mmol) was dissolved in 50 mL of trifluoroacetic acid, the reaction was stirred under nitrogen for 1 hour at ambient temperature, and the material concentrated to dryness. The residue was dissolved in a mixture of 15.6 mL of DMF and 90 mL of methylene chloride. This solution was cooled in a water bath as 18.8 mL (19.86 mmol) of POCl3 was added, then the reaction was stirred at ambient temperature for 16 hours. The reaction was quenched by pouring it into ice water, and the mixture was extracted with methylene chloride. The aqueous solution was adjusted to pH7 with NaOH and re-extracted with methylene chloride. The extracts were combined and washed with water, dried over MgSO4 and concentrated. The residue was purified by flash chromatography with 1:4 ethyl acetate:hexane to give 3.26 g of 2-(4-chloro-5-fluoro-3-methyl-2-pyridinyl)cyclopropaneacetonitrile as a colorless liquid after removal of the solvents. MS 225, 227 (M+H)+ ; 1H NMR (CDCl3)∂: 0.48 (m, 1H), 0.59 (m, 1H), 0.66 (m, 1H), 0.77 (m, 1H), 1.50 (m, 1H), 2.48 (s, 3H), 3.80 (d, 1H, J=8 Hz), 8.39 (s, 1H). IR (neat) 2240, 1570, 1460 cm-l.
Reaction SMILES: [CH:1]1([C:4]2[C:13]([CH:14]=[CH:15][C:16]#N)=[C:12]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH2:3][CH2:2]1.C([O-])=[O:26].[NH4+].O.C(O)(=O)C>[Ni].C(O)C>[CH:1]1([C:4]2[C:13]([CH:14]=[CH:15][CH:16]=[O:26])=[C:12]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH2:3][CH2:2]1
Reactant: N#CC=Cc1c(C2CC2)nc2ccccc2c1-c1ccc(F)cc1
Reactant: O=C[O-]
Agent: [Ni]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Solvent: CC(=O)O
Product: O=CC=Cc1c(C2CC2)nc2ccccc2c1-c1ccc(F)cc1
Temperature: 25 °C
Yield: 84.4 %

Procedure:
In a 200 mL-volume glass flask equipped with a stirrer, a thermometer and a dropping funnel were placed under nitrogen atmosphere 4.0 g (12.7 mmol) of 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enenitrile (prepared in Reference Example 1), 1.6 g (25.4 mmol) of ammonium formate, 4.4 g (37.5 mmol as nickel atom) of water-containing developed Raney-nickel (NDHT-90, nickel content 50 wt. %, available from Kawaken Fine Chemical Co., Ltd.), and 40 mL of acetic acid. The content was reacted at 65° C. for 4 hours. After the reaction was complete, the content was cooled to room temperature. After addition of 20 mL of ethanol, the catalyst was removed by filtration using a celite. The filtrate was concentrated under reduced pressure, and 40 mL of ethyl acetate was added. The mixture was washed successively with 5 mL of hydrochloric acid (1 mol/L), 10 mL of water, 20 mL of aqueous sodium hydroxide solution (1 mol/L), 14 mL of an aqueous alkaline DL-tartaric acid solution (1.0 g of DL-tartaric acid was dissolved in 1 mol/L aqueous sodium hydroxide solution), and 20 mL of saturated aqueous sodium chloride solution. The organic portion was dried over anhydrous magnesium sulfate. The organic portion was filtered and concentrated under reduced pressure, to obtain 3.4 g (yield 82%) of 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enal as a pale yellow crystalline product (purity 98%, in terms of an area percent according to high performance liquid chromatography).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([OH:13])=O)[CH:10]=2)[CH:7]=1.[CH3:14][C:15]1[C:19]([C:20]2[CH:21]=[CH:22][CH:23]=[C:24]3[C:29]=2[CH:28]([CH3:30])[NH:27][CH2:26][CH2:25]3)=[C:18]([CH3:31])[O:17][N:16]=1>>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([N:27]3[CH2:26][CH2:25][C:24]4[C:29](=[C:20]([C:19]5[C:15]([CH3:14])=[N:16][O:17][C:18]=5[CH3:31])[CH:21]=[CH:22][CH:23]=4)[CH:28]3[CH3:30])=[O:13])[CH:10]=2)[CH:7]=1
Reactant: O=C(O)c1cc2ncc(Br)cn2n1
Reactant: Cc1noc(C)c1-c1cccc2c1C(C)NCC2
Product: Cc1noc(C)c1-c1cccc2c1C(C)N(C(=O)c1cc3ncc(Br)cn3n1)CC2

Procedure:
In close analogy to the procedure described in Example 1, 6-bromo-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 8-(3,5-Dimethyl-isoxazol-4-yl)-1-methyl-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:30])[CH:5]([F:29])[CH:6]([C:8]1[N:20]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[C:11]2=[N:12][CH:13]=[C:14]([S:16]([CH3:19])(=[O:18])=[O:17])[CH:15]=[C:10]2[CH:9]=1)[OH:7])[CH3:2].ClCCl.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:30])[CH:5]([F:29])[C:6]([C:8]1[N:20]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)[C:11]2=[N:12][CH:13]=[C:14]([S:16]([CH3:19])(=[O:18])=[O:17])[CH:15]=[C:10]2[CH:9]=1)=[O:7])[CH3:2]
Reactant: CCOC(=O)C(F)C(O)c1cc2cc(S(C)(=O)=O)cnc2n1Cc1ccc(F)cc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CCOC(=O)C(F)C(=O)c1cc2cc(S(C)(=O)=O)cnc2n1Cc1ccc(F)cc1
Reaction time: 0.5 h
Yield: 89.3 %

Procedure:
A mixture of (1-(4-fluorobenzyl)-5-methanesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)carbaldehyde obtained in Example 36 (2) (100 mg), ethyl bromofluoroacetate (0.05 ml), zinc powder (28 mg) and tetrahydrofuran (3 ml) was heated under reflux for 15 minutes. The mixture was diluted with ethyl acetate, washed with a saturated aqueous sodium hydrogencarbonate solution, water and a saturated aqueous NaCl solution successively, dried and concentrated under reduced pressure. The resulting residue was separated using silica gel column chromatography (hexane:ethyl acetate=1:2) to obtain 2-fluoro-3-(1-(4-fluorobenzyl)-5-methanesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-hydroxypropionic acid ethyl ester (100 mg) in a yellow amorphous form. To a mixture of the resulting 2-fluoro-3-(1-(4-fluorobenzyl)-5-methanesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-hydroxypropionic acid ethyl ester (90 mg) and dichloromethane (2 ml) was added Dess Martin reagent (190 mg) at 15 to 30° C. and the mixture was stirred at the same temperature for 30 minutes. The mixture was diluted with ethyl acetate, washed with 5% aqueous sodium thiosulfate solution, a saturated aqueous sodium hydrogencarbonate solution, water and a saturated aqueous NaCl solution successively, dried and concentrated under reduced pressure. The resulting residue was separated using silica gel column chromatography (hexane:ethyl acetate=1:1) to obtain the desired product (80 mg) in a white amorphous form.
Reaction SMILES: [CH3:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:13][N:14]([C:17]3[CH:27]=[CH:26][C:20]([C:21]([N:23]=[N+]=[N-])=[O:22])=[CH:19][CH:18]=3)[CH2:15][CH3:16])[CH:8]=2)[N:3]=1.[CH2:28]([N:35]1[CH:39]=[CH:38][N:37]=[C:36]1[CH2:40]N)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>>[CH2:28]([N:35]1[CH:39]=[CH:38][N:37]=[C:36]1[CH2:40][NH:23][C:21](=[O:22])[C:20]1[CH:26]=[CH:27][C:17]([N:14]([CH2:13][C:7]2[CH:8]=[C:9]3[C:4](=[CH:5][CH:6]=2)[N:3]=[C:2]([CH3:1])[NH:11][C:10]3=[O:12])[CH2:15][CH3:16])=[CH:18][CH:19]=1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1
Reactant: CCN(Cc1ccc2nc(C)[nH]c(=O)c2c1)c1ccc(C(=O)N=[N+]=[N-])cc1
Reactant: NCc1nccn1Cc1ccccc1
Product: CCN(Cc1ccc2nc(C)[nH]c(=O)c2c1)c1ccc(C(=O)NCc2nccn2Cc2ccccc2)cc1
Yield: 21 %

Procedure:
Using the process described in Example 5, p-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-ethylamino]benzoyl azide was reacted with (1-benzylimidazol-2-yl)methylamine to give N-(1-benzylimidazol-2-yl)methyl-p-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-ethylamino]benzamide (containing 1.3 equivalents of water) in 21% yield, m.p. 217°-221° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C@@H:13]([C:28]2[C:33]([F:34])=[CH:32][CH:31]=[CH:30][N:29]=2)[NH:14][C:15](=[O:27])[C:16]2[CH:21]=[C:20]([N+:22]([O-])=O)[C:19]([O:25][CH3:26])=[CH:18][N:17]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]([F:12])([F:11])[F:10].CCOC(C)=O>[Ni].CO>[NH2:22][C:20]1[C:19]([O:25][CH3:26])=[CH:18][N:17]=[C:16]([C:15]([NH:14][C@@H:13]([C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]([F:10])([F:11])[F:12])=[C:2]([F:1])[CH:3]=2)[C:28]2[C:33]([F:34])=[CH:32][CH:31]=[CH:30][N:29]=2)=[O:27])[CH:21]=1
Reactant: COc1cnc(C(=O)N[C@@H](c2ccc(OC(F)(F)F)c(F)c2)c2ncccc2F)cc1[N+](=O)[O-]
Agent: [Ni]
Solvent: CO
Solvent: CCOC(C)=O
Product: COc1cnc(C(=O)N[C@@H](c2ccc(OC(F)(F)F)c(F)c2)c2ncccc2F)cc1N
Reaction time: 2 h

Procedure:
To a stirred suspension of Raney Nickel (0.4 g, Monarch, India) in MeOH (10 mL) was added (S)—N-((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-methoxy-4-nitropicolinamide (700 mg, 0.0014 mol) at rt. The reaction mixture was stirred under a hydrogen balloon for 2 h. After completion of the reaction, monitored by TLC (TLC eluent: 50% EtOAc in petroleum ether), the reaction mixture was filtered through Celite® brand filter agent and concentrated. The resulting product was triturated with petroleum ether to give the title compound as a white solid. MS (ESI, positive ion) m/z: 455.2 (M+H).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][S:4]([OH:7])(=[O:6])=[O:5].C(=O)([O-])[O-].[Na+:12].[Na+].Cl[C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=1)=[O:16].C(OCC)C>C(OCC)C.O>[N+:25]([C:22]1[CH:21]=[CH:20][C:19]([CH2:18][O:17][C:15]([NH:1][CH2:2][CH2:3][S:4]([O-:7])(=[O:6])=[O:5])=[O:16])=[CH:24][CH:23]=1)([O-:27])=[O:26].[Na+:12]
Reactant: O=C(Cl)OCc1ccc([N+](=O)[O-])cc1
Reactant: NCCS(=O)(=O)O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Product: O=C(NCCS(=O)(=O)[O-])OCc1ccc([N+](=O)[O-])cc1
Temperature: 0 °C
Reaction time: 15 h
Yield: 70.7 %

Procedure:
A mixture of 2-aminoethanesulfonic acid (5.0 g) and sodium carbonate (9.4 g) in ethyl ether-water (100 mL, 1:1, v/v), at 0° C., was treated with 4-nitrobenzyl chloroformate (8.6 g). After stirring vigorously at 0° C. for 10 min and at room temperature for 15 hr, ethyl ether was added to the reaction mixture. The precipitates were collected by filtration and washed with ethyl ether to afford the title compound (9.2 g) as a white powder: 1H NMR (400 MHz, D2O) δ 2.94 (t, J=6.4 Hz, 2H), 3.39 (t, J=6.4 Hz, 2H), 5.09 (s, 2H), 7.44 (d, J=8.3 Hz, 2H), and 8.11 (d, J=8.3 Hz, 2H).
Reaction SMILES: C1C=CC(O)=C(C2N=C(C3C=CC=CC=3O)N(C3C=CC(C(O)=O)=CC=3)N=2)C=1.[C:29]([OH:38])(=O)[C:30]1[C:31](=[CH:33][CH:34]=[CH:35][CH:36]=1)[OH:32].S(Cl)([Cl:41])=O>>[C:29]([Cl:41])(=[O:38])[C:30]1[C:31](=[CH:33][CH:34]=[CH:35][CH:36]=1)[OH:32]
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1ccccc1O
Agent: O=C(O)c1ccc(-n2nc(-c3ccccc3O)nc2-c2ccccc2O)cc1
Product: O=C(Cl)c1ccccc1O

Procedure:
WO2010023685 of Matrix describes the process for the preparation of Deferasirox as shown in scheme III. The process comprises the Salicylic acid reacted with thionyl chloride in the presence of solvent to give salicyloyl chloride, which is reacted with salicylamide to give 2-(2-hydroxyphenyl)-benz[1,3]-oxazine-4-one, then it is condensed with 4-hydrazino benzoic acid to give deferasirox.
Reaction SMILES: [N:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[N:10]1[CH2:15][CH2:14][CH2:13][C@H:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:11]1)=C=S.N(C1C=NC=CC=1N1CCC[C@H](NC(=O)OC(C)(C)C)C1)=[N+]=[N-].[P:47]([CH3:50])([CH3:49])[CH3:48]>C1COCC1>[CH3:48][P:47](=[N:1][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[N:10]1[CH2:15][CH2:14][CH2:13][C@H:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:11]1)([CH3:50])[CH3:49]
Reactant: CC(C)(C)OC(=O)N[C@H]1CCCN(c2ccncc2N=C=S)C1
Reactant: CP(C)C
Agent: CC(C)(C)OC(=O)N[C@H]1CCCN(c2ccncc2N=[N+]=[N-])C1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@H]1CCCN(c2ccncc2N=P(C)(C)C)C1
Reaction time: 0.17 h

Procedure:
tert-butyl ((3S)-1-(3-isothiocyanato-4-pyridinyl)-3-piperidinyl)carbamate. A dry, 3 neck, 100 mL Morton flask was configured as follows: opening 1: septa/Ar inlet; opening 2 (center): septa/PTFE addition needle; opening 3: septa. The flask was charged with tert-butyl ((3S)-1-(3-azido-4-pyridinyl)-3-piperidinyl)carbamate (3.25 g, 10.22 mmol), a stirbar, and dry THF (10 mL). The slurry was stirred for 10 min, and immersed into an ice-water bath. A syringe charged with 1.0 M PMe3 in THF (10.73 mL, 10.73 mmol, Aldrich) was fitted to the PTFE addition needle and added over a 15 min period via a syringe pump. The reaction was stirred for 15 min. The solution was charged to a dry 50 mL glass syringe via the PTFE addition needle to afford (S)-tert-butyl (1-(3-((trimethylphosphoranylidene)amino)pyridin-4-yl)piperidin-3-yl)carbamate. A dry, 250 mL, one neck round bottom flask was charged with dry THF (16 mL), carbon disulfide (6.17 mL, 102 mmol) and a stirbar. The flask was fitted with a septa/Ar inlet, and immersed into an ice-water bath. The solution was stirred for 15 min. The septa was pierced with the PTFE addition needle fitted to the 50 mL glass syringe containing the solution of (S)-tert-butyl (1-(3-((trimethylphosphoranylidene)amino)pyridin-4-yl)piperidin-3-yl)carbamate and the solution (19 mL) was added via syringe pump over a 1 h period. The reaction was stirred an additional 10 min and the solvent was removed in vacuo. The residue was further dried at <1 mm Hg at RT to afford tert-butyl ((3S)-1-(3-isothiocyanato-4-pyridinyl)-3-piperidinyl)carbamate. MS (ESI, pos. ion) m/z: 335.0 [M+H].
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[S:11]1[CH:15]=[CH:14][CH:13]=[C:12]1[CH2:16][CH2:17][NH2:18].C([O-])([O-])=O.[K+].[K+]>CN1CCCC1=O>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([NH:18][CH2:17][CH2:16][C:12]2[S:11][CH:15]=[CH:14][CH:13]=2)=[CH:3][CH:4]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: NCCc1cccs1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Product: O=[N+]([O-])c1ccc(NCCc2cccs2)cc1
Temperature: 60 °C
Yield: 93.8 %

Procedure:
2 g of 4-fluoronitrobenzene, 2.16 g of 2-thien-2-ylethanamine, and 2.35 g of K2CO3 were added to a solution of 20 ml of N-methyl-pyrrolidinone. The reaction medium was heated at 60° C. for 12 hours and, after cooling to room temperature, was then poured into a water+ice mixture. The yellow precipitate formed was filtered off, reslurried in water and then dried over P2O5. 3.3 g of N-(4-nitrophenyl)-N-(2-thien-2-ylethyl)amine (1) were obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.Cl[CH2:16][CH2:17][CH:18]1[O:22][C:21](=[O:23])[N:20]([CH3:24])[CH2:19]1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+]>C(O)CCC.CC(O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][N:12]([CH2:16][CH2:17][CH:18]3[O:22][C:21](=[O:23])[N:20]([CH3:24])[CH2:19]3)[CH2:11][CH2:10]2)=[CH:7][CH:8]=1
Reactant: CN1CC(CCCl)OC1=O
Reactant: COc1ccc(N2CCNCC2)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(C)O
Solvent: CCCCO
Product: COc1ccc(N2CCN(CCC3CN(C)C(=O)O3)CC2)cc1
Yield: 62.6 %

Procedure:
This compound was prepared according to the procedure of Example 2. A mixture of 2.4 g (0.012 mol) of 1-(4-methoxyphenyl)piperazine, 2.0 g (0.012 mol) of 5-(2-chloroethyl)-3-methyl-2-oxazolidinone, 4.2 g (0.04 mol) of anhydrous sodium carbonate and 0.4 g of potassium iodide in 100 mL of 1-butanol gave 2.4 g (63%) of pink solid, mp 103°-104° C. (2-propanol).
Reaction SMILES: C([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18](O)=[CH:17][CH:16]=2)=[CH:11][C:10]=1[Cl:22])CCCCCCC.C(C1C=CC(C2C=CC(OC)=C(Cl)C=2)=CC=1)CCCCCCC.[OH-].[Na+].Cl>>[Cl:22][C:10]1[CH:11]=[C:12]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:13]=[CH:14][CH:9]=1
Reactant: CCCCCCCCc1ccc(-c2ccc(O)cc2)cc1Cl
Agent: CCCCCCCCc1ccc(-c2ccc(OC)c(Cl)c2)cc1
Agent: Cl
Agent: [Na+]
Product: Clc1cccc(-c2ccccc2)c1
Reaction time: 24 h

Procedure:
4-phenyl-2-chlorophenol is methylated by means of well-known method steps and 4-phenyl-2-chloroanisole (hereinafter referred to as Material I) is extracted. 1/3 mole of Material I is dissolved into carbon disulfide 300cc and a Friedel Craft's reaction is effected in a MILO flask in which 1/3 mole of octanol chloride and 60 grams of anhydrous ammonium chloride are placed. As a result, 4-octanoyl-4'-methoxy-3'-chlorobiphenyl (hereinafter referred to as Compound 4) is extracted with a yield of 75%. As the result of reduction of said Compound 4, by the well-known Wolff-Kischner's reaction, 4-octyl-4'-methoxy-3'-chlorobiphenyl (hereinafter referred to as Compound 5) is extracted with a yield of 70 weight percent. 0.01 mole of 4-octyl-4'-hydroxy-3-chlorobiphenyl (hereinafter referred to as Material II), which is extracted from said Compound 5 by means of demethylation with HBr water, is dissolved into a mixed solution of 100cc pyridine and 50cc. of benzene. After this 0.012 mole of 4-octyloxy-benzoil chloride is added to the solution, this mixed solution is heated and stirred for 24 hours. Extraction is achieved by adding water (200cc) and benzene (100cc) to the solution. The resultant benzene layer is washed with a mixture of 1 mole of sodium hydroxide solution (50cc) and 1 mole of HCl liquid (100cc). The resultant compound in benzene layer is crystallized from ethyl alcohol (50cc). The result of the above method steps, 4-octyl-4'-(4"-octyloxy benzoil)-3'-chlorobiphenyl (Compound 1 in the above table), is extracted at the yield rate of 85%.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[N:5]=[C:4]([C:18]2[S:19][CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[N:22]=2)[N:3]=1.[CH:27]([C:30]1[N:31]=[C:32]([Sn](CCCC)(CCCC)CCCC)[S:33][CH:34]=1)([CH3:29])[CH3:28].COC1C=C(C2SC=C(C(F)(F)F)N=2)N=C(C2SC=C(C)N=2)C=1>C(Cl)Cl>[CH:27]([C:30]1[N:31]=[C:32]([C:2]2[CH:7]=[C:6]([O:8][CH2:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=3)[N:5]=[C:4]([C:18]3[S:19][CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[N:22]=3)[N:3]=2)[S:33][CH:34]=1)([CH3:29])[CH3:28]
Reactant: COc1ccc(COc2cc(Cl)nc(-c3nc(C(F)(F)F)cs3)n2)cc1
Reactant: CCCC[Sn](CCCC)(CCCC)c1nc(C(C)C)cs1
Agent: COc1cc(-c2nc(C)cs2)nc(-c2nc(C(F)(F)F)cs2)c1
Solvent: ClCCl
Product: COc1ccc(COc2cc(-c3nc(C(C)C)cs3)nc(-c3nc(C(F)(F)F)cs3)n2)cc1

Procedure:
Compound 25 was synthesized from compound 285 (1.87 mmol) and compound 219 (2.43 mmol) as described for compound 22 at a temperature of 110° C. DCM was added and the mixture was washed sequentially with saturated NH4Cl and brine. The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The crude was purified two times by silica gel chromatography (eluent: petroleum ether/EtOAc 5 to 10% and petroleum ether/DCM 20 to 60%) to give compound 25 as a colorless oil in 31% yield.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH:8]=[N:9][OH:10])=[C:6]([Cl:11])[CH:5]=[CH:4][N:3]=1.[Cl:12]N1C(=O)CCC1=O>CN(C=O)C>[Cl:1][C:2]1[C:7]([C:8]([Cl:12])=[N:9][OH:10])=[C:6]([Cl:11])[CH:5]=[CH:4][N:3]=1
Reactant: ON=Cc1c(Cl)ccnc1Cl
Reactant: O=C1CCC(=O)N1Cl
Solvent: CN(C)C=O
Product: ON=C(Cl)c1c(Cl)ccnc1Cl
Temperature: 64 °C
Reaction time: 1 h
Yield: 86.9 %

Procedure:
A solution of 2,4-dichloro-3-pyridinecarbaldehyde oxime (1.88 g, 9.9 mmol) in DMF (7.9 mL) was stirred as N-chlorosuccinimide (1.32 g, 9.9 mmol) was added. The solution was stirred in a 64° C. oil bath for 1 hour then allowed to cool to room temperature. The solution was poured onto ice. The solution was extracted with ether and the organic layer was washed with brine, dried with MgSO4, filtered and concentrated to yield 2,4-dichloro-N-hydroxy-3-pyridinecarboximidoyl chloride (1.94 g, 87%). 1H NMR (400 MHz, DMSO-d6): δ 12.89 (s, 1H), 8.52 (d, J=5 Hz, 1H), 7.81 (d, J=5 Hz, 1H).
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[NH:6]([CH2:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[CH:14]2)[C:7]([CH3:9])=[O:8].[OH-].[Na+].CN(C)[CH:24]=[O:25]>O>[NH:6]([CH2:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[C:14]2[CH:24]=[O:25])[C:7]([CH3:9])=[O:8]
Reactant: CC(=O)NCc1ccc2[nH]ccc2c1
Reactant: CN(C)C=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: O=P(Cl)(Cl)Cl
Product: CC(=O)NCc1ccc2[nH]cc(C=O)c2c1
Reaction time: 0.25 h
Yield: 60 %

Procedure:
Phosphorus oxychloride (0.38 ml, 0.004 mol) was slowly added at 0° C. under nitrogen atmosphere to anhydrous N,N-dimethylformamide (1.9 ml, 0.025 mol). The mixture was stirred for 15 minutes and a solution of 5-acetamino methylindole (0.73 g, 0.0039 mol) in anhydrous N,N-dimethylformamide (4 ml) was added dropwise below 2° C. The mixture was stirred at room temperature for 3 h and diluted with an equal volume of water. The solution was neutralized (pH 8) with 1 N aqueous solution of sodium hydroxide. The mixture was evaporated to dryness under reduced pressure and the residue was recrystallized from ethyl acetate to afford 0.5 g (60%) of the entitled product (mp 182–184° C.).