Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]=[CH:2][C:3](=[CH2:5])[CH3:4].[CH:6]([Si:9]([C:16]#[CH:17])([CH:13]([CH3:15])[CH3:14])[CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7]>[Zn+2].[I-].[I-].C1(P(CC)C2C=CC=CC=2)C=CC=CC=1.ClCCl>[CH:13]([Si:9]([CH:6]([CH3:7])[CH3:8])([CH:10]([CH3:12])[CH3:11])[C:16]1[CH2:17][CH:5]=[C:3]([CH3:4])[CH2:2][CH:1]=1)([CH3:14])[CH3:15]
Reactant: C=CC(=C)C
Reactant: C#C[Si](C(C)C)(C(C)C)C(C)C
Agent: CCP(c1ccccc1)c1ccccc1
Agent: [I-]
Agent: [Zn+2]
Solvent: ClCCl
Product: CC1=CCC([Si](C(C)C)(C(C)C)C(C)C)=CC1
Temperature: 30 °C
Reaction time: 0.5 h
Yield: 89.3 %

Procedure:
In a four-necked flask, 0.27 g (1.2 mmol) of CoBr2, 1.33 g (4.2 mmol) of ZnI2, 0.55 g (1.4 mmol) of diphenylphosphinoethane, and 60 ml of dichloromethane were added, and the mixture was stirred for 30 minutes at 30° C. Subsequently, 12.2 ml (122 mmol) of isoprene, 20 g (110 mmol) of triisopropylsilylacetylene, and 0.35 g (1.4 mmol) of Bu4NBH4 were added thereto, and the mixture was allowed to react for one hour at 30° C. Dichloromethane was evaporated, and then the residue was purified by silica gel flash column chromatography. Thus, 24.6 g of the title compound, triisopropyl(4-methyl-1,4-cyclohexadienyl)silane, was obtained at a yield of 89.7% (GC purity 80%).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:26])[C@@H:5]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:6][CH2:7][C:8]([O:10]CC1C=CC=CC=1)=[O:9])[CH3:2]>[C].[Pd].C(O)C>[CH2:1]([O:3][C:4](=[O:26])[C@@H:5]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:6][CH2:7][C:8]([OH:10])=[O:9])[CH3:2]
Reactant: CCOC(=O)[C@H](CCC(=O)OCc1ccccc1)NC(=O)OC(C)(C)C
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)[C@H](CCC(=O)O)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 178.9 %

Procedure:
To a mixture of (S)-2-tert-butoxycarbonylamino-pentanedioic acid 5-benzyl ester 1-ethyl ester (390 mg, 0.67 mmol; 63% purity) described in Manufacturing Example 4-1 and ethanol (4 mL) was added palladium-carbon (40 mg, 0.19 mmol; 50% water content) at room temperature, which was stirred overnight under a hydrogen atmosphere (1 atm) at room temperature. The reaction mixture was replaced with nitrogen and filtered through a Celite pad. The solvent was evaporated from the filtrate under a reduced pressure, so as to obtain (S)-2-tert-butoxycarbonylamino-pentanedioic acid 1-ethyl ester (330 mg) in a crude form. The crude product thus obtained was used directly in the next reaction. To a mixture of 3-(3-(4-(pyridin-2-yloxymethyl)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine (150 mg, 80.42 mmol) described in Reference Example 1 and acetonitrile (3 mL) were added (S)-2-tert-butoxycarbonylamino-pentanedioic acid 1-ethyl ester (crude, 230 mg), N-methylmorpholine (46 μL, 0.42 mmol), and 180 mg (0.46 mmol) of 047-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl-uronium hexafluorophosphate (180 mg, 0.46 mmol) were added in this order at 0° C., which was stirred overnight at room temperature. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=4:1), so as to obtain the titled compound (47 mg).
Reaction SMILES: O[CH2:2][CH2:3][CH:4]1[CH2:9][O:8][C:7]([CH3:11])([CH3:10])[O:6][CH2:5]1.C(Br)(Br)(Br)[Br:13].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CO>CN(C)C=O>[Br:13][CH2:2][CH2:3][CH:4]1[CH2:9][O:8][C:7]([CH3:11])([CH3:10])[O:6][CH2:5]1
Reactant: CC1(C)OCC(CCO)CO1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CO
Product: CC1(C)OCC(CCBr)CO1
Temperature: 0 °C
Reaction time: 8 h
Yield: 33.2 %

Procedure:
To an ice-cooled solution of 5-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxan (1.92 g, 12 mmol) and carbon tetrabromide (7.96 g, 24 mmol) in dimethylformamide (100 ml), triphenylphosphine (6.30 g, 24 mmol) was added and the solution was left at 4° C. overnight. To this solution methanol (20 ml) was added and the solvent was then evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, elutingwith hexane-acetone (12:1) to afford 5-(2-bromoethyl)-2,2-dimethyl-1,3-dioxan as a clear colourless liquid (0.89 g, 40%); νmax (film) 2940, 1370, 1270, 1260, 1200, and 1070 cm−1; δH (CDCl3) 1.42 (6H, s, C(CH3)2), 1.94 (3H, m, CHCH2CH2Br), 3.43 (2H, t, J 7 Hz, CH2Br), and 3.5-4.1 (4H, m, 2×CH2O); (Found: C, 42.84; H, 6.93%. C8H15BrO2 requires: C, 43.07; H, 6.78%. [M−CH3] found 207.0024; C7H12BrO2 requires 207.0021).
Reaction SMILES: O=P(Cl)(Cl)[Cl:3].[CH3:6][C@H:7]1[C:15]2[C:14](O)=[N:13][CH:12]=[N:11][C:10]=2[CH2:9][CH2:8]1>ClCCCl>[Cl:3][C:14]1[C:15]2[C@H:7]([CH3:6])[CH2:8][CH2:9][C:10]=2[N:11]=[CH:12][N:13]=1
Reactant: C[C@@H]1CCc2ncnc(O)c21
Reactant: O=P(Cl)(Cl)Cl
Solvent: ClCCCl
Product: C[C@@H]1CCc2ncnc(Cl)c21
Temperature: 25 °C
Yield: 61.1 %

Procedure:
Neat POCl3 (463.9 mL, 5067 mmol) was added slowly by addition funnel to a 0° C. solution of (R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ol (152.2 g, 1013 mmol) in DCE (1.2 L). After addition was complete, the reaction mixture was warmed to room temperature and then heated to reflux while being stirred at reflux for 70 minutes, after which the reaction was complete by HPLC. The reaction mixture was cooled to room temperature, and the excess POCl3 was quenched in 4 portions. The reaction mixture was transferred to a separatory funnel and dripped into a beaker containing ice and saturated NaHCO3 solution cooled in an ice bath. Once the addition of each portion of the reaction mixture was complete, the quenched mixture is stirred for 30 minutes to ensure complete destruction of POCl3 prior to transferring it to a separatory funnel. The mixture was transferred to a separatory funnel and extracted with DCM (2×). The combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was purified on silica gel (1 kg silica gel slurried in 9:1 hex:ethyl acetate onto a 3 L fritted funnel, silica settled under vacuum, topped with sand). The crude was loaded with a DCM/hexane mixture, and compound was eluted using 1 L sidearm flasks with vacuum. High Rf byproducts eluted first, then (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (104.4 g, 61.09% yield) as a brown oil. Triethylamine (93.0 mL, 534 mmol) and tert-butyl piperazine-1-carboxylate (34.8 g, 187 mmol) were added to a solution of (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (30.0 g, 178 mmol) in n-BuOH (250 mL). The reaction mixture was heated to reflux under nitrogen and stirred overnight (17 hours). The reaction mixture was concentrated on a rotavap. The resulting oil was dissolved in DCM, washed with H2O, dried (Na2SO4), filtered, and concentrated. The resulting brown oil was purified on silica gel eluting first with 2:1 hexanes:ethyl acetate until product eluting cleanly, then gradient 1:1 to 1:5 DCM:ethyl acetate to give (R)-tertbutyl 4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (42.0 g, 74.1% yield) as a beige powder. LC/MS (APCI+) m/z 319.1 [M+H]+.
Reaction SMILES: [C:1]1(=[O:16])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH:3]=[CH:2]1.[C:17]1(C)C=CC=CC=1>>[CH3:17][CH:14]1[CH2:15][C:1](=[O:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1
Reactant: O=C1C=CCCCCCCCCCCCC1
Reactant: Cc1ccccc1
Agent: O=C1/C=C/CCCCCCCCCCCC1
Product: CC1CCCCCCCCCCCCC(=O)C1
Reaction time: 15 h

Procedure:
In 10 ml of dried toluene was dissolved 5 mmol of (E)-2-cyclopentadecenone, and the solution was added dropwise to the above solution, followed by allowing the reaction to proceed at a temperature from -78° C. to -60° C. for 15 hours. Thereafter, the same procedures as in Example 14 were followed to obtain muscone in a chemical yield of 89 mol %. The resulting muscone was R-form having an optical rotation of -12.0° (at 21° C., c 5.07, MeOH) and an optical purity of 100%ee.
Reaction SMILES: [H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.Br[CH2:11][CH2:12][O:13][C:14](=[O:16])[CH3:15]>CN(C=O)C>[CH2:12]([O:13][C:14](=[O:16])[CH2:15][N:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]1=[O:3])[CH3:11]
Reactant: CC(=O)OCCBr
Reactant: Oc1ccccn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)Cn1ccccc1=O
Reaction time: 0.17 h
Yield: 64.8 %

Procedure:
To a slurry of sodium hydride, 1.73 g (43.2 mmol) in 100 mL of DMF was added 3.4 g (36.0 mmol) of 2-hydroxypyridine. The mixture was stirred 10 minutes then added to a solution of 3.3 mL (30.0 mmol) of bromoethylacetate in 100 mL DMF. The reaction mixture was stirred 72 hours at rt. then concentrated to dryness. The residue was partitioned between 20% isopropanol/chloroform and water and washed with saturated aqueous NaHCO3, washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by column chromatography using MeOH/chloroform as eluent and concentrated to dryness to yield 3.52 g (65%) of the desired product as a colorless oil. 1H—NMR is consistent with structure. MS (ion spray) 182.1 (M+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH:13]([OH:20])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH:7]=[CH:6]2.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C:13](=[O:20])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH:7]=[CH:6]2
Reactant: CCCCCCC(O)c1ccc2cc(OC)ccc2c1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CCCCCCC(=O)c1ccc2cc(OC)ccc2c1
Reaction time: 3 h
Yield: 81.3 %

Procedure:
To a stirred solution of the 1-(6-methoxy-2-naphthyl)heptan-1-ol (101.1 g, 371 mmol) in CH2Cl2 (1000 mL) under N2 was added pyridinium chlorochromate (120.02 g, 556.74 mmol). The reaction was stirred for a total of 3 h and then poured onto an alumina column (2000 g, basic Brockman activity, 60-325 mesh). Column was eluted with CH2Cl2. Product was collected, filtered, rotovap'd and dried in vacuo to give the product as a white solid (81.5 g, 301.44 mmol, 81%) with mp 69-72° C. 177 mg of crude ketone was recrystallized from methanol to give the desired product as a white solid (105 mg) mp 70-72° C.; 1H NMR (DMSO-d6) δ 0.86 (m, 3H), 1.25-1.40 (m, 6H), 1.60-1.70 (m, 2H), 3.07 (t, J=7.3 Hz, 2H), 3.90 (s, 3H), 7.24 (d, J=9 Hz, 1H), 7.39 (s, 1H), 7.87 (d, J=8.7 Hz, 1H), 7.93 (d, J=8.7 Hz, 1H), 8.02 (d, J=8.9, 1H) 8.58 (s, 1H); IR (solid) 2910, 2870, 1660, 1630, 1470, and 1180 cm−1; mass spectrum [EI], m/z 271 (M+H)+;
Reaction SMILES: C(OC([NH:8][C:9]1[S:13][C:12]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=2[F:21])=[N:11][C:10]=1[C:22]([NH:24][C:25]1[CH:29]=[N:28][N:27]([CH3:30])[C:26]=1[N:31]1[CH2:37][CH2:36][C@H:35](O)[C@H:34]([NH:39][C:40](=[O:46])[O:41]C(C)(C)C)[CH2:33][CH2:32]1)=[O:23])=O)(C)(C)C.[H-].[Na+].CO>CN(C=O)C.Cl.O1CCOCC1>[O:46]=[C:40]1[NH:39][C@@H:34]2[CH2:33][CH2:32][N:31]([C:26]3[N:27]([CH3:30])[N:28]=[CH:29][C:25]=3[NH:24][C:22]([C:10]3[N:11]=[C:12]([C:14]4[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=4[F:21])[S:13][C:9]=3[NH2:8])=[O:23])[CH2:37][CH2:36][C@@H:35]2[O:41]1
Reactant: Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2NC(=O)OC(C)(C)C)c1N1CC[C@H](O)[C@H](NC(=O)OC(C)(C)C)CC1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CO
Solvent: C1COCCO1
Product: Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)c1N1CC[C@@H]2OC(=O)N[C@@H]2CC1
Temperature: 25 °C
Yield: 37.5 %

Procedure:
To a stirred solution of tert-butyl N-((4R,5S)-1-(4-((5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)thiazole-4-carbonyl)amino)-2-methyl-pyrazol-3-yl)-5-hydroxy-azepan-4-yl)carbamate (199 mg, 0.30 mmol) in DMF (2 mL) at 0° C. was added sodium hydride (60% dispersion in oil, 26 mg, 0.66 mmol). The mixture was allowed to warm to room temperature over 2 hr, quenched with water (3 mL) and the resulting precipitate filtered off and dried under reduced pressure. The aqueous layer was extracted with EtOAc (3×3 mL) and the combined organic layers were passed through a phase separation cartridge, concentrated under reduced pressure and the residue combined with the precipitate collected earlier. A solution of this material (159 mg, 0.27 mmol) in HCl in dioxane (4 M, 10 mL) and MeOH (5 mL) was stirred at room temperature for 16 hr. The solvents were removed under reduced pressure. Purification via preparative HPLC gave 486 as a white solid (55 mg, 41% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.50 (s, 1H), 7.79 (s, 1H), 7.37-7.28 (m, 1H), 7.05 (t, J=8.8 Hz, 2H), 6.14 (s, 2H), 5.08-5.00 (m, 1H), 4.87 (s, 1H), 4.26 (td, J=9.3, 3.5 Hz, 1H), 3.75 (s, 3H), 3.45-3.33 (m, 2H), 3.16-3.07 (m, 2H), 2.34-2.27 (m, 2H), 2.20-2.09 (m, 1H), 2.06-1.97 (m, 1H). LCMS (ES+) m/z 490 (M+1)
Reaction SMILES: Cl[C:2]([O:4][CH3:5])=[O:3].[F:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:26][C:27]4[CH:32]=[CH:31][N:30]=[C:29]([NH2:33])[N:28]=4)=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)=[O:15])=[CH:9][C:8]=1[C:34]([F:37])([F:36])[F:35]>C(Cl)Cl.N1C=CC=CC=1.CCOC(C)=O.O>[CH3:5][O:4][C:2](=[O:3])[NH:33][C:29]1[N:28]=[C:27]([O:26][C:22]2[CH:23]=[CH:24][C:25]3[C:20](=[CH:19][CH:18]=[CH:17][C:16]=3[C:14](=[O:15])[NH:13][C:10]3[CH:11]=[CH:12][C:7]([F:6])=[C:8]([C:34]([F:37])([F:36])[F:35])[CH:9]=3)[CH:21]=2)[CH:32]=[CH:31][N:30]=1
Reactant: Nc1nccc(Oc2ccc3c(C(=O)Nc4ccc(F)c(C(F)(F)F)c4)cccc3c2)n1
Reactant: COC(=O)Cl
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: COC(=O)Nc1nccc(Oc2ccc3c(C(=O)Nc4ccc(F)c(C(F)(F)F)c4)cccc3c2)n1
Reaction time: 4 h

Procedure:
126 μl (1.64 mMol) methyl chloroformate are added portionwise to a solution of 300 mg (0.68 mMol) 6-(2-amino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide (Step 10.3) in 7 ml CH2Cl2 and 7 ml pyridine during 2 h. After 4 h, the solution is diluted with EtOAc and water, the aq. phase separated off and extracted twice with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Precipitation with DIPE and filtration gives the title compound: m.p.: 204-205° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:20])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]([CH3:19])([N+:16]([O-])=O)[CH3:15])=[CH:9][CH:8]=1)[CH3:2].[H][H]>C(O)C.[Pt]=O>[CH2:1]([O:3][C:4](=[O:20])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]([NH2:16])([CH3:15])[CH3:19])=[CH:9][CH:8]=1)[CH3:2]
Reactant: [H][H]
Reactant: CCOC(=O)COc1ccc(CC(C)(C)[N+](=O)[O-])cc1
Agent: O=[Pt]
Solvent: CCO
Product: CCOC(=O)COc1ccc(CC(C)(C)N)cc1
Yield: 28 %

Procedure:
A solution of ethyl(4-[2-methyl-2-nitropropyl]phenoxy)ethanoate (3.6 g, 12.8 mmol) in ethanol (35 mL) was charged with platinum oxide (0.72 g) and hydrogenated on a Parr shaker using 60 psi of hydrogen for 72 h at room temperature. The catalyst was filtered and the solution concentrated in vacuo. The resulting residue was purified by flash chromatography over silica gel eluting with 5% MeOH/CHCl3/NH3 to provide 0.9 g (28%) of a clear oil. MS (FD+): m/z 251.
Reaction SMILES: [CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10]([OH:12])[CH2:9][C@H:8]1[CH:13]=[C:14]([CH3:18])[C:15](=[O:17])[CH3:16])=[O:6])[CH:2]=[CH2:3].I[CH3:20]>[Ag]=O>[CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10]([O:12][CH3:20])[CH2:9][C@H:8]1[CH:13]=[C:14]([CH3:18])[C:15](=[O:17])[CH3:16])=[O:6])[CH:2]=[CH2:3]
Reactant: C=CCOC(=O)N1C[C@H](O)C[C@H]1C=C(C)C(C)=O
Reactant: CI
Agent: O=[Ag]
Product: C=CCOC(=O)N1C[C@H](OC)C[C@H]1C=C(C)C(C)=O
Reaction time: 48 h

Procedure:
To a solution of (2S,4R)-1-allyloxycarbonyl-4-hydroxy-2-(2-methyl-3-oxo-1-butenyl)pyrrolidine (3.0 g) in iodomethane (15 ml) was added silver oxide (10 g), and the mixture was allowed to stand at ambient temperature for 2 days. The resulting precipitate was removed by filtration and the filtrate was evaporated in vacuo. The residue was chromatographed on silica gel (60 ml) eluting with a mixture of n-hexane and ethyl acetate (6:4 V/V) to give (2S,4R)-1-allyloxycarbonyl-4-methoxy-2-(2-methyl-3-oxo-1-butenyl)pyrrolidine (3.23 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:13]=[CH:14][C:15]=1[N+:16]([O-])=O)[O:6][CH2:7][CH2:8][CH2:9][N:10]([CH3:12])[CH3:11].[H][H]>C(OCC)(=O)C.[Pd]>[CH3:12][N:10]([CH3:11])[CH2:9][CH2:8][CH2:7][O:6][C:5]1[CH:13]=[CH:14][C:15]([NH2:16])=[C:3]([O:2][CH3:1])[CH:4]=1
Reactant: [H][H]
Reactant: COc1cc(OCCCN(C)C)ccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COc1cc(OCCCN(C)C)ccc1N
Yield: 98.4 %

Procedure:
A mixture of [3-(3-methoxy-4-nitrophenoxy)propyl]dimethylamine (2.0 g, 7.7 mmol) and 5% Pd—C (0.4 g) in ethyl acetate (75 mL) was shaken under 50 psi of hydrogen for 24 hours. The mixture was filtered through Celite and evaporated, providing 1.7 g of the product as a light grey oil, in 97% yield: 1H NMR (CDCl3) δ 1.86-1.98 (m, 2H), 2.25 (s, 6H), 2.44 (t, J=7.3 Hz, 2H), 3.44 (br, 2H), 3.82 (s, 3H), 3.94 (t, J=6.5 Hz, 2H), 6.35 (dd, J=8.4 Hz, J=2.6 Hz, 1H), 6.46 (d, J=2.6 Hz, 1H), 6.62 (d, J=8.4 Hz, 1H).
Reaction SMILES: [CH2:1]([N:3]([CH2:24][CH3:25])[C:4](=[O:23])[C:5]1[CH:10]=[CH:9][C:8]([CH:11]([OH:22])[C:12]2[CH:13]=[CH:14][CH:15]=[C:16]3[C:21]=2[N:20]=[CH:19][CH:18]=[CH:17]3)=[CH:7][CH:6]=1)[CH3:2].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>C(Cl)Cl.CCCCCCC>[CH2:24]([N:3]([CH2:1][CH3:2])[C:4](=[O:23])[C:5]1[CH:6]=[CH:7][C:8]([C:11]([C:12]2[CH:13]=[CH:14][CH:15]=[C:16]3[C:21]=2[N:20]=[CH:19][CH:18]=[CH:17]3)=[O:22])=[CH:9][CH:10]=1)[CH3:25]
Reactant: CCN(CC)C(=O)c1ccc(C(O)c2cccc3cccnc23)cc1
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: c1cc[nH+]cc1
Solvent: CCCCCCC
Solvent: ClCCl
Product: CCN(CC)C(=O)c1ccc(C(=O)c2cccc3cccnc23)cc1
Reaction time: 24 h
Yield: 60.2 %

Procedure:
16 (3.0 g, 9.0 mmol) was dissolved in CH2Cl2 (25 mL) and powdered pyridinium dichromate (PDC) (5.0 g, 13 mmol) was added portionwise at 25° C. Two more portions of PDC (0.5 g) were added after 3 h and 12 h. After 24 h, the solution was diluted with heptane and filtered through silica gel. Eluton with EtOAc and evaporation in vacuo gave 17 (1.8 g, 60%). MS: 332, 303, 275, 260, 232, 204, 176, 156, 128, 115. 1H NMR (CDCl3): δ1.1, 1.3 (2m, 6H), 3.22, 3.55 (2m, 4H), 7.39 (d, J=8 Hz, 2H), 7.43 (m, 1H), 7.65 (m, 1H), 7.75 (m, 1H), 7.86 (d, J=8 Hz, 2H), 7.98 (m, 1H), 8.23 (m, 1H), 8.83 (m, 2H).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[S:13][CH:14]=[CH:15][N:16]=2)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[CH3:17][O:18][C:19]1[CH:28]=[CH:27][C:26]2[C:21](=[CH:22][CH:23]=[C:24]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=3)[CH:25]=2)[C:20]=1OB(O)O>>[CH3:17][O:18][C:19]1[CH:28]=[CH:27][C:26]2[C:21](=[CH:22][CH:23]=[C:24]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=3)[CH:25]=2)[C:20]=1[C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[S:13][CH:14]=[CH:15][N:16]=2)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1
Reactant: COc1cccc(-c2ccc3c(OB(O)O)c(OC)ccc3c2)c1
Reactant: O=S(=O)(Nc1nccs1)c1cccc(Br)c1
Product: COc1cccc(-c2ccc3c(-c4cccc(S(=O)(=O)Nc5nccs5)c4)c(OC)ccc3c2)c1
Yield: 14 %

Procedure:
The compound is prepared by the reaction of 3-bromo-N-(thiazol-2-yl)benzenesulfonamide (88.8 mg, 0.28 mmol, 1 eq) with 2-methoxy-6-(3-methoxyphenyl)-naphthalene-1-ylboric acid (100 mg, 0.36 mmol, 1.3 eq) according to method C. Purification by column chromatography with dichloromethane/methanol 95/5 yields the desired compound in a yield of 14%, 19 mg.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:17]3[C:12](=[C:13]4[CH:21]=[CH:20][CH:19]=[CH:18][C:14]4=[CH:15][CH:16]=3)[NH:11][C:10](=[O:22])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[C:23](OC(=O)C)(=[O:25])[CH3:24].N1C=CC=CC=1>O>[O:22]=[C:10]1[CH2:9][CH:8]([C:4]2[CH:3]=[C:2]([NH:1][C:23](=[O:25])[CH3:24])[CH:7]=[CH:6][CH:5]=2)[C:17]2[C:12](=[C:13]3[CH:21]=[CH:20][CH:19]=[CH:18][C:14]3=[CH:15][CH:16]=2)[NH:11]1
Reactant: Nc1cccc(C2CC(=O)Nc3c2ccc2ccccc32)c1
Reactant: CC(=O)OC(C)=O
Solvent: O
Solvent: c1ccncc1
Product: CC(=O)Nc1cccc(C2CC(=O)Nc3c2ccc2ccccc32)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 4-(3-Amino-phenyl)-3,4-dihydro-1H-benzo[h]quinolin-2-one (0.25 g, 0.87 mmol), acetic anhydride (1 ml) and anhydrous pyridine (1 ml) was stirred at ambient temperature overnight. Water was added and the precipitate was separated by filtration. Crystallization from methanol-acetonitrile afforded the title compound (0.06 g, 0.18 mmol).
Reaction SMILES: C([Li])CCC.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([S:13]([CH2:16][C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=2[F:24])(=[O:15])=[O:14])=[CH:9][CH:8]=1.[C:25]([O:28][CH2:29][CH2:30]Br)(=[O:27])[CH3:26].[Cl-].[NH4+]>C(COC)OC.CCCCCC>[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([S:13]([CH:16]([C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=2[F:24])[CH2:26][C:25]([O:28][CH2:29][CH3:30])=[O:27])(=[O:15])=[O:14])=[CH:9][CH:8]=1
Reactant: O=S(=O)(Cc1cc(F)ccc1F)c1ccc(Cl)cc1
Reactant: CC(=O)OCCBr
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: COCCOC
Solvent: CCCCCC
Product: CCOC(=O)CC(c1cc(F)ccc1F)S(=O)(=O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Under an argon atmosphere and at −78° C., n-butyl lithium (a 1.57M hexane solution, 7.01 ml) was added to a dimethoxyethane solution (50 ml) of the 2-[(4-chlorophenyl)sulfonylmethyl]-1,4-difluorobenzene (3.03 g, 10.0 mmol) obtained in Example 5. The temperature of the reaction mixture was raised to room temperature, at which stirring was conducted for 15 minutes. After cooling to −78° C., bromoethyl acetate (1.33 ml, 12.0 mmol) was added to the reaction mixture. The mixture was stirred at room temperature for 3 hours. To the reaction mixture was added a saturated ammonium chloride solution, followed by extraction with diethyl ether. The extracts were combined, washed successively with water, a saturated aqueous solution of sodium thiosulfate, and brine, dried over MgSO41 and then distilled under reduced pressure to remove the solvent. The residue thus obtained was recrystallized from hexane, whereby the title compound (1.95 g, 50%) was obtained as colorless needle crystals.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:11]=[C:10]([N+:12]([O-])=O)[CH:9]=[CH:8][C:5]=1[C:6]#[N:7])[CH3:2].O.O.[Sn](Cl)Cl.C(=O)([O-])O.[Na+]>C(O)C>[NH2:12][C:10]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:3][CH2:1][CH3:2])[CH:11]=1
Reactant: CCOc1cc([N+](=O)[O-])ccc1C#N
Agent: Cl[Sn]Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CCOc1cc(N)ccc1C#N
Temperature: 70 °C
Reaction time: 8 h

Procedure:
To a suspension of 2-ethoxy-4-nitro-benzonitrile (0.49 g, 2.54 mmol) in ethanol (50 ml) is added tin (II) chloride dihydrate (2.87 g, 12.7 mmol) and the suspension is stirred at 70° C. for 2 hours and at room temperature overnight. The reaction mixture is poured onto ice-water and the pH of the solution is adjusted to pH 7-8 by addition of sodium hydrogen carbonate solution (5% solution in water). The aqueous emulsion is filtered under vacuum and the product is extracted with ethyl acetate (2×150 ml). The organic portions are combined, washed with brine (100 ml), dried (MgSO4) and concentrated in vacuo to yield the titled product as a pale yellow solid which is used in the next step without further purification.