Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si:1]([O:18][CH:19]1[CH2:24][CH:23]2[CH:21]([CH:22]2[C:25](=[O:27])[CH3:26])[CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:38](OCC)(=[O:44])[C:39]([O:41][CH2:42][CH3:43])=[O:40]>O1CCCC1>[Si:1]([O:18][CH:19]1[CH2:24][CH:23]2[CH:21]([CH:22]2[C:25](=[O:27])[CH2:26][C:38](=[O:44])[C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(=O)C1C2CC(O[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)CC21
Reactant: CCOC(=O)C(=O)OCC
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CCOC(=O)C(=O)CC(=O)C1C2CC(O[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)CC21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 117.7 %

Procedure:
To a solution of 1-(3-((tert-butyldiphenylsilyl)oxy)bicyclo[3.1.0]hexan-6-yl)ethanone (27 g, 71 mmol) in anhydrous tetrahydrofuran (300 mL) was added lithium bis(trimethylsilyl)amide (106 mL, 106 mmol, 1 M in tetrahydrofuran) slowly at −78° C. under nitrogen. After 0.5 h, diethyl oxalate (15.63 g, 107.0 mmol) was added, and the reaction mixture was warmed to room temperature. After 6 h, the reaction mixture was quenched with 3 M aqueous hydrochloric acid until the solution reached pH ˜3. The mixture was extracted with ethyl acetate (2×200 mL). The combined organics were washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated to provided ethyl 4-(3-((tert-butyldiphenylsilyl)oxy)bicyclo[3.1.0]hexan-6-yl)-2,4-dioxobutanoate as an orange solid (40 g), which was used without further purification. LCMS: [M+H]+ 479.0, [M+Na]+ 501.0, [M+Na+CH3CN]+ 542.0.
Reaction SMILES: [ClH:1].Cl.Cl.[C:4]1([CH:10]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH:18]([C:20]3[CH:31]=[CH:30][C:23]4[N:24]([CH2:28][CH3:29])[C:25]([CH3:27])=[N:26][C:22]=4[CH:21]=3)O)[CH2:13][CH2:12]2)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.S(Cl)([Cl:40])=O>ClC(Cl)Cl>[ClH:40].[ClH:1].[ClH:40].[Cl:40][CH:18]([C:20]1[CH:31]=[CH:30][C:23]2[N:24]([CH2:28][CH3:29])[C:25]([CH3:27])=[N:26][C:22]=2[CH:21]=1)[CH2:17][N:14]1[CH2:15][CH2:16][N:11]([CH:10]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:12][CH2:13]1
Reactant: CCn1c(C)nc2cc(C(O)CN3CCN(C(c4ccccc4)c4ccccc4)CC3)ccc21
Reactant: O=S(Cl)Cl
Agent: Cl
Solvent: ClC(Cl)Cl
Product: CCn1c(C)nc2cc(C(Cl)CN3CCN(C(c4ccccc4)c4ccccc4)CC3)ccc21
Reaction time: 0.5 h
Yield: 85.8 %

Procedure:
To a stirred mixture of 10.3 parts of α-[4-(diphenylmethyl)-1-piperazinylmethyl]-1-ethyl-2-methyl-1H-benzimidazole-5-methanol trihydrochloride in 75 parts of trichloromethane are added dropwise 4.3 parts of thionyl chloride at room temperature. Upon completion, stirring is continued for 30 minutes at reflux temperature After cooling, the precipitated product is filtered off, washed with trichloromethane and with 2,2'-oxybispropane, and dried, yielding 9 parts (85.8%) of 5-{1-chloro-2-[4-(diphenylmethyl)-1-piperazinyl]-ethyl}1-ethyl-2-methyl-1H-benzimidazole trihydrochloride.
Reaction SMILES: [Cl:1][O-:2].[Cl-].[Ca+2:4].[Cl-].Cl[O-].[Ca+2].Cl[O-].[Cl:11]([O-])(=O)=[O:12].[Ca+2].[Cl:16]([O-])(=O)=[O:17]>>[OH2:12].[OH2:17].[Cl-:11].[Ca+2:4].[Cl-:16].[OH2:2].[OH2:12].[OH2:12].[OH2:12].[Cl-:1].[Ca+2:4].[Cl-:11].[OH2:12].[OH2:12].[OH2:12].[OH2:12].[OH2:12].[OH2:12].[Cl-:11].[Ca+2:4].[Cl-:11]
Reactant: [O-][Cl+2]([O-])[O-]
Reactant: [O-]Cl
Agent: [Ca+2]
Agent: [Cl-]
Product: O

Procedure:
In the flow diagram represented in FIG. 1, an aqueous filtrate from a hemibasic hypochlorite or dibasic hypochlorite process comprised of calcium chloride, calcium hypochlorite, and minor amounts of calcium chlorate is fed through line 7 to blender 8 where it is blended with calcium chlorate mother liquor fed to blender 8 through line 33. The blended solution passes through line 9 to first evaporative crystallizer 12. Crystallizer 12 is operated under vacuum and temperature conditions which produce crystalline calcium chloride dihydrate, calcium chloride tetrahydrate, or calcium chloride hexahydrate or mixtures thereof. The crystalline calcium chloride hydrate is separated from a first mother liquor and recovered through line 13. The first mother liquor is fed through line 29 to second evaporative crystallizer 30. Second evaporative crystallizer 30 is operated under vacuum and temperature conditions which will produce anhydrous crystalline calcium chlorate or crystalline calcium chlorate dihydrate or mixtures thereof. Crystals of the calcium chlorate product are separated from a second mother liquor and recovered through line 31. The second mother liquor is fed to blender 8 through line 33.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]([C:12]#[N:13])[C:5]2=O.P(Cl)(Cl)([Cl:17])=O>>[Cl:17][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([I:1])[CH:3]=2)[N:8]=[CH:7][C:6]=1[C:12]#[N:13]
Reactant: O=P(Cl)(Cl)Cl
Reactant: N#Cc1c[nH]c2ccc(I)cc2c1=O
Product: N#Cc1cnc2ccc(I)cc2c1Cl
Yield: 98 %

Procedure:
A mixture of 6 6-iodo-4-oxo-1,4-dihydro-quinoline-3-carbonitrile (example 14b) (100 g, 0.34 mol) in phosphorus oxychloride (300 mL) was refluxed under N2 for 7 h. After cooling, the solvent was removed by rotary evaporator and then by the oil pump. Sat. sodium bicarbonate (200 mL) and ice water were slowly added. The solid was collected by filtration, washed with sat. sodium bicarbonate, water and dried to obtain 4-chloro-6-iodo-quinoline-3-carbonitrile (58 g, 98%) as a yellow solid. LC-MS m/e 315 (MH+).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([NH:12][C:13]2[CH:17]=[CH:16][NH:15][N:14]=2)[N:3]=1.[C:18]([C:20]1[CH:21]=[C:22]([OH:26])[CH:23]=[CH:24][CH:25]=1)#[N:19]>>[NH:15]1[CH:16]=[CH:17][C:13]([NH:12][C:4]2[N:3]=[C:2]([O:26][C:22]3[CH:21]=[C:20]([CH:25]=[CH:24][CH:23]=3)[C:18]#[N:19])[C:11]3[C:6]([CH:5]=2)=[CH:7][CH:8]=[CH:9][CH:10]=3)=[N:14]1
Reactant: N#Cc1cccc(O)c1
Reactant: Clc1nc(Nc2cc[nH]n2)cc2ccccc12
Product: N#Cc1cccc(Oc2nc(Nc3cc[nH]n3)cc3ccccc23)c1

Procedure:
Similar procedure as described in example 10 was used, starting from (1-chloro-isoquinolin-3-yl)-(1H-pyrazol-3-yl)-amine and 3-cyano-phenol to give 3-[3-(1H-pyrazol-3-ylamino)-isoquinolin-1-yloxy]-benzonitrile. LC-MS m/e 328(MH+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[O:17][CH3:18].Cl.[CH3:20][NH:21][O:22][CH3:23].Cl.C(N=C=NCCCN(C)C)C.C(N(CC)C(C)C)(C)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:9][CH2:10][CH:11]([C:14]([N:21]([O:22][CH3:23])[CH3:20])=[O:16])[CH2:12][CH2:13]2)=[CH:4][C:3]=1[O:17][CH3:18]
Reactant: COc1cc(N2CCC(C(=O)O)CC2)ccc1Cl
Reactant: CNOC
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COc1cc(N2CCC(C(=O)N(C)OC)CC2)ccc1Cl
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A mixture of 1-(4-chloro-3-methoxyphenyl)piperidine-4-carboxylic acid (9.0 g, 33.4 mmol), N,O-dimethylhydroxylamine hydrochloride (4.88 g, 50.1 mmol) and DCM (15 mL) was treated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (9.59 g, 50.1 mmol) and 4-(dimethylamino)pyridine (0.408 g, 3.34 mmol). The mixture was cooled in an ice bath and treated with N,N-diisopropylethylamine (11.62 mL, 66.7 mmol) over 3 min. After 10 min, the cooling bath was removed and the mixture was stirred at RT overnight (ca. 14 h). At the conclusion of this period, the mixture was diluted with DCM (50 mL), and then washed successively with saturated NaHCO3 (3×25 mL), 1 M HCl (2×50 mL) and brine. The organic phase was dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography using a 120 g silica gel cartridge and 10:1 Hex/EtOAc to elute the product. The fractions containing the product were pooled and concentrated on a rotary evaporator to give 1-(4-chloro-3-methoxyphenyl)-N-methoxy-N-methylpiperidine-4-carboxamide as pale yellow oil.
Reaction SMILES: C(O[C@H:5]1[NH:8][C:7](=[O:9])[C@@H:6]1[C@H:10]([O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])[CH3:11])(=O)C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.[C:32]([CH:35]1[CH2:39][N:38]([C:40]([O:42][CH2:43][CH:44]=[CH2:45])=[O:41])[CH2:37][CH2:36]1)(=[O:34])[CH3:33].C(=O)([O-])O.[Na+]>ClCCl.O.C(OCC)(=O)C.C(N(CC)CC)C>[CH2:43]([O:42][C:40]([N:38]1[CH2:37][CH2:36][CH:35]([C:32](=[O:34])[CH2:33][C@H:5]2[NH:8][C:7](=[O:9])[C@@H:6]2[C@H:10]([O:12][Si:13]([C:16]([CH3:17])([CH3:18])[CH3:19])([CH3:14])[CH3:15])[CH3:11])[CH2:39]1)=[O:41])[CH:44]=[CH2:45]
Reactant: CC(=O)O[C@H]1NC(=O)[C@@H]1[C@@H](C)O[Si](C)(C)C(C)(C)C
Reactant: C=CCOC(=O)N1CCC(C(C)=O)C1
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CCN(CC)CC
Product: C=CCOC(=O)N1CCC(C(=O)C[C@H]2NC(=O)[C@@H]2[C@@H](C)O[Si](C)(C)C(C)(C)C)C1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 55.7 %

Procedure:
To a solution of (3R,4R)-4-acetoxy-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-2-oxoazetidine (2.2 g) and triethylamine (1.1 ml) in dichloromethane (20 ml) was added trimethylsilyl trifluoromethanesulfonate (1.5 ml) at -60° C. under nitrogen, and the mixture was stirred at 0° C. for 30 minutes (Solution A). To a solution of 4-acetyl-1-allyloxycarbonylpyrrolidine (1.0 g) and triethylamine (0.71 ml) in dichloromethane (10 ml) was added trimethylsilyl trifluoromethanesulfonate (0.98 ml) at -60° C. under nitrogen and the resulting mixture was stirred at 0° C. for 30 minutes. To this mixture was added dropwise the Solution A at 0° C. under nitrogen, and the mixture was stirred for additional 4 hours at 0° C. The reaction mixture was taken up into a mixture of ethyl acetate and water and the mixture was stirred at ambient temperature for 2 hours. After adjusting pH to around 6.5 with aqueous sodium hydrogen carbonate, the organic layer was separated, washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel eluting with a mixture of n-hexane and ethyl acetate (1:2, V/V) to give (3S,4R)-4-[2-(1-allyloxycarbonylpyrrolidin-3-yl)-2-oxoethyl]-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-2-oxoazetidine (1.2 g).
Reaction SMILES: [F:1][C:2]1[C:7]([CH:8]=[O:9])=[C:6]([OH:10])[C:5]([O:11][CH3:12])=[CH:4][CH:3]=1.C1COCC1.[BH4-].[Na+].Cl>C(O)C>[F:1][C:2]1[C:7]([CH2:8][OH:9])=[C:6]([OH:10])[C:5]([O:11][CH3:12])=[CH:4][CH:3]=1
Reactant: COc1ccc(F)c(C=O)c1O
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: C1CCOC1
Product: COc1ccc(F)c(CO)c1O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 88 %

Procedure:
To a solution of 6.85 g of 6-fluoro-2-hydroxy-3-methoxybenzaldehyde [CAS No. 457628-15-8] in 200 ml of an ethanol:THF=1:1 mixed solvent there was added 1.52 g of sodium borohydride while cooling on ice. After stirring at room temperature for 30 minutes, 1N hydrochloric acid was added to the reaction mixture while cooling on ice. The organic layer was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The desiccating agent was filtered off, and the filtrate was concentrated under reduced pressure to give 3-fluoro-2-hydroxymethyl-6-methoxyphenol (6.1 g, crude product).
Reaction SMILES: [Br:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[CH:9](=O)/[CH:10]=[CH:11]/[CH3:12]>Cl>[Br:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:3]=1[N:4]=[C:11]([CH3:12])[CH:10]=[CH:9]2
Reactant: C/C=C/C=O
Reactant: Nc1ccccc1Br
Agent: Cl
Product: Cc1ccc2cccc(Br)c2n1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
To a refluxed solution of 2-bromoaniline (5.0 g, 29.1 mmol) in 6 N hydrochloric acid (15 mL) was added crotonaldehyde (2.2409 g, 32.0 mmol) drop wise. After heated under reflux for 8 h, the reaction mixture was cooled down and washed with 20 ml of ether, followed by addition of zinc chloride (3.95 g). The reaction mixture was stirred for 30 min at room temperature and another 15 min at 0° C. to give yellow solid. The solid was collected and washed with 3 N cold hydrochloric acid, and then suspended in 2-propanol (20 mL) and stirred for 5 min at room temperature. The solid was filtered and washed with 2-propanol until the washing becomes colorless, then washed with 20 mL of ether and dried with air. The solid was suspended in 15 mL of cold water and 5 mL of concentrated ammonium hydroxide was added. Shake it and then extract with 3×20 mL of ether. Dried over magnesium sulfate and concentrated to give a dark solid. Purification by chromatography (EtOAC/Hexanes 10:90) yielded a white solid product. (3.62 g, 56%) 1H NMR(400 MHz CDCl3) δ8.02 (2H, t, J=8.4 Hz), 7.73 (1H, d, J=8 Hz), 7.33 (2H, t, J=8), 2.82 (3H, s); 13C NMR (300 MHz CDCl3) δ160.2, 144.7, 136.4, 132.8, 127.6, 127.3, 125.9, 124.0, 122.7, 25.6; EIMS, m/z 221/223 (M/(M+2)); Anal. Calcd for C10H8BrN: C, 54.08; H, 3.63; N, 6.31. Found: C, 54.25; H, 3.41; N, 5.89.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:12](O)[CH3:13])[C:5]([OH:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].C([SiH](CC)CC)C>FC(F)(F)C(O)=O>[Br:1][C:2]1[CH:3]=[C:4]([CH2:12][CH3:13])[C:5]([OH:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8]
Reactant: CC(O)c1cc(Br)cc(C(=O)O)c1O
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: CCc1cc(Br)cc(C(=O)O)c1O
Temperature: 90 °C
Yield: 61.7 %

Procedure:
974 mg (3.73 mmol) of 5-bromo-2-hydroxy-3-(1-hydroxy-ethyl)-benzoic acid was dissolved in trifluoroacetic acid under nitrogen. 715 μL (521 mg, 4.48 mmol) of triethyl silane was added and the resulting mixture was heated to 90° C. for 2 h. The mixture was evaporated and the residue purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes to afford 563 mg (2.30 mmol, 62%) of 5-bromo-3-ethyl-2-hydroxy-benzoic acid as a colorless solid. MS: m/z 243.0+244.9 (M+H+).
Reaction SMILES: [CH2:1]([N:3]1[CH2:8][CH2:7][CH:6]([N:9]([CH3:31])[C:10]2[C:11]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)=[N:12][C:13]3[C:18]([N:19]=2)=[CH:17][C:16]([C:20]([O:22]C)=[O:21])=[CH:15][CH:14]=3)[CH2:5][CH2:4]1)[CH3:2].[OH-].[Na+]>CO>[CH2:1]([N:3]1[CH2:8][CH2:7][CH:6]([N:9]([CH3:31])[C:10]2[C:11]([C:24]3[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=3)=[N:12][C:13]3[C:18]([N:19]=2)=[CH:17][C:16]([C:20]([OH:22])=[O:21])=[CH:15][CH:14]=3)[CH2:5][CH2:4]1)[CH3:2]
Reactant: CCN1CCC(N(C)c2nc3cc(C(=O)OC)ccc3nc2-c2ccc(F)cc2)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCN1CCC(N(C)c2nc3cc(C(=O)O)ccc3nc2-c2ccc(F)cc2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 71.8 %

Procedure:
To a solution of methyl 3-[(1-ethylpiperidin-4-yl)(methyl)amino]-2-(4-fluorophenyl)quinoxaline-6-carboxylate (53 mg, 0.12 mmol) in methanol (30 mL) was added sodium hydroxide (26.5 mg, 0.66 mmol), and the resulting mixture was stirred overnight at room temperature. The reaction mixture was concentrated in vacuo, dissolved in water (10 mL), and adjusted to pH 5 with HCl (3N) to give the precipitate, which was collected by filtration to afford 3-[(1-ethylpiperidin-4-yl)(methyl)amino]-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid as a light yellow solid (35.2 mg, 69%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:18](=O)[O:17][C:15](=[O:16])[C:5]2=[C:6]2[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[O:8][C:7]=12.[CH3:20][N:21]([CH3:25])[CH2:22][CH2:23][NH2:24]>C1(C)C=CC=CC=1>[CH3:20][N:21]([CH3:25])[CH2:22][CH2:23][N:24]1[C:15](=[O:16])[C:5]2[C:6]3[C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[O:8][C:7]=3[C:2]([CH3:1])=[CH:3][C:4]=2[C:18]1=[O:17]
Reactant: Cc1cc2c(c3c1oc1ccccc13)C(=O)OC2=O
Reactant: CN(C)CCN
Solvent: Cc1ccccc1
Product: Cc1cc2c(c3c1oc1ccccc13)C(=O)N(CCN(C)C)C2=O
Yield: 89.4 %

Procedure:
To 50 ml of toluene were added 140 mg of 4-methyldibenzofuran-1,2-dicarboxylic anhydride and 270 mg of N,N-dimethylethylenediamine. The mixture was azeotropicallyl refluxed for 2 hours. The solvent was removed by distillation under reduced pressure. The residue was recrystallized from ethanol to obtain 160 mg (yield: 89%) of 2-(2-dimethylaminoethyl)-5-methyl-1H-benzofuro[3,2-e]isoindole-1,3(2H)-dione as light yellow needles.
Reaction SMILES: [C:1]([O:9][CH3:10])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:11]1[CH2:16][CH2:15]C(O)[CH2:13][CH2:12]1.C(OC(C)C)(C)C.O1CCOCC1>>[C:1]([O:9][CH:10]1[CH2:15][CH2:16][NH:11][CH2:12][CH2:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OC1CCNCC1
Reactant: COC(=O)c1ccccc1
Solvent: C1COCCO1
Solvent: CC(C)OC(C)C
Product: O=C(OC1CCNCC1)c1ccccc1
Yield: 65 %

Procedure:
In an argon atmosphere, a mixture of methyl benzoate (3.0 mmol), piperidin-4-ol (3.6 mmol), Zn4(OCOCF3)6O (1.25 mol % in terms of mole number) and diisopropyl ether/1,4-dioxane (3/1) (5.0 ml) was heated to reflux for 46 hours, and as a result, piperidin-4-yl benzoate was obtained at a yield of 65%. The yield of N-benzoylpiperidin-4-yl benzoate was 30%.
Reaction SMILES: [Cl-].[Cl-].[NH3+:3][C@@H:4]([C:17]1[N:18]=[N:19][N:20]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:21]=1)[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])=[CH:7][NH+:6]=1.[C:28]([C:32]1[CH:37]=[CH:36][C:35]([CH2:38][C:39](O)=[O:40])=[CH:34][CH:33]=1)([CH3:31])([CH3:30])[CH3:29].Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>O.C(Cl)Cl>[CH2:26]([O:25][C:23](=[O:24])[CH2:22][N:20]1[CH:21]=[C:17]([C@H:4]([NH:3][C:39](=[O:40])[CH2:38][C:35]2[CH:36]=[CH:37][C:32]([C:28]([CH3:30])([CH3:29])[CH3:31])=[CH:33][CH:34]=2)[C:5]2[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]([F:16])([F:14])[F:15])=[CH:7][N:6]=2)[N:18]=[N:19]1)[CH3:27]
Reactant: CCOC(=O)Cn1cc([C@H]([NH3+])c2ccc(OCC(F)(F)F)c[nH+]2)nn1
Reactant: CC(C)(C)c1ccc(CC(=O)O)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: CCOC(=O)Cn1cc([C@H](NC(=O)Cc2ccc(C(C)(C)C)cc2)c2ccc(OCC(F)(F)F)cn2)nn1
Temperature: 25 °C
Reaction time: 2 h
Yield: 45.8 %

Procedure:
To a 100 ml round bottom flask equipped with a magnetic stir bar were added 2-{(S)-ammonio[1-(2-ethoxy-2-oxoethyl)-1H-1,2,3-triazol-4-yl]methyl}-5-(2,2,2-trifluoroethoxy)pyridinium dichloride (0.265 g, 0.614 mmol), 4-tert-butylphenylacetic acid (0.118 g, 0.614 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.118 g, 0.614 mmol), 1-hydroxy-7-azabenzotriazole (0.084 g, 0.614 mmol) and diisopropylethylamine (0.236 ml, 1.350 mmol) into 10.0 ml of CH2Cl2. The resulting solution was stirred at room temperature for 2 hours. The reaction mixture was diluted with water and the two layers were separated. The aqueous layer was extracted with CH2Cl2. The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuum. Purification by preparative HPLC (20-90% CH3CN/H2O over 30 min, 0.05% added TFA, C18 column) to afford 0.150 g (46%) of the title compound. 1H NMR (CDCl3, 400 MHz) δ 8.219 (s, 1H), 7.610 (m, 2H), 7.340 (m, 3H), 7.255 (m, 1H), 7.184 (m, 2H), 6.322 (d, J=7.96 Hz, 1H), 5.041 (s, 2H), 4.347 (q, J=7.97 Hz, 2H), 4.210 (q, J=7.14 Hz, 2H), 3.912 (br s, 1H), 3.585 (s, 2H), 1.278 (s, 9H), 1.249 (t, J=7.19 Hz, 3H). ES-MS [M+1]+: 534.3.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[C:11]([C:13]([O:15]CC)=[O:14])[N:10]=[C:9]2[C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[Cl:25])=[CH:4][CH:3]=1.[Li+].[OH-].O.Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH:12]=[C:11]([C:13]([OH:15])=[O:14])[N:10]=[C:9]2[C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[Cl:25])=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1cn(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2Cl)n1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1cn(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2Cl)n1
Temperature: 50 °C
Reaction time: 16 h
Yield: 98.2 %

Procedure:
To a magnetically stirred solution of ethyl 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-1H-imidazole-4-carboxylate (18.44 g, 0.0466 mol) in THF (240 ml) was added LiOH (2.24 g, 0.0932 mol) and H2O (240 ml). The resulting mixture was stirred at 50° C. for 16 h to give a clear solution. After cooling to room temperature, HCl (1 N solution, 95 ml) and H2O (240 ml) were added to give a precipitate which was collected by filtration, washed with water and dried in vacuo to give 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-1H-imidazole-4-carboxylic acid (16.83 g, 98% yield), mp 138-142° C. (decomposition); 1H-NMR (600 MHz, DMSO-d6) δ 7.08 (br d, J=8 Hz, 2H), 7.31-7.37 (m, 4H), 7.45 (d, J=8 Hz, 1H), 7.96 (s, 1H); 13C-NMR (150 MHz, DMSO-d6) δ 126.87, 127.85, 127.91, 128.47, 129.36, 129.66, 133.56, 133.99, 134.44, 134.49, 135.54, 135.99, 143.77, 163.67.
Reaction SMILES: [OH:1][C:2]1[CH:29]=[CH:28][C:5]([C:6]([C:8]2[CH:27]=[CH:26][C:11]([CH2:12][S:13][C:14]3[N:15]=[C:16]4[CH:25]=[CH:24][CH:23]=[CH:22][N:17]4[C:18](=[O:21])[C:19]=3[CH3:20])=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1.Cl.Cl[CH2:32][CH2:33][N:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:20][C:19]1[C:18](=[O:21])[N:17]2[CH:22]=[CH:23][CH:24]=[CH:25][C:16]2=[N:15][C:14]=1[S:13][CH2:12][C:11]1[CH:26]=[CH:27][C:8]([C:6](=[O:7])[C:5]2[CH:4]=[CH:3][C:2]([O:1][CH2:32][CH2:33][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[CH:29][CH:28]=2)=[CH:9][CH:10]=1
Reactant: Cc1c(SCc2ccc(C(=O)c3ccc(O)cc3)cc2)nc2ccccn2c1=O
Reactant: ClCCN1CCOCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1c(SCc2ccc(C(=O)c3ccc(OCCN4CCOCC4)cc3)cc2)nc2ccccn2c1=O
Yield: 66.4 %

Procedure:
A solution of 2-[4-(4-hydroxybenzoyl)benzylthio]-3-methyl-4H-pyrido[1,2-a]pyrimidin-4-one (214 mg), 4-(2-chloroethyl)morpholine hydrochloride (157 mg) and potassium carbonate (247 mg) in DMF (7 ml) was stirred at 80° C. for 4 hours. This reaction mixture was concentrated and the residue was dissolved in ethyl acetate, washed with water, and dried. Then, hydrogen chloride/ethyl acetate was added and the precipitated hydrochloride was recovered by filtration and dried to provide the title compound as colorless solid (182 mg).
Reaction SMILES: C[O:2][C:3]1[C:8]2[CH2:9][CH2:10][CH:11]([CH2:14][CH2:15][OH:16])[CH2:12][CH2:13][C:7]=2[C:6]([O:17]C)=[C:5]([O:19][CH3:20])[C:4]=1[O:21][CH3:22].N1C(C(O)=O)=CC=CC=1C(O)=O.C1COCC1.O=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+]>O>[OH:16][CH2:15][CH2:14][CH:11]1[CH2:10][CH2:9][C:8]2[C:3](=[O:2])[C:4]([O:21][CH3:22])=[C:5]([O:19][CH3:20])[C:6](=[O:17])[C:7]=2[CH2:13][CH2:12]1
Reactant: COc1c2c(c(OC)c(OC)c1OC)CCC(CCO)CC2
Agent: O=C(O)c1cccc(C(=O)O)n1
Agent: O=[N+]([O-])[O-]
Agent: [Ce+4]
Solvent: C1CCOC1
Solvent: O
Product: COC1=C(OC)C(=O)C2=C(CCC(CCO)CC2)C1=O
Reaction time: 0.25 h
Yield: 66.3 %

Procedure:
To a mixture of 2-(1,2,3,4-tetramethoxy-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-7-yl)ethanol (800 mg), 2,6-pyridinedicarboxylic acid (1.29 g), THF (16 ml), and water (8 ml) was dropwise added a solution of CAN (5.65 g) in water (8 ml) with cooling with ice. After the reaction mixture was stirred for 15 min, water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride and dried. The solvent was removed in vacuo. The residue was purified by silica gel column chromatography (hexane to hexane:ethyl acetate=2:1) and then with recrystallization from hexane-ethyl acetate to yield the entitled compound (479 mg) as crystals.