Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([CH:19]=[N:20][OH:21])[C:3]=1[S:22]([CH3:24])=[O:23].[O-][CH2:26]C.[Na+].IC>C(O)C>[CH3:26][O:21][N:20]=[CH:19][C:4]1[C:3]([S:22]([CH3:24])=[O:23])=[C:2]([NH2:1])[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=1
Reactant: CC[O-]
Reactant: CS(=O)c1c(C=NO)nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c1N
Agent: [Na+]
Solvent: CCO
Solvent: CI
Product: CON=Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1S(C)=O
Yield: 39.3 %

Procedure:
A solution of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)-phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime (0.15 g) in ethanol was added to a solution of sodium ethoxide (0.025 g)in ethanol at 20° C., followed by iodomethane (0.023 ml). The reaction was monitored by HPLC and over the next 24 hours three additional equivalents of iodomethane were added. The reaction mixture was then concentrated and partitioned between dichloromethane and water. The organic layer was water-washed, dried (MgSO4) and concentrated. This was then combined with crude product from another identical preparation and chromatographed on a silica gel column, eluting with hexane/ethyl acetate, to give 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(methyl)oxime (0.06 g)as a yellow solid m.p. 80° C. Compound 17.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][OH:5].CC(C)([O-])C.F[C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[N+:19]([O-:21])=[O:20]>C1COCC1.C(OCC)(=O)C>[F:18][C:16]1[CH:15]=[CH:14][C:13]([N+:19]([O-:21])=[O:20])=[C:12]([O:5][CH2:4][CH2:3][O:2][CH3:1])[CH:17]=1
Reactant: O=[N+]([O-])c1ccc(F)cc1F
Reactant: COCCO
Agent: CC(C)(C)[O-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COCCOc1cc(F)ccc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of 2-methoxy-ethanol in 4 ml dry THF, was added tert-butoxide (378 mg, 3.37 mmol) at 0° C. The resulting mixture was added dropwise to the solution of 2,4-difluoro-1-nitro-benzene (536 mg, 3.37 mmol) in 5 ml dry THF at 0° C. The mixture was stirred at 0° C. for 30 minutes, then diluted with ethyl acetate and washed with brine. The organic layers were combined and concentrated in vacuo to give 4-Fluoro-2-(2-methoxy-ethoxy)-1-nitro-benzene. 4-Fluoro-2-(2-methoxy-ethoxy)-1-nitro-benzene (1.35 g, 6.3 mmol) was treated with p-methoxybenzylamine (1.64 mL, 12.6 mmol) in dimethyl sulfoxide at 80° C. in a sealed tube for 4 hr. After work up with ethyl acetate and water isolated N-(4-methoxybenzyl)3-(2-methoxyethoxy)-4-nitrobenzenamine intermediate. RP-HPLC: 2.13 min; ES-MS (M+H)+=346; To this intermediate added trifluoroacetic acid and heated the reaction mixture at 80° C. for 1 hr to deprotect the p-methoxybenzyl functionality to give final product 3-(2-methoxyethoxy)-4-nitobenzenamine. RP-HPLC: 1.14 min; ES-MS (M+H)+=213; 1H-NMR (MeOH-d4) δ (ppm): 3.4 (s, 3 H), 3.8 (t, 2 H), 4.10 (t, 2 H), 6.2 (dd, 1 H), 6.26 (d, 1 H), 7.76 (d, 1 H).
Reaction SMILES: BrC1C=CC(Br)=CN=1.[F:9][C:10]1[CH:18]=[C:17]([C:19]2[CH:24]=[CH:23][C:22](Br)=[CH:21][N:20]=2)[CH:16]=[C:15]2[C:11]=1[CH2:12][CH:13]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[CH2:14]2.[CH2:34]=[CH:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41].B1C2CCCC1CCC2>>[F:9][C:10]1[CH:18]=[C:17]([C:19]2[CH:24]=[CH:23][C:22]([CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])=[CH:21][N:20]=2)[CH:16]=[C:15]2[C:11]=1[CH2:12][CH:13]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[CH2:14]2
Reactant: C=CCCCCCC
Reactant: CCCCCCCCC1Cc2cc(-c3ccc(Br)cn3)cc(F)c2C1
Agent: B1C2CCCC1CCC2
Agent: Brc1ccc(Br)nc1
Product: CCCCCCCCc1ccc(-c2cc(F)c3c(c2)CC(CCCCCCCC)C3)nc1

Procedure:
Obtained by reacting with 2,5-dibromopyridine to form 4-fluoro-6-(5-bromo-pyridine-2-yl)-2-octyl indane and subsequent reaction with the octene-9-BBN-adduct.
Reaction SMILES: [N:1]1([S:6]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)(=[O:8])=[O:7])[CH:5]=[CH:4][N:3]=[CH:2]1.[O:16](C)[S:17]([C:20]([F:23])([F:22])[F:21])(=[O:19])=[O:18]>C(Cl)Cl>[O-:19][S:17]([C:20]([F:23])([F:22])[F:21])(=[O:18])=[O:16].[CH3:20][N+:3]1[CH:4]=[CH:5][N:1]([S:6]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)(=[O:8])=[O:7])[CH:2]=1
Reactant: O=S(=O)(Oc1ccccc1)n1ccnc1
Reactant: COS(=O)(=O)C(F)(F)F
Solvent: ClCCl
Product: C[n+]1ccn(S(=O)(=O)Oc2ccccc2)c1
Product: O=S(=O)([O-])C(F)(F)F

Procedure:
A solution of phenyl 1H-imidazole-1-sulfonate (450 mg, 2.0 mmol) in DCM (15 mL) was treated with methyl triflate (390 mg, 2.4 mmol) at ambient temperature for 16 h. The solvent was removed and the residue was used for next step without further purification.
Reaction SMILES: [N:1]1([CH2:6][C:7]2[C:12]3[C:13]([C:16]4[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=4)=[N:14][O:15][C:11]=3[C:10]([OH:24])=[C:9]([C:25](OCC)=[O:26])[N:8]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.[NH2:30][CH2:31][C:32]([OH:34])=[O:33].C[O-].[Na+]>>[OH:24][C:10]1[C:11]2[O:15][N:14]=[C:13]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:12]=2[C:7]([CH2:6][N:1]2[CH:5]=[CH:4][CH:3]=[N:2]2)=[N:8][C:9]=1[C:25]([NH:30][CH2:31][C:32]([OH:34])=[O:33])=[O:26]
Reactant: NCC(=O)O
Reactant: CCOC(=O)c1nc(Cn2cccn2)c2c(-c3ccc(OC)cc3)noc2c1O
Agent: C[O-]
Agent: [Na+]
Product: COc1ccc(-c2noc3c(O)c(C(=O)NCC(=O)O)nc(Cn4cccn4)c23)cc1
Temperature: 25 °C
Yield: 68.9 %

Procedure:
Ethyl 4-((1H-pyrazol-1-yl)methyl)-7-hydroxy-3-(4-methoxyphenyl)isoxazolo[4,5-c]pyridine-6-carboxylate (19 mg, 0.048 mmol) and glycine (181 mg, 2.41 mmol) were added to sodium methoxide solution (3.6 mL, 1.81 mmol, 0.5 M in MeOH) and the mixture was refluxed for 3 days. The mixture was cooled to room temperature and the solvent was removed in vacuo. The residue was dissolved in 10 mL of water, and washed with EtOAc. The aqueous layer was acidified to pH 3 with 4M hydrochloric acid and extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated to give 14 mg of the title compound. MS: (+) m/z 424.31 (M+1).
Reaction SMILES: [C:1]([Cl:5])(=O)[CH2:2][CH3:3].[CH3:6][O:7][C:8]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:9]=1[CH2:10][CH2:11][C@H:12]([NH:19][CH2:20][CH2:21][CH3:22])[C@@H:13]2[CH3:18].C(N(CC)CC)C.[H-].[H-].[H-].[H-].[Li+].[Al+3]>CCOCC.C1COCC1>[ClH:5].[CH3:6][O:7][C:8]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:9]=1[CH2:10][CH2:11][C@H:12]([N:19]([CH2:1][CH2:2][CH3:3])[CH2:20][CH2:21][CH3:22])[C@@H:13]2[CH3:18]
Reactant: CCCN[C@H]1CCc2c(OC)cccc2[C@H]1C
Reactant: CCC(=O)Cl
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: CCCN(CCC)[C@H]1CCc2c(OC)cccc2[C@H]1C
Product: Cl
Yield: 42.8 %

Procedure:
Propionyl chloride (0.49 g, 5.2 mmol) in dry ether (10 ml) was added to a solution of cis-5-methoxy-1-methyl-2-(n-propylamino)tetralin (350 mg, 1.5 mmol) and triethylamine (0.49 g, 4.9 mmol) in dry ether (80 ml). After 30 min. at room temperature the reaction mixture was filtered and the ether was evaporated. The resulting crude amide was passed through an alumina column eluted with ether. The purified amide dissolved in dry THF (20 ml) was added to a suspension of LiAlH4 (1.0 g, 26 mmol) in dry THF (30 ml) under N2. After stirring under reflux for 3 h, the reaction mixture was hydrolyzed, the precipitate was filtered off and the solvent was evaporated. The oily residue was chromatographed on an alumina column with ether-light petroleum (1:1) as eluant. The hydrochloride was prepared and recrystallized from EtOH-ether to give 200 mg (42%) of title product: mp 170.5°-171.5° C.; GC (215° C.) isomeric purity >95%, retention time 2.45 min; NMR (MeOH-d4) δ1.05 (t,6H) δ1.32 (d,3H) δ1.64-3.66 (m,14H), δ3.80 (s,3H), δ6.71-6.82 (m,2H), δ7.10-7.20 (m,1H); MS (70 eV) m/z 275 (28%), 246 (100%), 176 (69%).
Reaction SMILES: [CH2:1]([CH:6]1[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5].S(OC)(O[CH3:17])(=O)=O>C1COCC1.[H-].[Na+]>[CH3:17][O:12][CH:9]1[CH2:8][CH2:7][CH:6]([CH2:1][CH2:2][CH2:3][CH2:4][CH3:5])[CH2:11][CH2:10]1
Reactant: COS(=O)(=O)OC
Reactant: CCCCCC1CCC(O)CC1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCCCC1CCC(OC)CC1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
Under argon, to a solution of 4-pentylcyclohexanol (2.0 g, 11.75 mmol) in anhydrous THF (60 mL), NaH was added (60%, 0.94 g, 23.5 mmol) at 0° C. and stirred for 30 minutes, followed by the addition of dimethyl sulfate (1.68 mL, 17.62 mmol). The mixture was refluxed for 12 hrs and cooled to 0° C. The reaction was quenched with saturated ammonium chloride solution (20 mL). THF was removed under vacuum and the residue was extracted with CH2Cl2 (3×25 mL). The collected organic portion was dried with Na2SO4 and concentrated. The crude product was purified by flash chromatography (hexanes/ethyl acetate: 15/1) to provide probe 1 (2.0 g, quant.) as a colorless liquid. 1H NMR (400 MHz, CDCl3): δ=0.79-0.85 (m, 10 H), 1.28-1.38 (m, 7 H), 1.46 (br, 2 H), 2.02 (br, 2 H), 3.32 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ=8.1, 20.9 (2 carbons), 24.1 (2 carbons), 30.2 (2 carbons), 32.6, 34.8, 45.2, 55.5, 74.8; MS (ESI) calcd for C12H25O [M+H]+/z: 185.19. found: 185.31.
Reaction SMILES: [Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[Si]([O:20][CH:21]([C:23]1[CH:57]=[CH:56][C:26]([CH2:27][N:28]2[C:33](=[O:34])[C:32]([CH2:35][C:36]3[CH:41]=[CH:40][C:39]([C:42]4[C:43]([C:48]#[N:49])=[CH:44][CH:45]=[CH:46][CH:47]=4)=[CH:38][CH:37]=3)=[C:31]([CH2:50][CH2:51][CH3:52])[N:30]3[N:53]=[CH:54][N:55]=[C:29]23)=[CH:25][CH:24]=1)[CH3:22])(C(C)(C)C)(C)C>C(OCC)(=O)C>[OH:20][CH:21]([C:23]1[CH:57]=[CH:56][C:26]([CH2:27][N:28]2[C:33](=[O:34])[C:32]([CH2:35][C:36]3[CH:41]=[CH:40][C:39]([C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=4[C:48]4[NH:49][C:4](=[O:7])[O:5][N:3]=4)=[CH:38][CH:37]=3)=[C:31]([CH2:50][CH2:51][CH3:52])[N:30]3[N:53]=[CH:54][N:55]=[C:29]23)=[CH:25][CH:24]=1)[CH3:22]
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(Cc2ccc(C(C)O[Si](C)(C)C(C)(C)C)cc2)c2ncnn12
Reactant: O=C([O-])O
Reactant: [NH3+]O
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CCCc1c(Cc2ccc(-c3ccccc3-c3noc(=O)[nH]3)cc2)c(=O)n(Cc2ccc(C(C)O)cc2)c2ncnn12
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 56.5 %

Procedure:
A mixture of hydroxylammonium chloride (2.4 g), sodium hydrogen carbonate (3.9 g) and dimethyl sulfoxide (15 mL) was stirred at 40° C. for 30 min, 4′-({4-[4-(1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)benzyl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (1.4 g) was added, and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (15 mL). N,N′-Carbonyldiimidazole (0.45 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.38 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (30 mL). Tetrabutylammonium bromide (1.0 M tetrahydrofuran solution, 5.8 mL) was added, and the mixture was stirred at 50° C. for 3 hr. The reaction mixture was extracted with 1 N hydrochloric acid and ethyl acetate, and the ethyl acetate layer was washed with saturated brine and concentrated. The residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.72 g, 56%).
Reaction SMILES: [CH2:1]([N:5]1[C:14](=[O:15])[C:13]2[NH:12][CH:11]=[N:10][C:9]=2[N:8]([CH2:16][CH2:17][CH2:18][CH3:19])[C:6]1=[O:7])[CH2:2][CH2:3][CH3:4].C1C(=O)N([I:27])C(=O)C1>CN(C=O)C>[CH2:1]([N:5]1[C:14](=[O:15])[C:13]2[NH:12][C:11]([I:27])=[N:10][C:9]=2[N:8]([CH2:16][CH2:17][CH2:18][CH3:19])[C:6]1=[O:7])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCn1c(=O)c2[nH]cnc2n(CCCC)c1=O
Reactant: O=C1CCC(=O)N1I
Solvent: CN(C)C=O
Product: CCCCn1c(=O)c2[nH]c(I)nc2n(CCCC)c1=O
Temperature: 25 °C
Reaction time: 23 h
Yield: 5.7 %

Procedure:
A stirred solution of 1,3-di-N-butyl xanthine (100 mg, 3.39 mmol) in anhydrous DMF (3 ml) was treated with NIS (94 mg, 3.75 mmol) and left to stir at rt. under nitrogen for 23 hours. The mixture was partitioned between sat. Na2SO3 (aq) solution and EtOAc. The organic layer was separated, washed with brine, dried (MgSO4) and concentrated in vacuo. The product was purified by passing down an SPE (Si, 5 g) cartridge eluting with EtOAc/cyclohexane mixtures. The product fraction was concentrated to afford the title compound as a white solid (75 mg, 51%); NMR; δH (400 MHz, d6-DMSO) (app. td, 6H, J=7.5 and 4 Hz), 1.21-1.34 (m, 4H), 1.45-1.54 (m, 2H), 1.56-1.66 (m, 2H), 3.84 (t, 2H, J=7.5 Hz), 3.93 (t, 2H, J=7.5 Hz), 14.10 (s, 1H); m/z 391.3[MH+].
Reaction SMILES: [C:1]([C:4]1[CH:13]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=2)[C:12]2[C:11](=[O:22])[NH:10][CH:9]=[CH:8][C:7]=2[NH:6][C:5]=1[CH3:23])(=[O:3])[CH3:2].[H-].[Na+].I[CH:27]([CH3:29])[CH3:28].CO>CN(C=O)C>[C:1]([C:4]1[CH:13]([C:14]2[CH:15]=[CH:16][C:17]([C:18]#[N:19])=[CH:20][CH:21]=2)[C:12]2[C:7](=[CH:8][CH:9]=[N:10][C:11]=2[O:22][CH:27]([CH3:29])[CH3:28])[NH:6][C:5]=1[CH3:23])(=[O:3])[CH3:2]
Reactant: CC(C)I
Reactant: CC(=O)C1=C(C)Nc2cc[nH]c(=O)c2C1c1ccc(C#N)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: CN(C)C=O
Product: CC(=O)C1=C(C)Nc2ccnc(OC(C)C)c2C1c1ccc(C#N)cc1
Reaction time: 24 h

Procedure:
100 mg (0.32 mmol) of 4-(3-acetyl-2-methyl-5-oxo-1,4,5,6-tetrahydro-1,6-naphthyridin-4-yl)-benzonitrile are suspended in DMF (4 ml), and 14 mg (0.36 mmol) of sodium hydride (60% in mineral oil) are added. Then 34 μl (0.34 mmol) of 2-iodopropane are added to the dark red solution. The solution is stiffed at RT for 24 h, then mixed with methanol and purified by preparative HPLC. 18 mg (16% of theory) of the title compound are obtained as a white solid.
Reaction SMILES: O/[C:2](/[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[C:3](/[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)\[CH:4]=O.CC1C=CC(S(O)(=O)=O)=CC=1.[CH3:29][NH:30][C:31]([NH2:33])=[O:32].C(OCC)C>C1(C)C=CC=CC=1.C(Cl)Cl>[CH3:29][N:30]1[C:2]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:3]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH:4]=[N:33][C:31]1=[O:32]
Reactant: CNC(N)=O
Reactant: O=C/C(=C(\O)c1ccccc1)c1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: ClCCl
Solvent: CCOCC
Product: Cn1c(-c2ccccc2)c(-c2ccccc2)cnc1=O

Procedure:
A solution of (Z)-3-hydroxy-2,3-diphenyl-propenal (105, 423 mg, 1.89 mmol), pTSA (30 mg, 7.56 mmol) and methyl urea (118 mg, 0.62 mmol) in toluene was heated at 110° C. overnight. The reaction was quenched with water, and the products were extracted with ethyl acetate. The organic layer was separated and washed with brine, and dried over MgSO4, and concentrated in vacuo to produce a yellow oil. The crude product was dissolved in CH2Cl2 and titrated with diethyl ether to give the title compound as a white solid.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[C:6]2[C:9]([CH3:12])=[CH:10][S:11][C:5]=2[N:4]=[C:3]1[SH:13].[OH-].[Na+].CN(C=O)C.[Cl:21][C:22]1[CH:37]=[CH:36][C:25]([C:26]([C:28]2[CH:35]=[CH:34][C:31]([CH2:32]Br)=[CH:30][CH:29]=2)=[O:27])=[CH:24][CH:23]=1>CO.O>[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([C:26]([C:28]2[CH:35]=[CH:34][C:31]([CH2:32][S:13][C:3]3[N:2]([CH3:1])[C:7](=[O:8])[C:6]4[C:9]([CH3:12])=[CH:10][S:11][C:5]=4[N:4]=3)=[CH:30][CH:29]=2)=[O:27])=[CH:36][CH:37]=1
Reactant: O=C(c1ccc(Cl)cc1)c1ccc(CBr)cc1
Reactant: Cc1csc2nc(S)n(C)c(=O)c12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CN(C)C=O
Solvent: CO
Product: Cc1csc2nc(SCc3ccc(C(=O)c4ccc(Cl)cc4)cc3)n(C)c(=O)c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 39.9 %

Procedure:
To a solution of 3,5-dimethyl-2-mercaptothieno[2,3-d]pyrimidin-4(3H)-one (1.06 g) and sodium hydroxide (205 mg) in 50% methanol (16 ml)-DMF (4 ml) was added 4-(4-chlorobenzoyl)benzyl bromide (1.69 g) and the mixture was stirred at room temperature for 1 hour. This reaction mixture was poured in water and the resulting crystals were collected by filtration, rinsed with water, and recrystallized from ethyl acetate to provide the title compound as colorless solid (878 mg).
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8](Cl)=[N:9]2)([O-])=O.[F:15][C:16]1[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1.[CH:26]1([NH2:31])[CH2:30][CH2:29][CH2:28][CH2:27]1>>[CH:26]1([NH:31][C:8]2[CH:7]=[CH:6][C:5]3[C:10](=[CH:11][CH:12]=[CH:13][C:4]=3[NH:1][S:22]([C:19]3[CH:20]=[CH:21][C:16]([F:15])=[CH:17][CH:18]=3)(=[O:24])=[O:23])[N:9]=2)[CH2:30][CH2:29][CH2:28][CH2:27]1
Reactant: O=S(=O)(Cl)c1ccc(F)cc1
Reactant: NC1CCCC1
Reactant: O=[N+]([O-])c1cccc2nc(Cl)ccc12
Product: O=S(=O)(Nc1cccc2nc(NC3CCCC3)ccc12)c1ccc(F)cc1

Procedure:
The title compound, MS: m/e=385.4 (M+H+), was prepared in accordance with the general method of example 13 from 5-nitro-2-chloroquinoline, 4-fluorobenzenesulfonyl chloride and cyclopentylamine.
Reaction SMILES: [CH3:1][I:2].[CH:3]([O:6][C:7]1[C:8]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[N:9][S:10][N:11]=1)([CH3:5])[CH3:4]>CC(C)=O>[I-:2].[CH:3]([O:6][C:7]1[C:8]([C:12]2[CH:13]=[N+:14]([CH3:1])[CH:15]=[CH:16][CH:17]=2)=[N:9][S:10][N:11]=1)([CH3:5])[CH3:4]
Reactant: CI
Reactant: CC(C)Oc1nsnc1-c1cccnc1
Solvent: CC(C)=O
Product: CC(C)Oc1nsnc1-c1ccc[n+](C)c1
Product: [I-]
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of methyl iodide (0.3 ml, 5 mmol) and 3-(4-isopropoxy-1,2,5-thiadiazol-3-yl)pyridine (540 mg, 2.4 mmol) in acetone (5 ml) was stirred at room temperature for 18 h. The title compound precipitated from the solution and was collected by filtration to yield 0.68 g (77%).
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]([Br:12])=[CH:5][N:6]=[CH:7]2.[C:13](Cl)(=[O:31])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]/[CH:21]=[CH:22]\[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]>>[Br:12][C:4]1[C:3]2[C:8](=[CH:9][CH:10]=[CH:11][C:2]=2[NH:1][C:13](=[O:31])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]/[CH:21]=[CH:22]\[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH:7]=[N:6][CH:5]=1
Reactant: Nc1cccc2cncc(Br)c12
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)Cl
Product: CCCCCCCC/C=C\CCCCCCCC(=O)Nc1cccc2cncc(Br)c12

Procedure:
5-Amino-4-bromoisoquinoline (prepared according to the process described by Gordon et al., J. Het. Chem., 4, 410 (1967)) was coupled with oleoyl chloride using the procedure described in Example 4, to give the title compound.
Reaction SMILES: COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:10])=CC=1.[F:23][C:24]1[CH:25]=[C:26]([N:30]([CH3:39])[C:31]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)=O)[CH:27]=[CH:28][CH:29]=1>C1(C)C=CC=CC=1>[F:23][C:24]1[CH:25]=[C:26]([N:30]([CH3:39])[C:31]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)=[S:10])[CH:27]=[CH:28][CH:29]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CN(C(=O)c1ccccn1)c1cccc(F)c1
Solvent: Cc1ccccc1
Product: CN(C(=S)c1ccccn1)c1cccc(F)c1
Yield: 87.4 %

Procedure:
Lawesson's reagent (3.20 g, 7.9 mmol) and N-(3-fluorophenyl)-N-methyl-2-pyridinecarboxamide (3.51 g, 15.2 mmol) were heated to reflux in toluene (45 mL) under nitrogen for 2 hours. The residue, after evaporation of the solvent, was dissolved in dichloromethane, preadsorbed onto silica gel, and flash chromatographed (250 g of silica gel eluted with 10% ethyl acetate in petroleum ether) to yield N-(3-fluorophenyl)-N-methyl-2-pyridinecarbothioamide as a yellow solid (1.70 g, 45%), m.p. 100°-103° C.
Reaction SMILES: CCCCCC.C([Li])CCC.Br[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[C:15]([CH2:23][C:24]2[S:28][C:27]3[CH:29]=[CH:30][C:31]([CH2:33][CH3:34])=[CH:32][C:26]=3[CH:25]=2)[CH:14]=1.[CH2:35]([O:42][CH:43]1[CH:48]([O:49][CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[CH:47]([O:57][CH2:58][C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[CH:46]([CH2:65][O:66][CH2:67][C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=2)[O:45][C:44]1=[O:74])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[Cl-].[NH4+]>C1COCC1>[CH2:35]([O:42][C@@H:43]1[C@H:48]([O:49][CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[C@@H:47]([O:57][CH2:58][C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=2)[C@@H:46]([CH2:65][O:66][CH2:67][C:68]2[CH:69]=[CH:70][CH:71]=[CH:72][CH:73]=2)[O:45][C:44]1([C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[C:15]([CH2:23][C:24]2[S:28][C:27]3[CH:29]=[CH:30][C:31]([CH2:33][CH3:34])=[CH:32][C:26]=3[CH:25]=2)[CH:14]=1)[OH:74])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1
Reactant: CCc1ccc2sc(Cc3cc(Br)c4ccccc4c3)cc2c1
Reactant: O=C1OC(COCc2ccccc2)C(OCc2ccccc2)C(OCc2ccccc2)C1OCc1ccccc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCc1ccc2sc(Cc3cc(C4(O)O[C@H](COCc5ccccc5)[C@H](OCc5ccccc5)[C@@H](OCc5ccccc5)[C@H]4OCc4ccccc4)c4ccccc4c3)cc2c1
Reaction time: 0.08 h
Yield: 0.1 %

Procedure:
In a nitrogen stream, an n-butyllithium hexane solution (1.6 M, 0.83 ml, 1.33 mmol) was added dropwise to a solution of 2-(4-bromonaphtalen-2-ylmethyl)-5-ethylbenzo-[b]thiophene (460 mg, 1.21 mmol) in THF (15 ml) at −78° C. The reaction mixture was stirred at the same temperature for five minutes and to this solution, a solution of 3,4,5-trisbenzyloxy-6-benzyloxymethyltetrahydro-pyran-2-one (844 mg, 1.57 mmol) in THF (5 ml) was added dropwise. The reaction solution was stirred at −78° C. for five minutes and a saturated ammonium chloride aqueous solution was added to stop the reaction. The reaction mixture was extracted with ethyl acetate and the organic layer was washed with a saturated sodium chloride aqueous solution and dried (anhydrous magnesium sulfate), and then the solvent was distilled under reduced pressure. The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:9)] to obtain the title compound (1.06 mg, 100%).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH2:13][N:14]2[CH:18]=[C:17]([I:19])[CH:16]=[C:15]2[CH:20]=[O:21])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[BH4-].[Na+].C(O)(=O)C>C(O)C>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([O:11][CH2:12][CH2:13][N:14]2[CH:18]=[C:17]([I:19])[CH:16]=[C:15]2[CH2:20][OH:21])(=[O:10])=[O:9])=[CH:6][CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)OCCn2cc(I)cc2C=O)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCO
Product: Cc1ccc(S(=O)(=O)OCCn2cc(I)cc2CO)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 94.8 %

Procedure:
2-(2-Formyl-4-iodo-pyrrol-1-yl)ethyl 4-methylbenzenesulfonate (2.1 g, 5.01 mmol) in ethanol (25 mL) was cooled to 0° C. and sodium borohydride (95 mg, 2.50 mmol) was added. After 30 min, the reaction mixture was allowed to warm to ambient temperature and stirred for a further 1 h, after which time acetic acid was added and the mixture was concentrated in vacuo. The residue was partitioned between water and dichloromethane and the organic phase was washed with water, brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give 2-[2-(hydroxymethyl)-4-iodo-pyrrol-1-yl]ethyl 4-methylbenzenesulfonate (2.0 g, 95%) as a brownish crystalline solid.