Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([C:4]2[N:8]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[N:7]=[CH:6][CH:5]=2)[CH2:3][CH2:2]1.[I:15]N1C(=O)CCC1=O.C(#N)C>C(OCC)(=O)C>[CH:1]1([C:4]2[N:8]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[N:7]=[CH:6][C:5]=2[I:15])[CH2:3][CH2:2]1
Reactant: c1ccc(-n2nccc2C2CC2)cc1
Reactant: O=C1CCC(=O)N1I
Solvent: CCOC(C)=O
Solvent: CC#N
Product: Ic1cnn(-c2ccccc2)c1C1CC1
Temperature: 70 °C
Reaction time: 6 h

Procedure:
5-cyclopropyl-1-phenyl-1H-pyrazole (200 mg, 1.09 mmol) and N-iodosuccinimide (366 mg, 1.63 mmol) were added to acetonitrile (5 ml). The reaction mixture was heated to 70° C. After 6 hours, the reaction mixture was diluted with ethyl acetate, washed with 1N aqueous sodium hydroxide and brine, then dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate/hexanes gradient) to afford 5-cyclopropyl-4-iodo-1-phenyl-1H-pyrazole.
Reaction SMILES: CC[C@H]1[O:18][C:16](=[O:17])[C@H:15](C)[C@@H:14]([O:20][C@@H]2O[C@@H](C)[C@H](O)[C@@](OC)(C)C2)[C@H:13](C)[C@@H:12]([O:33][C@@H]2O[C@H](C)C[C@H](N(C)C)[C@H]2O)[C@@:11](O)(C)C[C@@H](C)CN(C)[C@H](C)[C@@H](O)[C@@]1(O)C.O.O.CC(OC(C)=O)=O.N#N.C(Cl)(Cl)Cl>N1C=CC=CC=1>[CH3:11][C:12]([CH2:13][C:14]([CH2:15][C:16]([OH:18])=[O:17])=[O:20])=[O:33]
Reactant: CC[C@H]1OC(=O)[C@H](C)[C@@H](O[C@H]2C[C@@](C)(OC)[C@@H](O)[C@H](C)O2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@H](N(C)C)[C@H]2O)[C@](C)(O)C[C@@H](C)CN(C)[C@H](C)[C@@H](O)[C@]1(C)O
Agent: N#N
Solvent: O
Solvent: CC(=O)OC(C)=O
Solvent: ClC(Cl)Cl
Product: CC(=O)CC(=O)CC(=O)O
Temperature: 0 °C

Procedure:
To a solution of 1.5 g (0.002 mole) of N-methyl-11-aza-10-deoxo-10-dihydro erythromycin A in 20 ml of pyridine there were added 10 ml (0.106 mole) of acetanhydride and it was stirred in a N2 -stream for 36 hours while heating at 60° to 80° C. The reaction was stopped by the addition of approx. 100 cm3 of ice and the product was isolated by the extraction with chloroform (4×30 ml) at a pH of 8.5. The combined chloroform extracts were washed with a 5% w./w. NaHCO3 solution (2×50 ml) and dried over K2CO3. Subsequently to the evaporation of chloroform the residual precipitate was dried with benzene, whereupon it was purified by chromatography on a silica gel column, system chloroform:methanol=9:1. There were obtained 0.89 g (51%) of analytically pure triacetate.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([OH:12])=[C:4]([C:13]([OH:15])=O)[N:3]=1.F[P-](F)(F)(F)(F)F.N1([O+]=C(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Cl.[C:41]([O:45][C:46](=[O:55])[C@H:47]([NH2:54])[CH2:48][O:49][C:50]([CH3:53])([CH3:52])[CH3:51])([CH3:44])([CH3:43])[CH3:42].C(N(C(C)C)C(C)C)C>ClCCl>[C:41]([O:45][C:46](=[O:55])[C@H:47]([NH:54][C:13]([C:4]1[N:3]=[C:2]([Cl:1])[C:11]2[C:6]([C:5]=1[OH:12])=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:15])[CH2:48][O:49][C:50]([CH3:53])([CH3:52])[CH3:51])([CH3:44])([CH3:42])[CH3:43]
Reactant: O=C(O)c1nc(Cl)c2ccccc2c1O
Reactant: CC(C)(C)OC[C@@H](N)C(=O)OC(C)(C)C
Agent: CN(C)C(=[O+]n1nnc2ccccc21)N(C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC[C@@H](NC(=O)c1nc(Cl)c2ccccc2c1O)C(=O)OC(C)(C)C
Reaction time: 40 h
Yield: 31.9 %

Procedure:
To a mixture of 45 mg (0.2 mmol) of 1-chloro-4-hydroxy-isoquinoline-3-carboxylic acid, 76 mg (0.2 mmol) of benzotriazol-1-yl-(bis-dimethylamino-methylene)-oxonium hexafluoro phosphate (HBTU), 50.8 mg (R)-2-amino-3-tert-butoxy-propionic acid tert-butyl ester hydrochloride (0.2 mmol), and 1 ml of dichloromethane was added 122.5 μl (0.7 mmol) of ethyl-diisopropyl-amine with stirring. Stirring was continued at ambient temperature for 40 h. The product was isolated from the reaction mixture by flash column chromatography on silica gel using hexanes:ethyl acetate (9:1) as the eluent to give a colorless oil. 27 mg of the title compound was obtained; MS-(+)-ion: M+1=422.8 amu.
Reaction SMILES: [CH2:1]([C:4]1([CH:20]([CH3:22])[CH3:21])[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].B.C1C[O:27]CC1.[OH-].[Na+].OO.Cl>C1COCC1.O>[Cl:19][C:16]1[CH:15]=[CH:14][C:13]([C@@H:11]([N:7]2[CH2:6][CH2:5][C:4]([CH2:1][CH2:2][CH2:3][OH:27])([CH:20]([CH3:22])[CH3:21])[O:9][C:8]2=[O:10])[CH3:12])=[CH:18][CH:17]=1
Reactant: C=CCC1(C(C)C)CCN([C@@H](C)c2ccc(Cl)cc2)C(=O)O1
Reactant: C1CCOC1
Agent: B
Agent: Cl
Agent: OO
Solvent: O
Product: CC(C)C1(CCCO)CCN([C@@H](C)c2ccc(Cl)cc2)C(=O)O1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a solution of 6-allyl-3-((S)-1-(4-chlorophenyl)ethyl)-6-isopropyl-1,3-oxazinan-2-one (45 mg, 0.14 mmol) in dry THF (5 mL) was added dropwise 1 M BH3.THF (0.28 mL, 0.28 mmol) at 0° C. After 2 h at rt, the reaction mixture was cooled to 0° C., and water (1 mL), 3 M aqueous NaOH (1 mL, 3 M) and 30% H2O2 (0.5 mL) were successively added. The mixture was stirred for 2-3 h at rt and was then diluted with water (6 mL). The pH of the mixture was adjusted to 6-7 with 0.5 N HCl. The layers were separated, and the aqueous phase was extracted with EtOAc (3×5 mL). The combined organic layers were washed with a saturated aqueous NaHCO3 solution (8 mL) and brine (8 mL), dried over Na2SO4, and concentrated in vacuo to give the crude product, which was purified by preparative TLC followed by preparative HPLC to afford two isomers.
Reaction SMILES: [CH2:1]1[CH2:11]CN2C(=NCCC2)C[CH2:2]1.[OH:12][CH:13]([C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:29](=[O:30])[CH2:28][CH2:27][C@@H:26]2[CH2:31][CH2:32][CH2:33][C:34]2[S:38][C:37]([C:39]([OH:41])=[O:40])=[CH:36][CH:35]=2)=[CH:21][CH:20]=1)[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].IC(C)C>CC(C)=O>[CH:1]([O:40][C:39]([C:37]1[S:38][C:34]([CH2:33][CH2:32][CH2:31][C@H:26]2[CH2:27][CH2:28][C:29](=[O:30])[N:25]2[C:22]2[CH:21]=[CH:20][C:19]([CH:13]([OH:12])[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[CH:24][CH:23]=2)=[CH:35][CH:36]=1)=[O:41])([CH3:11])[CH3:2]
Reactant: CCCCCC(O)c1ccc(N2C(=O)CC[C@@H]2CCCc2ccc(C(=O)O)s2)cc1
Reactant: C1CCC2=NCCCN2CC1
Solvent: CC(C)I
Solvent: CC(C)=O
Product: CCCCCC(O)c1ccc(N2C(=O)CC[C@@H]2CCCc2ccc(C(=O)OC(C)C)s2)cc1
Reaction time: 0.17 h
Yield: 57.4 %

Procedure:
DBU (5.2 μL, 0.035 mmol) was added to a solution of acid 43 (7.5 mg, 0.017 mmol) in acetone (0.1 mL) at rt under nitrogen. After 10 min, 2-iodopropane (35 μL, 0.35 mmol) was added. After 21 h at rt, the reaction was quenched with 0.01 N HCl (3 mL) and extracted with EtOAc (3×4 mL). The combined extracts were washed with brine (5 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica (CH2Cl2→1% MeOH/CH2Cl2) afforded 4.6 mg (53%) of the title compound (44).
Reaction SMILES: [C:1]1([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][N:16]3[CH2:22][CH2:21][CH2:20][N:19]([CH2:23][CH2:24][C:25]([O:27]C)=[O:26])[CH2:18][CH2:17]3)=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].Cl>CO.O>[C:1]1([CH2:7][O:8][C:9]2[CH:10]=[CH:11][C:12]([CH2:15][N:16]3[CH2:22][CH2:21][CH2:20][N:19]([CH2:23][CH2:24][C:25]([OH:27])=[O:26])[CH2:18][CH2:17]3)=[CH:13][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)CCN1CCCN(Cc2ccc(OCc3ccccc3)cc2)CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)CCN1CCCN(Cc2ccc(OCc3ccccc3)cc2)CC1
Reaction time: 2 h
Yield: 100.5 %

Procedure:
A solution of methyl hexahydro-4-[[4-(phenylmethoxy)phenyl]methyl]-1H-1,4-diazepine-1-propanoate (0.1 g, 0.27 mmol) in methanol (2 mL) was treated with aqueous sodium hydroxide (2M, 1 mL). After 2 hours at ambient temperature, the reaction was diluted with water, neutralized with 1 N hydrochloric acid, and extracted with n-butanol. The combined extracts were dried and concentrated to give 0.1 g of hexahydro-4-[[4-(phenylmethoxy)phenyl]methyl]-1H-1,4-diazepine-1-propanoic acid; 1H NMR (300 MHz, CD3OD) δ 7.41 (d, 2H), 7.36 (dd, 2H), 7.34 (d, 2H), 7.29 (dd, 1H), 6.98 (d, 2H), 5.05 (s, 2H), 3.81 (s, 2H), 3.25 (m, 2H), 3.23 (m, 2H), 3.20 (t, 2H), 3.00 (m, 2H), 2.91 (m, 2H), 2.56 (t, 2H), 2.02 (m, 2H) ppm.
Reaction SMILES: [H-].[Na+].[S:3]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[NH:6][C:5](=[S:13])[CH2:4]1.[CH3:14]I>CN(C)C=O>[CH3:14][S:13][C:5]1[CH2:4][S:3][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]=1
Reactant: S=C1CSc2ccccc2N1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CSC1=Nc2ccccc2SC1
Reaction time: 0.08 h

Procedure:
In a one liter flask is placed 10.8 parts of prewashed sodium hydride in 150 parts of N,N-dimethyl-formamide (DMF) at room temperature. After stirring for five minutes under nitrogen atmosphere, 30 parts of 2H-1,4-benzothiazine-3(4H)-thione[J. Med. Chem., 12, 290(1969)] is added in portions over a period of 30 minutes and continuously stirred at room temperature for 20 minutes. To the reaction mixture is then added 15 parts of methyl iodide and the mixture stirred at room temperature for 20 minutes under nitrogen. Removal of solvent by vacuum distillation under nitrogen affords 3-methylthio-2H-1,4-benzothiazine as the residue. Since the product is subject to spontaneous hydrolytic decomposition, it is not usually isolated for the purposes of this invention but instead employed as the solution in DMF preparable via the foregoing procedure.
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([O:10][CH2:11][C:12]1[N:13]([CH2:25][C:26]([NH:29][C:30](=[O:44])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][NH:36]C(=O)OC(C)(C)C)([CH3:28])[CH3:27])[C:14]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:24]=1)[CH3:9]>ClCCl.O.[OH-].[NH4+]>[NH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][C:30]([NH:29][C:26]([CH3:27])([CH3:28])[CH2:25][N:13]1[C:14]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[CH:16][C:15]=2[N:24]=[C:12]1[CH2:11][O:10][CH2:8][CH3:9])=[O:44]
Reactant: CCOCc1nc2cnc3ccccc3c2n1CC(C)(C)NC(=O)CCCCCNC(=O)OC(C)(C)C
Agent: [NH4+]
Agent: [OH-]
Solvent: O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCOCc1nc2cnc3ccccc3c2n1CC(C)(C)NC(=O)CCCCCN
Reaction time: 1.5 h
Yield: 105.6 %

Procedure:
Trifluoroacetic acid (30 mL) was added slowly to a solution of tert-butyl 6-({2-[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethyl}amino)-6-oxohexylcarbamate (3.99 g, 7.82 mmol) in dichloromethane (80 mL) at room temperature. After 1.5 hours, the solution was concentrated under reduced pressure to afford an oil. The oil was dissolved in a small amount of water and concentrated ammonium hydroxide. The resulting basic mixture was extracted with dichloromethane multiple times. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford 3.4 g of 6-amino-N-{2-[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethyl}hexanamide, which was used in the next step without further purification.
Reaction SMILES: [CH3:1][N:2]1[CH2:8][CH2:7][CH2:6][C@H:3]1[CH2:4][OH:5].[OH-].[Na+].Cl[C:12]1[N:17]=[C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([Cl:27])[CH:20]=2)[N:15]=[C:14]([NH:28][CH:29]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)[N:13]=1>C1C=CC=CC=1>[Cl:27][C:21]1[CH:20]=[C:19]([NH:18][C:16]2[N:15]=[C:14]([NH:28][CH:29]3[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]3)[N:13]=[C:12]([O:5][CH2:4][CH:3]3[CH2:6][CH2:7][CH2:8][N:2]3[CH3:1])[N:17]=2)[CH:24]=[CH:23][C:22]=1[O:25][CH3:26]
Reactant: COc1ccc(Nc2nc(Cl)nc(NC3CCCCCC3)n2)cc1Cl
Reactant: CN1CCC[C@H]1CO
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccccc1
Product: COc1ccc(Nc2nc(NC3CCCCCC3)nc(OCC3CCCN3C)n2)cc1Cl
Temperature: 25 °C

Procedure:
A mixture of N-methyl prolinol (0.226 g, 1.96 mmol) and sodium hydroxide (79 mg, 1.96 mmol) in benzene (10 mL) was heated to reflux for 2 hours with stirring under nitrogen atmosphere and then cooled to 25° C. followed by the addition of compound 133 (0.25 g, 0.65 mmol) at same temperature. The mixture was heated to reflux for 6 hours, concentrated under vacuum and diluted with water (3 mL). The gum which separated was collected (by decanting out the liquid portion) and purified by column chromatography (1-3% MeOH-CHCl3) to afford the title compound E25 as a semi-solid (0.06 g, 20%). HPLC: Symmetry shield RP18 (250×4.6 mm) 5 microns [solvent A=0.01 M KH2PO4 (pH 3.0); solvent B=CH3CN], Gradient elution program: T/%B=0/35, 10/35, 40/80, 50/80, 55/35, 60/35; 270 nm, Rt 15.51 min, 99.55% purity; MS (CI): m/z 461 (M+H, 100).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([C:18](O)=[O:19])[CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B.O1CCCC1>O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:18][OH:19])[CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N[C@H](CCc1ccccc1)C(=O)O
Agent: B
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@@H](CO)CCc1ccccc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 68 %

Procedure:
N-tert-butoxycarbonyl-D-homophenylalanine (36 mmol) was dissolved in tetrahydrofuran (THF) (300 mL) and cooled to 0° C. Borane-THF complex (0.32 M in THF, 320 mL, 9 equivalents) was added dropwise over 2 hr and the solution stirred for an additional 2 hr at 0° C. The reaction mixture was quenched over several hours by the slow addition of MeOH (300 mL) and the resulting solution was concentrated to dryness. The residue was dissolved in EtOAc (200 mL), washed with 1 N NaOH (2×100 mL) and brine (1×75 mL). The organic layer was dried over Na2SO4, filtered and the filtrate concentrated to dryness. Recrystallization from hexanes gave the title compound (6.5 g, 84%) as a white solid: 1H NMR (CDCl3) δ 1.57 (9H, s), 1.91-1.93 (2H, m), 2.77-2.85 (2H, m), 3.68-3.82 (3H, m), 7.29-7.42 (5H, m); MS m/e 288 (100, M+1).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12](F)[N:11]=2)=[O:9])=[CH:6][C:5]([Br:17])=[CH:4][N:3]=1.[C:18]([N:25]1[CH2:31][CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C(=O)([O-])[O-].[K+].[K+]>>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([Br:17])=[CH:6][C:7]=1[C:8]([C:10]1[N:11]=[C:12]([N:28]2[CH2:29][CH2:30][CH2:31][N:25]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:26][CH2:27]2)[CH:13]=[CH:14][CH:15]=1)=[O:9]
Reactant: CC(C)(C)OC(=O)N1CCCNCC1
Reactant: Nc1ncc(Br)cc1C(=O)c1cccc(F)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CC(C)(C)OC(=O)N1CCCN(c2cccc(C(=O)c3cc(Br)cnc3N)n2)CC1
Temperature: 95 °C
Yield: 59 %

Procedure:
A mixture of (2-amino-5-bromopyridin-3-yl)(6-fluoropyridin-2-yl)methanone (190 mg, 0.64 mmol), 1-Boc-homopiperazine (0.14 ml, 0.70 mmol) and potassium carbonate (310 mg, 2.24 mmol) in dimethylfonmamide (4 ml) was heated at 95° C. for 48 hours. The reaction mixture was cooled down to room temperature and concentrated in vacuo. The residue was slurried in EtOAc and K2CO3 was filtered off. The mother liquors were concentrated in vacuo. The resulting residue was purified on silica gel by flash column chromatography (ISCO Companion|, 12 g column, 0-20% EtOAc/Petrol) to give the title compound as a yellow solid (180 mg, 59% yield).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([NH2:9])=[CH:5][CH:6]=[CH:7][CH:8]=1.[C:10](OC(=O)C)(=[O:12])[CH3:11]>>[CH3:11][C:10]([NH:9][C:4]1[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:12]
Reactant: CC(=O)OC(C)=O
Reactant: COc1ccccc1N
Product: COc1ccccc1NC(C)=O
Temperature: 45 °C

Procedure:
To 100 ml of acetic anhydride was added dropwise with stirring 100 g (0.813 mole) of o-anisidine, the temperature rising to about 60° C. during addition. The reaction mixture was heated on a steam bath for 15 minutes, allowed to cool to 45° C. and was poured onto 500 g of crushed ice. The white solid that precipitated was collected, washed free of acid with water and air dried to give 100 g, m.p. 84°-86° C., of product.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])([O-])=O>CO.CCOC(C)=O.[Pd]>[NH2:1][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14]
Reactant: COC(=O)CCNc1ccccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: COC(=O)CCNc1ccccc1N
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of methyl 3-((2-nitrophenyl)amino)propanoate (11 g, 48.9 mmol) and Pd/C (3.3 g, 10%) in 300 mL of MeOH and 20 mL of EtOAc was stirred overnight under H2 atmosphere at room temperature. The mixture was filtered off, and the filtrate was concentrated to give methyl 3-((2-aminophenyl)amino)propanoate as a yellow oil. (9.3 g, 98%). LRMS (M+H)+: 193 m/z.
Reaction SMILES: [O:1]1[C:5]2=[N:6][C:7]3[C:12]([C:13]([NH:14][C:15]4[CH:20]=[CH:19][C:18]([C:21](=[O:23])[CH3:22])=[CH:17][CH:16]=4)=[C:4]2[CH:3]=[CH:2]1)=[CH:11][CH:10]=[CH:9][CH:8]=3.[NH2:24][CH2:25][CH2:26][O:27][NH2:28].Cl.C([O-])([O-])=O.[K+].[K+]>CCO>[O:1]1[C:5]2=[N:6][C:7]3[C:12]([C:13]([NH:14][C:15]4[CH:20]=[CH:19][C:18]([C:21](=[O:23])[CH3:22])=[CH:17][CH:16]=4)=[C:4]2[CH:3]=[CH:2]1)=[CH:11][CH:10]=[CH:9][CH:8]=3.[NH2:24][CH2:25][CH2:26][O:27][N:28]=[C:21]([C:18]1[CH:19]=[CH:20][C:15]([NH:14][C:13]2[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[N:6]=[C:5]3[O:1][CH:2]=[CH:3][C:4]=23)=[CH:16][CH:17]=1)[CH3:22]
Reactant: NCCON
Agent: CC(=O)c1ccc(Nc2c3ccccc3nc3occc23)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CCO
Product: CC(=NOCCN)c1ccc(Nc2c3ccccc3nc3occc23)cc1
Yield: 96 %

Procedure:
1-(4-(furo[2,3-b]quinolin-4-ylamino)phenyl)ethanone (compound 1) was prepared according to the method as described in Example 4 of U.S. Pat. No. 6,750,223 B2. The thus obtained compound 1 (0.30 g, 1 mmol), 2-aminoethoxyamine.HCl (0.28 g, 2.5 mmol), and K2CO3 (0.69 g, 5.0 mmol) were added into EtOH (10 mL). The resultant mixture was subjected to reflux for 4 hours (TLC monitoring), followed by evaporation under reduced pressure. The residue thus acquired was dissolved in CH2Cl2 (50 mL). The CH2Cl2 layer was washed sequentially with H2O and brine, was dried using Na2SO4, and was subjected to an evaporation treatment. The resultant residue was purified via flash column chromatography (MeOH/CH2Cl2=1/50), followed by recrystallization from EtOH. The title compound 13a as a light yellow solid (0.45 g, 96% yield) was obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([CH3:13])=[C:5]([CH:10]=[CH:11][CH:12]=1)[C:6]([NH:8][NH2:9])=[O:7].[CH:14]1([CH:20]=O)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.C(O)(=O)C>C(O)C>[CH:14]1([CH:20]=[N:9][NH:8][C:6](=[O:7])[C:5]2[CH:10]=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[C:4]=2[CH3:13])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1
Reactant: COc1cccc(C(=O)NN)c1C
Reactant: O=CC1CCCCC1
Solvent: CC(=O)O
Solvent: CCO
Product: COc1cccc(C(=O)NN=CC2CCCCC2)c1C
Reaction time: 18 h

Procedure:
10.0 g (55.5 mmol) of 3-methoxy-2-methyl-benzoic acid hydrazide was dissolved in 200 mL of absolute ethyl alcohol. Cyclohexanecarbaldehyde (6.85 g, 61.0 mmol) and glacial acetic acid (3 mL) were added, and the reaction mixture was stirred for 18 h while monitoring by TLC. The precipitate was collected by filtration and washed with hexane. Product 3-methoxy-2-methyl-benzoic acid cyclohexylmethylene-hydrazide was obtained as a white solid (9.36 g, yield 61%): Rf=0.20 (3:1 EtOAc:n-Hexane); 1H NMR (400 MHz, CDCl3) δ 11.17 (s, 1H), 7.91 (s, 1H), 7.50 (d, J=4.8 Hz, 1H), 7.25 (t, J=6.4 Hz, 1H), 6.99 (t, J=5.6 Hz, 1H), 3.89 (s, 3H), 2.28 (s, 3H), 1.92-1.62 (m, 5H), 1.38-1.14 (m, 6H); HRMS (ESI) m/z calcd for C16H23N2O2 [M+H]+ 275.1760. found 275.1752, calcd for C16H22N2NaO2 [M+Na]+ 297.1579. found 297.1568.
Reaction SMILES: OC1C(C(CC)(C)C)=CC(C(CC)(C)C)=CC=1N=NC1C=CC=CC=1[N+]([O-])=O.[OH:29][C:30]1[C:35]([C:36]([CH3:39])([CH3:38])[CH3:37])=[CH:34][C:33]([C:40]([CH3:43])([CH3:42])[CH3:41])=[CH:32][C:31]=1[N:44]=[N:45][C:46]1[CH:51]=[C:50]([Cl:52])[CH:49]=[CH:48][C:47]=1[N+:53]([O-])=O>>[Cl:52][C:50]1[CH:49]=[CH:48][C:47]2=[N:53][N:44]([C:31]3[CH:32]=[C:33]([C:40]([CH3:43])([CH3:42])[CH3:41])[CH:34]=[C:35]([C:36]([CH3:39])([CH3:38])[CH3:37])[C:30]=3[OH:29])[N:45]=[C:46]2[CH:51]=1
Reactant: CC(C)(C)c1cc(N=Nc2cc(Cl)ccc2[N+](=O)[O-])c(O)c(C(C)(C)C)c1
Agent: CCC(C)(C)c1cc(N=Nc2ccccc2[N+](=O)[O-])c(O)c(C(C)(C)CC)c1
Product: CC(C)(C)c1cc(-n2nc3ccc(Cl)cc3n2)c(O)c(C(C)(C)C)c1
Yield: 80.4 %

Procedure:
When in Example 1, the 2'-hydroxy-3',5'-di-tert-amyl-2-nitroazobenzene was replaced by an equivalent amount of 2'-hydroxy-3',5'-di-tert-butyl-5-chloro-2-nitroazobenzene, the product 5-chloro-2-(2-hydroxy-3,5-di-tert-butylphenyl)-2H-benzotriazole was obtained after a reaction time of 5 hours in a yield of 80.4% of theory as an isolated product of melting point 151°-154° C. An additional 4.5% yield was present in the mother liquor for an overall yield of 84.9% of theory.
Reaction SMILES: [CH3:1][Si](C=[N+]=[N-])(C)C.[CH3:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:20]=[C:19]([C:21]([OH:23])=[O:22])[O:18][N:17]=2)=[CH:12][CH:11]=1>CCOCC.CO.C(Cl)Cl>[CH3:8][O:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH:20]=[C:19]([C:21]([O:23][CH3:1])=[O:22])[O:18][N:17]=2)=[CH:14][CH:15]=1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: COc1ccc(-c2cc(C(=O)O)on2)cc1
Solvent: ClCCl
Solvent: CO
Solvent: CCOCC
Product: COC(=O)c1cc(-c2ccc(OC)cc2)no1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Trimethylsilyldiazomethane (3.50 mL of a 2 M soln in Et2O, 7.01 mmol) was added to a stirred solution of 3-(4-methoxyphenyl)-5-isoxazolecarboxylic acid (0.96 g, 4.38 mmol) in dry MeOH (4.38 mL) and dry CH2Cl2 (39 mL) at 25° C. under N2. The reaction was stirred at 25° C. for 2 h. The reaction mixture was concentrated in vacuo to afford methyl 3-(4-methoxyphenyl)isoxazole-5-carboxylate, as a colorless solid. LCMS calc.=234.08. found=233.98 (M+H)+. 1H NMR (600 MHz, CDCl3): δ 7.76 (d, J=8.4 Hz, 2H); 7.19 (s, 1H); 6.98 (d, J=8.4 Hz, 2H); 3.99 (s, 3H); 3.86 (s, 3H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:14][CH2:13][CH2:12][C@H:11]2[CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:9])=[C:4]([F:21])[CH:3]=1.[F:22][C:23]([F:35])([F:34])[O:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1>>[F:21][C:4]1[CH:3]=[C:2]([C:27]2[CH:28]=[CH:29][CH:30]=[C:25]([O:24][C:23]([F:22])([F:34])[F:35])[CH:26]=2)[CH:7]=[CH:6][C:5]=1[C:8]([N:10]1[CH2:14][CH2:13][CH2:12][C@H:11]1[CH2:15][N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)=[O:9]
Reactant: OB(O)c1cccc(OC(F)(F)F)c1
Reactant: O=C(c1ccc(Br)cc1F)N1CCC[C@H]1CN1CCCC1
Product: O=C(c1ccc(-c2cccc(OC(F)(F)F)c2)cc1F)N1CCC[C@H]1CN1CCCC1

Procedure:
The title compound is prepared in a manner substantially analogous to Procedure SS starting from (4-bromo-2-fluoro-phenyl)-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone and 3-Trifluoromethoxybenzene boronic acid. MS (M+H) 437.1
Reaction SMILES: [N:1]1([C:7]#[N:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[NH2:9][OH:10]>>[OH:10][NH:9][C:7]([N:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1)=[NH:8]
Reactant: N#CN1CCOCC1
Reactant: NO
Product: N=C(NO)N1CCOCC1

Procedure:
The title compound was prepared from the reaction of morpholine nitrile and hydroxylamine (equimolar amounts) by a route analogous to that used for the preparation of Example 412A to yield 419A in quantitative yield. 1H NMR (400 MHz, DMSO-d6) δ 8.33 (s, 1H), 5.18 (S, 2H), 3.57 (m, 4H), 2.93 (m, 4H)