Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[NH:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[N:3]=1.[CH3:11][NH:12][CH3:13].O>CN(C=O)C>[CH3:11][N:12]([CH3:13])[C:2]1[NH:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[N:3]=1
Reactant: Clc1nc2ccccc2[nH]1
Reactant: CNC
Solvent: O
Solvent: CN(C)C=O
Product: CN(C)c1nc2ccccc2[nH]1
Temperature: 200 °C
Yield: 88.5 %

Procedure:
[step 1] Commercially available 2-chloro-1H-benzo[d]imidazole (250 mg, 1.64 mmol) was dissolved in DMF (4.7 mL), dimethylamine (50% aqueous solution, 0.50 mL, 4.92 mmol) was added, and the mixture was stirred with heating at 200° C. for 30 min in an Emrys Optimizer microwave synthesizer. Water was added to the mixture, and the precipitated crystals were collected by suction filtration to give N,N-dimethyl-1H-benzo[d]imidazole-2-amine (234 mg, 89%).
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][O:9][C:10]1[CH:11]=[C:12](/[CH:22]=[CH:23]/[C:24]2[N:45]=[C:27]3[CH:28]([CH:32]4[CH2:37][CH2:36][N:35](C(OC(C)(C)C)=O)[CH2:34][CH2:33]4)[CH2:29][CH2:30][CH2:31][N:26]3[N:25]=2)[CH:13]=[CH:14][C:15]=1[N:16]1[CH:20]=[C:19]([CH3:21])[N:18]=[CH:17]1.C(=O)(O)[O-].[Na+].C(OCC)(=O)C>C(Cl)Cl>[CH3:8][O:9][C:10]1[CH:11]=[C:12](/[CH:22]=[CH:23]/[C:24]2[N:45]=[C:27]3[CH:28]([CH:32]4[CH2:33][CH2:34][NH:35][CH2:36][CH2:37]4)[CH2:29][CH2:30][CH2:31][N:26]3[N:25]=2)[CH:13]=[CH:14][C:15]=1[N:16]1[CH:20]=[C:19]([CH3:21])[N:18]=[CH:17]1
Reactant: COc1cc(/C=C/c2nc3n(n2)CCCC3C2CCN(C(=O)OC(C)(C)C)CC2)ccc1-n1cnc(C)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1cc(/C=C/c2nc3n(n2)CCCC3C2CCNCC2)ccc1-n1cnc(C)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 57 %

Procedure:
Trifluoroacetic acid (1 ml) was added to a solution of tert-butyl 4-(2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridin-8-yl)piperidine-1-carboxylate (361 mg) in methylene chloride (3 ml), and the mixture was stirred at room temperature for two hours. A saturated sodium bicarbonate solution and ethyl acetate were added to the reaction solution, and the organic layer was separated. The organic layer was sequentially washed with a saturated sodium bicarbonate solution and brine. Since most of the target compound was present in the aqueous layers, the combined aqueous layers were extracted with methylene chloride three times. The methylene chloride extraction layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Chromatorex™ NH; elution solvent: chloroform-methanol system) to obtain 166 mg of the title compound. The property values of the compound are as follows.
Reaction SMILES: C[O:2][C:3]1[CH:19]=[CH:18][C:6]([C:7]([C:9]2[S:13][C:12]([S:14]([NH2:17])(=[O:16])=[O:15])=[CH:11][CH:10]=2)=[O:8])=[CH:5][CH:4]=1.Cl.N1C=CC=CC=1>O>[OH:2][C:3]1[CH:19]=[CH:18][C:6]([C:7]([C:9]2[S:13][C:12]([S:14]([NH2:17])(=[O:16])=[O:15])=[CH:11][CH:10]=2)=[O:8])=[CH:5][CH:4]=1
Reactant: COc1ccc(C(=O)c2ccc(S(N)(=O)=O)s2)cc1
Agent: Cl
Solvent: O
Solvent: c1ccncc1
Product: NS(=O)(=O)c1ccc(C(=O)c2ccc(O)cc2)s1
Temperature: 200 °C
Reaction time: 0.5 h

Procedure:
A mixture of 5-(4-methoxybenzoyl)thiophene-2-sulfonamide (5.48 g) and pyridine hydrochloride (50 g.) was heated to 200° C. for 0.5 hour. Water (400 mL) was added to the cooled reaction mixture and the solid collected by filtration. This solid was stirred with 1N hydrochloric acid (100 mL) for 0.5 hour, filtered, washed with water and dried at 70° C., 4.11 g, m.p. 183°-190° C. Treatment of this material with acetonitrile, followed by sodium bicarbonate solution then 3N hydrochloric acid, and recrystallization from water gave 1.70 g, m.p. 200°-201° C.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([Cl:10])[CH:3]=1.N1C=CC=CC=1.Cl[C:18]([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:19].CCOC(C)=O>C1COCC1>[Cl:10][C:4]1[CH:3]=[C:2]([NH:1][C:18](=[O:19])[O:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:9]=[CH:8][C:5]=1[C:6]#[N:7]
Reactant: O=C(Cl)Oc1ccccc1
Reactant: N#Cc1ccc(N)cc1Cl
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: N#Cc1ccc(NC(=O)Oc2ccccc2)cc1Cl
Temperature: 0 °C
Yield: 91.1 %

Procedure:
Dissolve 4-amino-2-chloro-benzonitrile (500 mg, 3.3 mmol) and pyridine (518 mg, 6.6 mmol) in THF (5 mL), cool to 0° C. and add slowly phenyl chloroformate (616 mg, 3.9 mmol). After addition, stir the reaction at room temperature for 2 hrs. TLC (EtOAc:PE=1:3) shows the reaction is complete. Add water, extract with DCM, separate the organic layer. Wash the organic layer with 1M HCl solution, brine sequentially, dry over anhydrous Na2SO4, and concentrate under reduced pressure to give the target compound (820 mg, 91.7%). MS: (M+1): 273.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:18]=[C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[CH:16]=[CH:15][C:10]=1[C:11]([O:13]C)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>O1CCOCC1.[OH-].[Na+]>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]([O:19][CH2:20][C:21]2[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][CH:26]=2)[CH:16]=[CH:15][C:10]=1[C:11]([OH:13])=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1ccc(OCc2ccc(Cl)cc2)cc1OCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: O=C(O)c1ccc(OCc2ccc(Cl)cc2)cc1OCc1ccccc1
Yield: 44.2 %

Procedure:
A solution of methyl 2-benzyloxy-4-(4-chlorobenzyloxy)benzoate (1.88 g) in dioxan (37 mL) and 1M NaOH (12.5 mL) is refluxed for 4 hours. The solution is evaporated, the residue diluted with water, and brought to pH 1 with 2M HCl. The precipitate is extracted with ethyl acetate, washed with water, dried and evaporated. The residue is recrystallized from ethyl acetate to yield 2-benzyloxy-4-(4-chlorobenzyloxy)benzoic acid (0.8 g, 44%) as colourless crystals, m.p. 150-152° C. 1H NMR (DMSO) 5.15 (2H,s), 5.2(2H,s), 6.7(1H,d), 6.8(1H,s), 7.3-7.5(9H,m), 7.7(1H,d).
Reaction SMILES: [CH:1]1([C:4]2[N:8]3[CH2:9][CH2:10][CH2:11][C@@H:12]([C:13]4[N:17]5[CH:18]=[CH:19][N:20]=[C:21]([NH:22][CH2:23][C:24]6[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:25]=6[O:32][CH3:33])[C:16]5=[C:15]([C:34]5[CH:43]=[CH:42][C:37]([C:38]([O:40]C)=[O:39])=[CH:36][CH:35]=5)[N:14]=4)[C:7]3=[N:6][N:5]=2)[CH2:3][CH2:2]1.O[Li].O.Cl>C1COCC1.CO.O>[CH:1]1([C:4]2[N:8]3[CH2:9][CH2:10][CH2:11][C@@H:12]([C:13]4[N:17]5[CH:18]=[CH:19][N:20]=[C:21]([NH:22][CH2:23][C:24]6[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:25]=6[O:32][CH3:33])[C:16]5=[C:15]([C:34]5[CH:43]=[CH:42][C:37]([C:38]([OH:40])=[O:39])=[CH:36][CH:35]=5)[N:14]=4)[C:7]3=[N:6][N:5]=2)[CH2:3][CH2:2]1
Reactant: COC(=O)c1ccc(-c2nc([C@@H]3CCCn4c(C5CC5)nnc43)n3ccnc(NCc4ccc(OC)cc4OC)c23)cc1
Agent: Cl
Agent: [Li]O
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: COc1ccc(CNc2nccn3c([C@@H]4CCCn5c(C6CC6)nnc54)nc(-c4ccc(C(=O)O)cc4)c23)c(OC)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 45.1 %

Procedure:
To a solution of (S)-methyl 4-(3-(3-cyclopropyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-8-yl)-8-((2,4-dimethoxybenzyl)amino)imidazo[1,5-a]pyrazin-1-yl)benzoate (300 mg, 0.51 mmol) in THF/MeOH/H2O (3 mL/3 mL/1 mL) was added LiOH.H2O (109 mg, 2.6 mmol). The mixture was stirred at RT overnight. After the reaction was completed, the reaction mixture was acidified by 2M HCl to pH=5˜6 and extracted with EA and water. The organic layer was dried and concentrated to give (S)-4-(3-(3-cyclopropyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridin-8-yl)-8-((2,4-dimethoxybenzyl)amino)imidazo[1,5-a]pyrazin-1-yl)benzoic acid (130 mg, yield 45%).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH:8]=[CH:7]2.C([Sn](CCCC)(CCCC)[C:23]([O:25][CH2:26][CH3:27])=[CH2:24])CCC>C1(C)C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:26]([O:25][C:23]([C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH:8]=[CH:7]2)=[CH2:24])[CH3:27]
Reactant: Brc1cccc2ccc(-c3ccccc3)nc12
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Product: C=C(OCC)c1cccc2ccc(-c3ccccc3)nc12
Temperature: 80 °C

Procedure:
In a sealed tube, to the suspension of 8-bromo-2-phenylquinoline (0.1 g, 0.352 mmol) in toluene (5 mL) was added PdCl2(PPh3)2 (0.012 g, 0.017 mmol) and tributyl (1-ethoxyvinyl)stannane (0.15 g, 0.422 mmol) under N2. The reaction was heated at 80° C. for 12 h, then cooled to RT. The solvent was removed and the crude material was used in the next step without further purification.
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([C:13]2([C:16]([O:18]C)=[O:17])[CH2:15][CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[Na+].Cl>CO>[F:1][C:2]([F:20])([F:21])[C:3]1[CH:4]=[C:5]([C:13]2([C:16]([OH:18])=[O:17])[CH2:15][CH2:14]2)[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=1
Reactant: COC(=O)C1(c2cc(C(F)(F)F)cc(C(F)(F)F)c2)CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)C1(c2cc(C(F)(F)F)cc(C(F)(F)F)c2)CC1
Temperature: 60 °C
Reaction time: 1.5 h
Yield: 80.9 %

Procedure:
To a solution of the compound (1.80 g) obtained in step 2 in methanol (10 mL) was added 8N aqueous sodium hydroxide solution (10 mL), and the mixture was stirred at 60° C. for 1.5 hr. The reaction mixture was cooled, and the mixture was acidified with 6N hydrochloric acid, and methanol was evaporated under reduced pressure. The residue was extracted twice with ethyl acetate, dried and concentrated under reduced pressure to give the title compound (1.39 g, 81%) as a white powder.
Reaction SMILES: FC(F)(F)[C:3]([C:5]1[C:13]2[C:8](=[C:9]([F:19])[CH:10]=[CH:11][C:12]=2[O:14][C:15]([F:18])([F:17])[F:16])[N:7]([CH2:20][CH2:21][O:22][CH3:23])[CH:6]=1)=[O:4].C[OH:27]>[OH-].[Na+]>[F:19][C:9]1[CH:10]=[CH:11][C:12]([O:14][C:15]([F:17])([F:18])[F:16])=[C:13]2[C:8]=1[N:7]([CH2:20][CH2:21][O:22][CH3:23])[CH:6]=[C:5]2[C:3]([OH:27])=[O:4]
Reactant: COCCn1cc(C(=O)C(F)(F)F)c2c(OC(F)(F)F)ccc(F)c21
Reactant: CO
Agent: [Na+]
Agent: [OH-]
Product: COCCn1cc(C(=O)O)c2c(OC(F)(F)F)ccc(F)c21
Temperature: 80 °C

Procedure:
A mixture of 7 (23.4 g, 62.6 mmol) in MeOH (100 mL) and 5 M NaOH (100 mL) is heated at 80° C. overnight. LC/MS indicates that the reaction is complete. The reaction mixture is cooled to rt, and then concentrated in vacuo to remove most of the MeOH. The residue is dissolved in H2O, and then washed with Et2O once. The aqueous layer is slowly acidified to pH ˜2 with conc. HCl. The acidified suspension is extracted with Et2O, and the organic extract is washed with H2O and brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue is suspended in DCM/heptane (10/90). The white powder 8 (19.4 g, 96%) in the suspension is collected by suction filtration and air-dried. 1H NMR (CDCl3) δ 8.02 (s, 1H), 7.15-7.05 (m, 1H), 7.00-6.90 (m, 1H), 4.49 (t, J=5.0 Hz, 2H), 3.75 (t, J=4.9 Hz, 2H), 3.33 (s, 3H); 19F NMR (CDCl3) δ −57.74 (s, 3F), −135.65 (d, J=11.3 Hz, 1F); MS 363 (M+CH3CN+1), 322 (M+1, 100%).
Reaction SMILES: [SH:1][CH2:2][CH:3]1[CH2:7][S:6][CH2:5][S:4]1.[Cl:8][CH2:9][CH2:10][C:11](Cl)=[O:12]>C1(C)C=CC=CC=1>[Cl:8][CH2:9][CH2:10][C:11]([S:1][CH2:2][CH:3]1[CH2:7][S:6][CH2:5][S:4]1)=[O:12]
Reactant: O=C(Cl)CCCl
Reactant: SCC1CSCS1
Solvent: Cc1ccccc1
Product: O=C(CCCl)SCC1CSCS1
Yield: 81.7 %

Procedure:
Into 500 ml glass reactor equipped with a stirrer and a cooling pipe, 91.2 g (0.60 moles) of 4-mercaptomethyl-1,3-dithiolane (2-1) produced in Example 1 was weighed and poured, and 80.0 g (0.63 moles) of 3-chloropropionic chloride was added dropwise into the reactor at 40° C. over 15 minutes. After reacted at 40° C. for eight hours with stirring, 200 g of toluene was added to the reaction mixture to dissolve the mixture. The mixture then was moved into a separating funnel to be rinsed three times with 300 g of 3 wt. % sodium hydrogen carbonate aqueous solution. Then, after the mixture was rinsed with 300 g of pure water until the water layer became neutral, the organic layer (toluene solution) was taken out. Toluene was evaporated off under reduced pressure, and 119 g of 4-(3-chloropropionylthiomethyl)-1,3-dithiolane was obtained as a transparent and colorless liquid.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[C:9]([CH3:12])([CH3:11])[CH3:10].[C:13](Cl)([Cl:15])=[S:14].[OH-].[Na+]>C(Cl)(Cl)Cl>[Cl:15][C:13]([O:8][C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[C:3]([C:9]([CH3:12])([CH3:11])[CH3:10])[CH:4]=1)=[S:14]
Reactant: S=C(Cl)Cl
Reactant: CC(C)(C)c1cc(O)ccc1Br
Agent: [Na+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Product: CC(C)(C)c1cc(OC(=S)Cl)ccc1Br
Temperature: 25 °C
Yield: 66.7 %

Procedure:
To 50 ml of chloroform were dissolved 11.5 g of 4-bromo-3-tert-butylphenol and 6.5 g of thiophosgene, and 60 ml of 1-N sodium hydroxide aqueous solution were added dropwise thereto with stirring at room temperature. After completion of this dropwise addition, the mixture was subjected to stirring over a period of 3 hours at room temperature. From the reaction mixture was separated chloroform layer, which was thereafter dried over anhydrous calcium chloride and then chloroform was distilled off therefrom. The residue was purified through a column chromatography (employing silica gel as carrier and hexane as developing solvent) to give 10.3 g of O-4-bromo-3-tert-butylphenyl chlorothioformate.
Reaction SMILES: [CH2:1]([CH:4]1[C:8](O)([CH3:9])[CH:7]=[CH:6][C:5]1=[O:11])[CH:2]=[CH2:3].[NH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(N(CC)CC)C.C1(C)C=CC=CC=1>[CH2:1]([C:4]1[C:5](=[O:11])[CH2:6][CH:7]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:8]=1[CH3:9])[CH:2]=[CH2:3]
Reactant: Nc1ccccc1
Reactant: C=CCC1C(=O)C=CC1(C)O
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: C=CCC1=C(C)C(Nc2ccccc2)CC1=O
Reaction time: 2 h
Yield: 96.9 %

Procedure:
Into the same flask as used in Example 1, 2-allyl-3-hydroxy-3-methyl-4-cyclopentenone (15.2 g), aniline (30 g), triethylamine (0.8 g) and toluene (45 g) were charged, and the mixture was stirred under a nitrogen stream at a temperature of 40° to 70° C. for 2 hours. After completion of the reaction, the mixture was treated and purified in the same manner as in Example 1 to obtain 2-allyl-3-methyl-4-anilino-2-cyclopentenone (22 g). Yield, 97%. nD20 1.5880.
Reaction SMILES: [NH2:1][C:2]1[C:12]([F:13])=[CH:11][C:10]([C:14]2[CH:15]=[C:16]3[C:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[O:29][CH3:30])=[CH:21][N:20]([S:31]([C:34]4[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=4)(=[O:33])=[O:32])[C:17]3=[N:18][CH:19]=2)=[CH:9][C:3]=1[C:4]([N:6]([CH3:8])[CH3:7])=[O:5].C(N(CC)C(C)C)(C)C.[F:50][C:51]([F:63])([F:62])[C:52]([N:54]1[CH2:61][CH2:60][CH2:59][C@H:55]1[C:56](Cl)=[O:57])=[O:53]>ClCCl>[CH3:7][N:6]([CH3:8])[C:4]([C:3]1[CH:9]=[C:10]([C:14]2[CH:15]=[C:16]3[C:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[O:29][CH3:30])=[CH:21][N:20]([S:31]([C:34]4[CH:35]=[CH:36][C:37]([CH3:40])=[CH:38][CH:39]=4)(=[O:32])=[O:33])[C:17]3=[N:18][CH:19]=2)[CH:11]=[C:12]([F:13])[C:2]=1[NH:1][C:56]([CH:55]1[CH2:59][CH2:60][CH2:61][N:54]1[C:52](=[O:53])[C:51]([F:63])([F:50])[F:62])=[O:57])=[O:5]
Reactant: O=C(Cl)[C@@H]1CCCN1C(=O)C(F)(F)F
Reactant: COc1ccccc1-c1cn(S(=O)(=O)c2ccc(C)cc2)c2ncc(-c3cc(F)c(N)c(C(=O)N(C)C)c3)cc12
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccccc1-c1cn(S(=O)(=O)c2ccc(C)cc2)c2ncc(-c3cc(F)c(NC(=O)C4CCCN4C(=O)C(F)(F)F)c(C(=O)N(C)C)c3)cc12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a scintillation vial was combined 32 mg (0.06 mmol) of 2-amino-3-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide and 15 uL (0.09 mmol) of N,N-diisopropylethylamine. To the vial was added 745 μL of a 0.1M solution of (S)-(−)-N-(trifluoroacetyl)prolylchloride in dichloromethane. The reaction was stirred at room temperature for 30 minutes, quenched with a few drops of methanol, and concentrated down. MS: m/z 752.1 (M+H+).
Reaction SMILES: [Pb]=[O:2].S(=O)(=O)(O)O.S([O-])([O-])(=O)=O.[Na+].[Na+].[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=1>O>[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]=[O:2])=[CH:19][CH:18]=1
Reactant: O=[Pb]
Reactant: COc1ccc(C)cc1
Agent: O=S(=O)(O)O
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: O
Product: COc1ccc(C=O)cc1
Reaction time: 3.33 h
Yield: 46 %

Procedure:
In this example a divided electrochemical cell provided with a lead oxide anode and cathode and an anion exchange membrane sold under the tradename IONAC 3475 was used. The anolyte was prepared by admixing 25 grams of sulfuric acid with 250 grams of water and thereafter adding 100 grams of manganous sulfate. The catholyte was prepared by adding 25 grams of sulfuric acid to 250 grams of water and thereafter adding 30 grams of sodium sulfate. The anolyte solution and catholyte solution were added to the respective reservoirs and thereafter 50 grams of p-methoxytoluene was slowly added to the anolyte solution. The electrical energy which was used consisted of an E applied voltage ranging from 4.0 to 6.0 volts along with about 2.0 amps while maintaining the current density at a rate of about 80 milliamps/cm2. In addition, the reaction was run at ambient temperature and atmospheric pressure. The solution was passed through the cell and condenser and back to the cell by use of a pump. The reaction was run for a period of 3.33 hours at the end of which time a gas liquid chromatographic analysis disclosed a yield of 46% anisaldehyde with a selectivity to the aldehyde of greater than 50%, current efficiencies of 85-100% being observed.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:3]=1[C:4](Cl)=[O:5].[CH:12]([N:15]([CH:26]([CH3:28])[CH3:27])[C:16]([S:18][C:19]1[CH:20]=[N:21][CH:22]=[CH:23][C:24]=1[NH2:25])=[S:17])([CH3:14])[CH3:13]>C(Cl)Cl>[CH:26]([N:15]([CH:12]([CH3:14])[CH3:13])[C:16]([S:18][C:19]1[CH:20]=[N:21][CH:22]=[CH:23][C:24]=1[NH:25][C:4](=[O:5])[C:3]1[C:2]([Cl:1])=[CH:10][CH:9]=[CH:8][C:7]=1[Cl:11])=[S:17])([CH3:28])[CH3:27]
Reactant: O=C(Cl)c1c(Cl)cccc1Cl
Reactant: CC(C)N(C(=S)Sc1cnccc1N)C(C)C
Solvent: ClCCl
Product: CC(C)N(C(=S)Sc1cnccc1NC(=O)c1c(Cl)cccc1Cl)C(C)C
Temperature: 20 °C
Reaction time: 0.5 h
Yield: 15.1 %

Procedure:
A solution of 2,6-dichlorobenzoyl chloride (62 mg, 0.30 mmol) in DCM (4 mL) was slowly added to a cooled (0° C.) solution of 4-aminopyridin-3-yl diisopropylcarbamodithioate (100 mg, 0.37 mmol) in DCM (15 mL). The solution was stirred at 20° C. for 30 minutes. The mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography, eluting with EtOAc/petroleum ether (1:4) to give the desired product as a yellow solid (20 mg, 15% yield). LCMS (ESI) m/z: 442.1 [M+H+].
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].ClCC#N.Cl.[C:14]([O-])(=[O:16])[CH3:15].[Na+]>[Cl-].[Zn+2].[Cl-].C(OCC)(=O)C>[OH:2][C:1]1[CH:8]=[CH:7][C:6]2[C:14](=[O:16])[CH2:15][O:5][C:4]=2[CH:3]=1
Reactant: Oc1cccc(O)c1
Reactant: CC(=O)[O-]
Agent: Cl
Agent: N#CCCl
Agent: [Cl-]
Solvent: CCOC(C)=O
Product: O=C1COc2cc(O)ccc21
Temperature: 5 °C
Reaction time: 2 h
Yield: 75.8 %

Procedure:
To a stirred solution of resorcinol (16.0 kg, 145 moles), chloroacetonitrile (13.2 kg, 175 moles) and ethyl acetate (193 kg, 214 L)under nitrogen was added zinc chloride (11.0 kg, 80.8 moles) and the mixture cooled to 5° C. Hydrogen chloride gas (31.2 kg, 855 moles) was bubbled in at such a rate that the internal temperature did not exceed 30° C. The thick slurry was stirred for an additional 2 hours and the solvent removed by vacuum distillation. Water (80 L) was added and the residual ethyl acetate removed by vacuum distillation. The mixture was heated to 60° C. and stirred for 1 hour. The temperature was cooled to 20° C. and then t-butyl methyl ether (146 L, 113 kg) was added and the mixture stirred for 15 minutes. The aqueous layer was separated and the organic layer washed with water (50 L). The layers were separated and the organic layer removed by vacuum distillation. 95% Ethanol (50 L) was added and the distillation continued until all of the t-butyl methyl ether had been removed. Then 95% ethanol (220 L) was added followed by the addition of sodium acetate (21.8 kg, 266 moles) and the mixture heated to reflux for 1 hour. Additional sodium acetate (3.54 kg, 43.2 moles) was added and the mixture refluxed for an additional 1 hour. The mixture was cooled to 5° C. and the solid collected by centrifugation. This was washed with 95% ethanol (51 L), water (800 L), 95% ethanol (29 L) and hexane (30 L). The material was dried at 40° C. under vacuum to afford the desired product (16.5 kg, 75%) which was used without any further purification.
Reaction SMILES: C1(O[C:8](=[O:19])[NH:9][C:10]2[CH:14]=[C:13]([C:15]([CH3:18])([CH3:17])[CH3:16])[O:12][N:11]=2)C=CC=CC=1.[N-]=C=O.[NH2:23][C:24]1[N:29]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([NH2:36])[CH:31]=2)[CH2:28][N:27]=[C:26]2[O:37][CH:38]=[CH:39][C:25]=12>>[NH2:23][C:24]1[N:29]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([NH:36][C:8]([NH:9][C:10]3[CH:14]=[C:13]([C:15]([CH3:16])([CH3:17])[CH3:18])[O:12][N:11]=3)=[O:19])[CH:31]=2)[CH2:28][N:27]=[C:26]2[O:37][CH:38]=[CH:39][C:25]=12
Reactant: CC(C)(C)c1cc(NC(=O)Oc2ccccc2)no1
Reactant: NC1=c2ccoc2=NCN1c1cccc(N)c1
Agent: [N-]=C=O
Product: CC(C)(C)c1cc(NC(=O)Nc2cccc(N3CN=c4occc4=C3N)c2)no1

Procedure:
The compound was prepared following the procedure described in Example 232(b), using (5-t-butyl-isoxazol-3-yl)-carbamic acid phenyl ester as the isocyanate of choice, and 4-Amino-3-(3-aminophenyl)furo[2,3-d]pyrimidine (10) as the diamine of choice. MS(ES) m/e 393 [M+H]+.
Reaction SMILES: [C:1]([O:4][C:5]1[C:24]([CH2:25][CH:26]=[C:27]([CH3:29])[CH3:28])=[C:23]([O:30]COC)[CH:22]=[C:21]([O:34]COC)[C:6]=1[C:7](=[O:20])[CH:8]=[CH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16]COC)=[CH:12][CH:11]=1)(=[O:3])[CH3:2].Cl.CO.C(=O)([O-])O.[Na+]>>[C:1]([O:4][C:5]1[C:24]([CH:25]=[CH:26][CH:27]([CH3:28])[CH3:29])=[C:23]([OH:30])[CH:22]=[C:21]([OH:34])[C:6]=1[C:7](=[O:20])[CH:8]=[CH:9][C:10]1[CH:11]=[CH:12][C:13]([OH:16])=[CH:14][CH:15]=1)(=[O:3])[CH3:2]
Reactant: COCOc1ccc(C=CC(=O)c2c(OCOC)cc(OCOC)c(CC=C(C)C)c2OC(C)=O)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Product: CC(=O)Oc1c(C=CC(C)C)c(O)cc(O)c1C(=O)C=Cc1ccc(O)cc1
Yield: 54.4 %

Procedure:
Then, a liquid mixture of 4.95 g of 2'-acetoxy4,4',6'-tris(methoxymethoxy)-3'-(3-methyl-2-butenyl)chalcone and 8 ml of a hydrochloric acid/methanol reagent was heated and refluxed for 10 minutes, and the temperature of the reaction mixture was lowered to room temperature and the reaction mixture was neutralized with an aqueous solution of sodium hydrogen-carbonate and extracted with 1 l of ethyl acetate. The ethyl layer was washed with water, shaken with a saturated aqueous solution of sodium chloride, dried with anhydrous sodium sulfate and filtered. The solvent was removed from the filtrate by distillation and the obtained residue was subjected to the silica gel column chromatography (130 g of [230-400 mesh silica gel, n-hexane/ethyl acetate=3/1, 0.3 kg/cm2). Fractions of 100 ml were collected and the 13th to 26th fractions were combined to obtain 2.0 g (yield=54.3%) of 2'-acetoxy-4,4',6'-trihydroxy-3'-(3-methyl-butenyl)chalcone in the form of a yellow powder.