Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16](S(C)(=O)=O)[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[CH3:26])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:31].[CH2:32]([NH2:35])[CH2:33][NH2:34]>C1COCC1.C(OCC)(=O)C.O>[NH2:34][CH2:33][CH2:32][NH:35][C:16]1[N:17]=[C:18]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[CH3:26])[C:13]2[CH:12]=[CH:11][C:10](=[O:31])[N:9]([C:3]3[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=3[F:8])[C:14]=2[N:15]=1
Reactant: NCCN
Reactant: Cc1cc(F)ccc1-c1nc(S(C)(=O)=O)nc2c1ccc(=O)n2-c1c(F)cccc1F
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cc1cc(F)ccc1-c1nc(NCCN)nc2c1ccc(=O)n2-c1c(F)cccc1F
Yield: 89.6 %

Procedure:
The title compound of Example 7 [8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-methanesulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one] (0.89 g, 0.002 mol) in dry THF, stirring at 23°, under Ar, was treated with ethylenediamine (668 uL, 0.01 mol). The color became bright orange. LC MS showed no starting material after 5 min. Reaction was stripped to dryness; the residue taken up in ethyl acetate-water. The layers were separated and the aqueous phase adjusted to pH 10.5 with 10% NaOH. Aqueous phase was extracted twice with ethyl acetate; combined organic layers were dried (Na2SO4), then evaporated to give 0.762 g (89%) of the title compound as an amber glass. LC MS (m/e)=426 (MH+). Rt=1.52 min.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH:10]=[C:11]([Cl:13])[Cl:12])[CH:5]=[C:4]([Cl:14])[C:3]=1[OH:15].C(=O)([O-])[O-].[K+].[K+].[C:22]([O:26][N:27]=[C:28]([CH2:30][O:31][CH2:32][CH2:33][CH2:34][CH2:35]OS(C)(=O)=O)[CH3:29])([CH3:25])([CH3:24])[CH3:23].Cl>CN(C)C=O>[C:22]([O:26][N:27]=[C:28]([CH2:30][O:31][CH2:32][CH2:33][CH2:34][CH2:35][O:15][C:3]1[C:2]([Cl:1])=[CH:7][C:6]([O:8][CH2:9][CH:10]=[C:11]([Cl:13])[Cl:12])=[CH:5][C:4]=1[Cl:14])[CH3:29])([CH3:25])([CH3:24])[CH3:23]
Reactant: Oc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Reactant: CC(COCCCCOS(C)(=O)=O)=NOC(C)(C)C
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(COCCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl)=NOC(C)(C)C
Temperature: 60 °C
Reaction time: 6 h
Yield: 76.3 %

Procedure:
First, 0.55 g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol, 0.30 g of potassium carbonate, 0.59 g of 4-(methanesulfonyloxy)butyloxyacetone O-tert-butyloxime, and 10 ml of N,N-dimethylformamide are placed in a reaction vessel. After stirring at 60° C. for 6 hours, the reaction mixture is poured into diluted hydrochloric acid, and extracted twice with ethyl acetate. The ethyl acetate layers are combined, washed with water, dried over anhydrous magnesium sulfate, and concentrated to give a crude product. This crude product is subjected to silica gel chromatography, which affords 0.71 g (yield, 77%) of 4-(2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)butyloxyacetone O-tert-butyloxime, nD25.0 1.5170.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH3:10].[Cl-].[Cl-].[Cl-].[Al+3].[C@@H:15]12[C:24](=[O:25])[O:23][C:21](=[O:22])[C@@H:16]1[CH2:17][CH2:18][CH2:19][CH2:20]2>ClCCl>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH:6]=[CH:5][C:4]=1[O:9][CH3:10])[C:24]([C@H:15]1[CH2:20][CH2:19][CH2:18][CH2:17][C@H:16]1[C:21]([OH:23])=[O:22])=[O:25]
Reactant: O=C1OC(=O)[C@@H]2CCCC[C@H]12
Reactant: COc1ccccc1OC
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: COc1ccc(C(=O)[C@H]2CCCC[C@H]2C(=O)O)cc1OC

Procedure:
0.5 mole of 1,2-dimethoxybenzene was added slowly to a suspension of 0.5 mole aluminiumtrichloride in 1 l of dichloromethane at 0° C. After complete addition, cis-cyclohexane-1,2-dicarboxylic anhydride was added to the solution. After 8 hours of reflux the solution was poured onto ice. The organic layer was dried over magnesium sulfate and evaporated. The residue was washed with diethyl ether and dried. M.p. 171°-175° C.
Reaction SMILES: C(OC[N:10]1[C:18]2[C:17]([NH2:19])=[N:16][C:15]([CH2:20][CH2:21][CH2:22][CH3:23])=[N:14][C:13]=2[C:12]([C:24]#[C:25][CH2:26][CH2:27][CH2:28][N:29]2[CH2:34][CH2:33][N:32]([CH:35]([CH3:37])[CH3:36])[CH2:31][CH2:30]2)=[CH:11]1)C1C=CC=CC=1.[H][H]>C(O)C.[Pd].CO.CS(C)=O>[CH2:20]([C:15]1[N:16]=[C:17]([NH2:19])[C:18]2[NH:10][CH:11]=[C:12]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][N:32]([CH:35]([CH3:37])[CH3:36])[CH2:33][CH2:34]3)[C:13]=2[N:14]=1)[CH2:21][CH2:22][CH3:23]
Reactant: CCCCc1nc(N)c2c(n1)c(C#CCCCN1CCN(C(C)C)CC1)cn2COCc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CS(C)=O
Solvent: CCO
Solvent: CO
Product: CCCCc1nc(N)c2[nH]cc(CCCCCN3CCN(C(C)C)CC3)c2n1
Yield: 35.5 %

Procedure:
5-((Benzyloxy)methyl)-2-butyl-7-(5-(4-isopropylpiperazin-1-yl)pent-1-yn-1-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine (77 mg, 0.153 mmol) in ethanol (20 mL) was passed through the H-cube (settings: 45° C., full hydrogen, 1 mL/min flow rate and 10% palladium on carbon CatCart30 as the catalyst). A new 10% palladium on carbon CatCart30 cartridge was inserted into the H-cube and the solution was again passed through the H-cube (settings: 45° C., full hydrogen, 1 mL/min flow rate). The solution was evaporated in-vacuo to yield a white solid. The solid was dissolved in MeOH:DMSO (1:1) (1 mL) and purified by MDAP (Method B). the appropriate fraction was evaporated in-vacuo to yield the title compound as a white solid (21 mg).
Reaction SMILES: FC1C=CN=C(NC(=O)C2C=CC(B3OC(C)(C)C(C)(C)O3)=CC=2)C=1.[F:26][C:27]1[CH:35]=[C:34]([B:36]2[O:40][C:39]([CH3:42])([CH3:41])[C:38]([CH3:44])([CH3:43])[O:37]2)[CH:33]=[CH:32][C:28]=1[C:29]([OH:31])=O.[CH2:45]([C:48]1[CH:53]=[CH:52][N:51]=[C:50]([NH2:54])[CH:49]=1)[CH2:46][CH3:47]>>[F:26][C:27]1[CH:35]=[C:34]([B:36]2[O:40][C:39]([CH3:42])([CH3:41])[C:38]([CH3:44])([CH3:43])[O:37]2)[CH:33]=[CH:32][C:28]=1[C:29]([NH:54][C:50]1[CH:49]=[C:48]([CH2:45][CH2:46][CH3:47])[CH:53]=[CH:52][N:51]=1)=[O:31]
Reactant: CCCc1ccnc(N)c1
Reactant: CC1(C)OB(c2ccc(C(=O)O)c(F)c2)OC1(C)C
Agent: CC1(C)OB(c2ccc(C(=O)Nc3cc(F)ccn3)cc2)OC1(C)C
Product: CCCc1ccnc(NC(=O)c2ccc(B3OC(C)(C)C(C)(C)O3)cc2F)c1
Yield: 63.3 %

Procedure:
This compound was prepared, in an analogous manner as described in Intermediate 4, starting from commercially available 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid and 4-propyl-pyridin-2-ylamine, to afford the title compound (830 mg, 63.3%).
Reaction SMILES: OC(C(F)(F)F)=O.[N:8]1([CH2:14][C:15]2[N:16]=[N:17][C:18]3[C:19](=[C:21]([NH2:26])[N:22]=[C:23]([NH2:25])[N:24]=3)[N:20]=2)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.[Cl:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32]Cl)=[CH:30][CH:29]=1.C(=O)([O-])[O-].[K+].[K+].CC#N.O>CN(C=O)C>[Cl:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][N:11]2[CH2:12][CH2:13][N:8]([CH2:14][C:15]3[N:16]=[N:17][C:18]4[C:19](=[C:21]([NH2:26])[N:22]=[C:23]([NH2:25])[N:24]=4)[N:20]=3)[CH2:9][CH2:10]2)=[CH:30][CH:29]=1
Reactant: Nc1nc(N)c2nc(CN3CCNCC3)nnc2n1
Reactant: ClCc1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Solvent: O
Product: Nc1nc(N)c2nc(CN3CCN(Cc4ccc(Cl)cc4)CC3)nnc2n1
Temperature: 25 °C
Reaction time: 24 h
Yield: 68 %

Procedure:
To a stirred solution of 3-Piperazin-1-ylmethyl-pyrimido[5,4-e][1,2,4]triazine-5,7-diamine TFA salt 5 (50 mg; 0.08 mmol; prepared in EXAMPLE 4) in dry DMF (1.0 mL) was added p-chlorobenzyl chloride (29 mg; 0.18 mmol) followed by potassium carbonate (55 mg; 0.40 mmol). The mixture was allowed to stir for 24 h at room temperature then taken up into CH3CN/H2O/0.1% TFA. The mixture was purified by reverse phase HPLC (Rainin C18, 0% CH3CN to 50% CH3CN gradient, CH3CN/H2O, 0.1% TFA) and the bright yellow fractions containing the product were lyophilized after removal of CH3CN in vacuo to give 21 mg of yellow colored 3-[4-(4-Chloro-benzyl)-piperazin-1-ylmethyl]-pyrimido[5,4-e][1,2,4]triazine-5,7-diamine as the trifluoroacetate salt.
Reaction SMILES: [C:1]1([C:7]2[NH:8][C:9]([CH:13]=[O:14])=[C:10]([Cl:12])[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N+:15]([C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Br)=[CH:20][CH:19]=1)([O-:17])=[O:16].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[N+:15]([C:18]1[CH:25]=[CH:24][C:21]([CH2:22][N:8]2[C:9]([CH:13]=[O:14])=[C:10]([Cl:12])[N:11]=[C:7]2[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[CH:20][CH:19]=1)([O-:17])=[O:16]
Reactant: O=[N+]([O-])c1ccc(CBr)cc1
Reactant: O=Cc1[nH]c(-c2ccccc2)nc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=Cc1c(Cl)nc(-c2ccccc2)n1Cc1ccc([N+](=O)[O-])cc1
Temperature: 0 °C
Yield: 79.8 %

Procedure:
In 50 ml of dimethylformamide, there were stirred 10.3 g of 2-phenyl-4-chloro-5-formylimidazole, 11.3 g of p-nitrobenzyl bromide and 5.2 g of anhydrous potassium carbonate at 110°-120° C. for 2 hours. The reaction mixture was poured in ice-water and the resulting precipitate was put on a column of 100 g silica gel, elution being carried out with chloroform. The first fraction was concentrated to dryness and recrystallized from ethanol. By the above procedure was obtained 13.6 g of 1-(p-nitrobenzyl)-2-phenyl-4-chloro-5-formylimidazole as colorless needles, m.p. 150°-152° C.
Reaction SMILES: [C:1]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:6]=[CH:5][C:4]([C:7]([OH:9])=O)=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.[CH3:22][N:23]([CH3:39])[CH:24]1[CH2:28][CH2:27][N:26]([C:29]2[S:30][C:31]3[CH:37]=[C:36]([NH2:38])[CH:35]=[CH:34][C:32]=3[N:33]=2)[CH2:25]1>CN(C=O)C.C(Cl)Cl>[CH3:22][N:23]([CH3:39])[CH:24]1[CH2:28][CH2:27][N:26]([C:29]2[S:30][C:31]3[CH:37]=[C:36]([NH:38][C:7]([C:4]4[CH:3]=[CH:2][C:1]([C:10]5[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=5)=[CH:6][CH:5]=4)=[O:9])[CH:35]=[CH:34][C:32]=3[N:33]=2)[CH2:25]1
Reactant: O=C(O)c1ccc(-c2ccccc2)cc1
Reactant: CN(C)C1CCN(c2nc3ccc(N)cc3s2)C1
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CN(C)C1CCN(c2nc3ccc(NC(=O)c4ccc(-c5ccccc5)cc4)cc3s2)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 28.9 %

Procedure:
Combine 4-biphenylcarboxylic acid (0.124 g, 0.623 mmol), dichloromethane (5.0 mL), and DMF (3 drops) with stirring. Add oxalyl chloride (0.11 mL, 1.25 mmol) and stir the mixture for 2 h at room temperature. Concentrate the mixture in vacuo, add hexane (approximately 10 mL), re-concentrate in vacuo, and re-dissolve in CH2Cl2 (4.0 mL). Transfer the mixture to a 40 mL reaction vial and add a mixture of 2-(3-dimethylamino-pyrrolidin-1-yl)-benzothiazol-6-ylamine (0.109 g, 0.415 mmol) (Example 1, step 3) in CH2Cl2 (2.0 mL). Stir the mixture overnight at room temperature. Dilute the reaction mixture with CH2Cl2 (25 mL), wash with saturated NaHCO3 (aqueous) (25 mL), and extract the aqueous phase with CH2Cl2 (25 mL). Wash the combined organic phases with saturated NaHCO3 (aqueous) (2×25 mL), dry over sodium sulfate, filter, and concentrate in vacuo to yield a yellow solid. Purify the crude product using silica gel chromatography (40 g column, 5% MeOH/CH2Cl2) to afford the title compound (53 mg, 29%). mass spectrum (m/e): 443.4 [M+1], 441.3 [M−1]. 1H NMR (400 MHz, CDCl3): δ 8.69-8.58 (m, 1H), 8.26 (s, 1H), 7.93 (d, 2H, J=8.0 Hz), 7.67 (d, 2H, J=7.6 Hz), 7.59 (d, 2H, J=7.2 Hz), 7.50-7.26 (m, 5H), 3.81 (t, 1H, J=10.4 Hz), 3.72 (t, 1H, J=8.8 Hz), 3.52 (m, 1H), 3.43 (m, 1H), 3.01 (m, 1H), 2.35 (s, 6H), 2.29 (m, 1H), 2.04 (m, 1H).
Reaction SMILES: S(O[CH:12]([C:14]1([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:19][O:18][CH2:17][O:16][CH2:15]1)[CH3:13])(C1C=CC(C)=CC=1)(=O)=O.C1CCN2C(=NCCC2)CC1>CCOCC>[CH2:23]([O:22][C:20]([C:14]1([CH:12]=[CH2:13])[CH2:19][O:18][CH2:17][O:16][CH2:15]1)=[O:21])[CH3:24]
Reactant: CCOC(=O)C1(C(C)OS(=O)(=O)c2ccc(C)cc2)COCOC1
Solvent: CCOCC
Solvent: C1CCC2=NCCCN2CC1
Product: C=CC1(C(=O)OCC)COCOC1
Temperature: 140 °C
Yield: 33.3 %

Procedure:
A mixture of ethyl 5-(1-(tosyloxy)ethyl)-1,3-dioxane-5-carboxylate (20.7 g, 58 mmol) and DBU (25 mL) was heated at 140° C. for 3 h. After being cooled to rt, the reaction mixture was poured into ether (300 mL), and the organic layer was washed with brine (3×). The ether layer was dried over sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with petroleum ether/ether 30:1 to 20:1 to give a crude product, which was distilled under reduced pressure (45-49° C./0.3 mbar) to afford the title compound (3.6 g, 33%) as colorless oil. 1H NMR (400 MHz, CDCl3) δ 1.29 (t, J=11.0 Hz, 3H), 3.70 (d, J=11.6 Hz, 2H), 4.25 (t, J=7.2 Hz, 2H), 4.44 (t, J=11.2 Hz, 2H), 4.71 (d, J=8.0 Hz, 1H), 4.95 (d, J=6.0 Hz, 1H), 5.24 (m, 1H), 5.27 (m, 1H), 5.65 (m, 1H). This 1H spectral data is in good agreement with that reported for the synthesis of the title compound, the which is described in Borremans, F. et al. Bull. Soc. Chim. Belg. 1976, 85, 681-696.
Reaction SMILES: [C:1](O)(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[H-].[Al+3].[Li+].[H-].[H-].[H-].OS(O)(=O)=O>CCOCC>[CH2:1]([OH:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: O=S(=O)(O)O
Agent: [Al+3]
Agent: [H-]
Solvent: CCOCC
Product: CCCCCCCC/C=C\CCCCCCCCO
Temperature: 0 °C
Yield: 97.3 %

Procedure:
A solution of compound II (12 g) in 50 ml of dry ether was slowly dripped into a stirred suspension of 2 g of lithium aluminum hydride in 100 ml of dry ether. Gentle refluxing was maintained during addition, and the mixture was then refluxed for an additional 30 minutes. The mixture was chilled in an ice bath and treated gradually with 35 ml of ice water followed by 50 ml of cold 10% H2SO4. The ether layer was separated, the aqueous layer was shaken with two portions of ether, and the combined ether layers were dried over anhydrous Na2SO4. Evaporation of the solvent and distillation of the residue gave 11.1 g (97%) of compound III which boiled at 150° (0.02 mm), nD25 1.4608.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)=[CH:10][C:9]2=[O:23])=[CH:4][C:3]=1[NH:24][CH3:25].[CH3:26][O:27][C:28]([CH:30]1[CH2:33][CH2:32][CH:31]1[C:34](O)=O)=[O:29].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[Cl:22][C:19]1[CH:18]=[CH:17][C:16]([CH2:15][O:14][C:11]2[CH:12]=[CH:13][N:8]([C:5]3[CH:6]=[CH:7][C:2]4[N:1]=[C:34]([CH:31]5[CH2:32][CH2:33][CH:30]5[C:28]([O:27][CH3:26])=[O:29])[N:24]([CH3:25])[C:3]=4[CH:4]=3)[C:9](=[O:23])[CH:10]=2)=[CH:21][CH:20]=1
Reactant: COC(=O)C1CCC1C(=O)O
Reactant: CNc1cc(-n2ccc(OCc3ccc(Cl)cc3)cc2=O)ccc1N
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)C1CCC1c1nc2ccc(-n3ccc(OCc4ccc(Cl)cc4)cc3=O)cc2n1C
Temperature: 25 °C
Reaction time: 2 h
Yield: 15.4 %

Procedure:
A mixture of 1-(4-amino-3-(methylamino)phenyl)-4-((4-chlorobenzyl)oxy)pyridin-2(1H)-one (830 mg), (1RS, 2SR)-2-(methoxycarbonyl)cyclobutanecarboxylic acid (406 mg), HATU (1.33 g), N,N-diisopropylethylamine (0.611 ml) and DMF (20 ml) was stirred at room temperature for 2 h. The mixture was quenched with water, and extracted with EtOAc. The organic layer was separated, washed with water and brine successively, dried over MgSO4 and concentrated in vacuo. Then a mixture of the obtained residue and AcOH (20 ml) was stirred at 80° C. for 30 min. After concentration of the mixture, the residue was poured into saturated NaHCO3 solution, and extracted with EtOAc. The organic layer was separated, washed with water and brine successively, dried over MgSO4, and concentrated in vacuo. The residual solid was washed with IPE to give the title compound (172 mg) as a brown solid.
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[C:5]([CH2:11][CH:12]([NH:16][C:17]([N:19]2[CH2:24][CH2:23][CH:22]([N:25]3[CH2:31][CH2:30][C:29]4[CH:32]=[CH:33][CH:34]=[CH:35][C:28]=4[NH:27][C:26]3=[O:36])[CH2:21][CH2:20]2)=[O:18])[C:13](O)=[O:14])[CH:6]=[CH:7][C:8]=1[CH2:9][CH3:10])[CH3:2].[N:37]1([CH:43]2[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]2)[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1>>[N:37]1([CH:43]2[CH2:48][CH2:47][N:46]([C:13](=[O:14])[CH:12]([NH:16][C:17]([N:19]3[CH2:24][CH2:23][CH:22]([N:25]4[CH2:31][CH2:30][C:29]5[CH:32]=[CH:33][CH:34]=[CH:35][C:28]=5[NH:27][C:26]4=[O:36])[CH2:21][CH2:20]3)=[O:18])[CH2:11][C:5]3[CH:6]=[CH:7][C:8]([CH2:9][CH3:10])=[C:3]([CH2:1][CH3:2])[CH:4]=3)[CH2:45][CH2:44]2)[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1
Reactant: CCc1ccc(CC(NC(=O)N2CCC(N3CCc4ccccc4NC3=O)CC2)C(=O)O)cc1CC
Reactant: C1CCN(C2CCNCC2)CC1
Product: CCc1ccc(CC(NC(=O)N2CCC(N3CCc4ccccc4NC3=O)CC2)C(=O)N2CCC(N3CCCCC3)CC2)cc1CC

Procedure:
Prepared analogously to Example 3f) from 3-(3,4-diethyl-phenyl)-2-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid and [1,4′]-bipiperidinyl.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]([CH3:26])=[C:5]([C:20]([O:22][CH:23]([CH3:25])[CH3:24])=[O:21])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([NH:18][OH:19])[CH:13]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9].[S:27]1[CH:31]=[CH:30][CH:29]=[C:28]1[CH:32]=O>>[CH3:1][C:2]1[NH:3][C:4]([CH3:26])=[C:5]([C:20]([O:22][CH:23]([CH3:24])[CH3:25])=[O:21])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N:18](=[O:19])=[CH:32][C:28]3[S:27][CH:31]=[CH:30][CH:29]=3)[CH:13]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9]
Reactant: O=Cc1cccs1
Reactant: COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1c1cccc(NO)c1
Agent: COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1c1cccc(/[N+]([O-])=C/c2cccs2)c1
Product: COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1c1cccc([N+]([O-])=Cc2cccs2)c1

Procedure:
The reaction of hydroxylamine 82 (0.71 g, 2 mmol) with 2-thiophenecarboxaldehyde (64) (0.224 g, 2 mmol) afforded after workup, a light yellow oil. The crude product was purified by flash chromatography with 1:1 ethyl acetate/petroleum ether as the eluant to obtain 0.64 g (1.41 mmol, 71%) of 87 as a light yellow oil. The oil crystallized from ether/pentane to yield yellow crystalline solid: mp 106°-109° C.; IR (CH2Cl2) 3440, 2940, 1695, 1620, 1555, 1470, 1375, 1300, 1215, 1100 cm-1 ; 1H NMR (CDCl3) δ 1.10 (d, J=6.2 Hz, 3H), 1.22 (d, J=6.2 Hz, 3H), 2.27 (s, 6H), 3.61 (s, 3H), 4.94 (septet, J=6.2 Hz, 1H), 5.06 (s, 1H), 6.98 (s, 1H), 7.17-7.77 (m, 7H), 8.44 (s, 1H); 13C NMR (CDCl3) δ 19.87, 22.49, 22.74, 40.59, 51.54, 67.68, 103.30, 104.00, 119.18, 121.52, 127.64, 128,95, 129.76, 130.60, 130.66, 131.78, 133.49, 145.64, 146.13, 147.07, 150.57, 167.62, 168.64. Anal. Calcd for C24H26N2O5S: C, 63.43; H, 5.72. Found: C, 63.26; H, 5.72.
Reaction SMILES: [CH2:1]([O:8][C:9]([C:11]1[CH:38]=[CH:37][C:14]([O:15][C:16]2[C:21]([F:22])=[C:20]([F:23])[C:19]([C:24]3[C:29]([F:30])=[C:28]([F:31])[C:27](F)=[C:26]([F:33])[C:25]=3[F:34])=[C:18]([F:35])[C:17]=2[F:36])=[CH:13][CH:12]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:39]([C:42]1[CH:48]=[CH:47][C:45]([O-:46])=[CH:44][C:43]=1[O:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)([O-:41])=[O:40].[K+]>CN(C)C=O>[N+:39]([C:42]1[CH:48]=[CH:47][C:45]([O:46][C:27]2[C:26]([F:33])=[C:25]([F:34])[C:24]([C:19]3[C:18]([F:35])=[C:17]([F:36])[C:16]([O:15][C:14]4[CH:37]=[CH:38][C:11]([C:9]([O:8][CH2:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)=[O:10])=[CH:12][CH:13]=4)=[C:21]([F:22])[C:20]=3[F:23])=[C:29]([F:30])[C:28]=2[F:31])=[CH:44][C:43]=1[O:49][CH2:50][C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)([O-:41])=[O:40]
Reactant: O=C(OCc1ccccc1)c1ccc(Oc2c(F)c(F)c(-c3c(F)c(F)c(F)c(F)c3F)c(F)c2F)cc1
Reactant: O=[N+]([O-])c1ccc([O-])cc1OCc1ccccc1
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C(OCc1ccccc1)c1ccc(Oc2c(F)c(F)c(-c3c(F)c(F)c(Oc4ccc([N+](=O)[O-])c(OCc5ccccc5)c4)c(F)c3F)c(F)c2F)cc1
Temperature: 80 °C
Reaction time: 24 h
Yield: 94 %

Procedure:
49.9 g of the 4-(4-benzyloxycarbonylphenoxy)nonafluorobiphenyl (0.092 mol) prepared as described in Example 1 and 26.1 g of potassium 4-nitro-3-benzyloxyphenoxide (0.092 mol) are dissolved in 400 ml of dimethylformamide, and the solution is heated to 80° C.; the reaction is complete after 24 hours. The solvent is then removed in a rotary evaporator. The solid residue obtained is washed three times with methanol, filtered off via a Büchner funnel and subsequently dried for 48 hours under nitrogen,at 40° C./10 mbar in a vacuum drying cabinet (yield: 94%).
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]([NH2:12])=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1.[Cl:13][C:14]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:15]=1[C:16]([N:18]=[C:19]=[O:20])=[O:17]>C(#N)C>[Cl:13][C:14]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:15]=1[C:16]([NH:18][C:19]([NH:12][C:4]1[O:3][C:2]([CH3:1])=[N:6][C:5]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:20])=[O:17]
Reactant: O=C=NC(=O)c1c(F)cccc1Cl
Reactant: CCOC(=O)c1nc(C)oc1N
Solvent: CC#N
Product: CCOC(=O)c1nc(C)oc1NC(=O)NC(=O)c1c(F)cccc1Cl
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To 0.6 g. 2-methyl-4-carbethoxy-5-aminooxazole dissolved in 25 ml. acetonitrile was added 0.8 2-chloro-6-fluorobenzoylisocyanate under nitrogen at about 25° C. The reaction mixture was stirred at 25° C. for 12 hours and the solid was collected. Yield 0.7 g.
Reaction SMILES: [H-].[Na+].[CH2:3]([CH:6]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:4]=[CH2:5].[CH:17]([C:19]([CH3:21])=[O:20])=[CH2:18]>C(O)C>[C:12]([C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH2:3][CH:4]=[CH2:5])[CH2:18][CH2:17][C:19](=[O:20])[CH3:21])([O:14][CH2:15][CH3:16])=[O:13]
Reactant: C=CC(C)=O
Reactant: C=CCC(C(=O)OCC)C(=O)OCC
Agent: [H-]
Agent: [Na+]
Solvent: CCO
Product: C=CCC(CCC(C)=O)(C(=O)OCC)C(=O)OCC
Temperature: 25 °C
Reaction time: 22 h
Yield: 87.8 %

Procedure:
To an ethanol solution (10.4 ml) containing sodium hydride (0.049 g, 1.13 mmol, 55% in oil) were added diethyl allylmalonate (3.0 g, 15 mmol) and methyl vinyl ketone (1.39 g, 19.9 mmol). The reaction liquid was stirred at room temperature for 22 hours. After treatment and purification as in Referential Example 1, there was obtained 3.56 g of 5,5-dicarboethoxy-7-octen-2-on (yields: 88%).
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH:16]=[CH:17][CH2:18][N:19]2C(=O)C3C(=CC=CC=3)C2=O)[CH2:11][CH2:10]1.NN>C(O)C>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:10][CH2:11][N:12]([CH2:15][CH:16]=[CH:17][CH2:18][NH2:19])[CH2:13][CH2:14]1
Reactant: O=C1c2ccccc2C(=O)N1CC=CCN1CCN(c2cccc(Cl)c2Cl)CC1
Agent: NN
Solvent: CCO
Product: NCC=CCN1CCN(c2cccc(Cl)c2Cl)CC1
Temperature: 0 °C

Procedure:
To a solution of 2-{4-[4-(2,3-Dichloro-phenyl)-piperazin-1-yl]-but-2-enyl}-isoindole-1,3-dione (5.12 g, 11.9 mmol) in absolute ethanol (100 ml) under an atmosphere of argon was added hydrazine (0.75 ml, 24 mmol), and the reaction mixture was refluxed for 2.5 h. The ice-cold reaction mixture was filtered and solvent was removed under reduced pressure. The residue was purified by column chromatography to yield 2.63 g (74%) as yellow oil.