Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](O)(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]C.C(OC(=O)C)(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Pd].O1CCCC1>[CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: CCCCCCCCCCCCCC(=O)O
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CC(=O)OC(C)=O
Product: C=CCCCCCCCCCCC
Temperature: 255 °C
Yield: 1308.4 %

Procedure:
A mixture of myristic acid (90.0 g, 0.394 mol) and acetic anhydride (40.2 g, 0.394 mol) was heated under reduced pressure (150 torr) using an oil bath maintained at 255° C. A small amount of a tetrahydrofuran solution containing dichlorobis(triphenylphosphine)palladium (0.453 g, 6.45×10-4 mol) and triphenylphosphine (2.97 g, 0.0113 mol) was then added to the reactor in order to initiate the decarbonylation reaction. The olefin product immediately distilled from the reaction mixture into a receiver. As material distilled from the reactor, it was continuously replaced with an equimolar mixture of myristic acid and acetic anhydride at a rate that maintained the initial level of the reactor contents throughout the course of the entire reaction. The solution of Pd-catalyst was added in a slow, continuous manner in order to keep the reaction temperature between ca. 215°-220° C. The decarbonylation reaction proceeded rapidly until the catalyst supply was exhausted, whereupon the reaction temperature gradually reached ca. 245° C. and conversion of myristic acid ceased. The combined product was washed with water and distilled to afford 940 g of 1-tridecene (bp 90° C./10 torr), which GC analysis showed to be 96.3% of the αolefin. TON=7985.
Reaction SMILES: Br[CH:2]([C:4]1[O:5][C:6](=[O:20])[C:7]2[C:12]([C:13]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH3:3].[NH:21]1[C:25]2=[N:26][CH:27]=[N:28][C:29]([NH2:30])=[C:24]2[CH:23]=[N:22]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[NH2:30][C:29]1[N:28]=[CH:27][N:26]=[C:25]2[N:21]([CH:2]([C:4]3[O:5][C:6](=[O:20])[C:7]4[C:12]([C:13]=3[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:11][CH:10]=[CH:9][CH:8]=4)[CH3:3])[N:22]=[CH:23][C:24]=12
Reactant: Nc1ncnc2[nH]ncc12
Reactant: CC(Br)c1oc(=O)c2ccccc2c1-c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(c1oc(=O)c2ccccc2c1-c1ccccc1)n1ncc2c(N)ncnc21
Yield: 34.3 %

Procedure:
The title compound was made in a similar way as that of the compound of example 15, 3-(1-bromoethyl)-4-phenyl-1H-isochromen-1-one (intermediate C7, 70 mg, 0.213 mmol), 1H-pyrazolo[3,4-d]pyrimidin-4-amine (40.2 mg, 0.298 mmol) and K2CO3 (41.1 mg, 0.298 mmol) in DMF (1 ml) at 80° C. for 4 hrs to give the title compound (28 mg, 34%).
Reaction SMILES: [Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.C[O:13][C:14]([C@H:16]1[CH2:19][C@@H:18](O)[CH2:17]1)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([C@H:18]3[CH2:19][C@H:16]([CH2:14][OH:13])[CH2:17]3)[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: COC(=O)[C@H]1C[C@@H](O)C1
Reactant: Clc1ncnc2[nH]cc(I)c12
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: OC[C@H]1C[C@H](n2cc(I)c3c(Cl)ncnc32)C1
Temperature: 75 °C

Procedure:
To a mixture of 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (prepared according to: L. B. Townsend et al., J. Med. Chem. 1990, 33 (7), 1984-92) (280 mg, 1.00 mmol), cis-3-hydroxycyclobutanecarboxylic acid methyl ester (trans/cis=1:5) (180 mg, 1.38 mmol), and PS-PPh3 (loading 2.02 mmol/g; 951 mg, 2.02 mmol) in dry THF (10 mL), cooled by ice/water, was added DIAD (295 μL, 303 mg, 1.50 mmol), then the cooling bath was removed, and the mixture was vortexed (220 rpm) for 2 d. The resin was filtered off and washed thoroughly with THF (≈80 mL), the filtrate and washings were combined, concentrated, and chromatographed on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with CH2Cl2 (1-14)→5% EtOAc in CH2Cl2 (15-30)], fractions containing product were combined and chromatographed again under the same conditions. This material was suspended in iPrOH (≈1.5 mL), heated to 75° C. for 10 min and cooled to −20° C. for 2 h. The solid was filtered off, washed with cold (−20° C.) iPrOH, and dried in vacuo, giving the title compound as white solid, trans/cis=5:1. 1H NMR (CDCl3, 400 MHz) δ 2.83-2.97 (m, 4H), 3.23-3.32 (m, 1H), 3.79 (s, 3H), 5.50 (quint, J=8.7 Hz, 1H), 7.51 (s, 1H), 8.61 (s, 1H). MS (ES+): m/z 391.9/393.9 (100/35) [MH+]. HPLC: tR=3.5 min (OpenLynx, polar—5 min).
Reaction SMILES: [O:1]([C:8]1[CH:15]=[CH:14][C:11]([CH:12]=O)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:16]1([NH2:22])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.C([BH3-])#N.[Na+]>CO>[CH:16]1([NH:22][CH2:12][C:11]2[CH:14]=[CH:15][C:8]([O:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:9][CH:10]=2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1
Reactant: O=Cc1ccc(Oc2ccccc2)cc1
Reactant: NC1CCCCC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: c1ccc(Oc2ccc(CNC3CCCCC3)cc2)cc1
Reaction time: 48 h
Yield: 91 %

Procedure:
4-Phenoxybenzaldehyde (5.0 g, 25.0 mmol) and cyclohexylamine (2.5 g, 25 mmol) were dissolved in methanol (85 mL) under nitrogen at room temperature. Sodium cyanoborohydride (1.57 g, 25.0 mmol) was added, and stirring was continued for 48 hours. The solvent was evaporated and the residue was suspended in ether, washed with brine, and dried over Na2SO4. The ether was evaporated, and the crude product was chromatographed on silica gel eluting with 3% methanol in methylene chloride to provide 6.4 g (91%) of the title compound as a colorless oil. 1H NMR (CDCl3, 300 MHz) δ 1.05-1.35 (m, 5H), 1.55-1.65 (m, 1H), 1.70-1.80 (m, 3H), 1.85-2.00 (m, 2H), 2.45-2.55 (m, 1 H) 3.80 (s, 2H), 6.95-7.04 (m, 4H), 7.05 (tt, J=7.5, 1.5 Hz, 1H), 7.25-7.35 (m, 4H). MS (DCl/NH3) m/e 282 (M+H)+.
Reaction SMILES: O[Li].O.[C:4]([C:8]1[CH:29]=[CH:28][CH:27]=[CH:26][C:9]=1[C:10]([NH:12][C@H:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([C:22]([O:24]C)=[O:23])[CH:20]=2)[CH2:15][CH2:14]1)=[O:11])([CH3:7])([CH3:6])[CH3:5].OS([O-])(=O)=O.[K+]>O.CO.C1COCC1>[C:4]([C:8]1[CH:29]=[CH:28][CH:27]=[CH:26][C:9]=1[C:10]([NH:12][C@H:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([C:22]([OH:24])=[O:23])[CH:20]=2)[CH2:15][CH2:14]1)=[O:11])([CH3:7])([CH3:5])[CH3:6]
Reactant: COC(=O)c1ccc2c(c1)[C@H](NC(=O)c1ccccc1C(C)(C)C)CC2
Agent: O=S(=O)([O-])O
Agent: [K+]
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: CC(C)(C)c1ccccc1C(=O)N[C@@H]1CCc2ccc(C(=O)O)cc21
Reaction time: 4 h

Procedure:
LiOH.H2O (700 g, 17.0 mmol, 6 eq), dissolved in water (30 ml), was added dropwise to a cooled (0° C.) solution of (R)-methyl 3-(2-tert-butylbenzamido)-2,3-dihydro-1H-indene-5-carboxylate (B-27) (1.0 g, 2.8 mmol, 1 eq) in MeOH:THF (1:1, 60 ml), and stirring was carried out for 4 h at RT. After monitoring by thin-layer chromatography, the reaction solution was reduced under reduced pressure and the residue was taken up in water (50 ml), acidified with KHSO4 solution and extracted with dichloromethane (2×100 ml). The combined organic phases were washed with sat. NaCl solution (50 ml), dried over sodium sulfate and concentrated and dried under reduced pressure. Yield: 900 mg
Reaction SMILES: [CH:1]1[NH:5][N:4]=[CH:3][C:2]=1[N+:6]([O-:8])=[O:7].[H-].[Na+].[CH3:11][O:12][CH2:13][CH2:14]Br.[Na+].[I-]>CN(C=O)C>[CH3:11][O:12][CH2:13][CH2:14][N:4]1[CH:3]=[C:2]([N+:6]([O-:8])=[O:7])[CH:1]=[N:5]1
Reactant: O=[N+]([O-])c1cn[nH]c1
Reactant: COCCBr
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCCn1cc([N+](=O)[O-])cn1
Reaction time: 0.17 h

Procedure:
To a solution of 4-nitropyrrazole (2.0 g) in DMF was added NaH (60% dispersion in oil) under ice cooling. After stirring at the same temperature for 10 minutes, 2-bromoethyl methyl ether (2.00 ml) and NaI (2.92 g) was added. The mixture was then stirred at room temperature for 3 hours, quenched by phosphate buffer solution (pH=7) and extracted with EtOAc. The extract was washed with H2O and brine, dried over MgSO4, and evaporated in vacuo. The residue was purified by column chromatography on silica gel to give 1-(2-methoxyethyl)-4-nitro-1H-pyrazole (2.15 g).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][C:12]=2[F:19])=[C:7]([CH:20]([OH:26])[C:21]([CH3:25])([CH3:24])[CH:22]=[CH2:23])[CH:6]=1)=[O:4].[H-].[Na+].[CH3:29]I.O>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][C:12]=2[F:19])=[C:7]([CH:20]([O:26][CH3:29])[C:21]([CH3:25])([CH3:24])[CH:22]=[CH2:23])[CH:6]=1)=[O:4]
Reactant: C=CC(C)(C)C(O)c1cc(C(=O)OC)ccc1-c1cc(OC)ccc1F
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: C=CC(C)(C)C(OC)c1cc(C(=O)OC)ccc1-c1cc(OC)ccc1F
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 47.2 %

Procedure:
To a solution of T21.4 (1530 mg, 4269 μmol) in DMF (40 mL), was added sodium hydride (60% in oil) (213 μL, 8538 μmol). The mixture was stirred at room temperature for 10 minutes and then methyl iodide (530 μL, 8538 μmol) was added in one portion and the mixture was stirred at room temperature for 30 minutes. Water was added and the mixture was, extracted with EtOAc. The organic phase was washed with water and brine and then dried over anhydrous sodium sulfate. After filtration, the organic solvent was removed in vacuo to give the product as a residue which was purified by chromatography to give the product as an oil (0.75 g, 47%). MS ESI m/e: 373.2 (M+18)+.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[S:15][C:16]3[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:17]=3[N:18]=2)[C@H:10]([CH2:27][O:28][CH3:29])[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:29][O:28][CH2:27][C@@H:10]1[CH2:9][NH:8][CH2:13][CH2:12][N:11]1[C:14]1[S:15][C:16]2[CH:22]=[C:21]([C:23]([F:26])([F:24])[F:25])[CH:20]=[CH:19][C:17]=2[N:18]=1
Reactant: COC[C@@H]1CN(C(=O)OC(C)(C)C)CCN1c1nc2ccc(C(F)(F)F)cc2s1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC[C@@H]1CNCCN1c1nc2ccc(C(F)(F)F)cc2s1
Temperature: 25 °C
Reaction time: 20 h
Yield: 95.9 %

Procedure:
To a solution of (S)-3-methoxymethyl-4-(6-trifluoromethyl benzothiazole-2-yl)piperazine-1-carboxylic acid t-butyl ester (167 mg) in methylene chloride (1.5 mL) was added trifluoroacetic acid (0.3 mL). The mixture was stirred at room temperature for 20 hours. The reaction solution was concentrated under reduced pressure. Saturated aqueous sodium hydrogencarbonate solution was added thereto and extracted with ethyl acetate. The organic layer was washed with brine, and dried over magnesium sulphate. The solvent was evaporated under reduced pressure to give the title compound (123 mg). Yield: 96%.
Reaction SMILES: [Cl:1][C:2]1[CH:54]=[CH:53][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[C@@H:17]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=4)[CH2:16][N:15]([CH2:28][CH2:29][S:30]([N:33](CC4C=CC(OC)=CC=4)CC4C=CC(OC)=CC=4)(=[O:32])=[O:31])[C:14]3=[O:52])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1>C(O)(C(F)(F)F)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]([N:13]3[C@@H:17]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:25])[F:26])[CH:19]=4)[CH2:16][N:15]([CH2:28][CH2:29][S:30]([NH2:33])(=[O:32])=[O:31])[C:14]3=[O:52])=[CH:11][CH:12]=2)=[CH:53][CH:54]=1
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)S(=O)(=O)CCN2C[C@H](c3cccc(C(F)(F)F)c3)N(c3ccc(Oc4ccc(Cl)cc4)cc3)C2=O)cc1
Solvent: O=C(O)C(F)(F)F
Product: NS(=O)(=O)CCN1C[C@H](c2cccc(C(F)(F)F)c2)N(c2ccc(Oc3ccc(Cl)cc3)cc2)C1=O
Yield: 78.8 %

Procedure:
A solution of (S)-2-(3-(4-(4-chlorophenoxy)phenyl)-2-oxo-4-(3-(trifluoromethyl)-phenyl)imidazolidin-1-yl)-N,N-bis(4-methoxybenzyl)ethanesulfonamide (2.2 g, 2.82 mmol) in TFA (30 mL) is stirred at room temperature for 14 h. Excess of TFA is removed under vacuum. The residue is treated with saturated NaHCO3 aqueous solution (30 mL) and extracted with EtOAc (3×50 mL). The combined organic layer is washed with brine and dried (MgSO4). After removing the drying agent, the solution is concentrated and purified by flash column chromatography (silica gel, EtOAc/hexane 0%˜90%) to provide the desired product (S)-2-(3-(4-(4-chlorophenoxy)phenyl)-2-oxo-4-(3-(trifluoromethyl)phenyl)-imidazolidin-1-yl)ethanesulfonamide as white solid (1.2 g, 83%). 1H NMR (CDCl3, 400 MHz) δ 7.55˜7.62 (m, 3H), 7.48 (t, 1H), 7.24 (d, 2H), 7.22 (d, 2H), 6.85 (m, 4H), 5.47 (s, 2H), 5.28 (dd, 1H), 3.90˜4.03 (m, 3H), 3.40 (dd, 1H), 3.28˜3.35 (m, 2H); HPLC-MS calculated for C24H21ClF3N3O4S (M+H+) 540.1, found 540.1.
Reaction SMILES: [OH:1][C:2]1[N:7]=[C:6]2[N:8]([CH3:12])[N:9]=[C:10]([CH3:11])[C:5]2=[CH:4][C:3]=1[C:13]#[N:14].[OH:15]S(O)(=O)=O>>[OH:1][C:2]1[N:7]=[C:6]2[N:8]([CH3:12])[N:9]=[C:10]([CH3:11])[C:5]2=[CH:4][C:3]=1[C:13]([NH2:14])=[O:15]
Reactant: O=S(=O)(O)O
Reactant: Cc1nn(C)c2nc(O)c(C#N)cc12
Product: Cc1nn(C)c2nc(O)c(C(N)=O)cc12
Temperature: 40 °C
Reaction time: 24 h

Procedure:
6-Hydroxy-1,3-dimethylpyrazolo[5,4-b]pyridine-5-carbonitrile (0.911 g) was dissolved in concentrated H2SO4 (3.0 mL) and stirred at 40° C. for 24 hrs. The solution was poured into ice-water and the precipitated solid was filtered, washed with water, and dried under high vacuum to give 6-hydroxy-1,3-dimethylpyrazolo[5,4-b]pyridin-5-carboxamide as a white solid. A portion of this material (0.122 g) was dissolved in DMF (2.0 mL). 2-Chlorotriethylamine hydrochloride (0.192 g) and potassium carbonate (0.304 g) were added to the solution. The reaction mixture was stirred at 60° C. for 18 h. The reaction mixture was poured into water, extracted with ethyl acetate. The extract was washed with saturated NaHCO3 solution and the brine, and dried over Na2SO4. The extract was evaporated under reduced pressure to give 6-[2-(diethylamino)ethoxy]-1,3-dimethylpyrazolo[5,4-b]pyridine-5-carboxamide as a white solid. A portion of this material (0.059 g) was dissolved in hot toluene (10 mL) and azeotroped for 2 hrs. The solution was cooled to room temperature. 4-Fluoro-3-(trifluoromethyl)phenylisocyanate (0.098 g) was added to the solution. The mixture was heated at reflux for 23 hrs, and then, cooled to room temperature. The solvent was evaporated under reduced pressure, and the residue was purified with the column chromatography (ethyl acetate). A portion of this material (20mg) was dissolved in tetrahydrofuran (1.0 mL) and treated with 1N hydrochloric acid solution (1.0 mL). The mixture was lyophilized to give {6-[2-(diethylamino)ethoxy]-1,3-dimethylpyrazolo[5,4-b]pyridin-5-yl}-N-({[4-fluoro-3-trifluoromethyl)phenyl]amino}carbonyl)carboxamide hydrochloride as a white solid.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]([CH:9]1[CH2:14][CH2:13][CH2:12][C:11](=[O:15])[CH2:10]1)#[N:8].[OH-].[Na+].Cl.C(OCC)C.C(=O)([O-])[O-].[K+].[K+].C([O:32][C:33]([C:35]1[CH:45]=[CH:44][CH:43]=[C:37]2C(N[C:41](=[O:42])[C:36]=12)=O)=O)C>O1CCCC1.O.C(#N)C>[OH:15][C@@H:11]1[CH2:12][CH2:13][CH2:14][C@H:9]([CH2:7][N:8]2[C:33](=[O:32])[C:35]3[C:36](=[CH:37][CH:43]=[CH:44][CH:45]=3)[C:41]2=[O:42])[CH2:10]1
Reactant: CCOC(=O)c1cccc2c1C(=O)NC2=O
Reactant: N#CC1CCCC(=O)C1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Al+3]
Solvent: CC#N
Solvent: O
Solvent: C1CCOC1
Product: O=C1c2ccccc2C(=O)N1C[C@H]1CCC[C@@H](O)C1
Reaction time: 5 h
Yield: 39.7 %

Procedure:
Under a nitrogen atmosphere, lithium aluminum hydride (92 mg, 2.44 mmol) was added to a solution of 1-cyanocyclohexan-3-one (100 mg, 0.812 mmol) in tetrahydrofuran (2 ml) at room temperature, and the resulting mixture was refluxed. After 5 hours, water, an aqueous sodium hydroxide solution and water were added in that order to the reaction solution, and the resulting mixture was filtered under reduced pressure. Thereafter, 1M-hydrochloric acid-diethyl ether (974 μl, 0.974 mmol) was added to the filtrate. The resulting mixture was concentrated under reduced pressure, and to an aqueous solution (4 ml) of the resulting residue were added potassium carbonate (202 mg, 1.46 mmol), ethoxycarbonylphthalimide (196 mg, 0.893 mmol) and acetonitrile (1 ml) at room temperature. After 21 hours, the reaction solution was poured into water and extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. The organic layer dried was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) and purified again by a silica gel column chromatography (eluent: chloroform/ethyl acetate) to obtain cis-2-[(3-hydroxycyclohexyl)methyl]-1H-isoindole-1,3(2H)-dione (83.5 mg, 40%, cis:trans=12:1).
Reaction SMILES: [C:1]([C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:18]=1[C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH:22]=O)=[CH:16][CH:15]=[CH:14][C:13]=2[C:27]([F:30])([F:29])[F:28])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:31][O:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][NH2:38])=[CH:35][CH:34]=1>>[CH3:31][O:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][NH:38][CH2:22][C:21]2[CH:20]=[C:19]([C:18]3[C:17]4[C:12](=[C:13]([C:27]([F:29])([F:30])[F:28])[CH:14]=[CH:15][CH:16]=4)[N:11]=[CH:10][C:9]=3[C:1]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:8])[CH:26]=[CH:25][CH:24]=2)=[CH:35][CH:34]=1
Reactant: O=Cc1cccc(-c2c(C(=O)c3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Reactant: COc1ccc(CN)cc1
Product: COc1ccc(CNCc2cccc(-c3c(C(=O)c4ccccc4)cnc4c(C(F)(F)F)cccc34)c2)cc1

Procedure:
The title compound was prepared from 3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]benzaldehyde and 4-methoxy-benzylamine according to the procedure of Example 66. MS (ES) m/z 527.2.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([F:11])[CH:3]=1.[CH3:12][CH:13]([CH3:16])[CH2:14][NH2:15]>>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:15][CH2:14][CH:13]([CH3:16])[CH3:12])=[O:8])=[C:4]([F:11])[CH:3]=1
Reactant: CC(C)CN
Reactant: O=C(O)c1ccc(Br)cc1F
Product: CC(C)CNC(=O)c1ccc(Br)cc1F

Procedure:
The sub-title compound was prepared by the method of example 18 step a) using 4-bromo-2-fluorobenzoic acid and 2-methyl-1-propanamine.
Reaction SMILES: [C:1]1([C:7]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:12][CH2:11][CH2:10][NH:9][C:8]2=[O:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)([O-])C.[K+].Br[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29]>O1CCCC1>[O:13]=[C:8]1[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:12][CH2:11][CH2:10][N:9]1[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29]
Reactant: CCOC(=O)CBr
Reactant: O=C1NCCCC1(c1ccccc1)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CCOC(=O)CN1CCCC(c2ccccc2)(c2ccccc2)C1=O
Temperature: 80 °C
Reaction time: 8 h

Procedure:
To a solution of the product of Example 1C (2.51 g, 10.00 mmol) in tetrahydrofuran (100 mL) was added potassium tert-butoxide (1.35 g, 12.00 mmol) under nitrogen followed by ethyl 2-bromoacetate (1.22 mL, 11.00 mmol). The reaction mixture was heated to 80° C. and stirred overnight. The reaction mixture was cooled to room temperature, concentrated and then diluted with ethyl acetate. The organic layer was washed with water and brine, dried over magnesium sulfate, filtered and concentrated. Silica gel chromatography eluting with ethyl acetate/hexane (20:80) gave the title compound. MS (DCI+) m/z 338 (M+H)+.
Reaction SMILES: Cl[C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].C[S:13](C)=O>O>[Cl:8][C:7]1[CH:6]=[CH:5][CH:4]=[C:3]([N+:9]([O-:11])=[O:10])[C:2]=1[SH:13]
Reactant: O=[N+]([O-])c1cccc(Cl)c1Cl
Reactant: CS(C)=O
Solvent: O
Product: O=[N+]([O-])c1cccc(Cl)c1S
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of 2,3-dichloronitrobenzene (Aldrich, 19.2 g, 100 mmol) in 300 mL of DMSO was added powdered Na2S.9H2O (Aldrich, 24.0 g, 100 mmol). The mixture was stirred at ambient temperature for 24 h, then was diluted with 2 L of water. The mixture was clarified by filtration and the filtrate was acidified to pH 4 with con. HCl. The mixture was extracted 3× with Et2O (400 mL). The organic layers were combined and washed twice with a brine solution (400 mL), dried over Na2SO4. Removal of the solvent under reduced pressure gave 18.4 g product. 1H NMR (400 MHz, DMSO) δ 8.11 (dd, J=8.3, 1.3 Hz, 1H), 7.93 (dd, J=8.0, 1.3 Hz, 1H), 7.40 (td, J=8.2, 1.3 Hz, 1H) 5.06 (s, 1H). MS (EI): m/z 188 (M−H).
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][CH:9]=1)[NH2:6].[Cl:10][CH2:11][CH2:12][C:13](Cl)=[O:14]>C1C=CC=CC=1>[CH3:1][S:2][C:3]1[CH:4]=[C:5]([NH:6][C:13](=[O:14])[CH2:12][CH2:11][Cl:10])[CH:7]=[CH:8][CH:9]=1
Reactant: O=C(Cl)CCCl
Reactant: CSc1cccc(N)c1
Solvent: c1ccccc1
Product: CSc1cccc(NC(=O)CCCl)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
3-Methylthioaniline (0.3 mole), β-chloropropionyl chloride (0.35 mole) and benzene (100 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. The reaction mixture is heated at reflux with stirring for a period of about 3 hours. After this time the reaction mixture is cooled to room temperature and is washed with dilute aqueous sodium bicarbonate, with dilute hydrochloric acid and with water. The washed mixture is then dried over anhydrous magnesium sulfate, filtered and stripped of benzene under reduced pressure to yield the desired product N-(3-methylthiophenyl)-β-chloropropionamide as the residue.
Reaction SMILES: [OH:1][N:2]=[C:3]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:4]([O:6][CH2:7][CH2:8][O:9][CH3:10])=[O:5].C(N(CC)CC)C.[C:24]1([CH3:34])[CH:29]=[CH:28][C:27]([S:30](Cl)(=[O:32])=[O:31])=[CH:26][CH:25]=1>O1CCCC1>[CH3:34][C:24]1[CH:29]=[CH:28][C:27]([S:30]([O:1][N:2]=[C:3]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:4]([O:6][CH2:7][CH2:8][O:9][CH3:10])=[O:5])(=[O:32])=[O:31])=[CH:26][CH:25]=1
Reactant: COCCOC(=O)C(=NO)c1ccccc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COCCOC(=O)C(=NOS(=O)(=O)c1ccc(C)cc1)c1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 78.1 %

Procedure:
A solution of 8.8 g (0.39 mol) of crude 2-methoxyethyl α-(hydroxyimino)-2-phenylacetate and 5.98 g of triethylamine in 65 ml tetrahydrofuran is cooled in an ice bath, and 8.3 g (0.043 mol) of p-toluenesulfonic acid chloride dissolved in 18 ml of tetrahydrofuran are added dropwise over 30 minutes. The resulting suspension is stirred for 16 hours at room temperature and then poured onto ice/water. The mixture is extracted with ethyl acetate, the organic layer washed with diluted HCI and water and dried over magnesium sulfate. Evaporation of the solvent gives an orange oil which is purified by chromatography on silica gel (eluent hexane/ethyl acetate 3:1). 12.68 g (86%) 2-Methoxyethyl α-(4-methylphenylsulfonyloxyimino)-2-phenylacetate are thus obtained as a colorless liquid. According to 1H-NMR-analysis, the product is a mixture of 72% of the trans isomer and 28% of the cis isomer.