Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([NH:4][CH2:5][C@@H:6]1[O:10][C:9](=[O:11])[N:8]([C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[C:14]([F:19])[CH:13]=2)[CH2:7]1)(=[O:3])[CH3:2].[CH:20](OC1C=CC([N+]([O-])=O)=CC=1)=[O:21].C(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C>C1COCC1>[C:1]([NH:4][CH2:5][C@@H:6]1[O:10][C:9](=[O:11])[N:8]([C:12]2[CH:17]=[CH:16][C:15]([NH:18][CH:20]=[O:21])=[C:14]([F:19])[CH:13]=2)[CH2:7]1)(=[O:3])[CH3:2]
Reactant: CC(=O)NC[C@H]1CN(c2ccc(N)c(F)c2)C(=O)O1
Reactant: O=COc1ccc([N+](=O)[O-])cc1
Agent: CC(C)(C)c1cccc(C(C)(C)C)n1
Solvent: C1CCOC1
Product: CC(=O)NC[C@H]1CN(c2ccc(NC=O)c(F)c2)C(=O)O1
Yield: 85.1 %

Procedure:
A solution of 5-(S)-acetamidomethyl-3-[4′-amino-3′-fluorophenyl]-oxazolidine-2-one (0.200 g, 0.748 mmol), p-nitrophenyl formate (0.188 g, 1.12 mmol), and 2,6-di-(tert-butyl)pyridine (0.336 mL, 1.50 mmol) in THF (4 mL) was stirred at 65° C. overnight. Solvent was removed under vacuum and the residue purified by PTLC (30% acetone in DCM) to give product as a white solid (0.188 g, 85%). M.p. 196-8° C.; MS (m/z): [M+H]+=296.
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]1[NH:12][C:7]2=[N:8][CH:9]=[CH:10][CH:11]=[C:6]2[C:5]=1[CH3:13].[CH2:14]([Cl:23])[C:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:16]>C(#N)C>[ClH:23].[CH3:1][O:2][CH2:3][C:4]1[N:12]=[C:7]2[N:8]([CH2:14][C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:16])[CH:9]=[CH:10][CH:11]=[C:6]2[C:5]=1[CH3:13]
Reactant: COCc1[nH]c2ncccc2c1C
Reactant: O=C(CCl)c1ccccc1
Solvent: CC#N
Product: COCc1nc2n(CC(=O)c3ccccc3)cccc-2c1C
Product: Cl
Yield: 20.4 %

Procedure:
A solution of 0,13 g (0,74 mmol) 2-methoxymethyl-3-methylpyrrolo[2,3 -b]pyridine and 0,16 g (1,1 mmol) phenacyl chloride in 20 ml acetonitrile was refluxed for 15 h. Working up in the same manner as ex. 17 gave 0,05 g (20%) of the title compound.
Reaction SMILES: [OH2:1].[CH3:2][O:3][C:4]([C:6]1[S:7][C:8]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:9][C:10]=1[N:11]([C:19]([CH:21]1[CH2:26][CH2:25][CH:24]([CH3:27])[CH2:23][CH2:22]1)=[O:20])[CH:12]1[CH2:17][CH2:16][C:15](=[CH2:18])[CH2:14][CH2:13]1)=[O:5].[OH-].[Na+].[BH4-].[Na+]>O1CCCC1>[CH3:2][O:3][C:4]([C:6]1[S:7][C:8]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[CH:9][C:10]=1[N:11]([CH:12]1[CH2:17][CH2:16][C:15]([OH:1])([CH3:18])[CH2:14][CH2:13]1)[C:19]([C@H:21]1[CH2:26][CH2:25][C@@H:24]([CH3:27])[CH2:23][CH2:22]1)=[O:20])=[O:5].[CH3:2][O:3][C:4]([C:6]1[S:7][C:8]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[CH:9][C:10]=1[N:11]([CH:12]1[CH2:17][CH2:16][C:15]([OH:1])([CH3:18])[CH2:14][CH2:13]1)[C:19]([C@H:21]1[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]1)=[O:20])=[O:5]
Reactant: C=C1CCC(N(C(=O)C2CCC(C)CC2)c2cc(-c3ccccc3)sc2C(=O)OC)CC1
Reactant: O
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: COC(=O)c1sc(-c2ccccc2)cc1N(C(=O)[C@H]1CC[C@@H](C)CC1)C1CCC(C)(O)CC1
Product: COC(=O)c1sc(-c2ccccc2)cc1N(C(=O)[C@H]1CC[C@H](C)CC1)C1CCC(C)(O)CC1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
To a solution of water (1 mL) and tetrahydrofuran (1 mL) was added mercuric acetate (83.0 mg, 0.277 mmol, 1 eq) at room temperature. After stirring 10 min, the yellow solution was cooled to 0° C. and a solution of 3-[(4-Methyl-cyclohexanecarbonyl)-(4-methylene-cyclohexyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (125 mg, 0.277 mmol, 1 eq) was added dropwise. The resulting mixture was stirred 1 h at 0° C. NaOH 3M (1 mL) was then added, followed by sodium borohydride (10.0 mg, 0.277 mmol, 1 eq) and the reaction mixture was stirred 15 min at room temperature. The reaction mixture was extracted with dichloromethane (3×30 mL). Organic phases were combined, dried over sodium sulfate and concentrated. The crude was purified by chromatography (50% ethyl acetate/hexanes) and diastereoisomers were separated to give 90 mg of cis-3-[(4-Hydroxy-4-methyl-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester and 6.5 mg of trans-3-[(4-Hydroxy-4-methyl-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (74%), both as a white solid. cis-3-[(4-Hydroxy-4-methyl-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester. NMR 1H (CDCl3, 400 MHz): 7.63 ppm (d, 2H); 7.40 ppm (m, 3H); 6.98 ppm (s, 1H); 4.50 ppm (tt, 1H); 3.85 ppm (s, 3H); 2.00 ppm (m, 1H); 1.80-1.20 ppm (m, 15H); 1.18 ppm (s, H); 0.78 ppm (d, 3H); 0.64 ppm (m, 2H).
Reaction SMILES: [CH2:1]([C:5]1[N:6]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20](=[O:31])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:27]([O:29][CH3:30])=[O:28])=[CH:16][CH:15]=2)[C:7]([CH2:11]O)=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4].S(Cl)([Cl:34])=O>C(Cl)(Cl)Cl>[ClH:10].[CH2:1]([C:5]1[N:6]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:20](=[O:31])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:27]([O:29][CH3:30])=[O:28])=[CH:18][CH:19]=2)[C:7]([CH2:11][Cl:34])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc(Cl)c(CO)n1Cc1ccc(C(=O)c2ccccc2C(=O)OC)cc1
Reactant: O=S(Cl)Cl
Solvent: ClC(Cl)Cl
Product: CCCCc1nc(Cl)c(CCl)n1Cc1ccc(C(=O)c2ccccc2C(=O)OC)cc1
Product: Cl
Temperature: 25 °C
Reaction time: 4 h
Yield: 103.9 %

Procedure:
2-Butyl-1-[4-(2-carbomethoxybenzoyl)benzyl]-4-chloro-5-hydroxymethylimidazole (5.00 g, 11.3 mmol, 1 eq) was dissolved in 50 mL chloroform and to this solution was dropwise added thionyl chloride (4.13 mL, 56.6 mmol, 5 eq) with stirring at room temperature. After 4 hours, the solvent and excess thionyl chloride were removed by rotary evaporation. Toluene (100 mL) was added to the residue and the solvent again removed by rotary evaporation. Toluene was again added and while evaporating the second time, product crystallized from solution yielding 2.91 g of a white solid; m.p. 139.0°-143.5°. NMR (200 MHz, CDCl3) δ 8.07 (d, 1H, J=7 Hz); 7.80 (d, 2H, J=10 Hz); 7.68 (t, 1H, J=7 Hz); 7.58 (t, 1H, J=7 Hz); 7.35 (d, 1H, J=7 Hz); 7.13 (d, 2H, J=10 Hz); 5.43 (s, 2H); 4.42 (s, 2H); 3.67 (s, 3H); 2.96 (m, 2H); 1.75 (m, 2H); 1.39 (m, 2H); 0.88 (t, 2H, J=7 Hz). Mass Calcd. for C24H24Cl2N2O3 : 458.1162. Found: 458.1160.
Reaction SMILES: [H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[C:14]([O:18][C:19]([N:21]([C:29]1[C:34]([CH3:35])=[CH:33][C:32]([CH2:36]Br)=[CH:31][N:30]=1)[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[O:20])([CH3:17])([CH3:16])[CH3:15].C(OCC)(=O)C>CN(C=O)C>[CH2:12]([O:11][C:3](=[O:10])[CH:4]([CH2:36][C:32]1[CH:31]=[N:30][C:29]([N:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:20])=[C:34]([CH3:35])[CH:33]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:13]
Reactant: CCOC(=O)CC(=O)OCC
Reactant: Cc1cc(CBr)cnc1N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)C(Cc1cnc(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)c(C)c1)C(=O)OCC
Reaction time: 0.25 h
Yield: 49.9 %

Procedure:
To a suspension of NaH (0.24 g, 6.0 mmol, 60%) in DMF (5 mL) was added diethyl malonate (0.91 mL, 6.0 mmol) and the mixture was stirred for 15 min. A solution 2-[N,N-bis(tert-butoxycarbonyl)amino]-5-bromomethyl-3-methyl-pyridin (2.0 g, 5.0 mmol) in DMF (5 mL) was added and the resulting solution stirred for 120 min at 60° C. Ethyl acetate was added and the mixture was washed with water and brine and dried. After evaporation of the solvent, the crude product was purified by flash chromatography (CH3OH/CH2Cl2, 1:100→1:20) to give 2-(6-[N,N-bis(tert-butoxycarbonyl)amino]-5-methyl-pyridin-3-ylmethyl)-malonic acid diethyl ester (1.2 g, 50%).
Reaction SMILES: I[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9]2[C:14]([CH3:15])=[CH:13][N:12]=[CH:11][C:10]=2[CH3:16])=[C:4]([CH3:17])[CH:3]=1.[C:18]([C:22]1[CH:27]=[C:26]([CH:28]=[CH2:29])[CH:25]=[C:24]([C:30]([CH3:33])([CH3:32])[CH3:31])[C:23]=1[OH:34])([CH3:21])([CH3:20])[CH3:19].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CC([O-])=O.CC([O-])=O.[Pd+2]>[C:18]([C:22]1[CH:27]=[C:26]([CH:28]=[CH:29][C:2]2[CH:7]=[C:6]([CH3:8])[C:5]([C:9]3[C:14]([CH3:15])=[CH:13][N:12]=[CH:11][C:10]=3[CH3:16])=[C:4]([CH3:17])[CH:3]=2)[CH:25]=[C:24]([C:30]([CH3:33])([CH3:32])[CH3:31])[C:23]=1[OH:34])([CH3:21])([CH3:20])[CH3:19]
Reactant: Cc1cncc(C)c1-c1c(C)cc(I)cc1C
Reactant: C=Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: Cc1cncc(C)c1-c1c(C)cc(C=Cc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)cc1C
Temperature: 100 °C
Reaction time: 36 h
Yield: 91 %

Procedure:
A flame-dried sealable Schlenk tube was charged with 11 (1.69 g, 5.0 mmol), 12 (2.32 g, 10.0 mmol), Pd(OAc)2 (112 mg, 0.50 mmol), and PPh3 (131 mg, 0.50 mmol), evacuated, and then backfilled with N2. Next, dry Et3N (10 mL) was added under an N2 flow. The Schlenk tube was next sealed, the mixture was degassed by 3 freeze-thaw cycles, and backfilled with N2. The Schlenk tube was then wrapped with aluminum foil and stirred at 100° C. for 36 h. The reaction mixture was then cooled to room temperature, diluted with methylene chloride (50 mL), filtered through a thin pad of silica gel, and concentrated in vacuo to afford a red solid. The crude product was purified by flash chromatography on silica gel, eluting with 3:1 hexane: ethyl acetate to give the title compound 2.01 g (91.2%) as a colorless solid: mp 234-235° C.; 1H NMR (400 MHz, CDCl3): δ 8.402 (s, 2H), 7.371 (s, 2H), 7.307 (s, 2H), 7.133 (d, 1H, J=16.4 Hz), 6.936 (d, 1H, J=16.0 Hz), 5.331 (s, 1H), 1.951 (s, 6H), 1.911 (s, 6H), 1.499 (s, 18H); 13C NMR (100 MHz, CDCl3): δ 153.971, 148.630, 148.502, 137.347, 136.301, 135.928, 134.817, 131.251, 129.595, 128.876, 125.837, 125.709, 123.598, 34.638, 30.534, 19.997, 16.822; HRMS (EI): m/z 441.3023 [M+]; calcd, 441.3032; Anal. Calcd. for C31H39NO.H2O: C, 81.00; H, 8.99; N, 3.05. Found; C, 81.01; H, 8.64; N, 3.02.
Reaction SMILES: C([Si](C)(C)[O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[C:19]([N+:23]([O-:25])=[O:24])=[C:18]([OH:26])[CH:17]=[CH:16]3)=[CH:9][CH:8]=1)(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.O>[OH:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[C:19]([N+:23]([O-:25])=[O:24])=[C:18]([OH:26])[CH:17]=[CH:16]3)=[CH:11][CH:12]=1
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(-c2ccc3c([N+](=O)[O-])c(O)ccc3c2)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: O=[N+]([O-])c1c(O)ccc2cc(-c3ccc(O)cc3)ccc12
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 60.5 %

Procedure:
To a solution of 6-[4-(tert-Butyl-dimethyl-silanyloxy)-phenyl]-1-nitro-2-naphthol (302 mg, 0.764 mmol) in THF (12 mL) was added TBAF (0.92 mL, 0.917 mmol, 1.0 M solution in THF). The solution was stirred for 10 minutes at room temperature, poured in water. The mixture was extracted with ethyl acetate. The combined organic layers were washed with brine, dried anhydrous Na2SO4, filtered, evaporation of the solvent, and purification on a silica column (20%-40% ethyl acetate-hexane) yielded 130 mg (61%) of a orange solid. An analytical sample was further purified by recrystallization with ethyl acetate-hexane to yield the title compound as a orange solid:: mp 199-201° C.; 1H NMR (DMDO-d6): δ 6.89(2H, d, J=8.51 Hz), 7.33 (1H, d, J=9.05 Hz), 7.62 (1H, d, J=8.94 Hz), 7.63(2H, d, 8.48 Hz), 7.91 (1H, dd, J=8.87 Hz, J=1.59 Hz), 8.06 (1H, d, 9.18 Hz), 8.17 (1H, d, J=1.31 Hz), 9.64(1H, s), 11.40 (1H,s); MS (ESI) m/z280 (M−H)−.
Reaction SMILES: [C:1]([O-:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]CCCCC.[Na+].[C:22]([O-])(=[O:40])[CH2:23]CCCCCCCCCCCCCCCC.[K+].C([O:45]CCOCCO)C>>[C:13]1(=[O:45])[O:40][CH2:22][CH2:23][O:20][C:1](=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1
Reactant: CCCCCCCCCCCCCCCCCC(=O)[O-]
Reactant: CCOCCOCCO
Agent: [K+]
Agent: [Na+]
Product: O=C1CCCCCCCCCCCC(=O)OCCO1
Yield: 73.2 %

Procedure:
A mixed metal catalyst prepared similarly to that of Example X, except that sodium stearate was substituted for the potassium stearate and ethyl cellusolve replaced with diethylene glycol monoethyl ether, was employed for the continuous depolymerization of poly(ethylene brassylate) in accordance with the procedure and conditions of Example I. Ethylene brassylate was continuously produced and distilled from the reactor at a rapid rate and the overall yield was 73.2%. Comparable results are obtained with a catalyst comprised of sodium benzoate and aluminum tricellusolve (Al(OCH2CH2OC2H5)3).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[NH:13][C:14]([CH:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)=[O:15].[CH:22]([C:24]1[CH:33]=[N:32][C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:25]=1)=[CH2:23].C(O)(=O)C.[OH-].[Na+]>C(O)C>[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[NH:13][C:14]([CH:16]1[CH2:21][CH2:20][N:19]([CH2:23][CH2:22][C:24]2[CH:33]=[N:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]=2)[CH2:18][CH2:17]1)=[O:15]
Reactant: COc1ccc2nccc(NC(=O)C3CCNCC3)c2n1
Reactant: C=Cc1cnc2ccccc2n1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CCO
Product: COc1ccc2nccc(NC(=O)C3CCN(CCc4cnc5ccccc5n4)CC3)c2n1
Yield: 12.9 %

Procedure:
A mixture of amine (1f) (0.403 g, 1.4 mmol), 2-vinyl-quinoxaline (b), (0.22 g, 1.4 mmol), acetic acid (0.1 ml) and ethanol (5.2 ml) was heated under reflux for 6 hours. The mixture was then made basic with aqueous sodium hydroxide and extracted with ethyl acetate. The organic phase was washed with water, dried over magnesium sulfate and concentrated. The residue was chromatographed on silica gel eluting with dichloromethane-methanol (99-1). After evaporation the residue was triturated with a small amount of ethyl acetate and crystallised. The solid was collected by filtration and dried to give the title compound (80 mg) mp.: 170° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.CO[C:15](=[O:29])[CH2:16][CH2:17][CH2:18][N:19]1[CH2:24][CH2:23][CH:22]([CH2:25][CH2:26][CH2:27][CH3:28])[CH2:21][CH2:20]1>C(Cl)Cl>[CH2:25]([CH:22]1[CH2:21][CH2:20][N:19]([CH2:18][CH2:17][CH2:16][C:15]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)=[O:29])[CH2:24][CH2:23]1)[CH2:26][CH2:27][CH3:28]
Reactant: CCCCC1CCN(CCCC(=O)OC)CC1
Reactant: Brc1ccccn1
Agent: [Li]CCCC
Solvent: ClCCl
Product: CCCCC1CCN(CCCC(=O)c2ccccn2)CC1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 12 %

Procedure:
To a dry 25 mL reaction flask was added 2-bromopyridine (200 mg, 1.3 mmol) dissolved in CH2Cl2 (3 mL) and the temperature was adjusted to −78° C. After being stirred for 20 min, addition of n-BuLi (0.84 mL, 1.4 mmol) was conducted under inert atmosphere. After additional 30 min, a solution of 23 dissolved in CH2Cl2 (2 mL) was added. The reaction mixture was left to warm to rt over-night before being quenched with H2SO4 (5 mL, 1 M). The reaction mixture was extracted with ethyl acetate (6×25 mL) and the combined organic phases were dried (MgSO4) and evaporated to dryness, to produce 0.31 g of crude 24. The crude product was subjected to CC [eluent: CH2Cl2: MEOH (10:1)] to give pure 24 (75 mg, 12%). LC-MS [M+H]+ 288 (cald. 288.2).
Reaction SMILES: [SH3+:1].[Br:2][CH:3]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[O:5][CH2:4]1.O.[Na].[CH3:16]S>C(O)C>[Br:2][CH:3]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[O:5][CH2:4]1.[CH3:16][S:1][CH:3]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[O:5][CH2:4]1
Reactant: CS
Reactant: [SH3+]
Agent: O=C1c2ccccc2OCC1Br
Agent: [Na]
Solvent: CCO
Solvent: O
Product: CSC1COc2ccccc2C1=O

Procedure:
The sulfonium salt compound expressed by structural formula [6] was synthesized as follows. First, the present inventor prepared 3-bromo-4-chromanone. The 3-bromo-4-chromanone was synthesized in accordance with the report by W. S. Johnson et. al. in J. Am. Chem. Soc., vol. 66, pages 218-220, 1944. 10.4 grams of 3-bromo-4-chromanone was dissolved in 42 milli-litters of ethanol. 21.3 milli-litters of 15% water solution of methyl-mercaptan sodium salt was dropped thereinto. The resultant solution was agitated at room temperature for 2 hours, and the resultant mixture was poured into cold water. An organic layer was extracted by using 200 milli-litters of ether, and the ether layer was washed in sodium chloride and, thereafter, water. The ether layer was dried by using magnesium sulfate, and the solvent was removed in low pressure. The residue was put in a silica gel column. Using eluate containing hexane and ethyl acetate at 3:1, the residue was separated and refined. Then, 1.52 grams of 3-methylthio-4-chromanone was obtained. The yield was 17%.
Reaction SMILES: [C:1]1([C:7]2[NH:8][C:9]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:24][N:25]([CH:27]=[N:28][S:29]([C:32]1[C:33]([C:38]2[CH:43]=[CH:42][C:41]([CH2:44]Br)=[CH:40][CH:39]=2)=[CH:34][CH:35]=[CH:36][CH:37]=1)(=[O:31])=[O:30])[CH3:26].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH3:26][N:25]([CH:27]=[N:28][S:29]([C:32]1[C:33]([C:38]2[CH:39]=[CH:40][C:41]([CH2:44][N:11]3[C:10]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)=[C:9]([C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)[N:8]=[C:7]3[C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:42][CH:43]=2)=[CH:34][CH:35]=[CH:36][CH:37]=1)(=[O:31])=[O:30])[CH3:24]
Reactant: CN(C)C=NS(=O)(=O)c1ccccc1-c1ccc(CBr)cc1
Reactant: c1ccc(-c2nc(-c3ccccc3)c(-c3ccccc3)[nH]2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CN(C)C=NS(=O)(=O)c1ccccc1-c1ccc(Cn2c(-c3ccccc3)nc(-c3ccccc3)c2-c2ccccc2)cc1
Yield: 94.2 %

Procedure:
1.5 g of 2,4,5-triphenylimidazole, 1.9 g of 4′-bromomethylbiphenyl-2-sulfonic acid dimethylaminomethylenamide (J. Med. Chem. 1995, 38, 2357) and 2.1 g of K2CO3 are stirred at RT for 6 days in 50 ml of DMF. The reaction mixture is poured onto 300 ml of water and extracted with 500 ml of EA. The organic phase is washed 3 times with 250 ml of a saturated aqueous NaCl solution each time and dried over Na2SO4, and the solvent is removed in vacuo. 2.8 g of a viscous oil are obtained.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[Mg].[Cl:13][C:14]1[CH:25]=[CH:24][C:17]([C:18](N(OC)C)=[O:19])=[CH:16][N:15]=1.[Cl-].[NH4+]>C1COCC1.BrCCBr.O>[Cl:13][C:14]1[N:15]=[CH:16][C:17]([C:18]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=2)=[O:19])=[CH:24][CH:25]=1
Reactant: CON(C)C(=O)c1ccc(Cl)nc1
Reactant: FC(F)(F)c1ccc(Br)cc1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: BrCCBr
Solvent: C1CCOC1
Solvent: O
Product: O=C(c1ccc(C(F)(F)F)cc1)c1ccc(Cl)nc1

Procedure:
Under an argon gas flow, half of a solution of 4-bromobenzotrifluoride (1.20 g, 5.33 mmol) in THF (6 mL) was added to magnesium (156 mg, 6.41 mmol). The resulting solution was stirred, and further 1,2-dibromoethane (3 drops) was added. Once the reaction began, the balance of the 4-bromobenzotrifluoride in THF solution was added dropwise, and once dropping had finished, the resulting solution was stirred for 30 minutes at 60° C. A solution of 6-chloro-N-methoxy-N-methylnicotinamide (990 mg, 5.36 mmol) in THF (3 mL) was charged into a separate reaction vessel, into which the above reaction solution was added dropwise under an argon gas flow and ice cooling. After dropping had finished, the resulting solution was stirred for 30 minutes at room temperature, and then heated to reflux for 1 hour. The reaction solution was cooled with ice, then aqueous ammonium chloride and water were added. The resulting solution was extracted with ethyl acetate, and washed with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=10:1), to thereby yield 610 mg of the title compound.
Reaction SMILES: [C:1]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)([O:3][C:4]([CH3:7])([CH3:6])C)=[O:2].C([Li])(C)(C)C.CCCCC.[C:25]([N:32]1[CH2:37]CC(=O)C[CH2:33]1)([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26]>O1CCCC1.C(OCC)C.CC(C)([O-])C.[K+]>[O:2]=[C:1]1[NH:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=2[C:4]2([CH2:6][CH2:37][N:32]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:33][CH2:7]2)[O:3]1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: CC(C)(C)OC(=O)Nc1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Agent: [Li]C(C)(C)C
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: CCCCC
Product: CC(C)(C)OC(=O)N1CCC2(CC1)OC(=O)Nc1ccccc12
Temperature: -70 °C
Reaction time: 0.5 h
Yield: 34 %

Procedure:
N-Boc-aniline (16.12 g, 83.4 mmol) was dissolved in anhydrous tetrahydrofuran (120 mL) and cooled to −70° C. To this solution was added dropwise, under nitrogen, a 1.7 M solution of tert-butyllithium in pentane (110 mL, 187 mmol) at −70° C. After 30 min at −70° C., the solution was warmed to −20° C. and maintained at that temperature for 2 h. The solution was again cooled to −70° C. and treated dropwise with a solution of N-Boc-4-piperidone (15.98 g, 80.2 mmol) in anhydrous tetrahydrofuran (50 mL). The solution was slowly warmed to room temperature, treated with potassium tert-butoxide (25 mg) and stirred at room temperature overnight under nitrogen. The solution was diluted with diethyl ether (300 mL), cooled in an ice-H2O bath and adjusted to pH 7 with 1.0 NHCl (aq). The layers were separated and the aqueous layer extracted once with diethyl ether (100 mL). The pooled organic layers were washed with H2O and saturated brine, then dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure to afford 39.09 g crude product as a viscous pale yellow oil. The crude product was purified via silica gel flash chromatography (25-50% ethyl acetate in hexanes) to afford tert-butyl 2-oxo-1,2-dihydrospiro[benzo[d][1,3]oxazine-4,4′-piperidine]-1′-carboxylate as a pale yellow solid (8.687 g, 34% yield). LC/MS m/z 319.0 [M+H]+, retention time 2.72 min (RP-C18, 10-99% CH3CN/0.05% TFA); 1H-NMR (400 MHz, CDCl3) δ 9.06 (br s, 1H), 7.28 (m, 1H), 7.12 (m, 2H), 6.91 (d, J=8.5 Hz, 1H), 4.12 (br d, J=9.9 Hz, 2H), 3.36 (br t, J=12.4 Hz, 2H), 2.13 (br d, J=13.1 Hz, 2H), 1.98 (m, 2H), 1.51 (s, 9H).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[O:6][C:7]([CH3:27])=[C:8]([CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:13]=2)[CH:9]=1)=[O:4].[F:28][CH:29]([F:38])[O:30][C:31]1[CH:36]=[CH:35][C:34](I)=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>O1CCOCC1>[CH3:1][O:2][C:3]([C:5]1[O:6][C:7]([CH3:27])=[C:8]([CH2:10][O:11][C:12]2[CH:13]=[CH:14][C:15]([C:34]3[CH:35]=[CH:36][C:31]([O:30][CH:29]([F:38])[F:28])=[CH:32][CH:33]=3)=[CH:16][CH:17]=2)[CH:9]=1)=[O:4]
Reactant: FC(F)Oc1ccc(I)cc1
Reactant: COC(=O)c1cc(COc2ccc(B3OC(C)(C)C(C)(C)O3)cc2)c(C)o1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: ClCCl
Solvent: C1COCCO1
Product: COC(=O)c1cc(COc2ccc(-c3ccc(OC(F)F)cc3)cc2)c(C)o1
Temperature: 80 °C
Reaction time: 4 h
Yield: 57.2 %

Procedure:
A degassed mixture of 5-methyl-4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxymethyl]-furan-2-carboxylic acid methyl ester (119) (200 mg, 0.54 mmoles), 4-difluoromethoxy-1-iodo-benzene (175 mg, 0.65 mmoles), 2M aqueous cesium carbonate (0.81 ml) and), [1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (20 mg) in 1,4-dioxan (10 ml), under an argon atmosphere was heated at 80° C. for 20 h. Further quantities of 4-difluoromethoxy-1-iodo-benzene (87.5 mg, 0.0.27 mmoles) and [1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (10 mg) were added and heating at 80° C. was continued for 4 hours. After cooling, the mixture was concentrated. The residue was dissolved in dichloromethane and washed with water and brine, and dried. The solvent was evaporated and the residue was purified by flash chromatography using petrol (40–60°)/diethyl ether 9:1v/v as eluent to afford compound 128(120 mg) as a wax. LC/MS System A; Rt=4.14 mins.