Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[C:2]([CH2:4][NH:5][C:6]([C@@H:8]1[CH2:12][C@@H:11]([S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])(=[O:15])=[O:14])[CH2:10][NH:9]1)=[O:7])#[N:3].[C:23]1([CH:29](O)[C:30]([F:33])([F:32])[F:31])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>>[C:2]([CH2:4][NH:5][C:6]([C@@H:8]1[CH2:12][C@@H:11]([S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])(=[O:14])=[O:15])[CH2:10][N:9]1[CH:29]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:30]([F:32])([F:31])[F:33])=[O:7])#[N:3]
Reactant: OC(c1ccccc1)C(F)(F)F
Reactant: N#CCNC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccccc2Cl)CN1
Agent: Cl
Product: N#CCNC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccccc2Cl)CN1C(c1ccccc1)C(F)(F)F

Procedure:
L6. (2S,4R)-4-(2-chloro-benzenesulfonyl)-pyrrolidine-2-carboxylic acid cyanomethyl-amide hydrochloride from experiment K1 was reacted with 1-phenyl-2,2,2-trifluoroethanol as described in experiment L5 to give (2S,4R)-4-(2-chloro-benzenesulfonyl)-1-(2,2,2-trifluoro-1-phenyl-ethyl)-pyrrolidine-2-carboxylic acid cyanomethyl-amide as a white amorphous solid. MS: 486.2 [M+H]+.
Reaction SMILES: [O:1]=[C:2]1[O:8][C@H:7]([C@H:9]([CH2:11][OH:12])[OH:10])[C:5]([OH:6])=[C:3]1[OH:4].[C:13](OC(C)=C)(=[O:15])[CH3:14]>O1CCCC1>[C:13]([O:12][CH2:11][C@H:9]([OH:10])[C@H:7]1[O:8][C:2](=[O:1])[C:3]([OH:4])=[C:5]1[OH:6])(=[O:15])[CH3:14]
Reactant: C=C(C)OC(C)=O
Reactant: O=C1O[C@H]([C@@H](O)CO)C(O)=C1O
Solvent: C1CCOC1
Product: CC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O
Reaction time: 22 h
Yield: 90.8 %

Procedure:
Four grams of the immobilized Lipase PS prepared by the same procedure as in Example 2 was added to 40 ml of a dry tetrahydrofuran solution containing 4 g of ascorbic acid and 3 g of isopropenyl acetate, and then the reaction was continued for 22 hours at 40° C. The reaction mixture was then filtered, concentrated and recrystallized from acetone-benzene to yield 4.5 g of ascorbic acid-6-acetate. The water content of the reaction system was 700 ppm.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12](=[O:16])[CH2:13][CH2:14][CH3:15])=[C:5]2[NH:17][C@H:18]1[CH2:23][CH2:22][C@H:21]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:20][CH2:19]1.[Cl:32][C:33]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[C:35]([Cl:48])[C:34]=1[OH:49]>>[C:12]([C:6]1[CH:7]=[N:8][C:9]2[C:4]([C:5]=1[NH:17][C@H:18]1[CH2:23][CH2:22][C@H:21]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:20][CH2:19]1)=[CH:3][C:2]([C:37]1[CH:38]=[C:33]([Cl:32])[C:34]([OH:49])=[C:35]([Cl:48])[CH:36]=1)=[CH:11][CH:10]=2)(=[O:16])[CH2:13][CH2:14][CH3:15]
Reactant: CC1(C)OB(c2cc(Cl)c(O)c(Cl)c2)OC1(C)C
Reactant: CCCC(=O)c1cnc2ccc(Br)cc2c1N[C@H]1CC[C@H](NC(=O)OC(C)(C)C)CC1
Product: CCCC(=O)c1cnc2ccc(-c3cc(Cl)c(O)c(Cl)c3)cc2c1N[C@H]1CC[C@H](NC(=O)OC(C)(C)C)CC1

Procedure:
Following general procedure D, tert-butyl (trans-4-((6-bromo-3-butyrylquinolin-4-yl)amino)cyclohexyl)carbamate (49 mg, 0.10 mmol) was reacted with 2,6-dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (47 mg, 0.16 mmol) to afford the desired product (35.2 mg, 61%) as a yellow-brown solid. ESI MS m/z 572 [C30H35Cl2N3O4+H]+
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[C:5]([F:9])=[CH:4][C:3]=1[CH:10]([CH3:25])[C:11]([C:17]1[CH:18]=[CH:19][C:20](=[O:24])[N:21]([CH3:23])[CH:22]=1)([OH:16])[C:12]([F:15])([F:14])[F:13].[F:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][C:32]=1[C:33]([O:35][CH3:36])=[O:34]>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.N1C=CC=CC=1>[CH3:36][O:35][C:33](=[O:34])[C:32]1[CH:31]=[CH:30][C:29]([O:8][C:6]2[CH:7]=[C:2]([Cl:1])[C:3]([CH:10]([CH3:25])[C:11]([OH:16])([C:17]3[CH:18]=[CH:19][C:20](=[O:24])[N:21]([CH3:23])[CH:22]=3)[C:12]([F:15])([F:14])[F:13])=[CH:4][C:5]=2[F:9])=[CH:28][C:27]=1[F:26]
Reactant: CC(c1cc(F)c(O)cc1Cl)C(O)(c1ccc(=O)n(C)c1)C(F)(F)F
Reactant: COC(=O)c1ccc(B(O)O)cc1F
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: c1ccncc1
Product: COC(=O)c1ccc(Oc2cc(Cl)c(C(C)C(O)(c3ccc(=O)n(C)c3)C(F)(F)F)cc2F)cc1F

Procedure:
In analogy to Example 151, step 8, 5-[2-(2-chloro-5-fluoro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1-methyl-1H-pyridin-2-one was reacted with 3-fluoro-4-methoxycarbonylphenylboronic acid, copper-(II)-acetate and pyridine to give the title compound as an off-white solid. MS (m/e)=532.2 [M+H+].
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([Cl:23])[C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:10][CH:9]=2)=[N:6][CH:7]=1.[CH2:24]([O:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1)[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31].C(=O)([O-])[O-].[Na+].[Na+].C(O)C>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:23][C:4]1[C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:10][CH:9]=2)=[N:6][CH:7]=[C:2]([C:36]2[CH:37]=[CH:38][C:33]([O:32][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[CH:34][CH:35]=2)[CH:3]=1
Reactant: CCCCCCCCOc1ccc(-c2ncc(Br)cc2Cl)cc1
Reactant: CCCCCCCCOc1ccc(B(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Solvent: CCO
Product: CCCCCCCCOc1ccc(-c2cnc(-c3ccc(OCCCCCCCC)cc3)c(Cl)c2)cc1
Yield: 48.9 %

Procedure:
2.00 g (5.40 mmol) of 5-bromo-3-chloro-2-(4-octyloxyphenyl)pyridine, 1.50 g (6.00 mmol) of 4-octyloxybenzeneboronic acid, 0.07 g (0.6 mmol) of tetrakis(triphenylphosphine)palladium(0) and 1.3 g (12.00 mmol) of sodium carbonate are heated at 80° C. for 3 hours in 20 ml of toluene, 10 ml of ethanol and 10 ml of water. The mixture is subsequently partitioned between aqueous sodium chloride solution and ether, the organic phase is washed with aqueous sodium chloride solution, dried over sodium sulfate and evaporated, and the product is purified by chromatography (silica gel/dichloromethane), giving 1.38 g of 3-chloro-2,5-di(4-octyloxyphenyl)pyridine. ##STR24##
Reaction SMILES: [N+](=[CH:3][C:4](=[O:13])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([I:12])=[CH:8][CH:7]=1)=[N-].Cl[O:15][C:16]([CH3:19])(C)C.[CH2:20]([OH:22])[CH3:21]>>[CH2:20]([O:22][CH:3]([O:15][CH2:16][CH3:19])[C:4](=[O:13])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([I:12])=[CH:8][CH:7]=1)[CH3:21]
Reactant: CC(C)(C)OCl
Reactant: CCO
Reactant: [N-]=[N+]=CC(=O)Cc1ccc(I)cc1
Product: CCOC(OCC)C(=O)Cc1ccc(I)cc1
Temperature: 0 °C

Procedure:
Under an argon atmosphere, 1-diazo-3-(4-iodophenyl)propan-2-one (13) (1.11 g, 3.88 mmol) was dissolved in anhydrous ethanol (10 mL) and cooled to 0° C. To this was added tert-butyl hypochlorite (440 μL, 3.89 mmol) and stirred for an hour at the same temperature. After concentrating under reduced pressure, the residue was purified by silica gel flash column chromatography (n-hexane/ethyl acetate=9/1) to give 1,1-diethoxy-3-(4-iodophenyl)propan-2-one (14) as a yellow oily substance (758 mg, 2.18 mmol, 56.1%).
Reaction SMILES: C(O[C:6](=[O:19])[NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([OH:18])=[CH:10][CH:9]=1)(C)(C)C.[F:20][C:21]1[CH:22]=[C:23]([CH:27]=[C:28]([N:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[CH:29]=1)C(O)=O.[O:36]1[CH:40]=[CH:39][C:38]([CH2:41]O)=[CH:37]1>>[F:20][C:21]1[CH:22]=[C:23]([CH:27]=[C:28]([N:30]2[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]2)[CH:29]=1)[C:6]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][CH2:41][C:38]2[CH:39]=[CH:40][O:36][CH:37]=2)=[CH:10][CH:9]=1)=[O:19]
Reactant: O=C(O)c1cc(F)cc(N2CCCCC2)c1
Reactant: CC(C)(C)OC(=O)Nc1ccc(O)c2ccccc12
Reactant: OCc1ccoc1
Product: O=C(Nc1ccc(OCc2ccoc2)c2ccccc12)c1cc(F)cc(N2CCCCC2)c1

Procedure:
Compound is prepared from tert-butyl(4-hydroxy-1-naphthyl)carbamate, 3-fluoro-5-piperidin-1-yl-benzoic acid and furan-3-yl-methanol according to conditions described in general procedure D. A pink solid is produced (12 mg). Mp: 152-153° C.; 1H NMR (300 MHz, CDCl3) δ 1.63-1.69(m, 6H), 3.20-3.27(m, 2H), 5.13(s, 2H), 6.58(s, 1H), 6.75(d, J=12.6 Hz, 1H), 6.89(d, J=8.4 Hz, 1H), 6.98(d, J=9.0 Hz, 1H), 7.30(s, 1H), 7.47-7.59(m, 4H), 7.12(d, J=8.1 Hz, 1H), 7.83(d, J=8.4 Hz, 1H), 7.95(s, 1H), 8.32(d, J=8.1 Hz, 1H); MS 445 (M+1).
Reaction SMILES: Cl.[CH2:2]([NH:4][CH2:5][C:6]1[CH:11]=[C:10]([Br:12])[CH:9]=[CH:8][C:7]=1[O:13][CH2:14][CH2:15][CH3:16])[CH3:3].Cl[C:18]1[N:19]=[N:20][C:21]([C:24]#[N:25])=[CH:22][CH:23]=1.C(=O)([O-])O.[Na+].C(OCC)(=O)C>CN1C(=O)CCC1>[Br:12][C:10]1[CH:9]=[CH:8][C:7]([O:13][CH2:14][CH2:15][CH3:16])=[C:6]([CH:11]=1)[CH2:5][N:4]([C:18]1[N:19]=[N:20][C:21]([C:24]#[N:25])=[CH:22][CH:23]=1)[CH2:2][CH3:3]
Reactant: CCCOc1ccc(Br)cc1CNCC
Reactant: N#Cc1ccc(Cl)nn1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN1CCCC1=O
Solvent: CCOC(C)=O
Product: CCCOc1ccc(Br)cc1CN(CC)c1ccc(C#N)nn1
Temperature: 110 °C
Yield: 76.1 %

Procedure:
N-ethyl 2-propoxy-5-bromobenzylamine hydrochloride 2 (5.17 g, 16.8 mmol) and 3-chloro-6-cyanopyridazine (2.65 g, 16.8 mmol) were dissolved in NMP (25 ml) and sodium hydrogen carbonate added (3.54 g, 42.1 mmol). The mixture was heated at 110 ° C. under argon for 7.5 hours and then allowed to cool to ambient temperature. The mixture was poured into ethyl acetate (200 ml) washed with water (5×200 ml) and brine (200 ml), the organic phase dried over MgSO4 and concentrated in vacuo. The residue was purified by MPLC (20% ethyl acetate/hexane) and then crystallised from ether/hexane to give the title product (4.80 g, 76%).
Reaction SMILES: [C:1]([NH:4][C:5]1[C:10]([F:11])=[CH:9][C:8]([Cl:12])=[C:7]([N+:13]([O-])=O)[CH:6]=1)(=[O:3])[CH3:2]>C(O)(=O)C.C(OCC)(=O)C.[Fe]>[C:1]([NH:4][C:5]1[C:10]([F:11])=[CH:9][C:8]([Cl:12])=[C:7]([NH2:13])[CH:6]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1cc([N+](=O)[O-])c(Cl)cc1F
Agent: [Fe]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: CC(=O)Nc1cc(N)c(Cl)cc1F
Temperature: 90 °C
Yield: 60.4 %

Procedure:
Iron powder (31.9 g) were suspended in a 5% acetic acid solution (60 ml), and the suspension was heated to 90° C. A solution of 4-(N-acetylamino)-1-chloro-5-fluoro2-nitrobenzene (13.3 g) in acetic acid (100 ml) and ethyl acetate (70 ml) was dropwise added thereto, and the resultant mixture was refluxed at 80° C. for 2 hours. The reaction mixture was filtered by celite. The filtrate was extracted with ethyl acetate, and the extract was neutralized with a saturated sodium hydrogen carbonate solution. The organic layer was washed with water, dried and concentrated under reduced pressure to give 7.0 g of 4-(N-acetylamino)-2-amino-1-chloro-5-fluorobenzene. M.P., 140.5°-141.5° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][C:8](=O)[CH2:7][CH2:6]2.[CH2:14]([NH2:16])[CH3:15].C(O)C.C(O)C.[H][H].[ClH:25]>[Pt]=O>[ClH:25].[CH2:14]([NH:16][CH:8]1[CH2:7][CH2:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:9]1)[CH3:15]
Reactant: CCN
Reactant: [H][H]
Reactant: COc1ccc2c(c1)CCC(=O)C2
Agent: O=[Pt]
Agent: Cl
Solvent: CCO
Product: CCNC1CCc2cc(OC)ccc2C1

Procedure:
28.0 g of 6-methoxy-2-tetralone, 200 ml of a 19% ethylamine-ethanol solution, 2.2 g of platinum oxide and 10 ml of absolute ethanol were mixed and the mixture was irradiated with infrared light in the presence of hydrogen to cause a catalytic hydrogenation to occur. After absorption of hydrogen had been completed, the platinum oxide catalyst was filtered off from the reaction solution and the filtrate was concentrated under reduced pressure, followed by extraction with chloroform. The chloroform layer obtained was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue obtained was dissolved in an ethanolic solution of hydrogen chloride having a concentration of about 18% and the solution was concentrated under reduced pressure. Acetone was added to the residue obtained to cause crystallization. The crystals were collected through filtration and recrystallized from ethanol-diethyl ether to give 29.7 g of N-ethyl-6-methoxy-1,2,3,4-tetrahydro-2-naphthylamine hydrochloride as colorless crystals having a melting point of 231°-232° C.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:18]3[C:17]([NH2:19])=[N:16][CH:15]=[N:14][C:13]=3[S:12][CH:11]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[Br:20]Br>C(O)(=O)C.CN(C=O)C.C([O-])(O)=O.[Na+]>[Br:20][C:11]1[S:12][C:13]2[N:14]=[CH:15][N:16]=[C:17]([NH2:19])[C:18]=2[C:10]=1[C:7]1[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=1
Reactant: Nc1ncnc2scc(-c3ccc([N+](=O)[O-])cc3)c12
Reactant: BrBr
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CC(=O)O
Product: Nc1ncnc2sc(Br)c(-c3ccc([N+](=O)[O-])cc3)c12
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A suspension of Example 58C (50 mg, 0.18 mmol) in acetic acid (1 mL) and DMF (3 mL) was heated with a heat gun to obtain a clear solution, cooled to 0° C., and treated with bromine (0.02 mL). The reaction mixture was stirred at 0° C. for 1 hour, diluted with saturated NaHCO3, and filtered. The filter cake was dried to provide 56 mg of the desired product.
Reaction SMILES: O.O.O.C([O-])(=O)C.[Pb+2:8].C([O-])(=O)C.[Pb]=O.[C:15]([OH:34])(=[O:33])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]/[CH:23]=[CH:24]\[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]>C1(OC2C=CC=CC=2)C=CC=CC=1>[C:15]([O-:34])(=[O:33])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]/[CH:23]=[CH:24]\[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32].[Pb+2:8].[C:15]([O-:34])(=[O:33])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]/[CH:23]=[CH:24]\[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: CC(=O)[O-]
Agent: O=[Pb]
Agent: [Pb+2]
Solvent: O
Solvent: c1ccc(Oc2ccccc2)cc1
Product: CCCCCCCC/C=C\CCCCCCCC(=O)[O-]
Temperature: 150 °C

Procedure:
1.421 g of lead acetate trihydrate (or lead oxide (PbO)) and 5 ml oleic acid were added into a reaction vessel containing 20 ml diphenyl ether solution and heated to a temperature of about 150° C. for 30 min to form a lead oleate. After cooling to 60° C., this solution was mixed with 12 ml TOPSe (or TOPTe) stock solution to prepare injecting precursor. Reaction was carried out at various injecting and reaction temperatures. Also various molar ratio of lead oleate to TOPSe stock solutions were tested for injecting precursor to find the optimum conditions of reaction. Typically, injecting the precursor solution at 130° C. of 30 ml diphenylether solution and keeping the reaction temperature at 110° C. for 5 min yielded approximately 5 nm sphere PbSe quantum dots. For the synthesis of larger size (>10 nm) cubic shape PbSe dots, lower injecting temperatures (<110° C.) or second injection of additional precursors at about 30% the amount of that in the first injection after the nucleation have been used were used
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][N:10]=2)[N:5]=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].C(N(CC)CC)C.[NH2:22][CH:23](C)[CH2:24][CH2:25][OH:26]>ClCCl.O>[N+:12]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[NH:22][CH2:23][CH2:24][CH2:25][OH:26])=[N:10][CH:9]=[CH:8][CH:7]=2)([O-:14])=[O:13]
Reactant: CC(N)CCO
Reactant: O=[N+]([O-])c1cnc2cccnc2c1Cl
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=[N+]([O-])c1cnc2cccnc2c1NCCCO
Reaction time: 4 h
Yield: 98 %

Procedure:
To a solution of 4-chloro-3-nitro[1,5]naphthyridine (18.0 g, 85.9 mmol) in dichloromethane (220 mL) at room temperature was added triethylamine (15.6 mL, 112 mmol) and 3-amino-1-butanol (7.20 mL, 94.5 mmol). The solution was stirred for 4 hours and then was concentrated under reduced pressure to yield an orange solid. The solid was slurried in water (250 mL) for 30 minutes, isolated by filtration, washed with water (3×30 mL), and dried at 70° C. in a vacuum oven to afford 20.9 g of 3-[(3-nitro[1,5]naphthyridin-4-yl)amino]propan-1-ol as a yellow solid.
Reaction SMILES: N1C=CC=CC=1.Cl.[NH2:8][OH:9].[C:10]([O:14][C:15]([O:17][C:18]1[C:30]([C:31]([F:34])([F:33])[F:32])=[CH:29][CH:28]=[C:27]([CH2:35][O:36][C:37]2[CH:42]=[CH:41][C:40]([C:43]3[CH:48]=[CH:47][C:46]([CH2:49][C:50]([O:52][CH3:53])=[O:51])=[CH:45][C:44]=3[CH:54]=O)=[CH:39][CH:38]=2)[C:19]=1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:16])([CH3:13])([CH3:12])[CH3:11]>C(O)C.C(OCC)(=O)C>[C:10]([O:14][C:15]([O:17][C:18]1[C:30]([C:31]([F:34])([F:33])[F:32])=[CH:29][CH:28]=[C:27]([CH2:35][O:36][C:37]2[CH:42]=[CH:41][C:40]([C:43]3[CH:48]=[CH:47][C:46]([CH2:49][C:50]([O:52][CH3:53])=[O:51])=[CH:45][C:44]=3[CH:54]=[N:8][OH:9])=[CH:39][CH:38]=2)[C:19]=1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:16])([CH3:13])([CH3:12])[CH3:11]
Reactant: COC(=O)Cc1ccc(-c2ccc(OCc3ccc(C(F)(F)F)c(OC(=O)OC(C)(C)C)c3C(=O)OC(C)(C)C)cc2)c(C=O)c1
Reactant: NO
Agent: Cl
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Solvent: CCO
Product: COC(=O)Cc1ccc(-c2ccc(OCc3ccc(C(F)(F)F)c(OC(=O)OC(C)(C)C)c3C(=O)OC(C)(C)C)cc2)c(C=NO)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 83.9 %

Procedure:
Pyridine (49 μl, 0.62 mmol) and hydroxylamine hydrochloride (42 mg, 0.62 mmol) were added to a solution of tert-butyl 2-[(tert-butoxycarbonyl)oxy]-6-[({2′-formyl-4′-[(methoxycarbonyl)methyl]-1,1′-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoate (198 mg, 0.307 mmol) obtained in Example (45-2) in ethanol (4 ml), and the mixture was stirred at room temperature for 4 hours. The reaction mixture was diluted with ethyl acetate, successively washed with water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was subjected to silica gel preparative thin layer chromatography (developing solvent: n-hexane/ethyl acetate=2/1) to give crude tert-butyl 2-[(tert-butoxycarbonyl)oxy]-6-[({2′-[(hydroxyimino)methyl]-4′-[(methoxycarbonyl)methyl]-1,1′-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoate (170 mg).
Reaction SMILES: [N:1](/[C:4](=[CH:9]\[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:12]([N+:24]([O-:26])=[O:25])[CH:11]=1)/[C:5]([O:7][CH3:8])=[O:6])=[N+]=[N-]>C1(C)C(C)=CC=CC=1>[CH2:17]([O:16][C:13]1[CH:14]=[C:15]2[C:10]([CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[NH:1]2)=[CH:11][C:12]=1[N+:24]([O-:26])=[O:25])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: COC(=O)/C(=C/c1ccc(OCc2ccccc2)c([N+](=O)[O-])c1)N=[N+]=[N-]
Solvent: Cc1ccccc1C
Product: COC(=O)c1cc2cc([N+](=O)[O-])c(OCc3ccccc3)cc2[nH]1
Temperature: 25 °C
Yield: 14.8 %

Procedure:
To a stirred solution of 200 ml of boiling xylene 4.93 g ((13.9 mmol) of methyl(Z)-2-azido-3-(4-benzyloxy-3-nitrophenyl)acrylate is added in small portions. After completion of the addition the reaction mixture is refluxed until the gas formation is over (about 0.5 h), then cooled to room temperature, the precipitated product is filtered off and washed with n-hexane to yield 0.67 g (15%) of the title compound. Mp.: 184-187° C. (xylene).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([OH:8])[C:5]([CH3:9])=[CH:4][CH:3]=1.[CH:10]([C:13]1[CH:14]=[CH:15][C:16]2[C:21]([NH:22][C:23]3[CH:24]=[C:25]([CH:29]=[CH:30][C:31]=3[S:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=3)[C:26](Cl)=[O:27])=[N:20][CH:19]=[N:18][C:17]=2[N:41]=1)([CH3:12])[CH3:11].C(N(CC)CC)C>ClCCl>[OH:8][C:6]1[CH:7]=[C:2]([NH:1][C:26](=[O:27])[C:25]2[CH:29]=[CH:30][C:31]([S:32][C:33]3[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=3)=[C:23]([NH:22][C:21]3[C:16]4[CH:15]=[CH:14][C:13]([CH:10]([CH3:11])[CH3:12])=[N:41][C:17]=4[N:18]=[CH:19][N:20]=3)[CH:24]=2)[CH:3]=[CH:4][C:5]=1[CH3:9]
Reactant: COc1ccc(Sc2ccc(C(=O)Cl)cc2Nc2ncnc3nc(C(C)C)ccc23)cc1
Reactant: Cc1ccc(N)cc1O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc(Sc2ccc(C(=O)Nc3ccc(C)c(O)c3)cc2Nc2ncnc3nc(C(C)C)ccc23)cc1
Reaction time: 18 h
Yield: 60.2 %

Procedure:
A solution of 5-amino-o-cresol (20.4 mg, 0.1655 mmol) and the product from Example 137B (70mg, 0.1655 mmol) in dichloromethane (4 mL) was treated with triethylamine (0.025 mL, 0.1806 mmol) at room temperature. The resulting solution was stirred for 18 hours. The reaction mixture was then washed with water and brine, and the combined organic layers were dried over MgSO4, the concentrated under vacuum to give a residue which was purified by silica gel chromatography using methanol and dichloromethane as eluent to provide the title compound (55 mg, 65%). 1H NMR (300 MHz, DMSO-D6) δ ppm: 1.34 (d, J=6.99 Hz, 6H), 2.07 (s, 3H), 3.17-3.28 (m, 1H), 3.77 (s, 3H), 6.86-7.10 (m, 5H), 7.30-7.46 (m, 3H), 7.64 (d, J=7.35 Hz, 1H), 7.72-7.86 (m, 1H), 7.95 (s, 1H), 8.43-8.68 (m, 1H), 8.77-8.97 (m, 1H), 9.27-9.46 (m, 1H), 10.02 (s, 1H), 10.21-10.40 (m, 1H); MS (APCI) m/z 552 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4](O)[CH:5]=[C:6]([CH:19]=1)[C:7]([NH:9][C:10]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:11]=1[CH:12]=[CH:13][NH:14]2)=[O:8].[C:21](=[O:24])([O-])[O-].[K+].[K+].C([CH:29]1[O:31][CH2:30]1)Cl>CC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][CH2:5][C:6]([O:31][CH2:30][CH:29]2[CH2:21][O:24]2)([CH:19]=1)[C:7]([NH:9][C:10]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:11]=1[CH:12]=[CH:13][NH:14]2)=[O:8]
Reactant: ClCC1CO1
Reactant: O=C([O-])[O-]
Reactant: O=C(Nc1cccc2[nH]ccc12)c1cc(O)cc(Cl)c1
Agent: [K+]
Solvent: CC(C)=O
Product: O=C(Nc1cccc2[nH]ccc12)C1(OCC2CO2)C=C(Cl)C=CC1

Procedure:
Using the procedure of Step D of Example 52, 3 g of the product of Step A, 100 ml of acetone, 1.47 g of potassium carbonate and 8.3 ml of epichlorohydrin were reacted to obtain 3.35 g of 5-chloro-1-[(2-oxiranyl)-methoxy]-N-(1H-indol-4-yl)-benzamide melting at 175° C.
Reaction SMILES: [CH:1]1([NH2:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:8][C:9]1[CH:17]=[CH:16][C:12]([C:13](Cl)=[O:14])=[CH:11][CH:10]=1>C1C=CC=CC=1>[CH:1]1([NH:7][C:13](=[O:14])[C:12]2[CH:16]=[CH:17][C:9]([Cl:8])=[CH:10][CH:11]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Reactant: NC1CCCCC1
Solvent: c1ccccc1
Product: O=C(NC1CCCCC1)c1ccc(Cl)cc1
Reaction time: 0.25 h

Procedure:
Cyclohexylamine (80 gm., 0.8 mole) is dissolved in 2.5 l. of benzene and treated dropwise with 70 gm. (0.4 mole) of p-chlorobenzoyl chloride in 250 ml. of benzene over 45 minutes with intermittent cooling to maintain reaction temperature between 22°-30°. After stirring an additional 15 minutes, the mixture is diluted with benzene and washed with water. A suspended solid is filtered and the filtrate concentrated to 1 l. to give a second crop; these are combined and recrystallized from methanol, 65.0 gm. (68.5%), m.p. 191°-193°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]#[N:11])=[CH:5][CH:4]=1.[K+].[Br-:13].[N+]([O-])(O)=O>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.ClC(Cl)C.ClCCl>[Br:13][C:4]1[CH:5]=[C:6]([CH2:9][C:10]#[N:11])[CH:7]=[CH:8][C:3]=1[O:2][CH3:1]
Reactant: COc1ccc(CC#N)cc1
Reactant: [Br-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [K+]
Solvent: CC(Cl)Cl
Solvent: O=[N+]([O-])O
Solvent: ClCCl
Product: COc1ccc(CC#N)cc1Br
Temperature: 25 °C
Reaction time: 20 h
Yield: 69.9 %

Procedure:
To a mixture of compound 4-methoxyphenyl acetonitrile (5.88 g, 40 mmol), KBr (9.52 g, 80 mmol), tetrabutylammonium chloride (332 mg, 1.2 mmol) in dichloroethane (80 mL), was added 21% w/w nitric acid (48 g, 160 mmol). The reaction mixture was stirred at rt for 20 h, diluted with dichloromethane (80 mL) and washed with sat. NaHCO3 aq. (2×50 mL), water (2×50 mL), brine and dried over Na2SO4. After removal of solvent under vacuum, the residue was triturated with Et2O (10 ml)/hexanes (40 ml) to give 6.32 g of product; Yield: 70%.