Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[CH:8][C:7]([S:10][CH2:11]Cl)=[CH:6][CH:5]=1.SC1C=CC(C(OC)=O)=CC=1.[Na].[I:26][C:27]1[CH:28]=[N:29][C:30](=[O:33])[NH:31][CH:32]=1>CN(C=O)C>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]([S:10][CH2:11][N:31]2[CH:32]=[C:27]([I:26])[CH:28]=[N:29][C:30]2=[O:33])=[CH:6][CH:5]=1)=[O:13]
Reactant: O=c1ncc(I)c[nH]1
Reactant: COC(=O)c1ccc(SCCl)cc1
Agent: COC(=O)c1ccc(S)cc1
Agent: [Na]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(SCn2cc(I)cnc2=O)cc1
Yield: 92 %

Procedure:
A solution of methyl4-(chloromethylthio)benzoate [The methyl 4-(chloromethylthio)benzoate reagent was made in the conventional manner as previously described for its analogues in Preparations 1 and 4 by chloromethylation of methyl 4-mercaptobenzoate; yield 92%] (8.2 mmol) in DMF (10 ml) was added dropwise to a stirred suspension of the sodium salt of 5-iodopyrimidin-2-one (8.2 mmol) in DMF (50 ml) and the final mixture heated at 60° C. for 3h. The solvent was then distilled off, the residue triturated with water and with a little ether. The product was a mixture of the N- and O-isomers in the ratio 4:1; yield 1.50g (45%). The title compound, the N-isomer, was obtained after fractional crystallisation from ethyl acetate and methanol, m.p. 210° C. NMR (TFA); δ 4.09 (Me), 5.60 (CH2), 7.4-8.2 (Ph), 8.67 (H-4, J4,6 3Hz) 8.87 (H-6). 1R (KBr): 1640 (CO), 1710 cm-1 (CO-ester). MS [70 eV, m/z (% rel. int.)].
Reaction SMILES: [OH:1][C@H:2]([C:5]1[O:6][C:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:9]=1)[CH2:3]O.COC(OC)(OC)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(Cl)Cl>[C:10]1([C:8]2[N:9]=[C:5]([C@@H:2]3[CH2:3][O:1]3)[O:6][C:7]=2[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: OC[C@H](O)c1nc(-c2ccccc2)c(-c2ccccc2)o1
Agent: COC(C)(OC)OC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Product: c1ccc(-c2nc([C@@H]3CO3)oc2-c2ccccc2)cc1
Reaction time: 0.5 h
Yield: 75.9 %

Procedure:
To a solution of 2-((1S)-1,2-dihydroxyethyl)-4,5-diphenyloxazole (20 g) in CH2Cl2 (400 ml) were added orthoacetic acid trimethyl ester (12.8 ml) and p-toluenesulfonic acid (130 mg) at room temperature under N2. After being stirred for 30 minutes, the solvent was evaporated in vacuo. The residue was diluted with CH2Cl2 (200 ml) and acetyl bromide (7.6 ml) was added to the solution at 0° C. under N2. After being stirred for 2 hours at room temperature, the solvent was evaporated in vacuo, the residue was diluted with methanol (200 ml), and K2CO3 (16 g) was added to the solution at 0° C. The mixture was stirred for 30 minutes at the same temperature and partitioned between ethyl acetate and water. The organic layer was washed with 1N-HCl, water, sat. NaHCO3 and brine. The dried solvent was evaporated in vacuo and the residue was purified by trituration with ether-hexane to give (2S)-2-(4,5-diphenyloxazol-2-yl)oxirane (14.2 g).
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]([CH3:11])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[Cl:29])[N:6]2[CH:12]1[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]1.[CH2:30]([N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1)[CH3:31].C(N(CC)CC)C>C(O)C>[Cl:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[C:5]1[N:6]([CH:12]2[CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15]2)[C:7]2[C:3]([N:4]=1)=[C:2]([N:35]1[CH2:36][CH2:37][N:32]([CH2:30][CH3:31])[CH2:33][CH2:34]1)[N:10]=[C:9]([CH3:11])[N:8]=2
Reactant: Cc1nc(Cl)c2nc(-c3ccccc3Cl)n(C3CN(C(=O)OC(C)(C)C)C3)c2n1
Reactant: CCN1CCNCC1
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCN1CCN(c2nc(C)nc3c2nc(-c2ccccc2Cl)n3C2CN(C(=O)OC(C)(C)C)C2)CC1
Yield: 48.8 %

Procedure:
Heat a solution of tert-butyl 3-(6-chloro-8-(2-chlorophenyl)-2-methyl-9H-purin-9-yl)azetidine-1-carboxylate (0.012 mol, 5.5 g), N-ethyl piperazine (0.013 mol, 1.59 g, 1.1 equiv.), and triethylamine (0.013 mol, 1.41 g, 1.1 equiv.) in ethanol (25.0 mL) at 90° C. for 16 hours. Concentrate the reaction mixture under reduced pressure. Dissolve the residue in dry dichloromethane. Wash with saturated sodium bicarbonate solution, water, and brine. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate under reduced pressure to give the residue. Purify the residue by silica gel chromatography eluting with dichloromethane:methanol 98:2 to give tert-butyl 3-(8-(2-chlorophenyl)-6-(4-ethylpiperazin-1-yl)-2-methyl-9H-purin-9-yl)azetidine-1-carboxylate (3.0 g). MS (m/z): 512.31 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([N:13]3[CH2:18][CH2:17][CH:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[O:25][CH3:26])[CH2:15][CH2:14]3)=[O:12])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.Cl[CH2:28][C:29]([NH:31][CH3:32])=[O:30]>>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([N:13]3[CH2:18][CH2:17][CH:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[O:25][CH3:26])[CH2:15][CH2:14]3)=[O:12])=[CH:7][N:8]2[CH2:28][C:29]([NH:31][CH3:32])=[O:30])=[CH:4][CH:3]=1
Reactant: CNC(=O)CCl
Reactant: COc1ccccc1C1CCN(C(=O)c2c[nH]c3cc(Cl)ccc23)CC1
Product: CNC(=O)Cn1cc(C(=O)N2CCC(c3ccccc3OC)CC2)c2ccc(Cl)cc21

Procedure:
Following general procedure II, the alkylation of (6-Chloro-1H-indol-3-yl)-[4-(2-methoxy-phenyl)-piperidin-1-yl]-methanone (preparation described herein), with (commercially available) 2-chloro-N-methyl-acetamide gave the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5](=[C:8]2C(=O)OC(C)(C)[O:10][C:9]2=[O:17])[NH:6][CH:7]=1>Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([OH:17])=[O:10])=[N:6][CH:7]=1
Reactant: CC1(C)OC(=O)C(=C2C=CC(Br)=CN2)C(=O)O1
Agent: Cl
Product: O=C(O)Cc1ccc(Br)cn1

Procedure:
A solution of 5-(5-bromopyridin-2(1H)-ylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (3) (40.0 g, 133.3 mmol) in HCl (30%, 400 mL) was heated gently to reflux, and was refluxed for 2 h. The solvent was removed in vacuo and the residue (29.75 g) was used in the next step without further purification. 1H-NMR (CDCl3, 300 MHz): δ 3.79 (s, 2H, CH2), 7.41 (d, 1H, ArH), 8.08 (dd, 1H, ArH), 8.66 (d, 1H, ArH).
Reaction SMILES: O[C@@H]1CCN(C(C2C=CC(OC(F)(F)F)=CC=2)=O)[C@H]1C(N[O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=O.NCCNCC(NC([C:44]1[CH:49]=[CH:48][C:47]([C:50]2C=CC(CC)=C[CH:51]=2)=[CH:46][CH:45]=1)=O)C(=O)NO.C1C[O:61]CC1>O.CCCCCC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:47]1([C:50]#[C:51][C:28]2[CH:27]=[CH:26][C:25]([C:24]([OH:23])=[O:61])=[CH:30][CH:29]=2)[CH:48]=[CH:49][CH:44]=[CH:45][CH:46]=1
Reactant: CCc1ccc(-c2ccc(C(=O)NC(CNCCN)C(=O)NO)cc2)cc1
Reactant: C1CCOC1
Reactant: O=C(NOCc1ccccc1)[C@H]1[C@H](O)CCN1C(=O)c1ccc(OC(F)(F)F)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCCCCC
Solvent: O
Product: O=C(O)c1ccc(C#Cc2ccccc2)cc1
Temperature: 10 °C
Reaction time: 2.5 h

Procedure:
The 4-iodo-benzoic acid methyl ester 1 (20.0 g, 76.34 mmol), ethynyl-benzene 2 (8.56 g, 83.96 mmol), PdCl2(PPh3)2 (0.65 g, 0.92 mmol), and CuI (0.35 g, 1.83 mmol) were mixed with THF (110 ml) in a round bottom under argon. The dry THF was sparged with dry, oxygen-free argon for at least 5 min. immediately before use. The reaction was cooled to 10° C. and TEA (16 ml) was added. The cooling bath was removed and the reaction was stirred at RT under argon. After 2.5 h, the reaction was diluted with EtOAc (400 ml) and the solids were filtered off through a pad of celite. The organic filtrate was washed with 1M HCl (60 ml), sat. aq. NaHCO3 (60 ml), water (60 ml), brine (60 ml), dried with Na2SO4, filtered and concentrated under reduced pressure. The crude solid methyl ester was dissolved in MeOH (400 ml), 6M NaOH (30 ml) and water (50 ml). The reaction was stirred at 70° C. until a clear solution was formed (about 1 h). The reaction could be followed by LCMS. The reaction was cooled and diluted with water (500 ml) and hexane (100 ml). The pH was adjusted to pH 6-7. The white solid that formed was collected and washed with water (3×60 ml) and hexane (3×60 ml). The solid 3 was dried in vacuo yielding 17.3 g (approximately quantitative yield in 99% purity).
Reaction SMILES: [OH:1][CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([CH:12]=[CH:13][C:14]=1[N+:15]([O-])=O)[C:8]([O:10][CH3:11])=[O:9].CCCCCC.C(OCC)(=O)C>C(O)C.[Pt]=O>[NH2:15][C:14]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]=1[O:4][CH2:3][CH2:2][OH:1]
Reactant: COC(=O)c1ccc([N+](=O)[O-])c(OCCO)c1
Agent: O=[Pt]
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: CCO
Product: COC(=O)c1ccc(N)c(OCCO)c1
Reaction time: 0.67 h
Yield: 101 %

Procedure:
To a sample of methyl 3-(2-hydroxyethoxy)-4-nitrobenzoate (3.28 g, 0.0136 mol) dissolved in ethanol was added platinum oxide (50 mg). The mixture was hydrogenated for 40 min at 35 psi. Thin-layer chromatographic analysis (SiO2, 3:2 hexane:ethyl acetate) showed disappearance of starting material along with the formation of a new, lower-running spot (Rf =01) indicating the reaction was complete. The mixture was then filtered through a pad of Celite and the pad washed with fresh ethanol. The filtrate was concentrated and dried in vacuo to give 2.9 g (100%) of methyl 4-amino-3-(2-hydroxyethoxy)benzoate as an off-white solid.
Reaction SMILES: [C:1]([O:12][CH3:13])(=[O:11])[C:2]1[CH:10]=[CH:9][C:5]([C:6]([O-:8])=[O:7])=[CH:4][CH:3]=1.CN(C)C=O.S(Cl)([Cl:21])=O.[CH:23]([N:26]([CH:29]([CH3:31])[CH3:30])[CH2:27][CH3:28])([CH3:25])[CH3:24]>COCCOC>[Cl-:21].[CH3:13][O:12][C:1](=[O:11])[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[CH:23]([N:26]([CH:29]([CH3:31])[CH3:30])[CH2:27][CH3:28])([CH3:25])[CH3:24].[Cl-:21].[CH3:13][O:12][C:1](=[O:11])[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1
Reactant: COC(=O)c1ccc(C(=O)[O-])cc1
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Solvent: COCCOC
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc(C(=O)O)cc1
Product: [Cl-]
Temperature: 10 °C
Reaction time: 0.5 h

Procedure:
A suspension of 10.00 g (55.51 mmol) of monomethyl terephthalate in 90 mL of 1,2-dimethoxyethane was stirred, while it is cooled in a cold bath at 10° C. To the suspension were added 2.0 mL of N,N-dimethylformamide and 6.61 g (52.75 mmol) of thionyl chloride in this order, and the suspension was stirred at 60° C. to 65° C. for 1 hour. The mixture was cooled, and 6.83 g (52.82 mmol) of diisopropylethylamine was added dropwise to the mixture under cooling with ice bath. Subsequently, the reaction mixture was stirred at room temperature, and the stirring was stopped 30 minute after the internal temperature had reached 20° C. The reaction mixture was placed in a 200-mL flask to yield 109.49 g of [terephthalic acid monomethyl ester chloride/diisopropylethylamine] (the content of terephthalic acid monomethyl ester chloride: 8.89 g) as a slightly tannish solution.
Reaction SMILES: CC1C=CC(S(O[C:12]2[C:13]3[CH2:23][CH2:22][CH2:21][CH2:20][C:19]([CH3:25])([CH3:24])[C:14]=3[N:15]=[C:16]([NH2:18])[N:17]=2)(=O)=O)=CC=1.C(O[C:31](=O)[N:32](C)[C@@H:33]1[CH2:37][CH2:36][NH:35][CH2:34]1)(C)(C)C.N1C[CH2:43][C@@H:42](NC(=O)OC(C)(C)C)[CH2:41]1>>[CH3:31][NH:32][C@@H:33]1[CH2:37][CH2:36][N:35]([C:14]2[C:13]3[CH2:23][CH2:22][CH2:21][CH:20]([C:19]4[CH:24]=[CH:43][CH:42]=[CH:41][CH:25]=4)[C:12]=3[N:17]=[C:16]([NH2:18])[N:15]=2)[CH2:34]1
Reactant: Cc1ccc(S(=O)(=O)Oc2nc(N)nc3c2CCCCC3(C)C)cc1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCNC1
Reactant: CN(C(=O)OC(C)(C)C)[C@@H]1CCNC1
Product: CN[C@@H]1CCN(c2nc(N)nc3c2CCCC3c2ccccc2)C1

Procedure:
The title compound was prepared according to the procedures of Examples 1E and 1F, substituting the product from Example 9C for the product from Example 1D and substituting (R)-tert-butylmethyl(pyrrolidin-3-yl)carbamate for (R)-tert-butyl pyrrolidin-3-ylcarbamate. 1H NMR (300 MHz, CDCl3) δ 7.24 (m, 2H), 7.16 (t, J=7.29 Hz, 1H), 7.07 (d, J=7.12 Hz, 2H), 4.53 (s, 2H), 3.96 (t, J=6.27 Hz, 1H), 3.74 (m, 3H), 3.47 (m, 1H), 3.29 (m, 1H), 2.73 (m, 2H), 2.49 (d, J=2.71 Hz, 3H), 2.14 (m, 2H), 1.80 (m, 4H). MS (ESI+) m/z 324 (M+H)+.
Reaction SMILES: N#N.[CH3:3][C:4]1([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([CH2:15][OH:16])[CH:10]=2)[O:8][CH2:7][CH2:6][O:5]1.CCN(CC)CC.[S:24](Cl)([CH3:27])(=[O:26])=[O:25]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:3][C:4]1([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([CH2:15][O:16][S:24]([CH3:27])(=[O:26])=[O:25])[CH:10]=2)[O:5][CH2:6][CH2:7][O:8]1
Reactant: CC1(c2ccnc(CO)c2)OCCO1
Reactant: CS(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Agent: N#N
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC1(c2ccnc(COS(C)(=O)=O)c2)OCCO1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of [4-(2-methyl-[1,3]dioxolan-2-yl)-pyridin-2-yl]-methanol (950 mg, 4.87 mmol) in dry CH2Cl2 (5 mL) was treated at 0° C. with Et3N (0.88 mL, 6.29 mmol) followed by DMAP (60 mg, 0.49 mmol) and Ms-Cl (0.49 mL, 6.15 mmol). After stirring at rt for 2 h, the reaction was quenched with water (5 mL). The org. layer was dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue by FC (5:1 to 2:1 hept-EA) gave the title compound as a yellow oil. LC-MS-conditions 02: tR=0.76 min, [M+H]+=274.30.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]([NH:17][C:18](=[O:30])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25](OCC)=[O:26])[CH:8]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:10]=1[OH:11])=[O:5])[CH3:2].[C:31]([O-])([O-])=O.[K+].[K+].S(OC)(OC)(=O)=O>CC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[N:7]([N:17]2[C:18](=[O:30])[C:19]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:25]2=[O:26])[CH:8]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:10]=1[O:11][CH3:31])=[O:5])[CH3:2]
Reactant: O=C([O-])[O-]
Reactant: CCOC(=O)c1ccccc1C(=O)Nn1cc(C(=O)OCC)c(O)c1C(=O)OCC
Agent: [K+]
Solvent: COS(=O)(=O)OC
Solvent: CC(C)=O
Product: CCOC(=O)c1cn(N2C(=O)c3ccccc3C2=O)c(C(=O)OCC)c1OC
Temperature: 50 °C
Yield: 75.1 %

Procedure:
A mixture of 393C (0.84 g, 2 mmol) and K2CO3 (1.0 g, 7.25 mmol) in acetone (5 ml) was heated at 50° C. for 30 min, then cooled to rt. Dimethyl sulfate (0.29 ml, 3.0 mmol) was added, the resulting mixture was heated at 40° C. until starting material consumed, quenched with brine and extracted with EtOAc. The organic layer was dried and concentrated, the residue was purified by silica gel flash column chromatography to afford 393D (0.58 g, 74% for 3 steps from 393B) (0%-5% EtOAc—CH2Cl2).
Reaction SMILES: C([O:4][CH2:5][CH2:6][O:7][C:8]1[C:13]2[CH2:14][C:15](=[CH:23][CH2:24][CH2:25][N:26]3[CH2:31][CH2:30][C:29]([C:33]4[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=4)([OH:32])[CH2:28][CH2:27]3)[C:16]3[C:17]([O:22][C:12]=2[CH:11]=[CH:10][CH:9]=1)=[N:18][CH:19]=[CH:20][CH:21]=3)(=O)C.[OH-].O.C(OCC)(=O)C>C(O)C>[Cl:39][C:36]1[CH:37]=[CH:38][C:33]([C:29]2([OH:32])[CH2:28][CH2:27][N:26]([CH2:25][CH2:24][CH:23]=[C:15]3[C:16]4[C:17](=[N:18][CH:19]=[CH:20][CH:21]=4)[O:22][C:12]4[CH:11]=[CH:10][CH:9]=[C:8]([O:7][CH2:6][CH2:5][OH:4])[C:13]=4[CH2:14]3)[CH2:31][CH2:30]2)=[CH:34][CH:35]=1
Reactant: CC(=O)OCCOc1cccc2c1CC(=CCCN1CCC(O)(c3ccc(Cl)cc3)CC1)c1cccnc1O2
Agent: [OH-]
Solvent: CCO
Solvent: O
Solvent: CCOC(C)=O
Product: OCCOc1cccc2c1CC(=CCCN1CCC(O)(c3ccc(Cl)cc3)CC1)c1cccnc1O2

Procedure:
To a solution of 1-[3—(7-(2-acetoxyethyl)oxy-5,11-dihydro[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]-4—(4-chlorophenyl)piperidin-4-ol (Example 50)(140 mg) in ethanol (5 ml) were added 15% sodiun hydroxide aqueous solution (2ml) and the mixture was heated to reflux for hour. Water and ethyl acetate were added to the reaction mixture, the organic layer was separated and washed with saturated aqueous sodium chloride, and dried with magnesium sulfate.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]=[N:8][O:9][CH2:10][CH2:11][OH:12].O[C:14]1[CH:46]=[CH:45][C:17]([CH2:18][CH:19]2[S:23][C:22](=[O:24])[N:21]([C:25]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]2=[O:44])=[CH:16][CH:15]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCNCC1)=O)=NC(N1CCNCC1)=O>>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]=[N:8][O:9][CH2:10][CH2:11][O:12][C:14]1[CH:46]=[CH:45][C:17]([CH2:18][CH:19]2[S:23][C:22](=[O:24])[N:21]([C:25]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]2=[O:44])=[CH:16][CH:15]=1
Reactant: O=C1SC(Cc2ccc(O)cc2)C(=O)N1C(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: OCCON=Cc1ccccn1
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCNCC1)N1CCNCC1
Product: O=C1SC(Cc2ccc(OCCON=Cc3ccccn3)cc2)C(=O)N1C(c1ccccc1)(c1ccccc1)c1ccccc1
Yield: 55 %

Procedure:
Following a procedure similar to that described in Example 3(a), but using 498 mg of 2-(2-pyridylmethyleneaminooxy)ethanol (prepared as described in Preparation 4), 1.13 g of 5-(4-hydroxybenzyl)-3-tritylthiazolidine-2,4-dione, 0.75 ml of tributylphosphine and 693 mg of 1,1'-(azodicarbonyl)dipiperazine, 0.82 g of the title compound was obtained as a foam-like solid.
Reaction SMILES: [C:1]1([C:7]2[C:11]([CH2:12][OH:13])=[CH:10][O:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[N+]1([O-])CCOCC1>ClCCl.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[C:1]1([C:7]2[C:11]([CH:12]=[O:13])=[CH:10][O:9][CH:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: OCc1cocc1-c1ccccc1
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Agent: C[N+]1([O-])CCOCC1
Solvent: ClCCl
Product: O=Cc1cocc1-c1ccccc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A mixture of 3-phenyl-4-furylmethanol (Compound 19, 458 mg, 2.63 mmol), powdered 4A molecular sieves (500 mg), 4-methyl-morpholine-N-oxide (462 mg, 3.95 mmol) and tetrapropylammonium perruthenate (46 mg, 0.13 mmol) in anhydrous dichloromethane (40 ml) were stirred at room temperature for 3 hours. Residue was filtered through silica and concentrated to a brown oil which was purified by flash chromatography on silica using 10% ethyl ether/hexanes to give the titled aldehyde
Reaction SMILES: Br[C:2]([F:16])([F:15])[C:3](F)([F:13])[O:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=[O:10])=[CH:7][CH:6]=1.O>[Zn].C(#N)C>[F:13][C:3]([O:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=[O:10])=[CH:7][CH:6]=1)=[C:2]([F:16])[F:15]
Reactant: O=Cc1ccc(OC(F)(F)C(F)(F)Br)cc1
Agent: [Zn]
Solvent: O
Solvent: CC#N
Product: O=Cc1ccc(OC(F)=C(F)F)cc1
Temperature: 79 °C
Yield: 63.3 %

Procedure:
Acetonitrile (300 ml) and granular zinc (30.0 g) are combined in a 1 liter round bottomed flask and stirred at 75° C. under nitrogen as 4-(2-bromotetrafluoroethoxy)benzaldehyde (111.39 g, 0.37 mole) is added slowly by dropping addition funnel. The resulting mixture is stirred and heated at 79° C. for 12 hours. After filtration to remove zinc salts and unreacted zinc, the acetonitrile is removed under vacuum on a rotary evaporator. The resulting oily residue is flash distilled on a rotary evaporator under high vacuum (26.6 Pa) to provide 47.33 g (0.234 mole) of a water white oil in 63.3 percent yield.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[OH:6][CH2:7][CH2:8][C:9]1[C:10]([N+:15]([O-:17])=[O:16])=[N:11][CH:12]=[CH:13][CH:14]=1.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH3:1][S:2]([O:6][CH2:7][CH2:8][C:9]1[C:10]([N+:15]([O-:17])=[O:16])=[N:11][CH:12]=[CH:13][CH:14]=1)(=[O:4])=[O:3]
Reactant: O=[N+]([O-])c1ncccc1CCO
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCc1cccnc1[N+](=O)[O-]

Procedure:
Methane sulfonyl chloride (0.16 mL, 2.14 mmol) was added to a solution of 3-(2-hydroxyethyl)-2-nitropyridine (0.300 g, 1.78 mmol) and triethylamine (0.37 mL, 2.67 mmol) in methylene chloride (5 mL) at 0° C. under argon. After 1 h the reaction was worked up with saturated sodium bicarbonate and methylene chloride, and the organic phase dried over sodium sulfate and concentrated to give the title compound MS 247 (M+1).
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:20])[N:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[CH:7]=1.[H-].[Na+].[C:23]1([CH3:29])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(Cl)C1C=CC=CC=1>C(OCC)(=O)C>[CH2:29]([NH:1][C:2]1[C:3](=[O:20])[N:4]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[CH:7]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: Cc1ccccc1
Reactant: Nc1cc(-c2ccccn2)cn(-c2ccccc2)c1=O
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClCc1ccccc1
Product: O=c1c(NCc2ccccc2)cc(-c2ccccn2)cn1-c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
40 mg of 3-amino-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one and 10 mg of sodium hydride were added to 1 ml of toluene, to which 30 mg of benzyl chloride was added dropwise at 70° C. The mixture was stirred for 30 minutes, and heated for 1 hour under reflux. The reaction mixture was left to cool to room temperature, diluted with ethyl acetate, and washed with a water and a saturated saline water. The organic layer was dried by magnesium sulfate, and refined by NH silica gel chromatography (ethyl acetate/hexane-based solvent), to obtain 13 mg of the subject compound.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH3:7])[N:6]=1.CO[CH:10](OC)[N:11]([CH3:13])[CH3:12]>C1(C)C=CC=CC=1>[CH3:7][C:5]1[N:6]=[C:2]([N:1]=[CH:10][N:11]([CH3:13])[CH3:12])[S:3][CH:4]=1
Reactant: Cc1csc(N)n1
Reactant: COC(OC)N(C)C
Solvent: Cc1ccccc1
Product: Cc1csc(N=CN(C)C)n1
Yield: 100 %

Procedure:
A solution 2-amino-4-methylthiazole (Formula C-1)(11.4 g) in toluene (100 ml) at 25° was treated with dimethylformamide dimethyl acetal (15.9 mL, 200 mmol), dropwise over five minutes. The mixture was heated to reflux temperature for 22 hours. The reaction was cooled to 25° and the solvent evaporated to an orange oil (17 g). The oil was triturated with hexane to yield yellow crystals. Recrystallization from warm hexane gave N′-(4-Methyl-2-thiazolyl)-N,N-dimethyl-methanimidamide (Formula C-2) (16.9 g, 99.6%), m.p. 54-56°.
Reaction SMILES: [Br:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([NH:9][CH2:10][C:11](O)=[O:12])=[C:4]([N+:14]([O-])=O)[CH:3]=1.BrC1C=C([N+]([O-])=O)C(F)=CC=1NCC(O)=O.O.O.[Sn](Cl)Cl>C(O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:5]([NH:9][CH2:10][C:11](=[O:12])[NH:14]2)=[CH:6][C:7]=1[F:8]
Reactant: O=C(O)CNc1cc(F)c(Br)cc1[N+](=O)[O-]
Agent: Cl[Sn]Cl
Agent: O=C(O)CNc1cc(F)c([N+](=O)[O-])cc1Br
Solvent: CCO
Solvent: O
Product: O=C1CNc2cc(F)c(Br)cc2N1
Temperature: 25 °C
Yield: 24 %

Procedure:
A solution of mixture of N-(4-bromo-5-fluoro-2-nitrophenyl)glycine and N-(2-bromo-5-fluoro-4-nitrophenyl)glycine (0.150 g, 0.512 mmol, as prepared above) and tin (II) chloride dihydrate (0.346 g, 1.53 mmol, Aldrich, used as received) in ethanol (3.0 mL) was refluxed for 30 min. It was then cooled to r.t. and the solvent was removed under vacuum. The residue was diluted with water (10 mL) and basified with saturated NaHCO3 (3.0 mL) to pH ~8. The resulting white suspension was extracted with ethyl acetate (30 mL). The extract was dried over Na2SO4 and evaporated to yield 0.050 g of crude product which was purified by precipitation from ethanol: water (1:1) to give 30 mg (24%) of pure title compound as a light yellow powder; m.p. 172° C. (decomposed); 1H NMR (DMSO-d6) 3.73 (s, 2H), 6.37 (s, 1H), 6.551 (d, 1H, J=10.2 Hz), 6.825 (d, 1H, J=6.6 Hz), 10.303 (s, 1H).