Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:19]#[N:20])(O[Si](C)(C)C)[CH2:6]1)=[O:4].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[H][H]>CO.[OH-].[OH-].[Pd+2]>[CH3:1][O:2][C:3]([CH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]([CH2:19][NH2:20])[CH2:6]1)=[O:4]
Reactant: [H][H]
Reactant: COC(=O)C1CC(C#N)(O[Si](C)(C)C)c2ccccc21
Agent: [Pd+2]
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COC(=O)C1CC(CN)c2ccccc21
Reaction time: 0.25 h
Yield: 88.9 %

Procedure:
To a solution of 5.79 g of 3-cyano-3-trimethylsilanyloxy-indan-1-carboxylic acid methyl ester (20.0 mmol, 1.0 equivalent) in 25 mL of methanol was added 5.71 g of p-toluenesulfonic acid monohydrate (30.0 mmol, 1.5 equivalent). The solution was stirred for 15 minutes and then 4.21 g of 20% palladium hydroxide on carbon, 50% wet by weight, (3.00 mmol, 0.15 equivalent) was added. The reaction mixture was subjected to hydrogenolysis at 50 psi of hydrogen over 24 hours. After this time, the reaction mixture was filtered through Celite and typically used filtrate in the next step (Example 60D). The isolation of the title compound was conducted as follows: the filtrate was concentrated in vacuo; the residue was partitioned between 30 mL of methylene chloride and 20 mL of a saturated aqueous solution of sodium carbonate; the aqueous layer was extracted with 15 mL of methylene chloride; the combined aqueous layers were washed with 40mL of a saturated aqueous solution of sodium chloride; the organic solution was dried over anhydrous sodium sulfate and concentrated to afford the title compound as an oil (3.65 g, 89%) with approximately a 10:1 ratio of diastereomers; (major diastereomer) 1H NMR (400 MHz, CDCl3): δ 7.43 (dd, J=6.9, 1.6 Hz, 1H), 7.29-7.25 (m, 3H), 4.09 (t, J=8.1 Hz, 1H), 3.80 (s, 3H), 3.31-3.24 (m, 1H), 3.14 (dd, J=12.8, 4.7 Hz, 1H), 2.98 (dd, J=12.8, 7.3 Hz, 1H), 2.62-2.52 (m, 1H), 2,31-2.42 (m, 1H), 1.3 (bs, 2H).
Reaction SMILES: [C:1]([O:4][CH2:5][N:6]1[CH:9]([S:10][C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)[CH:8]([CH2:20][CH2:21][CH3:22])[C:7]1=[O:23])(=[O:3])[CH3:2].ClC1C=CC=C(C(OO)=[O:32])C=1>C(Cl)Cl.C([O-])(O)=O.[Na+]>[C:1]([O:4][CH2:5][N:6]1[CH:9]([S:10]([C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)=[O:32])[CH:8]([CH2:20][CH2:21][CH3:22])[C:7]1=[O:23])(=[O:3])[CH3:2]
Reactant: CCCC1C(=O)N(COC(C)=O)C1Sc1ccc([N+](=O)[O-])cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCCC1C(=O)N(COC(C)=O)C1S(=O)c1ccc([N+](=O)[O-])cc1
Reaction time: 0.25 h
Yield: 33.3 %

Procedure:
To a solution of 46 mg (0.127 mmole) azetidinone from Step B in 4 ml CH2Cl2 and 4 ml saturated aqueous NaHCO3 was added 27 mg (0.127 mM) 80% m-chloroperbenzoic acid and the reaction mixture stirred vigorously 15 minutes. The phases were separated and the organic phase was dried over MgSO4, filtered and stripped to yield 57 mg crude product which was chromatographed on a 1000μ silica gel prep TLC plate in chloroform-ethyl acetate 4:1 to yield 15 mg (31%) of 1-acetoxymethyl-4-p-nitrophenylsulfinyl-3-n-propylazetidin-2-one.
Reaction SMILES: [Br:1]Br.[C:3]([C:6]1[CH:7]=[C:8]([NH:12][C:13](=[O:17])[O:14][CH2:15][CH3:16])[CH:9]=[CH:10][CH:11]=1)(=[O:5])[CH3:4]>O1CCOCC1.CCOCC>[Br:1][CH2:4][C:3]([C:6]1[CH:7]=[C:8]([NH:12][C:13](=[O:17])[O:14][CH2:15][CH3:16])[CH:9]=[CH:10][CH:11]=1)=[O:5]
Reactant: BrBr
Reactant: CCOC(=O)Nc1cccc(C(C)=O)c1
Solvent: CCOCC
Solvent: C1COCCO1
Product: CCOC(=O)Nc1cccc(C(=O)CBr)c1
Reaction time: 2 h
Yield: 97.8 %

Procedure:
24.1 gm of bromine were added slowly over a period of 30 minutes to a stirred suspension of 28.5 gm of ethyl N-(3-acetyl-phenyl)-carbamate in 13.3 gm of dry dioxane and 245 ml of dry ether. After stirring the reaction solution for 2 hours more, it was cooled, and the product which crystallized out was collected and washed with ether, yielding 38.5 gm of the title compound, m.p. 108°-110° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[OH:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[N:16]=[CH:15][CH:14]=[CH:13]2>CCOC(C)=O.C1CCCCC1>[Cl:8][C:4]1[CH:5]=[N:6][CH:7]=[C:2]([O:9][C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[CH:15][CH:14]=[CH:13]3)[N:3]=1
Reactant: Oc1ccc2ncccc2c1
Reactant: Clc1cncc(Cl)n1
Solvent: CCOC(C)=O
Solvent: C1CCCCC1
Product: Clc1cncc(Oc2ccc3ncccc3c2)n1
Yield: 75 %

Procedure:
Using Method DD with 2,6-dichloropyrazine (250 mg, 1.69 mmol) and 6-hydroxyquinoline (270 mg, 1.49 mmol), and purification by column chromatography (AcOEt cyclohexane, 1:1), the title compound was obtained (324 mg). Yield: 75%. 1H NMR (250 MHz, DMSO-d6) δ 7.56-7.59 (m, 1H, Harom 3), 7.70 (dd, 1H, Harom 7, Jm=2.6 Hz, Jo=9.1 Hz), 7.87 (d, 1H, Harom 5, J=2.4 Hz), 8.12 (d, 1H, Harom 8, J=9.0 Hz), 8.37 (d, 1H, Harom 4, J=8.1 Hz), 8.56 (s, 1H, HPz 5) 8.65 (s, 1H, HPz 3), 8.93 (dd, 1H, Harom 2, J=1.0 Hz, J=4.9 Hz). m/z: 258.0 [(M+H)+, calcd for C13H8ClN3O 257.0].
Reaction SMILES: [CH3:1][N:2]([CH:4]([CH:7]1[CH2:16][CH2:15][C:10]2([O:14][CH2:13][CH2:12][O:11]2)[CH2:9][CH2:8]1)[C:5]#N)[CH3:3].[C:17]1([Mg]Cl)[CH:22]=[CH:21]C=[CH:19][CH:18]=1.[Cl-].[NH4+].O>C1COCC1>[O:14]1[C:10]2([CH2:15][CH2:16][CH:7]([CH:4]([N:2]([CH3:3])[CH3:1])[C:5]3[CH:21]=[CH:22][CH:17]=[CH:18][CH:19]=3)[CH2:8][CH2:9]2)[O:11][CH2:12][CH2:13]1
Reactant: Cl[Mg]c1ccccc1
Reactant: CN(C)C(C#N)C1CCC2(CC1)OCCO2
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: O
Product: CN(C)C(c1ccccc1)C1CCC2(CC1)OCCO2
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A solution of the aminonitrile 4 (23.56 g, 105 mmol) in absol. THF (100 ml) was added dropwise to a 25 percent strength solution of phenylmagnesium chloride (144 ml, 262.5 mmol) in THF under argon and while cooling with ice, and the mixture was stirred at RT for 20 hours. The reaction mixture was worked up by adding saturated ammonium chloride solution (100 ml) and water (100 ml) while cooling with ice, and extracting the mixture with diethyl ether (3×100 ml). The organic phase was washed with water and saturated sodium chloride solution, dried (Na2SO4) and concentrated.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH:23]([C:24]([NH2:26])=O)[CH2:22][C:21]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[NH:14][C:13]=2[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[CH2:1]([O:8][C:9]([N:11]1[CH:23]([C:24]#[N:26])[CH2:22][C:21]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[NH:14][C:13]=2[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: NC(=O)C1Cc2c([nH]c3ccccc23)CN1C(=O)OCc1ccccc1
Solvent: O=P(Cl)(Cl)Cl
Solvent: c1ccncc1
Product: N#CC1Cc2c([nH]c3ccccc23)CN1C(=O)OCc1ccccc1
Reaction time: 2 h
Yield: 81.3 %

Procedure:
(3RS)-2-Benzyloxycarbonyl-1,2,3,4-tetrahydro-β-carboline-3-carboxamide (1.05 g) is dissolved in pyridine (6 ml) and thereto is added dropwise POCl3 (0.37 ml) at -5° C. The mixture is stirred at the same temperature for 2 hours, and the reaction mixture is poured onto ice-water and extracted with ethyl acetate. The ethyl acetate layer is washed with 10% HCl and water and dried, and then the solvent is distilled off to give the title compound (0.81 g, 82%) as white powder.
Reaction SMILES: [N:1]1[N:5]2[CH2:6][CH2:7][CH2:8][NH:9][C:4]2=[C:3]([CH:10]=[CH:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:2]=1>C(O)C.O1CCCC1.[C].[Pd]>[N:1]1[N:5]2[CH2:6][CH2:7][CH2:8][NH:9][C:4]2=[C:3]([CH2:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:2]=1
Reactant: CCOC(=O)C=Cc1cnn2c1NCCC2
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: CCOC(=O)CCc1cnn2c1NCCC2
Yield: 110.1 %

Procedure:
A solution of ethyl 3-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)acrylate (45 g) in a mixture of ethanol (800 ml) and tetrahydrofuran (400 ml) was treated with 10% palladium carbon (2.2 g) under a hydrogen atmosphere at room temperature for 22 hours. After the catalyst was filtered off, the filtrate was concentrated in vacuo to give ethyl 3-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)propionate (50 g) as an oil.
Reaction SMILES: Cl[C:2]1[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][C:13]([N+:19]([O-:21])=[O:20])=[CH:12][C:3]=1[C:4]([NH:6][CH2:7][CH:8]([OH:11])[CH2:9][OH:10])=[O:5].[NH:22]1[CH2:24][CH2:23]1>CCOC(C)=O>[N:22]1([C:2]2[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][C:13]([N+:19]([O-:21])=[O:20])=[CH:12][C:3]=2[C:4]([NH:6][CH2:7][CH:8]([OH:11])[CH2:9][OH:10])=[O:5])[CH2:24][CH2:23]1
Reactant: C1CN1
Reactant: O=C(NCC(O)CO)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1Cl
Solvent: CCOC(C)=O
Product: O=C(NCC(O)CO)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1N1CC1
Yield: 44.4 %

Procedure:
A stirred solution of 2-chloro-N-(2,3-dihydroxypropyl)-3,5-dinitrobenzamide (Palmer et al., J. Med. Chem. 1996, 39, 2518-2528) (670 mg, 2.10 mmol) in EtOAc (35 mL) was treated with aziridine (325 μL, 6 28 mmol) at room temperature for 3 h, then concentrated under reduced pressure. The residue was dissolved in warm EtOAc (220 mL) and filtered though a short column of silica gel to give 17 (304 mg, 44%). mp (EtOAc/petroleum ether) 154-155° C., 1NMR [(CD3)2SO] δ8.74 (d, J=2.7 Hz, 1H, H-4), 8.57 (t, J=5 6 Hz, 1H, NH), 8.36 (d, J=2.7 Hz, 1 H, H-6), 4 88 (d, J=5.3 Hz, 1H, CHOH), 4.64 (t, J=5.7 Hz, 1H, CH2OH), 3 73-3 63 (m, 1H, CHOH), 3.52-3.42 (m, 1H, NHCHH), 3.42-3.34 (m, 2H, CH2OH), 3.26-3.15 (m, 1H, NHCHH), 2.39 (s, 4H, aziridine-H). Anal. Calcd for C12H14N4O7. C, 44.2;H, 4.3, N, 17.2. Found: C, 44.3;H, 4.2, N, 17.3%.
Reaction SMILES: [Li]CCCC.[CH3:6][O:7][C:8]1[CH:9]=[C:10]([CH3:16])[CH:11]=[C:12]([O:14][CH3:15])[CH:13]=1.[C:17]1([CH2:23][CH2:24][CH2:25][CH2:26]Br)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1COCC1.C1(C)C=CC=CC=1>[CH3:15][O:14][C:12]1[CH:11]=[C:10]([CH3:16])[CH:9]=[C:8]([O:7][CH3:6])[C:13]=1[CH2:26][CH2:25][CH2:24][CH2:23][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: BrCCCCc1ccccc1
Reactant: COc1cc(C)cc(OC)c1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: COc1cc(C)cc(OC)c1CCCCc1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 1347.9 %

Procedure:
A solution of nBuLi in hexanes (1.7 M, 14 mL, 24 mmol) was added over 15 min to a solution of 3,5-dimethoxytoluene (2.93 mL, 20 mmol) in THF (20 mL) at 0° C. The reaction mixture was stirred at 0° C. for 1 h then at room temperature for 3 h. The reaction was cooled to 0° C. and a solution of the 4-phenylbutylbromide (4.13 mL, 1.2 mmol) in toluene (15 mL) was added over 5 min. The reaction mixture was allowed to warm to room temperature and heated to 80° C. for 3-4 h. The reaction was quenched slowly with water and partitioned over Et2O (100 mL) and water (100 mL). The phases were separated and the aqueous phase was extracted with Et2O (3×100 mL). The pooled organics were washed with brine (120 mL), dried over Na2SO4, and concentrated under vacuum and the crude product was purified by flash chromatography (silica-gel, petroleum ether/EtOAc 200:1) to afford the product as a clear oil (4.6 g, 81%). 1H NMR (CDCl3): δ 1.53-1.67 (m, 4H), 2.31 (s, 3H), 2.60-2.64 (m, 4H), 3.76 (s, 6H), 6.34 (s, 2H), 7.13-7.22 (m, 5H).
Reaction SMILES: [CH3:1][CH:2]([C:6](=[O:8])[CH3:7])[C:3](=[O:5])[CH3:4].[C:9]([O:13][CH2:14][CH3:15])(=[O:12])[CH:10]=[CH2:11]>N12CCCN=C1CCCCC2.C(OCC)C>[CH2:14]([O:13][C:9](=[O:12])[CH2:10][CH2:11][C:2]([C:6](=[O:8])[CH3:7])([CH3:1])[C:3](=[O:5])[CH3:4])[CH3:15]
Reactant: C=CC(=O)OCC
Reactant: CC(=O)C(C)C(C)=O
Solvent: C1CCC2=NCCCN2CC1
Solvent: CCOCC
Product: CCOC(=O)CCC(C)(C(C)=O)C(C)=O
Reaction time: 16 h
Yield: 59.3 %

Procedure:
30 g of 3-methyl-2,4-pentandione and 0.4 g of 1,8-diazabicyclo-[5.4.0]-undec-7-ene were mixed and 39.3 g of ethyl acrylate was added dropwise with the temperature being controlled by cooling with ice. Stirring was continued for 16 hours, the base was neutralized, 50 ml of diethyl ether was added, and the mixture was extracted with an aqueous sodium carbonate solution and water. Fractional distillation of the organic layer yielded 33.4 g of 4-acetyl-4-methyl-5-oxo-hexanoic acid ethyl ester (boiling point: 95° C./0.02 mbar; purity: 98%; colorless).
Reaction SMILES: [C:1]([NH:5][S:6]([C:9]1[CH:14]=[C:13]([NH:15][CH:16]=O)[CH:12]=[CH:11][C:10]=1[C:18]([O:20][CH3:21])=[O:19])(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].CO>C(Cl)(Cl)Cl>[C:1]([NH:5][S:6]([C:9]1[CH:14]=[C:13]([NH:15][CH3:16])[CH:12]=[CH:11][C:10]=1[C:18]([O:20][CH3:21])=[O:19])(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(=O)c1ccc(NC=O)cc1S(=O)(=O)NC(C)(C)C
Solvent: ClC(Cl)Cl
Solvent: CO
Product: CNc1ccc(C(=O)OC)c(S(=O)(=O)NC(C)(C)C)c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
9.92 g (0.032 mol) of N-tert-butyl-5-formylamino-2-methoxycarbonylbenzenesulfonamide are dissolved in 50 ml of CHCl3, and then 5 ml (0.053 mol) of boranedimethyl sulfide complex are added at 0° C. After 1 h at 0° C. and 3 h at room temperature the reaction mixture is cooled to 0° C. 30 ml of methanol are added and the mixture is washed with water. The organic phase is dried over magnesium sulfate, the solvent is removed by distillation, and 9.23 g (98% of theory) of N-tert-butyl-2-methoxycarbonyl-5-methylaminobenzenesulfonamide are obtained. m.p.: 120°-124° C.
Reaction SMILES: [C:1]([C:3]1[C:11]2[C:10](=[O:12])[N:9]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:8]=[CH:7][C:6]=2[N:5]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[CH:4]=1)#[CH:2].C(O)C.[H][H]>[Pd].O1CCCC1>[CH2:1]([C:3]1[C:11]2[C:10](=[O:12])[N:9]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:18])([CH3:19])[CH3:20])[N:8]=[CH:7][C:6]=2[N:5]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:27])([CH3:26])[CH3:28])[CH:4]=1)[CH3:2]
Reactant: [H][H]
Reactant: C#Cc1cn(COCC[Si](C)(C)C)c2cnn(COCC[Si](C)(C)C)c(=O)c12
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: CCc1cn(COCC[Si](C)(C)C)c2cnn(COCC[Si](C)(C)C)c(=O)c12
Yield: 92.6 %

Procedure:
To 8.56 g (20.4 mmol) of 3-ethynyl-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Reference example 19-(b) were added 300 ml of ethanol and 200 ml of tetrahydrofuran, then, 2.0 g of 5% palladium-active carbon was added to the mixture, and the mixture was stirred under 1 atm hydrogen atmosphere at room temperature for 15 hours. After completion of the reaction, insoluble material was removed from the reaction suspension by filtration, and the filtrate was concentrated under reduced pressure. The obtained residue was applied to silica gel column chromatography (Eluent; hexane:ethyl acetate=9:1→4:1 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 8.00 g of the title compound as a pale yellowish solid. (Yield: 93%)
Reaction SMILES: [S:1]1[CH:5]=[N:4][N:3]=[C:2]1[CH2:6][NH:7][SH:8](=[O:10])=[O:9].[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([CH:18]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[N:19]2[CH2:22][CH:21](O)[CH2:20]2)=[CH:14][CH:13]=1>>[Cl:30][C:27]1[CH:28]=[CH:29][C:24]([CH:18]([C:15]2[CH:14]=[CH:13][C:12]([Cl:11])=[CH:17][CH:16]=2)[N:19]2[CH2:22][CH:21]([N:7]([CH2:6][C:2]3[S:1][CH:5]=[N:4][N:3]=3)[SH:8](=[O:10])=[O:9])[CH2:20]2)=[CH:25][CH:26]=1
Reactant: O=[SH](=O)NCc1nncs1
Reactant: OC1CN(C(c2ccc(Cl)cc2)c2ccc(Cl)cc2)C1
Product: O=[SH](=O)N(Cc1nncs1)C1CN(C(c2ccc(Cl)cc2)c2ccc(Cl)cc2)C1
Yield: 15.3 %

Procedure:
N-{1-[Bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(1,2,3,4-thiadiazol-2-yl)methylsulfonamide may be prepared by carrying out the procedure as described in Example 13 (method 2), from 0.10 g of N-(1,3,4-thiadiazol-2-yl)methylsulfonamide and 0.215 g of 1-[bis(4-chlorophenyl)methyl]azetidin-3-ol. After chromatography on a silica gel column (particle size 0.06-0.04 mm, height 25 cm, diameter 1 cm), eluting under an argon pressure of 0.8 bar with an ethyl acetate/cyclohexane 20/80 and then 40/60 by volume mixture and collecting 60-cm3 fractions, fractions 26 to 31 are combined and concentrated to dryness under reduced pressure (2.7 kPa). After crystallization from dissopropyl ether, filtration and drying, 40 mg of N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(1,3,4-thiadiazol-2-yl)methylsulfonamide are obtained in the form of a white solid [1H NMR spectrum (300 MHz, CDCl3, δ in ppm): 3.01 (s:3H); 3.09 (split t, J=7 and 1.5 Hz:2H); 3.70 (split t, J=7 and 1.5 Hz:2H); 4.28 (s:1H); 4.76 (mt:1H); from 7.20 to 7.35 (mt:8H); 9.01 (s:1H)].
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([Sn](CCCC)(CCCC)CCCC)=[CH:7][CH:6]=1)(=[O:4])=[O:3].CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.C(N(CC)CC)C.Br[C:54]1[CH:55]=[C:56]2[C:60](=[CH:61][CH:62]=1)[NH:59][CH:58]=[C:57]2[CH2:63][C@H:64]1[CH2:68][CH2:67][CH2:66][N:65]1[CH3:69]>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:69][N:65]1[CH2:66][CH2:67][CH2:68][C@@H:64]1[CH2:63][C:57]1[C:56]2[C:60](=[CH:61][CH:62]=[C:54]([C:8]3[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:10][CH:9]=3)[CH:55]=2)[NH:59][CH:58]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(S(C)(=O)=O)cc1
Reactant: CN1CCC[C@@H]1Cc1c[nH]c2ccc(Br)cc12
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CN1CCC[C@@H]1Cc1c[nH]c2ccc(-c3ccc(S(C)(=O)=O)cc3)cc12

Procedure:
A mixture of 4-methylsulphonylphenyltri-n-butylstannane (see Preparation 15) (680 mg, 1.53 mmol) tri-o-tolyphosphine (120 mg, 0,394 mmol), palladium (II) acetate (15 mg, 0.067 mmol), triethylamine (0.40 ml, 2.87 mmol) and 5-bromo-3-(1-methylpyrrolidin-2(R)-ylmethyl)-1H-indole (400 mg, 1.36 mmol) (see Preparation 36) in anhydrous acetonitrile (5 ml) was heated under reflux, under nitrogen, for 18 hours. The reaction mixture was then evaporated under reduced pressure and dichloromethane (25 ml) was added. The resultant solution was washed with aqueous sodium carbonate, dried (Na2SO4) and evaporated. The residue was purified by column chromatography on silica gel, eluting with ethyl acetate/diethylamine (98:2) to afford, after combination and evaporation of the appropriate fractions, the title compound as a white foam, (189 mg). Found: C,68.17; H,6.81; N,7.53; C21H24N2O2S.1/20 CH2Cl2 requires: C,67.83; H,6.51; N,7.52%.
Reaction SMILES: [NH2:1][C@H:2]([C:7]([NH:9][C@H:10]([C:16]([NH:18][C@H:19]([C:22]([NH:24][C@H:25]([C:33](OC)=[O:34])[CH2:26][CH2:27][CH2:28][NH:29][C:30](=[NH:32])[NH2:31])=[O:23])[CH2:20][OH:21])=[O:17])[CH2:11][CH2:12][CH2:13][CH2:14][NH2:15])=[O:8])[CH2:3][C:4](=[O:6])[OH:5].[NH3:37]>CO>[NH2:1][C@H:2]([C:7]([NH:9][C@H:10]([C:16]([NH:18][C@H:19]([C:22]([NH:24][C@H:25]([C:33]([NH2:37])=[O:34])[CH2:26][CH2:27][CH2:28][NH:29][C:30](=[NH:32])[NH2:31])=[O:23])[CH2:20][OH:21])=[O:17])[CH2:11][CH2:12][CH2:13][CH2:14][NH2:15])=[O:8])[CH2:3][C:4](=[O:6])[OH:5]
Reactant: COC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC(=O)O
Reactant: N
Solvent: CO
Product: N=C(N)NCCC[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC(=O)O)C(N)=O

Procedure:
Asp-Lys-Ser-Arg-OMe is treated with a saturated solution of ammonia in methanol at room temperature for 2 days. The solvent is removed in vacuo to afford Asp-Lys-Ser-Arg-NH2.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:23]([CH:24]3O[CH:27]=[N:26][CH:25]3S(C3C=CC(C)=CC=3)(=O)=O)=[CH:22][C:12]3[N:13](CCS(C)(=O)=O)[CH:14]=[N:15][C:11]=3[C:10]=2[F:39])=[C:4]([Cl:40])[CH:3]=1.[NH3:41]>CO>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:23]([C:24]3[NH:41][CH:27]=[N:26][CH:25]=3)=[CH:22][C:12]3[NH:13][CH:14]=[N:15][C:11]=3[C:10]=2[F:39])=[C:4]([Cl:40])[CH:3]=1
Reactant: N
Reactant: Cc1ccc(S(=O)(=O)C2N=COC2c2cc3c(ncn3CCS(C)(=O)=O)c(F)c2Nc2ccc(Br)cc2Cl)cc1
Solvent: CO
Product: Fc1c(Nc2ccc(Br)cc2Cl)c(-c2cnc[nH]2)cc2[nH]cnc12
Temperature: 90 °C
Reaction time: 20 h
Yield: 7 %

Procedure:
(4-Bromo-2-chloro-phenyl)-{4-fluoro-1-(2-methanesulfonyl-ethyl)-6-[4-(toluene-4-sulfonyl)-4,5-dihydro-oxazol-5-yl]-1H-benzoimidazol-5-yl}-amine 10bb (0.072 g, 0.107 mmol) is treated with 2.4 mL of a 2.0 M NH3 in MeOH solution in a sealed pressure tube. The reaction mixture is then heated to 90° C. with stirring for 20 hours and furthered stirred at room temperature for 3 days. The reaction mixture is transferred to a round bottom flask and concentrated under reduced pressure. Purification by flash column chromatography, twice, eluted with 10:1 methylene chloride:MeOH, followed by successive triturations with methylene chloride and then diethyl ether provides 3 mg (7%) desired product: LC/MS ESI (+) m/z 408, 406 (M+ Br pattern) detected; 1H NMR (400 MHz, MeOH-d4) δ 8.23 (s, 1H), 7.87 (s, 1H), 7.74 (s, 1H), 7.46 (m, 1H), 7.32 (d, 1H), 7.05 (m, 1H), 6.20 (dd, 1H).
Reaction SMILES: S([O-])([O-])(=O)=O.[Al+3].S([O-])([O-])(=O)=O.S([O-])([O-])(=O)=O.[Al+3].[OH2:18].[F:19][C:20]1[C:25]([B:26](C2C(F)=C(F)C(F)=C(F)C=2F)[C:27]2[C:32]([F:33])=[C:31]([F:34])[C:30]([F:35])=[C:29]([F:36])[C:28]=2[F:37])=[C:24]([F:49])[C:23]([F:50])=[C:22]([F:51])[C:21]=1[F:52]>C1(C)C=CC=CC=1>[F:19][C:20]1[C:25]([B:26]([C:27]2[C:32]([F:33])=[C:31]([F:34])[C:30]([F:35])=[C:29]([F:36])[C:28]=2[F:37])[OH:18])=[C:24]([F:49])[C:23]([F:50])=[C:22]([F:51])[C:21]=1[F:52]
Reactant: O
Reactant: Fc1c(F)c(F)c(B(c2c(F)c(F)c(F)c(F)c2F)c2c(F)c(F)c(F)c(F)c2F)c(F)c1F
Agent: O=S(=O)([O-])[O-]
Agent: [Al+3]
Solvent: Cc1ccccc1
Product: OB(c1c(F)c(F)c(F)c(F)c1F)c1c(F)c(F)c(F)c(F)c1F

Procedure:
Moreover, that patent also discloses a method in which aluminum sulfate 18 hydrate is used instead of water. Specifically, aluminum sulfate 18 hydrate containing water of 1.77 molar equivalent vs. tris(pentafluorophenyl)borane is added to a toluene solution of tris(pentafluorophenyl)borane. After the solution is refluxed, insoluble aluminum sulfate is separated from the reaction mixture. A solvent of the filtrate is removed in vacuo. Toluene is added to the thus obtained residues. After stirring, the insoluble material is filtered through a G4 sintered-glass so as to be separated. The solvent of the filtrate is again removed in vacuo. Heptane is added to the residues. The solution is stirred and filtered so that a cake is obtained. Finally, the thus obtained cake is washed with heptane, and dried in vacuo so as to isolate bis(pentafluorophenyl)borinic acid. However, this method has such a problem that it is necessary to remove the byproduct aluminum sulfate and its process is so complicated.
Reaction SMILES: [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:12]([O:15][CH2:16][CH2:17][CH2:18][CH2:19]Br)(=[O:14])[CH3:13].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:10]([O:9][C:1](=[O:8])[CH:2]([CH2:19][CH2:18][CH2:17][CH2:16][O:15][C:12](=[O:14])[CH3:13])[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH3:11]
Reactant: CCOC(=O)CC(=O)OCC
Reactant: CC(=O)OCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)C(CCCCOC(C)=O)C(=O)OCC
Temperature: 25 °C
Reaction time: 0.03 h

Procedure:
Compound 3 was prepared by following a previously reported method.{Santra, 2004 #6} Briefly, diethyl malonate 1 (10 g, 62.5 mmol), 4-bromobutyl acetate 2 (15.84 g, 81.3 mmol) were placed in a round bottom flask containing acetonitrile (120 mL) and stirred for 2 min at room temperature. Then to this, we added potassium carbonate (34.5 g, 250.1 mmol) and refluxed for 36 h. Next, the mixture was filtered and the filtrate was concentrated to obtain a yellow liquid. This was extracted with ethyl acetate, and washed with water. The organic layers were combined and dried over Na2SO4, and purified by column chromatography using 4% ethyl acetate in petroleum ether as the eluent.