Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[C:5]([CH:39]=[CH:40][CH:41]=1)[C:6]([NH:8][C:9]1[CH:32]=[CH:31][C:30]([N:33]2[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]2)=[CH:29][C:10]=1[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)[N:15]=1)=[O:12])=[O:7].C(=O)([O-])[O-].[K+].[K+].[SH:48][C:49]1[CH:50]=[C:51]([CH2:55][C:56]([OH:58])=[O:57])[CH:52]=[CH:53][CH:54]=1>CN(C=O)C>[N:33]1([C:30]2[CH:31]=[CH:32][C:9]([NH:8][C:6]([C:5]3[CH:4]=[C:3]([CH:41]=[CH:40][CH:39]=3)[CH2:2][S:48][C:49]3[CH:50]=[C:51]([CH2:55][C:56]([OH:58])=[O:57])[CH:52]=[CH:53][CH:54]=3)=[O:7])=[C:10]([C:11](=[O:12])[NH:13][C:14]3[CH:18]=[CH:17][N:16]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:27])([F:28])[F:26])[CH:20]=4)[N:15]=3)[CH:29]=2)[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1
Reactant: O=C(O)Cc1cccc(S)c1
Reactant: O=C(Nc1ccc(N2CCCCC2)cc1C(=O)Nc1ccn(-c2cccc(C(F)(F)F)c2)n1)c1cccc(CCl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C(O)Cc1cccc(SCc2cccc(C(=O)Nc3ccc(N4CCCCC4)cc3C(=O)Nc3ccn(-c4cccc(C(F)(F)F)c4)n3)c2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Into a round bottom flask was placed a solution of 2-(3-(chloromethyl)benzamido)-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide 21b (0.23 mmol, 1 equiv) in DMF (1.2 mL), potassium carbonate (127.1 mg, 0.92 mmol, 4 equiv), and (3-mercaptophenyl)acetic acid (42.6 mg, 0.253 mmol, 1.1 equiv). The solution was stirred overnight at room temperature. The reaction progress was monitored by LCMS. After 16.5 h, more (3-mercaptophenyl)acetic acid (7 mg) was added to the solution, and the solution was stirred another 1 h. The solvent was removed. The residue was dissolved with DCM, washed with H2O and brine, and dried over sodium sulfate. The product was purified by reverse phase HPLC, eluting with 0.05% TFA in a water/acetonitrile gradient. MS (ES, m/z) 714 [M+H]+.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[C:6]([C:9]2[N:13]([C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)[N:12]=[CH:11][CH:10]=2)=[C:5]([CH3:22])[N:4]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=2)[C:3]1=[O:33].[Br:34]Br.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(O)(=O)C>[Br:34][C:10]1[CH:11]=[N:12][N:13]([C:14]2[CH:15]=[CH:16][C:17]([C:18]#[N:19])=[CH:20][CH:21]=2)[C:9]=1[C:6]1[C:7](=[O:8])[N:2]([CH3:1])[C:3](=[O:33])[N:4]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:30])([F:31])[F:32])[CH:24]=2)[C:5]=1[CH3:22]
Reactant: BrBr
Reactant: Cc1c(-c2ccnn2-c2ccc(C#N)cc2)c(=O)n(C)c(=O)n1-c1cccc(C(F)(F)F)c1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: CC(=O)O
Product: Cc1c(-c2c(Br)cnn2-c2ccc(C#N)cc2)c(=O)n(C)c(=O)n1-c1cccc(C(F)(F)F)c1
Temperature: 25 °C

Procedure:
To a solution of 4-(5-(3,6-dimethyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile (prepared in Example 1) (665 mg) in acetic acid (15 ml) was added at room temperature bromine (0.75 ml) dropwise and the resulting mixture was stirred at room temperature for fifteen minutes. To the reaction mixture was added 10% aqueous sodium thiosulfate solution (30 ml) and the solids formed were filtered and then washed with hexane (50 ml) and dried under reduced pressure to afford 4-(4-bromo-5-(3,6-dimethyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile (692.8 mg) as brown solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[C:6]([N+:17]([O-])=O)[C:5]=1[CH3:20]>C1COCC1.CO.[OH-].[OH-].[Pd+2]>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[C:6]([NH2:17])[C:5]=1[CH3:20]
Reactant: COC(=O)c1ccc(NC2CCCCC2)c([N+](=O)[O-])c1C
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: COC(=O)c1ccc(NC2CCCCC2)c(N)c1C
Yield: 78.7 %

Procedure:
4-Cyclohexylamino-2-methyl-3-nitrobenzoic acid methyl ester (150 mg) was dissolved in THF/MeOH (30 mL, 1:2 ratio) and stirred in the presence of H2 (1 atm) and a catalytic amount of Pd(OH)2 (20 mg) at room temperature for 14 h. The reaction mixture was then filtered, evaporated to dryness and purified by flash column chromatography, using 25% EtOAc in hexane with 0.2% NH4OH as the eluent, to give the pure aniline (106 mg).
Reaction SMILES: BrCCC[N:5]1[C:9](=O)[C:8]2=[CH:11]C=CC=C2C1=O.[P:16]([O:23]CC)([O:20][CH2:21][CH3:22])[O:17][CH2:18][CH3:19]>>[NH2:5][CH2:9][CH2:8][CH2:11][P:16](=[O:23])([O:20][CH2:21][CH3:22])[O:17][CH2:18][CH3:19]
Reactant: CCOP(OCC)OCC
Reactant: O=C1c2ccccc2C(=O)N1CCCBr
Product: CCOP(=O)(CCCN)OCC
Temperature: 140 °C
Yield: 34 %

Procedure:
70 ml of triethyl phosphite was added to 40 g of N-(3-bromopropyl)phthalimide (7). The mixture was heated to a temperature of 140° C. The by-produced ethyl bromide was distilled off. The system was then heated over 4 hours. Excess triethyl phosphite was distilled off under reduced pressure by an aspirator. 9 ml of ethanol and hydrazine hydrate were added to the concentrated solution. The system was heated under reflux over 20 minutes. The resulting crystals were filtered off. A mixture of 10 g of oxalic acid and 50 ml of acetone were added to the filtrate. The resulting crystals were filtered off. The filtrate was concentrated. A small amount of water and acetone were added to the residue. The resulting crystals were filtered off. The filtrate was cooled to deposit crystals of oxalic acid salt of diethyl 3-aminopropylphosphonate (8). The crystals were filtered and dried under reduced pressure by a vacuum pump to obtain 12 g of diethyl 3-aminopropylphosphonate (8) in the form of oxalate. (Yield: 34 %; m.p. 54° C.)
Reaction SMILES: [CH:1]([C:4]1[O:8][C:7]([C:9]2[CH:19]=[CH:18][C:12]([C:13]([N:15]=[C:16]=[O:17])=O)=[CH:11][CH:10]=2)=[N:6][N:5]=1)([CH3:3])[CH3:2].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][NH:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:23][C:22]=1[NH:35][NH:36]C(OC(C)(C)C)=O.FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][NH:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:23][C:22]=1[N:35]1[C:16](=[O:17])[NH:15][C:13]([C:12]2[CH:18]=[CH:19][C:9]([C:7]3[O:8][C:4]([CH:1]([CH3:3])[CH3:2])=[N:5][N:6]=3)=[CH:10][CH:11]=2)=[N:36]1
Reactant: CC(C)(C)OC(=O)NNc1cc(CNC(=O)C(C)(C)C)ccc1Cl
Reactant: CC(C)c1nnc(-c2ccc(C(=O)N=C=O)cc2)o1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)c1nnc(-c2ccc(-c3nn(-c4cc(CNC(=O)C(C)(C)C)ccc4Cl)c(=O)[nH]3)cc2)o1
Yield: 43.3 %

Procedure:
The title compound was prepared according to the procedure described in Example-83 by using 4-(5-isopropyl-1,3,4-oxadiazol-2-yl)benzoyl isocyanate (Intermediate-104, 0.196 g, 0.84 mmol), tert-butyl 2-(2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}phenyl)hydrazinecarboxylate (Intermediate-94, 0.150 g, 0.420 mmol), DCM (15 mL), and trifluoro acetic acid (3.0 mL) to afford 0.090 g of the desired product. 1H NMR (300 MHz, DMSO d6): δ 1.06 (s, 9H), 1.35 (s, 6H), 3.25 (m, 1H), 4.27 (d, J=5.4 Hz, 2H), 7.34 (d, J=8.1 Hz, 1H), 7.44 (s, 1H), 7.59 (d, J=8.4 Hz, 1H), 8.01-8.04 (m, 2H), 8.10-8.17 (m, 3H), 12.73 (s, 1H); MS (m/z): 495.39 (M+H)+.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([CH2:9][N:10]2[C:18]3[C:13](=[C:14]([O:20][CH3:21])[C:15]([F:19])=[CH:16][CH:17]=3)[C:12]([NH:22][S:23]([C:26]3[S:27][C:28]([Cl:31])=[CH:29][CH:30]=3)(=[O:25])=[O:24])=[N:11]2)[CH:6]=[CH:7][CH:8]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:65](O)(=[O:67])[CH3:66]>CN(C=O)C.CO.CS(C)=O>[Cl:31][C:28]1[S:27][C:26]([S:23]([NH:22][C:12]2[C:13]3[C:18](=[CH:17][CH:16]=[C:15]([F:19])[C:14]=3[O:20][CH3:21])[N:10]([CH2:9][C:5]3[CH:4]=[C:3]([CH2:2][NH:1][C:65](=[O:67])[CH3:66])[CH:8]=[CH:7][CH:6]=3)[N:11]=2)(=[O:25])=[O:24])=[CH:30][CH:29]=1
Reactant: CC(=O)O
Reactant: COc1c(F)ccc2c1c(NS(=O)(=O)c1ccc(Cl)s1)nn2Cc1cccc(CN)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CO
Solvent: CS(C)=O
Product: COc1c(F)ccc2c1c(NS(=O)(=O)c1ccc(Cl)s1)nn2Cc1cccc(CNC(C)=O)c1
Reaction time: 0.05 h
Yield: 27 %

Procedure:
A solution of N-[1-{[3-(aminomethyl)phenyl]methyl}-5-fluoro-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide (for a preparation see Intermediate 61) (49 mg, 0.10 mmol) in dry DMF (4 mL) was treated with HATU (38.7 mg, 0.10 mmol) and stirred under nitrogen for 3 min prior to the addition of DIPEA (0.018 mL, 0.10 mmol). The reaction mixture was stirred for a further 3 min prior to the addition of acetic acid (6.12 mg, 0.10 mmol) and stirring continued for a further 3 h. The reaction mixture was concentrated by nitrogen in a blowdown unit and the sample was loaded in dichloromethane onto aminopropyl ion-exchange cartridge (1 g) pre-equilibrated with DCM. The sample was eluted with methanol/dichloromethane and dried under a stream of nitrogen in the Radleys blowdown apparatus to give the crude product. The sample was dissolved in 1:1 MeOH-DMSO (1 mL) and purified by Mass Directed AutoPrep on Xbridge column using Acetonitrile Water with an ammonium carbonate modifier (Method C). The solvent was evaporated in vacuo using the Genevac to give the title compound (14.5 mg, 27%): LCMS (System A) RT=1.06 min, ES+ve m/z 523/525 (M+H)+.
Reaction SMILES: [CH3:1][Si](C=[N+]=[N-])(C)C.C[Li].[C:10]([O:14][C:15]([N:17]1[CH2:20][C:19]([C:22]2[CH:27]=[CH:26][C:25]([C:28](=O)[CH2:29][C:30]([C:36]3[CH:41]=[C:40]([Cl:42])[CH:39]=[C:38]([Cl:43])[CH:37]=3)([OH:35])[C:31]([F:34])([F:33])[F:32])=[CH:24][CH:23]=2)([F:21])[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].C(O)(=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>COCCOC>[C:10]([O:14][C:15]([N:17]1[CH2:20][C:19]([C:22]2[CH:23]=[CH:24][C:25]([C:28]3[CH2:29][C:30]([C:36]4[CH:41]=[C:40]([Cl:42])[CH:39]=[C:38]([Cl:43])[CH:37]=4)([C:31]([F:32])([F:33])[F:34])[O:35][CH:1]=3)=[CH:26][CH:27]=2)([F:21])[CH2:18]1)=[O:16])([CH3:12])([CH3:13])[CH3:11]
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: CC(C)(C)OC(=O)N1CC(F)(c2ccc(C(=O)CC(O)(c3cc(Cl)cc(Cl)c3)C(F)(F)F)cc2)C1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Agent: [Li]C
Solvent: COCCOC
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N1CC(F)(c2ccc(C3=COC(c4cc(Cl)cc(Cl)c4)(C(F)(F)F)C3)cc2)C1
Reaction time: 2 h
Yield: 9.1 %

Procedure:
To a stirred solution of trimethylsilyldiazomethane (2M in diethyl ether, 18.64 mL, 37.289 mmol) in 1,2-dimethoxyethane (DME, 100 mL) was added methyl lithium (1.6M in diethyl ether, 23.32 mL, 37.289 mmol) at −78° C. over period of 10 minutes and stirred reaction mixture for 30 minutes at −78° C. Pre-dissolved 3-{4-[3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-3-hydroxy-butyryl]-phenyl}-3-fluoro-azetidine-1-carboxylic acid tert-butyl ester (Example 1, Intermediate 1) (5 g, 9.322 mmol, 1eq.) in DME (50 mL) was added at −78° C. in drop wise manner over period of 10 minutes. Resulting reaction mixture was stirred for 1 hour at same temperature and then at room temperature for 2 hours. Acetic acid (1.60 mL, 27.967 mmol, 3 eq.) was added at room temperature over period of 5 minutes followed by addition of TBAF (27.92 mL, 27.967 mmol, 3 eq.) at room temperature over period of 10 minutes. After consumption of starting material, reaction mixture was quenched with water (150 mL) and extracted with ethyl acetate (5×150 mL). Combined organic layer was dried over sodium sulphate and concentrated in vacuo to get orange semisolid (6.1 g, crude). Crude was purified by column chromatography using 100-200 mesh silica gel. Desired compound was eluted in 10% ethyl acetate in hexane to afford off white semisolid (1.6 g, Impure). The product was again purified by trituration using DCM: pentane (1:5, 2×20 mL) to afford product as off white solid (0.45 g, 9.18%). Yield: −0.45 g (9.18%). 1H NMR (400 MHz, CDCl3) δ: 1.46 (s, 9H), 3.20 (d, J=17.24 Hz, 1H), 3.30 (d, J=17.24 Hz, 1H), 4.14-4.21 (m, 2H), 4.33-4.41 (m, 2H), 7.32-7.38 (m, 4H), 7.40 (t, J=1.78 Hz, 1H), 7.52 (d, J=1.36 Hz, 2H). LC-MS (m/z): =529.9 (M−H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]=O)=[CH:9][N:10]=2)[CH:7]=1.[NH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C(O)(=O)C.[BH4-].[Na+]>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[CH:9][N:10]=2)[CH:7]=1
Reactant: C1COCCN1
Reactant: O=Cc1cnc2ccc(Br)cn12
Agent: [BH4-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Product: Brc1ccc2ncc(CN3CCOCC3)n2c1
Yield: 42.4 %

Procedure:
Reflux a solution of 6-bromo-imidazo[1,2-a]pyridine-3-carbaldehyde (J. Med. Chem. 1970, 13(6), 1048-51; 0.45 g, 1.99 mmol), morpholine (1.7 g, 19.9 mmol), and acetic acid (0.12 mL, 1.99 mmol) in toluene (200 mL) for 3 h. Concentrate to dryness and re-dissolve in methanol (100 mL). Add sodium borohydride (0.226 g, 5.99 mmol) in portions and stir for 30 min. Concentrate to ˜25 mL, dilute with saturated aqueous sodium bicarbonate, extract into ethyl acetate, combine and concentrate. Flash chromatography gives the titled compound (0.25 g, 42%). MS ES+ m/e 295.8, 297.8 (M+1). 1H NMR (400 MHz, DMSO-d6) δ 8.69 (s, 1H), 7.54 (d, J=10 Hz, 1H), 7.51 (s, 1H), 7.35 (d, J=10 Hz, 1H), 3.81 (s, 2H), 3.52 (t, J=4 Hz, 1H), 2.35 (t,J=4 Hz, 4H).
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([NH:10][C:11]([C:13]2[NH:26][C:16]3=[CH:17][N:18]=[C:19]([O:21][CH2:22][CH2:23][O:24][CH3:25])[CH:20]=[C:15]3[CH:14]=2)=[O:12])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].CN(C=O)C.Br[CH2:33][C:34]([NH:36][C:37]1[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][N:38]=1)=[O:35].Cl>O.CC#N>[CH:1]([N:4]1[CH2:5][CH2:6][CH:7]([NH:10][C:11]([C:13]2[N:26]([CH2:33][C:34](=[O:35])[NH:36][C:37]3[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][N:38]=3)[C:16]3=[CH:17][N:18]=[C:19]([O:21][CH2:22][CH2:23][O:24][CH3:25])[CH:20]=[C:15]3[CH:14]=2)=[O:12])[CH2:8][CH2:9]1)([CH3:3])[CH3:2]
Reactant: O=C(CBr)Nc1ccc(Cl)cn1
Reactant: COCCOc1cc2cc(C(=O)NC3CCN(C(C)C)CC3)[nH]c2cn1
Agent: Cl
Solvent: CN(C)C=O
Solvent: O
Solvent: CC#N
Product: COCCOc1cc2cc(C(=O)NC3CCN(C(C)C)CC3)n(CC(=O)Nc3ccc(Cl)cn3)c2cn1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 461 mg (1.27 mmol) ) 5-(2-Methoxy-ethoxy)-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide in 20 mL absolute DMF 46 mg (1.91 mmol) NaH (96%) were added in an argon atmosphere. The mixture was stirred for 15 min. at room temperature. 479 mg (1.91 mmol) 2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide were added and the mixture stirred for 3 h at room temperature. The solvent was removed in vacuo, the residue dissolved in CH2Cl2 and the CH2Cl2 phase washed with H2O and dried over Na2SO4. After filtration, the organic phase was concentrated and the residue purified by chromatography over silica gel using CH2Cl2/MeOH/HOAc/H2O=90/10/1/1 as eluent followed by preparative HPLC (eluent: CH3CN/H2O/0.1% CF3COOH). The fractions containing the product were combined and concentrated in vacuo. The residue was lyophilized with 2 equivalents 1N HCl in a H2O/CH3CN mixture yielding the hydrochloride salt of the desired product.
Reaction SMILES: [CH:1]1([CH:7]([C:18]2[CH:22]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=3[Cl:30])[O:20][C:19]=2[CH3:31])[O:8][C:9]2[CH:17]=[CH:16][C:12]([C:13](O)=[O:14])=[CH:11][CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:32][NH:33][CH2:34][CH2:35][C:36]([O:38]CC)=[O:37]>>[CH:1]1([CH:7]([C:18]2[CH:22]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=3[Cl:30])[O:20][C:19]=2[CH3:31])[O:8][C:9]2[CH:17]=[CH:16][C:12]([C:13]([N:33]([CH3:32])[CH2:34][CH2:35][C:36]([OH:38])=[O:37])=[O:14])=[CH:11][CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CCOC(=O)CCNC
Reactant: Cc1oc(-c2ccc(Cl)cc2Cl)cc1C(Oc1ccc(C(=O)O)cc1)C1CCCCC1
Product: Cc1oc(-c2ccc(Cl)cc2Cl)cc1C(Oc1ccc(C(=O)N(C)CCC(=O)O)cc1)C1CCCCC1
Yield: 98.2 %

Procedure:
An operation similar to that in Example 1 (4) was performed using 4-{cyclohexyl[5-(2,4-dichlorophenyl)-2-methyl-3-furyl]methoxy}benzoic acid (165 mg) as well as ethyl 3-(methylamino)propanoate (56 mg) to give the title compound (192 mg, 98%) as an amorphous compound.
Reaction SMILES: [CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[C:10]1([C:16]2([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C@H:24]3[C@H:20]([CH2:21][NH:22][CH2:23]3)[C:19](=[O:25])[CH2:18][CH2:17]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>ClCCl.C(N(CC)CC)C>[CH2:1]([N:22]1[CH2:21][C@H:20]2[C@H:24]([C:16]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH2:17][CH2:18][C:19]2=[O:25])[CH2:23]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: BrCc1ccccc1
Reactant: O=C1CCC(c2ccccc2)(c2ccccc2)[C@@H]2CNC[C@H]12
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C1CCC(c2ccccc2)(c2ccccc2)[C@@H]2CN(Cc3ccccc3)C[C@H]12
Temperature: 20 °C
Reaction time: 2 h

Procedure:
7.9 cm3 of benzyl bromide are added to a solution, cooled to 0° C., of 21.7 g of (3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride in 300 cm3 of dichloromethane and 18.5 cm3 of triethylamine. After stirring for 1 hour at 0° C. and 2 hours at 20° C., the reaction mixture is washed with 50 cm3 of water, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (0.04-0.06 mm, diameter 5 cm, height 40 cm), eluting under a nitrogen pressure of 0.6 bar with an ethyl acetate and cyclohexane mixture (75/25 by volume) and collecting fractions of 250 cm3. Fractions 3 to 6 are pooled and concentrated to dryness under reduced pressure (2.7 kPa). 22.1 g of (3aR, 7aR)-2-benzyl-7,7-diphenyl-4-perhydroisoindolone are obtained in the form of a white solid; melting point 124° C. [α]20 =-279° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH2:5]Cl.[Cl:11][CH2:12][CH2:13][CH2:14][OH:15].[H-].[Na+]>CN(C=O)C>[Cl:11][CH2:12][CH2:13][CH2:14][O:15][CH2:5][C:4]1[CH:7]=[CH:8][CH:9]=[CH:10][C:3]=1[O:2][CH3:1]
Reactant: COc1ccccc1CCl
Reactant: OCCCCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccccc1COCCCCl
Temperature: 25 °C
Reaction time: 1 h
Yield: 74170.5 %

Procedure:
A solution of 24.6 g (0.157 mmol) of 2-methoxybenzyl chloride and 26 ml (29.4 g, 0.311 mmol) of 3-chloro-1-propanol in 150 ml of absolute DMF was treated portionwise at 10° C. within 2.5 hours with 8.4 g (0.196 mmol) of sodium hydride dispersion (55% in refined oil) and stirred at room temperature for 1 hour. Subsequently, a further 1.0 g (0.023 mmol) of sodium hydride dispersion was added at room temperature and the mixture was stirred for a further 3 hours. For the working-up, the reaction mixture was partitioned between 500 ml of water and 500 ml of ethyl acetate. The organic phase was separated. The aqueous phase was extracted four times with 250 ml of ethyl acetate each time. The combined organic phases were washed twice with 250 ml of water each time and finally the solvent was distilled off under reduced pressure. The crude product (44 g) was purified by chromatography on silica gel with a 1:2 mixture of methylene chloride and hexane as the eluent. There were obtained 25.0 g (74% of theory) of 2-methoxybenzyl 3-chloropropyl ether as a colourless oil; MS: 214. 216 (M)+.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([C:11]([NH:13][C@H:14]([C:16]2[NH:20][C:19]3[CH:21]=[CH:22][C:23]([Cl:25])=[CH:24][C:18]=3[N:17]=2)[CH3:15])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].C(N(C(C)C)CC)(C)C.[NH:35]1[CH2:41][CH2:40][CH2:39][NH:38][CH2:37][C:36]1=[O:42].ClCl>CN(C)C=O>[Cl:1][C:2]1[CH:10]=[C:9]([CH:8]=[CH:7][C:3]=1[C:4]([N:38]1[CH2:39][CH2:40][CH2:41][NH:35][C:36](=[O:42])[CH2:37]1)=[O:5])[C:11]([NH:13][C@H:14]([C:16]1[NH:20][C:19]2[CH:21]=[CH:22][C:23]([Cl:25])=[CH:24][C:18]=2[N:17]=1)[CH3:15])=[O:12]
Reactant: O=C1CNCCCN1
Reactant: C[C@H](NC(=O)c1ccc(C(=O)O)c(Cl)c1)c1nc2cc(Cl)ccc2[nH]1
Agent: ClCl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: C[C@H](NC(=O)c1ccc(C(=O)N2CCCNC(=O)C2)c(Cl)c1)c1nc2cc(Cl)ccc2[nH]1
Yield: 63 %

Procedure:
Prepared analogously to Example 1d from (1S)-2-chloro-4-{N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]aminocarbonyl}benzoic acid, PFTU, diisopropylethylamine, and [1,4]diazepan-2-one in dimethylformamide. Yield: 63%; C22H21Cl2N5O3 (474.346); mass spectrum: (M+H)+=474/476 (chlorine isotope).
Reaction SMILES: [C:1]([C:9]1[CH:35]=[CH:34][C:12]([O:13][CH2:14][CH:15]([OH:33])[CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24](=[O:31])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[C:20]([OH:32])[CH:19]=2)=[CH:11][C:10]=1[OH:36])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:37](O)(=[O:41])[C:38]([CH3:40])=[CH2:39]>>[C:37]([O:33][CH:15]([CH2:14][O:13][C:12]1[CH:34]=[CH:35][C:9]([C:1](=[O:8])[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:10]([OH:36])[CH:11]=1)[CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24](=[O:31])[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[C:20]([OH:32])[CH:19]=1)(=[O:41])[C:38]([CH3:40])=[CH2:39]
Reactant: C=C(C)C(=O)O
Reactant: O=C(c1ccccc1)c1ccc(OCC(O)COc2ccc(C(=O)c3ccccc3)c(O)c2)cc1O
Product: C=C(C)C(=O)OC(COc1ccc(C(=O)c2ccccc2)c(O)c1)COc1ccc(C(=O)c2ccccc2)c(O)c1
Yield: 77.8 %

Procedure:
97 g (0.2 mole) of 1,3-bis-(4-benzoyl-3-hydroxyphenoxy)-2-propanol were esterified analogously to Example 1 with 103 g (1.2 moles) of methacrylic acid. Crystallization from ethanol gave 86 g (78 percent of theory) of 1,3-bis-(4-benzoyl-3-hydroxyphenoxy)-prop-2-yl methacrylate in the form of colorless crystals having a melting point of 138° to 139° C. and a purity of 99 percent (HPLC). The UV spectrum gave two absorption maxima at wave lengths of 287 nm (extinction 0.517; extinction coefficient 28,570) and 324 nm (extinction 0.333; extinction coefficient 18,400).
Reaction SMILES: [CH2:1]([O:6][C:7](=O)[CH:8]([NH:16][C:17](=O)[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH2:2][CH2:3][CH:4]=[CH2:5].N1C=CC=CC=1.O(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O>C(Cl)Cl>[CH2:9]([C:8]1[N:16]=[C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:5]=[C:4]2[CH2:3][CH2:2][CH2:1][O:6][C:7]=12)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: C=CCCCOC(=O)C(Cc1ccccc1)NC(=O)C(=O)OCC
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCOC(=O)c1cc2c(c(Cc3ccccc3)n1)OCCC2
Temperature: 15 °C

Procedure:
Pent-4-en-1-yl2-(2-ethoxy-2-oxoacetamido)-3-phenylpropanoate (0.80 g, 1 eq) and DCM (15 mL) were added to a vessel with stirring. Pyridine (0.23 g, 1.2 eq) was then added and the mixture was cooled to 15° C. Tf2O (1.0 g, 1.5 eq) was added to the mixture over 15 min and the mixture was warmed to ambient temperature. The solution was stirred for 3.5 h after which time the reaction was quenched by DCM and 20 wt % aqueous NaOAc to form a biphasic mixture. The layers were separated and the organic layer was extracted with 6N HCl (3×10 mL). The combined acid layers were washed with DCM and the pH was adjusted to ˜9 with solid K2CO3. The basic aqueous layer was extracted with DCM. The organic layer was concentrated under reduced pressure to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.74 (s, 1H), 7.10-7.35 (m, 5H), 4.43 (q, J=7.12 Hz, 2H), 4.22-4.29 (m, 2H), 4.21 (s, 2H), 2.78 (t, J=6.41 Hz, 2H), 1.93-2.06 (m, 2H), 1.41 (t, J=7.12 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ ppm 165.08, 152.25, 149.62, 138.86, 138.06, 129.62, 128.61, 127.80, 125.61, 125.23, 66.70, 60.97, 38.55, 23.93, 20.92, 14.10; HRMS (M+H) m/z, calcd for C18H20NO3, 298.1443; found 298.1450.