Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH:12]=O)=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:14])[CH:3]=1.[NH2:15][C:16]1[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[C:18]([C:24]([F:27])([F:26])[F:25])[CH:17]=1.Cl.[BH4-].[Na+]>C(O)C>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][NH:15][C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[C:18]([C:24]([F:25])([F:26])[F:27])[CH:17]=3)=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:14])[CH:3]=1
Reactant: Cc1cc(Cl)c2ccc(C=O)cc2n1
Reactant: N#Cc1ccc(N)cc1C(F)(F)F
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: Cc1cc(Cl)c2ccc(CNc3ccc(C#N)c(C(F)(F)F)c3)cc2n1
Temperature: 25 °C
Reaction time: 16 h
Yield: 37.4 %

Procedure:
To a solution of 4-chloro-2-methyl-quinoline-7-carbaldehyde (example 13a, 180 mg, 0.875 mmol) in ethanol (3 mL) were added 4-amino-2-trifluoromethyl-benzonitrile (163 mg, 0.875 mmol), 25% aq. hydrochloric acid solution (1.5 mL), and sodium borohydride (207 mg, 5.25 mmol). The reaction mixture was stirred 16 h at r.t., then partitioned between ethyl acetate and 1 M aq. sodium hydroxide solution. The organic layer was washed with brine, dried (MgSO4), and evaporated. Flash chromatography (SiO2, hexane/ethyl acetate 1:1 afforded the title compound (123 mg, 37%). Off-white solid, ISP-MS: m/e=376.3 ([M+H]+).
Reaction SMILES: [C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([Br:14])=[CH:11][CH:12]=2)[C@H:7]([NH2:15])[CH2:6][C@@H:5]1[CH3:16])(=[O:3])[CH3:2].CCN(C(C)C)C(C)C.C1[C:31]([N+]([O-])=O)=[CH:30][CH:29]=[C:28]([O:35][C:36](Cl)=[O:37])C=1.C1(O)CCC1>ClCCl>[CH:28]1([O:35][C:36](=[O:37])[NH:15][C@H:7]2[C:8]3[C:13](=[CH:12][CH:11]=[C:10]([Br:14])[CH:9]=3)[N:4]([C:1](=[O:3])[CH3:2])[C@@H:5]([CH3:16])[CH2:6]2)[CH2:29][CH2:30][CH2:31]1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: CC(=O)N1c2ccc(Br)cc2[C@H](N)C[C@@H]1C
Agent: OC1CCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(=O)N1c2ccc(Br)cc2[C@H](NC(=O)OC2CCC2)C[C@@H]1C

Procedure:
(cis)-1-Acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine (for a preparation see Intermediate 4) (200 mg, 0.706 mmol) was dissolved in dichloromethane (DCM) (5 mL), mixed with DIPEA (0.370 mL, 2.119 mmol) followed by 4-nitrophenyl chloridocarbonate (157 mg, 0.777 mmol, available from Fluka) and stirred under nitrogen. Cyclobutanol (0.082 mL, 1.059 mmol) was added after 1.75 hours. The reaction was allowed to stir under nitrogen for 17 hours. The reaction was partitioned between distilled water (20 mL) and EtOAc (60 mL). The aqueous layer was extracted with EtOAc (60 mL) and the organic fractions were combined, washed (brine (50 mL)), dried (sodium sulfate) and evaporated to dryness to give a yellow solid (346 mg). The residue was purified by SP4 on a 25+M Biotage silica column, eluting with a gradient of 0 to 50% ethyl acetate in cyclohexane. Product-containing fractions were evaporated to dryness to give a clear, colourless solid (39 mg). LCMS (Method C): Rt=1.05, MH+=383
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH2:17][N:18]2[CH:22]=[N:21][CH:20]=[N:19]2)([CH2:13][CH2:14][CH2:15][CH3:16])[CH2:11][OH:12])=[CH:6][CH:5]=1.Cl[C:24]1[N:29]=[CH:28][CH:27]=[CH:26][N:25]=1.C(OCC)(=O)C>CCOCC>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH2:17][N:18]2[CH:22]=[N:21][CH:20]=[N:19]2)([CH2:13][CH2:14][CH2:15][CH3:16])[CH2:11][O:12][C:24]2[N:29]=[CH:28][CH:27]=[CH:26][N:25]=2)=[CH:6][CH:5]=1
Reactant: Clc1ncccn1
Reactant: CCCCC(CO)(Cn1cncn1)c1ccc(Cl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: CCCCC(COc1ncccn1)(Cn1cncn1)c1ccc(Cl)cc1
Temperature: 25 °C
Yield: 102.8 %

Procedure:
To a flask was charged 0.15 g (0.0034 mole) of 60% sodium hydride, washed with 2×30 mL hexane, in 20 mL of tetrahydrofuran. While stirring at room temperature, 1.0 g (0.0034 mole) of 2-(4-chlorophenyl)-2-[(1,2,4-triazol-1-yl)methyl]hexan-1-ol was added. The slurry was stirred at room temperature and 0.39 g of 2-chloropyrimidine (0.0034 mole) was added. The reaction was stirred overnight after which TLC using ethyl acetate indicated the reaction was complete. The product was isolated from ether after quenching and washing with water. After drying and removal of the solvent, 1.30 g (100% yield) of an oil resulted.
Reaction SMILES: C([Al]CC(C)C)C(C)C.[N:10]1([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21](OC)=[O:22])[N:16]=2)[CH:14]=[CH:13][CH:12]=[CH:11]1.C([O-])(=O)C(C(C([O-])=O)O)O.[K+].[Na+]>C1(C)C=CC=CC=1>[N:10]1([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][OH:22])[N:16]=2)[CH:11]=[CH:12][CH:13]=[CH:14]1
Reactant: COC(=O)c1cccc(-n2cccc2)n1
Agent: CC(C)C[Al]CC(C)C
Agent: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: OCc1cccc(-n2cccc2)n1
Temperature: -30 °C
Reaction time: 0.5 h
Yield: 91 %

Procedure:
38 ml of diisobutyl aluminum were added dropwise over one hour at -40° C. to a solution of 3.7 g of the product of Step D in 40 ml of toluene and the mixture was stirred at -30° C. for 30 minutes. 110 ml of an aqueous molar solution of double sodium potassium tartarate were slowly added to the mixture while keeping the temperature below 10° C. and the mixture was stirred for 16 hours at room temperature. The decanted organic phase was dried and evaporated to dryness under reduced pressure to obtain 2.9 g of 2-(pyrrol-1-yl)-6-pyridyl-methanol melting at 55° C.
Reaction SMILES: [F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]([CH3:34])([CH3:33])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21](Cl)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH2:37]1[NH:42][C:41](=[O:43])[CH2:40][N:39]2[CH2:44][CH2:45][CH2:46][C@H:38]12.CN(C)CN.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[Cu](I)I>[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]([CH3:34])([CH3:33])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([N:42]3[C:41](=[O:43])[CH2:40][N:39]4[CH2:44][CH2:45][CH2:46][C@@H:38]4[CH2:37]3)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
Reactant: O=C1CN2CCC[C@@H]2CN1
Reactant: Cc1cc(F)ccc1-c1cc(Cl)ncc1N(C)C(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Agent: I[Cu]I
Agent: CN(C)CN
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: Cc1cc(F)ccc1-c1cc(N2C[C@H]3CCCN3CC2=O)ncc1N(C)C(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: 80 °C
Yield: 50.4 %

Procedure:
The title compound was prepared starting from 100 mg (0.187 mmoles) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 79 mg (0.563 mmol) of (8aR)-hexahydropyrrolo[1,2-a]pyrazin-3(4H)-one (D14), 72 mg of copper iodide (0.378 mmol), 40 μl (0.375 mmol) of N,N-dimethylmethanediamine, 112.4 mg (0.375 mmol) of cesium carbonate; the reagents were dissolved in 4 ml of dioxane and heated at 80° C. for 4 h and then at 120° C. overnight. The crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 60 mg of the title compound as pale yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[N:8][CH:7]=[CH:6]2.[Al+3].[Cl-].[Cl-].[Cl-].[Br:17]Br.C([O-])([O-])=O.[Na+].[Na+]>ClCCl.O>[Br:17][C:4]1[C:3]([O:2][CH3:1])=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][N:8]=[CH:9]2
Reactant: COc1ccc2cnccc2c1
Reactant: BrBr
Agent: O=C([O-])[O-]
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: O
Product: COc1ccc2cnccc2c1Br
Reaction time: 0.5 h
Yield: 33.8 %

Procedure:
To a solution of 6-methoxyisoquinoline (2.38 g, 14.9 mmol) in dichloromethane (55 ml) was added AlCl3 (4.4 g, 33 mmol) under nitrogen at ambient temperature. The mixture was stirred for 30 min then Br2 (0.92 ml, 18 mmol) was added at 0° C. The mixture was stirred for 2 h, then poured into water and neutralised with solid Na2CO3. The mixture was filtered through celite and the filtrate extracted with dichloromethane and chloroform. The combined organics were washed with brine, dried (Na2SO4) and concentrated in vacuo to give a residue. Flash chromatography of the residue on silica (eluent: 50-100% ethyl acetate in heptane) gave 5-bromo-6-methoxyisoquinoline (1.2 g, 34% yield).
Reaction SMILES: [CH3:1][CH2:2][CH2:3][C:4]1[C:10]2[C:11]3[O:25][C:24]([CH3:27])([CH3:26])[CH2:23][CH2:22][C:12]=3[C:13]3[O:18][C@@H:17]([CH3:19])[C@H:16]([CH3:20])[C@H:15]([OH:21])[C:14]=3[C:9]=2[O:8][C:6](=[O:7])[CH:5]=1.[CH3:28][CH2:29][CH2:30]C1C2C3OC(C)(C)C=CC=3C3OC(C)C(C)C(O)C=3C=2OC(=O)C=1>CO.O=[Pt]=O>[CH3:20][C@@H:16]1[C@H:15]([OH:21])[C:14]2[C:9]3[O:8][C:6]([CH:5]=[C:4]([C:3]4[CH:28]=[CH:29][CH:30]=[CH:1][CH:2]=4)[C:10]=3[C:11]3[O:25][C:24]([CH3:27])([CH3:26])[CH:23]=[CH:22][C:12]=3[C:13]=2[O:18][C@H:17]1[CH3:19])=[O:7]
Reactant: CCCc1cc(=O)oc2c3c(c4c(c12)OC(C)(C)CC4)O[C@@H](C)[C@H](C)[C@@H]3O
Reactant: CCCc1cc(=O)oc2c3c(c4c(c12)OC(C)(C)C=C4)OC(C)C(C)C3O
Agent: O=[Pt]=O
Solvent: CO
Product: C[C@H]1[C@H](C)Oc2c3c(c4c(-c5ccccc5)cc(=O)oc4c2[C@H]1O)OC(C)(C)C=C3

Procedure:
This example illustrates the preparation of antiviral 7,8-dihydro compounds (FIG. 6) of series 2, specifically 7,8-dihydrocalanolide A, 7,8-dihydrocalanolide B, 7,8-dihydro-costatolide, and 7,8-dihydrosoulattrolide from the corresponding 7,8-unsaturated compounds of series 1. of these six compounds, only one structure (7,8-dihydrocostatolide; Stout, G. H., et al., J. Org. Chem., 29, 3604-3609 (1964)) had been previously reported, however none of the six were known heretofore to have antiviral activity. The 7,8-dihydro compounds were made by catalytic hydrogenation of the selected appropriate 7,8-unsaturated precursors. In a typical procedure, 10 mg of calanolide A was stirred with 2.5 mg PtO2 (Aldrich) in 4 ml MeOH under an atmosphere of H2 (a balloon filled with H2 was attached to the reaction vessel to provide a slightly positive pressure of H2) for 30 min. The mixture was filtered, and the solvent removed in vacuo to provide a light yellow oil which was purified by SiO2 HPLC (21.1×300 mm, Dynamax column) eluted with 25 ml/min hexane/EtOAc (7:3) to give 9.0 mg of 7,8-dihydrocalanolide A (EIMS m/z 372, appropriate for C22H28O5; 1H NR, see Table 5). In an exactly analogous fashion, 6 mg of calanolide B with 3 mg PtO2 in 4 ml MeOH was converted to 3.6 mg of 7,8-dihydrocalanolide B (EIMS m/z 372, appropriate for C22H28O5; 1H NMR, see Table 5); 100 mg of costatolide with 15 mg PtO2 in 20 ml MeOH was converted to 89.9 mg 7,8-dihydrocostatolide (EIMS m/z 372, appropriate for C22H28O5; 1H NMR, see Table 5); and 12 mg of soulattrolide with 3 mg Pto2 in 4 ml MeOH was converted to 8.9 mg 7,8-dihydrosoulattrolide (EIMS m/z 406, appropriate for C25H26O5; 1H NMR, see Table 5).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([CH3:14])[N:8]([CH3:13])[C:9]=1[C:10]([OH:12])=O)=[O:4].[CH3:15][N:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[N:18]=[C:17]1[CH2:25][CH2:26][NH2:27]>>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([CH3:14])[N:8]([CH3:13])[C:9]=1[C:10](=[O:12])[NH:27][CH2:26][CH2:25][C:17]1[N:16]([CH3:15])[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[N:18]=1)=[O:4]
Reactant: Cn1c(CCN)nc2ccccc21
Reactant: COC(=O)c1nc(C)n(C)c1C(=O)O
Product: COC(=O)c1nc(C)n(C)c1C(=O)NCCc1nc2ccccc2n1C

Procedure:
The product was obtained starting from 1,2-dimethyl-1H-imidazole-4,5-dicarboxylic acid 4-methyl ester (200 mg, 1.01 mmol) and 2-(1-methyl-1H-benzo[d]imidazol-2-yl)ethanamine (195 mg, 1.11 mmol) according to the method described in example 7, step 5 after aqueous work-up and purification by flash chromatography (using silica gel amine phase and a MeOH/ethyl acetate gradient) as light red gum (98 mg, 276 μmol, 27.3%). MS: M=356.1 (M+H)+
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][O:19][CH2:20][O:21][CH3:22])[N:6]=[C:5]([N:23]([CH3:25])[CH3:24])[CH:4]=1.[Br:26]N1C(=O)CCC1=O>C(#N)C>[Br:26][C:8]1[C:3]([O:2][CH3:1])=[CH:4][C:5]([N:23]([CH3:25])[CH3:24])=[N:6][C:7]=1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][O:19][CH2:20][O:21][CH3:22]
Reactant: COCOCCCCCCCCCCc1cc(OC)cc(N(C)C)n1
Reactant: O=C1CCC(=O)N1Br
Solvent: CC#N
Product: COCOCCCCCCCCCCc1nc(N(C)C)cc(OC)c1Br
Temperature: 23 °C
Reaction time: 3 h

Procedure:
To a stirred solution containing 213 mg (0.60 mmol) of 4-methoxy-6-(10-(methoxymethoxy)decyl)-N,N-dimethylpyridin-2-amine in 5 mL of acetonitrile were added 107 mg (0.60 mmol) of N-bromosuccinimide. The reaction mixture was stirred at 23° C. protected from light for 3 h. The reaction mixture was poured into 50 mL of satd. aq. sodium bicarbonate and extracted two 50-mL portions of ethyl acetate. The combined organic layer was washed with one 50-mL portion of brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (3×10 cm). Elution with 4:1 hexanes-ethyl acetate afforded the expected product as a yellowish oil: yield 114 mg (44%); silica gel TLC Rf 0.45 (4:1 hexanes-ethyl acetate); 1H NMR (CDCl3) δ 1.29 (br m, 12H), 1.56 (quint, 2H, J=7.2 Hz), 1.68 (quint, 2H, J=7.2 Hz), 2.55 (dd, 2H, J=7.6, 7.6 Hz), 3.03 (s, 6H), 3.33 (s, 3H), 3.48 (t, 2H, J=6.8 Hz), 3.85 (s, 3H), 4.59 (s, 2H) and 5.76 (s, 1H); 13C NMR (CDCl3) δ 26.17, 28.08, 29.40, 29.47, 29.51, 29.57, 29.65, 29.72, 37.31, 38.05, 38.05, 55.02, 55.65, 67.87, 86.47, 96.35, 97.29, 158.80, 159.11 and 162.60; mass spectrum (APCI), m/z (M+H)+431.1913 (C20H36N2O3Br requires 431.1909).
Reaction SMILES: [Cl:1][CH2:2][C@H:3]([OH:7])[CH2:4][CH2:5][OH:6].ClC[C@H](O)CC(OC)=O.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>C(Cl)Cl>[Cl:1][CH2:2][C@H:3]([OH:7])[CH2:4][CH2:5][O:6][S:30]([C:27]1[CH:28]=[CH:29][C:24]([CH3:34])=[CH:25][CH:26]=1)(=[O:32])=[O:31]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: OCC[C@@H](O)CCl
Agent: COC(=O)C[C@@H](O)CCl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)OCC[C@@H](O)CCl)cc1
Temperature: -20 °C
Reaction time: 0.5 h
Yield: 54.7 %

Procedure:
A solution of 5 g (40 mmole) of (3R)-4-chloro-1,3-butanediol in 30 ml of methylene chloride, said (3R)-4-chloro-1,3-butanediol being obtainable in a similar manner as in Example 1 starting from methyl (3R)-4-chloro-3-hydroxybutyrate, was cooled to -20° C. on a dry ice-acetone bath, and 8.13 g (80 mmole) of triethylamine was added dropwise thereto over 30 minutes. A solution of 7.66 g (40.2 mmole) of p-toluenesulfonyl chloride in 100 ml of methylene chloride was added dropwise thereto over 50 minutes. After returning to room temperature, the mixture was stirred for 20 hours. The reaction mixture was poured into 200 ml of ice-water for liquid separation. The organic layer was washed successively with 100 ml of 1N hydrochloric acid, 100 ml ×2 of a saturated sodium hydrogencarbonate aqueous solution and 100 ml of a saturated sodium chloride aqueous solution and then freed of the solvent by distillation to obtain 7.8 g of a concentrate. The concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=2:1 by volume) to obtain 6.1 g (yield: 54%) of the titled compound. 1H-NMR (CDCl3) δ ppm: 1.78-2.00 (m, 2H), 2.46 (s, 3H), 3.45-3.65 (dd, 2H), 3.95 (m, 1H), 4.20 (m, 2H), 7.40 (d, 2H), 7.80 (d, 2H)
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:25]#[N:26])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:10](=[O:24])[CH:9]=2)[CH:7]=1.FC(F)(F)S(O[CH2:33][CH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1)(=O)=O>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:25]#[N:26])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:33][CH:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[C:10](=[O:24])[CH:9]=2)[CH:7]=1
Reactant: COc1cn(CC(=O)OC(C)(C)C)c(=O)cc1-c1cc(Cl)ccc1C#N
Reactant: O=S(=O)(OCC1CCOCC1)C(F)(F)F
Solvent: C1CCOC1
Product: COc1cn(C(CC2CCOCC2)C(=O)OC(C)(C)C)c(=O)cc1-c1cc(Cl)ccc1C#N

Procedure:
1.65 g (4.41 mmol) of tert-butyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]acetate, 1.64 g (6.61 mmol) of tetrahydro-2H-pyran-4-ylmethyl trifluoromethanesulphonate and 5.73 ml (5.73 mmol) of bis(trimethylsilyl)lithium amide (1M in THF) in 37 ml of THF were reacted according to General Method 7B. Purification by column chromatography (80 g silica cartridge, flow rate: 60 ml/min, cyclohexane/ethyl acetate gradient) gave the title compound. Yield: 1.57 g (73% of theory)
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]2[S:8][C:9]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:5]2=[C:4]([C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH3:22])=[CH:17][CH:16]=2)[C:3]=1[CH:23]([CH2:28][CH2:29][CH3:30])[C:24]([O:26]C)=[O:25].[OH-].[Na+]>CO>[CH3:1][C:2]1[N:7]=[C:6]2[S:8][C:9]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:5]2=[C:4]([C:15]2[CH:16]=[CH:17][C:18]([CH2:21][CH3:22])=[CH:19][CH:20]=2)[C:3]=1[CH:23]([CH2:28][CH2:29][CH3:30])[C:24]([OH:26])=[O:25]
Reactant: CCCC(C(=O)OC)c1c(C)nc2sc3c(c2c1-c1ccc(CC)cc1)CCCC3
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCCC(C(=O)O)c1c(C)nc2sc3c(c2c1-c1ccc(CC)cc1)CCCC3
Temperature: 60 °C
Yield: 48.2 %

Procedure:
To a solution of methyl [2-methyl-4-(4-ethylphenyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]pentanoate (0.197 g; 0.468 mmol) in methanol (4.6 mL) was added a solution of sodium hydroxide 5 N (0.95 mL) and the mixture was heated at 60° C. for 18 h. After cooling, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and the mixture was acidified with HCl (1N) until pH 1. The organic layer was washed with brine, water, dried over magnesium sulphate and concentrated under reduced pressure to furnish 0.092 g (48%) of the title compound as a white solid.
Reaction SMILES: Br[C:2]1[C:3]2[C:8]([C:9]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:18][CH:17]=3)=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.CCCCCC.[B:32](OC(C)C)([O:37]C(C)C)[O:33]C(C)C.Cl>O1CCCC1>[C:22]([C:19]1[CH:18]=[CH:17][C:16]([C:9]2[C:10]3[C:15]([C:2]([B:32]([OH:37])[OH:33])=[C:3]4[C:8]=2[CH:7]=[CH:6][CH:5]=[CH:4]4)=[CH:14][CH:13]=[CH:12][CH:11]=3)=[CH:21][CH:20]=1)([CH3:24])([CH3:25])[CH3:23]
Reactant: CC(C)(C)c1ccc(-c2c3ccccc3c(Br)c3ccccc23)cc1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: Cl
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CC(C)(C)c1ccc(-c2c3ccccc3c(B(O)O)c3ccccc23)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
15.4 g of the above-mentioned 9-bromo-10-(4-tert-butylphenyl) anthracene was dissolved in 380 ml of tetrahydrofuran to drop 30 ml of n-butylithium (1.6 M-hexane solution) thereto under nitrogen atmosphere at a temperature of 0° C. The solution was stirred at a temperature of 0° C. for 30 minutes and thereafter cooled to a temperature of −80° C. to drop 18.2 ml of triisopropyl borate thereto. The solution was heated up to room temperature by standing at room temperature and thereafter stirred at room temperature for 3 hours. 400 ml of 10%-hydrochloric acid was dropped thereto and further stirred at room temperature for 2 hours to thereafter extract 300 ml of diethyl ether therefrom. The organic layer was washed in 100 ml of 5%-sodium carbonate aqueous solution, washed in 100 ml of water, then dried by magnesium sulfate and thereafter concentrated by evaporation. The organic layer was purified by silica gel column chromatography (developing solvent was in the order of dichloromethane/hexane=1/1, dichloromethane and dichloromethane/methanol=50/1) and vacuum dried to thereafter obtain 6.78 g of 9-(4-tert-butylphenyl)-10-anthraceneboronic acid.
Reaction SMILES: OS(O)(=O)=O.[S:6]1[CH2:11][CH2:10][CH2:9][S:8][CH:7]1[C:12]([OH:14])=O.C(Cl)(=O)C([Cl:18])=O>C1C=CC=CC=1>[S:6]1[CH2:11][CH2:10][CH2:9][S:8][CH:7]1[C:12]([Cl:18])=[O:14]
Reactant: O=C(O)C1SCCCS1
Reactant: O=C(Cl)C(=O)Cl
Agent: O=S(=O)(O)O
Solvent: c1ccccc1
Product: O=C(Cl)C1SCCCS1
Temperature: 25 °C

Procedure:
In a 500 ml. reaction flask equipped with a reflux condenser connected with a wash-bottle containing H2SO4, there are added 250 ml. of anhydrous benzene (distilled upon sodium), 42 g (0.25 mol) of 1.3-dithiane-2-carboxylic acid (as prepared in example 1) and 28 ml. (0.4 mol) of freshly distilled oxalyl chloride. The mixture is stirred at room temperature and at the end of gaseous evolution, the mixture is heated up to 45° C to complete the gas evolution. The solvent and the excess of oxalyl chloride are evaporated under reduced pressure and the residue is crystallized from dried cyclohexane to yield 1.3-dithiane-2-carboxylic acid chloride.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([N:8]=[C:9]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])[N:10]=2)[CH:7]=1.F[C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:19]=1[F:27].C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[F:27][C:19]1[CH:20]=[C:21]([N+:24]([O-:26])=[O:25])[CH:22]=[CH:23][C:18]=1[O:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([N:8]=[C:9]([NH:11][C:12]([CH:14]3[CH2:15][CH2:16]3)=[O:13])[N:10]=2)[CH:7]=1
Reactant: O=[N+]([O-])c1ccc(F)c(F)c1
Reactant: O=C(Nc1nc2ccc(O)cn2n1)C1CC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CS(C)=O
Product: O=C(Nc1nc2ccc(Oc3ccc([N+](=O)[O-])cc3F)cn2n1)C1CC1
Temperature: 25 °C
Reaction time: 17 h
Yield: 45.8 %

Procedure:
To a solution of N-(6-hydroxy[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide (2 g, 9.16 mmol) and 1,2-difluoro-4-nitrobenzene (1.46 g, 9.16 mmol) in dimethyl sulfoxide (20 mL) was added cesium carbonate (4.48 g, 13.7 mmol), and the mixture was stirred at room temperature for 17 hr. The reaction mixture was filtered through celite, and the filtrate was diluted with water and ethyl acetate, and extracted twice with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered, and the solvent was evaporated under reduced pressure. The obtained residue was washed with ethyl acetate to give the title compound (1.5 g, 46%) as a white solid.
Reaction SMILES: C[O:2][C:3](=O)[C:4]([NH:6][C:7]1[CH:8]=[C:9]([CH:14]=[CH:15][CH:16]=1)[C:10]([O:12][CH3:13])=[O:11])=[O:5].O.[NH2:19][NH2:20]>CO>[NH:19]([C:3](=[O:2])[C:4]([NH:6][C:7]1[CH:8]=[C:9]([CH:14]=[CH:15][CH:16]=1)[C:10]([O:12][CH3:13])=[O:11])=[O:5])[NH2:20]
Reactant: COC(=O)C(=O)Nc1cccc(C(=O)OC)c1
Reactant: NN
Solvent: O
Solvent: CO
Product: COC(=O)c1cccc(NC(=O)C(=O)NN)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 82 %

Procedure:
To a suspension of methyl 3-{[methoxy(oxo)acetyl]amino}benzoate (100 mg, 0.42 mmol) in MeOH (8 mL) was added hydrazine hydrate (0.2 mL). After stirring for 0.5 h at rt, the reaction mixture was filtered. Washing with MeOH (2×1 mL) and water (3×1 mL) and drying under vacuo at 70° C. for 2 hrs gave 82 mg of the title compound (82%) as a white solid in 97.1% purity by HPLC (MaxPlot detection between 230 and 400 nm).
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5](/[C:11](=C\C2C=CC=CC=2)/[C:12]([NH2:14])=[O:13])[CH:6]=[C:7](OC)[CH:8]=1.[Cl-].[Al+3].[Cl-].[Cl-].C(Cl)(Cl)Cl.[CH3:30][OH:31]>ClC1C=CC=CC=1>[OH:31][C:30]1[CH:4]=[C:3]([OH:2])[CH:8]=[C:7]2[C:6]=1[CH:5]=[CH:11][C:12](=[O:13])[NH:14]2
Reactant: CO
Reactant: COc1cc(OC)cc(/C(=C\c2ccccc2)C(N)=O)c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClC(Cl)Cl
Solvent: Clc1ccccc1
Product: O=c1ccc2c(O)cc(O)cc2[nH]1
Temperature: 130 °C
Reaction time: 0.5 h
Yield: 92 %

Procedure:
A solution of compound 2 (19.0 g, 67.1 mmol) in chlorobenzene (120 mL) was taken in a 500 mL round bottom flask equipped with a mechanical stirrer and a reflux condenser. Aluminium chloride (44.6 g, 335.6 mmol) was added in portions over a period of 10 min. The reaction mixture was heated at 130° C. for 3 h and cooled to room temperature (TLC chloroform: methanol 9:1, Rf=0.2). Poured into crushed ice (1 Kg) and stirred at room temperature for further 30 min. The solid separated was filtered and washed with water till neutral to pH. The solid was then washed with hexane (2×50 mL) and dried at 100° C. for 1 h to furnish 5,7-dihydroxy-1,2-dihydro-2-quinolinone (3, 10 g) in 92% yield as a dark brown solid. M.P.>300° C. The quinolinone obtained was further characterised as its diacetate.