Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[N:12]1[CH:17]=[C:16]([C:18]2[CH:19]=[C:20]([CH:22]=[CH:23][CH:24]=2)[NH2:21])[CH:15]=[N:14][CH:13]=1>>[N:12]1[CH:17]=[C:16]([C:18]2[CH:19]=[C:20]([NH:21][C:2]3[CH:7]=[CH:6][C:5]([I:8])=[CH:4][C:3]=3[N+:9]([O-:11])=[O:10])[CH:22]=[CH:23][CH:24]=2)[CH:15]=[N:14][CH:13]=1
Reactant: Nc1cccc(-c2cncnc2)c1
Reactant: O=[N+]([O-])c1cc(I)ccc1F
Product: O=[N+]([O-])c1cc(I)ccc1Nc1cccc(-c2cncnc2)c1
Yield: 79 %

Procedure:
N-(3-(5-Pyrimidyl)phenyl)-4-iodo-2-nitroaniline (6b) was prepared analogously from 1c (Example 1) and 2b (Example 2). Yield 79%. Mp 214-217° C.
Reaction SMILES: [CH3:1][N:2]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:5](=[O:6])[C:3]1=[O:4].[N+:13]([CH3:16])([O-:15])=[O:14]>O>[OH:6][C:5]1([CH2:16][N+:13]([O-:15])=[O:14])[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:2]([CH3:1])[C:3]1=[O:4]
Reactant: CN1C(=O)C(=O)c2ccccc21
Reactant: C[N+](=O)[O-]
Solvent: O
Product: CN1C(=O)C(O)(C[N+](=O)[O-])c2ccccc21
Temperature: 30 °C
Reaction time: 24 h

Procedure:
N-methyl isatin (0.08 g) and nitromethane (0.15 ml) were added to water and the reaction mixture was vigorously stirred at a temperature of 30° C. for 24 hours. The obtained product was extracted with ethyl acetate and purified by silica gel column chromatography using ethyl acetate/hexane as eluents to afford pure product.
Reaction SMILES: Cl.[O:2]=[C:3]1[CH:8]=[C:7]([CH2:9][N:10]2[C:14]([CH2:15][C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)=[CH:13][N:12]=[CH:11]2)[CH:6]=[CH:5][N:4]1[C:24]1C=CC=CC=1.ClC1[N:36]=[CH:35][CH:34]=[CH:33][N:32]=1.IC1C=CC=CC=1>>[O:2]=[C:3]1[CH:8]=[C:7]([CH2:9][N:10]2[C:14]([CH2:15][C:16]3[CH:17]=[CH:18][C:19]([C:20]#[N:21])=[CH:22][CH:23]=3)=[CH:13][N:12]=[CH:11]2)[CH:6]=[CH:5][N:4]1[C:24]1[N:36]=[CH:35][CH:34]=[CH:33][N:32]=1
Reactant: N#Cc1ccc(Cc2cncn2Cc2ccn(-c3ccccc3)c(=O)c2)cc1
Reactant: Clc1ncccn1
Agent: Cl
Solvent: Ic1ccccc1
Product: N#Cc1ccc(Cc2cncn2Cc2ccn(-c3ncccn3)c(=O)c2)cc1

Procedure:
4-[3-(2-Oxo-1-pyrimidin-2-yl-1,2-dihydro-pyridin-4-ylmethyl)-3H-imidazol-4-ylmethyl]-benzonitrile was prepared in a manner substantially similar to the procedure described above for 4-[3-(2-oxo-1-phenyl-1,2-dihydropyridin-4-ylmethyl)-3H-imidazol-4-ylmethyl]benzonitrile, hydrochloride, but substituting 2-chloropyrimidine for the iodobenzene in Step 3.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][N:18]2[C:22]([CH2:23][O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])=[C:21]([Cl:32])[N:20]=[C:19]2[CH2:33][CH2:34][CH2:35][CH3:36])=[CH:13][CH:12]=1)=O.[NH2:37][NH2:38]>>[CH2:33]([C:19]1[N:18]([CH2:17][C:14]2[CH:13]=[CH:12][C:11]([C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[C:3]([NH:37][NH2:38])=[O:2])=[CH:16][CH:15]=2)[C:22]([CH2:23][O:24][Si:25]([C:28]([CH3:29])([CH3:30])[CH3:31])([CH3:26])[CH3:27])=[C:21]([Cl:32])[N:20]=1)[CH2:34][CH2:35][CH3:36]
Reactant: NN
Reactant: CCCCc1nc(Cl)c(CO[Si](C)(C)C(C)(C)C)n1Cc1ccc(-c2ccccc2C(=O)OC)cc1
Product: CCCCc1nc(Cl)c(CO[Si](C)(C)C(C)(C)C)n1Cc1ccc(-c2ccccc2C(=O)NN)cc1
Yield: 60 %

Procedure:
According to the procedure of Example 2, 4'-[[2-butyl-4-chloro-5-(t-butyldimethylsilyloxymethyl)-1H-imidazol-1-yl]methyl][1,1'-biphenyl-2-yl]carboxylic acid methyl ester was treated with hydrazine to give 4'-[[2-butyl-4-chloro-5-(t-butyldimethylsilyloxymethyl)-1H-imidazol-1-yl]methyl][1,1'-biphenyl-2-yl]carboxylic acid hydrazide (60%) .
Reaction SMILES: [Na].[C:2]1([SH:8])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N:15]1[C:19](Cl)=[N:18][C:17]([OH:21])=[N:16]1>CO>[N:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N:15]1[C:19]([S:8][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[N:18][C:17]([OH:21])=[N:16]1
Reactant: Sc1ccccc1
Reactant: Oc1nc(Cl)n(-c2ccccn2)n1
Agent: [Na]
Solvent: CO
Product: Oc1nc(Sc2ccccc2)n(-c2ccccn2)n1
Temperature: 25 °C
Reaction time: 3 h
Yield: 70.5 %

Procedure:
To a solution of 2.3 g (0.10 m) of sodium metal dissolved in 125 ml of methanol was added a solution of 5.51 g (0.05 m) of thiophenol in 25 ml of methanol. To this mixture was added 9.8 g (0.05 m) of 1-(2-pyridinyl)-5-chloro-1H-1,2,4-triazol-3-ol and the mixture stirred for three hours at room temperature. The methanol was removed by evaporation under vacuum and the residue which remained was taken up in water and the water insoluble solids were removed by filtration. The aqueous layer was acidified with concentrated hydrochloric acid. The white solid which precipitated was recovered by filtration and dried under vacuum to yield 9.5 g (~70 percent of theoretical) of the desired 1-(2-pyridinyl)-5-(phenylthio)-1H-1,2,4-triazol-3-ol product. The product melted at 235°-237° C. and upon analysis was found to have carbon, hydrogen and nitrogen contents of 55.87, 3.79 and 19.90 percent, respectively, as compared with the theoretical contents of 55.91, 3.93 and 20.06 percent, respectively, calculated for the above named compound.
Reaction SMILES: [CH2:1]([N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]1=O)[CH3:2].COC1C=CC(P2(=S)SP(C3C=CC(OC)=CC=3)(=S)[S:19]2)=CC=1>C1C=CC=CC=1>[CH2:1]([N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]1=[S:19])[CH3:2]
Reactant: CCn1ccccc1=O
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: c1ccccc1
Product: CCn1ccccc1=S
Yield: 187 %

Procedure:
Under an inert atmosphere, 1.23 g of 1-ethyl-2-pyridone and 25 ml of benzene were mixed together and then under vigorous stirring, 2.02 g of 2,4-bis-(4-methoxyphenyl)-2,4-dithioxo1,3,2,4-dithiadiphosphetane (Lawesson's reagent) were added all at once with stirring at reflux for 2 hours. After cooling and filtering, the filtrate was taken to dryness by distilling under reduced pressure, and the 3.8 g of residue were chromatographed on silica and eluted with a mixture of methylene chloride and ethyl acetate (8/2) to obtain 1.3 g of the expected product melting at about 50° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([O:13][CH3:14])[C:10]=1[O:11][CH3:12])[CH2:6]O.N1C=CC=CC=1.P(Br)(Br)[Br:22]>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([O:13][CH3:14])[C:10]=1[O:11][CH3:12])[CH2:6][Br:22]
Reactant: COc1cc(CO)cc(OC)c1OC
Reactant: BrP(Br)Br
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: COc1cc(CBr)cc(OC)c1OC
Temperature: 0 °C
Reaction time: 1 h
Yield: 202.8 %

Procedure:
To a solution of 3,4,5-trimethoxybenzyl alcohol (20.2 g, 0.108 mol) in 300 ml of dry tetrahydrofuran was added 4.12 ml (0.052 mol) of pyridine, and cooled to 0° C. A solution of phosphorous tribromide (4.8 ml, 0.051 mol) in 20 ml of dry tetrahydrofuran was added dropwise to the above solution at 0 ° C. The mixture was stirred for 1 hr. Tetrahydrofuran was concentrated. The residue was then diluted with 200 ml of 10% hydrochloric acid, and then extracted with 200 ml of ethyl acetate. The extract was dried over magnesium sulfate, filtered, concentrated, and dried in vacuum overnight. 3,4,5-Trimethoxybenzyl bromide (27 g, 100% yield) was obtained as a white solid, which can be used without further purification.
Reaction SMILES: [CH3:1][OH:2].C[O-].[Na+].[Br:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9](Br)[N:8]=1>CO>[Br:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:2][CH3:1])[N:8]=1
Reactant: CO
Reactant: Brc1cccc(Br)n1
Agent: C[O-]
Agent: [Na+]
Product: COc1cccc(Br)n1
Temperature: 80 °C

Procedure:
250 ml of 28% sodium methoxide methanol solution was added dropwise into a mixture of 200 g of 2,6-dibromopyridine and 150 ml of methanol while heating at 80° C. stirring in an oil bath, followed by stirring under heating for 2 hours as it was. After cooling as it was, the mixture was extracted with diethyl ether-water, and the organic phase was washed with water and brine, dried over anhydrous magnesium sulfate and the solvent was removed, to give 150 g of the target compound.
Reaction SMILES: [BH4-].[Na+].[CH3:3][C:4]([Si:7]([CH3:31])([CH3:30])[O:8][CH2:9][CH2:10][CH:11]([C:19](=[O:29])[CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([I:28])=[CH:24][CH:23]=1)[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])([CH3:6])[CH3:5]>CO>[CH3:6][C:4]([Si:7]([CH3:30])([CH3:31])[O:8][CH2:9][CH2:10][CH:11]([CH:19]([OH:29])[CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([I:28])=[CH:24][CH:23]=1)[C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])([CH3:3])[CH3:5]
Reactant: CC(C)(C)OC(=O)C(CCO[Si](C)(C)C(C)(C)C)C(=O)CCc1ccc(I)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(C)(C)OC(=O)C(CCO[Si](C)(C)C(C)(C)C)C(O)CCc1ccc(I)cc1
Reaction time: 1.5 h
Yield: 67.7 %

Procedure:
Sodium borohydride (0.59 g, 15.6 mmol) was added portion wise to a stirred solution of 1,1-dimethylethyl 2-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-5-(4-iodophenyl)-3-oxopentanoate (7.55 g, 14.2 mmol) in methanol (100 mL) at 0° C. under nitrogen. On completion of addition stirring was continued for 1.5 h then the reaction was quenched with saturated aqueous ammonium chloride solution (100 mL). The resulting mixture was extracted with diethyl ether (3×200 mL) then the organic layers were combined, washed with brine (100 mL), dried (sodium sulfate) and the solvent evaporated. The residue was chromatographed on silica gel (25% to 50% diethyl ether:cyclohexane) to give the title compound (5.14 g, 68%) as a colourless oil which was a mixture of diastereomers.
Reaction SMILES: BrC1C(=O)[NH:4][C:5](=[O:18])[N:6]([CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])C=1C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C>C1COCC1>[F:16][C:15]1[CH:14]=[CH:13][CH:12]=[C:11]([F:17])[C:10]=1[CH2:9][NH:6][C:5]([NH2:4])=[O:18]
Reactant: Cc1c(Br)c(=O)[nH]c(=O)n1Cc1c(F)cccc1F
Agent: CC(C)(C)OC(=O)/N=N/C(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: NC(=O)NCc1c(F)cccc1F
Temperature: 25 °C
Reaction time: 16 h
Yield: 251.9 %

Procedure:
A solution of N-(t-butyloxycarbonyl)-D-α-alaninol (1.75 g, 10 mmol) in anhydrous THF (15 mL) was treated with 5-bromo-1-(2,6-difluorobenzyl)-6-methyluracil (3.31 g, 10 mmol) and triphenylphosphine (3.15 g, 12 mmol) at ambient temperature, then di-tert-butylazodicarboxylate (2.76 g, 12 mmol) was introduced. The reaction mixture was stirred at ambient temperature for 16 hours and volatiles were evaporated. The residue was partitioned between saturated NaHCO3/H2O and EtOAc. The organic layer was dried (sodium sulfate), evaporated, and purified by flash chromatography (silica, 1:2 EtOAc/hexanes) to give compound 1 (4.69 g, 96.1%), MS (CI) m/z 388.0, 390.0 (MH+-Boc).
Reaction SMILES: [CH:1]([O:4][C:5](=[O:21])[NH:6][C@@H:7]1[CH2:20][C:10]2[NH:11][C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:28]([O:31][C:32]1[C:33]([CH2:38]Cl)=[N:34][CH:35]=[CH:36][CH:37]=1)[CH:29]=[CH2:30].O>CN(C)C=O>[CH:1]([O:4][C:5](=[O:21])[NH:6][C@@H:7]1[CH2:20][C:10]2[N:11]([CH2:38][C:33]3[C:32]([O:31][CH2:28][CH:29]=[CH2:30])=[CH:37][CH:36]=[CH:35][N:34]=3)[C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2]
Reactant: C=CCOc1cccnc1CCl
Reactant: CC(C)OC(=O)N[C@@H]1Cc2[nH]c3ccc(C#N)cc3c2C1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: C=CCOc1cccnc1Cn1c2c(c3cc(C#N)ccc31)C[C@H](NC(=O)OC(C)C)C2
Temperature: 40 °C
Reaction time: 16 h
Yield: 84.3 %

Procedure:
((S)-7-Cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl)-carbamic acid isopropyl ester (25 g, 88.2 mmol) is dissolved in dimethylformamide (150 mL) under nitrogen. Cesium carbonate (57.5 g, 176.5 mmol) and 3-allyloxy-2-chloromethyl-pyridine (16.2 g, 88.2 mmol) are added sequentially. The reaction mixture is stirred at 40° C. for 16 h. The reaction is cooled to room temperature and added to water (1250 mL). After one hour of stirring a pale cream solid is filtered. The crude material is purified by recrystallization from i-PrOH and then dried under vacuum to constant weight to afford the title compound (32 g; 84%). LC-ES/MS m/z: 431.2 [M+H]+.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([NH:6][CH3:7])=[O:5].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:18]([CH:20]1[O:22][CH2:21]1)Br>C(#N)C>[CH3:7][NH:6][C:4](=[O:5])[C:3]1[CH:8]=[CH:9][CH:10]=[CH:11][C:2]=1[O:1][CH2:18][CH:20]1[CH2:21][O:22]1
Reactant: CNC(=O)c1ccccc1O
Reactant: BrCC1CO1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Product: CNC(=O)c1ccccc1OCC1CO1
Temperature: 50 °C
Yield: 62.7 %

Procedure:
To a solution of 2-Hydroxy-N-methyl-benzamide (0.5 g, 3.31 mmol prepared according to Cohen, Seth M et al J. Am. Chem. Soc., (1998), 120(25), 6277-6286.) and cesium carbonate (2.16 g, 6.62 mmol) in acetonitrile was added epibromohydrin (0.274 ml, 3.31 mmol). The mixture was heated at 50° C. for 2 hours and then after cooling to room temperature partitioned between water (50 ml) and dichloromethane (100 ml). The dichloromethane was dried and evaporated. Chromatography (EtOAc) gave 0.43 g (64%) of the product as a solid.
Reaction SMILES: Br[C:2]1[C:6]([CH3:7])=[C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14]C)=[CH:10][CH:9]=2)[S:4][C:3]=1[CH:16]1[O:20]CCO1.[CH:21]([C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][C:28]=1[O:29]C)=[O:22]>>[CH:21]([C:23]1[CH:24]=[C:25]([C:2]2[C:6]([CH3:7])=[C:5]([C:8]3[CH:9]=[CH:10][C:11]([OH:14])=[CH:12][CH:13]=3)[S:4][C:3]=2[CH:16]=[O:20])[CH:26]=[CH:27][C:28]=1[OH:29])=[O:22]
Reactant: COc1ccc(B(O)O)cc1C=O
Reactant: COc1ccc(-c2sc(C3OCCO3)c(Br)c2C)cc1
Product: Cc1c(-c2ccc(O)cc2)sc(C=O)c1-c1ccc(O)c(C=O)c1
Yield: 18.3 %

Procedure:
Starting from 2-[3-bromo-5-(4-methoxyphenyl)-4-methylthien-2-yl]-1,3-dioxolane (1.5 g, 4.2 mmol, made in Example 1, Step 1) and substituting 3-formyl-4-methoxyphenylboronic acid (0.83 g, 4.6 mmol) in place of 3-methoxyphenylboronic acid (Step 2), the title compound (0.26 g, 35%, m.p. 228-30° C.) was synthesized in essentially the same manner as described in Example 1, Steps 2-4.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][N:9]2[C:15]=1[CH:14]([CH3:16])[N:13]=[C:12]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[F:23])[C:11]1[CH:24]=[C:25](Br)[CH:26]=[CH:27][C:10]2=1)=[O:5])[CH3:2].[CH3:29][Si:30]([C:33]#[CH:34])([CH3:32])[CH3:31]>C(#N)C.C([O-])(=O)C.[Pd+2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])(=O)C>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][N:9]2[C:15]=1[CH:14]([CH3:16])[N:13]=[C:12]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[F:23])[C:11]1[CH:24]=[C:25]([C:34]#[C:33][Si:30]([CH3:32])([CH3:31])[CH3:29])[CH:26]=[CH:27][C:10]2=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1ncn2c1C(C)N=C(c1ccccc1F)c1cc(Br)ccc1-2
Reactant: C#C[Si](C)(C)C
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Product: CCOC(=O)c1ncn2c1C(C)N=C(c1ccccc1F)c1cc(C#C[Si](C)(C)C)ccc1-2
Temperature: 25 °C
Yield: 79 %

Procedure:
A mixture of 118 (69.3 mg, 0.16 mmol) and bis(triphenylphosphine) palladium(II) acetate (11.68 mg, 0.015 mmol) was dissolved in a mixed solvent system of acetonitrile (120 mL) and TEA (80 mL). The mixture was degassed under vacuum and argon gas was added, after which trimethylsilylacetylene (0.044 mL, 0.31 mmol) was added into the mixture. The mixture was degassed again under vacuum (argon) and heated to reflux. The mixture was heated at reflux until analysis by TLC (EtOAc) indicated that all of the starting material 118 had been consumed. The mixture was cooled to rt and the precipitate which formed was removed by filtration through celite. The filtrate was concentrated under reduced pressure and partitioned between H2O and EtOAc. The combined layers of EtOAc were washed with brine and dried (Na2SO4), after which the solvent was removed under reduced pressure and the residue was purified by flash chromatography (silica gel, EtOAc:hexane 1:1). The conditions for TLC were EtOAc on silica gel. A white solid 119 (58.1 mg, 79%) was obtained. mp 186-187° C.; IR (KBr, cm−1) 2410, 2358, 1716, 1497, 1253; 1H NMR (CDCl3) δ 7.92 (s, 1H), 7.72 (dd, J=8.5, 1.5 Hz, 1H), 7.6 (t, J=6.9 Hz, 1H), 7.48 (d, J=8.5 Hz, 1H), 7.42-7.49 (m, 2H), 7.23-7.29 (m, 1H), 7.05 (t, J=9.3 Hz, 1H), 6.71 (q, J=7.3 Hz, 1H), 4.41 (m, 2H), 1.42 (t, J=7.1 Hz, 3H), 1.29 (d, J=7.2, 3H), 0.24 (s, 9H). MS (EI) m/e (relative intensity) 459 (M+, 28), 445 (32), 399 (51), 371 (100), 235 (71), 178 (75); [α]26D=−27.8 (c 0.46, EtOAc).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8](=[O:27])[C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]3[C:21]([Cl:22])=[CH:20][C:19]([N+:23]([O-])=O)=[CH:18][C:17]=3[Cl:26])=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1.Cl[Sn]Cl>>[NH2:23][C:19]1[CH:18]=[C:17]([Cl:26])[C:16]([CH2:15][C:12]2[CH:11]=[CH:10][C:9]([C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[CH:7]=3)=[O:27])=[CH:14][CH:13]=2)=[C:21]([Cl:22])[CH:20]=1
Reactant: O=C(c1ccc(Cc2c(Cl)cc([N+](=O)[O-])cc2Cl)cc1)c1ccnc(Cl)c1
Agent: Cl[Sn]Cl
Product: Nc1cc(Cl)c(Cc2ccc(C(=O)c3ccnc(Cl)c3)cc2)c(Cl)c1
Yield: 91.7 %

Procedure:
The title compound was prepared as yellow oil at yield of 91.7%, in a similar manner as in Reference Example 7, by the reaction of 2-chloro-4-[4-(2,6-dichloro-4-nitrobenzyl)benzoyl]pyridine and SnCl2.
Reaction SMILES: [C:1]([O:5][C:6](=[O:23])[CH2:7][C@H:8]([NH:12][C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C:9]([OH:11])=O)([CH3:4])([CH3:3])[CH3:2].[B-](F)(F)(F)F.CCOC(C(C#N)=N[O:36][C:37]([N:41]([CH3:43])[CH3:42])=[N+](C)C)=O>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([O:5][C:37]([N:41]1[CH2:42][CH2:13][N:12]([C:9](=[O:11])[C@@H:8]([NH:12][C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH2:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:23])[CH2:8][CH2:43]1)=[O:36])[CH3:2]
Reactant: CC(C)(C)OC(=O)C[C@H](NC(=O)OCc1ccccc1)C(=O)O
Reactant: CCOC(=O)C(C#N)=NOC(N(C)C)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(=O)N1CCN(C(=O)[C@H](CC(=O)OC(C)(C)C)NC(=O)OCc2ccccc2)CC1
Reaction time: 16 h

Procedure:
To a solution of 15.4 g (S)-2-Benzyloxycarbonylamino-succinic acid 4-tert-butyl ester, 24.4 ml NEM and 15.6 g TOTU in 80 ml DMF 7.5 g piperazine-1-carboxylic acid ethyl ester were added at RT and stirred for 16 h. The reaction mixture was then diluted with ethyl acetate and washed with aqueous LiCl (4 w/w) and saturated aqueous sodium hydrogen carbonate. The organic phase was dried over MgSO4 and the solvents were removed under reduced pressure. The crude product was used in the subsequent reaction. Yield: 23.0 g.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][CH:7]=1)[CH:2]1[O:4][CH2:3]1.[CH3:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[C:22]=1[NH:28][CH2:29][CH2:30][NH2:31]>>[CH2:13]([O:12][C:9]1[CH:10]=[CH:11][C:6]([O:5][CH2:1][CH:2]([OH:4])[CH2:3][NH:31][CH2:30][CH2:29][NH:28][C:22]2[C:23]([CH3:27])=[CH:24][CH:25]=[CH:26][C:21]=2[CH3:20])=[CH:7][CH:8]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: Cc1cccc(C)c1NCCN
Reactant: c1ccc(COc2ccc(OCC3CO3)cc2)cc1
Product: Cc1cccc(C)c1NCCNCC(O)COc1ccc(OCc2ccccc2)cc1

Procedure:
5.12 g. 4-Benzyloxyphenyl glycidyl ether and 6.56 g. N-(2,6-dimethylphenyl)-ethylenediamine are heated for 20 hours at 70° C., while stirring. The reaction mixture is worked up by ion exchanger chromatography, using "Amberlite" CG 50 II pract. (Serva) in the manner described in Example 5. There are obtained 6.8 g. (81% of theory) of the desired product in the form of a light colored, viscous oil.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10]>C1C=CC=CC=1.C(OCC)C>[N:1]1([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1
Reactant: C1COCCN1
Reactant: CCOC(=O)CBr
Solvent: c1ccccc1
Solvent: CCOCC
Product: CCOC(=O)CN1CCOCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 71.2 %

Procedure:
Morpholine(1.65 ml, 18.9 mmol) was added dropwise to a soultion of ethyl bromoacetate(1 ml, 9.0 mmol) in benzene (9 ml). The reaction mixture was stirred for 2 hours at a room temperature, diluted with ethyl ether, and washed with saturated NaCl solution. The separated organic layer was dried over anhydrous sodium sulfate and concentrated under a reduced pressure to give 1.11 g of the titled compound as an oil. (Yield 71.2%)
Reaction SMILES: CN(C=[CH:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=1[N+:13]([O-:15])=[O:14])C.C1C[O:19]CC1>>[F:12][C:9]1[CH:10]=[CH:11][C:6]([CH:5]=[O:19])=[C:7]([N+:13]([O-:15])=[O:14])[CH:8]=1
Reactant: C1CCOC1
Reactant: CN(C)C=Cc1ccc(F)cc1[N+](=O)[O-]
Product: O=Cc1ccc(F)cc1[N+](=O)[O-]

Procedure:
N,N-Dimethyl-2-(4-fluoro-2-nitrophenyl)ethenylamine (6.72 g, 32 mmol) and NaIO4 (20.53 g, 96 mmol) were stirred in 50% aqueous THF (160 ml) at room temperature for 1.5 hours. The mixture was filtered in a celite pad and eluted with EtOAc. The organic layer was washed with NaHCO3 (saturated solution, 3×100 ml), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (50% CH2Cl2 /hexane) affording 4-fluoro-2-nitro benzaldehyde as an orange oil.
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH3:12])=[CH:8][NH:7][C:6]2=[O:13])[CH2:3][CH2:2]1.[CH2:14]([N:20]=[C:21]=[O:22])[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]>>[CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH3:12])=[CH:8][N:7]([C:21]([NH:20][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[O:22])[C:6]2=[O:13])[CH2:2][CH2:3]1
Reactant: Cc1c[nH]c(=O)n(CC2CC2)c1=O
Reactant: CCCCCCN=C=O
Product: CCCCCCNC(=O)n1cc(C)c(=O)n(CC2CC2)c1=O
Yield: 23 %

Procedure:
The title compound was obtained according to the procedure described for the synthesis of Example 1, starting from 3-(cyclopropylmethyl)-5-methyl-1H-pyrimidine-2,4-dione (0.05 g, 0.30 mmol); 1.8 equivalents of hexyl isocyanate were used herein. The crude product was purified by preparative HPLC-MS to afford the title compound (0.02 g, 23%) as colorless oil. 1H NMR (400 MHz, CDCl3): δ 0.36-0.44 (m, 2H), 0.44-0.53 (m, 2H), 0.89 (t, J=6.7 Hz, 3H), 1.17-1.48 (m, 6H), 1.50-1.77 (m, 3H), 2.00 (d, J=1.3 Hz, 3H), 3.38 (td, J=7.1, 5.5 Hz, 2H), 3.86 (d, J=7.2 Hz, 2H), 8.23 (q, J=1.3 Hz, 1H), 9.37 (t, J=5.5 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 4.02, 9.76, 13.47, 14.15, 22.66, 26.70, 29.35, 31.55, 41.34, 46.25, 111.81, 132.62, 150.77, 152.71, 163.16. MS (ESI) m/z: 308 [M-H]+.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([O:12][CH2:13][CH2:14][N:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1)[CH:6]=[CH:5]2.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)O1>>[N:15]1([CH2:14][CH2:13][O:12][C:7]2[CH:8]=[C:9]3[C:4](=[CH:5][CH:6]=2)[CH:3]=[C:2]([C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[CH:11]=[CH:10]3)[CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: Brc1ccc2cc(OCCN3CCCC3)ccc2c1
Reactant: CC1(C)OB(c2cccnc2)OC1(C)C
Product: c1cncc(-c2ccc3cc(OCCN4CCCC4)ccc3c2)c1

Procedure:
The product from Example 37B and 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine were processed as described in Example 38, except that a second column chromatography was done to provide 10 mg of the title compound. 1HNMR (300 MHz, CD3OD) δ 1.86 (m, 4H), 2.74 (m, 4H), 3.02 (t, 2H), 4.29 (t, 2H), 7.23 (dd, 1H), 7.31 (d, 1H), 7.56 (ddd, 1H), 7.76 (dd, 1H), 7.86-7.93 (m, 2H), 8.10 (d, 1H), 8.20 (ddd, 1H), 8.52 (dd, 1H), 8.91 (dd, 1H); MS (ESI) m/z 319 (M+H)+.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[C:5]([C@H:9]([S:22][CH2:23][C:24]2([CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH2:26][CH2:25]2)[CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([OH:21])([CH3:20])[CH3:19])[CH:6]=[CH:7][CH:8]=1>CCOC(C)=O.O=[Mn]=O>[CH:2]([C:3]1[CH:4]=[C:5]([C@H:9]([S:22][CH2:23][C:24]2([CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH2:25][CH2:26]2)[CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([OH:21])([CH3:20])[CH3:19])[CH:6]=[CH:7][CH:8]=1)=[O:1]
Reactant: COC(=O)CC1(CS[C@H](CCc2ccccc2C(C)(C)O)c2cccc(CO)c2)CC1
Agent: O=[Mn]=O
Solvent: CCOC(C)=O
Product: COC(=O)CC1(CS[C@H](CCc2ccccc2C(C)(C)O)c2cccc(C=O)c2)CC1
Yield: 82.8 %

Procedure:
To the dihydroxy ester from Step 16 (6.8 g, 15.4 mmol) in EtOAc (150 mL) at 50° C. was added MnO2 (6.7 g, 76.8 mmol). After stirring for 30 minutes at 50° C. more MnO2 (6.7 g) was added, and 30 minutes later, a third portion of MnO2 (6.7 g) was added. An hour later, the warm reaction mixture was filtered through celite and the cake was washed with additional EtOAc. Evaporation of the solvents gave the desired aldehyde 5.62 g (83%).