Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11].C(=O)([O-])[O-].[K+].[K+].[CH3:19][C:20]1[CH:21]=[C:22]([OH:27])[CH:23]=[C:24]([CH3:26])[CH:25]=1>C1COCC1>[CH3:19][C:20]1[CH:21]=[C:22]([CH:23]=[C:24]([CH3:26])[CH:25]=1)[O:27][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11]
Reactant: Cc1cc(C)cc(O)c1
Reactant: N#Cc1ccc(Cl)c([N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: Cc1cc(C)cc(Oc2ccc(C#N)cc2[N+](=O)[O-])c1
Temperature: 25 °C
Yield: 85.2 %

Procedure:
To a solution of 4-chloro-3-nitrobenzonitrile (12.00 g, 65.75 mmol) in THF was added potassium carbonate (45.58 g, 328.70 mmol) and 3,5-dimethylphenol (9.658 g, 78.88 mmol). The reaction mixture was refluxed for 17 hrs, whereupon the starting material was consumed (TLC, 25% EtOAc in hexanes). The reaction mixture was then cooled to room temperature, and potassium carbonate was filtered and washed with copious amounts of EtOAc. The filtrate was washed sequentially with saturated sodium bicarbonate solution, water, and saturated sodium chloride solution, dried over anhydrous MgSO4, filtered, and concentrated in vacuo to give the crude product as a yellow solid. The solid was triturated with hexanes and filtered to afford compound 21 as a whitish-yellow powder. (15.022 g, 85.2% yield, 100% HPLC purity). 1H NMR (500 MHz, DMSO-d6): δ 8.65 (d, J=2 Hz, 1H), 8.06 (dd, J1=9 Hz, J2=2 Hz, 1H), 7.12 (d, J=9 Hz, 1H), 6.97 (s, 1H), 6.84 (s, 2H), 2.29 (s, 6H).
Reaction SMILES: [CH:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1)=[O:2].[CH3:12][N:13]([CH3:17])[CH2:14][CH2:15][NH2:16].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:12][N:13]([CH3:17])[CH2:14][CH2:15][NH:16][C:7](=[O:9])[C:6]1[CH:5]=[CH:4][C:3]([CH:1]=[O:2])=[CH:11][CH:10]=1
Reactant: O=Cc1ccc(C(=O)O)cc1
Reactant: CN(C)CCN
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: CN(C)c1ccncc1
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: CN(C)CCNC(=O)c1ccc(C=O)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 4-formylbenzoic acid (24) (300 mg, 1.99 mmol) in DCM (4 mL) were added N,N-dimethylethane-1,2-diamine (193.8 mg, 2.19 mmol), HATU (911.8 mg, 2.4 mmol), NMM (505 mg, 5.0 mmol), and DMAP (24 mg, 0.199 mg) at RT. The reaction mixture was stirred at RT for 16 h. The reaction was monitored by LCMS. After 16 h, RM was washed with water and organic layer was concentrated after drying over Na2SO4. Column purification of crude material afforded pure product as oil.
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[F:5][C:6]1[CH:21]=[CH:20][C:9]2[C:10](=O)[C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[CH:13]=[CH:14][C:8]=2[CH:7]=1.O.C(Cl)Cl>O1CCCC1>[F:5][C:6]1[CH:21]=[CH:20][C:9]2[CH2:10][C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[CH:13]=[CH:14][C:8]=2[CH:7]=1
Reactant: O=c1c2ccccc2ccc2cc(F)ccc12
Agent: [Al+3]
Agent: [Cl-]
Solvent: C1CCOC1
Solvent: O
Solvent: ClCCl
Product: Fc1ccc2c(c1)C=Cc1ccccc1C2
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 95.9 %

Procedure:
LiA1H4 (0.0686 mol) was added dropwise to a suspension of AlCl3 (0.0718 mol) in tetrahydrofuran (75 ml), cooled on an ice-bath and under N2 atmosphere. The mixture was stirred for 10 minutes at 0° C. A solution of 2-fluoro-5H-dibenzo[a,d]cyclohepten-5-one (0.0653 mol and prepared as described in DE 3,644,462) in tetrahydrofuran (75 ml) was added dropwise and the resulting reaction mixture was allowed to warm to room temperature. Then, the reaction mixture was stirred and refluxed for 2 hours. The mixture was cooled on an ice-bath. Water and CH2Cl2 was added. The organic layer was washed with a saturated aqueous NaHCO3 solution, dried, filtered and the solvent was evaporated, yielding 13.16 g (96%) of 2-fluoro-5H-dibenzo[a.d]cycloheptene (intermediate 1)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH2:11][NH2:12].[CH3:13][O:14][C:15](=[O:23])[C:16](=[CH2:22])[CH2:17][C:18](OC)=[O:19]>CO>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH2:11][N:12]1[C:18](=[O:19])[CH2:17][CH:16]([C:15]([O:14][CH3:13])=[O:23])[CH2:22]1
Reactant: C=C(CC(=O)OC)C(=O)OC
Reactant: COc1ccc(CN)c(OC)c1
Solvent: CO
Product: COC(=O)C1CC(=O)N(Cc2ccc(OC)cc2OC)C1
Temperature: 30 °C
Reaction time: 10 h

Procedure:
The mixture of 1-(2,4-dimethoxyphenyl)methanamine (5.2 g, 32 mmol) and 2-methylene-succinic acid dimethyl ester (5.0 g, 32 mmol) in MeOH (200 mL) was stirred at 30° C. for 10 hours. The solvent was removed under reduced pressure. The residue was recrystallized by petroleum ether to afford compound methyl 1-(2,4-dimethoxybenzyl)-5-oxopyrrolidine-3-carboxylate. 1H NMR (400 MHz, CDCl3) δ 7.13˜7.14 (m, 1H), 6.43-6.45 (m, 2H), 4.41-4.42 (m, 2H), 3.79-3.82 (m, 6H), 3.69 (s, 3H), 3.46-3.49 (m, 2H), 3.19-3.23 (m, 2H), 2.70-2.77 (m, 1H). MS ESI calc'd. for C15H20NO5 [M+H]+ 294. found 294.
Reaction SMILES: [CH:1]1([N:7]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[C:8]([NH:10][C:11]2[S:12][C:13]([CH:16]=O)=[CH:14][N:15]=2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(=O)C.[NH:28]1[CH2:33][CH2:32][S:31][CH2:30][CH2:29]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH:1]1([N:7]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[C:8]([NH:10][C:11]2[S:12][C:13]([CH2:16][N:28]3[CH2:33][CH2:32][S:31][CH2:30][CH2:29]3)=[CH:14][N:15]=2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=Cc1cnc(NC(=O)N(C2CCCCC2)C2CCCCC2)s1
Reactant: C1CSCCN1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Product: O=C(Nc1ncc(CN2CCSCC2)s1)N(C1CCCCC1)C1CCCCC1
Yield: 9.2 %

Procedure:
Prepared as described in general procedure (P) using 1,1-dicyclohexyl-3-(5-formyl-thiazol-2-yl)-urea (60 mg. 0.18 mmol), acetic acid (11 μL, 0.18 mmol), thiomorpholine (21 μL, 0.22 mmol) and sodium triacetoxyborohydride (38 mg, 0.20 mmol) to afford 7 mg (9%) of the desired product after purification.
Reaction SMILES: O.ON1C2C=CC=CC=2N=N1.[CH:12]1([NH2:15])[CH2:14][CH2:13]1.Cl.C(N=C=NCCCN(C)C)C.[CH2:28]([O:35][C:36]([N:38]1[CH2:42][C@@H:41]([OH:43])[C@H:40]([C:44](O)=[O:45])[CH2:39]1)=[O:37])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>O1CCCC1>[CH:12]1([NH:15][C:44]([C@H:40]2[C@H:41]([OH:43])[CH2:42][N:38]([C:36]([O:35][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:37])[CH2:39]2)=[O:45])[CH2:14][CH2:13]1
Reactant: NC1CC1
Reactant: O=C(O)[C@@H]1CN(C(=O)OCc2ccccc2)C[C@H]1O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: C1CCOC1
Product: O=C(NC1CC1)[C@@H]1CN(C(=O)OCc2ccccc2)C[C@H]1O
Temperature: 25 °C
Yield: 48.9 %

Procedure:
17.9 g of 1-hydroxybenzotriazole hydrate (117 mmol), 16.9 mL of cyclopropylamine (244 mmol) and 22.4 g of 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (117 mmol) were successively added to a solution of (3R,4S)-1-benzyloxycarbonyl-4-hydroxypyrrolidine-3-carboxylic acid (25.9 g, 97.5 mmol) in 259 mL of dehydrated tetrahydrofuran under stirring at room temperature. The mixture was further stirred at room temperature for 5 hours. Subsequently, the reaction mixture was concentrated under reduced pressure, followed by addition of 130 mL of ethyl acetate and 260 mL of 1 mol/L hydrochloric acid and subsequent stirring for 30 minutes. The resulting crystals were collected by filtration and washed with 26 mL of ethyl acetate. The organic layer was collected and washed with 130 mL of a 10% aqueous sodium bicarbonate solution and 130 mL of 28% brine. To this layer, 39.0 g of anhydrous sodium sulfate was added and the mixture was stirred for 1 hour. The insoluble material was separated by filtration and washed with 52 mL of ethyl acetate. The filtrate was concentrated under reduced pressure. To the resulting residue, 156 mL of diisopropyl ether was added and the product was tritulated. The precipitated powder was collected by filtration and washed with 39 mL of diisopropyl ether. The washed product was dried by air-blowing at room temperature for 30 minutes. 25.6 g of the resulting crystals were added to 308 mL of ethyl acetate. The mixture was heated at an external temperature of 80° C. for 25 minutes under stirring, then allowed to cool in the air for 40 minutes under stirring, then cooled in a water bath for 5 minutes under stirring at an internal temperature of 40° C., and then stirred at room temperature for 5 minutes at an internal temperature of 25° C. The precipitated powder was collected by filtration and washed with 52 mL of diisopropyl ether. The washed product was dried for 1 hour by air-blowing. Further drying the product by air-blowing at 60° C. for 16 hours gave 14.5 g of the title compound as fluffy colorless crystals (43% yield in the 3 steps).
Reaction SMILES: CN([CH:4]=[O:5])C.CN(C)[CH:8]=[O:9].CN([C:14]1[CH:15]=CN=C[CH:19]=1)C.CN(C1C=[CH:27][CH:26]=[CH:25]N=1)C>CS(C)=O.CS(C)=O>[CH2:19]1[CH2:4][O:5][CH2:15][CH2:14]1.[O:9]1[CH2:8][CH2:27][CH2:26][CH2:25]1
Reactant: CN(C)c1ccncc1
Reactant: CN(C)c1ccccn1
Reactant: CN(C)C=O
Solvent: CS(C)=O
Product: C1CCOC1

Procedure:
DMF—dimethylformamide; DMSO—dimethylsulphoxide; DMAP—dimethylaminopyridine.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][C:4]2([C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH2:8][CH2:7]2)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].I[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]>CN(C=O)C>[CH2:22]([N:1]1[CH2:6][CH2:5][C:4]2([C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH2:8][CH2:7]2)[CH2:3][CH2:2]1)[CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]
Reactant: c1ccc2c(c1)CCC21CCNCC1
Reactant: CCCCCCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCN1CCC2(CCc3ccccc32)CC1
Yield: 52.6 %

Procedure:
In the same way as that described in Example 1, step 5, the title compound was synthesised using spiro[indane-1,4'-piperidine] (0.4 g, 2.2 mmol), DMF (15 ml), potassium carbonate (0.33 g, 2.4 mmol) and iodohexane (0.62 g, 2.9 mmol). The crude residue was chromatographed in 1:1 petrol:ether to give 1'-hexylspiro[indane-1,4'-piperidine] (314 mg, 52%) as a pale yellow oil.
Reaction SMILES: [CH:1]([N:4]([CH:19]([CH3:21])[CH3:20])[CH2:5][CH2:6][N:7]1[C:17]2[C:12](=[CH:13][C:14]([CH3:18])=[CH:15][CH:16]=2)[C:10](=O)[C:8]1=[O:9])([CH3:3])[CH3:2].Cl.[CH2:23]([NH:30][C:31](=[O:34])[NH:32][NH2:33])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[CH2:23]([NH:30][C:31](=[O:34])[NH:32]/[N:33]=[C:10]1/[C:8](=[O:9])[N:7]([CH2:6][CH2:5][N:4]([CH:19]([CH3:21])[CH3:20])[CH:1]([CH3:3])[CH3:2])[C:17]2[C:12]/1=[CH:13][C:14]([CH3:18])=[CH:15][CH:16]=2)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: NNC(=O)NCc1ccccc1
Reactant: Cc1ccc2c(c1)C(=O)C(=O)N2CCN(C(C)C)C(C)C
Agent: Cl
Product: Cc1ccc2c(c1)/C(=N\NC(=O)NCc1ccccc1)C(=O)N2CCN(C(C)C)C(C)C
Yield: 74.6 %

Procedure:
By using 1-(2-diisopropylaminoethyl)-5-methylisatin and 4-benzylsemicarbazide hydrochloride, a method analogous to that described in Example 6 was carried out to obtain (E)-1-(2-diisopropylaminoethyl)5-methylisatin 3-(4-benzylsemicarbazone) having a melting point of 159°-160° C. (yield: 74.6%, recrystallizing solvent: ethanol).
Reaction SMILES: [CH2:1]([C:4]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][C:5]=1[O:6][CH2:7][C:8](O)=[O:9])[CH:2]=[CH2:3].S(Cl)([Cl:21])=O>>[CH2:1]([C:4]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][C:5]=1[O:6][CH2:7][C:8]([Cl:21])=[O:9])[CH:2]=[CH2:3]
Reactant: C=CCc1ccc(C(F)(F)F)cc1OCC(=O)O
Reactant: O=S(Cl)Cl
Product: C=CCc1ccc(C(F)(F)F)cc1OCC(=O)Cl

Procedure:
Using the procedure of Step E of Example 16, 5.2 g of the product of Step B and 40 ml of thionyl chloride were reacted to obtain 5.55 g of the expected product which was used as is for Step D.
Reaction SMILES: [Cl:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[CH:4]=[C:5]([C:11]([CH2:13][O:14][CH2:15][CH2:16][N:17]1[C:21](=[O:22])[C:20]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:19]2[C:18]1=[O:27])=O)[C:6]([O:8][CH2:9][CH3:10])=[O:7].[CH2:32]([O:34][C:35](=[O:40])/[CH:36]=[C:37](\[NH2:39])/[CH3:38])[CH3:33]>CC(O)C>[Cl:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[CH:4]1[C:36]([C:35]([O:34][CH2:32][CH3:33])=[O:40])=[C:37]([CH3:38])[NH:39][C:11]([CH2:13][O:14][CH2:15][CH2:16][N:17]2[C:21](=[O:22])[C:20]3[C:19](=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:18]2=[O:27])=[C:5]1[C:6]([O:8][CH2:9][CH3:10])=[O:7]
Reactant: CCOC(=O)C(=Cc1ccccc1Cl)C(=O)COCCN1C(=O)c2ccccc2C1=O
Reactant: CCOC(=O)/C=C(/C)N
Solvent: CC(C)O
Product: CCOC(=O)C1=C(C)NC(COCCN2C(=O)c3ccccc3C2=O)=C(C(=O)OCC)C1c1ccccc1Cl
Temperature: 15 °C
Reaction time: 20 h

Procedure:
116.7 g of ethyl 2-(o-chlorobenzylidene)-4-(2-phthalimidoethoxy)acetoacetate was dissolved in 120 ml of 2-propanol at 80° C. 31.2 g of ethyl-3-aminocrotonate was added and the mixture was heated at the same temperature for 16 hours. The mixture was evaporated to dryness. The residue was dissolved in 180 ml of glacial acetic acid at 80° C. The mixture was cooled to 15° C. and stirred at the same temperature for 20 hours. The solid was filtered off and washed with 92 ml of glacial acetic acid. The solid was dissolved in 75 ml of ethanol at 80° C. The solution was cooled to 20° C. and the suspension was agitated for 2 h. The solid was filtered off, washed with 25 ml of ethanol. The wet product was recrystallized from 60 ml of ethyl acetate. Yield: 43.6 g (30%) of the product, purity (HPLC, IN) −98.4%; m.p. 142.5-144° C.
Reaction SMILES: C1N([N+]([O-])=O)CN([N+]([O-])=O)CN1[N+:13]([O-:15])=[O:14].C(O[N+]([O-])=O)C(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O.[CH3:37][N:38]([CH3:45])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C(#N)C>[CH3:37][N:38]([CH3:45])[C:39]1[CH:44]=[CH:43][C:42]([N+:13]([O-:15])=[O:14])=[CH:41][CH:40]=1
Reactant: O=[N+]([O-])N1CN([N+](=O)[O-])CN([N+](=O)[O-])C1
Reactant: CN(C)c1ccccc1
Agent: O=[N+]([O-])OCC(CO[N+](=O)[O-])(CO[N+](=O)[O-])CO[N+](=O)[O-]
Solvent: CC#N
Product: CN(C)c1ccc([N+](=O)[O-])cc1
Yield: 14 %

Procedure:
Considering the electrophilic nature of the NOx species generated by the photofragmentation of RDX and PETN and their resemblance to the active electrophiles in aromatic nitration reactions, reactions between electron-rich tertiary aromatic amines and the photofragments of RDX and PETN were selected. It was found that photolysis (λ=313 nm) of a mixture of N,N-dimethylaniline (DMA) and 2 equivalents of either RDX or PETN for 10 minutes in acetonitrile under anaerobic conditions afforded the formation of N,N-dimethyl-4-nitroaniline (DMNA) in 14% yield (GC yield). Higher yields of DMNA were obtained with longer photolysis times and DMNA was formed in ca. 80% yield after 1 hour. The photoreaction between DMA and either RDX or PETN under anaerobic conditions was observed to produce only a single, yellow-colored product (DMNA) and other side products were not evident by TLC or GC-MS analyses. The 1H-NMR, IR and high-resolution mass spectra of the isolated yellow product matched those obtained for an authentic commercial sample of DMNA. Conducting the photolysis under aerobic conditions resulted in partial demethylation of DMA and yielded a mixture of DMNA and its demethylated analog, N-methyl-4-nitroaniline (13) (see Scheme 1). Photolysis of DMA with ammonium nitrate was also found to produce DMNA, although relatively longer photolysis times (>30 minutes) were required and greater amounts of demethylated side products were observed (possibly due to the presence of water or other nucleophiles in the solutions).
Reaction SMILES: Cl[C:2]1[N:3]=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:6][CH:7]=1.O.[NH2:15][NH2:16].CCOCC>C(O)(C)C>[C:8]1([C:5]2[N:4]=[N:3][C:2]([NH:15][NH2:16])=[CH:7][CH:6]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: NN
Reactant: Clc1ccc(-c2ccccc2)nn1
Solvent: O
Solvent: CCOCC
Solvent: CC(C)O
Product: NNc1ccc(-c2ccccc2)nn1

Procedure:
As shown in FIG. 7, a mixture of 3-chloro-6-phenylpyridazine (compound 1006, 1 g, 5.3 mmol) and hydrazine monohydrate (0.51 mL, 10.53 mmol) in isopropanol was microwaved at 180° C. for 30 minutes. The reaction was treated with ether, the resulting precipitate filtered and washed with ether to yield 1-(6-phenylpyridazin-3-yl)hydrazine, which can be treated with 2M HCl in ether to give the corresponding hydrochloride salt (compound 1007) in quantitative yield. Compound 1007 (0.050 g, 0.22 mmol) and 2-(4-methoxyphenyl)acetic acid (0.044 g, 0.22 mmol) were heated neat to 100° C. for 10 minutes. The reaction mixture was diluted with ethyl acetate, and the organic layer was washed with water and brine. Purification by preparative reversed-phase HPLC yielded 3-(3,4-dimethoxybenzyl)-6-phenyl-[1,2,4]triazolo[4,3-b]pyridazine (compound 206, 0.0073 g, 0.021 mmol, 10% yield).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:23]=[CH:22][C:8]([CH:9]=[C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][CH2:12]/[C:11]/2=[N:20]\[OH:21])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[CH2:24](I)C.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>ClCCl.O>[CH3:24][O:21]/[N:20]=[C:11]1/[C:10](=[CH:9][C:8]2[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:23][CH:22]=2)[C:19]2[C:14]([CH2:13][CH2:12]/1)=[CH:15][CH:16]=[CH:17][CH:18]=2
Reactant: CCI
Reactant: CS(=O)(=O)c1ccc(C=C2/C(=N/O)CCc3ccccc32)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: ClCCl
Product: CO/N=C1\CCc2ccccc2C1=Cc1ccc(S(C)(=O)=O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.5 %

Procedure:
(E)-1-(4-methanesulfonyl-benzylidene)-3,4-dihydro-1H-naphthalene-2-one oxime (50 mg, 0.15 mmol), ethyl iodide (0.023 ml, 0.37 mmol) and potassium carbonate (0.063 g, 0.46 mmol) were added into dimethylformamide (2.0 ml). Then, the solution was stirred at 95˜100° C. overnight, and cooled to room temperature. Again, water and dichloromethane were added, and an organic layer was separated, washed with water and brine, and dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to remove organic solvent. The residue was purified through silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/3, v/v). As a result, 40.7 mg of the present compound (productive yield 78%) was obtained as a white solid crystal.
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:15]=[CH:14][CH:13]=[CH:12][C:4]=1[CH2:5][S:6][C:7]1[NH:8][CH:9]=[CH:10][N:11]=1.ClC1C=CC=C(C(OO)=[O:24])C=1.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.CO>[CH3:1][NH:2][C:3]1[CH:15]=[CH:14][CH:13]=[CH:12][C:4]=1[CH2:5][S:6]([C:7]1[NH:11][CH:10]=[CH:9][N:8]=1)=[O:24]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CNc1ccccc1CSc1ncc[nH]1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: ClC(Cl)Cl
Product: CNc1ccccc1CS(=O)c1ncc[nH]1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 66 %

Procedure:
To a solution of 900 mg (4.11 mmol) of 2-(2-methylaminobenzylthio)imidazole in a mixture of 40 ml of chloroform and 10 ml of methanol was portionwise added under chilling with ice 880 mg (4.11 mmol, purity 80%) of m-chloroperbenzoic acid. The mixture was then stirred for 30 min. To the stired mixture was added a saturated aqueous sodium hydrogencarbonate. The resulting aqueous solution was subjected to extraction with 50 ml of chloroform. The chloroform portion was taken out and the subjected to extraction with three portions of 10 ml of 0.1N aqueous NaOH and one portion of 20 ml of 0.1N aqueous NaOH to transfer a product into the aqueous fractions. The last three aqueous fractions were combined and made ammonia-alkaline by addition of 20% aqueous ammonium chloride to precipitate a crystalline product. The product was collected, washed sufficiently with water and dried under reduced pressure at room temperature to give 637 mg of the desired compound as a pale yellow crystalline product, yield 66%.
Reaction SMILES: [C:1]([NH:4][C:5]1[NH:6][C:7](=[O:21])[C:8]([CH2:18][CH:19]=O)=[C:9]([N:11]([C:15](=[O:17])[CH3:16])[C:12](=[O:14])[CH3:13])[N:10]=1)(=[O:3])[CH3:2].[NH2:22][C:23]1[CH:42]=[CH:41][C:26]([C:27]([NH:29][C@H:30]([C:37]([O:39][CH3:40])=[O:38])[CH2:31][CH2:32][C:33]([O:35][CH3:36])=[O:34])=[O:28])=[CH:25][CH:24]=1.C([BH3-])#N.[Na+]>C(O)(=O)C>[C:1]([NH:4][C:5]1[NH:6][C:7](=[O:21])[C:8]([CH2:18][CH2:19][NH:22][C:23]2[CH:24]=[CH:25][C:26]([C:27]([NH:29][C@H:30]([C:37]([O:39][CH3:40])=[O:38])[CH2:31][CH2:32][C:33]([O:35][CH3:36])=[O:34])=[O:28])=[CH:41][CH:42]=2)=[C:9]([N:11]([C:15](=[O:17])[CH3:16])[C:12](=[O:14])[CH3:13])[N:10]=1)(=[O:3])[CH3:2]
Reactant: COC(=O)CC[C@H](NC(=O)c1ccc(N)cc1)C(=O)OC
Reactant: CC(=O)Nc1nc(N(C(C)=O)C(C)=O)c(CC=O)c(=O)[nH]1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Product: COC(=O)CC[C@H](NC(=O)c1ccc(NCCc2c(N(C(C)=O)C(C)=O)nc(NC(C)=O)[nH]c2=O)cc1)C(=O)OC
Reaction time: 0.5 h
Yield: 44.3 %

Procedure:
A solution of 2-(2-acetylamino-4-diacetylamino-1,6-dihydro-6-oxo-5-pyrimidinyl)acetaldehyde (1.74 g, 5.92 mmol) and dimethyl N-(4-aminobenzoyl)-L-glutamate (J. Am. Chem. Soc., 1958, 80, 5779) (1.74 g, 5.92 mmol) in acetic acid (90 ml) was stirred for 10 minutes. Sodium cyanoborohydride (0.84 g, 13.4 mmol) was added in small portions over 1 hour. After an additional 30 minutes, the reaction was spin evaporated in vacuo to a thick oil. The oil was dissolved in ethyl acetate (500 ml) and washed with 5% aqueous sodium bicarbonate until neutral, water (50 ml), brine (50 ml), dried with magnesium sulfate and spin evaporated in vacuo. Recrystallization from ethyl acetate, with filtration to remove insolubles, yielded 1.5 g (49% of theory) of dimethyl N-[4-[2-(2-acetylamino-4-diacetylamino-1,6-dihydro-6-oxo-5-pyrimidinyl)ethylamino]benzoyl]-L-glutamate, mp 168°-178° C. Recrystallization from ethyl acetate (Norite) gave 0.830 g (25% of theory) of the analytical sample, mp 176°-179° C.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH:6]=[C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=2)[CH2:4][CH2:3]1.[F:17][C:18]1[CH:26]=[CH:25][C:21]([C:22](Cl)=[O:23])=[CH:20][CH:19]=1>>[F:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]([N:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][N:12]=3)[C:8]([C:5]3[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH:6]=3)=[CH:9]2)=[O:23])=[CH:20][CH:19]=1
Reactant: O=C(Cl)c1ccc(F)cc1
Reactant: CN1CC=C(c2c[nH]c3ncccc23)CC1
Product: CN1CC=C(c2cn(C(=O)c3ccc(F)cc3)c3ncccc23)CC1

Procedure:
(10.1 mg, 26%); from 3-(1-methyl-1,2,3,6-tetrahydro-4-pyridinyl)-1H-7-azaindole (24.8 mg, 0.12 mmol) and 4-fluorobenzoyl chloride (28 μL, 0.24 mmol); HRMS-FAB+ for C20H18N3OF: calculated MH+:336.15121; found:336.15100.