Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[C:7]1([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([OH:19])[CH:14]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Br[CH2:21][CH2:22][C:23]([CH2:33][CH3:34])([S:29]([CH3:32])(=[O:31])=[O:30])[C:24]([O:26][CH2:27][CH3:28])=[O:25]>O1CCCC1.C(OCC)(=O)C>[CH2:22]([C:23]([S:29]([CH3:32])(=[O:30])=[O:31])([CH2:33][CH2:34][N:16]1[CH:17]=[CH:18][C:13]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[CH:14][C:15]1=[O:19])[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH3:21]
Reactant: CCOC(=O)C(CC)(CCBr)S(C)(=O)=O
Reactant: Oc1cc(-c2ccccc2)ccn1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCOC(=O)C(CC)(CCn1ccc(-c2ccccc2)cc1=O)S(C)(=O)=O
Temperature: 55 °C
Reaction time: 72 h
Yield: 20 %

Procedure:
Cesium carbonate (0.71 g, 2.2 mmol, 4.0 equiv) was added to a solution of the 4-phenylpyridin-2-ol (0.10 g, 0.58 mmol, 1.05 equiv) and ethyl 4-bromo-2-ethyl-2-(methylsulfonyl)butanoate (0.17 g, 0.55 mmol, 1.0 equiv) in tetrahydrofuran (5 mL). The resulting mixture was heated to 55° C. and allowed to stir for 3 days. The reaction was diluted with ethyl acetate (20 mL), filtered through a pad of Celite, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (4:1-0:1 heptane/ethyl acetate) to provide a light yellow oil (43 mg, 20%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.15 (t, J=7.42 Hz, 3H) 1.33 (t, J=7.13 Hz, 3H) 2.07-2.19 (m, 1H) 2.26-2.36 (m, 1H) 2.44 (ddd, J=14.89, 11.18, 4.98 Hz, 1H) 2.59-2.71 (m, 1H) 3.15 (s, 3H) 4.19-4.37 (m, 4H) 6.45 (dd, J=7.03, 1.56 Hz, 1H) 6.72-6.78 (m, 1H) 7.38-7.48 (m, 4H) 7.53-7.60 (m, 2H).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:20][CH:19]=1)=[C:12]2[CH3:32])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[I:35][C:36]1[CH:43]=[CH:42][C:39]([CH2:40]Br)=[CH:38][CH:37]=1>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:40][C:39]1[CH:42]=[CH:43][C:36]([I:35])=[CH:37][CH:38]=1)[C:13]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:20][CH:19]=1)=[C:12]2[CH3:32])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1c(-c2ccc(OCc3ccccc3)cc2)[nH]c2ccc(OCc3ccccc3)cc12
Reactant: BrCc1ccc(I)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1c(-c2ccc(OCc3ccccc3)cc2)n(Cc2ccc(I)cc2)c2ccc(OCc3ccccc3)cc12
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 31.3 %

Procedure:
A solution of 5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indole (4.2 g, 10 mmol; see PCT/US98/21609 for synthesis) in DMF (40 mL) was cooled to 0° C. under nitrogen atmosphere. Sodium hydride (60% dispersion in mineral oil; 420 mg, 10.5 mmol) was added in one portion. The reaction mixture was stirred at 0° C. for 5 min, and then ice bath was removed and allowed to warm to room temperature. After 1 h, the reaction was cooled back to 0° C. and 4-iodobenzyl bromide (3.7 g, 12.5 mmol) was added slowly. After 5 minutes, the ice bath was removed and the reaction mixture was stirred at room temperature for 6 h. The reaction was diluted with water (200 mL), and ethyl acetate. The precipitate was sonicated, filtered off and dried to give 1.99 g of the desired product. The filtrate was extracted with ethyl acetate (50 mL), the organic layer was washed with water, washed with brine and dried (MgSO4), filtered, concentrated and purified by silica gel chromatography (20%-70% DCM in hexanes) to afford 2.62 g. The reaction resulted in total 4.6 g of 5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-iodobenzyl)-3-methyl-1H-indole as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 7.56 (d, 2H), 7.51-7.46 (m, 4H), 7.44-7.38 (m, 4H), 7.38-7.32 (m, 2H), 7.29 (d, 2H), 7.16 (d, 1H), 7.16-7.10 (m, 3H), 6.82 (dd, 1H), 6.62 (d, 2H), 5.20 (s, 2H), 5.14 (d, 4H), 2.17 (s, 3H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:29])[C:7]([O:10]/[N:11]=[C:12](/[C:16]1[N:17]=[C:18]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[S:19][CH:20]=1)\[C:13](O)=[O:14])([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:63]/[C:64](/[CH2:77][C@@H:78]1[C@H:81]([NH2:82])[C:80](=[O:83])[NH:79]1)=[CH:65]\[C:66](=[O:76])[CH2:67][NH:68][C:69](=[O:75])[O:70][C:71]([CH3:74])([CH3:73])[CH3:72]>C(Cl)Cl.CN(C=O)C>[NH2:63]/[C:64](=[CH:65]\[C:66](=[O:76])[CH2:67][NH:68][C:69]([O:70][C:71]([CH3:74])([CH3:73])[CH3:72])=[O:75])/[CH2:77][C@@H:78]1[C@H:81]([NH:82][C:13](=[O:14])/[C:12](=[N:11]\[O:10][C:7]([CH3:9])([CH3:8])[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:29])/[C:16]2[N:17]=[C:18]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[S:19][CH:20]=2)[C:80](=[O:83])[NH:79]1
Reactant: CC(C)(C)OC(=O)NCC(=O)/C=C(\N)C[C@H]1NC(=O)[C@H]1N
Reactant: CC(C)(C)OC(=O)Nc1nc(/C(=N/OC(C)(C)C(=O)OC(C)(C)C)C(=O)O)cs1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)NCC(=O)/C=C(\N)C[C@H]1NC(=O)[C@H]1NC(=O)/C(=N\OC(C)(C)C(=O)OC(C)(C)C)c1csc(NC(=O)OC(C)(C)C)n1

Procedure:
Prepared in analogous manner to example 4 step 4, using (Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (100 mg, 0.23 mmol), HATU (89 mg, 0.23 mmol), DIPEA (68 μl, 0.39 mmol), tert-butyl ((Z)-4-amino-5-((2R,3S)-3-amino-4-oxoazetidin-2-yl)-2-oxopent-3-en-1-yl)carbamate (58 mg, 0.19 mmol) and DCM:DMF (3:1, 2 mL). 79 mg. LCMS: Rt=0.98 min, m/z=710.4 (M+1). Method 2m_acidic.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH:13]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([N:20]3[CH2:26][CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[CH:15]=2)[CH2:12][C:11]([C:27]([F:33])([F:32])[C:28]([F:31])([F:30])[F:29])=[N:10]1.C(N(CC)CC)C.[CH3:41][S:42](Cl)(=[O:44])=[O:43]>ClCCl>[Cl:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH:13]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([N:20]3[CH2:26][CH2:25][CH2:24][N:23]([S:42]([CH3:41])(=[O:44])=[O:43])[CH2:22][CH2:21]3)[CH:15]=2)[CH2:12][C:11]([C:27]([F:33])([F:32])[C:28]([F:30])([F:31])[F:29])=[N:10]1
Reactant: CS(=O)(=O)Cl
Reactant: FC(F)(F)C(F)(F)C1=NN(c2ccccc2Cl)C(c2cccc(N3CCCNCC3)c2)C1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)N1CCCN(c2cccc(C3CC(C(F)(F)C(F)(F)F)=NN3c3ccccc3Cl)c2)CC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 10.3 %

Procedure:
1-(2-Chloro-phenyl)-5-[3-(homopiperazin-1-yl)-phenyl]-3-pentafluoroethyl-4,5-dihydro-1H-pyrazole hydrochloride (30.0 mg, 0.06 mmol) prepared in Step 1, triethylamine (41.0 uL, 0.30 mmol) and methanesulfonyl chloride (8.1 mg, 0.07 mmol) were added to dichloromethane (1.0 mL). The reaction mixture was stirred at room temperature for 3 hours, washed with distilled water, 1N hydrochloride, a saturated solution of sodium hydrogen carbonate, and brine, dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure to give a yellow liquid residue. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/2) to give 3.4 mg of the titled compound as a yellow liquid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.C1(C)C=CC=CC=1.C(N(CC)CC)C.ClC(Cl)(O[C:41](=[O:47])[O:42][C:43](Cl)(Cl)Cl)Cl.[F:49][C:50]1[CH:51]=[C:52]([CH:58]=[CH:59][CH:60]=1)[O:53][CH2:54][CH2:55]CO>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:41](=[O:47])[O:42][CH2:43][CH2:55][CH2:54][O:53][C:52]2[CH:58]=[CH:59][CH:60]=[C:50]([F:49])[CH:51]=2)=[CH:18][CH:17]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: OCCCOc1cccc(F)c1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=O)OCCCOc4cccc(F)c4)cc3)c2cc1OC
Temperature: 25 °C
Yield: 74.6 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (71 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (108 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(3-fluorophenoxy)-1-propanol (61 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 69%).
Reaction SMILES: CN(C)[CH:3]=[O:4].Br[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20](=[O:31])[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[N+:28]([O-:30])=[O:29].[NH2:32][CH2:33][CH:34]([C:36]1[CH:41]=[C:40]([Cl:42])[C:39]([NH2:43])=[C:38]([Cl:44])[CH:37]=1)[OH:35]>C(OCC)(=O)C.CO.C(N(CC)CC)C>[NH2:43][C:39]1[C:38]([Cl:44])=[CH:37][C:36]([CH:34]([OH:35])[CH2:33][NH:32][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20](=[O:31])[CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[N+:28]([O-:30])=[O:29])=[CH:41][C:40]=1[Cl:42].[C:3]([O-:4])(=[O:35])[C:20]([O-:31])=[O:19]
Reactant: NCC(O)c1cc(Cl)c(N)c(Cl)c1
Reactant: CN(C)C=O
Reactant: O=C(Cc1ccccc1[N+](=O)[O-])OCCCCCCCCCCCCBr
Solvent: CCOC(C)=O
Solvent: CO
Solvent: CCN(CC)CC
Product: Nc1c(Cl)cc(C(O)CNCCCCCCCCCCCCOC(=O)Cc2ccccc2[N+](=O)[O-])cc1Cl
Product: O=C([O-])C(=O)[O-]

Procedure:
According to method I (dimethylformamide, 3 hours at 90° C.) from (12-bromo-1-dodecyl)2-nitrophenylacetate and 2-amino-1-(4-amino-3,5-dichlorophenyl)ethanol. Working up by means of chromatography (ethyl acetate/methanol/triethylamine 20:2:1). Recrystallized as the oxalate from acetone. Melting point: 67°-68° C.
Reaction SMILES: [NH2:1][C:2]1[CH:17]=[CH:16][C:5]2[N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH:7]=[N:8][C:4]=2[C:3]=1[CH3:18].C([N:21]=[C:22](S)[N:23](C(OCC1C=CC=CC=1)=O)[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])C.[C:45]([O:48][CH2:49][CH3:50])(=[O:47])C>O1CCCC1>[C:12]([O:11][C:9]([N:6]1[C:5]2[CH:16]=[CH:17][C:2]([NH:1][C:22]([NH:23][C:24]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])=[N:21][C:45]([O:48][CH2:49][C:50]3[CH:16]=[CH:17][CH:2]=[CH:3][CH:4]=3)=[O:47])=[C:3]([CH3:18])[C:4]=2[N:8]=[CH:7]1)=[O:10])([CH3:13])([CH3:14])[CH3:15]
Reactant: Cc1c(N)ccc2c1ncn2C(=O)OC(C)(C)C
Reactant: CCN=C(S)N(C(=O)OCc1ccccc1)C(=O)OCc1ccccc1
Reactant: CCOC(C)=O
Solvent: C1CCOC1
Product: Cc1c(NC(=NC(=O)OCc2ccccc2)NC(=O)OCc2ccccc2)ccc2c1ncn2C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 500 mg of 5-amino-1-(tert-butoxycarbonyl)-4-methyl-benzimidazole in 20 mL of tetrahydrofuran are added 753 mg of ethyl N,N-bis(benzyloxycarbonyl)pseudothiourea and 645 mg of mercuric acetate and the mixture is stirred at room temperature for 1 hour. The resulting suspension is diluted with ethyl acetate and washed with water followed by brine. The aqueous layers are extracted with ethyl acetate; the combined organic layers are dried over magnesium sulfate, filtered and rotary evaporated. The residue is purified by flash column chromatography on silica gel, eluting with 50% ethyl acetate/hexanes followed by recrystallization from hexanes/methylene chloride to provide 927 mg of 1-(tert-butyloxycarbonyl)-5-[N2, N3-bis(benzyloxycarbonyl)-guanidino]-4-methylbenzimidazole as a white solid.
Reaction SMILES: C([O:4][C:5]1[C:10]2[CH:11]=[C:12]([CH3:14])[S:13][C:9]=2[CH:8]=[C:7]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:6]=1)(=O)C.C(=O)([O-])[O-].[K+].[K+]>C(O)C.ClCCl>[CH2:18]([O:17][C:15]([C:7]1[CH:6]=[C:5]([OH:4])[C:10]2[CH:11]=[C:12]([CH3:14])[S:13][C:9]=2[CH:8]=1)=[O:16])[CH3:19]
Reactant: CCOC(=O)c1cc(OC(C)=O)c2cc(C)sc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: ClCCl
Product: CCOC(=O)c1cc(O)c2cc(C)sc2c1
Temperature: 60 °C
Reaction time: 3 h
Yield: 79 %

Procedure:
Ethyl 4-(acetyloxy)-2-methyl-1-benzothiophene-6-carboxylate was dissolved in absolute ethanol (200 mL). Potassium carbonate (7 g, 50 mmol) was added. The reaction mixture was stirred for 3 h at 60° C. and diluted with 200 mL of dichloromethane. The suspension was filtered. The precipitate was washed by 100 mL of dichloromethane. The combined solutions were washed by 200 mL of a 10% aqueous solution of citric acid and evaporated in vacuum to dryness. The obtained crude product was chromatographed on a layer of silica gel (150×100 mm) with hexane/ethyl acetate mixture, 2:1 as eluent to give 5.5 g (23 mmol, 79%) of 4-Hydroxy-2-methyl-1-benzothiophene-6-carboxylate ethyl ester as a cream solid.
Reaction SMILES: [C:1]([N:4]=[C:5]=[S:6])(=[O:3])[CH3:2].[CH2:7]([N:11]1[C:16]([NH:17][NH2:18])=[CH:15][C:14](=[O:19])[N:13]([CH2:20][CH2:21][CH3:22])[C:12]1=[O:23])[CH2:8][CH2:9][CH3:10]>O1CCOCC1>[C:1]([NH:4][C:5](=[S:6])[NH:18][NH:17][C:16]1[N:11]([CH2:7][CH2:8][CH2:9][CH3:10])[C:12](=[O:23])[N:13]([CH2:20][CH2:21][CH3:22])[C:14](=[O:19])[CH:15]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)N=C=S
Reactant: CCCCn1c(NN)cc(=O)n(CCC)c1=O
Solvent: C1COCCO1
Product: CCCCn1c(NNC(=S)NC(C)=O)cc(=O)n(CCC)c1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 123.2 %

Procedure:
Acetylisothiocyanate(4.8 g) was added dropwise to a stirred solution of 1-butyl-6-hydrazino-3-propylpyrimidine-2,4(1H,3H)-dione(8.0 g) in dioxane(100 ml). The mixture was stirred for 3 hours at room temperature, then precipitating crystals were collected by filtration. Recrystallization from aqueous alcohol gave colorless crystals (14 g, 94%), m.p. 149°-152° C.
Reaction SMILES: Cl.[C:2]1([CH:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[O:9][NH2:10])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:17][CH2:18][C:19](Cl)=[O:20].C(Br)(Br)Br>CS(C)=O>[Cl:17][CH2:18][C:19]([NH:10][O:9][CH:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:20]
Reactant: NOC(c1ccccc1)c1ccccc1
Reactant: O=C(Cl)CCl
Agent: Cl
Solvent: CS(C)=O
Solvent: BrC(Br)Br
Product: O=C(CCl)NOC(c1ccccc1)c1ccccc1
Yield: 86 %

Procedure:
This compound was prepared from diphenylmethoxyamine hydrochloride and chloroacetyl chloride by the method described in Preparation 1; m.p. 115°-117° νmax (CHBr3) include 3400 (NH), 1692 cm-1 (CO-N), τ(DMSO d6) 0.55 (NH), 2.60 (Ph) 4.01 (CHPh2), 6.02 (CH2). Yield 86%.
Reaction SMILES: [C:1](OO)(=O)C.CS[C:8]1[N:12]=[C:11]([NH:13][CH2:14][CH2:15][CH2:16][CH2:17][O:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)[CH:20]=2)[NH:10][N:9]=1.C([O-])(=O)C.[Na+].[S:37]([O-:40])([O-])=[O:38].[Na+].[Na+]>C(O)(=O)C.O>[CH3:1][S:37]([C:8]1[N:12]=[C:11]([NH:13][CH2:14][CH2:15][CH2:16][CH2:17][O:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)[CH:20]=2)[NH:10][N:9]=1)(=[O:40])=[O:38]
Reactant: CSc1n[nH]c(NCCCCOc2cccc(CN3CCCCC3)c2)n1
Reactant: O=S([O-])[O-]
Reactant: CC(=O)OO
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: CS(=O)(=O)c1n[nH]c(NCCCCOc2cccc(CN3CCCCC3)c2)n1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Peracetic acid (1.8 ml) in acetic acid (13 ml) was added at 0° to a solution of 3-methylthio-N-[4-[3-(1-piperidinylmethyl)phenoxy]butyl]-1H-1,2,4-triazole-5-amine (1.6 g) and sodium acetate (0.69 g) in acetic acid (22 ml) and the mixture was stirred at room temperature, for 18 h. Excess peracetic acid was decomposed with sodium sulphite (3.0 g) in water and the resulting suspension evaporated. The residue was neutralised with sodium bicarbonate solution and extracted with chloroform. The extract was evaporated to give an oil which was crystallised from methyl acetate-petroleum ether (5:1) to give the title compound as a beige powder (0.75 g), m.p. 79°-81°.
Reaction SMILES: [N+]([O-])(O)=[O:2].C(O[C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[O:19][C:18](=[O:23])[CH:17]=[C:16]2[OH:24])C1C=CC=CC=1.[OH-:25].[Na+]>C(Cl)(Cl)Cl.C1C=CC=CC=1.O>[OH2:2].[OH:24][C:16]1[C:15]2[C:20](=[CH:21][C:22]([OH:25])=[CH:13][CH:14]=2)[O:19][C:18](=[O:23])[CH:17]=1
Reactant: [OH-]
Reactant: O=c1cc(O)c2cc(OCc3ccccc3)ccc2o1
Reactant: O=[N+]([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: c1ccccc1
Solvent: O
Product: O=c1cc(O)c2ccc(O)cc2o1
Reaction time: 1.5 h

Procedure:
Fuming nitric acid (13 ml) was added to a stirred suspension of 6-benzyloxy-4-hydroxycoumarin (m.p. 226°-8°; 3.13g) in chloroform (200 ml) at room temperature over 1.5 hours. After a further 1.5 hours, the solvent was removed in vacuo at room temperature and water (100 ml) added to the residue. Filtration gave an oily solid which was dissolved in benzene, filtered, and the filtrate evaporated to dryness to give a yellow solid, decomp. 170°. The solid was suspended in water (30 ml) and dilute sodium hydroxide solution added till the pH of the solution reached 14. Filtration gave the product, m.p. 262°-4°(d). (C10H10NO6Na requires C, 57.32; H, 3.01; N, 4.18; Na, 6.86. Found: C, 57.44; H, 3.31; N, 4.34; Na, 6.86. Found: C, 57.44; H, 3.31; N, 4.34; Na, 6.67) after washing with water and drying under vacuum.
Reaction SMILES: C[N:2]1[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.ClC(OCC(C)C)=O.[CH:16]1[CH:21]=CC(C(N)C(N)=O)=[CH:18][CH:17]=1.CC[N:29](CC)CC>C1COCC1.C1COCC1.O>[C:7]1([NH:2][CH2:3][C:4]([NH2:29])=[O:5])[CH:6]=[CH:18][CH:17]=[CH:16][CH:21]=1
Reactant: CCN(CC)CC
Reactant: NC(=O)C(N)c1ccccc1
Reactant: CN1CCOCC1
Agent: CC(C)COC(=O)Cl
Solvent: O
Solvent: C1CCOC1
Product: NC(=O)CNc1ccccc1
Reaction time: 1 h

Procedure:
To a solution of acid 9 (38 mg, 0.039 mmol) and N-methyl morpholine (4.5 μL, 0.041 mmol) in 1.5 mL of anhydrous THF cooled to 0° C. was added isobutyl chloroformate (5.2 μL, 0.040 mmol) and the mixture was stirred for 1 hour at that temperature. A solution of D-phenylglycinamide (8.6 mg, 0.057 mmol) and Et3N (10 μL) in 1 mL of THF/H2O 4:1 was added and the mixture was stirred for 1 h at 0° C. and 1 h at room temperature. After removal of the THF under vacuum, the residue was suspended in H2O (5 mL) and extracted with EtOAc (5 mL×3). The combined organic layers were dried over Na2SO4 and filtered. The solvent was removed under vacuum and the residue was purified by chromatography on a silica gel column (5-8% MeOH in CH2Cl2) to give conjugate S1 (28 mg, 66%) as a white solid: 1H NMR (600 MHz, DMSO-d6) δ8.41 (d, J=7.9 Hz, 1H), 8.31 (t, J=5.3 Hz, 3H), 7.65 (br. s., 1H), 7.25-7.45 (m, 14H), 7.13 and 7.12 (2×s, 2H), 5.36 (d, J=8.2 Hz, 1H), 3.11-3.17 (m, 6H), 2.35-2.48 (m, 2H), 2.30-2.34 (m, 2H), 2.28 (s, 9H), 2.21 (s, 9H), 1.58-1.67 (m, 6H), 1.37-1.44 (m, 6H); HRMS (ESI) calcd. for C55H63N6O18 (M+H)+: 1095.4193, found 1095.4203.
Reaction SMILES: [CH2:1]([C:3]1[N:8]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([CH3:21])([CH3:20])[CH:17]([OH:19])[CH3:18])=[CH:11][CH:10]=2)[C:7](=[O:22])[C:6]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[C:36]3[NH:40][C:39](=[O:41])[O:38][N:37]=3)=[CH:26][CH:25]=2)=[C:5]([CH2:42][CH2:43][CH3:44])[N:4]=1)[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C1=CC=CC=2)=O.C(OCC)(=O)C.S([O-])([O-])(=O)=S.[Na+].[Na+]>ClCCl.O>[CH3:21][C:16]([CH3:20])([O:15][C:12]1[CH:13]=[CH:14][C:9]([N:8]2[C:7](=[O:22])[C:6]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[C:36]4[NH:40][C:39](=[O:41])[O:38][N:37]=4)=[CH:26][CH:25]=3)=[C:5]([CH2:42][CH2:43][CH3:44])[N:4]=[C:3]2[CH2:1][CH3:2])=[CH:10][CH:11]=1)[C:17](=[O:19])[CH3:18]
Reactant: CCCc1nc(CC)n(-c2ccc(OC(C)(C)C(C)O)cc2)c(=O)c1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: O
Product: CCCc1nc(CC)n(-c2ccc(OC(C)(C)C(C)=O)cc2)c(=O)c1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1
Reaction time: 2 h
Yield: 90.3 %

Procedure:
To a solution of 2-ethyl-3-[4-(2-hydroxy-1,1-dimethylpropoxy)phenyl]-5-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-6-propylpyrimidin-4(3H)-one (0.2 g) in dichloromethane (6 mL) was added 1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3(1H)-one (0.21 g), and the mixture was stirred for 2 hr. Ethyl acetate, water and sodium thiosulfate were added to the reaction mixture, and the mixture was stirred for 30 min and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.18 g, 89%).
Reaction SMILES: C1(C2C=CC=CC=2)C=CC=CC=1.C1(OC2C=CC=CC=2)C=CC=CC=1.[C:26]([C:28]1[CH:33]=[CH:32][C:31]([NH:34][CH:35]=[C:36]2[C:41](=[O:42])OC(C)(C)OC2=O)=[CH:30][CH:29]=1)#[N:27]>CCCCCC>[OH:42][C:41]1[C:30]2[C:31](=[CH:32][CH:33]=[C:28]([C:26]#[N:27])[CH:29]=2)[N:34]=[CH:35][CH:36]=1
Reactant: CC1(C)OC(=O)C(=CNc2ccc(C#N)cc2)C(=O)O1
Solvent: c1ccc(-c2ccccc2)cc1
Solvent: c1ccc(Oc2ccccc2)cc1
Solvent: CCCCCC
Product: N#Cc1ccc2nccc(O)c2c1
Temperature: 250 °C
Reaction time: 1 h
Yield: 90.7 %

Procedure:
A mixture of biphenyl (10 ml) and diphenyl ether (30 ml) was heated at 250° C. and 5-(4-cyanophenylamino)methylidene-2,2-dimethyl-1,3-dioxane-4,6-dione (3.28 g) was added thereto. The mixture was stirred for 1 hr. The reaction mixture was cooled to 80° C. while stirring and hexane (100 ml) was added. The mixture was stirred in an ice bath for 0.5 hr. The resulting solid was collected by filtration and washed with hexane to give the object compound (1.86 g) as a yellow-brown powder.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:6][CH:7]=1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[Br:31]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.[W]>[Br:31][CH2:1][C:2]1[N:3]=[CH:4][C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:6][CH:7]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)c1cnc(C)cn1
Agent: [W]
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CCOC(=O)c1cnc(CBr)cn1
Yield: 45 %

Procedure:
Ethyl 5-methyl-2-pyrazinecarboxylate (10.0 g, 60.18 mmol), benzoyl peroxide (1.46 g, 6.02 mmol) and N-bromo succinimide (11.78 g, 66.19 mmol) in 80 mL CCl4 was heated to reflux while a 75 W tungsten lamp was shining on the reaction mixture. After 4 h the reaction mixture was cooled and the precipitate filtered off. The red filtrate was concentrated and the residue redissolved in EtOAc and washed with sat'd NaHCO3, 5% Na2S2O3, brine and the organics dried (Na2SO4), filtered and concentrated. Chromatography on silica gel using 1:1 Hexanes:EtOAc eluted the product. After concentration the title compound (6.64 g, 27.08 mmol, 45% yield) was isolated as a yellow oil: 1H NMR (CDCl3, 400 MHz) δ 9.22 (s, 1H), 8.80 (s, 1H), 4.58 (s, 2H), 4.49 (dd, J=14.3, 7.1 Hz, 2H), 1.43 (t, J=7.2 Hz, 3H).
Reaction SMILES: [OH:1][N:2]1[C:7]([CH3:9])([CH3:8])[CH2:6][CH:5]([OH:10])[CH2:4][C:3]1([CH3:12])[CH3:11].N(OC(C)(C)C)=O.[Br:20][C:21]1[CH:27]=[C:26]([Br:28])[CH:25]=[CH:24][C:22]=1N>[Cu](F)F.N1C=CC=CC=1>[Br:20][C:21]1[CH:27]=[C:26]([Br:28])[CH:25]=[CH:24][C:22]=1[O:1][N:2]1[C:7]([CH3:8])([CH3:9])[CH2:6][CH:5]([OH:10])[CH2:4][C:3]1([CH3:12])[CH3:11]
Reactant: Nc1ccc(Br)cc1Br
Reactant: CC1(C)CC(O)CC(C)(C)N1O
Agent: F[Cu]F
Agent: CC(C)(C)ON=O
Solvent: c1ccncc1
Product: CC1(C)CC(O)CC(C)(C)N1Oc1ccc(Br)cc1Br
Yield: 56.4 %

Procedure:
The procedure of Example 1 is repeated using 12.8 g (74 mmol) of 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine, 14.23 g (138 mmol) of tert-butyl nitrite, 0.73 g (0.74 mmol) of copper(II) fluoride, 200 mL of pyridine and 8.56 g (92 mmol) of 2,4-dibromoaniline at 65° C. The crude product obtained is purified by vacuum flash chromatography (5% ethyl acetate/heptane) to give 17 g of the title compound as a yellowish solid solid in 63.5% yield. The structure is confirmed by 1Hnmr analysis.