Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([N:11]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:12][CH2:13][OH:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C(#N)C.O.I(O)(=O)(=O)=[O:26]>O.[Ru](Cl)(Cl)Cl.C(Cl)Cl>[C:1]([N:11]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:12][C:13]([OH:26])=[O:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2]
Reactant: O=C(OCc1ccccc1)N(CCO)c1ccccc1
Reactant: [O-][I+3]([O-])([O-])O
Agent: Cl[Ru](Cl)Cl
Solvent: ClCCl
Solvent: CC#N
Solvent: O
Product: O=C(O)CN(C(=O)OCc1ccccc1)c1ccccc1
Temperature: 0 °C
Yield: 84.1 %

Procedure:
In a 100 mL round bottom flask equipped with a magnetic stirrer, N-Cbz phenyl glycinol (1.3 g, 5.0 mmol) was disssolved in CC14 (100 mL)and acetonitrile (100 mL). To this above solution was added water (15 mL) and periodic acid (4.7 g, 20.1 mmol, 4.1 eq). The reaction mixture was stirred until both phases became clear, then Ruthenium trichoride hydrate (0.025 g, 2.2 mol %). The reaction mixture was stirred at room temperature for 20 min and cooled to 0° C. then methylene cloride (30 mL) was added. The two phases were separated, the aqueous phase was extracted with chloroform (3×20 mL). The combined organic extracts were dried over (Na2SO4) and concentrated to afford the crud product. Flash chromatograpy (SiO2, 5×25 cm, 2-5% CH3OH—CHCl3 gradient elution) afforded pure pure N-Cbz phenyl glycine (1.2 g, 85%). Same Oxidation procedure was followed for compounds 1 and 2. No epimerization was observed during oxidation procedure.
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]1[C:8]([C:9]([O:11][CH3:12])=[O:10])=[CH:7][NH:6][N:5]=1.Cl[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[N:15]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:1][O:2][CH2:3][C:4]1[C:8]([C:9]([O:11][CH3:12])=[O:10])=[CH:7][N:6]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[N:15]=2)[N:5]=1
Reactant: COCc1n[nH]cc1C(=O)OC
Reactant: FC(F)(F)c1cccc(Cl)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COCc1nn(-c2cccc(C(F)(F)F)n2)cc1C(=O)OC
Temperature: 100 °C
Reaction time: 8 h
Yield: 74.9 %

Procedure:
To a solution of methyl 3-(methoxymethyl)-1H-pyrazole-4-carboxylate (5.1 g) synthesized in Example 29(1) in N,N-dimethylformamide (70 mL) were added 2-chloro-6-trifluoromethylpyridine (5.0 g) and potassium carbonate (6.2 g), and the mixture was stirred at 100° C. overnight. The reaction mixture was allowed to cool to room temperature and filtered through celite, water was added to the filtrate, and the mixture was extracted with diethyl ether. The extract was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4, volume ratio) to give the title object compound (6.5 g, 69%) as colorless crystals.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8]([C:10](=O)[CH3:11])[C:7]([C:13]([F:16])([F:15])[F:14])=[CH:6][C:5]=1[NH:17][C:18](=[O:20])[CH3:19].[CH2:22]([O:24][C:25](=[O:28])[NH:26][NH2:27])[CH3:23].CC1C=CC(S(N)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8]([C:10](=[N:27][NH:26][C:25]([O:24][CH2:22][CH3:23])=[O:28])[CH3:11])[C:7]([C:13]([F:16])([F:15])[F:14])=[CH:6][C:5]=1[NH:17][C:18](=[O:20])[CH3:19]
Reactant: COC(=O)c1cc(C(C)=O)c(C(F)(F)F)cc1NC(C)=O
Reactant: CCOC(=O)NN
Agent: Cc1ccc(S(N)(=O)=O)cc1
Solvent: Cc1ccccc1
Product: CCOC(=O)NN=C(C)c1cc(C(=O)OC)c(NC(C)=O)cc1C(F)(F)F
Temperature: 150 °C
Reaction time: 40 h
Yield: 40.5 %

Procedure:
In a round bottom flask fitted with a Dean-Stark, a solution of 5-acetyl-2-acetylamino-4-trifluoromethyl-benzoic acid methyl ester (2.384 g, 7.86 mmol) in toluene (16 mL) was treated with ethylcarbazate (2.61 g, 25 mmol,) followed by p-toluenesulfonamide (103 mg, 0.60 mmol). The reaction was stirred at 150° C. for 40 h. The solvent was removed by distillation and the residue was purified by flash column chromatography (silica gel, 1:1 EtOAc/hexanes) to give the title compound (1.24 g, 40%). API-ES: m/z 390.1 [M+H]+, rt 4.14 min, 4.20 min: mixture of cis and trans.
Reaction SMILES: [NH:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)=[CH:5][N:4]=1)[NH2:2].[Cl:17][C:18]1[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[C:20]([O:27][CH3:28])[CH:19]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1>C(Cl)Cl>[Cl:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]([NH:2][NH:1][C:3]2[CH:8]=[CH:7][C:6]([C:9]3[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=3)=[CH:5][N:4]=2)=[O:23])=[C:20]([O:27][CH3:28])[CH:19]=1
Reactant: COc1cc(Cl)ccc1C(=O)O
Reactant: COc1ccc(-c2ccc(NN)nc2)cc1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: COc1ccc(-c2ccc(NNC(=O)c3ccc(Cl)cc3OC)nc2)cc1
Yield: 81.2 %

Procedure:
A solution of 2-hydrazinyl-5-(4-methoxyphenyl)pyridine (200 mg, 0.93 mmol), 4-chloro-2-methoxybenzoic acid (210 mg, 1.12 mmol), BOP (500 mg, 1.12 mmol) and NMM (330 mg, 3.27 mmol) in DCM (9 mL) was stirred at room temperature under Nitrogen overnight. The resulting mixture was filtered, and the solid was washed with DCM, dried to give the title compound as white solids (290 mg, 81.2% yield), which was used for the next reaction without further purification. MS: m/z 384.2 [M+H+].
Reaction SMILES: [C:1]([O:4][C:5](=[O:7])[CH3:6])(=O)[CH3:2].[BrH:8].[F:9][C:10]([F:23])=[CH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]CCO>>[C:5]([O:4][CH2:1][CH2:2][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][C:10]([Br:8])([F:23])[F:9])(=[O:7])[CH3:6]
Reactant: OCCCCCCCCCCC=C(F)F
Reactant: CC(=O)OC(C)=O
Reactant: Br
Product: CC(=O)OCCCCCCCCCCCC(F)(F)Br
Temperature: 100 °C
Reaction time: 3 h

Procedure:
Acetic anhydride, 37 ml, was added slowly dropwise to 10 ml of stirred 47% hydrobromic acid. Upon completion of addition, 10.0 grams (0.045 mole) of 12,12-difluoro-11-dodecen-1-ol (prepared in Example 5) was added dropwise. Following this addition the reaction mixture was warmed to 100° C. where it was stirred for three hours. The reaction mixture was cooled to ambient temperature and then was extracted with three 20 ml portions of methylene chloride. The combined extracts were in turn washed with one 15 ml portion of water, three 15 ml portions of an aqueous solution saturated with sodium bicarbonate, one 15 ml portion of water, one 15 ml portion of aqueous 1N hydrochloric acid, one 15 ml portion of water and one 15 ml portion of an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was subjected to column chromatography on silica gel. Elution was accomplished using 10% ethyl acetate in heptane. The appropriate fractions were combined and concentrated under reduced pressure yielding 2.8 grams of 12-bromo-12,12-difluorododecanyl acetate. The nmr spectrum was consistent with the proposed structure.
Reaction SMILES: [NH2:1][C:2]1[C:11]([OH:12])=[C:10]2[C:5]([C:6](=[O:23])[C:7]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)=[C:8]([CH:13]([CH3:15])[CH3:14])[O:9]2)=[CH:4][CH:3]=1.[CH:24]([O-])=[O:25].[Na+]>C(O)=O>[Cl:22][C:19]1[CH:18]=[CH:17][C:16]([C:7]2[C:6](=[O:23])[C:5]3[C:10](=[C:11]([OH:12])[C:2]([NH:1][CH:24]=[O:25])=[CH:3][CH:4]=3)[O:9][C:8]=2[CH:13]([CH3:14])[CH3:15])=[CH:21][CH:20]=1
Reactant: CC(C)c1oc2c(O)c(N)ccc2c(=O)c1-c1ccc(Cl)cc1
Reactant: O=C[O-]
Agent: [Na+]
Solvent: O=CO
Product: CC(C)c1oc2c(O)c(NC=O)ccc2c(=O)c1-c1ccc(Cl)cc1
Temperature: 25 °C

Procedure:
A stirred mixture of 7-amino-3-(4-chlorophenyl)-8-hydroxy-2-isopropyl-chromen-4-one (1.1 g, 3.35 mmol) and sodium formate (0.23 g, 3.35 mmol) in formic acid (50 ml) is heated under reflux for 2 h. After cooling to room temperature, the reaction mixture is poured into ice/water (300 ml) with stirring. The resulting aqueous suspension is washed with ethyl acetate (2×100 ml). The combined organic layers are washed with water (3×100 ml) and brine (100 ml), dried (magnesium sulfate) and filtered. The solvent is removed by evaporation in vacuo to afford a dark brown oil. This is purified by flash chromatography (hexane/ethyl acetate=1:1, followed by 100% ethyl acetate) to afford the title compound.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([CH3:8])[CH:7]=1.[F:10][C:11]([F:22])([F:21])[C:12]1[CH:13]=[CH:14][C:15]([CH2:18][CH2:19][NH2:20])=[N:16][CH:17]=1>>[F:9][C:5]1[CH:4]=[CH:3][C:2]([NH:20][CH2:19][CH2:18][C:15]2[CH:14]=[CH:13][C:12]([C:11]([F:22])([F:10])[F:21])=[CH:17][N:16]=2)=[CH:7][C:6]=1[CH3:8]
Reactant: Cc1cc(Br)ccc1F
Reactant: NCCc1ccc(C(F)(F)F)cn1
Product: Cc1cc(NCCc2ccc(C(F)(F)F)cn2)ccc1F

Procedure:
In analogy to the procedure described for the synthesis example 71 (step 1), the title compound (4-fluoro-3-methyl-phenyl)-[2-(5-trifluoromethyl-pyridin-2-yl)-ethyl]-amine (MS m/e: 299.3 [M+H]+) was prepared from 5-bromo-2-fluorotoluene instead of 6-bromo-2,3-dihydro-benzofuran and 2-(5-trifluoromethyl-pyridin-2-yl)-ethylamine instead of 2-(6-trifluoromethyl-pyridin-3-yl)-ethylamine.
Reaction SMILES: CS(O[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH:16]2[O:28][CH2:29][C:30]2[CH:39]=[CH:38][C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH:31]=2)=[CH:11][CH:10]=1)(=O)=O.[Na].[NH:41]1[CH:45]=[N:44][CH:43]=[N:42]1>CN(C)C=O>[CH:31]1[C:32]2[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:38]=[CH:39][C:30]=1[CH2:29][O:28][CH:16]1[CH:15]([C:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:7][CH2:6][N:41]3[CH:45]=[N:44][CH:43]=[N:42]3)=[CH:10][CH:11]=2)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:17]1
Reactant: c1nc[nH]n1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(OCCOS(C)(=O)=O)cc2)C(OCc2ccc3ccccc3c2)C1
Agent: [Na]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC(c2ccc(OCCn3cncn3)cc2)C(OCc2ccc3ccccc3c2)C1
Temperature: 100 °C
Yield: 85 %

Procedure:
A solution of 11 0 mg (0.2 mmol) of crude tert-butyl (3RS,4RS)-4-[4-(2-methylsulphonyloxy-ethoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate in 5 ml of dimethylformamide was treated with 70 mg (1.0 mmol) of 1,2,4-triazole sodium salt and the reaction mixture was heated to 100° C. for 6 hours. Subsequently, the mixture was cooled to room temperature and the dimethylformamide was distilled off in an oil pump vacuum. The residue was taken up in 10 ml of methylene chloride, washed with 2 ml of water, the organic phase was dried over sodium sulphate and evaporated under reduced pressure. The residue was chromatographed on silica gel using a 95:5:0.1 mixture of methylene chloride, methanol and ammonia as the eluent. There were obtained 90 mg (85% of theory) of tert-butyl (3RS,4RS)-3-naphthalen-2-ylmethoxy-4-[4-(2-[1,2,4]triazol-1-yl-ethoxy)-phenyl]-piperidine-1-carboxylate as a colourless oil; MS: 529 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.O[CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([CH:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: Clc1ncnc2[nH]cc(I)c12
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(n2cc(I)c3c(Cl)ncnc32)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 35.8 %

Procedure:
At −10° C. and under N2 atmosphere, to a stirred solution of 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (3.0 g, 10.7 mmol), tert-butyl 4-hydroxypiperidine-1-carboxylate (5.4 g, 26.8 mmol), and PPh3 in anhydrous THF were slowly added DIAD over one hour. The resulting reaction mixture was subsequently warmed up to room temperature and stirred for additional 2 hours. Once the yellow precipitation was generated, the reaction mixture was cooled back to −5° C. and stirred overnight. While the solution was still cold, the yellow precipitation was quickly filtrated and washed with cold THF (30 mL) to afford tert-Butyl 4-(4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)piperidine-1-carboxylate (62) (1.77 g, 36%) as a white solid. LC-MS (ESI): m/z (M/M+2) 463.1/465.1.
Reaction SMILES: [NH:1]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH3:10]OC(OC)N(C)C>C1C=CC=CC=1>[N:1]12[CH:10]3[N:4]([CH2:5][CH2:6][N:7]3[CH2:8][CH2:9]1)[CH2:3][CH2:2]2
Reactant: C1CNCCNCCN1
Reactant: COC(OC)N(C)C
Solvent: c1ccccc1
Product: C1CN2CCN3CCN1C23

Procedure:
A reaction mixture of 4.00 g (31 mmol) of 1,4,7-triazacyclononane (perhydro-1,4,7-triazonine), 3.70 g (31 mmol) of dimethylformamide dimethyl acetal and 50 ml of dry benzene was distilled through a spinning band column until the by-products and solvent were removed (dimethylamine, benzene-methanol azeotrope, bp 58°, and benzene, bp 80°). The residue was then distilled through a shortpath apparatus giving 3.68 g (86%) of clear, colorless liquid, bp 80°-82° (2.5 mm), nD24 = 1.5175. Redistillation of a small sample in a molecular still at 80° (0.4 mm) gave an analytical sample of 1,4,7-triazatricyclo[5.2.1.04,10 ]decane.
Reaction SMILES: [C:1]([N-:5][CH:6]=[CH:7][N-:8][C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:4])([CH3:3])[CH3:2].[Li+].[Li+].[Li].Cl[SiH:17](Cl)Cl.[CH2:20]([NH:22][CH2:23][CH3:24])[CH3:21]>CCCCCC.O1CCCC1>[C:9]([N:8]1[CH:7]=[CH:6][N:5]([C:1]([CH3:3])([CH3:4])[CH3:2])[SiH:17]1[N:22]([CH2:23][CH3:24])[CH2:20][CH3:21])([CH3:12])([CH3:11])[CH3:10]
Reactant: CC(C)(C)[N-]C=C[N-]C(C)(C)C
Reactant: CCNCC
Reactant: Cl[SiH](Cl)Cl
Agent: [Li+]
Agent: [Li]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCN(CC)[SiH]1N(C(C)(C)C)C=CN1C(C)(C)C
Temperature: 25 °C
Reaction time: 4 h
Yield: 60 %

Procedure:
In an argon atmosphere, a dilithium(N,N′-di-tert-butyl-1,2-vinylenediaminide) solution prepared by using 32.00 g of tBuNCHCHNtBu, 50 mL of tetrahydrofuran, 150 mL of hexane and 2.67 g of lithium according to the procedure described in Reference Example-9 was added to a hexane (120 mL) solution containing 25.20 g (186.0 mmol) of trichlorosilane, and the mixture was stirred at room temperature for 4 hours. To this reaction mixture, 30.00 g (410.2 mmol) of diethylamine was added, and the mixture was stirred at room temperature for 5 hours. Insoluble matters produced were separated by filtration, and the solvent was removed by distillation from the filtrate under atmospheric pressure. The obtained residue was distilled under reduced pressure (distillation temperature: 102° C./4.0×102 Pa) to obtain 1,3-di-tert-butyl-2-diethylamino-1,3-diaza-2-silacyclopent-4-ene (Si(tBuNCHCHNtBu)(H)NEt2) as a pale yellow liquid (yielded amount: 30.29 g, yield: 60%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[C:11](=[O:26])[C@:10]([CH2:28][C:29](O)=[O:30])([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[F:46][C:47]([F:53])([F:52])[S:48]([NH2:51])(=[O:50])=[O:49]>CN(C=O)C.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[N:12]([CH:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[C:11](=[O:26])[C@:10]([CH2:28][C:29]([NH:51][S:48]([C:47]([F:53])([F:52])[F:46])(=[O:50])=[O:49])=[O:30])([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: CCC(CC)N1C(=O)[C@@](C)(CC(=O)O)C[C@H](c2cccc(Cl)c2)[C@H]1c1ccc(Cl)cc1
Reactant: NS(=O)(=O)C(F)(F)F
Agent: CN(C)c1ccncc1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: CCC(CC)N1C(=O)[C@@](C)(CC(=O)NS(=O)(=O)C(F)(F)F)C[C@H](c2cccc(Cl)c2)[C@H]1c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 47 mg (0.10 mmol) of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)acetic acid (Example 71, Step F) in DMF (4 mL) was added 64 mg (0.34 mmol) of EDC, 48 mg (0.36 mmol) of HOBt, and a catalytic amount of DMAP. After 30 min, 45.5 mg (0.30 mmol) of trifluoromethanesulfonamide was added. The resulting light yellow solution was stirred at room temperature for 3 h, and then was concentrated under reduced pressure. Purification of the residue by reversed phase prep. HPLC (Sunfire™ Prep C18 OBD 10 μm column (Waters, Milford, Mass.), gradient elution of 50% MeCN in water to 90% MeCN in water over a 30 min period, where both solvents contain 0.1% TFA) provided the title compound as a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([Br:8])[CH:3]=1.Cl[C:10](OC1C=CC=CC=1)=[O:11].[CH3:19][C@H:20]1[CH2:25][NH:24][C@H:23]([CH3:26])[CH2:22][N:21]1[C:27]1[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[C:29]([C:35]([F:38])([F:37])[F:36])[CH:28]=1>N1C=CC=CC=1>[Br:8][C:4]1[CH:3]=[C:2]([NH:1][C:10]([N:24]2[CH2:25][C@H:20]([CH3:19])[N:21]([C:27]3[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[C:29]([C:35]([F:38])([F:37])[F:36])[CH:28]=3)[CH2:22][C@H:23]2[CH3:26])=[O:11])[CH:7]=[CH:6][N:5]=1
Reactant: C[C@@H]1CN(c2ccc(C#N)c(C(F)(F)F)c2)[C@@H](C)CN1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: Nc1ccnc(Br)c1
Solvent: c1ccncc1
Product: C[C@@H]1CN(c2ccc(C#N)c(C(F)(F)F)c2)[C@@H](C)CN1C(=O)Nc1ccnc(Br)c1
Temperature: 25 °C
Reaction time: 96 h

Procedure:
A 1.66 g portion of 4-amino-2-bromopyridine was dissolved in 1.4 ml of pyridine, mixed with 2.0 g of phenyl chloroformate and stirred at room temperature for 4 days. Next, this was mixed with 2 g of (2S,5R)-4-(2,5-dimethylpiperazin-1-yl)-2-trifluoromethylbenzonitrile synthesized in Reference Example 11-1 and heated at 100° C. for 1 hour and 30 minutes. After evaporation of the solvent, the residue was dissolved in ethyl acetate, washed with water and then with saturated brine and dried over magnesium sulfate. After evaporation of the solvent, the residue was subjected to a silica gel column chromatography and eluted with chloroform-methanol (30:1, v/v), and the resulting fraction was subjected to crystallization from ethyl acetate-hexane to obtain 2.7 g of the title compound.
Reaction SMILES: [OH:1][CH:2]([C:15]1[CH:19]=[CH:18][O:17][C:16]=1[Si:20]([CH2:25][CH3:26])([CH2:23][CH3:24])[CH2:21][CH3:22])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[C:27]1([N:33]=[C:34]=[O:35])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.NCC1C=C([Si](CC)(CC)CC)OC=1>CN(C)C=O>[C:27]1([NH:33][C:34]([O:1][CH:2]([C:15]2[CH:19]=[CH:18][O:17][C:16]=2[Si:20]([CH2:25][CH3:26])([CH2:23][CH3:24])[CH2:21][CH3:22])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])=[O:35])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: CCCCCCCCCCCCC(O)c1ccoc1[Si](CC)(CC)CC
Reactant: O=C=Nc1ccccc1
Agent: CC[Si](CC)(CC)c1cc(CN)co1
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCC(OC(=O)Nc1ccccc1)c1ccoc1[Si](CC)(CC)CC

Procedure:
3-(1-Hydroxytridecyl)-2-triethylsilylfuran is reacted with phenyl isocyanate and copper (2) chloride in dimethylformamide to give 3-(1-phenylcarbamoyloxytridecyl)-2-triethylsilylfuran. Oxidizing the latter intermediate with singlet oxygen and thereafter reduction with sodium borohydride gives 3-(1-phenylcarbamoyloxytridecyl)-2(5H)-furanone. Substituting phenyl isocyanate with diethyl chlorophosphate, gives 3-(1-diethylphosphonooxytridecyl)-2(5H)-furanone. Substituting phenyl isocyanate with ethyl chloroformate, gives 3-(1-ethoxycarbonyloxytridecyl)- 2(5H)-furanone. Substituting phenyl isocyanate with methoxyethyl chloromethyl ether, gives 3-[1-(2-methoxy)ethoxymethoxy]tridecyl-2(5H)-furanone.
Reaction SMILES: Cl[C:2]1[C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:15])[CH:8]=2)[N:3]=1.[C:16]([NH:26][CH2:27][CH2:28][CH2:29][CH2:30][C@@H:31]([C:33]([OH:35])=[O:34])[NH2:32])([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17]>>[CH2:19]([O:18][C:16]([NH:26][CH2:27][CH2:28][CH2:29][CH2:30][C@H:31]([NH:32][C:2]1[C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:15])[CH:8]=2)[N:3]=1)[C:33]([OH:35])=[O:34])=[O:17])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: O=C(O)c1cc2cc(Cl)ccc2nc1Cl
Reactant: N[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)O
Product: O=C(NCCCC[C@H](Nc1nc2ccc(Cl)cc2cc1C(=O)O)C(=O)O)OCc1ccccc1
Yield: 43 %

Procedure:
In close analogy to the procedure described in Example 1, 2,6-dichloroquinoline-3-carboxylic acid is reacted with N(ε)-Cbz-L-lysine to provide the title compound in 43% yield as yellow needles (recrystallization from EtOH/water).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[CH:7]=[CH:8][CH:9]=[C:10]4[C:21]=3[C:14]([C:15]3[C:20]=2[C:19]=1[CH:18]=[CH:17][CH:16]=3)=[CH:13][CH:12]=[CH:11]4.[C:22]1([NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].[N+](C1C=CC=CC=1)([O-])=O>[Cu]>[C:29]1([N:28]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:2]2[CH:3]=[CH:4][C:5]3[C:6]4[CH:7]=[CH:8][CH:9]=[C:10]5[C:21]=4[C:14]([C:15]4[C:20]=3[C:19]=2[CH:18]=[CH:17][CH:16]=4)=[CH:13][CH:12]=[CH:11]5)[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1
Reactant: Brc1ccc2c3cccc4cccc(c5cccc1c52)c43
Reactant: c1ccc(Nc2ccccc2)cc1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=[N+]([O-])c1ccccc1
Product: c1ccc(N(c2ccccc2)c2ccc3c4cccc5cccc(c6cccc2c63)c54)cc1
Reaction time: 40 h

Procedure:
The following compounds were introduced into a vessel: (a) 3-bromoperylene; (b) diphenylamine; (c) potassium carbonate; (d) copper power; and (e) nitrobenzene. Then, the mixture was stirred at 200 degrees centigrade for 40 hours. After reaction has finished, nitrobenzene was removed under a reduced pressure. Then, chloroform was added to the mixture, and filtered for removing inorganic materials. A filtrate was condensed, and then, impurities were removed by silica gel column chromatography employing ligroin. As a result, there was obtained a target material, 3-diphenylaminoperylene.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=[O:3])[CH3:2].C1([SiH2]C2C=CC=CC=2)C=CC=CC=1.CO.Cl>O1CCCC1>[C:4]1([C@H:1]([OH:3])[CH3:2])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CC(=O)c1ccccc1
Agent: Cl
Agent: c1ccc([SiH2]c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CO
Product: C[C@@H](O)c1ccccc1

Procedure:
After dissolving a mixed solution of 0.25 mmol of [Rh(COD)Cl]2, 0.0005 mmolof(4S,4'S)-2,2'-bis(o-diarylphosphinophenyl)-4,4, 5,5'-tetrahydro-4,4'-bi(1,3-oxazole) prepared in Example 1 and 1 mmol acetophenone in 1 ml of tetrahydrofuran, the solution was stirred for an hour at room temperatures. At 0 ° C., 1 mmol of acetophenone and 1.5 mmol of diphenylsilane were added to the mixture. After the reaction mixture was stirred for 7 hours at 0° C., 5 ml of methanol and 10 ml of 0.1 N HCl aqueous solution were added. After the organic layer was extracted with diethyl ether and dried (Na2SO4), solvent was removed by vacuum distillation. The remainder was purified by using a silica column chromatography to obtain an optically active secondary alcohol, (R)-1-phenyl ethyl alcohol.
Reaction SMILES: Cl[C:2]([F:11])([F:10])[CH:3](Cl)[CH2:4][C:5]([F:8])([F:7])[F:6].C1S(=O)(=O)CCC1.[F-:19].[K+]>>[F:10][C:2]([F:11])([F:19])[CH:3]=[CH:4][C:5]([F:8])([F:7])[F:6]
Reactant: FC(F)(F)CC(Cl)C(F)(F)Cl
Reactant: [F-]
Agent: [K+]
Solvent: O=S1(=O)CCCC1
Product: FC(F)(F)C=CC(F)(F)F
Yield: 89.5 %

Procedure:
960 g of 1,2-dichloro-1,1,4,4,4-pentafluorobutane were added dropwise to a mixture of 3 1 of distilled tetramethylene sulphone and 830 g of dried potassium fluoride at 190° C. and 1,1,1,4,4,4-hexafluorobut-2-ene was distilled off as it was formed. The product thus obtained was redistilled to give 650 g of 1,1,1,4,4,4-hexafluorobut-2-ene having a boiling point of 8° C at atmospheric pressure.