Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: NC1C=CC=CC=1.[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=1.[Br-:16].[Br-].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.FC1C=CC(N)=CC=1>>[Br:16][C:10]1[CH:11]=[C:12]([CH3:15])[CH:13]=[CH:14][C:9]=1[NH2:8]
Reactant: Cc1ccc(N)cc1
Reactant: [Br-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: Nc1ccc(F)cc1
Solvent: Nc1ccccc1
Product: Cc1ccc(N)c(Br)c1
Yield: 66 %

Procedure:
To show that selectivity is still obtained using a highly activated aniline, bromination of p-toluidine using tetrabutylammonium tribromide was carried out as generally described in Example 4, but substituting p-toluidine for 4-fluoroaniline, on a 0.75 mole reaction. The desired product 2-bromo-4-methylaniline was obtained in 66% yield on the 0.75 mole reaction.
Reaction SMILES: C(OC([N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)=O)(C)(C)C.CN([CH:16]=[O:17])C.[H-].[Li+].[Cl:20][C:21]1[CH:22]=[C:23](F)[CH:24]=[C:25]([Cl:27])[CH:26]=1.[ClH:29]>CCO.CCOC(C)=O.CCOC(C)=O>[Cl:20][C:21]1[CH:22]=[C:23]([CH:24]=[C:25]([Cl:27])[CH:26]=1)[O:17][C@H:16]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C@@H:11]1[CH2:10][CH2:9][NH:8][CH2:12]1.[ClH:29]
Reactant: CC(C)(C)OC(=O)N1CCCC1
Reactant: CN(C)C=O
Reactant: Fc1cc(Cl)cc(Cl)c1
Agent: Cl
Agent: [H-]
Agent: [Li+]
Solvent: CCO
Solvent: CCOC(C)=O
Product: Clc1cc(Cl)cc(O[C@H](c2ccccc2)[C@@H]2CCNC2)c1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
(R)-3-(S)-hydroxyphenylmethyl)pyrrolidine-1-carboxylic acid t-butyl ester (2.0 g, 7.2 mmol) was dissolved in anhydrous DMF (10 mL, 100 mmol). Lithium hydride (86 mg, 11 mmol) was added in 3 separate portions. The mixture was stirred at room temperature for 15 minutes. Into the mixture was added 3,5-dichlorofluorobenzene (1.7 mL, 14 mmol), and the resultant mixture stirred at room temperature for 15 minutes. The mixture was then stirred at 70° C. overnight. The mixture was cooled to room temperature, and EtOAc (80 mL) and 1M HCl (50 mL) were added. After mixing, the phases were separated and the organic layer was washed with diluted aqueous NaCl (1×50 mL), dried over Na2SO4, and concentrated to dryness to yield 3.5 g of crude product. Into the crude product was added 25 mL cold HCl in an EtOH/EtOAc solution and stirred at room temperature for 3 hours. Most of the solvent was removed by rotary evaporation, EtOAc was added (50 mL) and most of the solvent was removed again. Recrystallization and reslurry from EtOAc (20 mL) gave (R)-3-[(S)-(3,5-dichlorophenoxy)phenylmethyl]pyrrolidine as an HCl salt (2 g, ˜99% purity).
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1)=O.[O:13]1CCN(C2CCCCC=2)CC1.Cl.[CH:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>>[O:13]=[C:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C:27]1=[CH:1][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1
Reactant: c1ccccc1
Reactant: C1=C(N2CCOCC2)CCCC1
Reactant: O=Cc1ccc(CC(=O)O)cc1
Agent: Cl
Product: O=C(O)Cc1ccc(C=C2CCCCC2=O)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 51.2 %

Procedure:
A solution of 3.28 g (0.02 mole) of p-formylphenylacetic acid and 10.1 g (0.056 mole) of 1-morpholinocyclohexene in 40 ml of benzene was stirred at room temperature for 12 hours, after which 20 ml of 6N hydrochloric acid were added thereto. The mixture was then stirred at room temperature for a further 1 hour, after which it was extracted with diethyl ether. The extract was washed with water and dried over anhydrous sodium sulfate, and the solvent was removed to afford an oily substance, which was purified by silica gel chromatography, eluted with a 1:1 by volume mixture of hexane and ethyl acetate, to give 2.5 g (yield 51.2%) of the title compound as a colorless oily substance.
Reaction SMILES: [C:1](=[O:3])=O.[CH3:4]C(C)=O.[OH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15](=[O:17])[CH3:16]>>[O:17]=[C:15]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[O:8][CH:4]=[C:16]1[CH:1]=[O:3]
Reactant: O=C=O
Reactant: CC(=O)c1ccccc1O
Reactant: CC(C)=O
Product: O=Cc1coc2ccccc2c1=O
Temperature: 25 °C
Reaction time: 13 h

Procedure:
In 80 volume parts of diemthylformamide there is dissolved 25 parts of orthohydroxyacetophenone and while the solution is externally cooled to about -20°C with dry ice-acetone, 80 volume parts of tetrachloropyrophosphate is added in small installments. The mixture is stirred at room temperature for 13 hours. The reaction mixture is then poured into ice-water and the resulting crystals are recovered by filtration, washed with water and ethanol and finally recrystallized from acetone. There is obtained a 19.6 parts yield of 4-oxo-4H-1-benzopyran-3-carboxaldehyde, as colorless crystals, melting at 152°-153°C.
Reaction SMILES: [CH3:1][C:2]1[O:3][CH:4]=[CH:5][C:6]=1[C:7](Cl)=[O:8].[NH2:10][C:11]1[CH:33]=[CH:32][C:14]([C:15]([N:17]2[CH2:23][C:22]3[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=3[CH2:20][C:19]3[CH:28]=[CH:29][CH:30]=[CH:31][C:18]2=3)=[O:16])=[CH:13][CH:12]=1>>[CH:28]1[C:19]2[CH2:20][C:21]3[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=3[CH2:23][N:17]([C:15]([C:14]3[CH:13]=[CH:12][C:11]([NH:10][C:7]([C:6]4[CH:5]=[CH:4][O:3][C:2]=4[CH3:1])=[O:8])=[CH:33][CH:32]=3)=[O:16])[C:18]=2[CH:31]=[CH:30][CH:29]=1
Reactant: Cc1occc1C(=O)Cl
Reactant: Nc1ccc(C(=O)N2Cc3ccccc3Cc3ccccc32)cc1
Product: Cc1occc1C(=O)Nc1ccc(C(=O)N2Cc3ccccc3Cc3ccccc32)cc1

Procedure:
As described for Example 9, 2-methyl-3-furanecarbonyl chloride is reacted with 5-(4-amino-benzoyl)-6,11-dihydro-5H-dibenz[b,e]azepine to give the product. Recrystallization from dichloromethanehexane gives crystals, m.p. 202°-204° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:12]2[O:13][C:14]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:15]=3[N:16]=2)[C:5]([NH:8][CH2:9][CH2:10][CH3:11])=[CH:6][CH:7]=1.[CH:22]1[C:27]([C:28]([OH:30])=[O:29])=[CH:26][C:25]2[C:31]([O:33][C:34](=O)[C:24]=2[CH:23]=1)=[O:32]>>[CH3:21][C:18]1[CH:19]=[CH:20][C:14]2[O:13][C:12]([C:4]3[CH:3]=[C:2]([N:1]4[C:31](=[O:32])[C:25]5[C:24](=[CH:23][CH:22]=[C:27]([C:28]([OH:30])=[O:29])[CH:26]=5)[C:34]4=[O:33])[CH:7]=[CH:6][C:5]=3[NH:8][CH2:9][CH2:10][CH3:11])=[N:16][C:15]=2[CH:17]=1
Reactant: CCCNc1ccc(N)cc1-c1nc2cc(C)ccc2o1
Reactant: O=C(O)c1ccc2c(c1)C(=O)OC2=O
Product: CCCNc1ccc(N2C(=O)c3ccc(C(=O)O)cc3C2=O)cc1-c1nc2cc(C)ccc2o1

Procedure:
Prepared by the method of Example 15f), from 2-(3-amino-6-propylaminophenyl)-5-methylbenzoxazole (112 mg, 0.4 mmol) and 1,2,4-benzenetricarboxylic anhydride (96 mg, 0.5 mmol) the title compound was obtained (92 mg, 50%). 1H NMR (DMSO) δ 8.60(t, 1H), 8.41(d, 1H), 8.29(s, 1H), 8.08(m, 2H), 7.54(d, 1H), 7.45(d, 1H), 7.30(t, 1H), 7.22(d, 1H), 6.99(d, 1H), 3.34(m, 2H), 2.59(s, 3H), 1.79(m, 2H), 1.12(t, 3H). MS 454.1 m/z (M−H)−.
Reaction SMILES: S(Cl)([Cl:3])=O.[CH2:5]([O:12][C:13]1[C:18]([O:19][CH3:20])=[CH:17][C:16]([CH2:21]O)=[CH:15][C:14]=1[Cl:23])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(OCC)C.O>ClCCl>[CH2:5]([O:12][C:13]1[C:18]([O:19][CH3:20])=[CH:17][C:16]([CH2:21][Cl:3])=[CH:15][C:14]=1[Cl:23])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: O=S(Cl)Cl
Reactant: COc1cc(CO)cc(Cl)c1OCc1ccccc1
Solvent: ClCCl
Solvent: CCOCC
Solvent: O
Product: COc1cc(CCl)cc(Cl)c1OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Thionyl chloride (2 mL) was added to solution of (4-benzyloxy-3-chloro-5-methoxy-phenyl)-methanol (CAB02170, 2.703 g, 9.7 mmol) in dichloromethane (10 mL). The solution was stirred for 1 h at room temperature, then diethyl ether (50 mL) and water (20 mL) were added. The organic layer was separated, washed with conc. sodium bicarbonate solution (10 mL), dried over sodium sulphate and concentrated under reduced pressure. The residue was dissolved in dichloromethane (5 mL) and precipitated by addition of hexane (ca. 50 mL). Yield: 2.730 g (95%) white powder. 1H-NMR (400 MHz, CDCl3) δ=3.89 (s, 3H, —OCH3), 4.52 (s, 2H), 5.07 (s, 2H), 6.87 (d, J=2.0 Hz, 1H), 7.03 (d, J=2.0 Hz, 1H), 7.33-7.43 (m, 3H), 7.53-7.58 (m, 2H). LRMS (FAB+): 91.0 (100), 296.0 (17, [M+H]+).
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:5][C:3]=1[NH2:4].C1(C)C=CC=CC=1.C(N(CC)CC)C.Cl[C:39](Cl)([O:41][C:42](=[O:48])OC(Cl)(Cl)Cl)Cl.[C:50]([C:54]1[CH:59]=[CH:58][C:57]([S:60][CH2:61][CH2:62]CO)=[CH:56][CH:55]=1)([CH3:53])([CH3:52])[CH3:51]>C(Cl)Cl>[Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:5][C:3]=1[NH:4][C:42](=[O:48])[O:41][CH2:39][CH2:62][CH2:61][S:60][C:57]1[CH:58]=[CH:59][C:54]([C:50]([CH3:51])([CH3:53])[CH3:52])=[CH:55][CH:56]=1
Reactant: CC(C)(C)c1ccc(SCCCO)cc1
Reactant: COc1cc2ncnc(Oc3ccc(N)c(Cl)c3)c2cc1OC
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COc1cc2ncnc(Oc3ccc(NC(=O)OCCCSc4ccc(C(C)(C)C)cc4)c(Cl)c3)c2cc1OC
Temperature: 25 °C
Yield: 50.3 %

Procedure:
2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (77 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (125 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[4-(tert-butyl)phenyl]sulfanyl-1-propanol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 47%).
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4](=[C:12]1[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[C:13]1=O)[NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.COCC(C1CCN(C(OCC2C=CC=CC=2)=O)C1=O)NC1C=CC=CC=1>>[CH3:1][O:2][CH2:3][C@H:4]1[C@H:12]2[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[C@H:13]2[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[NH:5]1
Reactant: COCC(Nc1ccccc1)=C1CCN(C(=O)OCc2ccccc2)C1=O
Agent: COCC(Nc1ccccc1)C1CCN(C(=O)OCc2ccccc2)C1=O
Product: COC[C@@H]1Nc2ccccc2[C@H]2[C@@H]1CCN2C(=O)OCc1ccccc1

Procedure:
In the same manner as in Example 36 except that (2S,4S)-tolyl-skewphos was used as an asymmetric ligand instead of (2S,4S)-skewphos, benzyl 3-(2-methoxy-1-(phenylamino)ethylidene)-2-oxopyrrolidine-1-carboxylate was hydrogenated. Quantification by high performance liquid chromatography confirmed that the starting material, benzyl 3-(2-methoxy-1-(phenylamino)ethylidene)-2-oxopyrrolidine-1-carboxylate remained by 21%, the reaction intermediate, benzyl 3-(2-methoxy-1-(phenylamino)ethyl)-2-oxopyrrolidine-1-carboxylate, remained by 32%, and the resultant product, (3aR,4R,9bR)-benzyl 4-(methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinoline-1-carboxylate, was produced by 42%. The optical purity of the resultant product was 54% ee.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=1)[CH3:2].[Cl-].[CH3:14][O:15][C:16]1[CH:31]=[CH:30][C:19]([C:20]([NH:22][C:23]2[C:24]([NH2:29])=[CH:25][CH:26]=[CH:27][CH:28]=2)=[O:21])=[CH:18][CH:17]=1.C(N(CC)CC)C>CN(C)C=O.C(Cl)Cl>[CH3:14][O:15][C:16]1[CH:17]=[CH:18][C:19]([C:20]([NH:22][C:23]2[C:24]([NH:29][C:8](=[O:10])[C:7]3[CH:6]=[CH:5][C:4]([O:3][CH2:1][CH3:2])=[CH:12][CH:11]=3)=[CH:25][CH:26]=[CH:27][CH:28]=2)=[O:21])=[CH:30][CH:31]=1
Reactant: CCOc1ccc(C(=O)O)cc1
Reactant: COc1ccc(C(=O)Nc2ccccc2N)cc1
Agent: [Cl-]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCOc1ccc(C(=O)Nc2ccccc2NC(=O)c2ccc(OC)cc2)cc1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 40.6 %

Procedure:
To a mixture of 4-ethoxybenzoic acid (0.332 g, 2.00 mmol) and a few drops of N,N-dimethylformamide in methylene chloride (50 mL) cooled to 0° C. was added oxayl chloride (0.21 mL, 2.2 mmole). After 30 min reaction the mixture was warmed to room temperature and stirred for an additional 10 min. The mixture was concentrated in vacuo, and the residue dissolved in methylene chloride (10 mL), and the resulting solution added in two portions to a mixture of N1-(4-methoxybenzoyl)-1,2-benzenediamine (0.455 g, 2.00 mmol) and triethylamine (0.281 mL, 2.00 mmol) in methylene chloride (40 mL) cooled to 0° C. After 4 h, the mixture was allowed to warm to room temperature and stirred for an additional 12 h. The reaction was quenched with cold dilute aqueous hydrochloric acid (50 mL), diluted with hexane, and shaken in a separatory funnel. The organic layer was washed with cold dilute aqueous hydrochloric acid and saturated aqueous sodium bicarbonate solution. The solution was dried (magnesium sulfate), filtered, and concentrated in vacuo. Recrystallization of the residue from methylene chloride/hexane provided 317 mg (41%) of title compound.
Reaction SMILES: [CH3:1][C@@H:2]1[O:9]C(=O)[C@H](C)[O:5][C:3]1=[O:4].C1OC(=O)COC1=O>>[C:3]([OH:5])(=[O:4])[CH2:2][OH:9].[C:3]([OH:5])(=[O:4])[CH:2]([CH3:1])[OH:9]
Reactant: C[C@@H]1OC(=O)[C@H](C)OC1=O
Agent: O=C1COC(=O)CO1
Product: CC(O)C(=O)O
Product: O=C(O)CO
Reaction time: 20 h

Procedure:
A PFA-made cylinder was charged with 100 g of recrystallized L-(-)-lactide and 100 g of glycolide, and the contents were dried at room temperature for about 30 minutes while introducing nitrogen gas. Then, 0.048 g of tin octanoate as a catalyst was added, and the contents were held at 130° C. for 20 hours while introducing nitrogen gas therein, thereby polymerizing the monomers. After completion of the polymerization, a bulk polymer taken out of the cylinder was ground into fine particles having a particle size of about 3 mm or smaller, and the fine particles were dried overnight at about 50° C. under reduced pressure of about 0.1 kPa to remove remaining monomers, thereby obtaining a glycolic acid/lactic acid copolymer [Polymer (P-C3)]. The same process was conducted repeatedly to prepare a necessary amount of Polymer (P-C3). The polymer thus obtained had a glass transition temperature, Tg of about 44° C. and was a noncrystalline amorphous substance.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]([CH2:22][C:23](O)=[O:24])[C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:26][NH:27][CH2:28][C:29]1[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=1>>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]([C:15]2[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=2)[CH2:22][C:23]([N:27]([CH3:26])[CH2:28][C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)=[O:24])(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: Cc1ccc(N(CC(=O)O)S(=O)(=O)c2ccc(C(C)(C)C)cc2)cc1
Reactant: CNCc1cccnc1
Product: Cc1ccc(N(CC(=O)N(C)Cc2cccnc2)S(=O)(=O)c2ccc(C(C)(C)C)cc2)cc1

Procedure:
prepared by reaction of [(4-tert-butyl-benzenesulfonyl)-p-tolyl-amino]-acetic acid with methyl-pyridin-3-ylmethyl-amine
Reaction SMILES: [CH:1]1[CH:5]=[C:4]([CH:6]=O)[O:3][CH:2]=1.C(O)(=O)[CH2:9][C:10]([OH:12])=[O:11].N1CCCCC1.Cl>N1C=CC=CC=1.O>[O:3]1[CH:2]=[CH:1][CH:5]=[C:4]1/[CH:6]=[CH:9]/[C:10]([OH:12])=[O:11]
Reactant: O=Cc1ccco1
Reactant: O=C(O)CC(=O)O
Agent: Cl
Solvent: C1CCNCC1
Solvent: c1ccncc1
Solvent: O
Product: O=C(O)/C=C/c1ccco1
Temperature: 100 °C
Reaction time: 3 h
Yield: 91.9 %

Procedure:
To a mixture of 2-furfural (500 g, 5.20 mol) and malonic acid (595 g, 5.72 mol) in pyridine (500 mL) was added piperidine (50 mL, 0.505 mol) at room temperature, and the mixture was stirred at 100° C. for 3 hr. The reaction solution was poured into water (1 L) and acidified with 6M hydrochloric acid. The resulting precipitate was collected by filtration to give the title compound (660 g, yield 92%).
Reaction SMILES: C([O:3][C:4]([C@@H:6]1[C@H:8]([C:9](=[O:39])[NH:10][C@@H:11]([CH2:35][CH:36]([CH3:38])[CH3:37])[C:12](=[O:34])[NH:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19](=[O:33])[CH2:20][CH2:21][CH2:22][CH2:23][C@H:24]2[C@@H:31]3[C@@H:27]([NH:28][C:29](=[O:32])[NH:30]3)[CH2:26][S:25]2)[O:7]1)=[O:5])C.[Li+].[OH-]>CO.O>[CH3:37][CH:36]([CH3:38])[CH2:35][C@H:11]([NH:10][C:9]([C@H:8]1[O:7][C@@H:6]1[C:4]([OH:5])=[O:3])=[O:39])[C:12](=[O:34])[NH:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19](=[O:33])[CH2:20][CH2:21][CH2:22][CH2:23][C@H:24]1[C@@H:31]2[C@@H:27]([NH:28][C:29](=[O:32])[NH:30]2)[CH2:26][S:25]1
Reactant: CCOC(=O)[C@H]1O[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCCCNC(=O)CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@@H]21
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC(C)C[C@H](NC(=O)[C@H]1O[C@@H]1C(=O)O)C(=O)NCCCCNC(=O)CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@@H]21
Yield: 24.6 %

Procedure:
Synthesized following general saponification procedure using the following quantities: the corresponding peptidomimetic epoxide ethyl ester 17h (155 mg, 0.3 mmol): LiOH (14 mg, 0.58 mmol); MeOH/H2O (1.5 mL: 0.5 mL: 0.5 mL); yielded 27 as a white solid (40 mg, 27.1%). 1H NMR (DMSO-d6, 400 MHz): 8.56 (d, 1H); 8.06 (t, 1H); 7.76 (t, 1H); 6.41 (s, 1H), 6.35 (s, 1H); 4.57 (m, 2H); 4.31 (m, 1H); 3.66 (d, 1H); 3.31 (d, 1H); 3.08 (m, 1H); 3.01 (m, 3H); 2.80 (dd, 1H); 2.56 (d, 1H); 2.04 (t, 2H); 1.53 (m, 6H); 1.43 (m, 3H); 1.36 (m, 2H); 0.89 (d, 3H); 0.84 (d, 3H). 13C NMR (DMSO-d6, 100 MHz): 171.80, 171.06, 568.78, 164.85, 162.68, 61.00, 59.16, 55.36, 52.65, 51.19, 41.14, 35.17, 28.17, 27.98, 26.59, 26.45, 25.28, 24.24, 22.87, 21.61. ESI-HRMS (m/z): no ionization, mass not seen. HPLC Method 1: Rt=14.8 min, purity=95.6%.
Reaction SMILES: C([Sn](CCCC)(CCCC)[C:6]1[N:7]=[CH:8][N:9]([C:11]2[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[C:13]([C:21]3[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=3)[N:12]=2)[CH:10]=1)CCC.[C:39]([NH:43][S:44]([C:47]1[S:51][C:50](Cl)=[N:49][CH:48]=1)(=[O:46])=[O:45])([CH3:42])([CH3:41])[CH3:40].CCCCCCC>C1(C)C=CC=CC=1.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>[C:39]([NH:43][S:44]([C:47]1[S:51][C:50]([C:6]2[N:7]=[CH:8][N:9]([C:11]3[CH:16]=[C:15]([C:17]([F:20])([F:18])[F:19])[CH:14]=[C:13]([C:21]4[CH:22]=[CH:23][C:24]([C:27]([F:30])([F:28])[F:29])=[CH:25][CH:26]=4)[N:12]=3)[CH:10]=2)=[N:49][CH:48]=1)(=[O:45])=[O:46])([CH3:42])([CH3:40])[CH3:41]
Reactant: CC(C)(C)NS(=O)(=O)c1cnc(Cl)s1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cn(-c2cc(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)n2)cn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCCCCCC
Solvent: Cc1ccccc1
Product: CC(C)(C)NS(=O)(=O)c1cnc(-c2cn(-c3cc(C(F)(F)F)cc(-c4ccc(C(F)(F)F)cc4)n3)cn2)s1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 69.7 %

Procedure:
A stirred mixture of 2-(4-tributylstannanyl-imidazol-1-yl)-4-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-pyridine (Example G.11) (0.575 g, 0.76 mmol), 2-chloro-thiazole-5-sulfonic acid tert-butylamide (Example H.1) (0.227 g, 0.85 mmol), tetrakis(triphenylphosphine)palladium (0.051 g, 0.038 mmol) in toluene (5 mL) was heated under reflux conditions for 4 h. Cooled to rt, some precipitate occurred, diluted with toluene (˜5 mL), placed in freezer for 30 min, added heptane (total volume: 25 mL), filtered the precipitate off, washed with toluene/heptane (ca. 1:1, 3×10 mL), dried in HV to give the title compound as an off-white solid (305 mg, 70%). MS (ISP) 576.3 [(M+H)+]; mp 236° C.
Reaction SMILES: [CH2:1]([S:17][CH2:18][CH:19]([N:22]1[N:26]=[N:25][C:24]([CH3:27])=[N:23]1)[CH2:20]O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].C(SCC(OC)C[NH2:48])CCCCCCCCCCCCCCC.C1(=O)NC(=O)C2=CC=CC=C12>>[CH2:1]([S:17][CH2:18][CH:19]([N:22]1[N:26]=[N:25][C:24]([CH3:27])=[N:23]1)[CH2:20][NH2:48])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCCCCCSCC(CN)OC
Reactant: CCCCCCCCCCCCCCCCSCC(CO)n1nnc(C)n1
Agent: O=C1NC(=O)c2ccccc21
Product: CCCCCCCCCCCCCCCCSCC(CN)n1nnc(C)n1

Procedure:
3-hexadecylthio-2-(5-methyl-2H-tetrazol-2-yl)propanol Vh1 is allowed to react and worked up by the same procedure as described in (3). The phthalimide compound: m.p. 82°-83° C. The summary of the experimental condition and the physical data of the product are listed in Tables 5 and 6.
Reaction SMILES: [Cl:1][C:2]1[C:3]([N:29]2[CH2:33][C@H:32]([O:34][Si](C(C)(C)C)(C)C)[CH2:31][C@H:30]2[C:42]([O:44][CH3:45])=[O:43])=[N:4][CH:5]=[C:6]([C:8]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[CH3:25])=[C:15]([CH2:26][O:27][CH3:28])[CH:14]=3)[O:10][N:9]=2)[CH:7]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.C(Cl)Cl.O>[Cl:1][C:2]1[C:3]([N:29]2[CH2:33][C@H:32]([OH:34])[CH2:31][C@H:30]2[C:42]([O:44][CH3:45])=[O:43])=[N:4][CH:5]=[C:6]([C:8]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[CH3:25])=[C:15]([CH2:26][O:27][CH3:28])[CH:14]=3)[O:10][N:9]=2)[CH:7]=1
Reactant: COCc1cc(-c2nc(-c3cnc(N4C[C@H](O[Si](C)(C)C(C)(C)C)C[C@H]4C(=O)OC)c(Cl)c3)no2)ccc1-c1ccccc1C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Solvent: ClCCl
Product: COCc1cc(-c2nc(-c3cnc(N4C[C@H](O)C[C@H]4C(=O)OC)c(Cl)c3)no2)ccc1-c1ccccc1C
Temperature: 25 °C
Reaction time: 18 h
Yield: 88.3 %

Procedure:
To a solution of methyl (2S,4R)-1-(3-chloro-5-(5-(2-(methoxymethyl)-2′-methylbiphenyl-4-yl)-1,2,4-oxadiazol-3-yl)pyridin-2-yl)-4-(tert-butyldimethylsilyloxy)-pyrrolidine-2-carboxylate (0.118 g; 0.18 mmol) in THF (2 mL) was added a solution of tetrabutylammonium fluoride (1.0 M in THF; 0.36 mL; 0.36 mmol). The reaction mixture was stirred at ambient temperature for 18 hours. The mixture was diluted with DCM and water and poured through a hydrophobic frit. The solvent was evaporated in vacuo and the residue was purified by flash chromatography on silica, eluting with iso-hexane/EtOAc (100% iso-hexane to 50%/50% iso-hexane/EtOAc) to afford the title product (0.085 g; 88%). 1H NMR (CDCl3, 400 MHz) δ 8.81 (1H, d, J=2 Hz), 8.40 (1H, d, J=1.2 Hz), 8.26 (1H, d, J=1.6 Hz), 8.15-8.13 (1H, m), 7.34-7.24 (4H, m), 7.14-7.12 (1H, m), 5.01 (1H, t, J=8 Hz), 4.66 (1H, s), 4.34-4.30 (1H, m), 4.22-4.21 (2H, m), 4.02-3.99 (1H, m), 3.74 (3H, s), 3.33 (3H, s), 2.38 (1H, m), 2.21-2.14 (1H, m), 2.08 (3H, s), 1.76 (1H, d, J=3.6 Hz).
Reaction SMILES: [CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([CH2:30][NH:31][CH2:32][CH2:33][O:34][CH3:35])=[CH:26][CH:25]=5)[S:23][C:16]=34)=[C:10]([F:36])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1.[CH3:37][C:38](OC(C)=O)=[O:39]>N1C=CC=CC=1>[CH:1]1([NH:4][C:5](=[O:6])[NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([CH2:30][N:31]([CH2:32][CH2:33][O:34][CH3:35])[C:38](=[O:39])[CH3:37])=[CH:26][CH:25]=5)[S:23][C:16]=34)=[C:10]([F:36])[CH:9]=2)[CH2:3][CH2:2]1
Reactant: CC(=O)OC(C)=O
Reactant: COCCNCc1ccc(-c2cc3nccc(Oc4ccc(NC(=O)NC5CC5)cc4F)c3s2)cc1
Solvent: c1ccncc1
Product: COCCN(Cc1ccc(-c2cc3nccc(Oc4ccc(NC(=O)NC5CC5)cc4F)c3s2)cc1)C(C)=O
Yield: 89.7 %

Procedure:
To a suspension of 113 (100 mg, 0.197 mmol) in pyridine (3 mL) was added Ac2O (30.2 mg, 0.296 mmol) and the reaction mixture was stirred for an hour. The mixture was concentrated then re-dissolved in EtOAc and washed with saturated CuSO4 solution then water. The organic phase was collected, dried over anhydrous Na2SO4, filtered and concentrated. The resultant solid was triturated with Et2O to afford title compound 114 (97 mg, 90% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.68 (s, 1H), 8.48 (m, 1H), 8.03 (s, 1H, rotamer), 7.83 (m, 2H, rotamer), 7.70 (m, 1H), 7.36 (m, 3H), 7.18 (m, 1H), 6.56 (m, 2H), 4.57 (s, 2H, rotamer) 3.43 (s, 3H), 3.29 (s, 2H), 3.20 (s, 2H, rotamer), 2.49 (m, 1H), 2.06 (s, 3H, rotamer), 0.63 (m, 2H), 0.41 (m, 2H). MS (m/z)=549.57 (M+H).