Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[C:20]([CH3:23])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].O>C1COCC1.CCO>[C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[C:20]([CH3:23])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)C(OC(C)(C)C)c1c(C)c(C)c2ccccc2c1-c1ccc(Cl)cc1
Solvent: C1CCOC1
Solvent: O
Solvent: CCO
Product: Cc1c(C(OC(C)(C)C)C(=O)O)c(-c2ccc(Cl)cc2)c2ccccc2c1C
Temperature: 100 °C
Yield: 40 %

Procedure:
A solution of the crude ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-3,4-dimethylnaphthalen-2-yl)acetate in THF (500 μL), EtOH (Absolute, 250 μL), and H2O (250 μL) was treated with LiOH monohydrate (61 mg, 1.45 mmol) and heated to 100° C. in a sealed vessel for 4 h. The reaction was cooled to 23° C., filtered through a 0.45 micron filter, and directly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA). The product-containing fractions were combined and lyophilized, giving the title compound (parent form) (8.0 mg, 40% over 2 steps). 1H NMR (400 MHz, DMSO-d6) δ 12.73 (s, broad, 1H), 8.15 (d, J=8.2 Hz, 1H), 7.72-7.62 (m, 2H), 7.57-7.47 (m, 2H), 7.39-7.32 (m, 2H), 7.19 (d, J=8.2 Hz, 1H), 5.07 (s, 1H), 2.63 (s, 3H), 2.51 (s, 3H), 0.93 (s, 9H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([N+:12]([O-])=O)[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[BH4-].[Na+]>CO>[NH2:12][C:10]1[CH:9]=[C:4]([CH:3]=[C:2]([Br:1])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]
Reactant: COC(=O)c1cc(Br)cc([N+](=O)[O-])c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COC(=O)c1cc(N)cc(Br)c1
Reaction time: 0.01 h
Yield: 98.4 %

Procedure:
To a stirred solution of methyl 3-bromo-5-nitrobenzoate (1.0 g, 3.8 mmol) in methanol (30 mL) was added NiCl2.6H2O (1.8 g, 7.6 mmol) and NaBH4 (430 mg, 11 mmol) successively at 0° C. The reaction mixture was stirred for 30 seconds and was then quenched by the addition of water. The mixture was extracted with ethyl acetate (30 mL×3). The combined organic layers were washed with brine and water, dried over anhydrous Na2SO4, and concentrated under vacuum to afford methyl 3-amino-5-bromobenzoate (860 mg, 97% yield). 1H NMR (400 MHz, d-DMSO) δ 7.14 (dd, J=2.0, 2.4 Hz, 1H), 7.11 (t, J=2.4 Hz, 1H), 6.94 (t, J=2.8 Hz, 1H), 5.72 (brs, 2H), 3.79 (s, 3H).
Reaction SMILES: F.C([Si](C)(C)[O:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:15](=[O:40])[N:16]([C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[CH:34]=2)[C:17]2[N:18]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)[N:19]=[C:20]3[C:25]=2[CH:24]=[CH:23][CH:22]=[CH:21]3)[CH2:10][CH2:9]1)(C)(C)C>C(OC(C)=O)(C)C.[Cl-].[Na+].O.C(Cl)Cl>[Cl:39][C:35]1[CH:34]=[C:33]([N:16]([C:17]2[N:18]([C:26]3[CH:27]=[CH:28][C:29]([Cl:32])=[CH:30][CH:31]=3)[N:19]=[C:20]3[C:25]=2[CH:24]=[CH:23][CH:22]=[CH:21]3)[C:15]([NH:14][C@H:11]2[CH2:10][CH2:9][C@H:8]([OH:7])[CH2:13][CH2:12]2)=[O:40])[CH:38]=[CH:37][CH:36]=1
Reactant: CC(C)(C)[Si](C)(C)O[C@H]1CC[C@H](NC(=O)N(c2cccc(Cl)c2)c2c3ccccc3nn2-c2ccc(Cl)cc2)CC1
Agent: F
Agent: [Cl-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)OC(C)C
Solvent: O
Product: O=C(N[C@H]1CC[C@H](O)CC1)N(c1cccc(Cl)c1)c1c2ccccc2nn1-c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Hydrofluoric acid (48%, 200 μl, 16 μmol) was added to a solution of trans-3-[4-(tert-butyl-dimethyl-silanyloxy)-cyclohexyl]-1-(3-chloro-phenyl)-1-[2-(4-chloro-phenyl)-2H-indazol-3-yl]-urea (10 mg, 16 μmol) in CH3CN/CH2Cl2 1/1 (400 μl). The reaction mixture was stirred for 4 h at ambient temperature, diluted with CH2Cl2 (5 ml) and washed with saturated aqueous NaHCO3 solution and brine. The organic layer was dried over Na2SO4. The solvent was removed under reduced pressure to give the title compound (2 mg, 4 μmol; 25%) as brown solid. MS: m/e=495.5 [M+H+].
Reaction SMILES: [CH:1]([N:3]1CCC[C:4]1=O)=C.[CH:9]([CH:11]1[CH2:18][CH2:17][CH2:16][CH2:15][NH:14][C:12]1=[O:13])=C.CN(CCCC=C(C)C(N)=O)C.[C:31]([C:39](=[CH2:43])[C:40]([NH2:42])=[O:41])([CH2:34][C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:33])[CH3:32].OS(O)(=O)=O>C(O)C>[CH3:9][C:11]([C:12]([NH:14][CH2:15][CH2:16][CH2:17][N:3]([CH3:4])[CH3:1])=[O:13])=[CH2:18].[C:31]([C:39](=[CH2:43])[C:40]([NH2:42])=[O:41])([CH2:34][C:35]([CH3:37])([CH3:38])[CH3:36])([CH3:32])[CH3:33]
Reactant: C=CC1CCCCNC1=O
Reactant: C=CN1CCCC1=O
Agent: C=C(C(N)=O)C(C)(C)CC(C)(C)C
Agent: CC(=CCCCN(C)C)C(N)=O
Agent: O=S(=O)(O)O
Solvent: CCO
Product: C=C(C)C(=O)NCCCN(C)C
Temperature: 68 °C

Procedure:
Vinyl pyrrolidone (VP) (55.6 g), vinyl caprolactam (VCL) (577.5 g), dimethylaminopropyl methacrylamide (DMAPMA) (42.6 g), tert-octyl acrylamide (18.3 g) and ethanol (848.2 g) were charged into a 2-liter water-jacketed resin flask. The reaction flask was equipped with a condenser, a thermometer, a septum (for catalyst addition), an anchor-type metal stirrer, and a nitrogen sparge tube. Nitrogen was bubbled the solution while the resin flask was heated to 68° C. using hot water circulating through the jacketed flask. After an additional half-hour of degassing at reflex, a first shot of Lupersol 11 (0.25 ml) was injected into the flask. Subsequently, Lupersol 11 additions were made at 10, 40, 70, 100 minutes after the first addition. The reaction temperature was increased to 74° C. and 2 shots of Lupersol 554 M75 (0.12 ml) was then added at 240 and 330 minutes. The contents were allowed to react for an additional 5 hours and cooled to 35°-40° C. After neutralization with 12.5 g of H2SO4 (conc) the product was discharged as a 45% solution in ethanol.
Reaction SMILES: Cl.[CH2:2]([O:4][C:5](=[O:8])[CH2:6][NH2:7])[CH3:3].CCN(CC)CC.[C:16](Cl)(=[O:20])[CH:17]([CH3:19])[CH3:18]>C(Cl)Cl>[CH2:2]([O:4][C:5](=[O:8])[CH2:6][NH:7][C:16](=[O:20])[CH:17]([CH3:19])[CH3:18])[CH3:3]
Reactant: CC(C)C(=O)Cl
Reactant: CCOC(=O)CN
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)CNC(=O)C(C)C

Procedure:
10.00 g of glycine ethyl ester hydrochloride (71.6 mmol) and 21.97 ml of NEt3 (2.2 eq.) were dissolved in 200 ml of CH2Cl2 and treated between 0° and 5° dropwise with 7.81 ml of isobutyryl chloride (1.05 eq.), dissolved in 50 ml of CH2Cl2. The reaction mixture was allowed to reach ambient temperature (2.5 h) and then quenched by carefully pouring onto crashed ice/HCl/AcOEt. Separation of the layers, additional extraction of the aqueous phase with AcOEt, washing with Na2CO3 and brine, drying of the combined organic phase over magnesium sulfate, and evaporation of the solvents, followed by flash chromatography (SiO2, hexane/AcOEt=6/4) yielded 11.74 g of the title compound as colorless oil.
Reaction SMILES: [N+](C1C=CC([O:10][C:11](=O)/[CH:12]=[CH:13]/[CH:14]=[C:15](/[C:22]2[CH:27]=[CH:26][C:25](OC)=[CH:24][CH:23]=2)\[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=CC=1)([O-])=O.[N:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][CH2:38][CH2:39][CH2:40][NH2:41])[CH:32]=1.[O:42]1CCC[CH2:43]1>>[CH3:43][O:42][C:26]1[CH:27]=[C:22](/[C:15](/[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[CH:14]\[CH:13]=[CH:12]\[C:11]([NH:41][CH2:40][CH2:39][CH2:38][CH2:37][C:33]2[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=2)=[O:10])[CH:23]=[CH:24][CH:25]=1
Reactant: NCCCCc1cccnc1
Reactant: COc1ccc(/C(=C/C=C/C(=O)Oc2ccc([N+](=O)[O-])cc2)c2ccccc2)cc1
Reactant: C1CCOC1
Product: COc1cccc(/C(=C\C=C\C(=O)NCCCCc2cccnc2)c2ccccc2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
As described in Example 134, (E,E)-5-(4-methoxyphenyl)-5-phenyl-2,4-pentadienoic acid 4-nitrophenyl ester (3.3 g) and 3-pyridinebutanamine (1.24 g) in tetrahydrofuran (20 mL) was stirred for 1 hour at room temperature. After the usual work up, the crude amide was purified by HPLC (ethyl acetate) and crystallized from ethyl acetate to furnish 2.7 g of (2E,4Z)-5-(3-methoxyphenyl)-5-phenyl-N-[4-(3-pyridinyl)butyl]-2,4-pentadienamide, mp 89°-91° C. A portion was recrystallized from the same solvent to provide the pure amide, mp 90°-92° C. Anal. Calcd for C27H28N2O2 : C, 78.61; H, 6.84; N, 6.79 Found: C, 78.88; H, 6.87; N, 6.66.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH2:13])(=[O:12])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].[O:14]1[CH2:19]O[CH2:17][O:16][CH2:15]1.CS(O)(=O)=O>C(O)(=O)C.O>[N:13]1([S:10]([C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=2)(=[O:11])=[O:12])[CH2:17][O:16][CH2:15][O:14][CH2:19]1
Reactant: NS(=O)(=O)c1ccc([N+](=O)[O-])cc1
Reactant: C1OCOCO1
Agent: CS(=O)(=O)O
Solvent: O
Solvent: CC(=O)O
Product: O=[N+]([O-])c1ccc(S(=O)(=O)N2COCOC2)cc1
Temperature: 35 °C
Reaction time: 0.33 h
Yield: 34.8 %

Procedure:
4-Nitrobenzenesulphonamide (2.02 g, 10 mmol) was added to a solution of 1,3,5-trioxane (1.96 g, 20 mmol) in acetic acid (5 ml). The mixture was cooled for 5 minutes ated methanesulphonic acid (10 ml) was added slowly. The mixture was then stirred at 35° C. for 20 minutes, cooled to 0° C., diluted with water and extracted with ethyl acetate. The combined extracts were washed twice with water and twice with 5% aqueous sodium hydrogen carbonate solution, then dried and the volatiles removed by evaporation. The residue was recrystallized from ethanol to give the title compound (955 mg, 35%). NMR: 4.87 (s, 2H), 5.30 (s, 4H), 8.20 (d, 2H), 8.42 (d, 2H).
Reaction SMILES: [Cl:1][C:2]1[C:3]2[N:4]([C:8]([CH:11]3[CH2:19][CH2:18][CH2:17][C:16]4[N:15]([CH3:20])[N:14]=[CH:13][C:12]3=4)=[N:9][CH:10]=2)[CH:5]=[CH:6][N:7]=1.C1C(=O)N([Br:28])C(=O)C1>CN(C=O)C>[Br:28][C:10]1[N:9]=[C:8]([CH:11]2[CH2:19][CH2:18][CH2:17][C:16]3[N:15]([CH3:20])[N:14]=[CH:13][C:12]2=3)[N:4]2[CH:5]=[CH:6][N:7]=[C:2]([Cl:1])[C:3]=12
Reactant: O=C1CCC(=O)N1Br
Reactant: Cn1ncc2c1CCCC2c1ncc2c(Cl)nccn12
Solvent: CN(C)C=O
Product: Cn1ncc2c1CCCC2c1nc(Br)c2c(Cl)nccn12
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 16 %

Procedure:
To a solution of 8-chloro-3-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)imidazo[1,5-a]pyrazine (1.0 g, 3.5 mmol) in DMF (20 mL) was added NBS (600 mg, 3.4 mmol) dropwise in DMF (20 mL) at 0° C. The mixture was stirred about 10 min under this condition, and then was poured into ice-water. The solid was filtered and dried under high vacuum to give 1-bromo-8-chloro-3-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)imidazo[1,5-a]pyrazine (200 mg, 15.6%). MS-ESI (m/z): 368 (M+1)+ (Acq Method: 10-80AB_2 min_220 &254.1 cm; Rt: 1.04 min)
Reaction SMILES: [CH2:1]([CH:4]1[CH2:9][CH:8]2[O:10][CH2:11][CH2:12][O:13][CH:7]2[CH2:6][C:5]1=O)[CH:2]=[CH2:3].[C:15]([O:19]C)(=O)[C:16]#[CH:17].[NH3:21]>>[CH2:1]([CH:4]1[C:5]2[NH:21][C:15](=[O:19])[CH:16]=[CH:17][C:6]=2[CH2:7][C:8]2([O:13][CH2:12][CH2:11][O:10]2)[CH2:9]1)[CH:2]=[CH2:3]
Reactant: C#CC(=O)OC
Reactant: N
Reactant: C=CCC1CC2OCCOC2CC1=O
Product: C=CCC1CC2(Cc3ccc(=O)[nH]c31)OCCO2
Temperature: 150 °C
Yield: 60 %

Procedure:
A mixture of 2 (1.96 g, 10 mmol), methyl propiolate (1.68 g, 20 mmol), and 40 mL of ammonia-saturated methanol in a 300 mL stainless steel Parr reaction vessel was heated to 150° C. for 6 h. After cooling, the solvent was removed under reduced pressure, and the crude product was purified by flash chromatography with 3% MeOH in CH2Cl2 as the eluent to afford 2.96 g (60%) of the pyridone 3: Rf =0.40 (10% MeOH in CH2Cl2); IR (KBr) 3448, 2887, 1649, 1618, 1093 cm-1 ; 1H NMR δ6.38 (d, 1H, J=9.3 Hz), 5.75 (m, 1H), 5.11 (m, 2H), 3.97 (m, 3H), 3.10 (m, 1H), 2.70 (m, 4H), 1.85 (m, 2H); 13C NMR δ164.7, 143.9, 143.2, 118.1, 118.0, 111.8, 107.4, 64.6, 64.4, 37.6, 36.8, 35.8, 34.8.
Reaction SMILES: [Br:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][NH:10][CH2:9][CH2:8][C:6]=2[N:7]=1.C(N(CC)CC)C.[CH3:19][S:20](Cl)(=[O:22])=[O:21]>C(Cl)Cl>[Br:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([S:20]([CH3:19])(=[O:22])=[O:21])[CH2:9][CH2:8][C:6]=2[N:7]=1
Reactant: CS(=O)(=O)Cl
Reactant: Brc1ncc2c(n1)CCNC2
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)N1CCc2nc(Br)ncc2C1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture of 2-bromo-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (0.1 g, 0.47 mmol) and triethylamine (0.2 mL) in 2 mL of DCM, at 0° C., was added MsCl (0.1 mL). The mixture was stirred at room temperature for 1 h then diluted with 20 mL of DCM and washed with a mixture of saturated NaHCO3 (15 mL) and water (15 mL). The DCM was evaporated to afford the crude 59a.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][C:9]2=NNC(N)=S)=[CH:4][CH:3]=1.C[OH:18].NNC(N)=S>CC(O)=O>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][C:9]2=[O:18])=[CH:4][CH:3]=1
Reactant: CO
Reactant: NC(=S)NN=C1CCCc2ccc(Br)cc21
Agent: NNC(N)=S
Solvent: CC(=O)O
Product: O=C1CCCc2ccc(Br)cc21
Yield: 68 %

Procedure:
7-Bromo-1-tetralone thiosemicarbazone (21) Into a round bottom flask containing the appropriate ketone (0.347 g, 1.54 mmol), 10 mL of anhydrous methanol were added and the solution was refluxed for about 10 minutes. To the warm ketone solution, thiosemicarbazide (0.246 g, 2.70 mmol) and 0.7 mL of 1% solution of HOAc were added. The reaction mixture was refluxed under nitrogen atmosphere for 18 h, at which point, the solvent was evaporated. The crude reaction mixture was purified by flash chromatography (30% EtOAc/70% hex) which afforded 0.314 g (1.05 mmol) of the product in a 68% yield.
Reaction SMILES: CN(C=O)C.[C:6]([NH2:9])(=[O:8])[CH3:7].[Cl:10][C:11]1[CH:12]=[C:13]([F:18])[C:14](F)=[N:15][CH:16]=1.Cl>C1COCC1>[C:6]([NH:9][C:14]1[C:13]([F:18])=[CH:12][C:11]([Cl:10])=[CH:16][N:15]=1)(=[O:8])[CH3:7]
Reactant: CC(N)=O
Reactant: Fc1cc(Cl)cnc1F
Agent: Cl
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CC(=O)Nc1ncc(Cl)cc1F
Temperature: 50 °C
Reaction time: 2 h
Yield: 72.2 %

Procedure:
Under a nitrogen atmosphere, DMF (200 mL) and THF (830 mL) were added to acetamide (94.8 g, 1.61 mol), and the mixture was warmed to 50° C. A 40 wt % sodium hexamethyldisilazide THF solution (629 g, 1.37 mol) was added dropwise thereto, and the mixture was stirred for 2 hours at the same temperature. 5-Chloro-2,3-difluoropyridine (100.0 g, 0.67 mol) was then added, THF (20 mL) was further added, and the mixture was stirred for 3 hours at the same temperature. The reaction mixture was cooled to 0° C., 2.8 M HCl (500 mL) was added, the mixture was warmed to room temperature, and the organic layer was separated. The organic layer was washed with a 20 wt % sodium chloride aqueous solution (500 mL), and the solvent was distilled off under reduced pressure. THF (500 mL) was added to the residue, and the mixture was heated to 70° C. to dissolve the residue. After cooling to room temperature and confirming the precipitation of solids, n-heptane (1500 mL) was added, and the mixture was further cooled to 0° C. and stirred for 3 hours at that temperature. The precipitated crystals were collected by filtration, washed with a mixed solvent of THF (100 mL) and n-heptane (500 mL), and dried under reduced pressure to obtain the title compound (91.2 g).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=1)=[O:7].[NH:18]1[CH2:23][CH2:22][CH:21]([C:24]2[CH:25]=[C:26]([NH:30][C:31]([CH:33]3[CH2:35][CH2:34]3)=[O:32])[CH:27]=[CH:28][CH:29]=2)[CH2:20][CH2:19]1>>[O:7]=[C:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=1)[CH2:5][CH2:4][CH2:3][CH2:2][N:18]1[CH2:23][CH2:22][CH:21]([C:24]2[CH:25]=[C:26]([NH:30][C:31]([CH:33]3[CH2:34][CH2:35]3)=[O:32])[CH:27]=[CH:28][CH:29]=2)[CH2:20][CH2:19]1
Reactant: O=C(Nc1cccc(C2CCNCC2)c1)C1CC1
Reactant: O=C(CCCCCl)c1ccc(C(F)(F)F)cc1
Product: O=C(CCCCN1CCC(c2cccc(NC(=O)C3CC3)c2)CC1)c1ccc(C(F)(F)F)cc1

Procedure:
Prepared by Procedure K and Scheme B1 using 5-chloro-1-[4-(trifluoromethyl)phenyl]-1-pentanone and N-[3-(4-piperidinyl)phenyl]cyclopropanecarboxamide: ESMS m/e: 473.2 (M+H)+.
Reaction SMILES: I[C:2]1[CH:15]=[CH:14][C:13]2[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[CH:6]=[CH:5][C:4]=2[CH:3]=1.C([Li])CCC.[B:21](OC(C)C)([O:26]C(C)C)[O:22]C(C)C.Cl>CCCCCC.CCOCC>[CH:3]1[C:4]2[CH:5]=[CH:6][C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[C:13]=2[CH:14]=[CH:15][C:2]=1[B:21]([OH:26])[OH:22]
Reactant: Ic1ccc2c(ccc3ccccc32)c1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CCOCC
Product: OB(O)c1ccc2c(ccc3ccccc32)c1
Temperature: -60 °C
Reaction time: 1 h
Yield: 58.7 %

Procedure:
Under an argon atmosphere, 98 g of 2-iodophenanthrene and 3 L of dehydrated ether were loaded, and then the reaction solution was cooled to −60° C. After that, 210 mL of a 1.6-M solution of n-butyllithium in hexane were added to the reaction solution. The reaction solution was stirred for 1 hour while its temperature was increased to 0° C. The reaction solution was cooled to −60° C. again, and then a solution of 151 g of triisopropyl borate in 100 mL of dehydrated ether was dropped to the reaction solution. The reaction solution was continuously stirred for 5 hours while its temperature was increased to room temperature. Subsequently, 1 L of a 10% aqueous solution of hydrochloric acid was added to the reaction solution, and then the mixture was stirred for 1 hour. The water layer was removed, and the organic layer was washed with water and a saturated salt solution, and was then dried with magnesium sulfate. After magnesium sulfate had been separated by filtration, the organic layer was concentrated. The resultant solid was washed with hexane and toluene. Thus, 42 g of phenanthrene-2-boronic acid as a target were obtained (in 58% yield).
Reaction SMILES: [Si:1]([O:8][CH:9]1[CH2:14][N:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:12][CH:11]=[CH:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[OH:20]C1C2C(O2)CN(C(OCC)=O)C1>>[Si:1]([O:8][CH:9]1[CH:10]2[CH:11]([O:20]2)[CH2:12][N:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:14]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CCOC(=O)N1CC(O)C2OC2C1
Reactant: CCOC(=O)N1CC=CC(O[Si](C)(C)C(C)(C)C)C1
Product: CCOC(=O)N1CC2OC2C(O[Si](C)(C)C(C)(C)C)C1

Procedure:
Compound 239F was prepared from 239D in a same reaction as Compound 239E as an oil.
Reaction SMILES: CC(C)[O-].[Al+3].CC(C)[O-].CC(C)[O-].[CH3:14][C@@H:15]1[O:34][C:32](=[O:33])[C:31]2[C:30]([OH:35])=[CH:29][C:28]([OH:36])=[CH:27][C:26]=2[CH:25]=[CH:24][CH2:23][CH2:22][CH2:21][C:19](=[O:20])[CH2:18][CH2:17][CH2:16]1>CC(O)C>[CH3:14][C@@H:15]1[O:34][C:32](=[O:33])[C:31]2[C:30]([OH:35])=[CH:29][C:28]([OH:36])=[CH:27][C:26]=2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][C@@H:19]([OH:20])[CH2:18][CH2:17][CH2:16]1
Reactant: C[C@H]1CCCC(=O)CCCC=Cc2cc(O)cc(O)c2C(=O)O1
Agent: CC(C)[O-]
Agent: C[C@H]1CCCC(=O)CCC/C=C/c2cc(O)cc(O)c2C(=O)O1
Agent: [Al+3]
Solvent: CC(C)O
Product: C[C@H]1CCC[C@H](O)CCCCCc2cc(O)cc(O)c2C(=O)O1
Temperature: 75 °C
Reaction time: 24 h
Yield: 45 %

Procedure:
Aluminum isopropoxide (300 g, 1.4688 moles) is added to a solution of Zearalenone (100 g, 0.3141 moles) in 1000 g (1270 mL) of 2-propanol. The mixture is stirred at 75° C. for 24 hours then the mixture is distilled to a volume of about 500 mL, cooled to ambient room temperature, 400 mL of water and 550 mL of 6N HCl are added ensuring that the reaction temperature is maintained below 40° C. The reaction is cooled to ambient room temperature and 886 g (990 mL) of ethyl acetate is added. The aqueous layer is separated and the ethyl acetate layer is extracted 2×325 mL with water and 1×325 mL with brine. The ethyl acetate is replaced with methanol by distilling off the ethyl acetate and replacing it with 380 g (480 mL) of methanol. The methanol mixture is filtered to remove insoluble matter and 10% Palladium on carbon (10 g) is added followed by hydrogen (1 atmosphere of pressure) at ambient room temperature. The reaction is stirred for 8 hours then Celite (20 g) is added and the reaction stirred for an additional hour. The reaction mixture is filtered to remove insoluble matter and water (725 mL) is added. The mixture is stirred at ambient room temperature for 4 hours during which time solid precipitate. The solids are isolated by filtration and washed with heptane (1000 mL). The solids are dissolved in methanol (890 mL) and water (470 mL) is added at ambient room temperature and solids begin to crystallize from solution. The mixture is stirred for an additional 4 hours and the solids are isolated by filtration, dried under vacuum to a moisture content of less than 0.5% to yield pure Zeranol (45.6 g, 45%).
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]([CH3:29])=[C:5]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[CH:6]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][OH:22])[CH:16]=2)[C:7]=1[C:8]([O:10][CH2:11][CH2:12][O:13][CH3:14])=[O:9].[S:30]1[CH:34]=[CH:33][CH:32]=[C:31]1[CH:35]=O>>[CH3:1][C:2]1[NH:3][C:4]([CH3:29])=[C:5]([C:23]([O:25][CH:26]([CH3:27])[CH3:28])=[O:24])[CH:6]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([N:21](=[O:22])=[CH:35][C:31]3[S:30][CH:34]=[CH:33][CH:32]=3)[CH:16]=2)[C:7]=1[C:8]([O:10][CH2:11][CH2:12][O:13][CH3:14])=[O:9]
Reactant: O=Cc1cccs1
Reactant: COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1c1cccc(NO)c1
Agent: COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1c1cccc(/[N+]([O-])=C/c2cccs2)c1
Product: COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1c1cccc([N+]([O-])=Cc2cccs2)c1

Procedure:
The reaction of hydroxylamine 55 (0.80 g, 2 mmol) with 2-thiophenecarboxaldehyde (64) (0.224 g, 2 mmol) afforded, after workup, a light yellow oil. The crude product was purified by flash chromatography with 2:1 ethyl acetate/hexane as the eluant to obtain 0.86 g (1.73 mmol, 86%) of 75 as a yellow gum: IR (CH2Cl2) 3440, 2940, 1698, 1625, 1560, 1472, 1375, 1298, 1215, 1105, cm-1 ; 1H NMR (CDCl3) δ 1.09 (d, J=6.2 Hz, 3H), 1.21 (d, J=6.2 Hz, 3H), 2.28 (s, 6H), 3.32 (s, 3H), 3.56 (t, J=4.8 Hz, 2H), 4.18 (m, 2H), 4.94 (septet, J=6.2 Hz, 1H), 5.09 (s, 1H), 6.99-8.52 (m, 8H); 13C NMR (CDCl3) δ 19.32, 19.44, 21.99, 22.22, 40.12, 58.85; 62.81, 67.18, 70.74, 102.75, 103.53, 118.83, 120.88, 127.19, 128.53, 129.34, 130.21, 130.29, 131.42, 133.00, 145.12, 145.91, 146.37, 149.97, 167.09, 167.55. Anal. calcd for C26H30N2O6S: C, 62.65; H, 6.02. Found: C, 62.47; H, 6.10.
Reaction SMILES: [OH:1][CH:2]([C:19]1[S:20][CH:21]=[CH:22][N:23]=1)[C:3]1[CH:4]=[C:5]([C:16]([OH:18])=O)[CH:6]=[C:7]([C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=2)[CH:8]=1.Cl.Cl.[CH3:26][C:27]1[N:32]=[CH:31][C:30]([C@H:33]([NH2:35])[CH3:34])=[CH:29][CH:28]=1.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[OH:1][CH:2]([C:19]1[S:20][CH:21]=[CH:22][N:23]=1)[C:3]1[CH:4]=[C:5]([C:16]([NH:35][C@@H:33]([C:30]2[CH:31]=[N:32][C:27]([CH3:26])=[CH:28][CH:29]=2)[CH3:34])=[O:18])[CH:6]=[C:7]([C:9]2[CH:10]=[CH:11][C:12]([CH3:15])=[CH:13][CH:14]=2)[CH:8]=1
Reactant: Cc1ccc(-c2cc(C(=O)O)cc(C(O)c3nccs3)c2)cc1
Reactant: Cc1ccc([C@@H](C)N)cn1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(-c2cc(C(=O)N[C@H](C)c3ccc(C)nc3)cc(C(O)c3nccs3)c2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a stirred solution of 5-(hydroxy(thiazol-2-yl)methyl)-4′-methylbiphenyl-3-carboxylic acid (31 mg, 0.095 mmol) in N,N-dimethylformamide (1 mL) were added (R)-1-(6-methylpyridin-3-yl)ethanamine dihydrochloride (50 mg, 0.24 mmol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (100 mg, 0.26 mmol), and N,N-diisopropylethylamine (300 μL, 1.72 mmol). The reaction mixture was stirred for 16 hours at 25° C., and then purified by preparative HPLC to afford the final product as a light brown solid.