Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@H:2]([C:18]([NH:20][C@H:21]([C:23]([O:25]C)=[O:24])[CH3:22])=[O:19])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:6][CH:5]=1.[Li+].[OH-]>C1COCC1>[NH:1]([C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])[C@H:2]([C:18]([NH:20][C@H:21]([C:23]([OH:25])=[O:24])[CH3:22])=[O:19])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:8][CH:9]=1
Reactant: COC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(OCc2ccccc2)cc1)NC(=O)OC(C)(C)C
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: C[C@H](NC(=O)[C@H](Cc1ccc(OCc2ccccc2)cc1)NC(=O)OC(C)(C)C)C(=O)O

Procedure:
Same procedure as above with N-Boc-Tyr(Bn)-Ala-OMe (1.55 g, 3.39 mmol), aqueous LiOH (1 M, 4 mL, 4 mmol) in THF (4 mL). A white solid was obtained (1.25 g, 83%) which was used in the next step without further purification. 1H NMR (200 MHz, CDCl3) δ 1.41 (s large, 12H, CH3, (CH3)3), 3.01 (m, 2H, CH2), 4.38 (m, 1H, CHα), 4.53 (m, 1H, CHα), 5.04 (s, 2H, CH2 (Bn)), 5.16 (broad s, 1H, NHBoc), 6.68 (m, 1H, NH amide), 6.91 (d, J=8.6 Hz, 2 aromatic H), 7.12 (d, J=8.6 Hz, 2 aromatic H), 7.33-7.44 (m, 5 aromatic H). 13C NMR (75 MHz, CDCl3) δ 18 (CH3), 28.2 ((CH3)3), 37.5 (CH2 Tyr), 48.2 (CHα Ala), 55.6 (CHα Tyr), 70 (CH2 (Bn)), 80.5 (C(CH3)3), 115, 127.4, 128, 128.5, 128.6, 130.4, 137 (11 aromatic C), 155.8, 157.8 (Car-O, CO carbamate), 171.6, 175.5 (CO acid, CO amide).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[CH:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[CH:15][CH:14]=1.[CH2:23]([N:25]([CH2:28]C)[CH2:26]C)C>C1COCC1.ClCCl>[CH3:23][N:25]([CH:28]=[N:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[CH:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[CH:15][CH:14]=1)[CH3:26]
Reactant: Nc1ccc2c(c1)C(=Cc1ccnc3ccccc13)C(=O)N2
Reactant: CCN(CC)CC
Solvent: C1CCOC1
Solvent: ClCCl
Product: CN(C)C=Nc1ccc2c(c1)C(=Cc1ccnc3ccccc13)C(=O)N2
Reaction time: 1 h
Yield: 60 %

Procedure:
To a solution of 5-amino-3-(4-quinolylmethylen)-2-oxindole (287 mg, 1 mmol) and triethylamine (121 mg, 1.2 mmol) in THF (20 ml) was added portionwise at, 0° C. chlorodimethyl-formimminium chloride (154 mg, 1.2 mmol) and the stirring was continued at room temperature for 1 h. Then the reaction mixture was diluted with dichloromethane, the organic layer washed with brine, dried over sodium sulfate and concentrated under vacuum. The residue was chromatographed on silica gel (eluant ethyl acetate/methanol 1:1) to give pure title compound in 60% yield (205 mg).
Reaction SMILES: [Br:1][C:2]1[N:3]=[CH:4][NH:5][CH:6]=1.O1CCCC1.CS([C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][N:17]=1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[Br:1][C:2]1[N:3]=[CH:4][N:5]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][N:17]=2)[CH:6]=1
Reactant: Brc1c[nH]cn1
Reactant: CS(=O)(=O)c1ccc(C(F)(F)F)cn1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: FC(F)(F)c1ccc(-n2cnc(Br)c2)nc1
Temperature: 105 °C
Yield: 85.7 %

Procedure:
A dried pressure tube was charged with 4-bromo-1H-imidazole (100 mg, 667 μmol), tetrahydrofuran (3 ml), N,N-dimethylformamide (2 ml), 2-(methylsulfonyl)-5-(trifluoromethyl)pyridine (150 mg, 667 μmol), and cesium carbonate (261 mg, 800 μmol). The tube was sealed and heated at 105° C. for 16 hours. For the workup, the reaction mixture was evaporated at reduced pressure and the residue directly purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 60:30 as the eluent. The 2-(4-bromo-1H-imidazol-1-yl)-5-(trifluoromethyl)pyridine (167 mg, 86% yield) was obtained as a crystalline white solid. MS (ISP): m/z=292.0 [M+H]+ and 294.2 [M+2+H]+.
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3].C1(C2C=CC([C:21]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[O:22])=CC=2)C=CC=CC=1>>[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:21]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[O:22])=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3]
Reactant: CCOC(=O)C(=O)c1ccc(-c2ccccc2)cc1
Reactant: CC(C)Cc1ccccc1
Product: CCOC(=O)C(=O)c1ccc(CC(C)C)cc1
Yield: 81 %

Procedure:
A mixture of 27 g (200 mmol) of isobutylbenzene and 24 mL (215 mmol) of ethyl oxalylchloride underwent Friedel-Crafts acylation reaction in an analogous fashion as described for the synthesis of ethyl 4-phenylbenzoylformate to yield 38 g (81% yield) of ethyl 4-isobutylbenzoylformate as a colorless oil.
Reaction SMILES: [CH2:1]([CH2:3][NH2:4])[OH:2].[C:5](O)(=[O:23])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]/[CH:13]=[CH:14]\[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>CCCCCC>[CH3:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]/[CH:14]=[CH:13]\[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][C:5]([NH:4][CH2:3][CH2:1][OH:2])=[O:23]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Reactant: NCCO
Solvent: CCCCCC
Product: CCCCCCCC/C=C\CCCCCCCC(=O)NCCO

Procedure:
This experiment was carried out according to the procedure of using free fatty acid as acyl donor (Plastina et al., Lett. Org. Chem. 6:444-47 (2009), which is hereby incorporated by reference in its entirety). Ethanolamine (1 mmol) in hexane (1 mL) was mixed with oleic acid (1 mmol) in a 10-mL round bottom flask in the presence of the lipase (50%, relative to total reactants). The reaction was conducted with agitation at ambient temperature for 4, 8, and 24 hours or at 65° C. for 4, 8, and 20 hours before hexane was removed under reduced pressure.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][C:3]=1[S:11]([NH2:14])(=[O:13])=[O:12].[H][H]>[Pd].O1CCCC1>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[S:11]([NH2:14])(=[O:12])=[O:13]
Reactant: [H][H]
Reactant: Nc1ccc([N+](=O)[O-])cc1S(N)(=O)=O
Agent: [Pd]
Solvent: C1CCOC1
Product: Nc1ccc(N)c(S(N)(=O)=O)c1

Procedure:
A mixture of 2-amino-5-nitrobenzenesulfonamide (Example 17b, 10 g, 46.08 mmol), 10% palladium on charcoal (˜1 g) in tetrahydrofuran (250 mL) was hydrogenated for 26 h at 25° C. under 1 atmosphere of hydrogen gas via balloon. The mixture was then filtered through Celite, washed with tetrahydrofuran, and the solvent removed in vacuo to afford the desired product. The catalyst/Celite mixture was slurried in methanol (400 mL) for 16 h, filtered and the solvent was removed in vacuo to afford a second batch of the desired product, 2,5-diaminobenzenesulfonamide (combined: 7.79 g, 41.65 mmol, 90.4% yield) as a light-brown solid. 1H NMR (400 MHz, DMSO-d6) δ: 4.54 (2H, bs), 4.98 (2H, bs), 6.55-6.60 (2H, m), 6.87 (1H, d, J=2.2 Hz), 6.99 (2H, bs). LC-MS (ESI) calcd for C6H9N3O2S 187.04. found 188.3 [M+H+].
Reaction SMILES: O=O.[C:3]([OH:6])(=[S:5])[CH3:4].C(O[CH:11]1[NH:14][C:13](=[O:15])[CH2:12]1)(=O)C.C([O-])(O)=O.[Na+]>O>[C:3]([S:5][CH:11]1[NH:14][C:13](=[O:15])[CH2:12]1)(=[O:6])[CH3:4]
Reactant: CC(=O)OC1CC(=O)N1
Reactant: CC(O)=S
Agent: O=C([O-])O
Agent: O=O
Agent: [Na+]
Solvent: O
Product: CC(=O)SC1CC(=O)N1
Reaction time: 2.75 h

Procedure:
To a cold (0°-5°) oxygen-free 1 N NaOH solution (803 ml.) was added over 20 minutes thioacetic acid (57 ml., 61 g., 0.803 mole). The resulting solution was added in ca 20 minutes to a cold (10°) oxygen-free solution of 4-acetoxyazetidinone (94 g., 0.730 mole) in water (300 ml.). The pH of the resulting solution was immediately adjusted to 7.4 with solid NaHCO3. The cooling bath was removed and the solution was stirred for 2.75 hours. The mixture was then extracted with chloroform, the combined organic extracts washed with water (150 ml.) and dried over sodium sulfate. Concentration on a rotary evaporator left a yellow oil (95.3 g., 90%) which solidified to a yellow solid on cooling and seeding. This solid was found identical (by IR, NMR and TLC) to the product obtained in Preparation 1.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=1)[NH2:7])([CH3:3])[CH3:2].C(N(CC)CC)C.[N+:18]([C:21]1[CH:29]=[CH:28][CH:27]=[CH:26][C:22]=1[C:23](Cl)=[O:24])([O-:20])=[O:19]>C1COCC1>[CH:1]([C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=1)[NH:7][C:23](=[O:24])[C:22]1[CH:26]=[CH:27][CH:28]=[CH:29][C:21]=1[N+:18]([O-:20])=[O:19])([CH3:3])[CH3:2]
Reactant: O=C(Cl)c1ccccc1[N+](=O)[O-]
Reactant: CC(C)c1cccc(N)c1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)c1cccc(NC(=O)c2ccccc2[N+](=O)[O-])c1
Temperature: 0 °C

Procedure:
One gram of 3-isopropylaniline and 0.8 gram of triethylamine were dissolved in 50 ml of THF, cooled to 0° C. and agitated. A solution prepared by dissolving 1.37 grams of 2-nitrobenzoyl chloride in 20 ml of THF was dropwisely added. After agitating for 30 minutes, the reaction mixture was filtered and THF in the filtrate was distilled off under reduced pressure. The residue was extracted with benzene, and rinsed with 3N-HCl, a saturated sodium bicarbonate solution and water successively in this order. The benzene layer was dried by adding anhydrous magnesium sulfate and then benzene was distilled off under reduced pressure to obtain the desired product. The yield was 1.79 grams (85%), and the product had a melting point of 65.5° to 68.5° C. and an IR absorption peak at 1660 cm-1 (c=0).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH:11]([CH2:16][C:17]([OH:19])=[O:18])[CH2:12][C:13]([OH:15])=O)=[CH:4][CH:3]=1.[C:20](OC(=O)C)(=[O:22])[CH3:21]>>[C:20]([O:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][CH2:10][CH:11]2[CH2:12][C:13](=[O:15])[O:18][C:17](=[O:19])[CH2:16]2)=[CH:6][CH:7]=1)(=[O:22])[CH3:21]
Reactant: CC(=O)OC(C)=O
Reactant: O=C(O)CC(CCCc1ccc(O)cc1)CC(=O)O
Product: CC(=O)Oc1ccc(CCCC2CC(=O)OC(=O)C2)cc1

Procedure:
3-[3-(4-Hydroxyphenyl)propyl]glutaric acid (533 mg) is reacted with acetic anhydride as described in Example 1C to afford 3-[3-[4-(acetyloxy)phenyl]propyl]glutaric anhydride, melting point 55°-57° C.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.C([Li])CCC.[C:12](#[N:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>O>[S:3]1[CH:4]=[CH:5][N:6]=[C:2]1[NH:1][C:12](=[NH:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: N#Cc1ccccc1
Reactant: Nc1nccs1
Agent: [Li]CCCC
Solvent: O
Product: N=C(Nc1nccs1)c1ccccc1
Yield: 65.5 %

Procedure:
Procedure as described for Amidine I using the following amounts and modifications: 5.01 g of 2-aminothiazole (50.0 mmol), 26.0 mL of 2.0 M butyllithium (52.0 mmol), 5.20 mL of benzonitrile (51.0 mmol). After refluxing overnight, the solution was green-brown. Addition of water yielded a red-brown solution with suspended solid. Solution was taken to dryness yielding 6.66 g (66%) of yellow-orange material. 1H NMR (400 MHz, C6D6): 10.1 (br, 1H), 7.68 (d, 2H), 7.34 (d, 1H), 7.04 (m, 3 H), 6.40 (d, 1H), 5.35 (br, 1H), 2.26 (s, 6H).
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:10]=[C:9]([CH3:11])[O:8][N:7]=1)[CH:2]([CH3:4])[CH3:3].[I:12]Cl.S([O-])([O-])=O.[Na+].[Na+]>CC(O)=O.O>[I:12][C:10]1[C:6]([O:5][CH2:1][CH:2]([CH3:4])[CH3:3])=[N:7][O:8][C:9]=1[CH3:11]
Reactant: ClI
Reactant: Cc1cc(OCC(C)C)no1
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: Cc1onc(OCC(C)C)c1I
Temperature: 80 °C
Reaction time: 14 h
Yield: 68.4 %

Procedure:
To a stirred solution of 3-isobutoxy-5-methyl-isoxazole (570 mg, 3.67 mmol) in AcOH (15 mL) and water (18 mL) at ambient temperature was added ICl (716 mg, 4.40 mmol) and the reaction mixture heated at 80° C. After 2 h the reaction mixture was cooled to room temperature. After 14 h, a solution of sodium sulfite (Na2SO3, 1 g) in water (15 mL) was added and the reaction mixture extracted into ethyl acetate (2×50 mL). The combined extracts were washed with water (3×30 ml) and brine then dried over sodium sulfate, filtered and concentrated. Purification by chromatography (silica, 0-10% ethyl acetate in heptane) gave the title compound (706 mg, 68%) as a colourless liquid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6](F)[CH:5]=[CH:4][C:3]=1[S:9]([C@H:12]1[CH2:16][N:15]([C:17]2[N:21]([CH2:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[N:20]=[C:19]([CH3:30])[CH:18]=2)[C@H:14]([C:31]([NH:33][C:34]2([C:37]#[N:38])[CH2:36][CH2:35]2)=[O:32])[CH2:13]1)(=[O:11])=[O:10].[F:39][C:40]([F:44])([F:43])[CH2:41][OH:42]>>[CH2:41]([OH:42])[C:40]([F:44])([F:43])[F:39].[C:37]([C:34]1([NH:33][C:31]([C@@H:14]2[CH2:13][C@@H:12]([S:9]([C:3]3[CH:4]=[CH:5][C:6]([O:42][CH2:41][C:40]([F:44])([F:43])[F:39])=[CH:7][C:2]=3[Cl:1])(=[O:11])=[O:10])[CH2:16][N:15]2[C:17]2[N:21]([CH2:22][CH2:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[N:20]=[C:19]([CH3:30])[CH:18]=2)=[O:32])[CH2:35][CH2:36]1)#[N:38]
Reactant: Cc1cc(N2C[C@H](S(=O)(=O)c3ccc(F)cc3Cl)C[C@H]2C(=O)NC2(C#N)CC2)n(CCc2ccccc2)n1
Solvent: OCC(F)(F)F
Product: Cc1cc(N2C[C@H](S(=O)(=O)c3ccc(OCC(F)(F)F)cc3Cl)C[C@H]2C(=O)NC2(C#N)CC2)n(CCc2ccccc2)n1

Procedure:
In analogy to the procedure described in example 392, (2S,4R)-4-(2-chloro-4-fluorophenylsulfonyl)-N-(1-cyanocyclopropyl)-1-(3-methyl-1-phenethyl-1H-pyrazol-5-yl)pyrrolidine-2-carboxamide (example 484c) was reacted with 2,2,2,-trifluoroethanol (CAS Reg. No. 75-89-8 99) to give the title compound as colorless oil. MS (ESI): m/z=636.2 [M+H]+.
Reaction SMILES: [BH4-].[Na+].[CH3:3][N:4]([CH3:17])[CH:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=2[C:7](=[O:16])[CH2:6]1.[Cl-].[Na+]>O.C(O)C>[CH3:3][N:4]([CH3:17])[CH:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=2[CH:7]([OH:16])[CH2:6]1
Reactant: CN(C)C1CCc2ccccc2C(=O)C1
Agent: [BH4-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CN(C)C1CCc2ccccc2C(O)C1
Temperature: 20 °C
Reaction time: 2 h
Yield: 91.1 %

Procedure:
A solution of 8.7 g of sodium borohydride in 87 ml of water was added to a solution of 8.7 g of the product of Step A in 435 ml of ethanol and the mixture was stirred at 20° C for 11/2 hours and was then poured into ice water. The mixture was saturated with sodium chloride and was extracted with ethyl acetate. The organic phase was washed with aqueous sodium chloride solution, was dried and evaporated to dryness to obtain 8 g of raw 7-dimethylamino-5-hydroxy-6,7,8,9-tetrahydro [5H] benzocycloheptene which was used as is for the next step.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:12][C@@H:11]([CH2:13][O:14][Si](C(C)(C)C)(C3C=CC=CC=3)C3C=CC=CC=3)[O:10][C:9]2=[O:32])=[N:6][CH:7]=1.[N+](CCCC)(CCCC)(CCCC)CCCC.[F-]>O1CCCC1.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:12][C@@H:11]([CH2:13][OH:14])[O:10][C:9]2=[O:32])=[N:6][CH:7]=1
Reactant: CC(C)(C)[Si](OC[C@@H]1CN(c2ccc(Br)cn2)C(=O)O1)(c1ccccc1)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: O=C1O[C@H](CO)CN1c1ccc(Br)cn1
Temperature: 0 °C
Yield: 83.5 %

Procedure:
Compound 25b (1.4 g, 2.83 mmol) was dissolved in tetrahydrofuran, cooled to 0° C., and nBu4NF (4.2 mL, 4.2 mmol, 4.2 M solution in tetrahydrofuran) was added. The mixture was allowed to react for 5 hrs and monitored by TLC. After the reaction completed, the mixture was diluted with water, and extracted with ethyl acetate. The organic phase was wash with saturated saline solution, dried over anhydrous sodium sulfate. Column chromatography afforded 645 mg of white solid, yield 83%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([CH:8]=1)[NH2:7].[I:12]Cl>CC(O)=O.CC([O-])=O.[Na+]>[Cl:1][C:2]1[C:3]([I:12])=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([NH2:7])[CH:8]=1
Reactant: ClI
Reactant: Nc1cc(Cl)ccc1[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: Nc1cc(Cl)c(I)cc1[N+](=O)[O-]

Procedure:
The title compound was prepared from 5-chloro-2-nitroaniline by iodination with iodine monochloride in HOAc/NaOAc according to the general procedure A (80° C.). Obtained as an orange solid.
Reaction SMILES: [C:1]([O-:4])(=[O:3])[CH3:2].[C:5]([O-:8])(=[O:7])[CH3:6].[C:9]([O-:12])(=[O:11])[CH3:10].C([O-])(=O)C.[Pb+4:17].[Br:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[C:21]([CH2:28][CH3:29])[CH:20]=1>>[C:1]([O-:4])(=[O:3])[CH3:2].[C:5]([O-:8])(=[O:7])[CH3:6].[C:9]([O-:12])(=[O:11])[CH3:10].[Br:18][C:19]1[CH:24]=[CH:23][C:22]([Pb+3:17])=[C:21]([CH2:28][CH3:29])[CH:20]=1
Reactant: [Pb+4]
Reactant: CCc1cc(Br)ccc1B(O)O
Agent: CC(=O)[O-]
Product: CCc1cc(Br)ccc1[Pb+3]
Temperature: 40 °C
Yield: 44.8 %

Procedure:
To a mixture of lead tetraacetate (53 g, 0.12 mol) and mercuric diacetate (2.5 g, 0.0078 mol), thoroughly flushed with nitrogen, is added anhydrous chloroform (250 ml). This mixture is warmed to 40° C. and 4-bromo-2-ethylphenylboronic acid (25 g, 0.11 mol) is added in one portion and the mixture is stirred and heated at this temperature for 4 hours. After cooling to room temperature, cooled in an ice bath, filtered through a plug of diatomaceous earth and the filtrate is concentrated to approximately a quarter of its volume. Hexane is added to induce crystallization and the solvents evaporated under reduced pressure. Trituration with hexane gives 4-bromo-2-ethylphenyl lead triacetate (28 g).
Reaction SMILES: [Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.[CH:41]([C:43]1[CH:57]=[CH:56][C:46]([O:47][C:48]2[CH:55]=[CH:54][C:51]([C:52]#[N:53])=[CH:50][N:49]=2)=[C:45]([CH3:58])[CH:44]=1)=O>C1COCC1>[CH3:2][O:3][CH:4]=[CH:41][C:43]1[CH:57]=[CH:56][C:46]([O:47][C:48]2[CH:55]=[CH:54][C:51]([C:52]#[N:53])=[CH:50][N:49]=2)=[C:45]([CH3:58])[CH:44]=1
Reactant: COC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Cc1cc(C=O)ccc1Oc1ccc(C#N)cn1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: COC=Cc1ccc(Oc2ccc(C#N)cn2)c(C)c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 76 %

Procedure:
Suspend (methoxymethyl)triphenylphosphonium chloride (1.14 g, 3.34 mmol) in THF (11 mL) under N2 and cool the mixture at 0° C., add slowly 0.5M KHMDS in toluene (6.7 mL, 3.34 mmol) and stir at 0° C. for 30 min. Cool the mixture at −78° C. and add a solution of aldehyde from step 1 above (663 mg, 2.78 mmol) in THF (2 mL). Warm the mixture slowly to room temperatures and stir for 1 h. Add water and extract the aqueous layer with Et2O. Dry the organic layer over MgSO4. Eliminate the solvent and purify by flash chromatography on silica gel (eluent: gradient from EtOAc/hexane 10/90 to 20/80) to get the title compound (530 mg, 76%). Electrospray MS M+1 ion=267. 1H-NMR (CDCl3, 300 MHz, mixture of isomers): 8.47-8.45 (m, 2H), 7.92-7.86 (m, 2H), 7.50-7.45 (m, 1H), 7.15-6.93 (m, 5H), 6.14 (d, 1H, J=7.1 Hz), 5.79 (d, 1H, J=13.2 Hz), 5.20 (d, 1H, J=7.1 Hz), 3.78 (s, 3H), 3.68 (s, 3H), 2.11 (s, 3H), 2.10 (s, 3H).
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:14]=[CH:13][C:9]([C:10](Cl)=[O:11])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4].[NH3:15]>C(Cl)(Cl)Cl>[CH2:1]([O:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([NH2:15])=[O:11])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOc1ccc(C(=O)Cl)cc1
Reactant: N
Solvent: ClC(Cl)Cl
Product: CCCCOc1ccc(C(N)=O)cc1

Procedure:
Chilled to 20°, a solution of 84 g (0.39 mole) of a solution of 4-n-butoxybenzoyl chloride in 700 ml of AR chloroform, then saturated with anhydrous ammonia. The mixture was stirred for 20 min. to 0°, then the white precipitate collected, washed with cold water and oven-dried to 60° to give 76 g, m.p. shrinks 160°, melts 162°-164°.
Reaction SMILES: [Si](Br)(C)(C)C.CS(C)=O.[S:10]1[CH:14]=[CH:13][C:12]([CH2:15][CH:16]=O)=[CH:11]1.[CH3:18][N:19]([CH2:21][C:22]1[CH:23]=[C:24]([NH:28][C:29]2[S:30]C(C3C=CC=CC=3)=C[N:33]=2)[CH:25]=[CH:26][CH:27]=1)[CH3:20]>CC#N>[CH3:20][N:19]([CH2:21][C:22]1[CH:23]=[C:24]([NH:28][C:29]2[S:30][C:15]([C:12]3[CH:13]=[CH:14][S:10][CH:11]=3)=[CH:16][N:33]=2)[CH:25]=[CH:26][CH:27]=1)[CH3:18]
Reactant: O=CCc1ccsc1
Reactant: CN(C)Cc1cccc(Nc2ncc(-c3ccccc3)s2)c1
Agent: C[Si](C)(C)Br
Solvent: CS(C)=O
Solvent: CC#N
Product: CN(C)Cc1cccc(Nc2ncc(-c3ccsc3)s2)c1
Temperature: 0 °C
Reaction time: 0.83 h

Procedure:
Me3SiBr (0.23 mL, 1.75 mmol, 1.1 equiv) and DMSO (0.12 mL, 1.75 mmol, 1.1 equiv) are added sequentially and dropwise to a cold (−35° C.) solution of 3-thiophenylacetaldehyde (200 mg, 1.59 mmol) in CH3CN (3.0 mL), under an argon atmosphere. The resulting mixture is allowed to warm to 0° C., to stir for 50 min, then to warm to room temperature and to stir for 10 min. CH3CN (5.0 mL) is added to the reaction mixture, followed by addition of (3-dimethylaminomethyl-phenyl)-thiourea (Example 2) (333 mg, 1.59 mmol). The reaction mixture is heated to reflux for 1 h, allowed to cool to RT and concentrated in vacuo. MPLC (CH3CN/H2O/TFA) purification affords the title compound: ES-MS: 316.0 [M+H]+; single peak at tR=3.19 min (System 2).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([S:9]([N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]2[C:18]([OH:20])=O)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1.[CH:21]1[CH:30]=[C:29]2[C:24]([CH:25]=[C:26]([NH:31][C:32]([C@@H:34]([NH2:45])[CH2:35][C:36]3[C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[NH:38][CH:37]=3)=[O:33])[CH:27]=[CH:28]2)=[CH:23][CH:22]=1.CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>ClCCl.CN(C1C=CN=CC=1)C>[NH:38]1[C:39]2[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:36]([CH2:35][C@H:34]([NH:45][C:18]([C@@H:13]2[CH2:14][CH2:15][CH2:16][CH2:17][N:12]2[S:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=2)(=[O:10])=[O:11])=[O:20])[C:32](=[O:33])[NH:31][C:26]2[CH:27]=[CH:28][C:29]3[C:24](=[CH:23][CH:22]=[CH:21][CH:30]=3)[CH:25]=2)=[CH:37]1
Reactant: COc1cccc(S(=O)(=O)N2CCCC[C@H]2C(=O)O)c1
Reactant: N[C@@H](Cc1c[nH]c2ccccc12)C(=O)Nc1ccc2ccccc2c1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: On1nnc2ccccc21
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: COc1cccc(S(=O)(=O)N2CCCC[C@H]2C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)Nc2ccc3ccccc3c2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 75.4 %

Procedure:
To a solution of 0.78 g (2.60 mmol) of (S)-1-(3-methoxy-benzenesulfonyl)-piperidine-2-carboxylic acid and 1.03 g (3.12 mmol) of (S)-2-amino-3-(1-indol-3-yl)-naphthalen-2-yl-propionamide in dichloromethane (100 ml) was added 0.16 g (1.30 mmol) DMAP followed by addition of 4-methylmorpholine 1.37 g (13.54 mmol), HOBT 0.84 g (6.25 mmol) and EDCI 1.39 g (7.29 mmol). The mixture was stirred at room temperature overnight. The reaction mixture was then washed with water, dried (sodium sulfate). Chromatography on silica gel eluting with 50% ethyl acetate/heptane proved 1.2 g (1.96 mmol) of the title compound. 1H NMR (300 MHz, CDCl3): 1.34-1.01 (m, 5H); 2.07 (bd, 1H); 2.21 (dd, 1H); 3.43-3.48 (m, 3H); 3.83 (s, 3H); 4.34 (b, 1H); 4.98 (q, 1H); 6.98 (d, 1H); 7.09-7.47 (m, 11H); 7.68-7.80 (m, 4H); 8.15 (s, 1H); 8.21 (s, 1H); 8.40 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([OH:11])[C:9]=1[OH:10])[CH:5]=[O:6].[C:12]([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[Cl:1][C:2]1[C:9]2[O:10][CH2:12][O:11][C:8]=2[CH:7]=[C:4]([CH:5]=[O:6])[CH:3]=1
Reactant: O=C([O-])[O-]
Reactant: O=Cc1cc(O)c(O)c(Cl)c1
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: O=Cc1cc(Cl)c2c(c1)OCO2
Temperature: 60 °C
Reaction time: 8 h
Yield: 70.7 %

Procedure:
To a solution of 3-chloro-4,5-dihydroxybenzaldehyde (8.0 g, 46 mmol) and BrClCH2 (23.9 g, 185 mmol) in dry DMF (100 mL) was added Cs2CO3 (25 g, 190 mmol). The mixture was stirred at 60° C. overnight and was then poured into water. The resulting mixture was extracted with EtOAc (50 mL×3). The combined extracts were washed with brine (100 mL), dried over Na2SO4 and concentrated under reduced pressure to afford 7-chlorobenzo[d][1,3]dioxole-5-carbaldehyde (6.0 g, 70%). 1H NMR (400 MHz, CDCl3) δ 9.74 (s, 1H), 7.42 (d, J=0.4 Hz, 1H), 7.26 (d, J=3.6 Hz, 1H), 6.15 (s, 2H).