Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:6]([C:7]2[C:16](=O)[C:15]3C(O)=CC(O)=CC=3OC=2)=[CH:5][CH:4]=[C:3](O)[CH:2]=1.[OH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]([CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:29].C(OCC)(=O)C=CC1C=CC=CC=1>>[C:6]1([CH:7]=[CH:16][C:15]2[O:21][C:22]3[C:23]([C:28](=[O:29])[C:30]=2[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:1]=[CH:2][CH:3]=[CH:4][CH:5]=1
Reactant: O=C(Cc1ccccc1)c1ccccc1O
Reactant: O=c1c(-c2ccc(O)cc2)coc2cc(O)cc(O)c12
Agent: CCOC(=O)C=Cc1ccccc1
Product: O=c1c(-c2ccccc2)c(C=Cc2ccccc2)oc2ccccc12

Procedure:
In the earlier years, from about 1928 to about 1952, two synthetic routes to genistein and related isoflavones were predominantly available. The first route involved the reaction of a 2-hydroxydeoxybenzoin with a cinnamic acid ester, e.g. ethyl cinnamate, to afford the corresponding 2-(2-phenylethenyl)-isoflavone, followed by oxidation with potassium permanganate and thermal decarboxylation to the isoflavanone compound: see W. Baker et al., J. Chem. Soc. 1926, 2713; ibid. 1928, 3115; and ibid. 1933, 274. The second route involved the reaction of a 2-hydroxydeoxybenzoin with sodium and ethyl formate to produce the appropriate 2H-isoflavone compound directly: see H. S. Mahal et al., J. Chem. Soc. 1934, 1769; F. Wessely et al., Chem. Ber. 66, 685 (1933); and R. L. Shriner, J. Org. Chem. 10, 288 (1945). Both routes in whatever variation led to inadequate yields of the desired isoflavone compound.
Reaction SMILES: Cl[C:2]1[CH:17]=[CH:16][C:5]2[NH:6][C:7](=[O:15])[O:8][C:9]([CH3:14])([C:10]([F:13])([F:12])[F:11])[C:4]=2[CH:3]=1.[CH3:18][O:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Cl-].[NH4+]>O1CCOCC1.C(OCC)(=O)C>[CH3:18][O:19][C:20]1[CH:25]=[C:24]([C:2]2[CH:17]=[CH:16][C:5]3[NH:6][C:7](=[O:15])[O:8][C:9]([CH3:14])([C:10]([F:13])([F:12])[F:11])[C:4]=3[CH:3]=2)[CH:23]=[CH:22][CH:21]=1
Reactant: CC1(C(F)(F)F)OC(=O)Nc2ccc(Cl)cc21
Reactant: COc1cccc(B(O)O)c1
Agent: O=P([O-])([O-])[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: COc1cccc(-c2ccc3c(c2)C(C)(C(F)(F)F)OC(=O)N3)c1
Temperature: 95 °C
Yield: 19.8 %

Procedure:
A mixture of 6-chloro-4-methyl-4-trifluoromethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one (0.2 g, 0.75 mmol), 3-methoxyphenyl boronic acid (0.13 g, 0.9 mmol), potassium phosphate (0.23 g, 1.1 mmol), and nickel (II) (diphenylphosphino)ferrocenyl dichloride (52 mg, 0.076 mmol) in anhydrous dioxane was subject to a blanket of nitrogen to remove oxygen and heated at 95° C. under nitrogen for 48 hours. Another portion of 3-methoxyphenyl boronic acid (0.3 g, 0.9 mmol) and nickel (II) (diphenylphosphino)ferrocenyl dichloride (52 mg, 0.076 mmol) was added and the reaction solution was heated at 95° C. under nitrogen for 48 hours. The reaction solution was cooled to room temperature. Saturated aqueous ammonium chloride solution (30 mL) and ethyl acetate (50 mL) was added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic layer was washed with brine and dried (MgSO4). After removal of solvent, the residue was purified by a flash chromatography (silica gel, hexane:ethyl acetate/4:1) to afford the title compound as a white solid (50 mg, 20%): mp 178-179° C.; 1H-NMR (DMSO-d6) δ 10.85 (bs, 1H, D2O exchangeable), 7.73 (m, 2H), 7.38 (t, 1H, J=7.9 Hz), 7.23 (d, 1H, J=7.7 Hz), 7.19 (d, 1H, J=1.9 Hz), 7.02 (d, 1H, J=8.2 Hz), 6.94 (dd, 1H, J=8.2, 2.4 Hz), 3.88 (s, 3H), 1.98 (s, 3H), 19F-NMR (DMSO-d6) δ −81.88 (s, 1F), Anal. Calc. For C17H14F3NO3: C, 60.54; H, 4.18; N, 4.15. Found: C, 60.58; H, 4.44; N, 4.19.
Reaction SMILES: Cl[C:2]([C:4]1[CH:13]=[CH:12][CH:11]=[CH:10][C:5]=1/[CH:6]=[CH:7]\[C:8]#[N:9])=[O:3].[O:14]1CCOCC1>CC(C)=O>[OH:14][C:8]1[CH:7]=[CH:6][C:5]2[CH:10]=[CH:11][CH:12]=[CH:13][C:4]=2[C:2](=[O:3])[N:9]=1
Reactant: N#C/C=C\c1ccccc1C(=O)Cl
Reactant: C1COCCO1
Solvent: CC(C)=O
Product: O=c1nc(O)ccc2ccccc12
Reaction time: 8 h
Yield: 36.9 %

Procedure:
59.0 g (0.308 mole) of (I) is taken up in dry dioxane (800 ml) and purged with HCl gas at 70° for 5 hours. Solvent is removed, the residue is azeotropically distilled three times with benzene and the residue taken up in dimethoxyethane (200 ml) and water (22 ml). After standing overnight at room temperature, the reaction mixture is evaporated to dryness, taken up in ethyl acetate (1.5 liters) and washed twice with saturated NaHCO3 solution (630 ml portions). The NaHCO3 phase is back-washed with ethyl acetate (1.0 liter), the organic extracts are combined and washed 3 times with 500 ml portions of water. The organic layer is evaporated. The solid obtained is taken up in acetone (1.0 liter), charcoaled and evaporated. The product is recrystallized from benzene (500 ml) and petroleum ether (650 ml). Yield: 20.7 g, percent yield: 36.9%, single spot, Rf 0.30 (alumina, CHCl3 :EtOAc-6:4). mp=129°-131° (crude); mp on recrystallization: 135°-136°.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:12]([C:16]([O:18][CH2:19]C)=[O:17])=[N:11][C:10]([OH:21])=[C:9]([OH:22])[C:8]=2[C:7]1=[O:23].[CH3:28][O-].[Mg+2].C[O-]>CN(C=O)C.CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:22])[C:10](=[O:21])[N:11]([CH3:28])[C:12]=2[C:16]([O:18][CH3:19])=[O:17])[C:7]1=[O:23]
Reactant: CCOC(=O)c1nc(O)c(O)c2c1CCN(Cc1ccc(F)c(Cl)c1)C2=O
Reactant: C[O-]
Agent: [Mg+2]
Solvent: CO
Solvent: CN(C)C=O
Product: COC(=O)c1c2c(c(O)c(=O)n1C)C(=O)N(Cc1ccc(F)c(Cl)c1)CC2
Temperature: 45 °C
Reaction time: 1 h

Procedure:
To a stirred suspension of ethyl 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate (40 g) in DMF (200 mL) was added magnesium methoxide in methanol (100 mL). The mixture heated at 40-50° C. for 3 hours. The excess methanol distilled off, and methyl tosylate (18 mL) was added. The reaction mixture was heated at 50° C. overnight, then cooled to 25° C., and then quenched into 1N HCl (100 mL). The suspension stirred for 1 hour at ambient temperature. The product was isolated by filtration, and the filter cake washed with water (2×100 mL) and then dried on the filter under an atmosphere of nitrogen. The crude product was suspended in methanol (460 mL), heated at reflux temperature for 1 hour, and then allowed to cool to ambient temperature. The product was isolated by filtration and the filter cake washed with cold methanol (2×40 mL) and dried to give the title product.
Reaction SMILES: Br[C:2]1[CH:21]=[N:20][C:5]2[N:6]([CH2:16][CH:17]([CH3:19])[CH3:18])[CH2:7][CH2:8][CH2:9][C:10]([C:12]([O:14][CH3:15])=[O:13])=[CH:11][C:4]=2[CH:3]=1.[CH2:22]([O:26][CH2:27][CH2:28][O:29][C:30]1[CH:35]=[CH:34][C:33](OB(O)O)=[CH:32][CH:31]=1)[CH2:23][CH2:24][CH3:25].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:22]([O:26][CH2:27][CH2:28][O:29][C:30]1[CH:31]=[CH:32][C:33]([C:2]2[CH:21]=[N:20][C:5]3[N:6]([CH2:16][CH:17]([CH3:19])[CH3:18])[CH2:7][CH2:8][CH2:9][C:10]([C:12]([O:14][CH3:15])=[O:13])=[CH:11][C:4]=3[CH:3]=2)=[CH:34][CH:35]=1)[CH2:23][CH2:24][CH3:25]
Reactant: COC(=O)C1=Cc2cc(Br)cnc2N(CC(C)C)CCC1
Reactant: CCCCOCCOc1ccc(OB(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCO
Solvent: Cc1ccccc1
Product: CCCCOCCOc1ccc(-c2cnc3c(c2)C=C(C(=O)OC)CCCN3CC(C)C)cc1
Temperature: 115 °C
Reaction time: 0.5 h
Yield: 79.3 %

Procedure:
A suspension of methyl 3-bromo-10-isobutyl-7,8,9,10-tetrahydropyrido[2,3-b]azocine-6-carboxylate (690 mg), 4-(2-butoxyethoxy)phenylboric acid (605 mg) and potassium carbonate (702 mg) in toluene (15 ml), ethanol (1.5 ml) and water (1.5 ml) was stirred under an argon atmosphere for 30 minutes. Tetrakis(triphenylphosphine)palladium (113 mg) was added thereto, and the mixture was heated at 115° C. for 5 hours under an argon atmosphere. The solution was allowed to cool. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1→hexane:ethyl acetate=4:1) to give methyl 3-[4-(2-butoxyethoxy)phenyl]-10-isobutyl-7,8,9,10-tetrahydropyrido[2,3-b]azocine-6-carboxylate (723 mg) as a yellow oily material.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([N+:13]([O-])=O)[CH:8]=1.[Cl-].[NH4+].CO.O1CCCC1>[Fe].O>[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([NH2:13])[CH:8]=1
Reactant: O=[N+]([O-])c1cccc(OCc2cccc(F)c2)c1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: Nc1cccc(OCc2cccc(F)c2)c1
Reaction time: 0.5 h
Yield: 93.2 %

Procedure:
To a solution of the product from Example 199A (0.494 g, 2.0 mmol), iron powder (0.56 g, 10.0 mmol) and ammonium chloride (0.54 g, 10.0 mmol) in a methanol (20 mL), tetrahydrofuran (20 mL), and water (10 mL) solution was heated to reflux for 2 hours. The resultant mixture was filtered through a pad of celite, and the filtrate was concentrated. Then ethyl acetate was added, stirred for 30 minutes, filtered and concentrated under vacuum to provide the title compound (0.405 g, 93%).
Reaction SMILES: FC(F)(F)C(O)=O.[C:8]1([C:14]2([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH2:22][C:21]3[N:20]([S:23]([C:26]4[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=4)(=[O:25])=[O:24])[N:19]=[C:18]([NH:33]C(=O)OC(C)(C)C)[C:17]=3[CH:16]=[CH:15]2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>ClCCl>[C:41]1([C:14]2([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH2:22][C:21]3[N:20]([S:23]([C:26]4[CH:27]=[CH:28][C:29]([CH3:32])=[CH:30][CH:31]=4)(=[O:25])=[O:24])[N:19]=[C:18]([NH2:33])[C:17]=3[CH:16]=[CH:15]2)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1
Reactant: Cc1ccc(S(=O)(=O)n2nc(NC(=O)OC(C)(C)C)c3c2CC(c2ccccc2)(c2ccccc2)C=C3)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)n2nc(N)c3c2CC(c2ccccc2)(c2ccccc2)C=C3)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 49.1 %

Procedure:
0.5 cm3 of trifluoroacetic acid is added to a solution of 0.2 g of tert-butyl [6,6-diphenyl-1-(4-toluenesulphonyl)-6,7-dihydro-1H-indazol-3-yl]carbamate in 2 cm3 of dichloromethane, cooled to a temperature in the region of 0° C. After one hour at a temperature in the region of 0° C., the reaction mixture is stirred for one hour at a temperature in the region of 20° C. and then concentrated to dryness under reduced pressure (13 kPa). The residue is taken up in 25 cm3 of dichloromethane and 10 cm3 of water. The pH is brought to about 10 by addition of a normal aqueous sodium hydroxide solution. After separation of the phases by settling, the aqueous phase is extracted with twice 10 cm3 of dichloromethane. The combined organic phases are successively washed with once 20 cm3 of 0.1N aqueous sodium hydroxide solution, twice 30 cm3 of water and once 30 cm3 of saturated aqueous sodium chloride solution and then dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (13 kPa). The residue is taken up in 3 cm3 of diethyl ether, washed with twice 1 cm3 of diethyl ether and then dried under reduced pressure (13 kPa) at a temperature in the region of 50° C. 0.08 g of 6,6-diphenyl-1-(4-toluenesulphonyl)-6,7-dihydro-1H-indazol-3-ylamine is thus obtained in the form of a white solid, the characteristics of which are as follows:
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]([SH:11])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([OH:19])[N:6]2[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+].[C:26]1(=[O:41])[N:30]([CH2:31][CH2:32][CH2:33][CH2:34]Br)[C:29](=[O:36])[C:28]2=[CH:37][CH:38]=[CH:39][CH:40]=[C:27]12>CN(C)C=O>[NH2:1][C:2]1[N:10]=[C:9]([S:11][CH2:34][CH2:33][CH2:32][CH2:31][N:30]2[C:26](=[O:41])[C:27]3=[CH:40][CH:39]=[CH:38][CH:37]=[C:28]3[C:29]2=[O:36])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([OH:19])[N:6]2[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCCBr
Reactant: Nc1nc(S)nc2c1nc(O)n2Cc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Nc1nc(SCCCCN2C(=O)c3ccccc3C2=O)nc2c1nc(O)n2Cc1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 74.3 %

Procedure:
6-Amino-9-benzyl-8-hydroxy-2-mercaptopurine (120 mg, 0.44 mmol) was suspended in dimethylformamide (10 ml). To the suspension were added potassium carbonate (60 mg, 0.43 mmol) and 4-phthalimidobutyl bromide (113 mg, 0.40 mmol) in order. The mixture was stirred at room temperature for 2 hours. The solvent was removed in vacuo, and water and methanol were added to the residue, and the resulting crystals were taken by filtration to give the subject compound (141 mg, yield 74%).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:6]([CH:7]=O)[C:5]([OH:10])=[CH:4][CH:3]=1.[OH:11][C:12]1[CH:13]=[C:14]([CH:23]=[CH:24][C:25]=1[O:26][CH3:27])[NH:15][S:16]([CH2:19][C:20](O)=[O:21])(=[O:18])=[O:17]>C(O)(=O)C>[Cl:1][C:2]1[CH:9]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:10][C:20](=[O:21])[C:19]([S:16]([NH:15][C:14]1[CH:23]=[CH:24][C:25]([O:26][CH3:27])=[C:12]([OH:11])[CH:13]=1)(=[O:17])=[O:18])=[CH:7]2
Reactant: O=Cc1cc(Cl)ccc1O
Reactant: COc1ccc(NS(=O)(=O)CC(=O)O)cc1O
Solvent: CC(=O)O
Product: COc1ccc(NS(=O)(=O)c2cc3cc(Cl)ccc3oc2=O)cc1O

Procedure:
A solution of 5-chlorosalicylaldehyde (1 mmol) and 3-hydroxy-4-methoxyanilinosulfonyl acetic acid (1 mmol) in acetic acid (10 mL) was subjected to the General Procedure 1, Method A to yield the title compound; m.p. 225-226° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:13]([OH:15])[CH3:14])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19](F)[C:18]=1[N+:24]([O-:26])=[O:25]>>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:13]([O:15][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([F:16])[C:18]=1[N+:24]([O-:26])=[O:25])[CH3:14])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C[C@@H](O)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: O=[N+]([O-])c1c(F)cccc1F
Product: C[C@@H](Oc1cccc(F)c1[N+](=O)[O-])[C@H](NC(=O)OC(C)(C)C)C(=O)O

Procedure:
In analogous manner to that described in example 5a), the reaction of (2S,3R)-2-tert-butoxycarbonylamino-3-hydroxy-butyric acid and 2,6-difluoro-nitrobenzene yielded (78% of theory) the title compound as a brown oil, MS m/e (%): 357.3 (M−H+, 100).
Reaction SMILES: FC(F)(F)C(O)=O.[F:8][C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[C:16]1([OH:27])[CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17]1>ClCCl>[F:8][C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[C:16]1([OH:27])[CH2:19][NH:18][CH2:17]1
Reactant: CC(C)(C)OC(=O)N1CC(O)(c2cccc(F)c2F)C1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: OC1(c2cccc(F)c2F)CNC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 100.3 %

Procedure:
Trifluoroacetic acid (2 ml) was added to a solution of tert-butyl 3-(2,3-difluorophenyl)-3-hydroxyazetidine-1-carboxylate (0.80 g, 2.80 mmol) in dichloromethane (30 ml). The reaction mixture was stirred at ambient temperature for 1 h. The solvent was evaporated and the crude product was purified on a Biotage Isolute SCX-3 SPE column (washed with methanol and eluted with methanol/triethylamine, 4:1) to give the title compound (0.52 g). MS m/z (rel. intensity, 70 eV) 185 (M+, 1), 141 (68), 127 (bp), 114 (82), 63 (40).
Reaction SMILES: Cl.[N+:2]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][NH2:13])=[CH:7][CH:6]=1)([O-:4])=[O:3].F[C:15](F)(F)C(OC(=O)C(F)(F)F)=O.[H-].[Na+].[OH-].[Na+]>ClCCl.CO.C(N(CC)CC)C>[N+:2]([C:5]1[CH:6]=[CH:7][C:8]([CH2:11][CH2:12][NH:13][CH3:15])=[CH:9][CH:10]=1)([O-:4])=[O:3]
Reactant: NCCc1ccc([N+](=O)[O-])cc1
Reactant: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CO
Solvent: ClCCl
Product: CNCCc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 40 %

Procedure:
25 g of 2-(4-nitrophenyl)-ethylamine hydrochloride were suspended in 500 ml of dichloromethane and reacted with 33 ml of triethylamine. 52 g of trifluoroacetic acid anhydride were added slowly dropwise to the reaction mixture at 0° C. After addition was complete, the reaction mixture was stirred for 2 hours at room temperature and then extracted by shaking twice, each time with 200 ml of 5% aqueous hydrochloric acid solution and twice with saturated aqueous sodium hydrogen carbonate solution. Then the dichloromethane phase was dried with sodium sulfate and concentrated. The residue was added to 500 ml tetrahydrofuran and reacted with 44 ml of methyl iodide. Then 10 g of sodium hydride were added batchwise and the reaction mixture was stirred for 2 hours at room temperature. After the reaction was complete, the reaction mixture was filtered and concentrated over silica gel. The residue obtained was purified by flash chromatography using 2:1 methyl-tert-butyl ether/cyclohexane as the eluent. The oil obtained was dissolved in 300 ml of methanol. 50 ml of a 20% aqueous sodium hydroxide solution were added to the solution and the mixture was stirred for 2 hours at room temperature. Then the main quantity of methanol was distilled off and 100 ml of water were added. The solution was shaken twice with 240 ml of dichloromethane each time. The organic phases were combined, dried, and concentrated. The remaining oily reaction product was purified by flash chromatography using dichloromethane/methanol/concentrated aqueous ammonia solution as the eluent. 8.9 g of N-[2-(4-nitrophenyl)-ethyl]-N-methylamine were obtained as an oil.
Reaction SMILES: Cl.Cl.NC1CCN(S(C2C=C3C(=CC=2)C=NC=C3)(=O)=O)CC1.[C:23]([O:27][C:28](N(CCCO)C[C@@H](NS(C1C=C2C(=CC=1)C=NC=C2)(=O)=O)C)=[O:29])([CH3:26])([CH3:25])[CH3:24].Cl.Cl.[Br:54][C:55]1[C:64]([S:65]([N:68]2[CH2:75][CH2:74][CH2:73][CH2:72][NH:71][CH2:70][C@H:69]2[CH3:76])(=[O:67])=[O:66])=[CH:63][CH:62]=[C:61]2[C:56]=1[CH:57]=[CH:58][N:59]=[CH:60]2>>[Br:54][C:55]1[C:64]([S:65]([N:68]2[CH2:75][CH2:74][CH2:73][CH2:72][N:71]([C:28]([O:27][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:29])[CH2:70][C@H:69]2[CH3:76])(=[O:67])=[O:66])=[CH:63][CH:62]=[C:61]2[C:56]=1[CH:57]=[CH:58][N:59]=[CH:60]2
Reactant: C[C@@H]1CNCCCCN1S(=O)(=O)c1ccc2cnccc2c1Br
Reactant: C[C@@H](CN(CCCO)C(=O)OC(C)(C)C)NS(=O)(=O)c1ccc2cnccc2c1
Agent: Cl
Agent: NC1CCN(S(=O)(=O)c2ccc3cnccc3c2)CC1
Product: C[C@@H]1CN(C(=O)OC(C)(C)C)CCCCN1S(=O)(=O)c1ccc2cnccc2c1Br

Procedure:
The compound of interest was synthesized (colorless oil, 41%) according to the production method of Step 1 of Example 12 using Reference Compound 4 instead of Reference Compound 2 and using Reference Compound 23 instead of Reference Compound 9.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].O=[C:17]1[CH2:21][CH2:20][CH2:19][CH:18]1[C:22]([O:24][CH3:25])=[O:23].C(N(CC)C(C)C)(C)C>C(Cl)Cl>[CH3:25][O:24][C:22]([C:18]1[CH2:19][CH2:20][CH2:21][C:17]=1[O:6][S:3]([C:2]([F:15])([F:14])[F:1])(=[O:5])=[O:4])=[O:23]
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: COC(=O)C1CCCC1=O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COC(=O)C1=C(OS(=O)(=O)C(F)(F)F)CCC1
Reaction time: 72 h
Yield: 72.9 %

Procedure:
Trifluoromethanesulfonic anhydride (1.5 mL, 8.9 mmol) was slowly added to a solution of methyl 2-oxocyclopentanecarboxylate (1.0 mL, 8.1 mmol) and N,N-diisopropylethylamine (2.2 mL, 13.0 mmol) in methylene chloride (30 mL) under a nitrogen atmosphere at room temperature. The reaction was stirred for 72 h, and then partitioned between methylene chloride and water. The organic layer was washed with 1 N HCl, aqueous NaHCO3, and brine; dried over magnesium sulfate; and concentrated to give an oil. The product was purified by FCC on silica gel eluting ethyl ether:hexane (5:95) to give 2-trifluoromethanesulfonyloxy-cyclopent-1-enecarboxylic acid methyl ester (1.62 g, 73%) as a yellow oil.
Reaction SMILES: [CH:1]1([N:7]([CH3:36])[C:8](=[O:35])[CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[N:19]=[C:18]([NH:23][C:24](=[O:26])[CH3:25])[N:17]([CH2:27][C:28]([O:30][C:31](C)(C)[CH3:32])=[O:29])[CH2:16]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br>C(OCC)(=O)C.C(O)C.C(O)(=O)C>[CH:1]1([N:7]([CH3:36])[C:8](=[O:35])[CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[N:19]=[C:18]([NH:23][C:24](=[O:26])[CH3:25])[N:17]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:16]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CC(=O)NC1=Nc2ccc(OCCCC(=O)N(C)C3CCCCC3)cc2CN1CC(=O)OC(C)(C)C
Agent: Br
Solvent: CCO
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CCOC(=O)CN1Cc2cc(OCCCC(=O)N(C)C3CCCCC3)ccc2N=C1NC(C)=O
Reaction time: 8 h

Procedure:
A solution of N-cyclohexyl-N-methyl-4-[2-acetamido-3-tert-butyloxycarbonylmethyl-3,4-dihydroquinazolin-6-yl]oxybutyramide (13.7 g, 25 mmol) was dissolved in a mixture of ethyl acetate and ethanol (10 mL each), and to the mixture was added saturated HBr in acetic acid. After stirring overnight, the mixture was concentrated, dissolved in ethyl acetate and the organic layer was washed with half-saturated sodium bicarbonate and brine, otherwise dried, filtered and evaporated. Column chromatography over silica gel (3:1 dichloromethane-ethyl acetate) afforded the title compound as an amorphous foam which crystalled from cold ether, mp 96°-7° C.
Reaction SMILES: [F:1][C:2]1[C:7]([C:8]2[NH:12][CH:11]=[C:10]([CH:13]=[O:14])[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[H-].[Na+].C1OCCOCCOCCOCCOC1.[O:32]1[CH:36]=[CH:35][CH:34]=[C:33]1[S:37](Cl)(=[O:39])=[O:38]>O1CCCC1.C(=O)([O-])O.[Na+]>[F:1][C:2]1[C:7]([C:8]2[N:12]([S:37]([C:33]3[O:32][CH:36]=[CH:35][CH:34]=3)(=[O:39])=[O:38])[CH:11]=[C:10]([CH:13]=[O:14])[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: O=S(=O)(Cl)c1ccco1
Reactant: O=Cc1c[nH]c(-c2cccnc2F)c1
Agent: C1COCCOCCOCCOCCO1
Agent: O=C([O-])O
Agent: [H-]
Solvent: C1CCOC1
Product: O=Cc1cc(-c2cccnc2F)n(S(=O)(=O)c2ccco2)c1
Reaction time: 0.17 h
Yield: 75.6 %

Procedure:
To a solution of 5-(2-fluoropyridin-3-yl)-1H-pyrrole-3-carbaldehyde (220 mg) in tetrahydrofuran (30 mL) was added sodium hydride (60% in oil, 84 mg) at room temperature and the mixture was stirred for 10 min. 15-Crown-5 (464 mg) was added dropwise, and the mixture was stirred for 5 min. Furan-2-sulfonyl chloride (263 mg) was added, and the mixture was further stirred for 30 min. The reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=1:1) and crystallized from diethyl ether to give the title compound as colorless crystals (yield 280 mg, 83%).
Reaction SMILES: [CH:1]1[CH:10]=[C:9]2[C:4]([CH:5]=[C:6]([SH:11])[CH:7]=[CH:8]2)=[CH:3][CH:2]=1.Br[CH2:13][CH:14]=[C:15]([CH3:22])[CH2:16][CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20]>>[CH:5]1[C:4]2[C:9](=[CH:10][CH:1]=[CH:2][CH:3]=2)[CH:8]=[CH:7][C:6]=1[S:11][CH2:13][CH:14]=[C:15]([CH3:22])[CH2:16][CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20]
Reactant: CC(C)=CCCC(C)=CCBr
Reactant: Sc1ccc2ccccc2c1
Product: CC(C)=CCCC(C)=CCSc1ccc2ccccc2c1

Procedure:
2-thionaphthol is reacted with 1-bromo-3,7-dimethyl-octa-2,6-diene to produce 3,7-dimethyl-octa-2,6-dienyl 2-naphthyl sulphide (boiling point = 138° C/0.25 mmHg;