Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1]O.[CH2:3]([S:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[S:17]([NH2:20])(=[O:19])=[O:18])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>C(O)(=O)C>[CH2:3]([S:10]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[S:17]([NH2:20])(=[O:19])=[O:18])=[O:1])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: NS(=O)(=O)c1ccccc1SCc1ccccc1
Reactant: OO
Solvent: CC(=O)O
Product: NS(=O)(=O)c1ccccc1S(=O)Cc1ccccc1
Reaction time: 5 h
Yield: 94.6 %

Procedure:
102 ml of 30% hydrogen peroxide solution are added dropwise at a temperature of +10° C. to a solution in 500 ml of concentrated acetic acid of 219 g of 2-benzylthiophenylsulfonamide obtained in accordance with Example H1. The reaction mixture is then stirred for 5 hours at a temperature of +25° C., in the course of which the product crystallizes out slowly. After the crystals have been separated off, washed with water and dried, 219 g (94.6%) of 2-benzylsulfinylphenylsulfonamide are obtained in the form of colourless crystals having a melting point of +206° to +209° C.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:11][O:12][CH3:13])[C:8]([OH:10])=[O:9])[N:6]=1.[Cl:14]N1C(=O)CCC1=O>CN(C=O)C>[NH2:1][C:2]1[S:3][C:4]([Cl:14])=[C:5]([C:7](=[N:11][O:12][CH3:13])[C:8]([OH:10])=[O:9])[N:6]=1
Reactant: CON=C(C(=O)O)c1csc(N)n1
Reactant: O=C1CCC(=O)N1Cl
Solvent: CN(C)C=O
Product: CON=C(C(=O)O)c1nc(N)sc1Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To 500 mL of DMF were added 50.0 g (250 mmol) of 2-amino-α-(methoxyimino)-4-thiazoleacetic acid and 35 g (260 mmol) of N-chlorosuccinimide. The mixture was stirred at room temperature overnight, after which time mass spectral analysis showed no more starting material to be present. The light brown solution was used without further purification.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[NH:7]1[CH:11]=[CH:10][N:9]=[CH:8]1.[NH2:12]OS(O)(=O)=O.O.[C:19]1([CH3:29])[CH:24]=[CH:23][C:22]([S:25]([OH:28])(=[O:27])=[O:26])=[CH:21][CH:20]=1>O.C(Cl)(Cl)Cl>[C:19]1([CH3:29])[CH:20]=[CH:21][C:22]([S:25]([OH:28])(=[O:26])=[O:27])=[CH:23][CH:24]=1.[NH2:12][N:7]1[CH:11]=[CH:10][N:9]=[CH:8]1
Reactant: NOS(=O)(=O)O
Reactant: c1c[nH]cn1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: ClC(Cl)Cl
Product: Nn1ccnc1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
In 50 ml of water was dissolved 2.76 g (20 mmol) of potassium carbonate and 1.36 g (20 mmol) of imidazole was added thereto. 2.26 g (20 mmol) of hydroxylamine-O-sulfonic acid was added thereto and the mixture was stirred at room temperature for 6 hours. The resulting precipitate was filtered off and the filtrate was concentrated under the reduced pressure. To the concentrate were slowly added 10 ml of chloroform and a solution of 3.8 g (20 mmol) of p-toluenesulfonic acid monohydrate in 10 ml of chloroform. Stirring for 30 min, filtration and drying of the mixture gave 1.74 g of the desired compound(34%).
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.[CH2:12]([OH:16])[CH2:13][CH:14]=[CH2:15]>>[C:6]([C:5]1[CH:10]=[CH:11][C:2]([CH2:15][CH2:14][CH2:13][CH:12]=[O:16])=[CH:3][CH:4]=1)([O:8][CH3:9])=[O:7]
Reactant: COC(=O)c1ccc(Br)cc1
Reactant: C=CCCO
Product: COC(=O)c1ccc(CCCC=O)cc1

Procedure:
condensing methyl p-bromobenzoate with 3-buten-1-ol; extracting the reaction mixture with an organic solvent to obtain an organic extract; decolorizing the organic extract with silica gel, and then removing the organic solvent to give 4-(4-carbomethoxyphenyl) butanal.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:14][C:15]1[CH:16]=[C:17]([N+:22]([O-:24])=[O:23])[CH:18]=[CH:19][C:20]=1F>CS(C)=O.C(OCC)(=O)C>[F:14][C:15]1[CH:16]=[C:17]([N+:22]([O-:24])=[O:23])[CH:18]=[CH:19][C:20]=1[N:1]1[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: c1c[nH]cn1
Reactant: O=[N+]([O-])c1ccc(F)c(F)c1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: O=[N+]([O-])c1ccc(-n2ccnc2)c(F)c1
Temperature: 90 °C
Yield: 92.2 %

Procedure:
A solution of 2.14 g(31.4 mmol) of imidazole and 10.9 g(62.8 mmol) of dibasic potassium phosphate in 190 mL DMSO was treated with 5.25 g(3.7 mL, 50.9 mmol) of 3,4-difluoronitrobenzene followed by warming at 90° C. for 18 h. The solution was diluted with ethyl acetate and was extracted with water. The water layer was back-extracted with ethyl acetate and the combined organic layers were then extracted with water (2×). The organic layer was dried (Na2SO4) and concentrated in vacuo to afford a brown solid. This material was chromatographed over 250 g of 230-400 mesh silica gel, eluting with dichloromethane, and then with 1%(v/v) methanol in dichloromethane, and finally with 2%(v/v) methanol in dichloromethane. These procedures afforded 6.0 g(92%) of the title compound as a bronze colored solid. 1H NMR (CDCl3): δ8.17, 7.96, 7.63, 7.35, 7.26.
Reaction SMILES: C([O:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH:10][CH2:11][CH2:12][S:13][CH2:14][C:15]2[NH:19][CH:18]=[N:17][C:16]=2[CH3:20])[N:5]=1)C>Cl>[CH3:20][C:16]1[N:17]=[CH:18][NH:19][C:15]=1[CH2:14][S:13][CH2:12][CH2:11][NH:10][C:6]1[NH:5][C:4](=[O:3])[CH:9]=[CH:8][CH:7]=1
Reactant: CCOc1cccc(NCCSCc2[nH]cnc2C)n1
Agent: Cl
Product: Cc1nc[nH]c1CSCCNc1cccc(=O)[nH]1
Reaction time: 8 h

Procedure:
A solution of this ethoxypyridine (3.4 g. of base) in 5N hydrochloric acid (100 ml) was heated under reflux for 21/2 hours. The reaction mixture was evaporated to dryness, the residue dissolved in a minimum amount of water, the solution basified with aqueous potassium carbonate, washed once with chloroform, and allowed to stand at 0° overnight. Crystals of 2-[2-(4-methyl-5-imidazolylmethylthio)ethylamino]-(1H)-pyrid-6-one were collected and recrystallised from water to give the pure product, m.p. 85°.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([O:11][CH2:12][CH:13]=[CH2:14])=[O:10])[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Br[C:22]([CH3:31])([CH3:30])[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24].O>CN(C)C=O>[CH2:12]([O:11][C:9]([CH2:8][C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=1)[O:1][C:22]([CH3:31])([CH3:30])[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:10])[CH:13]=[CH2:14]
Reactant: C=CCOC(=O)Cc1cccc(O)c1
Reactant: CC(C)(C)OC(=O)C(C)(C)Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: C=CCOC(=O)Cc1cccc(OC(C)(C)C(=O)OC(C)(C)C)c1
Temperature: 80 °C
Reaction time: 13 h

Procedure:
Allyl 3-hydroxyphenylacetate (2.64 g, 13.7 mmol), potassium carbonate (3.79 g, 27.4 mmol), and tert-butyl 2-bromoisobutyrate (7.65 g, 34.3 mmol) were dissolved in dimethylformamide (5 mL), and the mixture was stirred for 13 hours at 80° C. The reaction mixture was added to water, and the resultant mixture was extracted with diethyl ether. Washing was performed sequentially with water and saturated brine, followed by drying over magnesium sulfate. The mixture was subjected to concentration under reduced pressure and purification by silica gel column chromatography (n-hexane/ethyl acetate=20/1), whereby the target compound was obtained (3.47 g, 10.38 mmol, 75.7%).
Reaction SMILES: I[C:2]1[CH:3]=[C:4]([CH:12]=[CH:13][CH:14]=1)[O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1.[N:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:21](O)=O.[OH2:24].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu]I.CS(C)=O>[N:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[O:5][C:4]1[CH:3]=[C:2]([CH:14]=[CH:13][CH:12]=1)[O:24][C:2]1[CH:14]=[CH:13][C:18]2[C:17]3[CH:10]=[CH:9][CH:8]=[CH:21][C:16]=3[N:15]3[CH:11]=[CH:6][N:7]=[C:20]3[C:19]=2[CH:3]=1
Reactant: O=C(O)c1ccccn1
Reactant: Ic1cccc(Oc2ccccn2)c1
Reactant: O
Agent: [Cu]I
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: c1ccc(Oc2cccc(Oc3ccc4c5ccccc5n5ccnc5c4c3)c2)nc1
Temperature: 100 °C
Yield: 135 %

Procedure:
2-(3-Iodophenoxy)pyridine (0.634 g, 2.13 mmol), imidazo[1,2-]phenanthridin-11-ol (0.5 g, 2.13 mmol), copper(I) iodide (0.122 g, 0.640 mmol), picolinic acid (0.394 g, 3.20 mmol) and potassium phosphate monohydrate (1.72 g, 7.47 mmol) were added to 70 mL DMSO and degassed for 30 minutes with bubbling nitrogen gas. The reaction mixture was heated to 100° C. for 24 h, cooled to room temperature and poured over 100 mL water. The organic materials were extracted with ethyl acetate (3×50 mL) and the combined extracts washed with 1N NaOH (1×50 mL) and saturated ammonium chloride solution (1×50 mL), dried over sodium sulfate and the solvents were removed under reduced pressure. The crude material was purified by column chromatography over silica gel using ethyl acetate/hexanes as eluent to give 11-(3-(pyridin-2-yloxy)phenoxy)imidazo[1,2-f]phenanthridine (0.58 g, 67%) was isolated as a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:31]=[CH:30][C:5]2[NH:6][C:7]([C:12]3[C:13](=[O:29])[C:14]([CH2:24][CH:25]4[CH2:28][CH2:27][CH2:26]4)([CH3:23])[C:15]4[C:20]([C:21]=3[OH:22])=[CH:19][CH:18]=[CH:17][CH:16]=4)=[N:8][S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1.N1C=CC=CC=1.[CH3:38][S:39](Cl)(=[O:41])=[O:40]>ClCCl>[CH:25]1([CH2:24][C:14]2([CH3:23])[C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:21]([OH:22])=[C:12]([C:7]3[NH:6][C:5]4[CH:30]=[CH:31][C:2]([NH:1][S:39]([CH3:38])(=[O:41])=[O:40])=[CH:3][C:4]=4[S:9](=[O:11])(=[O:10])[N:8]=3)[C:13]2=[O:29])[CH2:28][CH2:27][CH2:26]1
Reactant: CC1(CC2CCC2)C(=O)C(C2=NS(=O)(=O)c3cc(N)ccc3N2)=C(O)c2ccccc21
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC1(CC2CCC2)C(=O)C(C2=NS(=O)(=O)c3cc(NS(C)(=O)=O)ccc3N2)=C(O)c2ccccc21
Reaction time: 12 h
Yield: 81.1 %

Procedure:
To a stirring solution of Example 56 (0.080 g, 0.189 mmol) and pyridine (0.122 mL, 1.512 mmol) in dichloromethane was added methanesulfonyl chloride (0.017 mL, 0.227 mmol) dropwise over 5 minutes and the resulting reaction mixture stirred for 12 hours. The solution was concentrated in. vacuo and purified by flash chromatography on SiO2 eluting with a 0-100% ethyl acetate/hexane gradient yielding the title compound (0.079 g, 84% yield) as a light yellow solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.85 (m, 2H) 1.15 (m, 1H) 1.26 (m, 4H) 1.47 (m, 3H) 1.57 (s, 3H) 1.72 (m, 2H) 2.14 (m, 1H) 2.31 (m, 1H) 3.08 (s, 3H) 7.53 (m, 1H) 7.61 (dd, J=11.77, 2.21 Hz, 1H) 8.15 (d, J=7.35 Hz, 1H) 10.25 (s, 1H) 13.83 (s, 1H). MS (ESI+) m/z=516 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:8]=[C:7]([Cl:9])[CH:6]=[CH:5][C:3]=1[NH2:4].Br[CH:11]([CH:31]([CH3:33])[CH3:32])[C:12]([O:14]C(C#N)C1C=CC=C(OC2C=CC=CC=2)C=1)=[O:13]>>[F:1][C:2]1[CH:8]=[C:7]([Cl:9])[CH:6]=[CH:5][C:3]=1[NH:4][C@H:11]([C:12]([OH:14])=[O:13])[CH:31]([CH3:33])[CH3:32]
Reactant: CC(C)C(Br)C(=O)OC(C#N)c1cccc(Oc2ccccc2)c1
Reactant: Nc1ccc(Cl)cc1F
Product: CC(C)[C@H](Nc1ccc(Cl)cc1F)C(=O)O

Procedure:
Following the procedure of Example 6, 2-fluoro-4-chloroaniline is reacted with m-phenoxy-α-cyanobenzyl α-bromoisovalerate to give the m-phenoxy-α-cyanobenzyl ester of N-(2-fluoro-4-chlorophenyl)valine, MS m/e 452 (M+). Alternatively 2-fluoro-4-chloroaniline is reacted with the sodium salt of α-bromo-isovaleric acid to give N-(2-fluoro-4-chlorophenyl)valine, which is then esterified using m-phenoxy-α-cyanobenzyl bromide or mesylate.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[N:7][CH:8]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([NH:17][CH2:18][CH2:19][N:20]([CH2:28][C@@H:29]([C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[CH:39]=3)[O:30][Si](C(C)(C)C)(C)C)C(OC(C)(C)C)=O)[CH:12]=2)[CH:10]=1)=[O:4].Cl.O.[OH-].[Li+].O1CCCC1.O>O1CCOCC1>[Cl:44][C:40]1[CH:39]=[C:38]([C@@H:29]([OH:30])[CH2:28][NH:20][CH2:19][CH2:18][NH:17][C:13]2[CH:12]=[C:11]([C:9]3[CH:10]=[C:5]([C:3]([OH:4])=[O:2])[CH:6]=[N:7][CH:8]=3)[CH:16]=[CH:15][CH:14]=2)[CH:43]=[CH:42][CH:41]=1
Reactant: COC(=O)c1cncc(-c2cccc(NCCN(C[C@H](O[Si](C)(C)C(C)(C)C)c3cccc(Cl)c3)C(=O)OC(C)(C)C)c2)c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: C1COCCO1
Product: O=C(O)c1cncc(-c2cccc(NCCNC[C@H](O)c3cccc(Cl)c3)c2)c1

Procedure:
n.m.r. (CD3OD) δ values include 3.11-3.29 (m, 1 H), 3.58 (t, 2 H), 4.97 (dd, 1 H), 6.76 (d, 1 H), 6.97 (s, 1 H), 6.99 (d, 1 H), 7.26-7.35 (m, 4 H), 7.46 (s, 1 H), 8.51 (s, 1 H), 8.76 (s, 1 H), 9.00 (s, 1 H); from (R)-5-[3-[[2-[[2-(3-chlorophenyl)-2-[[(tert-butyl)dimethylsilyl]oxy]ethyl][(tert-butoxy)carbonyl]amino]ethyl]amino]phenyl]-3-pyridinecarboxylic acid methyl ester (251 mg), 4 N hydrochloric acid in 1,4-dioxane (10 mL) and lithium hydroxide monohydrate (96 mg) in 3:1 tetrahydrofuran-water (20 mL).
Reaction SMILES: [CH:1]1([OH:4])[CH2:3][CH2:2]1.Cl[C:6]1[N:7]=[CH:8][C:9]([C:12]([O:14][CH3:15])=[O:13])=[N:10][CH:11]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[CH:1]1([O:4][C:6]2[N:7]=[CH:8][C:9]([C:12]([O:14][CH3:15])=[O:13])=[N:10][CH:11]=2)[CH2:3][CH2:2]1
Reactant: OC1CC1
Reactant: COC(=O)c1cnc(Cl)cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1cnc(OC2CC2)cn1
Temperature: 25 °C
Reaction time: 15 h
Yield: 54.3 %

Procedure:
Cyclopropanol (542 μL, 8.69 mmol) is added to a suspension of methyl 5-chloropyrazine-2-carboxylate (1.0 g, 5.79 mmol) and potassium carbonate (1.60 g, 11.59 mmol) in dimethylformamide (11.6 mL). The reaction mixture is stirred for 15 hours at room temperature then for 24 hours at 50° C. The reaction is cooled to ambient temperature, diluted with water, and extracted with ethyl acetate (3 times). The organic layers are combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give a brown oil. The crude product is purified by silica gel flash chromatography, eluting with ethyl acetate/hexane (0:100) to ethyl acetate/hexane (35:65) to give the title compound (610 mg, 54%). ES/MS (m/e): 195.0 (M+1).
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[OH:9].[N+:10]([O-])([O-:12])=[O:11].[Na+].S(=O)(=O)(O)O.N([O-])=O.[Na+]>C(Cl)Cl>[N+:10]([C:4]1[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[C:3]=1[OH:9])([O-:12])=[O:11]
Reactant: Oc1cccc(Cl)c1Cl
Reactant: O=[N+]([O-])[O-]
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: ClCCl
Product: O=[N+]([O-])c1ccc(Cl)c(Cl)c1O
Reaction time: 24 h
Yield: 43.3 %

Procedure:
2,3-dichlorophenol (3.26 g, 20 mmol) was dissolved in methylene chloride(40 mL) followed by the addition of sodium nitrate (1.88 g, 22 mmol). The addition of sulfuric acid (20 mL/3M) was then made, followed by addition of a catalytic amount of sodium nitrite. The mixture was allowed to stir. After 24 hours, the reaction mixture was diluted with methylene chloride and extracted with water. The organic layer was dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4% MeOH/CH2Cl2) gave the desired product(1.8 g, 44%). 1H NMR (CD3COCD3): δ 8.04 (d,1H), 7.15 (d, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([CH2:14][NH:15][C:16]([NH:18][CH2:19][CH2:20][CH3:21])=[S:17])[O:13][CH2:12][CH2:11][O:10]2)=[CH:5][CH:4]=1.[I:22][CH3:23]>C(O)C>[IH:22].[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([CH2:14][NH:15][C:16]([S:17][CH3:23])=[N:18][CH2:19][CH2:20][CH3:21])[O:13][CH2:12][CH2:11][O:10]2)=[CH:5][CH:4]=1
Reactant: CCCNC(=S)NCC1(c2ccc(OC)cc2)OCCO1
Reactant: CI
Solvent: CCO
Product: CCCN=C(NCC1(c2ccc(OC)cc2)OCCO1)SC
Product: I
Temperature: 50 °C

Procedure:
A mixture of 5 parts of N-[2-(4-methoxyphenyl)-1,3-dioxolan-2-ylmethyl]-N'-propylthiourea, 3.5 parts of iodomethane and 60 parts of ethanol is stirred and heated for 2 hours at about 50° C. The reaction mixture is evaporated and the oily residue is crystallized from ethyl acetate. The product is filtered off and dried, yielding 5.5 parts of methyl N-[2-(4-methoxyphenyl)-1,3-dioxolan-2-ylmethyl]-N'-propylcarbamimidothioate monohydroiodide; mp. 91.2° C.
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[C:14](/[CH:16]=[CH:17]/[CH:18]([C:23]2[CH:28]=[C:27]([Cl:29])[C:26]([Cl:30])=[C:25]([Cl:31])[CH:24]=2)[C:19]([F:22])([F:21])[F:20])[CH:13]=[CH:12][C:3]=1[CH2:4][NH:5][C:6](=[O:11])[CH2:7][CH2:8]SC.O[O:33][S:34]([O-:36])=O.[K+].[CH3:38]C(C)=O>O>[Cl:1][C:2]1[CH:15]=[C:14](/[CH:16]=[CH:17]/[CH:18]([C:23]2[CH:24]=[C:25]([Cl:31])[C:26]([Cl:30])=[C:27]([Cl:29])[CH:28]=2)[C:19]([F:22])([F:21])[F:20])[CH:13]=[CH:12][C:3]=1[CH2:4][NH:5][C:6](=[O:11])[CH2:7][CH2:8][S:34]([CH3:38])(=[O:36])=[O:33]
Reactant: CSCCC(=O)NCc1ccc(/C=C/C(c2cc(Cl)c(Cl)c(Cl)c2)C(F)(F)F)cc1Cl
Reactant: O=S([O-])OO
Reactant: CC(C)=O
Agent: [K+]
Solvent: O
Product: CS(=O)(=O)CCC(=O)NCc1ccc(/C=C/C(c2cc(Cl)c(Cl)c(Cl)c2)C(F)(F)F)cc1Cl
Yield: 60 %

Procedure:
(E)-N-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-3-(methylthio)propanamide (0.15 g, 0.28 mmol) was treated with oxone (0.175 g, 0.569 mmol) in 1:1 acetone:water (20 mL) for 4 h at ambient temperature. The acetone was evaporated to obtain a white solid (0.095 g, 60%): mp 101-104° C.; 1H NMR (400 MHz, CDCl3) δ 7.41 (m, 4H), 7.24 (m, 1H), 6.53 (d, J=16.0 Hz, 1H), 6.35 (dd, J=16.0, 8.0 Hz, 1H), 6.12 (br s, 1H), 4.53 (m, 2H), 4.10 (m, 1H), 3.42 (m, 2H), 2.91 (s, 3H), 2.78 (m, 2H); ESIMS m/z 559.75 ([M−H]−).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[C:6](=[O:9])[CH2:7][CH2:8][C:2]1=2.[H-].[Na+].C([O:14][C:15](=O)[C:16]1[CH:21]=[C:20]([Cl:22])[CH:19]=[C:18]([Cl:23])[CH:17]=1)C.Cl>C1COCC1.C(OCC)(=O)C.O>[Cl:22][C:20]1[CH:21]=[C:16]([CH:17]=[C:18]([Cl:23])[CH:19]=1)[C:15]([CH:7]1[CH2:8][C:2]2[S:1][CH:5]=[CH:4][C:3]=2[C:6]1=[O:9])=[O:14]
Reactant: O=C1CCc2sccc21
Reactant: CCOC(=O)c1cc(Cl)cc(Cl)c1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: O=C(c1cc(Cl)cc(Cl)c1)C1Cc2sccc2C1=O
Temperature: 100 °C
Yield: 34 %

Procedure:
5,6-Dihydro-cyclopenta[b]thiophen-4-one (2.1 g, 15.0 mmol) in 15 ml of THF was treated with NaH (60 percent, 1.5 g, 36 mmol). After the addition of 3,5-Dichloro-benzoic acid ethyl ester, the reaction mixture was heated at 100° C. for 8 hr. The solution was cooled to room temperature and poured into water. The resulting mixture was acidified with concentrated HCl and was added with ethyl acetate (70 mL). The organic layer was collected, brined, dried over MgSO4(s), and concentrated under reduced pressure. The resultant precipitate was collected and recrystallized from ethanol to provide the corresponding 5-(3,5-Dichloro-benzoyl)-5,6-dihydro-cyclopenta[b]thiophen-4-one (1.5 g, 4.8 mmol) as brown solid in 34% yield.
Reaction SMILES: F[P-](F)(F)(F)(F)F.[CH3:8][N+:9](C)=[C:10](N(C)C)ON1C2N=CC=CC=2N=N1.[C:25]([O:29][C:30]([NH:32][C@@H:33]([CH2:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH:45]([CH3:47])[CH3:46])=[CH:40][CH:39]=1)[C:34](O)=[O:35])=[O:31])([CH3:28])([CH3:27])[CH3:26].C(N(CC)C(C)C)(C)C.CNC.O1CCCC1>CN(C)C=O>[CH3:8][N:9]([CH3:10])[C:34](=[O:35])[C@@H:33]([NH:32][C:30](=[O:31])[O:29][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH:45]([CH3:47])[CH3:46])=[CH:40][CH:39]=1
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: CC(C)Oc1ccc(C[C@H](NC(=O)OC(C)(C)C)C(=O)O)cc1
Agent: CNC
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CC(C)Oc1ccc(C[C@H](NC(=O)OC(C)(C)C)C(=O)N(C)C)cc1
Reaction time: 0.17 h
Yield: 71.3 %

Procedure:
N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (88 mg, 0.23 mmol) was added to a solution of (2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-isopropoxyphenyl)propanoic acid (50 mg, 0.2 mmol) in N,N-dimethylformamide (5 mL) and N,N-diisopropylethylamine (54 uL, 0.31 mmol). The reaction was stirred for 10 min, and the 2.00 M of dimethylamine in tetrahydrofuran (0.4 mL, 0.6 mmol) was added. The reaction was stirred for 2 h. at r.t. and was partitioned between water and ethyl acetate. The organic phase was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give the crude product, (S)-tert-butyl 1-(dimethylamino)-3-(4-isopropoxyphenyl)-1-oxopropan-2-ylcarbamate (50 mg, 90%). Analytical LCMS (M+H-Boc)+: m/z=251.0.
Reaction SMILES: [OH:1][CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]([OH:15])=[O:14])=[CH:5][CH:4]=1.[CH3:16]O>C(OCC)(=O)C.CCCCCC>[OH:1][CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]([O:15][CH3:16])=[O:14])=[CH:5][CH:4]=1
Reactant: O=C(O)c1ccc(CO)c2ccccc12
Reactant: CO
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(CO)c2ccccc12
Yield: 35 %

Procedure:
A mixture of 4-hydroxymethylnaphthoic acid (10 g, 50 mmol), methanol (300 mL), and conc. H2 SO4 (2 mL) was refluxed overnight. The insolubles were filtered off and the filtrate was concentrated. The residue was taken up in ethyl acetate and washed with aqueous NaHCO3 (2×), brine, dried over MgSO4, and concentrated to give a yellow oil. Silica gel column chromatography using ethyl acetate/hexane (1/3) gave the desired product as a yellow oil (3.3 g, 35%).
Reaction SMILES: CC([O-])(C)C.[K+].CC1C=CC(S([CH2:17][N+:18]#[C-])(=O)=O)=CC=1.[CH2:20]([O:27][C:28]1[CH:29]=[C:30]([CH:33]=[CH:34][C:35]=1[O:36][CH3:37])[CH:31]=O)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CO>C1COCC1.O>[CH2:20]([O:27][C:28]1[CH:29]=[C:30]([CH2:31][C:17]#[N:18])[CH:33]=[CH:34][C:35]=1[O:36][CH3:37])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: COc1ccc(C=O)cc1OCc1ccccc1
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: COc1ccc(CC#N)cc1OCc1ccccc1
Reaction time: 0.25 h
Yield: 38 %

Procedure:
To a suspension of t-BuOK (20.15 g, 0.165 mol) in THF (250 mL) was added a solution of TosMIC (16.1 g, 82.6 mmol) in THF (100 mL) at −78° C. The mixture was stirred for 15 minutes, treated with a solution of 3-benzyloxy-4-methoxy-benzaldehyde (10.0 g, 51.9 mmol) in THF (50 mL) dropwise, and continued to stir for 1.5 hours at −78° C. To the cooled reaction mixture was added methanol (50 mL). The mixture was heated at reflux for 30 minutes. Solvent of the reaction mixture was removed to give a crude product, which was dissolved in water (300 mL). The aqueous phase was extracted with EtOAc (100 mL×3). The combined organic layers were dried and evaporated under reduced pressure to give crude product, which was purified by column chromatography (Petroleum Ether/EtOAc 10:1) to afford 2-(3-(benzyloxy)-4-methoxyphenyl)acetonitril (5.0 g, 48%). 1H NMR (300 MHz, CDCl3) δ 7.48-7.33 (m, 5H), 6.89-6.86 (m, 3H), 5.17 (s, 2H), 3.90 (s, 3H), 3.66 (s, 2H). 13C NMR (75 MHz, CDCl3) δ 149.6, 148.6, 136.8, 128.8, 128.8, 128.2, 127.5, 127.5, 122.1, 120.9, 118.2, 113.8, 112.2, 71.2, 56.2, 23.3.
Reaction SMILES: F[P-](F)(F)(F)(F)F.[N:8]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:12]2[CH:13]=CC=C[C:11]=2N=N1.[OH:28][CH:29]1[CH2:32][N:31]([C:33]2[CH:41]=[CH:40][C:36]([C:37]([OH:39])=O)=[CH:35][CH:34]=2)[CH2:30]1.CC(N)C.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[OH:28][CH:29]1[CH2:30][N:31]([C:33]2[CH:34]=[CH:35][C:36]([C:37]([NH:8][CH:12]([CH3:13])[CH3:11])=[O:39])=[CH:40][CH:41]=2)[CH2:32]1
Reactant: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Reactant: O=C(O)c1ccc(N2CC(O)C2)cc1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CC(C)N
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)NC(=O)c1ccc(N2CC(O)C2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 94.3 %

Procedure:
Benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (4.64 g, 10.5 mmol, Aldrich: Cat. #226084) was added to a mixture of 4-(3-hydroxyazetidin-1-yl)benzoic acid (1.93 g, 10.0 mmol), 2-propanamine (4.26 mL, 50.0 mmol) and N,N-diisopropylethylamine (3.88 g, 30.0 mmol) in dichloromethylene (10 mL). The mixture was stirred at room temperature for 2 hours, and diluted with DCM. The mixture was washed with aqueous NaHCO3 and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexane (gradient: 0-50%) to afford the desired product (2.21 g, 94.3%). LCMS (M+H)+: m/z=235.1.