Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1](NC(C)C)(C)C.C([Li])CCC.[CH3:13][O:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=[O:20])=[C:17]([CH3:24])[CH:16]=1.C=O>C1COCC1.O>[CH3:13][O:14][C:15]1[CH:16]=[C:17]2[C:18](=[CH:22][CH:23]=1)[C:19](=[O:21])[O:20][CH2:1][CH2:24]2
Reactant: COc1ccc(C(=O)O)c(C)c1
Reactant: CC(C)NC(C)C
Agent: C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc2c(c1)CCOC2=O
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a solution of diisopropylamine (33.5 ml) in dry THF (190 ml) was added dropwise, at −78° C., n-butyllithium (1.6 M solution in hexane, 145.9 ml). Subsequently, the reaction mixture was warmed to room temperature for 5 minutes and then cooled again to −78° C., and a solution of 4-methoxy-2-methylbenzoic acid (10 g) in dry THF (210 ml) was added dropwise. After stirring at this temperature for 10 minutes, paraformaldehyde (7 g) was added. The reaction mixture was then allowed to come to room temperature and stirred at this temperature for 4 hours. The reaction mixture was admixed with water, then the THF was removed under reduced pressure and then the aqueous phase was extracted with diethyl ether. The aqueous phase was acidified with conc. HCl, and the resulting precipitate was filtered off and washed repeatedly with water. The product was thus obtained with the molecular weight of 178.06 (C10H10O3); MS (ESI): 179 (M+H+).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][S:3][C:2]1=[C:6]([C:13]([O:15]C(=O)C(C)(C)C)=O)[C:7]([O:9][CH:10]([CH3:12])[CH3:11])=[O:8].[CH:22]([NH2:25])([CH3:24])[CH3:23]>C(Cl)Cl>[S:3]1[CH:4]=[CH:5][S:1][C:2]1=[C:6]([C:13](=[O:15])[NH:25][CH:22]([CH3:24])[CH3:23])[C:7]([O:9][CH:10]([CH3:11])[CH3:12])=[O:8]
Reactant: CC(C)N
Reactant: CC(C)OC(=O)C(C(=O)OC(=O)C(C)(C)C)=C1SC=CS1
Solvent: ClCCl
Product: CC(C)NC(=O)C(C(=O)OC(C)C)=C1SC=CS1
Temperature: 25 °C
Reaction time: 5 h
Yield: 82.1 %

Procedure:
A mixture of isopropyl 2-(1,3-dithiol-2-ylidene)-2-(pivaloyloxycarbonyl)acetate (13.2g), isopropylamine (2.6 g) and methylene chloride (60 ml) was stirred at room temperature for 5 hrs. The reaction mixture was washed with aqueous sodium hydroxide solution and water. After removal of solvent the residue was distilled to give the titled compound (9.43 g, 66%) as a yellow oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9][CH2:10][CH2:11][NH:12][C:13](=[O:16])[O:14][CH3:15])=[CH:5][CH:4]=1.C=O.[C:19]([O-])([O-])=[O:20].[Cs+].[Cs+]>C1COCC1>[OH:20][CH2:19][N:12]([CH2:11][CH2:10][S:9][C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[C:13](=[O:16])[O:14][CH3:15]
Reactant: O=C([O-])[O-]
Reactant: COC(=O)NCCSc1ccc(OC)cc1
Agent: C=O
Agent: [Cs+]
Solvent: C1CCOC1
Product: COC(=O)N(CO)CCSc1ccc(OC)cc1
Temperature: 70 °C
Reaction time: 3 h

Procedure:
A mixture of compound 7 (2.0 g), paraformaldehyde (1.5 g), Cs2CO3 (1.2 eq.) in THF (50 mL) was stirred at 70° C. for 3 hours. Filtration and concentration of the solvent gave the title product 9 as pure white solid. Yield: 2.2 g, 98%.
Reaction SMILES: C(=O)([O-])O.[Na+].CC(O[CH2:10][C:11]1[CH2:20][S:19][C@@H:14]2[C@H:15]([NH2:18])[C:16](=[O:17])[N:13]2[C:12]=1[C:21]([OH:23])=[O:22])=O.[SH:24][C:25]1[S:29][CH:28]=[N:27][C:26]=1[C:30]([O:32][CH3:33])=[O:31]>O>[NH2:18][CH:15]1[C:16](=[O:17])[N:13]2[C:12]([C:21]([OH:23])=[O:22])=[C:11]([CH2:10][S:24][C:25]3[S:29][CH:28]=[N:27][C:26]=3[C:30]([O:32][CH3:33])=[O:31])[CH2:20][S:19][C@H:14]12
Reactant: COC(=O)c1ncsc1S
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](N)[C@H]2SC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: COC(=O)c1ncsc1SCC1=C(C(=O)O)N2C(=O)C(N)[C@H]2SC1
Reaction time: 5 h
Yield: 67.1 %

Procedure:
1.7 g (2 eq.) of sodium hydrogencarbonate were added to a suspension of 2.7 g (10 mmol) of 7-ACS in 20 ml of water and 1.7 g (10 mmol) of methyl 5mercapthothiazole-4carboxylate (Preparation Example 5) were added after dissolution. The solution was then kept at 65° C. for 5 h and extracted twice with ethyl acetate after cooling. The aqueous phase was then acidified to pH 3 and the precipitated product was filtered off with suction and dried. 2.6 g (68%) of the desired title compound were obtained.
Reaction SMILES: C([O:3][C:4](=[O:35])[C:5]1[CH:10]=[CH:9][C:8]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]([CH3:33])[C:20]([OH:32])([C:25]3[CH:30]=[CH:29][N:28]=[C:27]([CH3:31])[CH:26]=3)[C:21]([F:24])([F:23])[F:22])=[C:15]([Cl:34])[CH:14]=2)=[CH:7][CH:6]=1)C.[Li+].[OH-]>C1COCC1.CO>[Cl:34][C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][C:16]=1[CH:19]([CH3:33])[C:20]([OH:32])([C:25]1[CH:30]=[CH:29][N:28]=[C:27]([CH3:31])[CH:26]=1)[C:21]([F:23])([F:24])[F:22])[O:12][CH2:11][C:8]1[CH:7]=[CH:6][C:5]([C:4]([OH:35])=[O:3])=[CH:10][CH:9]=1
Reactant: CCOC(=O)c1ccc(COc2ccc(C(C)C(O)(c3ccnc(C)c3)C(F)(F)F)c(Cl)c2)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: Cc1cc(C(O)(C(C)c2ccc(OCc3ccc(C(=O)O)cc3)cc2Cl)C(F)(F)F)ccn1
Temperature: 50 °C
Reaction time: 0.25 h

Procedure:
4-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(2-methyl-pyridin-4-yl)-propyl]-phenoxymethyl}-benzoic acid ethyl ester (250 mg) was dissolved in THF/methanol=5/1 (6 mL) followed by the addition of aqueous LiOH solution (1.0M, 0.54 mL). The mixture was heated to 50° C. for 3.5 hours. The reaction was cooled and concentrated in vacuo. The residue was dissolved in water (5 mL) and aqueous HCl solution (1.0M, 0.54 mL) was added. The mixture was stirred at r.t. for 15 minutes and then at 0° C. for 1 hour. The resulting precipitate was filtered off and washed with cold water. The residual water was removed by co-evaporation with toluene. The resulting solid was dried in vacuo. The title compound was obtained as a colorless solid (220 mg, 93%). MS (m/e)=480.1 [MH+].
Reaction SMILES: [CH3:1][C@H:2]([O:6][C:7]1[N:15]=[C:14]2[C:10]([N:11]=[C:12]([O:22][CH3:23])[N:13]2C2CCCCO2)=[C:9]([NH2:24])[N:8]=1)[CH2:3][CH2:4][CH3:5].[F:25][C:26]([F:31])([F:30])[C:27]([OH:29])=[O:28]>CO>[F:25][C:26]([F:31])([F:30])[C:27]([OH:29])=[O:28].[CH3:1][C@H:2]([O:6][C:7]1[NH:8][C:9]([NH2:24])=[C:10]2[C:14]([N:15]=1)=[N:13][C:12]([O:22][CH3:23])=[N:11]2)[CH2:3][CH2:4][CH3:5]
Reactant: CCC[C@H](C)Oc1nc(N)c2nc(OC)n(C3CCCCO3)c2n1
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Product: CCC[C@H](C)Oc1nc2nc(OC)nc-2c(N)[nH]1
Temperature: 20 °C
Reaction time: 72 h
Yield: 81.1 %

Procedure:
2-{[(1S)-1-methylbutyl]oxy}-8-(methyloxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (6 g, 17.89 mmol) was dissolved in methanol (50 ml). Trifluoroacetic acid (20.67 ml, 268 mmol) was added dropwise, and the mixture stirred at 20° C. for 72 hours under an atmosphere of nitrogen. The solvent was removed in vacuo, and the resulting solid was washed with ethyl acetate and filtered. The filtrate was stripped and the residue washed with ethyl acetate. The combined solid residues were dried in the vacuum oven for 2 hours to give the title compound as an off-white solid (5.3 g).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:15]([F:16])=[CH:14][C:12]([NH2:13])=[C:11]([F:17])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH:18]1([C:21]([NH2:23])=[O:22])[CH2:20][CH2:19]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:13][C:12]1[C:11]([F:17])=[CH:10][C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:23][C:21]([CH:18]3[CH2:20][CH2:19]3)=[O:22])[CH:7]=2)=[C:15]([F:16])[CH:14]=1
Reactant: NC(=O)C1CC1
Reactant: Nc1cc(F)c(Oc2ccnc(Cl)c2)cc1F
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: Nc1cc(F)c(Oc2ccnc(NC(=O)C3CC3)c2)cc1F
Temperature: 25 °C
Yield: 47 %

Procedure:
A mixture of Example A2 (100 mg, 0.39 mmol), cyclopropanecarboxamide (100 mg, 1.17 mmol), Xantphos [4,5-bis(diphenylphosphino)-9,9-dimethylxanthene] (23 mg, 0.039 mmol), Cs2CO3 (254 mg, 0.78 mmol) and Pd2(dba)3 (22 mg, 0.023 mmol) in dioxane (10 mL) was heated at 100° C. for 2 hours. The mixture was cooled to RT and filtered to remove inorganic salts. The filtrate was concentrated under vacuum. The residue was diluted with water (100 mL) and extracted with EtOAc (3×100 mL). The combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel chromatography to afford N-(4-(4-amino-2,5-difluorophenoxy)pyridin-2-yl)cyclopropanecarboxamide (56 mg, 47% yield). MS (ESI): m/z 306.1 (M+H+).
Reaction SMILES: [F:1][C:2]1[N:7]=[C:6]([C:8]2[N:17]=[C:11]3[CH:12]=[C:13]([NH2:16])[CH:14]=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:4][CH:3]=1.[CH2:18]([O:20][C:21]([C:23]1[CH:24]=[N:25][N:26]([CH3:31])[C:27]=1[C:28](O)=[O:29])=[O:22])[CH3:19]>>[CH2:18]([O:20][C:21]([C:23]1[CH:24]=[N:25][N:26]([CH3:31])[C:27]=1[C:28](=[O:29])[NH:16][C:13]1[CH:14]=[CH:15][N:10]2[N:9]=[C:8]([C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([F:1])[N:7]=3)[N:17]=[C:11]2[CH:12]=1)=[O:22])[CH3:19]
Reactant: CCOC(=O)c1cnn(C)c1C(=O)O
Reactant: Nc1ccn2nc(-c3cccc(F)n3)nc2c1
Product: CCOC(=O)c1cnn(C)c1C(=O)Nc1ccn2nc(-c3cccc(F)n3)nc2c1
Yield: 40.4 %

Procedure:
The product was prepared in the same manner as described in example 44d using 2-(6-fluoropyridin-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-7-amine (350 mg, 1.53 mmol) and 4-(ethoxycarbonyl)-1-methyl-1H-pyrazole-5-carboxylic acid (363 mg, 1.83 mmol) as starting materials. The reaction affords 5-[2-(6-fluoro-pyridin-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl]-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (253.1 mg, 40.5%) as white solid. mp.: 290° C., MS: m/z=410.0 (M+H+).
Reaction SMILES: COC1C=C(OC)C=CC=1C[NH:6][C:7]1[S:11][N:10]=[CH:9][N:8]=1.[Li].Cl[S:20]([C:23]1[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][C:24]=1[F:32])(=[O:22])=[O:21]>C1COCC1.[Cl-].[Na+].O>[F:32][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:23]=1[S:20]([NH:6][C:7]1[S:11][N:10]=[CH:9][N:8]=1)(=[O:22])=[O:21])[C:27]([OH:29])=[O:28]
Reactant: O=C(O)c1ccc(S(=O)(=O)Cl)c(F)c1
Reactant: COc1ccc(CNc2ncns2)c(OC)c1
Agent: [Cl-]
Agent: [Li]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)c1ccc(S(=O)(=O)Nc2ncns2)c(F)c1
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 15.7 %

Procedure:
N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (Preparation 26, 500 mg, 2.1 mmol, 1.0 eq) was dissolved in THF (10 ml) and cooled to −78° C. 1,1,1,3,3,3-Hexanemethyldisilazane lithium salt (LiHMDS, 1M in THF, 4.2 ml, 4.19 mmol, 2.0 eq) was added dropwise and the reaction mixture stirred for a further 10 minutes. A solution of 4-(chlorosulfonyl)-3-fluorobenzoic acid (Preparation 9, 500 mg, 2.1 mmol, 1 eq) in THF (3 ml) was added dropwise and the reaction mixture stirred at −78° C. for 1 hour then at room temperature for 18 hours. The reaction mixture was diluted with brine, extracted into ethyl acetate, dried over sodium sulphate, filtered and evaporated in vacuo. The crude material was passed through a SCX cartridge to remove remaining amine. The material was redissolved in 4M HCl in dioxane and stirred at room temperature for 2 hours. The resulting precipitate was collected by filtration and washed with diethylether to yield the title compound (100 mg, 0.33 mmol, 16%).
Reaction SMILES: [CH3:1][C:2]1[C:3]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:4][NH:5][CH:6]=1.C1C(=O)N([Br:19])C(=O)C1>C1COCC1>[Br:19][C:6]1[NH:5][CH:4]=[C:3]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[C:2]=1[CH3:1]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)c1c[nH]cc1C
Solvent: C1CCOC1
Product: CCOC(=O)c1c[nH]c(Br)c1C
Temperature: -30 °C
Reaction time: 1 h
Yield: 86 %

Procedure:
To a solution of ethyl 4-methyl-3-pyrrolecarboxylate (1.57 g, 10 mmol) in anhyd THF (30 mL) cooled to −78° C. was added NBS (1.9 g, 10 mmol). After stirring 1 h at −30° C., the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography, eluting with EtOAc-Hex (0:100 to 30:70), to yield ethyl 5-bromo-4-methyl-1H-pyrrole-3-carboxylate (2.0, 86%) as a white solid. 1H-NMR (CDCl3): δ 8.54 (1H, brs), 7.38 (1H, d), 4.27 (2H, q), 2.24 (3H, s), 1.33 (3H, t).
Reaction SMILES: [C:1]([OH:24])(=[O:23])[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][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[OH-].[Na+:26]>C(O)C>[C:1]([O-:24])(=[O:23])[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][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[Na+:26]
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCCCCCCCCCCCCCCCCCCCCC(=O)[O-]

Procedure:
8.5 g of behenic acid were dissolved under heating in 150 ml of ethanol with stirring and to the solution was added dropwise a 100 ml aqueous sodium hydroxide solution containing 1 g of sodium hydroxide under heating with stirring to give sodium behenate. Then, 200 ml of hot water were added thereto and the sodium behenate was completely dissolved with continuation of heeating and stirring. Subsequently, an aqueous nitric acid acidic solution containing silver nitrate in an amount equimolar to the behenic acid used was added dropwise under heating with stirring to convert the sodium behenate dissolved to insoluble silver behenate. The silver behenate thus obtained was recovered by filtration and repeatedly washed with hot water and hot ethanol, followed by drying.
Reaction SMILES: [C:1]1([N:7]2[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:10]([CH2:18][C:19]([OH:21])=[O:20])[C:9]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:28]O.S(=O)(=O)(O)O>C(Cl)(Cl)(Cl)Cl>[CH3:28][O:20][C:19](=[O:21])[CH2:18][C:10]1[C:9]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)=[N:8][N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=C(O)Cc1c(-c2ccccc2)nn(-c2ccccc2)c1-c1ccccc1
Reactant: CO
Agent: O=S(=O)(O)O
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)Cc1c(-c2ccccc2)nn(-c2ccccc2)c1-c1ccccc1
Yield: 91 %

Procedure:
15 grams 1,3,5-triphenyl-pyrazol-4-acetic acid, 50 milliliters methanol, 40 milliliters carbon tetrachloride and 0.64 gram concentrated sulfuric acid were mixed and the mixture heated to the boiling temperature under reflux for 11 hours. The cooled reaction mixture was then extracted, first with sodium carbonate solution and thereafter with water. The organic phase was then dried and evaporated. The residue was recrystallized from a mixture of methanol and water. 14.2 grams 1,3,5-triphenyl-pyrazol-4-acetic acid-methyl ester, melting at 80.5°-81.5° C., were obtained, representing a yield of 91%.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[OH:9])=[CH:4][CH:3]=1.[CH3:23][O:24][C:25](=[O:39])[C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35]Cl)=[C:28]([O:37][CH3:38])[CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+]>CN(C)C=O>[CH3:23][O:24][C:25](=[O:39])[C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35][N:13]2[CH2:12][CH2:11][CH:10]([C:8]([C:16]3[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=3)([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[OH:9])[CH2:15][CH2:14]2)=[C:28]([O:37][CH3:38])[CH:27]=1
Reactant: COC(=O)c1ccc(OCCCCl)c(OC)c1
Reactant: OC(c1ccc(F)cc1)(c1ccc(F)cc1)C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(OCCCN2CCC(C(O)(c3ccc(F)cc3)c3ccc(F)cc3)CC2)c(OC)c1

Procedure:
A mixture of α,α-bis(4-fluorophenyl)-4-piperidinemethanol (6.0 g, 0.02 mole), 4-(3-chloropropoxy)-3-methoxybenzoic acid methyl ester (5.4 g, 0.021 mole), anhydrous sodium carbonate (7.4 g, 0.07 mole), and potassium iodide (0.3 g) in 150 ml of dimethylformamide was heated on a steam bath for about 20 hr. The mixture was concentrated under reduced pressure, and the residue was partitioned between water and organic solvent (benzene). The organic layer was washed with water and brine and dried over sodium sulfate and eventually crystallized from 2-propanol to give the title compound as a white solid, mp 131°-132.5° C. (2-propanol).
Reaction SMILES: FC(F)(F)C(O)=O.[OH:8][C:9]1[CH:38]=[CH:37][C:36]([C:39]2[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=2)=[CH:35][C:10]=1[C:11]([NH:13][C:14]1[CH:26]=[C:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[O:33][CH3:34])[CH:24]=[CH:23][C:15]=1[C:16]([O:18]C(C)(C)C)=[O:17])=[O:12]>>[OH:8][C:9]1[CH:38]=[CH:37][C:36]([C:39]2[CH:40]=[CH:41][N:42]=[CH:43][CH:44]=2)=[CH:35][C:10]=1[C:11]([NH:13][C:14]1[CH:26]=[C:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[O:33][CH3:34])[CH:24]=[CH:23][C:15]=1[C:16]([OH:18])=[O:17])=[O:12]
Reactant: COc1ccccc1-c1ccc(C(=O)OC(C)(C)C)c(NC(=O)c2cc(-c3ccncc3)ccc2O)c1
Solvent: O=C(O)C(F)(F)F
Product: COc1ccccc1-c1ccc(C(=O)O)c(NC(=O)c2cc(-c3ccncc3)ccc2O)c1

Procedure:
A trifluoroacetic acid (4.0 mL) solution of the obtained tert-butyl 2-(2-hydroxy-5-(pyridin-4-yl)benzamido)-4-(2-methoxyphenyl)benzoate was stirred at room temperature for 1 hour and 30 minutes. The solvent was evaporated under reduced pressure, and toluene was added to the residue. The solvent was evaporated under reduced pressure, and diisopropyl ether was added to the obtained residue. The solid substance was collected by filtration to obtain 0.027 g of 2-(2-hydroxy-5-(pyridin-4-yl)benzamido)-4-(2-methoxyphenyl)benzoic acid as a light yellow solid.
Reaction SMILES: C(OC(=O)[CH:5]([S:7][C:8]1[S:12][C:11]([NH:13][C:14]([N:16]([CH:23]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)=[O:15])=[N:10][CH:9]=1)C)C.C1(NC2CCCCC2)CCCCCC1.NC1SC=NC=1.C([O:53][C:54](=[O:57])[CH2:55]S)C>>[CH:23]1([N:16]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[C:14](=[O:15])[NH:13][C:11]2[S:12][C:8]([S:7][CH2:5][CH2:55][C:54]([OH:53])=[O:57])=[CH:9][N:10]=2)[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]1
Reactant: CCOC(=O)C(C)Sc1cnc(NC(=O)N(C2CCCCCC2)C2CCCCC2)s1
Reactant: CCOC(=O)CS
Agent: C1CCCC(NC2CCCCC2)CC1
Agent: Nc1cncs1
Product: O=C(O)CCSc1cnc(NC(=O)N(C2CCCCCC2)C2CCCCC2)s1

Procedure:
[2-(3-Cycloheptyl-3-cyclohexyl-ureido)-thiazol-5-ylsulfanyl]-propionic acid ethyl ester pre-pared as described in general procedure (A) using cycloheptyl-cyclohexylamine and 5-aminothiazole-2-mercaptoacetic acid ethyl ester. Hydrolysis using general procedure (F) gave the title compound
Reaction SMILES: C1C(CS(N)(=O)=O)CNC1.C([O:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[CH2:20])=[CH:17][CH:16]=1)(=O)C>>[CH:19]([C:18]1[CH:21]=[CH:22][C:15]([OH:14])=[CH:16][CH:17]=1)=[CH2:20]
Reactant: C=Cc1ccc(OC(C)=O)cc1
Agent: NS(=O)(=O)CC1CCNC1
Product: C=Cc1ccc(O)cc1

Procedure:
The procedure of Example 6 is followed starting with the copolymer of PMSA and p-acetoxystyrene (10.20 g) produced in Example 5, to obtain a copolymer of PMS with p-vinylphenol containing free mercapto and hydroxyl groups.
Reaction SMILES: [OH:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][CH2:7][C:8]([C:10]2[C:11](=[CH:13][C:14](=[CH:16][C:17]=2[OH:18])[OH:15])[OH:12])=[O:9])=[CH:4][CH:3]=1>C(O)C.[Pd]>[OH:1][CH:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][C:8]([C:10]2[C:17](=[CH:16][C:14](=[CH:13][C:11]=2[OH:12])[OH:15])[OH:18])=[O:9])=[CH:19][CH2:20]1
Reactant: O=C(CCc1ccc(O)cc1)c1c(O)cc(O)cc1O
Agent: [Pd]
Solvent: CCO
Product: O=C(CCC1=CCC(O)C=C1)c1c(O)cc(O)cc1O
Yield: 90 %

Procedure:
A solution of phloretin (1 g) in 80% ethanol (20 ml) containing 50 mg of 5% palladium on carbon is stirred under a hydrogen atmosphere. After 6 hrs the mixture is filtered, and the filtrate is concentrated under vacuo to give dihydrophloretin in about 90% yield.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.Br[C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[O:19][CH2:18][CH2:17][CH2:16]2>>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[O:19][CH2:18][CH2:17][CH2:16]3)[CH:3]=1
Reactant: Brc1ccc2c(c1)CCCO2
Reactant: Clc1ccnc2ccccc12
Product: Clc1cc(-c2ccc3c(c2)CCCO3)nc2ccccc12

Procedure:
The title compound, MS: m/e=295 (M+), was prepared from 4-chloro-quinoline and 6-bromo-chroman.
Reaction SMILES: [CH3:1][C:2](C)=CCBr.[CH2:7]1[O:15][C:14]2[CH:13]=[CH:12][C:11](O)=[CH:10][C:9]=2O1.CCCCC>[Cl-].[Cl-].[Zn+2].C1C=CC=CC=1>[O:15]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:2][CH2:1][CH2:7]1
Reactant: Oc1ccc2c(c1)OCO2
Reactant: CC(C)=CCBr
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CCCCC
Solvent: c1ccccc1
Product: c1ccc2c(c1)CCCO2
Yield: 190.4 %

Procedure:
5.1 gm of 3-methyl-1-bromo-2-butene was combined with 4 gm of 3,4-methylenedioxyphenol and dissolved in 50 ml. of pentane and 50 ml. benzene. 2 gm of anhydrous ZnCl2 was added and the reaction mixture refluxed for 1 hour and cooled. The mixture was extracted with ether and washed successively with 100 ml. of water, 100 ml. 5% sodium carbonate and 100 ml. of saturated salt solution. After drying the extract over anhydrous sodium sulfate, the solvent was removed in vacuo leaving 7.4 g of crude chromane. The crude material was fractionated on a column of Florisil and eluted with increasing concentrations of ether in petroleum ether to yield 4.5 g of pure chromane.
Reaction SMILES: ClS([N:5]=C=O)(=O)=O.[Br:8][C:9]1[N:10]([O:25][CH3:26])[C:11]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[C:12]([Br:17])[C:13]=1[C:14](O)=O.CN(C)C=O>C(#N)C.O.C(Cl)Cl.C(OCC)(=O)C>[Br:8][C:9]1[N:10]([O:25][CH3:26])[C:11]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[C:12]([Br:17])[C:13]=1[C:14]#[N:5]
Reactant: COn1c(Br)c(C(=O)O)c(Br)c1-c1ccc(Cl)cc1
Reactant: O=C=NS(=O)(=O)Cl
Solvent: CCOC(C)=O
Solvent: O
Solvent: ClCCl
Product: COn1c(Br)c(C#N)c(Br)c1-c1ccc(Cl)cc1
Temperature: 5 °C
Reaction time: 3 h
Yield: 12 %

Procedure:
Chlorosulfonyl isocyanate (1.66 g, 0.0117 mol) is added to a 5° C. stirred solution of 2,4-dibromo-5-(p-chlorophenyl)-1-methoxypyrrole-3-carboxylic acid (2.0 g, 0.0049 mol) in acetonitrile. The solution is heated to 45°-50° C. for 2 hours, acetonitrile is added, cooled to 5° C. and dimethylformamide (1.9 mL, 0.0244 mol) is added. The reaction mixture is stirred at room temperature for 3 hours, diluted with water and extracted with chloroform. The combined chloroform extracts are washed sequentially with water and saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate and concentrated in vacuo to give a yellow solid. Chromatography using silica gel, methylene chloride and 3% ethyl acetate in methylene chloride as eluent yields the title compound as an off-white solid (0.23 g, 12%), mp 195°-197° C.