Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=1.[Cl-].[Al+3].[Cl-].[Cl-].[C:16](Cl)(=[O:18])[CH3:17]>[N+](C1C=CC=CC=1)([O-])=O>[C:16]([C:7]1[CH:6]=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([Br:1])[CH:3]=2)[CH:8]=1)(=[O:18])[CH3:17]
Reactant: CC(=O)Cl
Reactant: Brc1ccc2ccccc2c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: O=[N+]([O-])c1ccccc1
Product: CC(=O)c1ccc2cc(Br)ccc2c1
Temperature: 25 °C
Yield: 43.6 %

Procedure:
To a cold (10° C.) mixture of 44.0 g (0.212 mol) of 2-bromonaphthalene and 34.0 g (0.255 mol) of aluminum chloride in 400 ml of nitrobenzene was added 21.0 g (267 mmol) of acetyl chloride. The mechanically stirred reaction mixture was warmed to room temperature, and heated to 40° C. for 18 hours. After cooling to 0° C. in an ice bath, the reaction was quenched by the addition of 12M HCl (70 ml). The layers were separated and the organic phase was washed with water and dilute aqueous Na2CO3. Kugelrohr distillation, followed by recrystallization from 10% EtOAc-hexane yielded 23 g of the title compound as a tan solid. 1H NMR (CDCl3): δ8.44 (1H, br s), 8.04-8.10 (2H, m), 7.85 (1H, d, J=8.5 Hz), 7.82 (1H, d, J=8.8 Hz), 7.64 (1H, d, J=8.8 Hz), 2.73 (3H, s).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[S:10][C:9]([C:15]4[N:16]([CH:20]([CH3:22])[CH3:21])[N:17]=[CH:18][N:19]=4)=[N:8][C:7]=3[C:6]=2[CH:23]=1.[CH3:24][O:25][C:26]1[CH:27]=[N:28][CH:29]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:31]=1>>[CH:20]([N:16]1[C:15]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:5]4[CH:4]=[CH:3][C:2]([C:30]5[CH:29]=[N:28][CH:27]=[C:26]([O:25][CH3:24])[CH:31]=5)=[CH:23][C:6]=4[C:7]=3[N:8]=2)=[N:19][CH:18]=[N:17]1)([CH3:22])[CH3:21]
Reactant: CC(C)n1ncnc1-c1nc2c(s1)CCOc1ccc(Br)cc1-2
Reactant: COc1cncc(B2OC(C)(C)C(C)(C)O2)c1
Product: COc1cncc(-c2ccc3c(c2)-c2nc(-c4ncnn4C(C)C)sc2CCO3)c1
Yield: 60 %

Procedure:
Following the procedure for 128, 9-Bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene from Example 6 and 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine were reacted to give 343 (0.062 g, 60%). 1H NMR (500 MHz, DMSO) δ 8.72 (d, J=2.4, 1H), 8.50 (d, J=1.8, 1H), 8.29 (d, J=2.7, 1H), 8.11 (s, 1H), 7.71 (dd, J=8.4, 2.4, 1H), 7.64 (dd, J=2.6, 2.0, 1H), 7.21 (d, J=8.4, 1H), 5.82 (dd, J=13.2, 6.6, 1H), 4.43 (t, J=5.0, 2H), 3.92 (s, 3H), 3.49 (t, J=5.0, 2H), 1.56 (d, J=6.6, 6H). MS (ESI(+)): m/z 420.1 (M+H)
Reaction SMILES: [C:1]([NH:9][C@H:10]([C:18]([OH:20])=O)[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[C:28]1([O:38][C:39](=[O:69])[C@H:40]([CH2:42][CH2:43][CH2:44][N:45]([C:59]([O:61][CH2:62][C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)=[O:60])[C:46](=[NH:58])[NH:47][C:48]([O:50][CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)=[O:49])[NH2:41])[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=[CH:30][CH:29]=1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[C:28]1([O:38][C:39](=[O:69])[C@H:40]([CH2:42][CH2:43][CH2:44][N:45]([C:59]([O:61][CH2:62][C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)=[O:60])[C:46](=[NH:58])[NH:47][C:48]([O:50][CH2:51][C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=2)=[O:49])[NH:41][C:18](=[O:20])[C@H:10]([CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[NH:9][C:1](=[O:8])[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=[CH:30][CH:29]=1
Reactant: O=C(N[C@@H](Cc1ccccc1)C(=O)O)c1ccccc1
Reactant: N=C(NC(=O)OCc1ccccc1)N(CCC[C@H](N)C(=O)Oc1cccc2ccccc12)C(=O)OCc1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Product: N=C(NC(=O)OCc1ccccc1)N(CCC[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)c1ccccc1)C(=O)Oc1cccc2ccccc12)C(=O)OCc1ccccc1
Reaction time: 3 h
Yield: 56.9 %

Procedure:
In 8 ml of DMF were dissolved 808 mg of benzoyl-L-phenylalanine and 2.05 g of Nδ,Nω -dibenzyloxycarbonyl-L-arginine 1-naphthyl ester trifluoroacetate, after which 681 mg of DCC, 405 mg of HOBt and 304 mg of TEA were added thereto with ice-cooling, and the mixture was stirred for 3 hrs, and then at room temperature for a further 24 hrs. After the reaction, the DCU thus precipitated was removed by filtration, and ethyl acetate was added to the filtrate, after which the mixture was washed with 10% citric acid solution, saturated sodium bicarbonate solution and saturated sodium chloride solution in this order, and then dried over anhydrous magnesium sulfate. The solvent was removed by evaporation under reduced pressure, and the residue thus obtained was recrystallized from chloroform-diethyl ether to obtain 1.4 g (yield 57%) of benzoyl-L-phenylalanyl-Nδ,Nω -dibenzyloxycarbonyl-L-arginine 1-naphthyl ester, m.p. 177°-185° C.
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[C:5]2[N:10]=[C:9]([CH3:11])[CH:8]=[C:7]([CH3:12])[N:6]2[CH:13]=1.[CH3:14][N:15]1[CH:19]=[C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[NH:17][C:16]1=[S:26].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:12][C:7]1[N:6]2[CH:13]=[C:3]([CH2:2][S:26][C:16]3[N:15]([CH3:14])[CH:19]=[C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[N:17]=3)[N:4]=[C:5]2[N:10]=[C:9]([CH3:11])[CH:8]=1
Reactant: Cc1cc(C)n2cc(CCl)nc2n1
Reactant: Cn1cc(-c2ccccc2)[nH]c1=S
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc(C)n2cc(CSc3nc(-c4ccccc4)cn3C)nc2n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 468.6 %

Procedure:
A mixture of 2-chloromethyl-5,7-dimethyl-imidazo[1,2-a]pyrimidine (1.55 g, 0.8 mmol), 1-methyl-4-phenyl-1,3-dihydro-imidazole-2-thione (1.5 g, 0.8 mmol) and K2CO3 (3.31 g, 2.4 mmol) in dry DMF (20 mL) was stirred under N2 at room temperature overnight. After removal of the solvent under vacuum, the residue was purified by preparative HPLC to afford the title compound (1.31 g, 47%) as a white solid. LC-MS: m/z=350.2 (MH+), tR=2.14 min, method D.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[N:6][CH:7]=1.[H-].[Na+].[Cl:11][CH2:12][CH2:13][CH2:14]I.[Na+].[Cl-]>CN(C)C=O.O>[Cl:1][C:2]1[CH:7]=[N:6][CH:5]=[C:4]([O:8][CH2:14][CH2:13][CH2:12][Cl:11])[CH:3]=1
Reactant: ClCCCI
Reactant: Oc1cncc(Cl)c1
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: ClCCCOc1cncc(Cl)c1
Temperature: 25 °C
Yield: 72.2 %

Procedure:
Under a nitrogen atmosphere, a solution of 5-chloro-3-pyridinol (15.00 g, 115.8 mmol) in N,N-dimethylformamide (DMF) (10 mL) was added drop-wise over 5 min to a cold (0-5° C.), stirring slurry of sodium hydride (3.69 g of an 80% dispersion in mineral oil, 123.0 mmol) in DMF (15 mL). The mixture was allowed to stir and warm to ambient temperature over 1 h. Next, 1-chloro-3-iodopropane (28.4 g, 138.9 mmol) was added drop-wise over 5 min. The resulting dark-brown mixture was stirred at ambient temperature for 4 h. Water (25 mL) was added, followed by saturated NaCl solution (25 mL), and the mixture was extracted with ether (4×50 mL). The combined ether extracts were dried (Na2SO4), filtered, and concentrated by rotary evaporation to a residue that was dried briefly under high vacuum to give 17.22 g (73.0%) of an oil.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]([NH:10][C:11]2[C:12]([O:18][CH3:19])=[N:13][CH:14]=[CH:15][C:16]=2[CH3:17])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH:20]1([NH2:23])[CH2:22][CH2:21]1>>[CH:20]1([NH:23][C:2]2[C:7]([C:8]([NH:10][C:11]3[C:12]([O:18][CH3:19])=[N:13][CH:14]=[CH:15][C:16]=3[CH3:17])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:22][CH2:21]1
Reactant: NC1CC1
Reactant: COc1nccc(C)c1NC(=O)c1cccnc1Cl
Product: COc1nccc(C)c1NC(=O)c1cccnc1NC1CC1
Temperature: 110 °C
Yield: 86 %

Procedure:
2-Chloro-N-(2-methoxy-4-methyl-3-pyridinyl)-3-pyridinecarboxamide (0.55 g, 2 mmol) was placed in a sealed tube containing cyclopropylamine (0.5 mL, 7 mmol) and heated to 110° C. overnight. Removal of the cyclopropylamine by rotary evaporation followed by flash chromatography of the residue on silica gel (1:1 EtOAc:hexanes) gave the desired compound in 86% yield (0.51 g). m.p.: 151°-152° C. (Recrystallized from heptane).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:6]=[CH:7][CH:8]=1.[Li]C(C)(C)C.[I:22]I.[O-]S([O-])(=S)=O.[Na+].[Na+]>C(OCC)C.CCCCC>[I:22][C:4]1[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][C:5]=1[NH:9][C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:15])[CH3:14]
Reactant: II
Reactant: COc1cccc(NC(=O)OC(C)(C)C)c1
Agent: O=S([O-])([O-])=S
Agent: [Li]C(C)(C)C
Agent: [Na+]
Solvent: CCOCC
Solvent: CCCCC
Product: COc1cccc(NC(=O)OC(C)(C)C)c1I
Temperature: 25 °C
Reaction time: 3 h
Yield: 73.6 %

Procedure:
To the solution of tert-butyl (3-methoxyphenyl)-carbamate (5 g, 22.4 mmol, 1 eq) in dry diethyl ether (50 mL) was added pentane solution of t-BuLi (35 mL, 49.3 mmol, 2.2 eq) at −20° C., and the mixture was stirred at 3 hours. To this mixed solution was added the solution of iodine (6.83 g, 26.9 mmol, 1.2 eq) in diethylether (60 mL) at −78° C., and after heating the whole solution to room temperature, the solution was stirred for 20 hours. After adding saturated aqueous solution of Na2S2O3 (100 mL), the mixture was extracted three times with diethyl ether (100 mL). The extract was washed with aqueous solution of sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting concentrate was applied to silica gel (eluate: hexane-AcOEt=90-10) to give white solid of the title compound (5.755 g, yield 74%).
Reaction SMILES: [CH:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][N:2]=1.C(=O)([O-])[O-:12].[Na+].[Na+].ClC1C=CC=C(C(OO)=O)C=1>C(Cl)Cl>[CH:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][N+:2]=1[O-:12]
Reactant: O=C([O-])[O-]
Reactant: c1cc2c(cn1)CCCC2
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Solvent: ClCCl
Product: [O-][n+]1ccc2c(c1)CCCC2

Procedure:
5,6,7,8-Tetrahydroisoquinoline (10 g) was added to methylene chloride (100 ml) and a 10% aqueous solution (100 ml) of sodium carbonate. Under vigorous stirring, a 70% solution of m-chloroperbenzoic acid (20 g) in methylene chloride (100 ml) was dropped thereinto at 0° C. Then the reaction solution was extracted with methylene chloride. The methylene chloride layer was washed with brine, dried and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (methylene chloride/methanol system) to give the title compound (7.50 g) as a colorless oil. (283-2) 5,6,7,8-Tetrahydroisoquinolin-5-ol
Reaction SMILES: [Br:1]/[CH:2]=[C:3]1\[CH2:4][CH2:5][CH2:6][C@@:7]2([CH3:15])[C@H:11]\1[CH2:10][CH2:9][C@@H:8]2[C@@H:12]([OH:14])[CH3:13].C[N+]1([O-])CCOCC1>C(#N)C.C(OCC)(=O)C.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[Br:1]/[CH:2]=[C:3]1\[CH2:4][CH2:5][CH2:6][C@@:7]2([CH3:15])[C@H:11]\1[CH2:10][CH2:9][C@@H:8]2[C:12](=[O:14])[CH3:13]
Reactant: C[C@H](O)[C@H]1CC[C@H]2/C(=C/Br)CCC[C@]12C
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Agent: C[N+]1([O-])CCOCC1
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CC(=O)[C@H]1CC[C@H]2/C(=C/Br)CCC[C@]12C
Reaction time: 0.08 h
Yield: 100.9 %

Procedure:
Under a nitrogen atmosphere, a solution of (S)-1-{(E,3S,3aS,7aR)-7-(bromomethylene)-octahydro-3a-methyl-1H-indene-3-yl}ethanol (Compound 18: 58.1 mg, 0.2127 mmol) and N-methylmorpholine-N-oxide (37.4 mg, 0.3190 mmol) in acetonitrile (2 ml) was cooled in an ice bath, and tetra-n-propylammonium perruthenate (3.7 mg, 0.01064 mmol) was added thereto. The reaction mixture was stirred at the same temperature for 5 minutes, and at room temperature (22° C.) for 50 minutes, and the resulting mixture was diluted with ethyl acetate. The mixture was filtered through Celite, and the solids were washed with ethyl acetate, followed by evaporation of the filtrate under reduced pressure. The obtained crude product was purified by flash column chromatography to obtain 1-{(E,3S,3aS,7aR)-7-(bromomethylene)-octahydro-3a-methyl-1H-indene-3-yl}ethanone (58.2 mg, 100%). The spectrum data thereof agreed with the data described in Example 7.
Reaction SMILES: CC(C)([O-])C.[K+].[Cl:7][C:8]1[CH:13]=[C:12]([OH:14])[CH:11]=[CH:10][C:9]=1[CH2:15][N:16]1[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:31])[C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])=[N:17]1.Br[CH2:33][CH2:34][CH2:35][CH3:36]>CS(C)=O.CO>[CH2:33]([O:14][C:12]1[CH:11]=[CH:10][C:9]([CH2:15][N:16]2[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:31])[C:23]3[C:24]([F:30])=[CH:25][CH:26]=[CH:27][C:28]=3[F:29])=[N:17]2)=[C:8]([Cl:7])[CH:13]=1)[CH2:34][CH2:35][CH3:36]
Reactant: O=C(Nc1ccn(Cc2ccc(O)cc2Cl)n1)c1c(F)cccc1F
Reactant: CCCCBr
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CO
Product: CCCCOc1ccc(Cn2ccc(NC(=O)c3c(F)cccc3F)n2)c(Cl)c1
Reaction time: 0.08 h

Procedure:
Potassium t-butoxide (9.7 mg, 0.086 mmol, Aldrich) was added to a solution of N-{1-[(2-chloro-4-hydroxyphenyl)methyl]-1H-pyrazol-3-yl}-2,6-difluorobenzamide (for a preparation see Example 31)(29.4 mg, 0.081 mmol) in DMSO (0.5 ml). The reaction was stirred for 5 min before adding 1-bromobutane (10.42 μL, 0.097 mmo, Acros). The reaction was stirred for 56 h at ambient temperature. The reaction mixture was diluted with methanol (0.5 ml) and the sample purified by MDAP on Sunfire C18 column using Acetonitrile-Water with a Formic acid modifier. (Method B). The solvent was evaporated in vacuo to give the title compound as a yellow gum (14.5 mg); LCMS: (System 4) MH+=420, tRET=3.45 min.
Reaction SMILES: [NH2:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([CH2:16][C:17]#[CH:18])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1.[C:24]([N:32]=[C:33]=[S:34])(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>ClCCl>[C:24]([NH:32][C:33](=[S:34])[NH:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([CH2:16][C:17]#[CH:18])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: O=C(N=C=S)c1ccccc1
Reactant: C#CCc1c(C)nc2c(OCc3c(C)cccc3N)cccn12
Solvent: ClCCl
Product: C#CCc1c(C)nc2c(OCc3c(C)cccc3NC(=S)NC(=O)c3ccccc3)cccn12
Reaction time: 1 h

Procedure:
To a solution of 8-(2-amino-6-methylbenzyloxy)-2-methyl-3-(2-propynyl)imidazo[1,2-a]pyridine (9.3 g) in dichloromethane (140 ml) was added dropwise benzoyl isothiocyanate and the mixture was stirred for 1 hour. The solvent was evaporated under reduced pressure and the residue was triturated with ether (50 ml) to give a crystalline product. The crystals were recrystallized from ethanol to give 8-{2-[3-(benzoyl)thioureido]-6-methylbenzyloxy}-2-methyl-3-(2-propynyl)imidazo[1,2-a]pyridine (11.7 g).
Reaction SMILES: [CH3:1][S:2]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:17])[C:14]([OH:16])=O)=[CH:8][CH:7]=1)(=[O:4])=[O:3].[CH3:18][O:19][C:20]1[CH:32]=[CH:31][C:23]([CH2:24][CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[CH:22][CH:21]=1>C(OCC)C>[CH3:1][S:2]([NH:5][C:6]1[CH:7]=[CH:8][C:9]([NH:12][C:13](=[O:17])[C:14]([N:28]2[CH2:29][CH2:30][CH:25]([CH2:24][C:23]3[CH:22]=[CH:21][C:20]([O:19][CH3:18])=[CH:32][CH:31]=3)[CH2:26][CH2:27]2)=[O:16])=[CH:10][CH:11]=1)(=[O:3])=[O:4]
Reactant: CS(=O)(=O)Nc1ccc(NC(=O)C(=O)O)cc1
Reactant: COc1ccc(CC2CCNCC2)cc1
Solvent: CCOCC
Product: COc1ccc(CC2CCN(C(=O)C(=O)Nc3ccc(NS(C)(=O)=O)cc3)CC2)cc1

Procedure:
The title compound is prepared from N-(4-methanesulfonylamino-phenyl)-oxalamic acid and 4-(4-methoxy-benzyl)-piperidine according to the method described in Example 1c. Melting Point: 206-208° C. (diethylether)
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10]O)=[CH:4][CH:3]=1.Br.NC(N)=[S:15]>O>[I:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][SH:15])=[CH:4][CH:3]=1
Reactant: OCCCc1ccc(I)cc1
Reactant: NC(N)=S
Agent: Br
Solvent: O
Product: SCCCc1ccc(I)cc1
Yield: 66 %

Procedure:
62 g of 3-(p-iodophenyl) propanol was combined in solution with 161 g of hydrobromic acid (48%) and 23 g of thiourea in 100 ml of water and the thiol product vacuum distilled at 114°-117° and 0.1 mm Hg. A 66% yield of 3-(p-iodophenyl) propane thiol was confirmed having a refractive index of n25D = 1.6202.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[S:16][C:15]([S:17]([NH2:20])(=[O:19])=[O:18])=[N:14][N:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:28](Cl)(=[O:38])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37]>C(#N)C>[S:17]([C:15]1[S:16][C:12]([NH:11][S:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:1][C:28](=[O:38])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])=[CH:3][CH:4]=2)(=[O:10])=[O:9])=[N:13][N:14]=1)(=[O:18])(=[O:19])[NH2:20]
Reactant: CCCCCCCCCC(=O)Cl
Reactant: Nc1ccc(S(=O)(=O)Nc2nnc(S(N)(=O)=O)s2)cc1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCCCCCCCCC(=O)Nc1ccc(S(=O)(=O)Nc2nnc(S(N)(=O)=O)s2)cc1
Temperature: 0 °C
Yield: 60 %

Procedure:
5-(4-Aminophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide (7, 50 mg, 0.15 mmol) was suspended in anhydrous acetonitrile (5 mL). Triethylamine (17.1 mg, 0.17 mmol) was added with stirring at 0° C. A solution of decanoyl chloride (32.4 mg, 0.17 mmol) dissolved in anhydrous acetonitrile (1 mL) was added dropwise, and the reaction mixture was stirred at 0° C. for 2 h and overnight at room temperature. Volatiles were removed in vacuo and the residue was washed with water (5 mL). The residue was subjected to chromatography on silica gel (70-230 mesh) eluted with CH2Cl2:methanol 9:1, giving the pure product as a solid (42 mg, 0.09 mmol, 60% yield), mp 242-243° C.; 1H NMR (300 MHz, DMSO-d6) δ 0.84 (t, 3H, J=6.9 Hz), 1.24 (m, 12H), 1.56 (m, 2H), 2.32 (t, 2H, J=7.5 Hz), 7.66 (s, 4H), 7.91 (s, 2H), 10.13 (s, 1H); 13C NMR (75 MHz, DMSO-d6) δ 14.1, 22.3, 25.2, 28.8, 29.0, 31.5, 36.6, 118.6, 127.0, 137.4, 142.2, 157.8, 170.8, 172.1; LRMS (LCQ, ESI−) calcd for C18H26N5O5S3 488.1. found 488.1 (M−H)−. HRMS (ESI−, m/z) calcd for C18H26N5O5S3 488.1102. found 487.1101 (M−H)−.
Reaction SMILES: [CH2:1]([N:3]([CH2:21][CH3:22])[C:4]1[CH:20]=[CH:19][C:7]([C:8]([C:10]2[C:11]([C:16]([OH:18])=[O:17])=[N:12][CH:13]=[CH:14][N:15]=2)=O)=[CH:6][CH:5]=1)[CH3:2].[C:23]1([NH:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(OC(=O)C)(=O)C>>[CH2:21]([N:3]([CH2:1][CH3:2])[C:4]1[CH:20]=[CH:19][C:7]([C:8]2([N:29]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:10]3=[N:15][CH:14]=[CH:13][N:12]=[C:11]3[C:16](=[O:17])[O:18]2)=[CH:6][CH:5]=1)[CH3:22]
Reactant: CCN(CC)c1ccc(C(=O)c2nccnc2C(=O)O)cc1
Reactant: c1ccc(Nc2ccccc2)cc1
Solvent: CC(=O)OC(C)=O
Product: CCN(CC)c1ccc(C2(N(c3ccccc3)c3ccccc3)OC(=O)c3nccnc32)cc1
Reaction time: 72 h

Procedure:
A mixture of 0.1 g. of 3-[4-(diethylamino)benzoyl]-2-pyrazinecarboxylic acid, 0.1 g. of diphenylamine and 2 ml. of acetic anhydride was warmed for several hours and then allowed to stand for three days. The product, 7-[4-(diethylamino)phenyl]-7-(diphenylamino)furo[3,4-b]pyrazine-5(7H)-one was isolated by column chromatography as a light orange solid, m.p. 140°-142.6° C. A toluene solution of this product contacted with acidic clay or phenolic resin developed a red image.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]1[CH:8]=[CH:9][C:10](=[O:13])[NH:11][CH:12]=1.[CH3:14][C:15](C)([O-])C.[K+].BrCC>CN(C=O)C>[CH2:14]([N:11]1[CH:12]=[C:7]([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][N:1]=2)[CH:8]=[CH:9][C:10]1=[O:13])[CH3:15]
Reactant: O=c1ccc(-c2cnccn2)c[nH]1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCBr
Solvent: CN(C)C=O
Product: CCn1cc(-c2cnccn2)ccc1=O
Reaction time: 0.75 h

Procedure:
A suspension of 5-(2-pyrazinyl)-2(1H)-pyridone (6.5 g) and 6.6 g of potassium t-butoxide in 250 ml of dry DMF is stirred with warming until all the solid is dissolved. The stirred solution is cooled in an ice bath and 4.6 ml of bromoethane are added when the temperature reaches 5° C. The ice bath is removed and stirring is continued for 45 minutes at which time 0.5 ml of additional bromoethane is added. Stirring is continued over the weekend. 10 g of sodium bisulfate in distilled H2O are added to the reaction mixture which is filtered. The filtrate is evaporated and the residue taken up in boiling isopropanol. The isopropanol solution is treating with decolorizing charcoal and filtered while hot. The filtrate is evaporated in vacuum to remove residual DMF, resulting in the formulation of a solid. The solid is recrystallized from acetonitrile with hot filtration. The starting material crystallizes out. The acetonitrile mother liquid is evaporated and the residue chromatographed on 100 g of silica gel. The column is eluted with ethyl acetate, toluene and finally with methanol in ethyl acetate. The early fractions are discarded and the latter fractions are combined and recrystallized from hot toluene/decane and air dried, resulting in the desired 1-ethyl-5-(2-pyrazinyl)-2-pyridone, M.P. 119.5°-120.7° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([CH2:14]CCN1C(=O)C3C(=CC=CC=3)C1=O)[C:7]([CH3:28])=[C:6]2[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.[C:35]([NH:42][CH2:43]CBr)([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([CH2:14][CH2:43][NH:42][C:35](=[O:36])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:7]([CH3:28])=[C:6]2[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: CC(C)(C)OC(=O)NCCBr
Reactant: COc1ccc2c(=O)n(CCCN3C(=O)c4ccccc4C3=O)c(C)c(-c3ccccc3)c2c1
Product: COc1ccc2c(=O)n(CCNC(=O)OC(C)(C)C)c(C)c(-c3ccccc3)c2c1

Procedure:
Following the procedure for 2-[3-(6-methoxy-3-methyl-1-oxo-4-phenylisoquinolin-2(1H)-yl)propyl]-1H-isoindole-1,3(2H)-dione, using 2-(Boc-amino)ethyl bromide in place of 3-phthalimido-1-bromopropane, tert-butyl 2-(6-methoxy-3-methyl-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethylcarbamate was obtained.
Reaction SMILES: [C:1]1([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:6]=[CH:5][C:4]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16](O)=[O:17])=[CH:11][CH:10]=2)=[CH:3][CH:2]=1.[NH2:25][CH2:26][CH2:27][N:28]([CH3:36])[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32].CCN=C=NCCCN(C)C.ON1C2C=CC=CC=2N=N1>C1COCC1.C(N(CC)CC)C>[C:1]1([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:6]=[CH:5][C:4]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]([NH:25][CH2:26][CH2:27][N:28]([CH3:36])[C:29](=[O:35])[O:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:17])=[CH:11][CH:10]=2)=[CH:3][CH:2]=1
Reactant: CN(CCN)C(=O)OC(C)(C)C
Reactant: O=C(O)Cc1ccc(OCc2ccc(-c3ccccc3)cc2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CN(CCNC(=O)Cc1ccc(OCc2ccc(-c3ccccc3)cc2)cc1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 20 h
Yield: 39.5 %

Procedure:
4-(4-Biphenylylmethoxy)phenylacetic acid (1.51 g), tert-butyl 2-aminoethyl(methyl)carbamate (826 mg), WSC (1 g), 1-hydroxybenzotriazole (798 mg), and triethylamine (2.2 ml) were added to THF (90 ml). The reaction mixture was stirred at room temperature for 20 hr and poured onto water, followed by extraction with ethyl acetate-THF (1:1). The organic layer was washed with water, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride sequentially, dried with sodium sulfate, and concentrated. The residue was purified by alumina column chromatography (eluent; methanol:THF=1:1) followed by recrystallization from THF-IPE gave the titled compound (888 mg).