Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [K+].[N+:2]([C:5]1[CH:6]=[C:7]([S:15]([O-:18])(=O)=[O:16])[CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[C:10]=1[Cl:11])([O-:4])=[O:3].P(Cl)(Cl)([Cl:21])=O>C(#N)C.C1S(=O)(=O)CCC1>[N+:2]([C:5]1[CH:6]=[C:7]([S:15]([Cl:21])(=[O:18])=[O:16])[CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[C:10]=1[Cl:11])([O-:4])=[O:3]
Reactant: O=[N+]([O-])c1cc(S(=O)(=O)[O-])cc([N+](=O)[O-])c1Cl
Reactant: O=P(Cl)(Cl)Cl
Agent: [K+]
Solvent: O=S1(=O)CCCC1
Solvent: CC#N
Product: O=[N+]([O-])c1cc(S(=O)(=O)Cl)cc([N+](=O)[O-])c1Cl

Procedure:
760 g (2 moles) 3,5-dinitro-4-chlorobenzenesulfonic acid potassium salt (approx. 85%) and 614 g (4 moles) phosphorus oxychloride were reacted as in Example 1(a) in 800 ml acetonitrile and 800 ml tetramethylenesulfone.
Reaction SMILES: Cl.[CH3:2][C:3]1[S:4][C:5]2[CH2:11][CH2:10][NH:9][CH2:8][CH2:7][C:6]=2[N:12]=1.[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[N:21]=[C:22]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:23]([CH2:25][C:26](O)=[O:27])[CH:24]=2)=[CH:16][C:15]=1[CH3:35].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[N:21]=[C:22]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:23]([CH2:25][C:26]([N:9]3[CH2:10][CH2:11][C:5]4[S:4][C:3]([CH3:2])=[N:12][C:6]=4[CH2:7][CH2:8]3)=[O:27])[CH:24]=2)=[CH:16][C:15]=1[CH3:35]
Reactant: Cc1cc(-c2cn(CC(=O)O)c(-c3ccccc3)n2)ccc1F
Reactant: Cc1nc2c(s1)CCNCC2
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Product: Cc1nc2c(s1)CCN(C(=O)Cn1cc(-c3ccc(F)c(C)c3)nc1-c1ccccc1)CC2
Temperature: 25 °C
Yield: 22.5 %

Procedure:
45 mg 2-methyl-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine hydrochloride was added to 60 mg (4-(4-fluoro-3-methyl-phenyl)-2-phenyl-imidazol-1-yl)-acetic acid, 70 mg TBTU, 0.06 mL TEA in 1 mL DMF. The reaction was stirred over night at RT. The mixture was purified by HPLC (ZORBAX StableBond C18; 5 μm; 30×100 mm; gradient: water (+0.3% formic acid)/acetonitril=90/10-10/90 in 9 min; flow: 50 ml/min.) to give 20 mg desired product. Rt: 0.94 (method A), (M+H)+: 461
Reaction SMILES: [CH3:1][C@@H:2]([CH2:16][CH3:17])[CH2:3][NH:4][C:5]1[N:15]=[CH:14][CH:13]=[CH:12][C:6]=1[C:7]([O:9][CH2:10]C)=[O:8].C(C(CC)CNC1N=CC=CC=1C(OCC)=[O:26])C>>[CH3:1][C@@H:2]([CH2:16][CH3:17])[CH2:3][N:4]1[C:5]2[N:15]=[CH:14][CH:13]=[CH:12][C:6]=2[C:7](=[O:8])[O:9][C:10]1=[O:26]
Reactant: CCOC(=O)c1cccnc1NC[C@@H](C)CC
Reactant: CCOC(=O)c1cccnc1NCC(CC)CC
Product: CC[C@H](C)Cn1c(=O)oc(=O)c2cccnc21

Procedure:
The title compound was prepared according to the procedure of Example 3B substituting the product of Example 20A for the product of Example 3A (0.400 g, 68%). MS (DCI) m/z 252 (M+NH4)+.
Reaction SMILES: S([O-])(O[O-])(=O)=[O:2].[K+].[K+].[CH:9]([O:12][C:13]1[N:18]=[CH:17][C:16](B2OC(C)(C)C(C)(C)O2)=[CH:15][N:14]=1)([CH3:11])[CH3:10]>CC(C)=O.C(OCC)C>[CH:9]([O:12][C:13]1[N:18]=[CH:17][C:16]([OH:2])=[CH:15][N:14]=1)([CH3:11])[CH3:10]
Reactant: O=S(=O)([O-])O[O-]
Reactant: CC(C)Oc1ncc(B2OC(C)(C)C(C)(C)O2)cn1
Agent: [K+]
Solvent: CCOCC
Solvent: CC(C)=O
Product: CC(C)Oc1ncc(O)cn1
Temperature: 25 °C
Reaction time: 2 h
Yield: 34.3 %

Procedure:
An aqueous solution (5 mL) of potassium peroxymonosulfate (1.40 g, 2.27 mmol) was added dropwise to a solution of 2-isopropoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (Preparation 100, 500 mg, 1.89 mmol) in acetone (5 ml) under a nitrogen atmosphere at 0° C. The mixture was stirred at room temperature for 2 hours, then filtered, the filtrate diluted with water (30 mL) and extracted with EtOAc (1×20 mL). The organic layer was washed with brine (2×20 mL), dried over sodium sulfate, filtered and evaporated in vacuo. The resulting oil was dissolved in dichloromethane and purified by silica gel chromatography eluting with 0 to 5% MeOH (with 10% aqueous ammonia) in dichloromethane to yield a solid. The solid was suspended in diethyl ether and evaporated to yield the title compound as a white solid (100 mg, 34%):
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([CH:8]=O)[CH:5]=[C:4]([Cl:10])[N:3]=1.[C:11]([CH:16]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:13][CH2:14][CH3:15])=[O:12]>ClCCl>[CH2:14]([O:13][C:11](=[O:12])[CH:16]=[CH:8][C:6]1[CH:7]=[C:2]([Cl:1])[N:3]=[C:4]([Cl:10])[CH:5]=1)[CH3:15]
Reactant: CCOC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=Cc1cc(Cl)nc(Cl)c1
Solvent: ClCCl
Product: CCOC(=O)C=Cc1cc(Cl)nc(Cl)c1
Yield: 71.5 %

Procedure:
The above aldehyde (1.2 g) was dissolved in dichloromethane (40 ml) and carboethoxymethylenetriphenylphosphorane (2.4 g) was added. After 18 hours at 25° the solution was concentrated in vacuo and the residue washed with hexane. Combined hexane washings were concentrated in vacuo to give ethyl-3-(2,6-dichloro-4-pyridyl)propenoate (1.2 g). NMR 1H : 7.50(2H,d), 2.28(2H,s), 6.52(2H,d), 4 29(2H,q), 1.32(3H,t).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=1>C(C(C)=O)C>[CH3:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][O:1][C:2]2[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=2)=[CH:20][CH:19]=1
Reactant: O=Cc1ccc(O)cc1
Reactant: Cc1ccc(CCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: Cc1ccc(COc2ccc(C=O)cc2)cc1
Yield: 52.8 %

Procedure:
18.3 g of p-hydroxybenzaldehyde is dissolved in 200 ml of methyl ethyl ketone, and then 22.8 g of potassium carbonate and 23.2 g of α-chloro-p-xylene are added thereto. The resulting mixture is refluxed for 10 hours in a stream of nitrogen. Insoluble substances produced are removed by filtration, and then the solvent is distilled away. The resulting residue is distilled under reduced pressure to obtain 17.9 g of 4-(4-methylbenzyloxy)benzaldehyde in the form of white crystal.
Reaction SMILES: C(N(CC)CC)C.[C:8]([NH:11][C:12]1[C:13]([I:27])=[C:14]([C:18]([I:26])=[C:19]([NH:22][C:23](=[O:25])[CH3:24])[C:20]=1[I:21])[C:15](Cl)=[O:16])(=[O:10])[CH3:9].Cl.[CH2:29]([O:31][C:32](=[O:36])[CH2:33][NH:34][CH3:35])[CH3:30]>CN(C)C=O>[CH2:29]([O:31][C:32](=[O:36])[CH2:33][N:34]([C:15](=[O:16])[C:14]1[C:13]([I:27])=[C:12]([NH:11][C:8](=[O:10])[CH3:9])[C:20]([I:21])=[C:19]([NH:22][C:23](=[O:25])[CH3:24])[C:18]=1[I:26])[CH3:35])[CH3:30]
Reactant: CCOC(=O)CNC
Reactant: CC(=O)Nc1c(I)c(NC(C)=O)c(I)c(C(=O)Cl)c1I
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCOC(=O)CN(C)C(=O)c1c(I)c(NC(C)=O)c(I)c(NC(C)=O)c1I
Temperature: 25 °C
Reaction time: 1 h

Procedure:
840 ml (6.1 Mol) triethylamine is added to a solution of 759 g (1.2 Mol) 3,5-diacetamido-2,4,6-triiodobenzoyl chloride and 276 g (1.8 Mol) sarcosine ethyl ester hydrochloride in 7600 ml N,N-dimethylformamide and stirred for 1 hr. at 60° C. The reaction mixture is cooled to room temperature, the crystallized triethyl ammonium chloride is filtered, washed with N,N-dimethylformamide and reduced under vacuum in a rotary evaporator. The residue is dissolved in 650 ml methanol and added dropwise to 3 l ethyl acetate. The precipitate is crystallized overnight, filtered to a dry state and finally washed with water, 1N hydrochloric acid, cold saturated sodium bicarbonate, water and dried under vacuum at 60° C. Yield: 685 g (80%).
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:11]1([CH3:18])[CH:16]=[CH:15][CH:14]=[C:13]([NH2:17])[CH:12]=1.CCN(CC)CC>CN(C=O)C>[N+:8]([C:7]1[C:2]([NH:17][C:13]2[CH:12]=[C:11]([CH3:18])[CH:16]=[CH:15][CH:14]=2)=[N:3][CH:4]=[CH:5][CH:6]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1cccnc1Cl
Reactant: Cc1cccc(N)c1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1cccc(Nc2ncccc2[N+](=O)[O-])c1
Temperature: 90 °C
Reaction time: 16 h
Yield: 70 %

Procedure:
A mixture of 2-chloro-3-nitropyridine (2.28 g, 14.4 mmol), m-tolylamine (2.78 g, 25.9 mmol) and Et3N (3.6 mL, 25.9 mmol) in DMF (10 mL) was stirred at 90° C. for 16 h under a nitrogen atmosphere. The reaction mixture was partitioned between DCM and water. The aqueous phase was extracted with DCM (×3) and the combined organic layers were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 30-100% DCM in cyclohexane) to afford the title compound as an orange solid (2.31 g, 70%). LCMS (Method C): RT 3.81 min [M+H]+ 230.1.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](O)(=[O:10])=[O:9])=[C:4]([N+:12]([O-:14])=[O:13])[CH:3]=1.O=S(Cl)[Cl:17]>CN(C=O)C>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([Cl:17])(=[O:10])=[O:9])=[C:4]([N+:12]([O-:14])=[O:13])[CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: Cc1ccc(S(=O)(=O)O)c([N+](=O)[O-])c1
Solvent: CN(C)C=O
Product: Cc1ccc(S(=O)(=O)Cl)c([N+](=O)[O-])c1

Procedure:
In a similar fashion using route 39 general procedure 96, 4-methyl-2-nitro-benzenesulfonic acid 448 (6.2 g, Salt form), SOCl2 (15 ml) and DMF (0.28 ml) gave the title compound (3.10 g) which was used in the next step without further purification. The structure was confirmed by 1H NMR.
Reaction SMILES: [CH2:1]([CH:4]([CH2:15][CH:16]=[CH2:17])[CH2:5][O:6][SiH2:7][C:8]1[CH:13]=[CH:12][C:11](I)=[CH:10][CH:9]=1)[CH:2]=[CH2:3].C(=O)([O-])[O-].[K+].[K+].[C:24]1(B(O)O)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C1(C)C=CC=CC=1>CCOCC>[CH2:1]([CH:4]([CH2:15][CH:16]=[CH2:17])[CH2:5][O:6][SiH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:10][CH:9]=1)[CH:2]=[CH2:3]
Reactant: OB(O)c1ccccc1
Reactant: C=CCC(CC=C)CO[SiH2]c1ccc(I)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: C=CCC(CC=C)CO[SiH2]c1ccc(-c2ccccc2)cc1
Yield: 78 %

Procedure:
At first, a mixture of the 4-(diallylethoxysilyl)iodobenzene (148 mg, 0.41 mmol) obtained in Example 2, tetrakistriphenylphosphine palladium (Pd(PPh3)4: 14.3 mg, 0.012 mmol), potassium carbonate (K2CO3: 85.1 mg, 0.62 mmol), and phenyl boronic acid (60 mg, 0.49 mmol) was added with distilled toluene (dist.toluene: 5 mL). Subsequently, the resultant mixture was stirred under a nitrogen atmosphere at 80° C. for 13 hours to obtain a reaction mixture. Thereafter, the reaction mixture was diluted with ether, and a salt thus formed was removed by filtering with celite. The solvent was distilled from the organic layer with an evaporator to obtain a crude product. After that, the crude product thus obtained was separated and purified by silica gel column chromatography (hexane/EtOAc=10/1), and thereby 4-(diallylethoxysilyl)biphenyl (a second organosilane compound of the present invention) was obtained (99.6 mg, 78% yield).
Reaction SMILES: [Si]([O:8][CH2:9][C:10]1[CH:11]=[C:12]([CH2:25][CH2:26][C:27]2[CH:28]=[C:29](/[C:33](/[CH3:43])=[CH:34]/[CH:35]=[CH:36]/[C:37]([CH2:41][CH3:42])([OH:40])[CH2:38][CH3:39])[CH:30]=[CH:31][CH:32]=2)[CH:13]=[CH:14][C:15]=1[CH2:16][O:17][Si](C(C)(C)C)(C)C)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.CO>C1COCC1>[OH:8][CH2:9][C:10]1[CH:11]=[C:12]([CH2:25][CH2:26][C:27]2[CH:28]=[C:29](/[C:33](/[CH3:43])=[CH:34]/[CH:35]=[CH:36]/[C:37]([CH2:38][CH3:39])([OH:40])[CH2:41][CH3:42])[CH:30]=[CH:31][CH:32]=2)[CH:13]=[CH:14][C:15]=1[CH2:16][OH:17]
Reactant: CCC(O)(/C=C/C=C(\C)c1cccc(CCc2ccc(CO[Si](C)(C)C(C)(C)C)c(CO[Si](C)(C)C(C)(C)C)c2)c1)CC
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CO
Solvent: C1CCOC1
Product: CCC(O)(/C=C/C=C(\C)c1cccc(CCc2ccc(CO)c(CO)c2)c1)CC
Reaction time: 0.5 h

Procedure:
340 mg of (4E,6E)-7-(3-{2-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenyl]ethyl}phenyl)-3-ethylocta-4,6-dien-3-ol (0.5 mmol) are dissolved in 10 ml of THF and 1.5 ml (1.5 mmol) of a tetrabutylammonium fluoride solution (1M in THF) are added dropwise. After 30 minutes, 10 ml of methanol are added and the mixture is concentrated under reduced pressure. After purification of the residue by chromatography on a silica column, a colourless oil is obtained (m=163 mg; Y=88%).
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[C:10]([Cl:11])=[CH:9][C:8]([C:12]([F:15])([F:14])[F:13])=[CH:7][N:6]=1)=[O:4].[C:16]1(=[O:26])[NH:20][C:19](=[O:21])[C:18]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:17]12.[K].O>CN(C)C=O.[I-].[K+]>[Cl:11][C:10]1[C:5]([C:3](=[O:4])[CH2:2][N:20]2[C:19](=[O:21])[C:18]3=[CH:22][CH:23]=[CH:24][CH:25]=[C:17]3[C:16]2=[O:26])=[N:6][CH:7]=[C:8]([C:12]([F:15])([F:14])[F:13])[CH:9]=1
Reactant: O=C(CBr)c1ncc(C(F)(F)F)cc1Cl
Reactant: O=C1NC(=O)c2ccccc21
Agent: [I-]
Agent: [K+]
Agent: [K]
Solvent: O
Solvent: CN(C)C=O
Product: O=C(CN1C(=O)c2ccccc2C1=O)c1ncc(C(F)(F)F)cc1Cl
Temperature: 85 °C
Reaction time: 1 h
Yield: 34.9 %

Procedure:
To 1.43 g of 2-bromo-1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethanone in 10 ml of N,N-dimethylformamide, 0.68 g of potassium phthalimide and 0.01 g of potassium iodide were added, and the mixture was stirred at 85° C. for 1 hour. After completion of the reaction, the reaction mixture was allowed to cool to room temperature, mixed with 10 ml of water and extracted with ethyl acetate (10 ml×3), the resulting organic layers were combined, washed with water and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by preparative medium pressure liquid chromatography (preparative medium pressure chromatograph: YFLC-Wprep manufactured by Yamazen Science, Inc.) using ethyl acetate-hexane (with a gradient of from 5:95 to 46:60) as the eluent to obtain 0.47 g of the desired product as a pale yellow resinous substance.
Reaction SMILES: [O:1]=[CH:2][C:3]1[CH:11]=[CH:10][C:7]([O:8][CH3:9])=[C:5]([OH:6])[CH:4]=1.[CH2:12](I)[CH2:13][CH3:14].C([O-])([O-])=O.[K+].[K+].C(OC1C=C(C=CC=1C)C=O)C>CN(C=O)C>[CH3:9][O:8][C:7]1[CH:10]=[CH:11][C:3]([CH:2]=[O:1])=[CH:4][C:5]=1[O:6][CH2:12][CH2:13][CH3:14]
Reactant: COc1ccc(C=O)cc1O
Reactant: CCCI
Agent: CCOc1cc(C=O)ccc1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCOc1cc(C=O)ccc1OC

Procedure:
The title compound was prepared by reaction of isovanillin with propyl iodide in DMF using K2CO3 as base in analogy to the preparation of 3-ethoxy-4-methyl-benzaldehyde (intermediate B19, vide infra).
Reaction SMILES: [C:1]1([CH3:10])[CH:6]=[CH:5][CH:4]=[C:3]([C:7]([NH2:9])=[O:8])[CH:2]=1.Cl[C:12]([S:14]Cl)=[O:13]>C1(C)C=CC=CC=1.CC1CCCCC1>[C:1]1([CH3:10])[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[O:8][C:12](=[O:13])[S:14][N:9]=2)[CH:2]=1
Reactant: Cc1cccc(C(N)=O)c1
Reactant: O=C(Cl)SCl
Solvent: CC1CCCCC1
Solvent: Cc1ccccc1
Product: Cc1cccc(-c2nsc(=O)o2)c1
Reaction time: 5.5 h
Yield: 45.8 %

Procedure:
m-Toluamide (116 g, 0.86 mol) and chlorocarbonylsulfenyl chloride (144 g, 1.1 mol, 28% excess) was heated to 100° C. in 400 ml of toluene, with stirring, for 5.5 hours. Cooling resulted in an orange solid. The solid, isolated by filtration, was dissolved in hot methylcyclohexane and decolorized. The light yellow product was recrystallized once from methylcyclohexane to give 76.05 g (45.8%) of white solid, m.p. 82.5°-84°.
Reaction SMILES: [CH3:1][N:2]([CH3:6])[C:3](Cl)=[O:4].C(N(CC)CC)C.[NH2:14][CH2:15][CH2:16][CH2:17][Si:18]([O:23][CH3:24])([O:21][CH3:22])[O:19][CH3:20]>O1CCOCC1>[CH3:1][N:2]([CH3:6])[C:3]([NH:14][CH2:15][CH2:16][CH2:17][Si:18]([O:23][CH3:24])([O:19][CH3:20])[O:21][CH3:22])=[O:4]
Reactant: CO[Si](CCCN)(OC)OC
Reactant: CN(C)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: CO[Si](CCCNC(=O)N(C)C)(OC)OC
Temperature: 50 °C
Yield: 82.5 %

Procedure:
5.0 g (46.5 mmol) N,N-dimethylcarbamoyl chloride (Sigma-Aldrich, Switzerland) and 40 mL dried dioxane (Sigma-Aldrich, Switzerland) were added to a 250-mL round-bottom two-neck flask equipped with a reflux cooler. 4.71 g (46.5 mmol) triethylamine (Sigma-Aldrich, Switzerland) and 8.34 g (46.5 mmol) 3-aminopropyltrimethoxysilane (Silquest A-1110, Momentive Performance Materials Inc., USA) were added dropwise under nitrogen, with stirring. After the exothermic reaction subsided, the resulting whitish suspension was stirred at 90° C. for 3 hours. A gradual color change to orange was observed. After cooling to 50° C., the solid was separated by double filtration, and the solvent was removed at 60° C. for 1 hour on a rotary evaporator. 9.6 g of the desired silane was obtained as a brown liquid. The silane was designated as DMA1100 and used without further purification.
Reaction SMILES: [CH2:1]([NH:8][C:9]([C:11]1[C:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH2:23][NH2:24])=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:25][C:26]1[CH:27]=[C:28]([S:32](Cl)(=[O:34])=[O:33])[CH:29]=[CH:30][CH:31]=1.C(NC(C1C(C2C=CC=CC=2C(S(C2C=CC=C(F)C=2)(=O)=O)N)=CC=CC=1)=O)C1C=CC=CC=1>>[CH2:1]([NH:8][C:9]([C:11]1[C:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH2:23][NH:24][S:32]([C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([F:25])[CH:27]=2)(=[O:34])=[O:33])=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=S(=O)(Cl)c1cccc(F)c1
Reactant: NCc1ccccc1-c1ccccc1C(=O)NCc1ccccc1
Agent: NC(c1ccccc1-c1ccccc1C(=O)NCc1ccccc1)S(=O)(=O)c1cccc(F)c1
Product: O=C(NCc1ccccc1)c1ccccc1-c1ccccc1CNS(=O)(=O)c1cccc(F)c1

Procedure:
From 0.28 mmol of 2′-aminomethylbiphenyl-2-carboxylic acid benzylamide (precursor 5b) and 3-fluorophenylsulfonyl chloride, according to the general working procedure 112 mg of 2′-(3-fluorophenylsulfonyl-aminomethyl)biphenyl-2-carboxylic acid benzylamide were obtained;
Reaction SMILES: Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=1)=[O:3].Cl.[CH3:15][O:16][C:17](=[O:23])[C@H:18]([CH:20]([CH3:22])[CH3:21])[NH2:19].CN1CCOCC1>C(Cl)Cl>[CH3:15][O:16][C:17](=[O:23])[C@H:18]([CH:20]([CH3:22])[CH3:21])[NH:19][C:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=1)=[O:3]
Reactant: COC(=O)[C@@H](N)C(C)C
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Agent: Cl
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: COC(=O)[C@@H](NC(=O)Oc1ccc([N+](=O)[O-])cc1)C(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 66.1 g (0.328 mol) of 4-nitrophenyl chloroformate in 1.2 liters of CH2Cl2 was cooled to 0° C. and treated with L-valine methyl ester hydrochloride. The resulting mixture was treated slowly, with stirring, with 68.9 ml (0.626 mol) of 4-methylmorpholine. The resulting solution was allowed to slowly warm to ambient temperature and was stirred overnight. After washing with 3 portions of 10% aqueous NaHCO3, the solution was dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography by eluting with chloroform to provide the desired compound. 1H NMR (DMSO-d6) δ0.94 (d, J=7 Hz, 3H), 0.95 (d, J=7 Hz, 3H), 2.12 (octet, J=7 Hz, 1H), 3.69 (s, 3H), 4.01 (dd, J=8, 6 Hz, 1H), 7.41 (dt, J=9, 3 Hz, 2H), 8.27 (dt, J=9, 3 Hz, 2H), 8.53 (d, J=8 Hz, 1H). Mass spectrum: (M+NH4)+ =314.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([CH2:14][CH2:15][CH2:16][C:17](O)=[S:18])=[N:12][N:11]=[N:10]2)=[CH:5][CH:4]=1)[CH3:2].[CH2:20]1[CH2:30][CH2:29][N:28]2[C:23](=NC[CH2:26][CH2:27]2)[CH2:22][CH2:21]1.ClC(OCC(C)C)=O.C(NC1CCCCC1)C>O1CCCC1>[CH2:27]([N:28]([CH:23]1[CH2:22][CH2:21][CH2:20][CH2:30][CH2:29]1)[C:17](=[S:18])[CH2:16][CH2:15][CH2:14][C:13]1[N:9]([C:6]2[CH:7]=[CH:8][C:3]([CH2:1][CH3:2])=[CH:4][CH:5]=2)[N:10]=[N:11][N:12]=1)[CH3:26]
Reactant: CCc1ccc(-n2nnnc2CCCC(O)=S)cc1
Reactant: C1CCC2=NCCCN2CC1
Agent: CC(C)COC(=O)Cl
Agent: CCNC1CCCCC1
Solvent: C1CCOC1
Product: CCc1ccc(-n2nnnc2CCCC(=S)N(CC)C2CCCCC2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 43 %

Procedure:
4-[1-(4-Ethylphenyl)-1,2,3,4-tetrazol-5-yl]thio-butyric acid (45 mmole) is dissolved in tetrahydrofuran (50 ml), and thereto is added DBU (50 mmole). To the mixture is added dropwise with stirring isobutyl chloroformate (50 mmol) under ice-cooling, and the mixture is stirred at room temperature for 30 minutes. To the mixture is added dropwise N-ethyl-cyclohexylamine (54 mmole), and the mixture is further stirred at room temperature for 2 hours. The solvent is distilled off under reduced pressure and the resulting residue is extracted with chloroform. The chloroform layer is washed with 5% aqueous hydrochloric acid, an aqueous saturated sodium hydrogen carbonate solution and an aqueous saturated sodium chloride solution and then dried over anhydrous sodium sulfate. Chloroform is distilled off and the resulting residue is subjected to column chromatography (Wakogel C-200, eluting solvent, benzene:chloroform=4:1, V/V) to isolate N-ethyl-N-cyclohexyl-4-[1-(4-ethylphenyl)-1,2,3,4-tetrazol-5-yl]thio-butyramide (yield: 43%), colorless liquid, nD19 =1.5533.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:11]([OH:13])=O)=[CH:4][NH:5][C:6]=1[C:7]([O:9][CH3:10])=[O:8].[CH3:14][N:15](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CN>CN(C=O)C>[Cl:1][C:2]1[C:3]([C:11]([NH:15][CH3:14])=[O:13])=[CH:4][NH:5][C:6]=1[C:7]([O:9][CH3:10])=[O:8]
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: COC(=O)c1[nH]cc(C(=O)O)c1Cl
Agent: CN
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CNC(=O)c1c[nH]c(C(=O)OC)c1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 57.7 %

Procedure:
To a solution of 4-chloro-5-[(methyloxy)carbonyl]-1H-pyrrole-3-carboxylic acid (0.075 g, 0.368 mmol) in DMF (1 ml) was added HATU (0.168 g, 0.442 mmol), DIPEA (0.097 ml, 0.553 mmol) and methyl amine (2M in THF) (0.276 ml, 0.553 mmol). The reaction mixture was stirred at RT overnight. Purification was accomplished by HPLC, the desired fractions collected and lypholized to afford methyl 3-chloro-4-[(methylamino)carbonyl]-1H-pyrrole-2-carboxylate (0.046 g, 57.6% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 12.39 (br. s., 1H) 7.73-7.83 (m, 1H) 7.46 (d, 1H) 3.80 (s, 3H) 2.70 (d, 3H). MS: m/z 217.0 (M+1).
Reaction SMILES: [CH2:1]([N:4]=[C:5]=[O:6])[CH2:2][CH3:3].[CH2:7]([O:10][C:11]([NH:13][CH:14]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([NH:27][S:28]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([NH2:37])[CH:32]=2)(=[O:30])=[O:29])[CH:22]=1)[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[O:12])[CH:8]=[CH2:9]>O1CCOCC1>[CH2:7]([O:10][C:11]([NH:13][CH:14]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([NH:27][S:28]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([NH:37][C:5]([NH:4][CH2:1][CH2:2][CH3:3])=[O:6])[CH:32]=2)(=[O:30])=[O:29])[CH:22]=1)[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[O:12])[CH:8]=[CH2:9]
Reactant: C=CCOC(=O)NC(CC(=O)OCC)c1cccc(NS(=O)(=O)c2cccc(N)c2)c1
Reactant: CCCN=C=O
Solvent: C1COCCO1
Product: C=CCOC(=O)NC(CC(=O)OCC)c1cccc(NS(=O)(=O)c2cccc(NC(=O)NCCC)c2)c1
Temperature: 50 °C
Reaction time: 18 h
Yield: 32.1 %

Procedure:
9.6 g of propyl isocyanate were added to a solution of 50 g of enantiopure ethyl 3-{[(allyloxy)-carbonyl]-amino}-3-{{3-{[(3-aminophenyl)-sulfonyl]-amino}-phenyl}}-propanoate from fraction 1 from Example II.2.f in 500 ml of dioxane, and the mixture was stirred for 18 h at 50° C. After evaporation of the solvent, 1.5 L of 1 M hydrochloric acid were added, and the solution was extracted with dichloromethane. The organic phase was dried over magnesium sulphate and concentrated. Chromatography on silica gel (dichloromethane/methanol=30:1) yielded 19.1 g of the compound.