Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH:8]([OH:13])[C:9]([O:11][CH3:12])=[O:10])=[C:6]([CH3:14])[N:5]=[C:4]2[S:15][C:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=3[C:3]=12.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.I[CH2:33][CH3:34]>CN(C=O)C>[Cl:1][C:2]1[C:7]([CH:8]([O:13][CH2:33][CH3:34])[C:9]([O:11][CH3:12])=[O:10])=[C:6]([CH3:14])[N:5]=[C:4]2[S:15][C:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=3[C:3]=12
Reactant: CCI
Reactant: COC(=O)C(O)c1c(C)nc2sc3c(c2c1Cl)CCCC3
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CN(C)C=O
Product: CCOC(C(=O)OC)c1c(C)nc2sc3c(c2c1Cl)CCCC3
Temperature: -15 °C
Reaction time: 0.25 h
Yield: 36.8 %

Procedure:
To a cold solution of methyl 2-[4-chloro-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]-2-hydroxyacetate (0.100 g; 0.307 mmol) in dry DMF (1.5 ml) at −15° C. under nitrogen atmosphere was added LHMDS (1M in THF) (0.338 mL; 0.338 mmol) dropwise and the mixture was stirred at −15° C. for 15 min. Then, iodoethane (0.049 mL; 0.614 mmol) was added and the mixture was allowed to warm up to room temperature. After 72 h, the reaction was quenched by adding a saturated solution of ammonium chloride, extracted with dichloromethane and the combined organics were washed with brine, dried over magnesium sulphate and concentrated under reduced pressure. Purification by flash chromatography on silica gel using a gradient of ethylacetate (5-40%) in heptane furnished 0.040 g (37%) of the title compound as a solid.
Reaction SMILES: C(OC([N:8]1[CH2:11][CH2:10][C@H:9]1[C:12]([OH:14])=[O:13])=O)(C)(C)C.S(=O)(=O)(O)O.Cl.C(=O)([O-])[O-].[Na+].[Na+].[N+:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[S:36](Cl)(=[O:38])=[O:37])([O-:29])=[O:28]>O.O1CCCC1>[N+:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[S:36]([N:8]1[CH2:11][CH2:10][C@H:9]1[C:12]([OH:14])=[O:13])(=[O:38])=[O:37])([O-:29])=[O:28]
Reactant: CC(C)(C)OC(=O)N1CC[C@H]1C(=O)O
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)Cl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)[C@@H]1CCN1S(=O)(=O)c1ccccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 89.8 %

Procedure:
A mixed solution of tetrahydrofuran (70 ml)/water (60 ml) containing (S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (20.51 g; also containing (R)-isomer) and sulfuric acid (10.03 g) was stirred for 1 hour under ice cooling, 1.5 hours at room temperature, and for 28 hours under heating at 45 to 48° C. On the way, 6 N hydrochloric acid (20 ml) was further added after about 20 hours. The reaction mixture was cooled with ice, and sodium carbonate (38.92 g), 2-nitrobenzenesulfonyl chloride (29.42 g), tetrahydrofuran (50 ml) and water (60 ml) were added in turn thereto, followed by stirring for 70 minutes under ice cooling and for 37 hours at room temperature. On the way, sodium carbonate (5.45 g) was further added after 30 minutes. Water (140 ml) was added to the reaction mixture, and the organic solvent was removed by evaporation under reduced pressure. Then, water (40 ml) and ethyl acetate (140 ml) were added, followed by extraction and solution separation, and the organic layer was extracted again with water (100 ml). Ethyl acetate (30 ml) and concentrated hydrochloric acid (40 ml) were added to the resulting aqueous layer, and ethyl acetate (100 ml) was further added, followed by extraction and solution separation. The aqueous layer was extracted again with ethyl acetate (120 ml). The resulting organic layer was dried over sodium sulfate, filtered, concentrated and dried under vacuum to obtain (S)-N-(2-nitrobenzenesulfonyl)azetidine-2-carboxylic acid (26.2 g; yield: 89.8%). Analysis according to high performance liquid chromatography (HPLC) resulted in 46.4% ee.
Reaction SMILES: [CH:1]1(O)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.C(Cl)(Cl)Cl.[N+](C1C=C([N+]([O-])=O)C=CC=1C([O-])=O)([O-])=[O:16]>CCCCCC.C(O)(C)C>[C@@H:4]12[CH2:3][CH2:2][CH2:1][C@@H:9]1[CH2:8][CH2:7][CH2:6][C@@H:5]2[OH:16]
Reactant: O=C([O-])c1ccc([N+](=O)[O-])cc1[N+](=O)[O-]
Reactant: OC1CCc2ccccc21
Solvent: CCCCCC
Solvent: CC(C)O
Solvent: ClC(Cl)Cl
Product: O[C@H]1CCC[C@H]2CCC[C@H]21

Procedure:
Racemic 19 (86 mg, 0.62 mmol) was dissolved in THF (5 mL), vinyl acetate (0.5 mL) was added. Amano lipase PS-30 (60 mg) was added and the resulting suspension was stirred at 23° C. until 50% conv. was reached (NMR) in ca. 6 h. The resulting suspension was diluted with Et2O and filtered on celite, the filter cake rinsed with Et2O. After evaporation of the remaining solvent, the residue was purified by column chromatography using hexanes/EtOAc (8:1, 6:1 then 4:1) to yield acetate 21 and the desired enantioenriched (−)-indanol (−)-19 (38.5 mg, 45% yield). [α]D20-28.3° (c 1.02, CHCl3), ([α]D20 lit. −27.2° (c 1.0, CHCl3).38 The enantiomeric excess of the 2,4-dinitrobenzoate derivative was determined to be 89.9% ee by chiral HPLC, Column ChiralPak IA, hexane/isopropanol (100/0 to 90/10, 15 min; 90/10 to 80/20, 15 min), 1 mL/min, Rt minor=16.58 min, Rt Major=19.5 min.
Reaction SMILES: [NH2:1][C@H:2]([C:4]([N:6]1[CH2:13][C@@H:12]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:11][C@H:7]1[C:8]([OH:10])=[O:9])=[O:5])[CH3:3].O=[C:22]([CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:23]([O:25][CH2:26][CH3:27])=[O:24].C([BH3-])#N.[Na+]>C(O)C>[CH2:26]([O:25][C:23]([C@@H:22]([NH:1][C@H:2]([C:4]([N:6]1[CH2:13][C@@H:12]([CH2:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:11][C@H:7]1[C:8]([OH:10])=[O:9])=[O:5])[CH3:3])[CH2:28][CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:24])[CH3:27]
Reactant: C[C@H](N)C(=O)N1C[C@@H](Cc2ccccc2)C[C@H]1C(=O)O
Reactant: CCOC(=O)C(=O)CCc1ccccc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)[C@H](CCc1ccccc1)N[C@@H](C)C(=O)N1C[C@@H](Cc2ccccc2)C[C@H]1C(=O)O

Procedure:
A solution of 1-(L-alanyl)-4-(S)-(phenylmethyl)-L-proline and ethyl 2-oxo-4-phenylbutyrate in ethanol is stored at room temperature with powdered molecular sieves. Over the course of several hours, sodium cyanoborohydride is added and the reaction mixture is filtered and concentrated under reduced pressure. The residue is purified by absorption on ion exchange resin to yield 1-[N-(1-(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl]-4-(S)-(phenylmethyl)-L-proline.
Reaction SMILES: [Li]CCCC.Br[C:7]1[CH:8]=[C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=1)[N:13]=[C:12]([O:18][CH3:19])[C:11]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=1)=[C:10]2[Cl:27].[CH3:28][N:29]1[C:33]([C:34]([C:36]2[CH:37]=[N:38][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:40][CH:41]=2)=[O:35])=[CH:32][N:31]=[CH:30]1>C1COCC1>[Cl:27][C:10]1[C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=[C:7]([C:34]([C:33]3[N:29]([CH3:28])[CH:30]=[N:31][CH:32]=3)([C:36]3[CH:37]=[N:38][C:39]([C:42]([F:44])([F:43])[F:45])=[CH:40][CH:41]=3)[OH:35])[CH:8]=2)[N:13]=[C:12]([O:18][CH3:19])[C:11]=1[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=1
Reactant: COc1nc2c(C)cc(Br)cc2c(Cl)c1-c1cccc(F)c1
Reactant: Cn1cncc1C(=O)c1ccc(C(F)(F)F)nc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COc1nc2c(C)cc(C(O)(c3ccc(C(F)(F)F)nc3)c3cncn3C)cc2c(Cl)c1-c1cccc(F)c1
Temperature: -78 °C
Reaction time: 0.02 h

Procedure:
n-BuLi (1.6 M in hexane, 2.19 mL, 3.50 mmol) was added over approximately 1 min to a solution of 6-bromo-4-chloro-3-(3-fluorophenyl)-2-methoxy-8-methylquinoline (1.40 g, 3.68 mmol, Intermediate 52) in THF (5 mL) under argon at −78° C. After 1 min, a solution of (1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (939 mg, 3.68 mmol, Intermediate 15, step c) in 5 mL THF under argon was added via cannula. The resulting mixture was stirred at −78° C. for 10 min, then transferred to an ice water bath and stirred 30 min. The reaction was quenched by addition of saturated aqueous NH4Cl, diluted with water and extracted with EtOAc (3×). The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 45-60% CH3CN in [2% conc. aqueous NH4OH in DCM, aqueous phase removed]) to afford the title compound as a white foam.
Reaction SMILES: CC(C)([O-])C.[K+].[CH3:7][S:8]([CH2:11]P(=O)(OCC)OCC)(=[O:10])=[O:9].[CH:20]([C@H:22]1[CH2:27][CH2:26][C@H:25]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:24][CH2:23]1)=O>O1CCCC1>[CH3:7][S:8]([CH:11]=[CH:20][C@H:22]1[CH2:23][CH2:24][C@H:25]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:26][CH2:27]1)(=[O:9])=[O:10]
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@H](C=O)CC1
Reactant: CCOP(=O)(CS(C)(=O)=O)OCC
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@H]1CC[C@H](C=CS(C)(=O)=O)CC1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of 1.0 M potassium tert-butoxide in tetrahydrofuran (THF) (1.0 mL, 1.0 mmol) was added diethyl [(methylsulfonyl)methyl]phosphonate (0.21 g, 0.92 mmol) dropwise at 0° C. and the resulting mixture was stirred at 0° C. for 1 h. A solution of tert-butyl (trans-4-formylcyclohexyl)carbamate (0.15 g, 0.66 mmol) in tetrahydrofuran (4.6 mL) was added dropwise, then cooling bath was removed and the mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with EtOAc, washed with water, concentrated and purified on silica gel (eluting with 0 to 5% MeOH in dichloromethane) to give the desired product (0.14 g, 70%) as a mixture of E- and Z-isomers. LCMS calculated for C14H25NO4SNa (M+Na)+: m/z=326.2. Found: 326.1.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([NH:12][C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)=[O:14])[C:9]([OH:11])=O.[S:23]1[CH2:27][CH2:26][N:25]([C:28]([C:30]2[CH:35]=[CH:34][C:33]([NH2:36])=[CH:32][CH:31]=2)=[O:29])[CH2:24]1.C(Cl)CCl>CN(C=O)C>[S:23]1[CH2:27][CH2:26][N:25]([C:28]([C:30]2[CH:35]=[CH:34][C:33]([NH:36][C:9](=[O:11])[CH:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[CH3:1])[NH:12][C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)=[O:14])=[CH:32][CH:31]=2)=[O:29])[CH2:24]1
Reactant: Cc1ccccc1C(NC(=O)Nc1ccc(Cl)cc1)C(=O)O
Reactant: Nc1ccc(C(=O)N2CCSC2)cc1
Solvent: CN(C)C=O
Solvent: ClCCCl
Product: Cc1ccccc1C(NC(=O)Nc1ccc(Cl)cc1)C(=O)Nc1ccc(C(=O)N2CCSC2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 21 %

Procedure:
To a solution of 2-(2-methylphenyl)-2-(4-chlorophenylaminocarbonylamino)-acetic acid (46 mg, 0.14 mmol) and 4-(thiazolidin-3-ylcarbonyl)phenylamine (30 mg, 0.14 mmol) in DMF (2 mL), EDC (54 mg, 0.28 mmol) was added. The reaction mixture was stirred at room temperature overnight. It was then concentrated in vacuo. The residue was purified by HPLC to give the titled compound as a white powder (15 mg). MS 509.2 and 511.2 (M+H, Cl pattern).
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][C:6]=2[N:12]1[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]1.[I-:19].[K+].C1(C)C=CC=CC=1.Cl>CN(C)P(N(C)C)(N(C)C)=O.[Cu]I>[I:19][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][C:6]=2[N:12]1[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]1
Reactant: [I-]
Reactant: CN1CCN(c2cccc3cc(Br)cnc23)CC1
Agent: [Cu]I
Agent: Cl
Agent: [K+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: Cc1ccccc1
Product: CN1CCN(c2cccc3cc(I)cnc23)CC1
Temperature: 150 °C
Reaction time: 0.08 h

Procedure:
A mixture of 3-bromo-8-(4-methyl-piperazin-1-yl)-quinoline (D1)(1.75 g, 5.7 mmol), copper (I) iodide (5.4 g, 28.5 mmol) and potassium iodide (9.6 g, 57.8 mmol) in hexamethylphosphoramide (20 ml) was heated in an oil bath at 150° C. for 21 h under argon. To the cooled reaction mixture was added toluene (120 ml) and 1M hydrochloric acid (120 ml) and the whole was shaken vigorously for 5 minutes. The insoluble brown solid was then collected by filtration, washed with methanol (3×40 ml) and resuspended in a mixture of dichloromethane (150 ml) and 2M sodium hydroxide (150 ml). After shaking the mixture vigorously, the insoluble material was filtered, washed with dichloromethane (2×50 ml) and discarded. The filtrate and washings were transferred to a separating funnel and the layers were separated. The aqueous phase was extracted with dichloromethane (2×100 ml) and the combined organic extracts were dried (MgSO4) and concentrated to a brown oil (1.5 g) which was identified by NMR spectroscopy as a mixture of the title compound (D2) and 3-bromo-8-(4-methyl-piperazin-1-yl)-quinoline (D1) in a ratio of 4:1. This mixture was used directly in the next stage (see Example 1).
Reaction SMILES: [N:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:30]=[CH:29][C:13]3[N:14]4[CH:19]=[C:18]([C:20]5[CH:25]=[CH:24][C:23]([N+:26]([O-])=O)=[CH:22][CH:21]=5)[N:17]=[C:15]4[S:16][C:12]=3[CH:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.CO.[H][H]>[Ni].C1COCC1>[N:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:30]=[CH:29][C:13]3[N:14]4[CH:19]=[C:18]([C:20]5[CH:21]=[CH:22][C:23]([NH2:26])=[CH:24][CH:25]=5)[N:17]=[C:15]4[S:16][C:12]=3[CH:11]=2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1
Reactant: [H][H]
Reactant: O=[N+]([O-])c1ccc(-c2cn3c(n2)sc2cc(OCCN4CCOCC4)ccc23)cc1
Agent: [Ni]
Solvent: CO
Solvent: C1CCOC1
Product: Nc1ccc(-c2cn3c(n2)sc2cc(OCCN4CCOCC4)ccc23)cc1

Procedure:
7-(2-Morpholin-4-yl-ethoxy)-2-(4-nitrophenyl)imidazo[2,1-b]benzothiazole was dissolved into methanol and THF and placed in a hydrogenator. Raney nickel was added and the vessel was pressurized with hydrogen and stirred for >24 hours. The reaction mixture was concentrated to a thick paste and diluted with methyl tert-butyl ether. The resulting solids were filtered and washed with methyl tert-butyl ether and dried under vacuum to give 7-(2-morpholin-4-yl-ethoxy)-2-(4-aminophenyl) imidazo[2,1-b]benzothiazole.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C:12]1[CH:20]=[C:19]2[C:15]([C:16]3[C:24]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[F:31])=[CH:23][N:22]=[C:21]([C:32]([O:34]CC)=[O:33])[C:17]=3[NH:18]2)=[CH:14][CH:13]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[OH-].[Li+]>O1CCCC1.CO.O>[CH2:1]([O:8][C:9]([NH:11][C:12]1[CH:20]=[C:19]2[C:15]([C:16]3[C:24]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[F:31])=[CH:23][N:22]=[C:21]([C:32]([OH:34])=[O:33])[C:17]=3[NH:18]2)=[CH:14][CH:13]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)c1ncc(-c2ccccc2F)c2c1[nH]c1cc(NC(=O)OCc3ccccc3)ccc12
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: O=C(Nc1ccc2c(c1)[nH]c1c(C(=O)O)ncc(-c3ccccc3F)c12)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.5 %

Procedure:
To a solution of ethyl 7-(benzyloxycarbonylamino)-4-(2-fluorophenyl)-9H-pyrido[3,4-b]indole-1-carboxylate (0.238 g, 0.492 mmol) in tetrahydrofuran (12 mL) and methanol (4 mL) at room temperature was added a solution of lithium hydroxide hydrate (0.083 g, 1.969 mmol) in water (1.8 mL). The mixture was stirred at room temperature for 1 hr, and then concentrated under vacuum. To the residue was added water (5 ml), and the mixture was acidified to pH 5 with 1 N HCl. The precipitating product (0.214 g, 0.470 mmol, 95% yield) was collected by suction filtration and dried over Drierite under vacuum.
Reaction SMILES: [C:1]([CH:3]=[C:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:20][C@@H:19]([CH2:21][N:22]=[N+]=[N-])[O:18][C:17]3=[O:25])=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)#[N:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O>[C:1]([CH:3]=[C:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([N:16]3[CH2:20][C@H:19]([CH2:21][NH2:22])[O:18][C:17]3=[O:25])=[CH:14][CH:15]=2)[CH2:6][CH2:5]1)#[N:2]
Reactant: N#CC=C1CCN(c2ccc(N3C[C@@H](CN=[N+]=[N-])OC3=O)cc2)CC1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Product: N#CC=C1CCN(c2ccc(N3C[C@H](CN)OC3=O)cc2)CC1
Reaction time: 3 h
Yield: 71 %

Procedure:
To a mixture of (S)-{3-[4-(4-cyanomethylidene-piperidin-1-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-azide (2.94 mmol), triphenylphosphine (3.81 mmol) was stirred for 3 hours. It was refluxed by adding water overnight. Removal of solvent and purification of the product on silica gel column chromatography provided (S)-{3-[4-(4-cyanomethylidene-piperidin-1-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-amine in 71% yield.
Reaction SMILES: C(O)(=O)C.[F:5][C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1)[CH:9]=O.[N+:22]([CH3:25])([O-:24])=[O:23].C([O-])(=O)C.[NH4+]>C(OCC)(=O)C.O>[F:5][C:6]1[CH:7]=[C:8](/[CH:9]=[CH:25]/[N+:22]([O-:24])=[O:23])[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1
Reactant: O=Cc1ccc(OCc2ccccn2)c(F)c1
Reactant: C[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Solvent: O
Product: O=[N+]([O-])/C=C/c1ccc(OCc2ccccn2)c(F)c1
Temperature: 110 °C
Reaction time: 2 h
Yield: 90.4 %

Procedure:
To an acetic acid (25.0 mL) solution of 3-fluoro-4-(pyridin-2-ylmethoxy)-benzaldehyde (2.80 g, 12.1 mmol) described in Manufacturing Example 87-1-1 were added nitromethane (3.69 g, 60.5 mmol) and ammonium acetate (1.87 g, 24.2 mmol) under nitrogen atmosphere at room temperature, which was stirred for 2 hours at 110° C. Water and ethyl acetate were added to the reaction mixture, and the organic layer was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure to obtain the title compound (3.00 g) as a crude product.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:13]=[CH:14][C:15]=1[N:16]=[N:17][C:18]1[C:23]([N+:24]([O-:26])=[O:25])=[CH:22][C:21]([N+:27]([O-:29])=[O:28])=[CH:20][C:19]=1Cl)[N:8]([CH2:11][CH3:12])[CH2:9][CH3:10])(=[O:3])[CH3:2].[C-:31]#[N:32].[Na+].O>C(CCSCCC#N)#N>[C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:13]=[CH:14][C:15]=1[N:16]=[N:17][C:18]1[C:23]([N+:24]([O-:26])=[O:25])=[CH:22][C:21]([N+:27]([O-:29])=[O:28])=[CH:20][C:19]=1[C:31]#[N:32])[N:8]([CH2:11][CH3:12])[CH2:9][CH3:10])(=[O:3])[CH3:2]
Reactant: [C-]#N
Reactant: CCN(CC)c1ccc(N=Nc2c(Cl)cc([N+](=O)[O-])cc2[N+](=O)[O-])c(NC(C)=O)c1
Agent: N#CCCSCCC#N
Agent: [Na+]
Solvent: O
Product: CCN(CC)c1ccc(N=Nc2c(C#N)cc([N+](=O)[O-])cc2[N+](=O)[O-])c(NC(C)=O)c1
Temperature: 132.5 °C
Reaction time: 0.5 h
Yield: 82.5 %

Procedure:
7.175 parts of cuprous bromide are dissolved in 350 parts of bis-(β-cyanoethyl) sulfide. 43.45 parts of 3-acetamido-4-(2'-chloro-4',6'-dinitrophenylazo)-N,N-diethylaniline are introduced, and the mass is brought to 130° C. During 1 hour 30 minutes, in an open reactor, a solution of 6.35 parts of sodium cyanide in 20 parts of water is added to the mixture and the mixture is stirred for 4 hours at 130-135° C. The product formed is separated as in Example 1; 35.12 parts of 3-acetamido-4-(2'-cyano-4', 6'-dinitrophenylazo)-N,N-diethylaniline are obtained. The yield is 82.5%.
Reaction SMILES: [F:1][C:2]([F:29])([F:28])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:10][C:11]3[C:16]([C:17](=[O:20])[C:18]=2[OH:19])=[C:15]([OH:21])[CH:14]=[C:13]([OH:22])[C:12]=3[CH2:23][CH:24]=[C:25]([CH3:27])[CH3:26])=[CH:5][CH:4]=1.[C:30](=O)([O-])[O-].[Cs+].[Cs+].C(Br)C=C(C)C.Cl>O>[F:29][C:2]([F:1])([F:28])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:10][C:11]3[C:16]([C:17](=[O:20])[C:18]=2[O:19][CH3:30])=[C:15]([OH:21])[CH:14]=[C:13]([OH:22])[C:12]=3[CH2:23][CH:24]=[C:25]([CH3:26])[CH3:27])=[CH:5][CH:4]=1
Reactant: CC(C)=CCc1c(O)cc(O)c2c(=O)c(O)c(-c3ccc(C(F)(F)F)cc3)oc12
Reactant: O=C([O-])[O-]
Agent: CC(C)=CCBr
Agent: Cl
Agent: [Cs+]
Solvent: O
Product: COc1c(-c2ccc(C(F)(F)F)cc2)oc2c(CC=C(C)C)c(O)cc(O)c2c1=O
Reaction time: 8 h
Yield: 16.5 %

Procedure:
Intermediate 2-(4-trifluorophenyl)-3-methoxy-5,7-dihydroxy-4H-chrom-4-one (500 mg, 1.42 mmol) of compound 1 and cesium carbonate (4.95 g, 15 mmol) were dissolved into 25 mL water, and prenyl bromide (220 mg, 1.5 mmol) was dropped into the solution under icewater bath condition. After that, the solution was kept overnight under room temperature, and pH was adjusted about 6 with 2N hydrochloride. The solution was extracted with ethyl acetate for 2 times. Organic phases were combined, washed with saturated sodium chloride aqueous solution and dried with anhydrous sodium sulfate. After filtration, crude product was eluted with ethyl acetate/petroleum through silica gel column. Yellow target compound (95 mg, yield 16.5%) was obtained.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:16]=[CH:17][C:18]=1[CH3:19])[C:7]([NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:8])([O-])=O.[H][H]>[Ni].O1CCCC1.CO>[NH2:1][C:4]1[CH:5]=[C:6]([CH:16]=[CH:17][C:18]=1[CH3:19])[C:7]([NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:8]
Reactant: [H][H]
Reactant: Cc1ccc(C(=O)Nc2ccccc2)cc1[N+](=O)[O-]
Agent: [Ni]
Solvent: CO
Solvent: C1CCOC1
Product: Cc1ccc(C(=O)Nc2ccccc2)cc1N
Temperature: 25 °C
Yield: 101.3 %

Procedure:
Raney nickel (1 g) was added to a solution of 3-nitro-4-methyl-N-phenyl-benzamide (6.2 g, 24 mmol) in a mixture of tetrahydrofuran (50 mL) and methanol (100 mL) and shaken at room temperature under an atmosphere of hydrogen, initially at a pressure of 50 psi, until the required amount of hydrogen was taken up. The catalyst was removed by filtration, and the filtrate was stripped of solvent by rotary evaporator. The residue was dried under reduced pressure to afford the pure product (5.5 g); m.p. 149-151° C.
Reaction SMILES: [CH3:1][O:2][N:3]=C1C2C=CN=NC=2OC1.[Cl:13][C:14]1[CH:19]=[N:18][CH:17]=[C:16]2[O:20][CH2:21][C:22](=O)[C:15]=12>>[CH3:1][O:2][N:3]=[C:22]1[C:15]2[C:16](=[CH:17][N:18]=[CH:19][C:14]=2[Cl:13])[O:20][CH2:21]1
Reactant: CON=C1COc2nnccc21
Reactant: O=C1COc2cncc(Cl)c21
Product: CON=C1COc2cncc(Cl)c21

Procedure:
This compound was prepared using a method analogous to that of furo[2,3-c]pyridazin-5(6H)-one O-methyl oxime (A.2.3.3), 4-chlorofuro[2,3-c]pyridin-3(2H)-one replacing furo[2,3-c]pyridazin-5(6H)-one;
Reaction SMILES: [C:1](Cl)(Cl)=[S:2].[Cl:5][C:6]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]([Cl:15])[C:7]=1[NH2:8]>O1CCCC1.C(=O)([O-])O.[Na+]>[Cl:5][C:6]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]([Cl:15])[C:7]=1[N:8]=[C:1]=[S:2]
Reactant: COc1cc(Cl)c(N)c(Cl)c1
Reactant: S=C(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1cc(Cl)c(N=C=S)c(Cl)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.8 %

Procedure:
Thiophosgene (1.62 mL, 21.8 mmol) was added dropwise to a stirred mixture of 2,6-dichloro-4-methoxyaniline (2.00 g, 10.4 mmol) in tetrahydrofuran (25 mL) and saturated aqueous sodium hydrogen carbonate (25 mL) at 0° C. The mixture was stirred at room temperature for 1 h, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was washed with n-hexane to give the title compound as a brown solid (2.21 g, 9.44 mmol, 91%).
Reaction SMILES: [OH:1][C:2]1[CH:17]=[C:16]([OH:18])[CH:15]=[CH:14][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][C:7]=1[OH:13])=[O:5].[C:19](Cl)(=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21]>N1C=CC=CC=1>[C:19]([O:1][C:2]1[CH:17]=[C:16]([O:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])[CH:15]=[CH:14][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][C:9]([O:12][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:8][C:7]=1[O:13][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[O:5])(=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21]
Reactant: CC(C)(C)C(=O)Cl
Reactant: O=C(c1ccc(O)cc1O)c1ccc(O)cc1O
Solvent: c1ccncc1
Product: CC(C)(C)C(=O)Oc1ccc(C(=O)c2ccc(OC(=O)C(C)(C)C)cc2OC(=O)C(C)(C)C)c(OC(=O)C(C)(C)C)c1

Procedure:
A solution of 2.4 g (0.01 mole) of 2,2',4,4'-tetrahydroxybenzophenone and 5 g (0.04 mole) of pivaloylchloride was warmed to 50° C. in 75 mls of dry pyridine for 2 hrs with a drying tube attached. The solvent was removed via rotary evaporator and the residue was partitioned between H2O and CH2Cl2 ; the organic layer was washed with dilute K2CO3 and dried over MgSO4. After removal of solvent via rotary evaporation, the title compound was crystallized from ethanol. 4 g. (69%) yield. M.P.~154°-156° C.