Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([N:4]1[C@H:8]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:7][O:6][C:5]1=[O:16])(=[O:3])[CH3:2].C(N(C(C)C)CC)(C)C.[N+:26](/[CH:29]=[CH:30]/[C:31]1[CH:32]=[C:33]([CH:42]=[CH:43][CH:44]=1)[O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([O-:28])=[O:27]>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[N+:26]([CH2:29][C@@H:30]([C:31]1[CH:44]=[CH:43][CH:42]=[C:33]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:32]=1)[CH2:2][C:1]([N:4]1[C@H:8]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:7][O:6][C:5]1=[O:16])=[O:3])([O-:28])=[O:27]
Reactant: CC(=O)N1C(=O)OC[C@H]1Cc1ccccc1
Reactant: O=[N+]([O-])/C=C/c1cccc(OCc2ccccc2)c1
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(C[C@@H](C[N+](=O)[O-])c1cccc(OCc2ccccc2)c1)N1C(=O)OC[C@H]1Cc1ccccc1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
At −78° C., titanium(iv) chloride (1.0 M solution in DCM) (17.8 mL, 17.8 mmol) was added slowly to a solution of (R)-3-acetyl-4-benzyloxazolidin-2-one (available from Aldrich) (3.55 g, 16.2 mmol) in DCM (80 mL), followed by slow addition of diisopropylethyl amine (3.38 mL, 19.4 mmol). The mixture was stirred at −78° C. for 30 minutes and then a solution of (E)-1-((3-(2-nitrovinyl)phenoxy)methyl)benzene (94.1A) (4.13 g, 16.2 mmol) (commercially available from Aldrich) in DCM (17 mL) was added dropwise (over 15 minutes). Then TiCl4 (16 mL, 1.0 M solution in DCM) was added slowly to the reaction. The mixture was stirred at −78° C. for 2 hours and then quenched with NH4Cl solution. The mixture was extracted with EtOAc (350 mL) and the organic phase was washed with sodium bicarbonate solution and brine, dried over anhydrous Na2SO4. After removing solvent, the residue was recrystallized from MeOH, 94.1B (727 mg), white solid was obtained. MS ESI (np0s.) m/e: 475 (M+H)+.
Reaction SMILES: [C:1]([OH:13])(=[O:12])/[CH:2]=[CH:3]/[C:4]1[CH:11]=[CH:10][C:8]([OH:9])=[C:6]([OH:7])[CH:5]=1.[CH3:14]C1C=CC(S(O)(=O)=O)=CC=1.COC(OC)(C)C>CO>[C:1]([O:13][CH3:14])(=[O:12])/[CH:2]=[CH:3]/[C:4]1[CH:11]=[CH:10][C:8]([OH:9])=[C:6]([OH:7])[CH:5]=1
Reactant: O=C(O)/C=C/c1ccc(O)c(O)c1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Solvent: COC(C)(C)OC
Solvent: CO
Product: COC(=O)/C=C/c1ccc(O)c(O)c1
Yield: 98 %

Procedure:
Put a 10 g caffeic acid (1) in a reaction bottle, and add 1 g TsOH and 3 ml 2,2-dimethoxypropane and 10 ml methanol thereinto, followed by refluxing for 6 hours. After the refluxation, remove the solvent and pour the resultant solution into 100 ml water, followed by being extracted by the ethyl acetate for three times, neutralizing with 3% NaHCO3, and finally performing a column chromatography. Therefore, the product, methyl caffeate (the compound 2) is obtained with 98% yield.
Reaction SMILES: [CH3:1][CH:2]([CH3:24])[CH2:3][CH:4]([C:8]1[CH:9]=[C:10](C2C=CC=CC=2)[CH:11]=[C:12](C(F)(F)F)[CH:13]=1)[C:5]([OH:7])=[O:6].[F:25][C:26]([F:39])([F:38])[C:27]1[CH:32]=[CH:31][C:30](/[CH:33]=[CH:34]/B(O)O)=[CH:29][CH:28]=1>>[CH3:24][CH:2]([CH3:1])[CH2:3][CH:4]([C:8]1[CH:9]=[C:10]([C:30]2[CH:31]=[CH:32][C:27]([C:26]([F:39])([F:38])[F:25])=[CH:28][CH:29]=2)[CH:11]=[C:12]([CH:34]=[CH:33][C:30]2[CH:31]=[CH:32][C:27]([C:26]([F:39])([F:38])[F:25])=[CH:28][CH:29]=2)[CH:13]=1)[C:5]([OH:7])=[O:6]
Reactant: CC(C)CC(C(=O)O)c1cc(-c2ccccc2)cc(C(F)(F)F)c1
Reactant: OB(O)/C=C/c1ccc(C(F)(F)F)cc1
Product: CC(C)CC(C(=O)O)c1cc(C=Cc2ccc(C(F)(F)F)cc2)cc(-c2ccc(C(F)(F)F)cc2)c1

Procedure:
The title compound was prepared from a Nigishi coupling of 4-methyl-2-(5-trifluoromethyl-biphenyl-3-yl)pentanoic acid (intermediate compound 1g) with trans-2-(4-trifluoromethylphenyl)-vinyl-boronic acid under the conditions described in Example 14; 1H NMR (400 MHz, MeOD) δ ppm 0.78-0.89 (m, 6 H), 1.47 (dt, J=13.39, 6.63 Hz, 1 H), 1.62 (ddd, J=13.63, 7.09, 6.91 Hz, 1 H), 1.91-1.98 (m, 1 H), 3.68 (t, J=7.83 Hz, 1 H), 7.33 (d, J=16.4 Hz, 1 H), 7.26 (d, J=16.5 Hz, 1 H), 7.48-7.58 (m, 4 H), 7.64-7.70 (m, 5 H), 7.75-7.78 (m, 2 H).
Reaction SMILES: [NH2:1][C:2]1[CH:12]=[C:11]([NH:13][C:14](=[O:16])[CH3:15])[CH:10]=[CH:9][C:3]=1[C:4]([O:6]CC)=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.Cl[C:30]1[N:35]=[N:34][C:33]([C:36]([O:38][CH3:39])=[O:37])=[CH:32][CH:31]=1>C1(C)C=CC=CC=1>[C:14]([NH:13][C:11]1[CH:10]=[CH:9][C:3]2[C:4](=[O:6])[N:35]3[N:34]=[C:33]([C:36]([O:38][CH3:39])=[O:37])[CH:32]=[CH:31][C:30]3=[N:1][C:2]=2[CH:12]=1)(=[O:16])[CH3:15]
Reactant: CCOC(=O)c1ccc(NC(C)=O)cc1N
Reactant: COC(=O)c1ccc(Cl)nn1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: COC(=O)c1ccc2nc3cc(NC(C)=O)ccc3c(=O)n2n1

Procedure:
A solution of ethyl 2-amino-4-(acetylamino)benzoate (4.03 g, 18.13 mmol, Example 4, Step A), p-toluenesulfonic acid, monohydrate (0.5 g, 2.63 mmol) and methyl 6-chloro-3-pyridazinecarboxylate [3.13 g, 18.14 mmol, prepared according to the procedure of Barlin, G. B. and Yap, C. Y. (Aust. J. Chem. 1977, 30, 2319-2322)] in 500 mL of toluene was refluxed under Dean-Stark conditions for 12 h. The mixture was concentrated, dissolved into chloroform, washed with saturated sodium bicarbonate solution, dried (MgSO4), filtered and concentrated. Medium pressure chromatography (silica gel, 5% methanol in chloroform) afforded methyl 7-acetylamino-10-oxo-10H-pyridazino[6,1-b]-quinazoline-2-carboxylate as a yellow solid, mp 281°-285° C., dec.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[CH3:11][C@@H:12]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[C:13](Cl)=[O:14]>>[CH3:11][C@@H:12]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[C:13]([O:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1)=[O:14]
Reactant: O=C(O)c1ccc(O)cc1
Reactant: CCCCCCCC[C@H](C)C(=O)Cl
Product: CCCCCCCC[C@H](C)C(=O)Oc1ccc(C(=O)O)cc1
Yield: 32.6 %

Procedure:
Using p-hydroxybenzoic acid (3.25 g, 23.5 mmol) and (S)-2-methyldecanoylchloride (4.83 g, 23.6 mmol), the reaction was carried out in the same manner as described in Example 4, (1}, to give 2.35 g of the title compound as white crystals; mp. 92.5°-96.5° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH3:20])[CH2:9][CH2:10][C:11]1[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:21][C:22]([F:75])([F:74])[C:23]1[CH:24]=[C:25]([CH:67]=[C:68]([C:70]([F:73])([F:72])[F:71])[CH:69]=1)[C:26]([N:28]1[CH2:32][C@@:31]([CH2:40][CH2:41][N:42]2[CH2:47][CH2:46][C:45]3([C:55]4[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=4)[CH2:49][C@@H:48]3[O:56][CH2:57][C:58]([N:60]([CH3:66])[CH2:61][CH2:62][CH2:63][NH:64][CH3:65])=[O:59])[CH2:44][CH2:43]2)([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[O:30][CH2:29]1)=[O:27]>>[F:73][C:70]([F:71])([F:72])[C:68]1[CH:67]=[C:25]([CH:24]=[C:23]([C:22]([F:21])([F:75])[F:74])[CH:69]=1)[C:26]([N:28]1[CH2:32][C@@:31]([CH2:40][CH2:41][N:42]2[CH2:43][CH2:44][C:45]3([C:55]4[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=4)[CH2:49][C@@H:48]3[O:56][CH2:57][C:58]([N:60]([CH3:66])[CH2:61][CH2:62][CH2:63][N:64]([CH3:65])[C:15]([C:14]3[CH:13]=[CH:12][C:11]([CH2:10][CH2:9][N:8]([CH3:20])[C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:19][CH:18]=3)=[O:17])=[O:59])[CH2:46][CH2:47]2)([C:33]2[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=2)[O:30][CH2:29]1)=[O:27]
Reactant: CN(CCc1ccc(C(=O)O)cc1)C(=O)OC(C)(C)C
Reactant: CNCCCN(C)C(=O)CO[C@H]1Cc2ccccc2C12CCN(CC[C@@]1(c3ccc(F)cc3)CN(C(=O)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)CO1)CC2
Product: CN(CCCN(C)C(=O)c1ccc(CCN(C)C(=O)OC(C)(C)C)cc1)C(=O)CO[C@H]1Cc2ccccc2C12CCN(CC[C@@]1(c3ccc(F)cc3)CN(C(=O)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)CO1)CC2
Yield: 61.4 %

Procedure:
The compound (140 mg, 0.501 mmol) obtained in Example 50a and the compound (260 mg, 334 mol) obtained in Example 1k were used to give the title compound (320 mg; yield, 92%) as a white solid according to the method described in Example 41a.
Reaction SMILES: C[O:2][C:3]1[CH:27]=[CH:26][C:6]([O:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[N:18]=[C:17]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)[O:16][N:15]=3)=[CH:10][CH:9]=2)=[CH:5][CH:4]=1.B(Br)(Br)Br.O>C(Cl)Cl>[F:25][C:22]1[CH:21]=[CH:20][C:19]([C:17]2[O:16][N:15]=[C:14]([C:11]3[CH:12]=[CH:13][C:8]([O:7][C:6]4[CH:26]=[CH:27][C:3]([OH:2])=[CH:4][CH:5]=4)=[CH:9][CH:10]=3)[N:18]=2)=[CH:24][CH:23]=1
Reactant: COc1ccc(Oc2ccc(-c3noc(-c4ccc(F)cc4)n3)cc2)cc1
Agent: BrB(Br)Br
Solvent: O
Solvent: ClCCl
Product: Oc1ccc(Oc2ccc(-c3noc(-c4ccc(F)cc4)n3)cc2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 99.9 %

Procedure:
3-(4-(4-Methoxyphenoxy)phenyl)-5-(4-fluorophenyl)-1,2,4-oxadiazole (150 mg, 0.414 mmol) was suspended in dry methylene chloride (10.0 mL) and the mixture was placed under nitrogen and cooled to −80 C. Boron tribromide (1.0 M in CH2Cl2, 2.07 mmol) was added dropwise over 10 minutes. The mixture was allowed to warm to room temperature and stirred for 19 hours 30 minutes. The reaction mixture was then cooled to −80 C and H2O (2.0 mL) was added dropwise. The organic layer was removed under reduced pressure and the compound was purified by column chromatography (Hex/EtOAc 2:1) to give a white powder (144 mg, 100%). 1H NMR (500 MHz, DMSO-d6) δ(ppm): 6.83 (2H, d, J=8.8 Hz), 6.98 (2H, d, J=8.8 Hz), 7.04 (2H, t, J=8.8 Hz), 7.49 (2H, t, J=8.8 Hz), 8.03 (2H, d, J=9.0 Hz), 8.23 (2H, dd, J=8.8, 5.4 Hz), 9.49 (1H, s). 13C NMR (125 MHz, DMSO-d6) δ(ppm): 116.5 (CH), 116.9 (CH, d, J=22.5 Hz), 116.9 (CH), 119.7, 121.6 (CH, d, J=3.8 Hz), 121.7 (CH), 129.1, 130.8 (CH, d, J=10.0 Hz), 146.6, 154.5, 161.3, 164.9 (C, d, J=251.2 Hz), 167.8, 174.4. 19F (282 MHz, DMSO-d6) δ(ppm): −105.1-−105.2 (1F, m). MS (FAB+): 348 (MH+). HRMS for C20H13FN2O3 (MH+): calculated: 348.0910; found 348.0897.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[O:11][CH:12]=[C:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[N:14]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].C([O-])([O-])=O.[K+].[K+].Br[CH2:27][CH:28]=[C:29]([CH3:31])[CH3:30]>CC(C)=O>[CH3:8][C:7]1[CH:6]=[CH:5][C:4]([NH:9][C:10]2[O:11][CH:12]=[C:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[N:14]=2)=[CH:3][C:2]=1[O:1][CH2:27][CH:28]=[C:29]([CH3:31])[CH3:30]
Reactant: CCOC(=O)c1coc(Nc2ccc(C)c(O)c2)n1
Reactant: CC(C)=CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)c1coc(Nc2ccc(C)c(OCC=C(C)C)c2)n1
Yield: 30 %

Procedure:
Following the general procedure for O-alkylation, Method A, a mixture of ethyl 2-(3-hydroxy-4-methylphenylamino)oxazole-4-carboxylate (118 mg, 0.45 mmol) and K2CO3 (68 mg, 0.50 mmol) in acetone (4.5 mL) was treated with 4-bromo-2-methyl-2-butene (0.063 mL, 0.54 mmol) at 60° C. Reaction control by TLC showed full conversion after 4 h. The title compound was obtained after purification by flash chromatography on silica gel (hexane:EtOAc 7/3) in 30% yield (45 mg).
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.[CH2:27](I)[CH:28]([CH3:30])[CH3:29]>>[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]([CH2:27][CH:28]([CH3:30])[CH3:29])[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: CC(C)CI
Reactant: COc1cn(CC(=O)OC(C)(C)C)c(=O)cc1-c1cc(Cl)ccc1C#N
Product: COc1cn(C(CC(C)C)C(=O)OC(C)(C)C)c(=O)cc1-c1cc(Cl)ccc1C#N

Procedure:
309 mg (0.80 mmol) of tert-butyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]acetate and 191 mg (1.04 mmol) of isobutyl iodide were reacted according to General Method 7A. Yield: 178 mg (purity 92%, 48% of theory) of product.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:5]=1[OH:11])=[O:3].[CH:12](=O)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[OH-].[Na+].OS(O)(=O)=O>O>[O:3]=[C:2]([C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:5]=1[OH:11])[CH:1]=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CC(=O)c1cc(Cl)ccc1O
Reactant: O=Cc1ccccc1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(C=Cc1ccccc1)c1cc(Cl)ccc1O
Reaction time: 1 h
Yield: 74.8 %

Procedure:
34.1 g of 5-chloro-2-hydroxyacetophenone and 22 g of benzaldehyde were added to a mixture of 180 ml of H2O and 37 g of 50% strength sodium hydroxide solution at room temperature. The mixture was heated to 55°-60° C., with thorough stirring, and was stirred at this temperature for about 1 hour. It was then rendered weakly acid with 25% strength H2SO4 (about 100 ml), with thorough cooling, and the precipitate was filtered off with suction, washed thoroughly with H2O and recrystallized from a 9:1 mixture of methanol and acetone to give 38.7 g of 3-oxo-1-phenyl-3-(2'-hydroxy-5'-chlorophenyl)-propene of melting point 88°-90° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH2:17][OH:18]>>[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH2:17][O:18][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1cnccc1Cl
Reactant: OCc1ccccn1
Product: O=[N+]([O-])c1cnccc1OCc1ccccn1
Yield: 68.3 %

Procedure:
In accordance with the same procedures as in Preparation 2, except for using 4-chloro-3-nitropyridine prepared in Step 1 of Preparation 1 and 2-pyridyl carbinol, the titled compound was obtained as a yellow solid. (Yield: 68.3%)
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][C:9]=1[Cl:10])[NH2:6].N1C=CC=CC=1.[Cl:19][C:20]([Cl:25])([Cl:24])[C:21](Cl)=[O:22]>ClCCl>[Cl:19][C:20]([Cl:25])([Cl:24])[C:21]([NH:6][C:5]1[CH:7]=[CH:8][C:9]([Cl:10])=[C:3]([C:2]([F:1])([F:11])[F:12])[CH:4]=1)=[O:22]
Reactant: O=C(Cl)C(Cl)(Cl)Cl
Reactant: Nc1ccc(Cl)c(C(F)(F)F)c1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(Nc1ccc(Cl)c(C(F)(F)F)c1)C(Cl)(Cl)Cl
Reaction time: 1 h
Yield: 79.1 %

Procedure:
The clear solution of 3-trifluoromethyl-4-chloroaniline (45 g, 0.230 mol) and pyridine (37 ml, 0.460 mol) in dichloromethane (450 ml) cooled at 0° C. to −5° C. and a solution of trichloroacetyl chloride (31 ml, 0.2876 mol) in dichloromethane (100 ml) was added drop wise maintaining temperature of the reaction mass below 0° C. The reaction mass was then stirred for 1 hour below 0° C. and quenched with water (250 ml) below 5° C. The organic phase was separated and aqueous layer was re-extracted with dichloromethane. The combined dichloromethane layer was washed with water, dried over sodium sulfate and evaporated under vacuum to obtain (62 g) of the desired product, i.e., 2,2,2-trichloro-N-(4-chloro-3-(trifluoromethyl)phenyl)acetamide.
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[C:6](=[O:7])[CH:5]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([S:14][CH3:15])=[CH:10][CH:9]=2)[O:3]1.ClC1C=C(C=CC=1)C(OO)=[O:22]>ClCCl>[CH3:1][C:2]1([CH3:16])[C:6](=[O:7])[CH:5]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:15])=[O:22])=[CH:10][CH:9]=2)[O:3]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSc1ccc(C2=CC(=O)C(C)(C)O2)cc1
Solvent: ClCCl
Product: CS(=O)c1ccc(C2=CC(=O)C(C)(C)O2)cc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 107.7 %

Procedure:
To a stirred solution of 2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone (10 g) in 200 ml dichloromethane at 0° C., was added slowly dropwise 4.8 g of m-chloroperoxybenzoic acid (m-CPBA) dissolved in 50 ml dichloromethane. After the reaction mixture was stirred at 0° C. for another two hours, the reaction solution was concentrated in vacuo. The resulting residue was extracted with water and dichloromethane (50 ml×3), followed by washing with aqueous sodium carbonate. The organic layer was concentrated and the crude product was purified by column chromatography (hexane/ethylacetate) to obtain 7.5 g of 2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone as a solid. mp: 108-109° C. NMR: δ1.51 (s, 6H), 2.78 (s, 3H), 6.06 (s, 1H), 7.78 (d, J=8.4 Hz, 2H), 8.02 (d, J=8.4 Hz, 2H). IR (cmu−1): 2925, 1697, 1603, 1558, 1173, 1087, 1049.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[CH:6]=[CH:7][N+:8]([O-:10])=[O:9].[CH2:16]([N:18]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:19](=[S:21])[S-:20])[CH3:17].[NH4+]>>[CH2:16]([N:18]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:19](=[S:20])[S:21][CH:6]([CH2:7][N+:8]([O-:10])=[O:9])[C:5]1[CH:11]=[CH:12][C:13]([O:14][CH3:15])=[C:3]([O:2][CH3:1])[CH:4]=1)[CH3:17]
Reactant: COc1ccc(C=C[N+](=O)[O-])cc1OC
Reactant: CCN(C(=S)[S-])c1ccccc1
Agent: [NH4+]
Product: CCN(C(=S)SC(C[N+](=O)[O-])c1ccc(OC)c(OC)c1)c1ccccc1

Procedure:
Reaction of 3,4-dimethoxy-β-nitrostyrene with ammonium ethyldithiocarbanilate by the above procedure yields 3,4-dimethoxy-α-(nitromethyl)benzyl ethyldithiocarbanilate.
Reaction SMILES: [NH2:1][CH:2]1[C:12]2[C:13]3[C:5](=[C:6]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[NH:7][C:8]=3[CH:9]=[CH:10][CH:11]=2)[CH2:4][CH2:3]1.[C:20](OC(=O)C)(=O)C.C(O)=O>O1CCCC1>[CH3:20][NH:1][CH:2]1[C:12]2[C:13]3[C:5](=[C:6]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[NH:7][C:8]=3[CH:9]=[CH:10][CH:11]=2)[CH2:4][CH2:3]1
Reactant: CC(=O)OC(C)=O
Reactant: NC1CCc2c(-c3ccccc3)[nH]c3cccc1c23
Solvent: C1CCOC1
Solvent: O=CO
Product: CNC1CCc2c(-c3ccccc3)[nH]c3cccc1c23
Reaction time: 0.33 h
Yield: 85 %

Procedure:
A portion (100 mg) of the compound obtained in Example 81 was suspended in tetrahydrofuran (THF; 3 ml) and to the suspension was added a solution (1M; 0.5 ml) of an acid anhydride prepared from acetic anhydride and formic acid in THF at -20° C. The mixture was stirred for 20 minutes. The solid obtained by concentrating the reaction mixture was suspended in THF (3 ml) and to the suspension was added a solution of borane-methyl sulfide complex in THF (10M; 100 μl). The mixture was heated to reflux for 1 hour and allowed to cool. 3N solution (10 ml) of hydrochloric acid in methanol was added to the reaction mixture, followed by stirring for 1 hour at room temperature. The reaction mixture was made basic with 3N aqueous solution of sodium hydroxide and extracted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. Then, the solvent was distilled off under reduced pressure to yield 90 mg (85%) of the titled compound.
Reaction SMILES: [Br:1]Br.[CH3:3][C:4]1[CH:8]=[CH:7][S:6][C:5]=1[CH:9]=[O:10]>C(Cl)(Cl)Cl.C(Cl)Cl>[Br:1][C:7]1[S:6][C:5]([CH:9]=[O:10])=[C:4]([CH3:3])[CH:8]=1
Reactant: Cc1ccsc1C=O
Reactant: BrBr
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: Cc1cc(Br)sc1C=O
Temperature: 25 °C
Yield: 72.7 %

Procedure:
Bromine (104 mL, 2.02 mol) was added dropwise to a 0° C. solution of 255 g of 3-methylthiophene-2-carboxaldehyde (2.02 mol) in 1.7 L of chloroform cooled with an external ice bath. After the addition was complete, the mixture was allowed to slowly warm to room temperature, and then heated at reflux temperature for 2 hours. The red mixture was diluted with 1 L methylene chloride and successively washed with water, saturated bicarbonate solution, and brine. The organic fraction was dried over anhydrous sodium sulfate and concentrated to a red oil. The crude oil was then vacuum distilled to isolate fractions which eluted at 101-106° C. at ca. 2 torr, which produced 301 g of a pale yellow-green solid. 1H NMR (CDCl3, 200 MHz): δ=9.87 (s, 1H), 6.94 (s, 1H) 2.53 (s, 3H).
Reaction SMILES: [C:1]1([S:11]([N:14]2[C:22]3[C:17](=[C:18]([NH2:23])[CH:19]=[CH:20][CH:21]=3)[CH:16]=[CH:15]2)(=[O:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl.Cl[CH2:26][CH2:27][NH:28][CH2:29][CH2:30]Cl.C(N(C(C)C)CC)(C)C>ClC1C=CC=CC=1>[C:1]1([S:11]([N:14]2[C:22]3[C:17](=[C:18]([N:23]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)[CH:19]=[CH:20][CH:21]=3)[CH:16]=[CH:15]2)(=[O:12])=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: Nc1cccc2c1ccn2S(=O)(=O)c1cccc2ccccc12
Reactant: ClCCNCCCl
Agent: Cl
Solvent: Clc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Product: O=S(=O)(c1cccc2ccccc12)n1ccc2c(N3CCNCC3)cccc21
Reaction time: 4 h

Procedure:
A mixture of 461 mg (1.43 mmole) 1-(naphthalene-1-sulfonyl)-1H-indol-4-ylamine, 255 mg (1.43 mmole) bis(2-chloroethyl)amine hydrochloride, and 0.5 mL diisopropylethylamine in 5 mL chlorobenzene was heated under reflux. After 4 hours, 0.25 mL diisopropylethylamine was added and heating under reflux was continued for 15 hours. The mixture was partitioned between 25 mL ethyl acetate and 10 mL 5% sodium hydroxide. The organic phase was washed with 5 mL saturated sodium chloride solution, dried (magnesium sulfate) and concentrated under reduced pressure. The residue was subjected to low pressure column chromatography over silica gel 230-400 mesh eluting with 8% methanol in chloroform. 1-(Naphthalene-1-sulfonyl)-4-piperazin-1-yl-1H-indole (1) was isolated as the hydrochloride salt from ethyl acetate/ether, 54 mg, M+H=392.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=2[CH3:28])[CH2:9]/[C:10](/[C:13]2[CH:14]=[CH:15][C:16](=[O:20])[N:17]([CH3:19])[CH:18]=2)=[N:11]\[OH:12])=[CH:4][CH:3]=1.[NH2:29][C:30]1[CH:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][CH:31]=1>>[NH2:29][C:30]1[CH:31]=[CH:32][C:33]([C:2]2[CH:3]=[CH:4][C:5]([CH:8]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=3[CH3:28])[CH2:9]/[C:10](/[C:13]3[CH:14]=[CH:15][C:16](=[O:20])[N:17]([CH3:19])[CH:18]=3)=[N:11]\[OH:12])=[CH:6][CH:7]=2)=[CH:34][CH:35]=1
Reactant: CC1(C)OB(c2ccc(N)cc2)OC1(C)C
Reactant: Cc1cc(F)ccc1C(C/C(=N\O)c1ccc(=O)n(C)c1)c1ccc(Br)cc1
Product: Cc1cc(F)ccc1C(C/C(=N\O)c1ccc(=O)n(C)c1)c1ccc(-c2ccc(N)cc2)cc1

Procedure:
In analogy to example 166, from (E)-5-(3-(4-bromophenyl)-3-(4-fluoro-2-methylphenyl)-1-(hydroxyimino)propyl)-1-methylpyridin-2(1H)-one (example 224) and 4-aminophenylboronic acid pinacol ester (CAS RN: [214360-73-3]) was prepared the title compound as a light brown foam, MS (ESI+): m/z=456.21 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[N:6]=[C:5]([N:7]2[CH2:12][CH2:11][C:10](=O)[CH2:9][CH2:8]2)[S:4][N:3]=1.[Cl:14][C:15]1[CH:16]=[C:17]([CH:25]=[CH:26][CH:27]=1)[CH2:18][N:19]1[CH:23]=[N:22][C:21]([NH2:24])=[N:20]1>>[Cl:14][C:15]1[CH:16]=[C:17]([CH:25]=[CH:26][CH:27]=1)[CH2:18][N:19]1[CH:23]=[N:22][C:21]([NH:24][CH:10]2[CH2:11][CH2:12][N:7]([C:5]3[S:4][N:3]=[C:2]([CH3:1])[N:6]=3)[CH2:8][CH2:9]2)=[N:20]1
Reactant: Nc1ncn(Cc2cccc(Cl)c2)n1
Reactant: Cc1nsc(N2CCC(=O)CC2)n1
Product: Cc1nsc(N2CCC(Nc3ncn(Cc4cccc(Cl)c4)n3)CC2)n1

Procedure:
Prepared in analogy to example 1 step h) starting from 1-(3-methyl-[1,2,4]thiadiazol-5-yl)-piperidin-4-one (example 1c) and 1-(3-chloro-benzyl)-1H-[1,2,4]triazol-3-ylamine. The title compound was obtained as a colorless oil.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH:2]1[O:4][CH2:3]1.[NH2:12][CH2:13][CH2:14][NH:15][C:16]1[C:25]([CH3:26])=[N:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]=1.O>CN(C)C=O>[O:5]([CH2:1][CH:2]([OH:4])[CH2:3][NH:12][CH2:13][CH2:14][NH:15][C:16]1[C:25]([CH3:26])=[N:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: c1ccc(OCC2CO2)cc1
Reactant: Cc1nc2ccccc2nc1NCCN
Solvent: O
Solvent: CN(C)C=O
Product: Cc1nc2ccccc2nc1NCCNCC(O)COc1ccccc1
Temperature: 40 °C

Procedure:
5.6 g. Phenyl glycidyl ether and 15 g. 2-(2-aminoethylamino)-3-methylquinoxaline are dissolved in a little dimethylformamide and warmed to 40° C. for 32 hours. The reaction mixture is then poured into water, extracted with methylene chloride, dried and purified chromatographically on silica gel in the manner described in Example 25. There are obtained 4.2 g. (33% of theory) of the desired product in the form of a viscous oil.