Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([C:5]1[N:6]([CH2:17][C@@H:18]2[CH2:22][O:21][C:20]([CH3:24])([CH3:23])[O:19]2)[C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([N+:14]([O-])=O)=[CH:9][CH:8]=2)(C)(C)C.C([O-])=O.[NH4+]>C(O)C.O.[Pd]>[CH3:23][C:20]1([CH3:24])[O:19][CH:18]([CH2:17][N:6]2[C:7]3[C:12](=[CH:11][C:10]([NH2:14])=[CH:9][CH:8]=3)[CH:13]=[CH:5]2)[CH2:22][O:21]1
Reactant: CC1(C)OC[C@@H](Cn2c(C(C)(C)C)cc3cc([N+](=O)[O-])ccc32)O1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: CC1(C)OCC(Cn2ccc3cc(N)ccc32)O1
Temperature: 25 °C
Reaction time: 1 h
Yield: 120.4 %

Procedure:
To a stirred solution of (R)-2-tert-butyl-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-nitro-1H-indole (1.0 g, 3.0 mmol) in ethanol (20 mL) and water (5 mL) was added ammonium formate (0.76 g, 12 mmol) followed by slow addition of 10% palladium on carbon (0.4 g). The mixture was stirred at room temperature for 1 h. The reaction mixture was filtered through a plug of celite and rinsed with ethyl acetate. The filtrate was evaporated under reduced pressure and the crude product was dissolved in ethyl acetate. The organic layer was washed with water (2×5 mL) and brine (2×5 mL). The organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure to give (R)-2-tert-butyl-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl-1H-indol-5-amine (0.89 g, 98%). 1H NMR (400 MHz, CDCl3) δ 7.04 (d, J=4 Hz, 1H), 6.70 (d, J=2.2 Hz, 1H), 6.48 (dd, J=2.2, 8.6 Hz, 1H), 6.05 (s, 1H), 4.38-4.1 (m, 2H), 4.21 (dd, J=7.5, 16.5 Hz, 1H), 3.87 (dd, J=6.0, 8.6 Hz, 1H), 3.66 (dd, J=6.0, 8.6 Hz, 1H), 3.33 (br s, 2H), 1.40 (s, 3H), 1.34 (s, 9H), 1.25 (s, 3H).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1[NH:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:21])=[CH:11][CH:10]=[CH:9][CH:8]=2)([O-])=O>[Pt].C1(C)C=CC=CC=1>[NH2:1][C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1[NH:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:21])=[CH:11][CH:10]=[CH:9][CH:8]=2
Reactant: O=C(CCCCCNc1c([N+](=O)[O-])cnc2ccccc12)c1ccccc1
Agent: [Pt]
Solvent: Cc1ccccc1
Product: Nc1cnc2ccccc2c1NCCCCCC(=O)c1ccccc1
Reaction time: 3 h
Yield: 100.3 %

Procedure:
A mixture of 6-(3-nitroquinolin-4-ylamino)-1-phenylhexan-1-one (2.27 g, 6.25 mmol) and 5% platinum on carbon catalyst (0.50 g) in toluene (60 mL) was hydrogenated on a Parr shaker at 50 psi (3.4×105 Pa) for 3 hours. After filtration through CELITE filter agent and concentration under reduced pressure, 6-(3-aminoquinolin-4-ylamino)-1-phenylhexan-1-one (2.09 g) was obtained as a dark yellow oil that was used directly in the next step without further purification.
Reaction SMILES: C(O[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:15][CH:14]=2)=[CH:9][CH:8]=1)CCCC.C1(N=C=NC2CCCCC2)CCCCC1.FC1C(O)=C(F)C(F)=C(F)C=1F>C(OCC)(=O)C>[C:10]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)=[CH:15][CH:14]=2)[CH:9]=[CH:8][CH:7]=[CH:12][CH:11]=1
Reactant: CCCCCOc1ccc(-c2ccc(-c3ccccc3)cc2)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Oc1c(F)c(F)c(F)c(F)c1F
Solvent: CCOC(C)=O
Product: c1ccc(-c2ccc(-c3ccccc3)cc2)cc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a mixture of 4"-(n-pentyloxy)- 1,1':4',1"-terphenyl!-4-carboxylic acid (10.5 mmol) and dicyclohexylcarbodiimide (10.5 mmol) in ethyl acetate at 0° C. is added pentafluorophenol (11.5 mmol). The mixture is stirred at 25° C. for a period of 18 h, producing a precipitate. The mixture is filtered. The filtrate is washed with water and brine and dried with magnesium sulfate. The solvent is removed in vacuo to obtain pentafluorophenyl 4"-(n-pentytoxy)- 1,1':4',1"-terphenyl!-4-carboxylate, C30H23F5O3, M.W.=526.5.
Reaction SMILES: [CH:1]([CH2:3][CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][C:5]1([C:16](=[N:27][CH3:28])[S:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1)[C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1)=[O:2].CC(C)[O-].[Al+3].CC(C)[O-].CC(C)[O-]>C(O)(C)C>[OH:2][CH2:1][CH2:3][CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][C:5]1([C:16](=[N:27][CH3:28])[S:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1)[C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1
Reactant: CN=C(SCc1ccc(OC)cc1)C1(c2cccnc2)CCCCC1CC=O
Agent: CC(C)[O-]
Agent: [Al+3]
Solvent: CC(C)O
Product: CN=C(SCc1ccc(OC)cc1)C1(c2cccnc2)CCCCC1CCO
Yield: 49.8 %

Procedure:
A mixture of 2-formylmethyl-1-((N-methylimino)-(4-methoxybenzylthio)methyl)-1-(pyrid-3-yl)cyclohexane (1 g, 2.52 mmol) and aluminium isopropoxide (1.03 g, 5.04 mmol) in dry isopropanol (50 ml) were heated at reflux under a McIntyre head under argon for 5 hr. After cooling, the solution was concentrated in vacuo and the residue treated with dichloromethane (50 ml) and Rochelle salt solution (20 ml). The layers were filtered and separated, and the organic layer washed with water, dried (MgSO4) and concentrated in vacuo to give a cream solid. Recrystallisation from ethyl acetate gave 2-(2-hydroxyethyl)-1-((N-methylimino)-(4-methoxybenzylthio)methyl)-1-(pyrid-3-yl)cyclohexane (0.5 g) as a white solid, m.p. 145°-146° C.;
Reaction SMILES: C(OC([N:6]1[CH2:11][CH2:10][C@H:9]([OH:12])[CH2:8][C@@H:7]1[C:13]1[CH:18]=[CH:17][C:16]([C:19]([CH3:27])([CH3:26])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[CH:15][C:14]=1[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=O)C.[OH-].[K+]>C(O)C.C(O)CO.O>[CH2:29]([O:28][C:14]1[CH:15]=[C:16]([C:19]([CH3:26])([CH3:27])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH:17]=[CH:18][C:13]=1[C@H:7]1[CH2:8][C@@H:9]([OH:12])[CH2:10][CH2:11][NH:6]1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1
Reactant: CCCCCCC(C)(C)c1ccc([C@H]2C[C@@H](O)CCN2C(=O)OCC)c(OCc2ccccc2)c1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Solvent: OCCO
Product: CCCCCCC(C)(C)c1ccc([C@H]2C[C@@H](O)CCN2)c(OCc2ccccc2)c1
Temperature: 185 °C
Yield: 79.7 %

Procedure:
To a solution of 4.62 g (9.59 mmole) of N-ethoxycarbonyl-cis-2-[2-benzyloxy-4-(1,1-dimethylheptyl)phenyl]-4-piperidinol in 5 ml ethanol is added a solution of 4.2 g (75 mmole) of potassium hydroxide in 25 ml ethylene glycol and 4.2 ml water. The resultant mixture is evaporated at reduced pressure to remove ethanol and is then heated to reflux (bath 185° C.). After 24 hours material boiling at 80°-100° C. is removed by distillation, 6 ml ethylene glycol is added and the reaction continued at reflux for 17 hours. After cooling, the mixture is added to 500 ml dichloromethane and 80 ml water. The organic extract is washed with 80 ml saturated sodium chloride, dried over magnesium sulfate and evaporated in vacuo. The resulting crude oil is purified via column chromatography on 300 g of silica gel eluting in 20 ml fractions with 2.5% triethylamine, 2.5% methanol, 95% ethyl ether (fractions 1-109) and 5% triethylamine, 5% methanol, 90% ethyl ether (fractions 110-200). Fractions 138-190 gave 3.13 g (83%) of the title compound.
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[C:9]([C:14]([O:16][CH3:17])=[O:15])[S:10][C:11]=2[CH:12]=[CH2:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>CCO.[Pd]>[CH2:12]([C:11]1[S:10][C:9]([C:14]([O:16][CH3:17])=[O:15])=[CH:8][C:7]=1[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH3:13]
Reactant: C=Cc1sc(C(=O)OC)cc1-c1ccccc1
Agent: [Pd]
Solvent: CCO
Product: CCc1sc(C(=O)OC)cc1-c1ccccc1
Reaction time: 5 h
Yield: 98.1 %

Procedure:
At a normal pressure under a hydrogen gas atmosphere, to a solution of methyl 4-phenyl-5-vinylthiophene-2-carboxylate (250 mg) in EtOH (5 mL) was added Pd/C (50% wet) (50 mg) at 25° C., followed by stirring for 5 hours. The reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure to obtain methyl 5-ethyl-4-phenylthiophene-2-carboxylate (247.3 mg) as a colorless liquid.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH:10]2[O:12][CH2:11]2)=[CH:4][C:3]=1[C:13]([CH3:15])=[O:14].[CH2:16](Br)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([O-])([O-])=O.[K+].[K+].O>CC(C)=O>[CH2:16]([O:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH:10]2[O:12][CH2:11]2)=[CH:4][C:3]=1[C:13]([CH3:15])=[O:14])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: BrCc1ccccc1
Reactant: CC(=O)c1cc(OCC2CO2)ccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: CC(=O)c1cc(OCC2CO2)ccc1OCc1ccccc1

Procedure:
A solution containing 1 g (0.0048 mole) of the product of example 39, 0.856 ml (0.00072 mole) of benzyl bromide and 0.924 g (0.0072 mole) of K2CO3 in 12 ml of acetone are heated for 6 hours under reflux in nitrogen. Then 0.5 ml (0.0042 mole) of benzyl bromide are added and the mixture heated for a further 7 hours. The substance is poured into water, extracted with ethyl acetate and the solvent evaporated off . The reaction product is purified by chromatography, eluting with an 8/2 mixture of hexane and acetone. The required product is obtained, MP: 45-48° C.
Reaction SMILES: [F:1][C:2]([F:31])([C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][N:25]=1)[C:3]1[N:12]=[C:11]([NH:13][C:14]2[CH:18]=[C:17]([CH3:19])[NH:16][N:15]=2)[C:10]2[C:5](=[C:6]([C:20]([O:22]C)=[O:21])[CH:7]=[CH:8][CH:9]=2)[N:4]=1>[OH-].[Na+].O1CCOCC1>[F:31][C:2]([F:1])([C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][N:25]=1)[C:3]1[N:12]=[C:11]([NH:13][C:14]2[CH:18]=[C:17]([CH3:19])[NH:16][N:15]=2)[C:10]2[C:5](=[C:6]([C:20]([OH:22])=[O:21])[CH:7]=[CH:8][CH:9]=2)[N:4]=1
Reactant: COC(=O)c1cccc2c(Nc3cc(C)[nH]n3)nc(C(F)(F)c3ccc(F)cn3)nc12
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: Cc1cc(Nc2nc(C(F)(F)c3ccc(F)cn3)nc3c(C(=O)O)cccc23)n[nH]1
Yield: 93.4 %

Procedure:
A solution of methyl 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazoline-8-carboxylate (26.7 g, 62.3 mmol) in 1:1 3N NaOH/dioxane (200 mL) was stirred at rt for 2 h. The mixture was concentrated under reduced pressure, and the resulting aqueous solution was acidified with 3N HCl. The resulting precipitate was collected by filtration, washed with water, and dried in air to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazoline-8-carboxylic acid as a solid (24.1 g, 93%). LC-MS (ESI) m/z 415.6 (M+H). 1H NMR (500 MHz, DMSO-d6) δ 15.61 (1H, br s), 12.39 (1H, br s), 11.41 (1H, br s), 9.00 (1H, d, J=8.2 Hz), 8.71 (1H, s), 8.59 (1H, d, J=7.36 Hz), 8.09-8.03 (2H, m), 7.83 (1H, t, J=7.86 Hz), 6.07 (1H, s), 2.20 (3H, s).
Reaction SMILES: [Br:1][C:2]([Br:16])=[CH:3][C:4]1[S:5][C:6]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[CH:7][CH:8]=1.C(N(CC)CC)C.[C:24](Cl)(=[O:26])[CH3:25]>O1CCCC1.C(OCC)C>[Br:16][C:2]([Br:1])=[CH:3][C:4]1[S:5][C:6]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:24](=[O:26])[CH3:25])=[CH:11][CH:10]=2)=[CH:7][CH:8]=1
Reactant: CC(=O)Cl
Reactant: Oc1ccc(-c2ccc(C=C(Br)Br)s2)cc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: CC(=O)Oc1ccc(-c2ccc(C=C(Br)Br)s2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 41.4 %

Procedure:
To a stirred mixture of 2-(2,2-dibromoethenyl)-5-(4-hydroxyphenyl)thiophene (1.0 g, 0.003 mole) and triethylamine (1.2 g, 0.08 mole) in tetrahydrofuran (20 mL) was added acetyl chloride (0.44 g, 0.0056 mole). The reaction mixture was stirred at room temperature for approximately 18 hours. The mixture was diluted with diethyl ether and washed in succession with an aqueous 5% sodium hydroxide solution, water, and an aqueous saturated sodium chloride solution. The washed mixture was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure, yielding 0.5 g of 2-(2,2-dibromoethenyl)-5-(4-acetyloxyphenyl)thiophene as a solid (mp 115°-115.5° C.).
Reaction SMILES: CC1C=CC(S(O[CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[C:19]([F:30])[CH:20]=[C:21]([C:22]4[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=4[Cl:29])[C:15]=3[O:14]2)(=O)=O)=CC=1.[CH3:31][NH2:32]>>[Cl:29][C:23]1[CH:24]=[CH:25][C:26]([Cl:28])=[CH:27][C:22]=1[C:21]1[C:15]2[O:14][CH:13]([CH2:12][NH:32][CH3:31])[CH2:17][C:16]=2[CH:18]=[C:19]([F:30])[CH:20]=1
Reactant: Cc1ccc(S(=O)(=O)OCC2Cc3cc(F)cc(-c4cc(Cl)ccc4Cl)c3O2)cc1
Reactant: CN
Product: CNCC1Cc2cc(F)cc(-c3cc(Cl)ccc3Cl)c2O1

Procedure:
The title compound was prepared (0.123 g, 80%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,5-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.2 g, 0.43 mmol) and methylamine (0.133 g, 4.3 mmol). mp 166-168° C.
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:3]=1[C:4]([C:6]1[C:11]([CH3:12])=[CH:10][C:9]([O:13][CH3:14])=[C:8]([O:15]C)[C:7]=1[O:17]C)=[O:5].Br.C(O)(=O)C>O>[Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:3]=1[C:4]([C:6]1[C:11]([CH3:12])=[CH:10][C:9]([O:13][CH3:14])=[C:8]([OH:15])[C:7]=1[OH:17])=[O:5]
Reactant: COc1cc(C)c(C(=O)c2c(Cl)cccc2Cl)c(OC)c1OC
Agent: Br
Solvent: O
Solvent: CC(=O)O
Product: COc1cc(C)c(C(=O)c2c(Cl)cccc2Cl)c(O)c1O
Temperature: 75 °C
Reaction time: 2 h

Procedure:
A mixture of 2,6-dichloro-2',3',4'-trimethoxy-6'-methyl-benzophenone (1.78 g; 5 mmol) hydrobromic acid (7.5 ml; 30% in acetic acid) and acetic acid (7.5 ml) is stirred at 75° C. for 2 hours. Water is added and the mixture extracted with methylenechloride. The extract is washed with waterand shaken with 2N sodium hydroxide. The alcaline solution is acidified with hydrochloric acid, the separated compound dissolved in methylenechloride and the solution washed with water. After evaporation ofthe solvent purification is carried out by chromatography (flash column, filled with 36 g of silicagel; elution with 500 ml of petrolether/ethylacetate (4:1; v/v) and 250 ml of petrolether/ethylacetate(1:1; v/v)). the fraction containing the compound is concentrated, the compound crystallized. The yellow crystals are washed with petrolether andsucked off; 0.64 g (39% y), mp. 182° C.
Reaction SMILES: [NH2:1][C:2]1[N:3]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:4]=[C:5]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]#[CH:13])[N:6]=1.[N:21]([CH2:24][CH2:25][NH:26][C:27]([C:29]1[NH:30][CH:31]=[C:32]([Br:34])[CH:33]=1)=[O:28])=[N+:22]=[N-:23]>>[NH2:1][C:2]1[N:3]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:4]=[C:5]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]2[N:23]=[N:22][N:21]([CH2:24][CH2:25][NH:26][C:27]([C:29]3[NH:30][CH:31]=[C:32]([Br:34])[CH:33]=3)=[O:28])[CH:13]=2)[N:6]=1
Reactant: C#CCCCCCc1cn(C(=O)OC(C)(C)C)c(N)n1
Reactant: [N-]=[N+]=NCCNC(=O)c1cc(Br)c[nH]1
Product: CC(C)(C)OC(=O)n1cc(CCCCCc2cn(CCNC(=O)c3cc(Br)c[nH]3)nn2)nc1N

Procedure:
tert-butyl 2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.104 g, 0.375 mmol) was reacted with N-(2-azidoethyl)-4-bromo-1H-pyrrole-2-carboxamide (0.131 g, 0.375 mmol) following the general click procedure to give tert-butyl 2-amino-4-(5-(1-(2-(4-bromo-1H-pyrrole-2-carboxamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate 1H NMR (300 MHz, CDCl3) δ 11.44 (s, 1H), δ 7.84 (s, 1H), δ 7.28 (s, 1H), δ 6.84 (s, 1H), δ 6.74 (s, 1H), δ 6.46 (s, 1H), δ 4.89 (s, 2H), δ 3.82 (s, 2H), δ 2.57 (s, 2H), δ 2.28 (s, 2H), δ 1.55 (m, 13H), δ 1.29 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 186.8, 161.4, 150.7, 149.3, 148.2, 137.6, 126.3, 122.5, 122.1, 113.1, 100.4, 96.9, 85.4, 49.6, 29.1, 28.7, 28.2, 27.7, 25.5 ppm; HRMS (ESI) calcd for C22H31BrN8O3(M+) 534.1703. found 534.1705, which was subsequently deprotected to give N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-bromo-1H-pyrrole-2-carboxamide hydrochloride (0.129 g, 73% yield). 1H NMR (400 MHz, CD3OD) δ 8.42 (s, 1H), δ 6.93 (s, 1H), δ 6.82 (s, 1H), δ 6.47 (s, 1H), δ 4.76 (s, 2H), δ 3.87 (s, 2H), δ 2.79 (s, δ 2.45 (s, 2H), δ 1.69 (s, δ 1.60 (s, 2H), δ 1.37 (s, 2H) ppm; 13C NMR (100 MHz, CD3OD) δ 161.4, 159.5, 159.1, 147.3, 147.2, 127.6, 125.8, 122.3, 122.1, 112.8, 108.6, 108.5, 96.4, 51.9, 38.9, 28.0, 27.9, 27.6, 24.1, 23.6 ppm; HRMS (ESI) calcd for C17H23BrN8O (M+) 434.1178. found 434.1171.
Reaction SMILES: [C:1]1([C@H:7]([CH2:9][OH:10])[NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[Cl:18][CH2:19][C:20](Cl)=[O:21]>C(Cl)Cl>[Cl:18][CH2:19][C:20]([NH:8][C@H:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH2:9][OH:10])=[O:21]
Reactant: N[C@@H](CO)c1ccccc1
Reactant: O=C(Cl)CCl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(CCl)N[C@@H](CO)c1ccccc1
Reaction time: 0.33 h

Procedure:
To a solution of (R)-2-phenylglycinol (10 g, 73 mmol) and triethylamine (10.2 mL, 73 mmol) in CH2Cl2 (500 mL) at 0° C. was slowly added chloroacetyl chloride (5.8 mL, 73 mmol). After 20 min, the reaction mixture was quenched with saturated aqueous NaHCO3 (150 mL) and extracted with CH2Cl2 (2×250 mL). The combined organic extracts were washed with 10% citric acid, then brine, then dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound. MS: m/z=214 (M+1).
Reaction SMILES: [C:1]([O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24](Cl)=[O:25])=[CH:20][CH:19]=2)=[CH:14][CH:13]=1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C1COCC1.[Cl:32][C@H:33]([CH3:36])[CH2:34][OH:35].C(N(CC)CC)C>CCOCC>[Cl:32][CH:33]([CH3:36])[CH2:34][O:35][C:24]([C:21]1[CH:20]=[CH:19][C:18]([C:15]2[CH:16]=[CH:17][C:12]([O:11][C:1]([O:3][CH2:4][C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)=[O:2])=[CH:13][CH:14]=2)=[CH:23][CH:22]=1)=[O:25]
Reactant: O=C(OCc1ccccc1)Oc1ccc(-c2ccc(C(=O)Cl)cc2)cc1
Reactant: C[C@@H](Cl)CO
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: CC(Cl)COC(=O)c1ccc(-c2ccc(OC(=O)OCc3ccccc3)cc2)cc1
Reaction time: 6 h
Yield: 68 %

Procedure:
61.5 m moles(22.6 g) of 4'-carbobenzoxyoxybiphenyl-4-carboxylic acid chloride was added dropwise into a THF solution of 61.5 m moles(5.2 g) of (R)-(-)-2-chloro-1-propanol and 10 ml of triethylamine, and stirred for 6 hours. After the reaction, the reaction solution was ether extracted. The extrate was purified by column chromatography to obtain 15.9 g of the ester compound [[α]D23 =+22.5°(CHCl3)]. (yield: 61%)
Reaction SMILES: C([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1O)C.Br.OC1C=CC=CC=1C(O)=O.C(O)C.Cl.[H-].[Na+].C(Br)C=C>CN(C=O)C>[C:4]([OH:12])(=[O:3])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: CCOC(=O)c1ccccc1O
Agent: Br
Agent: Cl
Agent: O=C(O)c1ccccc1O
Solvent: C=CCBr
Solvent: CCO
Solvent: CN(C)C=O
Product: O=C(O)c1ccccc1
Reaction time: 4 h

Procedure:
13.6 g of 4-(2-<5-chloro-2-methoxy-benzamido>-ethyl)-2-hydroxy-benzoic acid ethyl ester, M.p. 88°-89° C., (prepared by treatment of 4-(2-aminoethyl)-2-methoxy-benzoic acid. HCl with hydrobromic acid/glacial acetic acid, reaction of the resulting 4-(2-<5-chloro-2-methoxy-benzamido>-ethyl)-2-hydroxy-benzoic acid with ethanol/HCl) were dissolved in 75 ml of DMF and combined with 1.2 g of sodium hydride/80% strength in white oil. The whole was stirred for half an hour, 4.4 g of allyl bromide were added and stirring was continued for 4 hours at 65° C. The dimethylformamide was then eliminated by distillation under reduced pressure, the residue was dissolved in ether, washed with sodium hydroxide solution and water, the ether solution was concentrated by evaporation and the residue was hydrolyzed by heating with 100 ml of 10% sodium hydroxide solution in the presence of a small amount of ethanol. After cooling, the solution was acidified, the substance that had precipitated was re-precipitated from ammonia with the aid of charcoal and then crystallized from dilute methanol. The 2-allyloxy-4-(2-<5-chloro-2-methoxy-benzamido>-ethyl)-benzoic acid so obtained was found to melt at 122°-123° C.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[N:8]=[CH:7][C:6]([C:9]([OH:11])=O)=[CH:5][CH:4]=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.[CH:47]1([NH2:53])[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1>CN(C=O)C>[CH:47]1([NH:53][C:9]([C:6]2[CH:7]=[N:8][C:3]([C:2]([F:1])([F:13])[F:12])=[CH:4][CH:5]=2)=[O:11])[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1
Reactant: O=C(O)c1ccc(C(F)(F)F)nc1
Reactant: NC1CCCCC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NC1CCCCC1)c1ccc(C(F)(F)F)nc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 89.9 %

Procedure:
To 6-(trifluoromethyl)-3-pyridinecarboxylic acid (2.0 g, 10.5 mmol) in DMF (10 mL) was added HATU (4.18 g, 11.0 mmol) followed by Hunig's base (1.83 mL, 10.5 mmol). After 15 minutes, cyclohexylamine (2.40 mL, 20.9 mmol) was added, and the reaction mixture was stirred for 45 minutes at room temperature. The reaction was poured onto water (˜300 mL). After 5 minutes, the resulting aqueous mixture was filtered, and the white solid was air dried for ˜15 minutes to afford the title compound (2.57 g). LC-MS (ES) m/z=273 [M+H]+.
Reaction SMILES: [C:1]([C:6]1[NH:7][C:8]([CH2:19][CH3:20])=[C:9]([CH3:18])[C:10]=1[CH2:11][CH2:12][C:13]([O:15]CC)=[O:14])(OCC)=O.C=O>>[CH3:1][C:6]1[NH:7][C:8]([CH2:19][CH3:20])=[C:9]([CH3:18])[C:10]=1[CH2:11][CH2:12][C:13]([OH:15])=[O:14]
Reactant: CCOC(=O)CCc1c(C(=O)OCC)[nH]c(CC)c1C
Agent: C=O
Product: CCc1[nH]c(C)c(CCC(=O)O)c1C

Procedure:
2-Carbethoxy-3-carbethoxyethyl-4-methyl-5-ethyl pyrrole was reductively alkylated with paraformaldehyde to yield 2,4-dimethyl-3-carboxyethyl-5-ethyl pyrrole. ##STR113##
Reaction SMILES: [NH2:1][C@H:2]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][C:4](=[O:6])[OH:5].[NH:12]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C@H:13]([C:24](ON1C(=O)CCC1=O)=[O:25])[C@@H:14]([CH3:23])[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1COCC1.CN(C=O)C>C(N(CC)CC)C>[NH:12]([C:34]([O:36][C:37]([CH3:38])([CH3:40])[CH3:39])=[O:35])[C@H:13]([C:24]([NH:1][C@H:2]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][C:4](=[O:5])[OH:6])=[O:25])[C@@H:14]([CH3:23])[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: CCOC(=O)[C@@H](N)CC(=O)O
Reactant: C[C@@H](OCc1ccccc1)[C@H](NC(=O)OC(C)(C)C)C(=O)ON1C(=O)CCC1=O
Solvent: CN(C)C=O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCOC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)OC(C)(C)C)[C@@H](C)OCc1ccccc1
Reaction time: 1 h
Yield: 86.6 %

Procedure:
To a suspension consisting of 2.3 g of H-Asp-OEt, 5.8 g of Boc-Thr(Bzl)-OSu, 20 ml of THF and 20 ml of DMF was added 2 ml of triethylamine under ice-cooling condition, and the mixture was stirred for 1 hour, then the pH of the reaction mixture was controlling to about pH 7, and the reaction was continued for 36 hours at room temperature. The reaction mixture was concentrated under reduced pressure, and the thus obtained residue was acidified by adding 1N-hydrochloric acid, then was extracted with ethyl acetate (80 ml×3 times). The organic layer was washed with water, then with a saturated sodium chloride aqueous solution, and dried over anhydrous magnesium sulfate, then concentrated under reduced pressure. Crystallized and recrystallized from diethyl ether-petroleum ether to obtain 5.59 g (yield: 86.6%) of the above-mentioned objective product.