Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[CH2:5][CH2:6][NH2:7].[S:11]1[CH2:17][C:15](=[O:16])[NH:14][C:12]1=S.CCN(C(C)C)C(C)C>C(#N)C>[F:1][C:2]1[CH:3]=[C:4]([CH2:5][CH2:6][NH:7][C:12]2[S:11][CH2:17][C:15](=[O:16])[N:14]=2)[CH:8]=[CH:9][CH:10]=1
Reactant: NCCc1cccc(F)c1
Reactant: O=C1CSC(=S)N1
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: O=C1CSC(NCCc2cccc(F)c2)=N1
Temperature: 0 °C
Reaction time: 48 h
Yield: 76.6 %

Procedure:
To a solution of 3-fluoro phenethylamine (3.06 g, 22 mmol) and Rhodanine (2.66 g, 20 mmol) in acetonitrile (70 mL) was added DIPEA (7.66 mL, 44 mmol) at room temperature. Then, this solution was cooled to 0° C. and mercuric chloride (5.97 g, 22 mmol) was added in two portions within 10 min. After addition, the suspension was allowed to warm to room temperature and stirred for 2 days. The resulting black solids were filtered through a plug of celite and washed with acetonitrile (1.0 L) and ethyl acetate (500 mL). The combined solvents were removed under the vacuum and the crude residue was dissolved in ethyl acetate (100 mL) and water (100 mL). The two layers were separated and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined extracts were washed with brine solution and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the filtrate was removed under the vacuum and the crude residue was dissolved in acetonitrile (25 mL) at hot condition. After cooling in the refrigerator overnight, the solids were collected by filtration and washed with acetonitrile. After drying in air, 3.65 g (76.6% yield) of 2-[2-(3-fluoro-phenyl)-ethylamino]-thiazol-4-one was isolated as a white solid: HRES(+) m/e calcd for C11H11FN2OS (M+H)+ 239.0649. found 239.0647.
Reaction SMILES: [C:1]([C:3]1([OH:9])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)#[CH:2].I[C:11]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:12]=1/[C:13](=[CH:21]/[C:22]1[NH:23][CH:24]=[CH:25][C:26]=1[O:27][CH3:28])/[C:14](=[O:20])[NH:15]2>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CN(C=O)C.CCN(CC)CC>[OH:9][C:3]1([C:1]#[C:2][C:11]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:12]=2/[C:13](=[CH:21]/[C:22]2[NH:23][CH:24]=[CH:25][C:26]=2[O:27][CH3:28])/[C:14](=[O:20])[NH:15]3)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1
Reactant: COc1cc[nH]c1/C=C1\C(=O)Nc2cccc(I)c21
Reactant: C#CC1(O)CCCCC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COc1cc[nH]c1/C=C1\C(=O)Nc2cccc(C#CC3(O)CCCCC3)c21

Procedure:
Using Method C above, 1-ethynyl-1-cyclohexanol (60 mg, 0.48 mmol) (Aldrich) was coupled with (Z)-1,3-dihydro-4-iodo-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one (146 mg, 0.4 mmol) (Starting Material 2 supra) using (Ph3P)2PdCl2 (20 mg) and CuI (10 mg) as catalyst in DMF (2 mL) and Et3N (2 mL) as solvent at 70° C. for 15 h to yield (Z)-1,3-dihydro-4-[(1-hydroxycyclohexyl)ethynyl]-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one. (Yield 94 mg, 65%).
Reaction SMILES: [O:1]=[O+][O-].C1(C=[CH:11][C@H:12]2[N:15]([Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[C:14](=[O:23])[C@H:13]2[CH2:24][CH2:25][CH2:26][NH:27][C:28]([NH:40][C:41]([O:43][CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[O:42])=[N:29][C:30]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[O:31])C=CC=CC=1>C(Cl)Cl>[CH:11]([C@H:12]1[N:15]([Si:16]([C:19]([CH3:20])([CH3:22])[CH3:21])([CH3:17])[CH3:18])[C:14](=[O:23])[C@H:13]1[CH2:24][CH2:25][CH2:26][NH:27][C:28]([NH:40][C:41]([O:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:42])=[N:29][C:30]([O:32][CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)=[O:31])=[O:1]
Reactant: O=[O+][O-]
Reactant: CC(C)(C)[Si](C)(C)N1C(=O)[C@@H](CCCNC(=NC(=O)OCc2ccccc2)NC(=O)OCc2ccccc2)[C@H]1C=Cc1ccccc1
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)N1C(=O)[C@@H](CCCNC(=NC(=O)OCc2ccccc2)NC(=O)OCc2ccccc2)[C@H]1C=O
Reaction time: 16 h

Procedure:
Ozone was passed through a -78° C. methylene chloride (100 mL) solution of compound 4b (4.73 g, 7.22 mmol) until a blue color was maintained. Excess ozone was purged with nitrogen. Dimethyl sulfide (10 mL) was added. The solution was allowed to stand for 16 h and concentrated to afford the title product which was not further purified but used directly in Step B.
Reaction SMILES: [CH3:1][N:2]([CH3:21])[CH2:3][CH2:4][NH:5][C:6](N1CCN(C2C=CC(F)=CC=2)CC1)=[O:7].C(N1C=CN=C1)(N1C=CN=C1)=O.CN(CCN)C.[CH3:40][O:41][C:42]1[CH:43]=[C:44]([N:52]2[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]2)[CH:45]=[C:46]([O:50][CH3:51])[C:47]=1[O:48][CH3:49].[ClH:58]>O1CCCC1>[ClH:58].[CH3:1][N:2]([CH3:21])[CH2:3][CH2:4][NH:5][C:6]([N:55]1[CH2:56][CH2:57][N:52]([C:44]2[CH:43]=[C:42]([O:41][CH3:40])[C:47]([O:48][CH3:49])=[C:46]([O:50][CH3:51])[CH:45]=2)[CH2:53][CH2:54]1)=[O:7]
Reactant: CN(C)CCNC(=O)N1CCN(c2ccc(F)cc2)CC1
Reactant: COc1cc(N2CCNCC2)cc(OC)c1OC
Agent: CN(C)CCN
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: COc1cc(N2CCN(C(=O)NCCN(C)C)CC2)cc(OC)c1OC
Yield: 56 %

Procedure:
This compound was prepared according to the procedure used to synthesize the compound of Example 11. A mixture of 2.4 g (0.015 mole) of 1,1'-carbonyldiimidazole, 13 g (0.015 mole) of unsym-dimethylethylenediamine and 3.8 g (0.025 mole) of 1-(3,4,5-trimethoxyphenyl)piperazine in a total volume of 100 ml of tetrahydrofuran gave an oil as residue. The hydroxhloride was formed in ethereal hydrogen chloride and the collected solid was recrystallized from methanol-ethyl ether to yield 3.7 g (56%) of the title compound as a white solid, m.p. 205°-208° C.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[OH:34][CH2:35][C@@H:36]1[CH2:40][CH2:39][CH2:38][N:37]1[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42].[S:48]1[CH:52]=[CH:51][C:50]2[CH:53]=[C:54](O)[CH:55]=[CH:56][C:49]1=2.C(N(CC)CC)C>ClCCl>[S:48]1[CH:52]=[CH:51][C:50]2[CH:53]=[C:54]([O:34][CH2:35][C@@H:36]3[CH2:40][CH2:39][CH2:38][N:37]3[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH:55]=[CH:56][C:49]1=2
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1CO
Reactant: Oc1ccc2sccc2c1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC[C@H]1COc1ccc2sccc2c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Polystyrene supported triphenylphosphine (2.9 mmol/g, 1.70 g, 4.95 mmol) was treated with diisopropylazodicarboxylate (0.779 mL, 3.96 mmol) at 0° C. in anhydrous dichloromethane. A mixture of (S)-tert-butyl 2-(hydroxymethyl)pyrrolidine-1-carboxylate (0.5 g, 3.3 mmol), benzo[b]thiophen-5-ol (0.5 g, 3.3 mmol) and triethylamine (0.689 mL, 4.95 mmol) in dichloromethane (5 mL) was then added to the reaction. The mixture was then allowed to warm up to room temperature and stirred overnight. The reaction was then filtered off and the filtrate purified by column chromatography on silica gel using a gradient of 15 to 50% ethyl acetate in hexanes to obtain a clear oil that solidied into an off-white solid on standing. Yield=0.48 g. MS (M+H)+ 334.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([OH:13])=O.[NH2:14][C:15]([NH2:17])=[O:16]>S(Cl)(Cl)=O>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([NH:14][C:15]([NH2:17])=[O:16])=[O:13]
Reactant: O=C(O)c1ccc2ccccc2c1
Reactant: NC(N)=O
Solvent: O=S(Cl)Cl
Product: NC(=O)NC(=O)c1ccc2ccccc2c1
Yield: 69.5 %

Procedure:
The above compound was prepared, following the procedure of Example 14a from 2-napthoic acid (8.2 g, 47.7 mmol), thionyl chloride (40 ml) and urea (10 g, 167 mmol) to give the title compound (7.1 g), mp 207°-208° C.
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1.[CH2:12]([N:19]=[C:20]=[O:21])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]>CN(C)C1C=CN=CC=1.C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:20]([NH:19][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[O:21])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1
Reactant: CCCCCCCN=C=O
Reactant: Nc1ccc(F)cc1[N+](=O)[O-]
Agent: CN(C)c1ccncc1
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: CCCCCCCNC(=O)Nc1ccc(F)cc1[N+](=O)[O-]
Reaction time: 5 h
Yield: 65.7 %

Procedure:
4-fluoro-2-nitroaniline (1.56 g), heptyl isocyanate (1.41 g) and 4-dimethylaminopyridine (0.37 g) were stirred in toluene (5 ml) at 80°-90 C. for 5 hrs. This solution was diluted with ethyl acetate, washed with 1N hydrochloric acid, sodium hydrogen carbonate solution, water and saturated saline, dried over anhydrous MgSO4, and the solvent was distilled off. The resulted crystals were washed with hexane to give 1-(4-fluoro-2-nitrophenyl)-3-heptylurea (1.95 g, 66%).
Reaction SMILES: Br[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([F:9])=[CH:4][N:3]=1.CCN(CC)CC.C[CH2:18][O:19][C:20](C)=[O:21]>CO.ClCCl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:18][O:19][C:20]([C:2]1[C:7]([CH3:8])=[CH:6][C:5]([F:9])=[CH:4][N:3]=1)=[O:21]
Reactant: CCOC(C)=O
Reactant: Cc1cc(F)cnc1Br
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Solvent: CO
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)c1ncc(F)cc1C
Reaction time: 20 h

Procedure:
To a solution of 2-bromo-5-fluoro-3-methyl-pyridine (4.90 g) in AcOEt (100 ml) and MeOH (10 ml) was subsequently added NEt3 (5.4 ml) and 1,1′-bis(diphenylphosphino) ferrocene-palladium(II)dichloride dichloromethane adduct (490 mg) and the mixture was carbonylated at 100 bar CO and 110° C. for 20 h. The mixture was evaporated and the residue purified by chromatography on silica gel using n-heptane/AcOEt (7:1) to give the title compound (3.44 g) as a pale red solid. MS: m/z=170.1 [M+H]+.
Reaction SMILES: C[Al](C)C.[Cl-].[NH4+:6].[Cl:7][C:8]1[CH:16]=[C:15]2[C:11]([C:12]([C:26]#[N:27])=[N:13][N:14]2[CH2:17][CH2:18][C:19]([F:25])([F:24])[C:20]([F:23])([F:22])[F:21])=[CH:10][CH:9]=1.CO>C1(C)C=CC=CC=1>[Cl:7][C:8]1[CH:16]=[C:15]2[C:11]([C:12]([C:26](=[NH:6])[NH2:27])=[N:13][N:14]2[CH2:17][CH2:18][C:19]([F:25])([F:24])[C:20]([F:21])([F:23])[F:22])=[CH:10][CH:9]=1
Reactant: N#Cc1nn(CCC(F)(F)C(F)(F)F)c2cc(Cl)ccc12
Reactant: [NH4+]
Agent: C[Al](C)C
Agent: [Cl-]
Solvent: CO
Solvent: Cc1ccccc1
Product: N=C(N)c1nn(CCC(F)(F)C(F)(F)F)c2cc(Cl)ccc12
Temperature: 0 °C
Reaction time: 3 h

Procedure:
Trimethylaluminum (2.0M in toluene, 23.17 mL, 46.3 mmol) was added dropwise to a suspension of ammonium chloride (2.49 g, 46.5 mmol) in 69 mL toluene cooled to 0° C. The solution was then stirred at room temperature for 3 hours. This solution was then added to the intermediate from Step D (3.0 g, 9.27 mmol) and then heated at 110° C. for 6 hours. The solution was then cooled to room temperature and carefully poured to silica gel (ca 150 mL) and methanol (ca 250 mL). After stirring for 1.5 hours the suspension was filtered and the filtrate concentrated to give the indicated product which was used in the next step without further purification. 1H NMR (400 MHz, CH3 CN-d3): selected peaks δ 8.26 (d, J=8.7 Hz, 1H); 7.70 (d, J=1.7 Hz, 1H); 7.24 (dd, J=8.7, 1.8 Hz, 1H); 4.67 (t, J=7.1 Hz, 2H); 3.01-2.78 (m, 2H). m/z=341.1 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[C:8](C(O)=O)[CH2:9][O:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:30])C=CC=CC=1.Cl>ClCCl.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][C:8](=[O:30])[CH2:9][O:10]2)=[CH:5][CH:4]=1
Reactant: COc1ccc2c(c1)OCC(C(=O)O)=C2
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Agent: Cl
Solvent: Cc1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc2c(c1)OCC(=O)C2
Temperature: 60 °C
Reaction time: 1.5 h
Yield: 28 %

Procedure:
7-Methoxy-2H-chromene-3-carboxylic acid (6.07 g, 29.44 mmol) and triethylamine (4.8 ml, 34.48 mmol) were dissolved in dichloromethane (60 ml). Diphenylphosphoryl azide (6.54 ml, 29.44 mmol) was dissolved in toluene (24 ml) and added dropwise to the reaction mixture while slowly increasing the temperature to 60° C. 60 ml of toluene were added and the reaction mixture was stirred at 70° C. for 90 minutes. A 10 molar HCl solution (28 ml) was then added and the reaction mixture was stirred at reflux for 2 hours. After cooling to room temperature the phases were separated. The organic phase was extracted with an aq. NaHCO3 solution. The organic layer was dried over magnesium sulfate, filtered, and the solvent evaporated under reduced pressure. The crude product was purified by chromatography using silica gel with cyclohexane/ethyl acetate (100:0 to 95:5) as eluent, yielding the title product (1.47 g, 24% yield).
Reaction SMILES: [I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[CH3:9][N:10]([CH:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25](=[O:27])[CH3:26])[CH2:20][CH2:19]1)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14].O>CS(C)=O>[CH3:9][N:10]([CH:18]1[CH2:19][CH2:20][N:21]([CH2:24][C:25]2([CH3:2])[CH2:26][O:27]2)[CH2:22][CH2:23]1)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:14])[CH3:15]
Reactant: CC(=O)CN1CCC(N(C)C(=O)OC(C)(C)C)CC1
Reactant: C[S+](C)(C)=O
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CN(C(=O)OC(C)(C)C)C1CCN(CC2(C)CO2)CC1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 86.9 %

Procedure:
Trimethylsulfoxonium iodide (1.96 g, 8.89 mmol) was gradually added to a suspension of sodium hydride (372 mg, 9.32 mmol) in dimethylsulfoxide (20 ml), and the mixture was stirred at room temperature for 1.5 hours. To which a solution of tert-butyl N-methyl-[1-(2-oxopropyl)piperidin-4-yl]carbamate (2.3 g, 8.5 mmol) in dimethylsulfoxide (20 ml) was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into iced water, and extracted with diethyl ether. The extract was washed with a saturated saline solution, dried over magnesium sulfate, and then filtered. The resultant filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1) to afford tert-butyl N-methyl-[1-(2-methyl-2-oxiranylmethyl)piperidin-4-yl]carbamate (2.1 g, yield 86%) as a light yellow oily material.
Reaction SMILES: [C:1]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:6]=[CH:5][C:4]([C:7]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:16][CH:15]=2)=[CH:8]/[CH:9]=[CH:10]/[C:11]([OH:13])=[O:12])=[CH:3][CH:2]=1.[N+:32]([C:35]1[CH:40]=[CH:39][C:38](O)=[CH:37][CH:36]=1)([O-:34])=[O:33].C1(N=C=NC2CCCCC2)CCCCC1>ClCCl>[N+:32]([C:35]1[CH:40]=[CH:39][C:38]([O:12][C:11](=[O:13])/[CH:10]=[CH:9]/[CH:8]=[C:7]([C:4]2[CH:5]=[CH:6][C:1]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[CH:2][CH:3]=2)[C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:16][CH:15]=2)=[CH:37][CH:36]=1)([O-:34])=[O:33]
Reactant: O=[N+]([O-])c1ccc(O)cc1
Reactant: O=C(O)/C=C/C=C(c1ccc(-c2ccccc2)cc1)c1ccc(-c2ccccc2)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Product: O=C(/C=C/C=C(c1ccc(-c2ccccc2)cc1)c1ccc(-c2ccccc2)cc1)Oc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 100.5 %

Procedure:
As in Example 115, a solution of (E)-5,5-bis [(1,1'-biphenyl)-4-yl]-2,4-pentadienoic acid (0.673 g) and 4-nitrophenol (0.256 g) in dichloromethane (7 mL) was treated with 1,3-dicyclohexylcarbodiimide (0.345 g). The mixture was stirred at room temperature for 1.5 hours. The usual work up furnished 0.88 g of (E)-5,5-bis[(1,1'-biphenyl)-4-yl]-2,4-pentadienoic acid 4-nitrophenyl ester.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[SH:9].Br[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-])=O)[CH:13]=1.[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[C:24]([F:32])[CH:23]=1>>[NH2:18][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=1)[CH2:11][S:9][C:3]1[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=1[NH:1][S:28]([C:25]1[CH:26]=[CH:27][C:22]([Cl:21])=[CH:23][C:24]=1[F:32])(=[O:30])=[O:29]
Reactant: Nc1cc(Cl)ccc1S
Reactant: O=[N+]([O-])c1cccc(CBr)c1
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1F
Product: Nc1cccc(CSc2ccc(Cl)cc2NS(=O)(=O)c2ccc(Cl)cc2F)c1

Procedure:
Following General Procedure A, B, and K, the title compound was prepared from 2-amino-4-chloro-benzenethiol, 1-bromomethyl-3-nitro-benzene, and 4-chloro-2-fluoro-benzenesulfonyl chloride.
Reaction SMILES: [C:1]1([SH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1CCN2C(=NCCC2)CC1.[CH3:19][C@H:20]1[CH2:25][O:24][CH2:23][CH2:22][N:21]1[C:26]1[CH:31]=[C:30]([CH2:32]OS(C)(=O)=O)[N:29]=[C:28]([C:38]2[CH:43]=[CH:42][C:41]([NH:44][C:45]([NH:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[O:46])=[CH:40][CH:39]=2)[N:27]=1>C(#N)C>[CH3:19][C@H:20]1[CH2:25][O:24][CH2:23][CH2:22][N:21]1[C:26]1[CH:31]=[C:30]([CH2:32][S:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:29]=[C:28]([C:38]2[CH:39]=[CH:40][C:41]([NH:44][C:45]([NH:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[O:46])=[CH:42][CH:43]=2)[N:27]=1
Reactant: Sc1ccccc1
Reactant: C[C@H]1COCCN1c1cc(COS(C)(=O)=O)nc(-c2ccc(NC(=O)Nc3ccccc3)cc2)n1
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Product: C[C@H]1COCCN1c1cc(CSc2ccccc2)nc(-c2ccc(NC(=O)Nc3ccccc3)cc2)n1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Thiophenol (0.029 mL) was dissolved in Acetonitrile (3 mL). DBU (0.043 mL) was then added to the solution and was allowed to stir at RT for 15 minutes. 1-[4-[4-[(3S)-3-Methylmorpholin-4-yl]-6-(methylsulfonyloxymethyl)pyrimidin-2-yl]phenyl]-3-phenyl-urea (80 mg) was added to the reaction and stirred for 30 minutes. The reaction was concentrated in vacuo and the residue chromatographed on silica, eluting with 5% methanol in DCM, to give the desired material (62 mg) as a white solid, Mass Spectrum; M+H+ 512.
Reaction SMILES: [CH3:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][CH:5]=[CH:4][C:3]=1[NH:11][S:12]([CH3:15])(=[O:14])=[O:13].O.O.[Sn](Cl)Cl.C(=O)(O)[O-].[Na+]>C(O)C.C(OCC)(=O)C>[NH2:8][C:7]1[C:2]([CH3:1])=[C:3]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:4]=[CH:5][CH:6]=1
Reactant: Cc1c(NS(C)(=O)=O)cccc1[N+](=O)[O-]
Agent: Cl[Sn]Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: O
Product: Cc1c(N)cccc1NS(C)(=O)=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 76.6 %

Procedure:
A mixture of N-(2-methyl-3-nitro-phenyl)-methanesulfonamide (1.5 g) and tin(II) chloride dihydrate (7.4 g) in ethanol (15 mL) and ethyl acetate (15 mL, from Burdick and Jackson, Muskegon, Mich.) was stirred at room temperature overnight. The reaction mixture was treated with saturated sodium bicarbonate solution to pH>9. The mixture was filtered and the filtrate was washed with water and brine. After drying over anhydrous sodium sulfate and evaporation of solvent, N-(3-amino-2-methyl-phenyl)-methanesulfonamide (1 g) was obtained.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[C:12]([O:21][CH3:22])[CH:13]=[C:14]3[CH2:20][CH2:19][CH2:18][CH2:17][C:15]3=2)[CH:10]=[C:9]1[CH2:23][CH3:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(Br)(Br)Br.C(=O)([O-])[O-].[Cs+].[Cs+].BrC[C:37]([O:39][CH3:40])=[O:38]>C(Cl)Cl.O>[CH3:40][O:39][C:37](=[O:38])[CH2:22][O:21][C:12]1[CH:13]=[C:14]2[CH2:20][CH2:19][CH2:18][CH2:17][C:15]2=[C:16]2[C:11]=1[CH:10]=[C:9]([CH2:23][CH3:24])[N:8]2[CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)CBr
Reactant: CCc1cc2c(OC)cc3c(c2n1Cc1ccccc1)CCCC3
Agent: BrB(Br)Br
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: ClCCl
Solvent: O
Product: CCc1cc2c(OCC(=O)OC)cc3c(c2n1Cc1ccccc1)CCCC3
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 63.4 %

Procedure:
A solution of 1-benzyl-2-ethyl-4-methoxy-6,7,8,9-tetrahydro-1H-benz[g]indole (660 mg, 2.07 mmol) in methylene chloride (10 mL) was cooled to 0° C. and treated with boron tribromide (0.38 mL, 4.0 mmol). The mixture was stirred for 10 min, poured into ice water, and extracted twice with methylene chloride. The combined methylene chloride layers were washed once with saturated sodium bicarbonate solution, dried (sodium sulfate), filtered, and concentrated in vacuo. The residue was dissolved in N,N-dimethylformamide (10 mL) and treated with cesium carbonate (652 mg, 2.00 mmol) and methyl bromoacetate (0.28 mL, 2.0 mmol) at room temperature for 3 h. The mixture was diluted with water and extracted three times with ether. The combined ether extracts were washed once with water, dried (magnesium sulfate), filtered, and concentrated in vacuo. Chromatography (silica gel, methylene chloride) provided 479 mg (62%) of the title compound as an off-white solid. 1H NMR (CDCl3) δ 7.25 (m, 3H), 6.85 (d, J=7.6 Hz, 2H), 6.52 (s, 1H), 6.16 (s, 1H), 5.57 (s, 2H), 4.79 (s, 2H), 3.86 (s, 3H), 2.97 (m, 2H), 2.84 (m, 2H), 2.59 (q, J=7.3 Hz, 2H), 1.72 (m, 4H), 1.32 (t, J=7.3 Hz, 3H); MS ES+ m/e 378 (p+1); IR (CHCl3, cm1) 2830, 1756, 1732.
Reaction SMILES: [CH:1](=O)/[CH:2]=[CH:3]/[CH3:4].[C:6]1([S:12]([C:15]#[N:16])(=[O:14])=[O:13])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.B(OCCCC)(OCCCC)OCCCC>C1(C)C=CC=CC=1>[C:6]1([S:12]([C:15]2[CH:4]=[CH:3][CH:2]=[CH:1][N:16]=2)(=[O:13])=[O:14])[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: C/C=C/C=O
Reactant: N#CS(=O)(=O)c1ccccc1
Agent: CCCCOB(OCCCC)OCCCC
Solvent: Cc1ccccc1
Product: O=S(=O)(c1ccccc1)c1ccccn1
Temperature: 110 °C
Yield: 86.9 %

Procedure:
First, 8.20 g (115 mmol) of crotonaldehyde and 9.55 g (57.2 mmol) of benzenesulfonyl cyanide were introduced to the same reaction vessel as in Example 1. Toluene (15 ml) was added as the solvent, and 1.33 g (5.78 mol) of tributyl borate was added. Then the mixture was heated under reflux for 3 hours while agitating at an internal temperature of 110° C. in a nitrogen atmosphere, separating and removing water that was produced. After this solution was cooled to room temperature, the low-boiling components, such as solvent, etc., were removed under reduced pressure and the resulting concentrate was cooled in an ice bath to precipitate crystals. The crystals were filtered with a glass filter and washed with 10 ml of toluene that had been cooled to 5° C. or lower. Then the crystals were dried for 2 hours in vacuo to give 10.9 g of 2-benzenesulfonylpyridine as colorless crystals (purity of 98%, yield of 85% based on benzenesulfonyl cyanide).
Reaction SMILES: C([O:9][CH2:10][C@H:11]1[O:15][C@@H:14]([C:16]2[S:17][CH:18]=[C:19]([C:21](OCC)=[O:22])[N:20]=2)[C@H:13]([OH:26])[C@@H:12]1[OH:27])(=O)C1C=CC=CC=1.[NH3:28]>C(O)C>[C@@H:14]1([C:16]2[S:17][CH:18]=[C:19]([C:21]([NH2:28])=[O:22])[N:20]=2)[O:15][C@H:11]([CH2:10][OH:9])[C@@H:12]([OH:27])[C@H:13]1[OH:26]
Reactant: CCOC(=O)c1csc([C@@H]2O[C@H](COC(=O)c3ccccc3)[C@@H](O)[C@H]2O)n1
Reactant: N
Solvent: CCO
Product: NC(=O)c1csc([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)n1
Temperature: 25 °C
Reaction time: 12 h
Yield: 90 %

Procedure:
Ethyl 2-(5′-O-Benzoyl-β-D-ribofuiranosyl)thiazole-4-carboxylate (11, 3.7 g, 942 mmol) was placed in a steel bomb and mixed with freshly prepared cold methanolic ammonia (70 ml, saturated at 0° C. The mixture was protected from moisture and stirred at room temperature for 12 hr. The steel bomb was cooled to 0° C., opened carefully and evaporated to a sticky foam. The residue was triturated with dry toluene (3×50 ml) and the toluene layer was discarded. The residue that obtained was treated with anhydrous ethanol (60 ml) and triturated to give light yellow solid. The solid was filtered, washed with ethyl acetate and dried. The solid was crystallized from ethanol-ethyl acetate to provide 2.25g (90%) of pure product: mp 145-147° C. 1H NMR (DMSO-d6): δ 3.57 (M,2 H), 3.89) (s,2 H), 4.07(m, 1 H), 4.83 (t, 1H), 4.92 (d, 1H), 5.05 (d, 1 H), 5.36 (d, 1 H), 7.56 (s, 1), 7.69 (s, 1) and 8.20 (s,1).
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]1=[O:10].[Cl:11][C:12]([O:15]C(Cl)=O)(Cl)Cl>O1CCCC1>[O:10]=[C:2]1[N:3]([C:12]([Cl:11])=[O:15])[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[NH:1]1
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Reactant: O=c1[nH]c2ccccc2[nH]1
Solvent: C1CCOC1
Product: O=C(Cl)n1c(=O)[nH]c2ccccc21

Procedure:
It was prepared by suspending 5 g of 2,3-dihydro-1H-benzimidazole-2-one in 200 ml of distilled tetrahydrofuran and by adding 13.5 ml of trichloromethylchloroformate. The reaction mixture was refluxed fro 3 hrs until a clear solution was obtained. After cooling the separated solid was removed by filtration and after concentration to dryness of the mother liquors 6.5 g of the title compound were obtained. M.p. 188°-190° C. (dec.).