Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:9][C:10]2[C:11]([N:16]=1)=[N:12][CH:13]=[CH:14][CH:15]=2.[OH:17]O>C(O)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:9][C:10]2[C:11]([N:16]=1)=[N+:12]([O-:17])[CH:13]=[CH:14][CH:15]=2
Reactant: Fc1ccccc1-c1nc2ncccc2o1
Reactant: OO
Solvent: CC(=O)O
Product: [O-][n+]1cccc2oc(-c3ccccc3F)nc21
Temperature: 0 °C

Procedure:
A solution of 1 g. of 2-(2-fluorophenyl)oxazolo[4,5-b]pyridine (from Example 6) in 10 ml. of acetic acid was treated with 2 ml. of 30% hydrogen peroxide and heated on the steam bath for 16 hours. After cooling the mixture was diluted with ice-water. The precipitate was collected and recrystallized from dioxane-ether to give 2-(2-fluorophenyl)oxazolo[4,5-b]pyridine-4-oxide, m.p. 214°-216° C.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:23]=[CH:22][C:9]2[CH2:10][CH:11]([CH2:17][C:18]([O:20][CH3:21])=[O:19])[C:12](=[O:16])[N:13]([CH3:15])[CH2:14][C:8]=2[CH:7]=1.CS[C:26]1[NH:27][CH2:28][CH2:29][N:30]=1.C(N(C(C)C)CC)(C)C>CC(N(C)C)=O>[NH:30]1[CH2:29][CH2:28][N:27]=[C:26]1[NH:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:23]=[CH:22][C:9]2[CH2:10][CH:11]([CH2:17][C:18]([O:20][CH3:21])=[O:19])[C:12](=[O:16])[N:13]([CH3:15])[CH2:14][C:8]=2[CH:7]=1
Reactant: CSC1=NCCN1
Reactant: COC(=O)CC1Cc2ccc(OCCCN)cc2CN(C)C1=O
Solvent: CC(=O)N(C)C
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)CC1Cc2ccc(OCCCNC3=NCCN3)cc2CN(C)C1=O
Temperature: 100 °C
Reaction time: 2 h
Yield: 61.8 %

Procedure:
A mixture of methyl (±)-8-[3-amino-1-propyloxy]-2-methyl-3-oxo-2,3,4,5-tetrahydro-1H-2-benzazepine-4-acetate (0.3 g, 1 mmol), 2-methylthioimidazoline (0.46 g, 2 mmol), diisopropylethylamine (0.42 mL, 2 mmol) and dimethylacetamide (3 mL) was heated to 100° C. under argon. After 2 hr, the reaction was concentrated under vacuum and the residue was partitioned between CHCl3 and H2O. The organic phase was dried (MgSO4) and concentrated, and the residue was purified by preparative HPLC to give the title compound (0.24 g, 51%) as a yellow oil: MS (ES) m/e 389.4 (M+H)+.
Reaction SMILES: ClC1C=CC(C[N:7]2[CH2:12][CH2:11][CH:10]([CH2:13][NH:14][C:15](=[O:31])[CH2:16][NH:17][C:18](=[O:30])[C:19]3[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][C:20]=3[NH2:29])[CH2:9][CH2:8]2)=CC=1>C(O)=O.CO.[OH-].[OH-].[Pd+2]>[NH2:29][C:20]1[CH:21]=[CH:22][C:23]([C:25]([F:28])([F:26])[F:27])=[CH:24][C:19]=1[C:18]([NH:17][CH2:16][C:15]([NH:14][CH2:13][CH:10]1[CH2:9][CH2:8][NH:7][CH2:12][CH2:11]1)=[O:31])=[O:30]
Reactant: Nc1ccc(C(F)(F)F)cc1C(=O)NCC(=O)NCC1CCN(Cc2ccc(Cl)cc2)CC1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Solvent: O=CO
Product: Nc1ccc(C(F)(F)F)cc1C(=O)NCC(=O)NCC1CCNCC1
Temperature: 50 °C
Reaction time: 14 h
Yield: 85.2 %

Procedure:
A suspension of 1-(4-chlorobenzyl)-4-[{(N-(2-amino-5-trifluoromethylbenzoyl)glycyl)amino}methyl]piperidine (447 mg, 0.93 mmol) and Pd(OH)2 (60 mg, 0.23 mmol) in 5% HCO2H/methanol (10 mL) was stirred at 50° C. for 14 h. The Pd catalyst was filtered off through Celite, and the filtrate was concentrated. To the residue was added 1 N aqueous NaOH solution (15 mL) and the mixture was extracted with ethyl acetate (30 mL×3). The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography (SiO2, AcOEt/MeOH/Et3N=70/25/5) gave 4-[{(N-(2-amino-5-trifluoromethylbenzoyl)glycyl)amino}methyl ]piperidine (284 mg, 86%): ESI/MS m/e 359.0 (M++H, Cl16H21F3N4O2).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:22][C:23]1[N:28]=[CH:27][C:26]2[C:29](=O)[O:30][CH2:31][C:25]=2[C:24]=1[Cl:33].Cl>C1COCC1>[Cl:22][C:23]1[N:28]=[CH:27][C:26]2[C:29](=[C:5]3[C:4]4[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=4)[NH:7][C:6]3=[O:11])[O:30][CH2:31][C:25]=2[C:24]=1[Cl:33]
Reactant: O=C1OCc2c1cnc(Cl)c2Cl
Reactant: O=C1Cc2cc(F)ccc2N1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Product: O=C1Nc2ccc(F)cc2C1=C1OCc2c1cnc(Cl)c2Cl
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 67.6 %

Procedure:
A solution of 5-fluoro-1,3-dihydro-indol-2-one (1.44 g, 9.54 mmol.) in THF (10 mL) is cooled to 0° C. under an argon atmosphere and treated with a solution of lithium bis(trimethylsilyl)amide (19 mL of a 1 M solution in THF, 19.0 mmol) dropwise. The resulting solution is stirred at 0° C. for 10 min and warmed room temperature. A solution of 6,7-dichloro-1H-furo[3,4-c]pyridin-3-one (1.28 g, 6.27 mmol) in THF (9 mL) is added dropwise to the reaction mixture. The resulting solution is stirred at room temperature for 4 h and the reaction mixture is then poured into aqueous 10% HCl solution (200 mL). The resulting mixture is heated to 90° C. for 2 h and stirred at room temperature for 36 h. The precipitate which formed is collected by filtration, washed with small volumes of ethyl acetate (10×3 mL) and dried under vacuum to give the title compound as a yellow solid (1.43 g, 68%).
Reaction SMILES: [NH2:1][CH:2]([CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].C([O:23][C:24]1[C:25](=[O:56])[C:26](=O)[C:27]=1[NH:28][C:29]1[CH:30]=[N:31][N:32]([CH3:54])[C:33]=1[NH:34][C:35]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)C.C(N(CC)CC)C>C(O)C>[CH3:54][N:32]1[C:33]([NH:34][C:35]([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[C:29]([NH:28][C:27]2[C:24](=[O:23])[C:25](=[O:56])[C:26]=2[NH:1][CH:2]([CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8])[CH:30]=[N:31]1
Reactant: CC(C)(C)OC(=O)NCC(N)CNC(=O)OC(C)(C)C
Reactant: CCOc1c(Nc2cnn(C)c2NC(c2ccccc2)(c2ccccc2)c2ccccc2)c(=O)c1=O
Solvent: CCO
Solvent: CCN(CC)CC
Product: Cn1ncc(Nc2c(NC(CNC(=O)OC(C)(C)C)CNC(=O)OC(C)(C)C)c(=O)c2=O)c1NC(c1ccccc1)(c1ccccc1)c1ccccc1
Yield: 84.5 %

Procedure:
To a suspension of di-tert-butyl (2-amino-1,3-propanediyl)biscarbamate (810 mg) and 3-ethoxy-4-{[1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]amino}-3-cyclobutene-1,2-dione (957 mg) in ethanol (10 ml) was added triethylamine (0.279 ml), and the mixture was stirred under reflux for 1 day. The reaction mixture was concentrated to about 5 ml in vacuo. To the concentrate was added diisopropyl ether. The precipitated crystals were collected by filtration and dried in vacuo to give di-tert-butyl {2-[(2-{[1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]amino}-3,4-dioxocyclobut-1-en-1-yl)amino]-1,3-propanediyl}biscarbamate (1.22 g) as a solid.
Reaction SMILES: Cl[C:2]1[C:11]2[N:12]=[CH:13][N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.[NH2:19][NH2:20].C(O)(=O)C>O>[NH:19]([C:2]1[C:11]2[N:12]=[CH:13][N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1)[NH2:20]
Reactant: NN
Reactant: CC(C)Cn1cnc2c(Cl)nc3ccccc3c21
Solvent: O
Solvent: CC(=O)O
Product: CC(C)Cn1cnc2c(NN)nc3ccccc3c21

Procedure:
4-Chloro-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinoline (10.0 g, 0.0385 moles, U.S. Pat. No. 4,689,338 Example 77) was added to hydrazine (30 mL). The mixture heated rapidly to reflux. The solid dissolved with a vigorous heat of reaction then a precipitate formed as the reaction mixture refluxed. The reaction mixture was diluted with water. The precipitate was isolated by filtration then suspended in water (100 mL). The solid was brought into solution by the addition of acetic acid. The solution was filtered to remove traces of undissolved solid. The filtrate was made basic by the addition of ammonium hydroxide. The resulting precipitate was isolated by filtration, washed with water then dried to provide 8.0 g of crude product as a white solid. A sample of this material was recrystallized from methanol to provide 4-hydrazino-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinoline, m.p. 202°-205° C. Analysis: Calculated for C14H17 N5 : % C, 65.86; % H, 6.71; % N, 27.43; Found: % C, 65.20; % H, 6.6; % N, 27.5.
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([N:14]([CH2:22][C:23]2[CH:24]=[C:25]([CH:30]=[CH:31][CH:32]=2)[C:26](OC)=[O:27])[CH2:15][CH:16]([OH:21])[C:17]([F:20])([F:19])[F:18])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:34][NH:35][O:36][CH3:37].C([Mg]Cl)(C)C>O1CCCC1>[CH3:37][O:36][N:35]([CH3:34])[C:26](=[O:27])[C:25]1[CH:30]=[CH:31][CH:32]=[C:23]([CH2:22][N:14]([C:10]2[CH:11]=[CH:12][CH:13]=[C:8]([O:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:9]=2)[CH2:15][CH:16]([OH:21])[C:17]([F:20])([F:18])[F:19])[CH:24]=1
Reactant: CNOC
Reactant: COC(=O)c1cccc(CN(CC(O)C(F)(F)F)c2cccc(Oc3ccccc3)c2)c1
Agent: CC(C)[Mg]Cl
Agent: Cl
Solvent: C1CCOC1
Product: CON(C)C(=O)c1cccc(CN(CC(O)C(F)(F)F)c2cccc(Oc3ccccc3)c2)c1
Temperature: -15 °C
Reaction time: 1 h
Yield: 66 %

Procedure:
EX-620A) To a slurry of methyl 3-[[(3-phenoxyphenyl)(3,3,3-trifluoro-2-hydroxypropyl)amino]methyl]benzoate (1.03 g, 0.0023 mol) and N,O-dimethylhydroxylamine hydrochloride (386 mg, 0.0040 mol) in 4.6 mL of tetrahydrofuran at −15° C. was added a 2.0 M solution of isopropylmagnesium chloride in THF (4.6 mL, 0.0092 mol) over 15 min. The reaction was stirred for 1 h at −15° C. then quenched with 20% aqueous ammonium chloride and extracted with ethyl acetate. The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude product was purified by column chromatography on silica gel eluting with 1:1 ethyl acetate:hexane to afford 0.72 g (66%) of the desired N-methoxy-N-methyl-3-[[(3-phenoxyphenyl)-(3,3,3-trifluoro-2-hydroxypropyl)amino]methyl]benzamide product as an off-white solid. HRMS calcd. for C25H25N2O4F3: 475.1845 [M+H]+, found: 475.1840.
Reaction SMILES: [C:1]([O-])(=O)[CH3:2].[Na+].[Cl:6][CH2:7][CH2:8][NH:9][C:10]([CH2:16][C:17]([O:19][CH3:20])=[O:18])=[CH:11][C:12]([O:14][CH3:15])=[O:13].CC(C)=O>O>[Cl:6][CH2:7][CH2:8][N:9]1[CH:2]=[CH:1][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]1[CH2:16][C:17]([O:19][CH3:20])=[O:18]
Reactant: CC(=O)[O-]
Reactant: COC(=O)C=C(CC(=O)OC)NCCCl
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: COC(=O)Cc1c(C(=O)OC)ccn1CCCl
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 90.2 %

Procedure:
The hydrolysis solution was added to a mechanically-stirred slurry of sodium acetate (17.8 g, 212 mmol) in water (15 mL) at 0° C. over 1 hour, then stirred for a further 10 minutes. Dimethyl 3-(2-chloroethylamino)-2-pentenedioate (20.0 g, 85 mmol) was added, followed by acetone (50 mL), and the solution allowed to warm to room temperature and stirred for 20 hours. The resulting slurry was cooled to 0° C. and kept at that temperature for 4 hours, then filtered through a coarse frit. The precipitate was washed with water (300 mL) and dried, to give 19.9 g (90% yield) of methyl N-(2-chloroethyl)-3-methoxycarbonyl-2-pyrroleacetate as white crystals, m.p. 110°-111° C.,
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([C:6]([C:9]2[O:13][CH:12]=[N:11][C:10]=2[CH3:14])(O)[CH3:7])=[CH:2]1.C[Si]([N:19]=[N+:20]=[N-:21])(C)C.B(F)(F)F.O>C1C=CC=CC=1>[N:19]([C:6]([C:3]1[CH:4]=[CH:5][O:1][CH:2]=1)([C:9]1[O:13][CH:12]=[N:11][C:10]=1[CH3:14])[CH3:7])=[N+:20]=[N-:21]
Reactant: Cc1ncoc1C(C)(O)c1ccoc1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Agent: FB(F)F
Solvent: O
Solvent: c1ccccc1
Product: Cc1ncoc1C(C)(N=[N+]=[N-])c1ccoc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1-(3-Furyl)-1-(4-methyl-5-oxazolyl)ethanol (1 g) was suspended in benzene (4 ml). Trimethylsilylazide (822 μl) was added followed by boron trifluoride diethyletherate (770 μl). The mixture was stirred overnight at room temperature, then poured into water and extracted to give the title compound.
Reaction SMILES: [CH:1]([OH:3])=O.OO.[C:6]1([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[F:18])C[CH2:9][CH2:8][CH:7]=1>>[F:18][C:12]1[CH:13]=[C:14]([F:17])[CH:15]=[CH:16][C:11]=1[CH:6]1[CH2:7][CH2:8][CH2:9][C:1]1=[O:3]
Reactant: O=CO
Reactant: Fc1ccc(C2=CCCC2)c(F)c1
Agent: OO
Product: O=C1CCCC1c1ccc(F)cc1F
Temperature: 40 °C
Yield: 45.5 %

Procedure:
A mixture of 90% formic acid (26.4 mL, 689 mmol) and 30% hydrogen peroxide (6.0 mL, 39.2 mmol) was warmed at 40° C. for 10 min. The resulting solution was carefully added to 1-cyclopentenyl-2,4-difluorobenzene (7.064 g, 39.2 mmol) under stirring. The two-phase system was initially stirred at room temperature. After a certain period of time, a spontaneous exothermic reaction took place, and the temperature rose to about 50° C. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched by careful addition of a saturated sodium bicarbonate solution. Ether was added and the content of the separatory funnel was vigorously shaken. The organic layer was separated and the aqueous layer was extracted with ether. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 2-(2,4-difluorophenyl)cyclopentanone (3.503 g, 17.85 mmol, 45.5% yield) as colorless oil. LC-MS (M+H)+=195.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.08 (1H, td, J=8.4, 6.4 Hz), 6.76-6.86 (2H, m), 3.42 (1H, dd, J=12.2, 8.9 Hz), 2.42-2.53 (2H, m), 2.28-2.39 (1H, m), 2.13-2.23 (1H, m), 1.86-2.10 (2H, m).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:16]3[O:15][C:14](=O)[NH:13][C:12](=[O:18])[C:11]=3[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[OH-].[NH4+:20]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:16]3[NH:20][C:14](=[O:15])[NH:13][C:12](=[O:18])[C:11]=3[CH2:10][CH2:9]2)=[CH:4][CH:3]=1
Reactant: O=c1[nH]c(=O)c2c(o1)C(c1ccc(F)cc1)CC2
Reactant: [NH4+]
Agent: [OH-]
Product: O=c1[nH]c2c(c(=O)[nH]1)CCC2c1ccc(F)cc1
Temperature: 0 °C
Yield: 34.7 %

Procedure:
A solution of 7-(4-fluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (13.527 g, 54.7 mmol) in concentrated ammonium hydroxide (150 mL, 3852 mmol) was heated at 100° C. in a high-pressure (350 mL) vessel overnight. The reaction mixture was cooled to 0° C. and filtered. The precipitate was consecutively washed with water and dried by passing air through the filter and subsequently under vacuum to give 7-(4-fluorophenyl)-6,7-dihydro-1H-cyclopenta[d]pyrimidine-2,4(3H,5H)-dione (4.670 g, 18.97 mmol, 34.7% yield). LC-MS (M+H)+=247.3. 1H NMR (500 MHz, CDCl3) δ ppm 11.70-11.81 (2H, br s), 7.31-7.39 (2H, m), 7.16-7.22 (2H, m), 4.30-4.38 (1H, m), 2.63-2.73 (1H, m), 2.53-2.63 (2H, m), 1.84-1.95 (1H, m).
Reaction SMILES: [CH2:1]([NH:8][C:9]([C:11]1[N:12]=[N:13][C:14](Cl)=[CH:15][CH:16]=1)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[N:18]1([C:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[C:32]([F:35])([F:34])[F:33])=[O:25])[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1>>[CH2:1]([NH:8][C:9]([C:11]1[N:12]=[N:13][C:14]([N:21]2[CH2:22][CH2:23][N:18]([C:24](=[O:25])[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]([F:35])([F:33])[F:34])[CH2:19][CH2:20]2)=[CH:15][CH:16]=1)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: O=C(c1ccccc1C(F)(F)F)N1CCNCC1
Reactant: CCCCCCCNC(=O)c1ccc(Cl)nn1
Product: CCCCCCCNC(=O)c1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1

Procedure:
Following the procedure of Example 15, making variations only as required to use 6-chloropyridazine-3-carboxylic acid heptylamide in place of 6-chloropyridazine-3-carboxylic acid (2-cyclopropyl-2-hydroxyethyl)amide to react with piperazin-1-yl-(2-trifluoromethyl-phenyl)methanone, the title compound was obtained as a white powder (41% yield). 1H NMR (300 MHz, CDCl3) δ 8.05, 7.85, 7.72, 7.58, 7.34, 6.98, 4.03, 3.94-3.64, 3.47-3.28, 1.58, 1.32-1.25, 0.84. 13C NMR (75 MHz, CDCl3) δ 167.6, 162.9, 160.0, 145.5, 134.3, 132.4, 129.5, 126.9, 126.3, 125.4, 121.8, 112.6, 46.4, 44.5, 41.3, 39.4, 31.7, 29.6, 29.0, 26.9, 22.6, 14.1. MS (ES+) m/z 478.2 (M+1).
Reaction SMILES: [CH:1](/[N:14]=[CH:15]/[C:16]1[O:20][N:19]=[C:18]([CH3:21])[C:17]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]([C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=1)=[O:29])([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(Cl)Cl.[Si]([C:44]#[N:45])(C)(C)C>C([O-])(O)=O.[Na+]>[CH:1]([NH:14][CH:15]([C:16]1[O:20][N:19]=[C:18]([CH3:21])[C:17]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28](=[O:29])[C:30]1[CH:31]=[CH:32][C:33]([Cl:36])=[CH:34][CH:35]=1)[C:44]#[N:45])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: Cc1noc(/C=N/C(c2ccccc2)c2ccccc2)c1-c1ccccc1C(=O)c1ccc(Cl)cc1
Reactant: C[Si](C)(C)C#N
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: Cc1noc(C(C#N)NC(c2ccccc2)c2ccccc2)c1-c1ccccc1C(=O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 88.8 %

Procedure:
To a round bottomed flask was added (E)-(2-(5-((benzhydrylimino)methyl)-3-methylisoxazol-4-yl)phenyl)(4-chlorophenyl)methanone (320 mg, 0.652 mmol), DCM (4.5 mL), and Yt(OTf)3 (40.4 mg, 0.065 mmol). To this solution was added TMS-CN (175 μl, 1.304 mmol) and the reaction was stirred overnight at room temperature. This solution was diluted with saturated aqueous NaHCO3. The layers were separated and the aqueous phase was extracted with DCM. The combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude residue was purified via Biotage (EtOAc/hex) to afford the titled compound (300 mg, 0.579 mmol). LC/MS m/z 518 [M+H]+.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH2:8][CH2:7]2)([O-:3])=[O:2].[OH-].[K+].[CH3:15]I.O>CC(C)=O>[CH3:15][N:9]1[C:10]2[C:6](=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=2)[CH2:7][CH2:8]1
Reactant: O=[N+]([O-])c1ccc2c(c1)CCN2
Reactant: CI
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)=O
Product: CN1CCc2cc([N+](=O)[O-])ccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 92.2 %

Procedure:
To a solution of 5-nitro-2,3-dihydro-1H-indole (1 g, 6.09 mmol) in acetone (12 ml) was added powdered potassium hydroxide (1.7 g, 30.45 mmol), followed by methyl iodide (1.2 g, 9.14 mmol) and stirred overnight at ambient temperature. The solvent was evaporated under vacuum to give a residue, to which water was added and the product extracted with ethyl acetate. Drying and concentration of the organic layer yielded 1-methyl-5-nitro-2,3-dihydro-1H-indole (1 g, 92%) as solid.
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][C:9]([N+:13]([O-:15])=[O:14])=[CH:10][CH:11]=2)[C:6](=[C:16](OCC)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:5]1=[O:26])(=O)C.[C:27]([O:31][C:32]([NH:34][CH2:35][C:36]([NH:38][CH2:39][C:40]1[CH:41]=[C:42]([CH:44]=[CH:45][CH:46]=1)[NH2:43])=[O:37])=[O:33])([CH3:30])([CH3:29])[CH3:28].[OH-].[Na+]>CN(C=O)C.CO>[C:27]([O:31][C:32]([NH:34][CH2:35][C:36]([NH:38][CH2:39][C:40]1[CH:41]=[C:42]([NH:43]/[C:16](=[C:6]2\[C:5](=[O:26])[NH:4][C:12]3[C:7]\2=[CH:8][C:9]([N+:13]([O-:15])=[O:14])=[CH:10][CH:11]=3)/[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:44]=[CH:45][CH:46]=1)=[O:37])=[O:33])([CH3:30])([CH3:28])[CH3:29]
Reactant: CCOC(=C1C(=O)N(C(C)=O)c2ccc([N+](=O)[O-])cc21)c1ccccc1
Reactant: CC(C)(C)OC(=O)NCC(=O)NCc1cccc(N)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: CO
Product: CC(C)(C)OC(=O)NCC(=O)NCc1cccc(N/C(=C2\C(=O)Nc3ccc([N+](=O)[O-])cc32)c2ccccc2)c1

Procedure:
Prepared analogously to Example 82 from 1-acetyl-3-(1-ethoxy-1-phenyl-methylidene)-5-nitro-2-indolinone and 3-tert.butoxycarbonylaminomethylcarbonylaminomethyl-aniline in DMF and subsequent treatment with sodium hydroxide solution in methanol.
Reaction SMILES: [C:1]1([C:7]2C3C=CC=CC=3N3C=NN=[C:10]3[CH2:9][N:8]=2)C=CC=CC=1.C(NCCC)CC.[Cl:28][C:29]1[CH:30]=[CH:31][C:32]2[N:38]3[C:39]([CH2:42]Cl)=[N:40][N:41]=[C:37]3[CH2:36][N:35]=[C:34]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:33]=2[CH:50]=1>>[Cl:28][C:29]1[CH:30]=[CH:31][C:32]2[N:38]3[C:39]([CH2:42][N:8]([CH2:9][CH3:10])[CH2:7][CH3:1])=[N:40][N:41]=[C:37]3[CH2:36][N:35]=[C:34]([C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=3)[C:33]=2[CH:50]=1
Reactant: ClCc1nnc2n1-c1ccc(Cl)cc1C(c1ccccc1)=NC2
Reactant: c1ccc(C2=NCc3nncn3-c3ccccc32)cc1
Solvent: CCCNCCC
Product: CCN(CC)Cc1nnc2n1-c1ccc(Cl)cc1C(c1ccccc1)=NC2

Procedure:
In the manner given in Example 4, 8-chloro-1-[di-propylamino)methyl]-6-phenyl-4H-s-triazolo[4,3-a][1,4]-benzodiazepine is prepared by reacting dipropylamine with 8-chloro-1-(chloromethyl)-6-phenyl-4H-s-triazolo[4,3-a]-[1,4]-benzodiazepine.
Reaction SMILES: O[CH2:2][CH2:3][NH:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)=[CH:9][CH:8]=1)=[O:6].C(Br)(Br)(Br)Br.N1C(C)=CC=CC=1C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[N:4]1([C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH2:13][CH2:14][CH:15]3[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH2:19][CH2:20]3)=[CH:11][CH:12]=2)=[O:6])[CH2:2][CH2:3]1
Reactant: CC(C)(C)OC(=O)N1CCC(CCc2ccc(C(=O)NCCO)cc2)CC1
Agent: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: Cc1cccc(C)n1
Product: CC(C)(C)OC(=O)N1CCC(CCc2ccc(C(=O)N3CC3)cc2)CC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 51 %

Procedure:
Tert-butyl 4-[2-(4-{[(2-hydroxyethyl)amino]carbonyl}phenyl)ethyl]piperidine-1-carboxylate (280 mg), carbon tetrabromide (247 mg) and 2,6-lutidine (103 μl) were dissolved in dichloromethane (5.6 ml), and under ice cooling, triphenylphosphine (195 mg) was added thereto, followed by stirring at room temperature for 3 hours. The solvent was evaporated, and the residue was purified by silica gel column chromatography (eluent: hexane:EtOAc=3:7 (v/v)) to obtain tert-butyl 4-{2-[4-(1-aziridinylcarbonyl)phenyl]ethyl}-1-piperidinecarboxylate (136 mg) as a colorless oil.
Reaction SMILES: [C:1]([C:3]1[C:7]([CH3:8])=[N:6][N:5]([CH3:9])[C:4]=1[NH:10][C:11](=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18])#[N:2].[OH:20]O.Cl>[OH-].[Na+]>[F:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:11]1[NH:2][C:1](=[O:20])[C:3]2[C:7]([CH3:8])=[N:6][N:5]([CH3:9])[C:4]=2[N:10]=1
Reactant: OO
Reactant: Cc1nn(C)c(NC(=O)c2ccccc2F)c1C#N
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: Cc1nn(C)c2nc(-c3ccccc3F)[nH]c(=O)c12
Temperature: 90 °C
Yield: 67 %

Procedure:
N-(4-Cyano-2,5-dimethyl-2H-pyrazol-3-yl)-2-fluoro-benzamide (5.0 g, 19.36 mmole) was suspended in 38 ml 1M sodium hydroxide and heated to 90° C. for 3 hours followed by addition of 30% hydrogen peroxide (10 ml) and further heating overnight. The reaction mixture was cooled to room temperature and acidified with dilute hydrochloric acid. The product was isolated by filtration, washed with water, and dried overnight under vacuum to obtain 3.39 g of product. (Yield 67%).