Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[CH:3]=1.C([Li])CCC.[Br:14]Br.S([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>O1CCCC1.O>[Br:14][C:3]1[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=1[Cl:1]
Reactant: Fc1cccc(Cl)c1
Reactant: BrBr
Agent: O=S([O-])[O-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: Fc1cccc(Cl)c1Br
Reaction time: 2.5 h

Procedure:
A solution of 261.1 g (2.0 mol) of 1-chloro-3-fluorobenzene in 2000 ml of dry tetrahydrofuran under nitrogen is cooled to −78°. To the solution is added 960 ml (2.4 mol) of 2.5 M n-butyllithium in hexanes over a period of 40 minutes. After stirring for 2.5 hours, a slurry of 155 ml of bromine cooled to −78° is added over 30 minutes and the mixture is stirred for 40 minutes before warming to −10°. The reaction is quenched with an aqueous solution of 151.3 g (1.2 mol) of sodium sulfite and 16.0 g (0.4 mol) of sodium hydroxide in 500 ml of water. The organic layer is separated, the solvents are removed at ambient pressure, and the product is distilled at 92-96° (20 mm Hg) to obtain 2-bromo-3-fluoro-chlorobenzene as a colorless oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:21]=[C:22]([N+:24]([O-])=O)[CH:23]=1)[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([N:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[N:14]=2)[CH:11]=1.Cl.C(O)C.[CH3:31][N:32]1[C:36]([C:37](Cl)=[O:38])=[CH:35][C:34]([CH3:40])=[N:33]1>C(=O)([O-])O.[Na+].O>[CH:18]1([C:16]([NH:15][C:13]2[N:14]=[C:9]3[CH:8]=[CH:7][C:6]([O:5][C:4]4[CH:21]=[C:22]([NH:24][C:37]([C:36]5[N:32]([CH3:31])[N:33]=[C:34]([CH3:40])[CH:35]=5)=[O:38])[CH:23]=[C:2]([F:1])[CH:3]=4)=[CH:11][N:10]3[N:12]=2)=[O:17])[CH2:20][CH2:19]1
Reactant: Cc1cc(C(=O)Cl)n(C)n1
Reactant: O=C(Nc1nc2ccc(Oc3cc(F)cc([N+](=O)[O-])c3)cn2n1)C1CC1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Cc1cc(C(=O)Nc2cc(F)cc(Oc3ccc4nc(NC(=O)C5CC5)nn4c3)c2)n(C)n1
Reaction time: 1 h
Yield: 27.5 %

Procedure:
A mixture of N-[6-(3-fluoro-5-nitrophenoxy)[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide (130 mg, 0.364 mmol), reduced iron (150 mg), concentrated hydrochloric acid (300 μL), ethanol (3 mL) and water (3 mL) was stirred under refluxing conditions for 1 hr. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was dissolved in N,N-dimethylacetamide (3 mL). 1,3-Dimethyl-1H-pyrazole-5-carbonyl chloride (69.3 mg, 0.437 mmol) was added thereto with stirring under ice-cooling, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (NH silica gel, ethyl acetate) and recrystallized from ethyl acetate to give the title compound (45.0 mg, 28%) as a white solid.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:8]([O:10][CH3:11])=[O:9])=[N:4][CH:5]=[CH:6][N:7]=1.[F:12]F.C(=O)([O-])O.[Na+].C(OCC)(=O)C>C(O)(=O)C>[NH2:1][C:2]1[C:3]([C:8]([O:10][CH3:11])=[O:9])=[N:4][C:5]([F:12])=[CH:6][N:7]=1
Reactant: FF
Reactant: COC(=O)c1nccnc1N
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: COC(=O)c1nc(F)cnc1N
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
In 10 mL of acetic acid was dissolved 0.5 g of methyl 3-amino-2-pyrazinecarboxylate. At room temperature, 10% fluorine gas (a fluorine gas diluted with nitrogen gas) was introduced into the solution at a rate of 23 mL per minute for a period of 32 minutes. After stirring the solution for 30 minutes at room temperature, the reaction mixture was added to a mixture of 50 mL of saturated aqueous solution of sodium hydrogen carbonate and 50 mL of ethyl acetate, and the organic layer was separated. The organic layer thus obtained was washed successively with 10 mL of water and 10 mL of saturated aqueous solution of sodium chloride and dried on anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent: n-hexane:ethyl acetate=3:1] to obtain 0.01 g of methyl 3-amino-6-fluoro-2-pyrazinecarboxylate as a light yellow-colored solid product.
Reaction SMILES: Br[C:2]1[CH:24]=[CH:23][C:5]2[N:6]=[C:7]([O:9][CH:10]3[CH2:15][CH2:14][N:13]([C:16]4[N:21]=[CH:20][C:19]([F:22])=[CH:18][N:17]=4)[CH2:12][CH2:11]3)[S:8][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH:34]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:22][C:19]1[CH:18]=[N:17][C:16]([N:13]2[CH2:14][CH2:15][CH:10]([O:9][C:7]3[S:8][C:4]4[CH:3]=[C:2]([C:33]5[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH:34]=5)[CH:24]=[CH:23][C:5]=4[N:6]=3)[CH2:11][CH2:12]2)=[N:21][CH:20]=1
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Reactant: Fc1cnc(N2CCC(Oc3nc4ccc(Br)cc4s3)CC2)nc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: CC(C)(C)OC(=O)N1CC=C(c2ccc3nc(OC4CCN(c5ncc(F)cn5)CC4)sc3c2)CC1
Temperature: 100 °C
Reaction time: 4 h
Yield: 91.2 %

Procedure:
To a degassed solution of 6-bromo-2-(1-(5-fluoropyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazole (1.112 g, 2.72 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (1.26 g, 4.08 mmol), and potassium carbonate (1.127 g, 8.15 mmol) in dioxane (15 mL) and water (5 mL) was added Pd(Ph3P)4 (126 mg, 0.109 mmol). The mixture was stirred at 100° C. for 4 h. The reaction mixture was cooled to rt, diluted with water (40 mL), and extracted with CH2Cl2 (3×30 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 45% EtOAc) to afford tert-butyl 4-(2-(1-(5-fluoropyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate (1.27 g, 2.482 mmol, 91% yield) as a white solid. LCMS (m/z)=512 (M+H)+.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([CH:13]=[O:14])[C:7]2[O:11][CH:10]=[CH:9][C:8]=2[CH:12]=1)(=[O:3])[CH3:2].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[OH:14][CH2:13][C:6]1[C:7]2[O:11][CH:10]=[CH:9][C:8]=2[CH:12]=[C:4]([C:1](=[O:3])[CH3:2])[CH:5]=1
Reactant: CC(=O)c1cc(C=O)c2occc2c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CC(=O)c1cc(CO)c2occc2c1
Yield: 57.8 %

Procedure:
A solution of 5-acetyl-benzofuran-7-carbaldehyde (471 mg) in dry toluene (40 ml) was treated with sodium triacetoxyborohydride (1.12 ml) and heated at reflux for 5.5 h. The reaction mixture was poured into 8% sodium bicarbonate (40 ml) and the phases were separated. The aqueous phase was extracted with ethyl acetate (40 ml), the combined organic phases were dried, filtered, and the filtrate evaporated in vacuo to give a yellow gum. Purification by FCC eluted with hexane:ethyl acetate (2:1→1:1) gave the title compound as a pale yellow oil (275 mg) which slowly solidified.
Reaction SMILES: [C:1]1([C:7]2[CH:16]=[CH:15][C:14]3[C:9](=[CH:10][C:11]([C:17]4[C:25]5[C:24](=O)[NH:23][CH:22]=[N:21][C:20]=5[S:19][CH:18]=4)=[CH:12][CH:13]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O=P(Cl)(Cl)[Cl:29]>>[Cl:29][C:24]1[C:25]2[C:17]([C:11]3[CH:10]=[C:9]4[C:14]([CH:15]=[CH:16][C:7]([C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)=[N:8]4)=[CH:13][CH:12]=3)=[CH:18][S:19][C:20]=2[N:21]=[CH:22][N:23]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=c1[nH]cnc2scc(-c3ccc4ccc(-c5ccccc5)nc4c3)c12
Product: Clc1ncnc2scc(-c3ccc4ccc(-c5ccccc5)nc4c3)c12
Temperature: 110 °C
Reaction time: 1 h

Procedure:
A mixture of 5-(2-phenylquinolin-7-yl)-3H-thieno[2,3-d]pyrimidin-4-one (30 mg, max. 0.084 mmol, 77% purity) and POCl3 (1.0 ml) was stirred at 110° C. for 1 h under N2. The excess POCl3 was removed in vacuo, and the residue was basified by cold NH3 (2M in isopropanol). The precipitate that was formed was filtered off. The filtrate [crude 7-(4-chlorothieno[2,3-d]pyrimidin-5-yl)-2-phenylquinoline] was used without further purification for the next step. MS (ES+): 374.2/376.2 (M/M+2). HPLC: tR=6.8 min (MicromassZQ, polar—15 min).
Reaction SMILES: C([Li])CCC.[CH3:6][P:7](=[O:12])([O:10][CH3:11])[O:8][CH3:9].[CH3:13][C:14]([CH3:28])=[CH:15][CH2:16][CH2:17]/[C:18](/[CH3:27])=[CH:19]/[CH2:20][CH2:21]/[C:22](/[CH3:26])=[CH:23]/[CH:24]=[O:25].C(=O)(O)[O-].[Na+]>C1COCC1>[OH:25][CH:24](/[CH:23]=[C:22](\[CH3:26])/[CH2:21][CH2:20]/[CH:19]=[C:18](\[CH3:27])/[CH2:17][CH2:16][CH:15]=[C:14]([CH3:28])[CH3:13])[CH2:6][P:7](=[O:12])([O:10][CH3:11])[O:8][CH3:9]
Reactant: CC(C)=CCC/C(C)=C/CC/C(C)=C/C=O
Reactant: COP(C)(=O)OC
Agent: O=C([O-])O
Agent: [Li]CCCC
Agent: [Na+]
Solvent: C1CCOC1
Product: COP(=O)(CC(O)/C=C(\C)CC/C=C(\C)CCC=C(C)C)OC
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
n-Butyllithium (0.698 ml of a 2.5M solution in hexanes, 1.75 mmol) was added to a stirred solution of dimethyl methylphosphonate (0.189 ml, 1.75 mmol) in THF (4 ml), under argon at -78° C. The resulting colorless solution was stirred at this temperature for 20 min. Farnesal (350 mg, 1.59 mmol) in THF (4 ml) was added over 5 min and the resulting mixture stirred a further 30 min and then treated with saturated sodium bicarbonate solution (5 ml) and allowed to warm to r.t. The THF was evaporated in vacuo and the aqueous extracted twice with ethylacetate, washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was chromatographed on silica gel eluted with ethylacetate to afford the title compound as an oil.
Reaction SMILES: [NH:1]([C:8]1[CH:16]=[C:15]([C:17](O)=[O:18])[C:14]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:13][C:9]=1[C:10](O)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.COC1C=CC(NC2C=C(C(O)=O)C(NC3C=CC(OC)=CC=3)=CC=2C(O)=O)=CC=1.CO>O>[CH:24]1[CH:25]=[C:26]2[C:17]([C:15]3[C:14]([NH:20][C:21]2=[CH:22][CH:23]=1)=[CH:13][C:9]1[C:10]([C:7]2[C:2]([NH:1][C:8]=1[CH:16]=3)=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:11])=[O:18]
Reactant: O=C(O)c1cc(Nc2ccccc2)c(C(=O)O)cc1Nc1ccccc1
Agent: COc1ccc(Nc2cc(C(=O)O)c(Nc3ccc(OC)cc3)cc2C(=O)O)cc1
Solvent: O
Solvent: CO
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12
Temperature: 130 °C

Procedure:
A mixture (one part) of 2,5-dianilino-terephthalic acid (80 wt. %) and 2,5-dianisidino-terephthalic acid (20 wt. %) was dissolved in polyphosphoric acid (6.14 parts at 118.5%). The solution, already at 110° C., was heated to 130° C. for 3 hours, cooled to 100° C. and diluted to a fluid mass with water (0.5 parts). The solution was drowned into methanol (11.6 parts) and heated at 120° C. for 4 hours. A very bluish, transparent quinacridone pigment was obtained.
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[CH:9]=[CH:8][S:7][C:6]=1[CH3:10])=[O:4].C([Li])CCC.[O:16]1[CH2:20][CH2:19][O:18][CH:17]1[C:21]1[CH:28]=[CH:27][C:24](C#N)=[CH:23][CH:22]=1>O1CCCC1>[O:16]1[CH2:20][CH2:19][O:18][CH:17]1[C:21]1[CH:28]=[CH:27][C:24]([C:1]2[NH:2][C:3](=[O:4])[C:5]3[CH:9]=[CH:8][S:7][C:6]=3[CH:10]=2)=[CH:23][CH:22]=1
Reactant: CNC(=O)c1ccsc1C
Reactant: N#Cc1ccc(C2OCCO2)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: O=c1[nH]c(-c2ccc(C3OCCO3)cc2)cc2sccc12
Temperature: -70 °C
Reaction time: 1.5 h
Yield: 17.5 %

Procedure:
To a solution of N-methyl-2-methylthiophene-3-carboxamide (18.5 g) in tetrahydrofuran (350 ml) was dropwise added 2.5M n-butyl lithium (100 ml) at −70° C. The resulting solution was stirred at −70° C. for 1.5 hr, followed by the addition of a solution of 4-(1,3-dioxolan-2-yl)benzonitrile (20.9 g) in tetrahydrofuran (100 ml) at once. After the dry ice/acetone bath was removed, the reaction mixture was back to room temperature. Three hours later, an aqueous solution of saturated ammonium chloride was added thereto, and the organic layer was separated, washed with water and dried. The filtrate was concentrated, and the resulting solid was washed with ethyl acetate, tetrahydrofuran/ether and n-hexane in this order. The resulting solid was then dried, to give the title compound as white crystals (6.24 g, yield; 31.7%).
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C@H:10]([CH:14]([CH3:16])[CH3:15])[C:11]([OH:13])=[O:12])=[CH:5][CH:4]=1.[Cl:19]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Cl:19][C:7]1[CH:8]=[C:3]([C:2]([F:17])([F:18])[F:1])[CH:4]=[CH:5][C:6]=1[NH:9][C@H:10]([CH:14]([CH3:16])[CH3:15])[C:11]([OH:13])=[O:12]
Reactant: CC(C)[C@@H](Nc1ccc(C(F)(F)F)cc1)C(=O)O
Reactant: O=C1CCC(=O)N1Cl
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)[C@@H](Nc1ccc(C(F)(F)F)cc1Cl)C(=O)O

Procedure:
To 35 ml of carbon tetrachloride are added 2.81 g (10.0 mmol) of (R)-2-(4-trifluoromethylphenylamino)-3-methylbutanoic acid and 1.33 g (9.96 mmol) of N-chlorosuccinimide, and the mixture is heated to reflux for 1 hour. The mixture is worked up by partition between ether/water. The layers are separated and the aqueous phase is extracted with ether (2×). The combined organic extracts are washed with water and with brine, dried over magnesium sulfate, filtered and evaporated, giving (R)-2-(2-chloro-4-trifluoromethylphenylamino)-3-methylbutanoic acid.
Reaction SMILES: CN([CH:4]=[O:5])C.[CH:6]([C:8]1[CH:13]=[CH:12][C:11]([Mg]Cl)=[CH:10][CH:9]=1)=[CH2:7]>O1CCCC1>[CH:4]([C:11]1[CH:12]=[CH:13][C:8]([CH:6]=[CH2:7])=[CH:9][CH:10]=1)=[O:5]
Reactant: CN(C)C=O
Reactant: C=Cc1ccc([Mg]Cl)cc1
Solvent: C1CCOC1
Product: C=Cc1ccc(C=O)cc1
Temperature: 20 °C
Reaction time: 2 h

Procedure:
A solution of 17.06 mL (0.220 moles) of anhydrous N,N′-dimethylformamide in 100 mL of anhydrous tetrahydrofuran was cannula transferred into the 125 mL addition funnel and then added dropwise over a period of 1 hour to the previously prepared solution of p-vinylphenylmagnesium chloride (0.199 moles). The temperature was maintained at 20° C. during the addition (higher temperatures resulted in polymer formation and lower yields). The reaction mixture was stirred for 2 hours and then allowed to remain overnight under a nitrogen atmosphere. The reaction mixture was quenched with 200 mL saturated aqueous ammonium chloride solution causing an initial exotherm (up to 45° C.) and then the precipitation of a voluminous “gelatinous” white solid (magnesium hydroxides). The resultant emulsion was broken by centrifuging aliquots of the mixture at 4000 rpm for 3 minutes and the resultant clarified two phase mixture poured into a 500 mL separating funnel and the organic layer partitioned and collected. The remaining aqueous layer was extracted twice with 100 mL of Et2O; the organic extracts were then combined and dried over anhydrous MgSO4. The drying mixture was filtered and the collected solid washed with 2×50 mL portions of Et2O. The filtrate and washings were combined and the solvent was stripped off in vacuo using a rotary evaporator and the residue was distilled in vacuo in the presence of a heaped spatula measure of phenothiazine with two fractions coming over: Fraction 1 (53° C. at 0.425 torr; v. pale yellow liquid), Fraction 2 (48-50° C. at 0.350 torr; v. pale yellow liquid). Fraction 1 was discarded and fraction 2 retained and a yield taken. Yield: 18.325 g (70%, very pale yellow liquid). 1H NMR (CDCl3) δ 5.46 (d, 1H, ═C—H), 5.93 (d, 1H, ═C—H), 6.79 (dd, 1H, ═C—H), 7.57 (d, 2H, ArH), 7.86 (d, 2H, ArH), 10.01 (s, 1H, —CH═O).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:19])[CH2:4][NH:5][C:6](=[O:18])[NH:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16].[C:20](=[O:25])=[N:21][C:22](Cl)=[O:23].N1C=CC=CC=1>C(Cl)Cl>[F:14][C:12]1[CH:11]=[CH:10][C:9]([N+:15]([O-:17])=[O:16])=[C:8]([N:7]2[C:22](=[O:23])[NH:21][C:20](=[O:25])[N:5]([CH2:4][C:3]([O:2][CH3:1])=[O:19])[C:6]2=[O:18])[CH:13]=1
Reactant: O=C=NC(=O)Cl
Reactant: COC(=O)CNC(=O)Nc1cc(F)ccc1[N+](=O)[O-]
Solvent: c1ccncc1
Solvent: ClCCl
Product: COC(=O)Cn1c(=O)[nH]c(=O)n(-c2cc(F)ccc2[N+](=O)[O-])c1=O
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
A solution of N-[(5-fluoro-2-nitrophenyl)carbamoyl]glycine methyl ester (20.47 g, 75.46 mmol) in methylene chloride is cooled in an ice-bath, treated with N-(chlorocarbonyl) isocyanate (7 mL, 86.94 mmol), treated dropwise with pyridine (7.5 mL, 92.92 mmol), warmed to and stirred at room temperature for 90 minutes, and filtered. The filtrate is poured into 0.11M hydrochloric acid (450 mL), the phases are separated and the aqueous phase is extracted with methylene chloride. The organic phase and extracts are combined, washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to obtain the title product as a yellow solid.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14](OS(C)(=O)=O)[CH2:13][C@H:12]1[CH2:21][O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C-:30]#[N:31].[Na+].O.C(OCC)(=O)C>CS(C)=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@@H:14]([C:30]#[N:31])[CH2:13][C@H:12]1[CH2:21][O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)[Si](C)(C)OC[C@@H]1C[C@@H](OS(C)(=O)=O)CN1C(=O)OCc1ccccc1
Reactant: [C-]#N
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)OC[C@@H]1C[C@H](C#N)CN1C(=O)OCc1ccccc1
Yield: 48.6 %

Procedure:
A solution of (2S,4R)-1-benzyloxycarbonyl-2-(tert-butyldimethylsilyloxy)methyl-4-methanesulfonyloxypyrrolidine (10.246 g) and sodium cyanide (3.6 g) in dimethyl sulfoxide (100 ml) was heated for three hours at 92° C. The reaction mixture was poured into a mixture of water (300 ml) and ethyl acetate (300 ml). The organic layer was separated, and the remaining aqueous layer was reextracted with ethyl acetate (200 ml). The organic layers were combined, washed with brine, and dried over magnesium sulfate. Evaporation of the solvent gave an oil, which was chromatographed on silica gel (200 ml) eluting with a mixture of hexane and ethyl acetate (2:1, V/V) to give (2S,4S)-1-benzyloxycarbonyl-2-(tert-butyldimethylsilyloxy)methyl-4-cyanopyrrolidine (4.2 g).
Reaction SMILES: C(O[C:5]1[CH:39]=[CH:38][CH:37]=[CH:36][C:6]=1[C:7]([NH:9][CH2:10][C@@H:11]([C:33]([OH:35])=[O:34])[NH:12][C:13](=[O:32])[C:14]1[CH:19]=[CH:18][C:17]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)=[O:21])=[CH:16][C:15]=1[Cl:31])=[O:8])(=O)C.ClC1C=C(C(NCC2C=CC=C(O)C=2)=O)C=CC=1[C:43](N[C@H](C(O)=O)CNC(=O)C1C=CC(OCC)=CC=1)=[O:44].ClC1C=C(C(NCC2C=CC=C(O)C=2)=O)C=CC=1C(N[C@H](C(O)=O)CNC(=O)C1C=CC=CC=1OC)=O.ClC1C=C(C(NCC2C=CC=C(O)C=2)=O)C=CC=1C(N[C@H](C(O)=O)CNC(=O)C1C=CC(OC)=CC=1)=O.ClC1C=C(C(NCC2C=CC=C(O)C=2)=O)C=CC=1C(N[C@H](C(O)=O)CNC(=O)C1C=CC=C(C(OC)=O)C=1)=O.ClC1C=C(C(NCC2C=CC=C(O)C=2)=O)C=CC=1C(N[C@H](C(O)=O)CNC(=O)C1C=CC(OCCCCC)=CC=1)=O>>[Cl:31][C:15]1[CH:16]=[C:17]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)=[O:21])[CH:18]=[CH:19][C:14]=1[C:13]([NH:12][C@H:11]([C:33]([OH:35])=[O:34])[CH2:10][NH:9][C:7](=[O:8])[C:6]1[CH:5]=[CH:39][CH:38]=[C:37]([O:44][CH3:43])[CH:36]=1)=[O:32]
Reactant: CCOc1ccc(C(=O)NC[C@H](NC(=O)c2ccc(C(=O)NCc3cccc(O)c3)cc2Cl)C(=O)O)cc1
Reactant: CC(=O)Oc1ccccc1C(=O)NC[C@H](NC(=O)c1ccc(C(=O)NCc2cccc(O)c2)cc1Cl)C(=O)O
Agent: CCCCCOc1ccc(C(=O)NC[C@H](NC(=O)c2ccc(C(=O)NCc3cccc(O)c3)cc2Cl)C(=O)O)cc1
Agent: COC(=O)c1cccc(C(=O)NC[C@H](NC(=O)c2ccc(C(=O)NCc3cccc(O)c3)cc2Cl)C(=O)O)c1
Agent: COc1ccc(C(=O)NC[C@H](NC(=O)c2ccc(C(=O)NCc3cccc(O)c3)cc2Cl)C(=O)O)cc1
Product: COc1cccc(C(=O)NC[C@H](NC(=O)c2ccc(C(=O)NCc3cccc(O)c3)cc2Cl)C(=O)O)c1

Procedure:
3-(2-acetoxybenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine; N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-ethoxybenzoyl)amino-L-alanine; N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-methoxybenzoyl)amino-L-alanine; N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-methoxybenzoyl)amino-L-alanine; N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[3-(methoxycarbonyl)benzoyl]amino-L-alanine; N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-pentyloxybenzoyl)amino-L-alanine; N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]aminolcarbonyl]benzoyl]-3-(3 ,4,5-trimethoxybenzoyl)amino-L-alanine;
Reaction SMILES: C([O:4][CH2:5][CH2:6][O:7][C:8]1[C:9]([Se:22][C:23]2[CH:33]=[CH:32][C:26]([C:27]([O:29]CC)=[O:28])=[CH:25][CH:24]=2)=[CH:10][C:11]2[C:12]([CH3:21])([CH3:20])[CH2:13][CH2:14][C:15]([CH3:19])([CH3:18])[C:16]=2[CH:17]=1)(=O)C.[OH-].[Na+]>C1COCC1.C(O)C>[OH:4][CH2:5][CH2:6][O:7][C:8]1[C:9]([Se:22][C:23]2[CH:24]=[CH:25][C:26]([C:27]([OH:29])=[O:28])=[CH:32][CH:33]=2)=[CH:10][C:11]2[C:12]([CH3:21])([CH3:20])[CH2:13][CH2:14][C:15]([CH3:18])([CH3:19])[C:16]=2[CH:17]=1
Reactant: CCOC(=O)c1ccc([Se]c2cc3c(cc2OCCOC(C)=O)C(C)(C)CCC3(C)C)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: CC1(C)CCC(C)(C)c2cc([Se]c3ccc(C(=O)O)cc3)c(OCCO)cc21

Procedure:
In a manner similar to that of Example 2, by reaction of 322 mg (0.62 mmol) of ethyl 4-[3-(2-acetoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl]benzoate with 250 mg (6.2 mmol) of sodium hydroxide in a THF/ethanol mixture (3 ml/3 ml), 226 mg (81%) of a white powder are obtained. m.p.: 197° C.
Reaction SMILES: [BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[NH:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1.[CH2:20]([O:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][C:30]=1[OH:31])[CH:26]=O)[CH3:21].[OH-].[Na+]>C(Cl)Cl.O>[CH2:20]([O:22][C:23]1[CH:24]=[C:25]([CH2:26][N:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[CH:28]=[CH:29][C:30]=1[OH:31])[CH3:21]
Reactant: CCOc1cc(C=O)ccc1O
Reactant: C1CCNC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: CCOc1cc(CN2CCCC2)ccc1O
Yield: 72.3 %

Procedure:
NaB(OAc)3H (8 g, 0.038 mol) was added in portions for 30 min to a mixture of pyrrolidine (3.1 mL, 0.038 mol) and 3-ethoxy-4-hydroxybenzaldehyde (5 g, 0.03 mol) in CH2Cl2 (50 mL) under vigorous stirring and cooling with an ice bath in an atmosphere of argon Ar. The mixture was stirred for 12 h and cooled with an ice bath. 10N NaOH (3.8 mL) and water (30 mL) were added. The organic layer was separated. The aqueous one was extracted with chloroform (2×100 mL). The extracts were evaporated. The residue was purified by chromatography (silica gel 40-63μ, 100 g, CCl4—CHCl3, CHCl3/MeOH 100:0→90:10) to give the title compound (4.8 g, 73%) was obtained as dark-yellow crystals. 1H NMR data (DMSO-d6): 8.65 (s, 1H ArOH), 6.81 (d, 1H, J=1.71, Ar—H), 6.70 (d, 1H, J=7.8, Ar—H); 6.65 (dd, 1H, J1=7.8, J2=1.7, Ar—H), 3.98 (q, 2H, CH2CH3), 3.42 (s, 2H, ArCH2), 2.33-2.45 (m, 4H, pyrrolidine (CH2)2N), 1.59-1.73 (m, 4H, CH2CH2CH2CH2); 1.31 (t, 3H, J=6.9, CH2CH3).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:40])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][C:17](B3OC(C)(C)C(C)(C)O3)=[CH:16][C:15]=2[CH2:29][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:31][CH3:32])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2].Br[C:42]1[CH:43]=[CH:44][C:45]([O:48][CH2:49][CH3:50])=[N:46][CH:47]=1>>[CH2:1]([O:3][C:4](=[O:40])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][C:17]([C:42]3[CH:47]=[N:46][C:45]([O:48][CH2:49][CH3:50])=[CH:44][CH:43]=3)=[CH:16][C:15]=2[CH2:29][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:31][CH3:32])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2]
Reactant: CCOc1ccc(Br)cn1
Reactant: CCOC(=O)Cc1ccc(OC)c(-c2ccc(B3OC(C)(C)C(C)(C)O3)cc2CN(CC)C(=O)OC(C)(C)C)c1
Product: CCOC(=O)Cc1ccc(OC)c(-c2ccc(-c3ccc(OCC)nc3)cc2CN(CC)C(=O)OC(C)(C)C)c1

Procedure:
Prepared according to the procedure described in Example 1, Step 4, using the following starting materials: [2′-[(tert-butoxycarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-biphenyl-3-yl]-acetic acid ethyl ester and 5-bromo-2-ethoxypyridine.