Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[N:7]([C:11]2[C:16]([CH3:17])=[CH:15][CH:14]=[CH:13][C:12]=2[O:18][CH3:19])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[Br:20]Br>C(O)(=O)C.O>[Br:20][C:9]1[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[N:6][N:7]([C:11]2[C:16]([CH3:17])=[CH:15][CH:14]=[CH:13][C:12]=2[O:18][CH3:19])[C:8]=1[NH2:10]
Reactant: BrBr
Reactant: COc1cccc(C)c1-n1nc(C(C)(C)C)cc1N
Solvent: CC(=O)O
Solvent: O
Product: COc1cccc(C)c1-n1nc(C(C)(C)C)c(Br)c1N
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 108.2 %

Procedure:
To a solution of 3-tert-butyl-1-(2-methoxy-6-methylphenyl)-1H-pyrazol-5-amine (2.00 g, 7.71 mmol) (Intermediate C) in acetic acid (15 mL) was added bromine (1170 mg, 0.38 mL, 7.33 mmol) dropwise. The reaction mixture was stirred for 5 min at rt, and then diluted with water (100 mL), causing a solid to precipitate. The solid was collected by filtration, then dissolved in EtOAc. The organic phase was then washed with saturated NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated under reduced pressure to afford product (2683 mg, 102%) containing minor impurities. ES-MS m/z 338.2 (MH+); HPLC RT (min) 3.06.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([NH:14][C:15](=[O:19])OCC)=[N:5]2.[CH3:20][C:21]1[CH:22]=[C:23]([N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)[CH:24]=[CH:25][CH:26]=1>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([NH:14][C:15]([N:30]1[CH2:31][CH2:32][N:27]([C:23]3[CH:24]=[CH:25][CH:26]=[C:21]([CH3:20])[CH:22]=3)[CH2:28][CH2:29]1)=[O:19])=[N:5]2
Reactant: CCOC(=O)Nc1nc2cc(Cl)ccc2nc1OC
Reactant: Cc1cccc(N2CCNCC2)c1
Product: COc1nc2ccc(Cl)cc2nc1NC(=O)N1CCN(c2cccc(C)c2)CC1
Yield: 90 %

Procedure:
Ethyl N-(6-chloro-2-methoxyquinoxalin-3-yl)carbamate and 1-(3-methylphenyl)piperazine were reacted by the same way with the example 22 to obtain the titled compound (yield, 90%). 1H NMR (300 MHz, CDCl3): δ 3.20-3.30 (m, 4H), 3.74-3.77 (m, 3H), 4.11-4.14 (m, 4H), 6.74-6.77 (m, 3H), 7.16-7.25 (m, 4H), 7.64-7.81 (m, 1H).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][N:3]=1.[NH:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1>C1COCC1>[N+:8]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:7]=1)([O-:10])=[O:9]
Reactant: C1CCNC1
Reactant: O=[N+]([O-])c1ccnc(Cl)c1
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccnc(N2CCCC2)c1
Temperature: 80 °C
Reaction time: 8 h
Yield: 23.8 %

Procedure:
2-Chloro-4-nitropyridine (2.0 g, 12.2 mmol) was dissolved in THF (30 mL) and the solution was added with pyrrolidine (3.25 mL, 38.9 mmol), followed by stirring at 80° C. overnight. After an insoluble matter of the reaction mixture was filtered off, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80) to obtain 4-nitro-2-(pyrrolidin-1-yl)pyridine (560 mg, 24%).
Reaction SMILES: [F:1][CH:2]([F:25])[O:3][C:4]1[CH:24]=[CH:23][C:7]([CH2:8][C:9]2[C:10]([CH3:22])=[C:11]([CH3:21])[C:12]([CH:19]=O)=[C:13]([CH:18]=2)[C:14](OC)=[O:15])=[CH:6][CH:5]=1.[NH2:26][C@@H:27]1[C@@H:32]([OH:33])[CH2:31][CH2:30][O:29][CH2:28]1>C1COCC1>[F:1][CH:2]([F:25])[O:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][C:9]2[CH:18]=[C:13]3[C:12]([CH2:19][N:26]([C@@H:27]4[C@@H:32]([OH:33])[CH2:31][CH2:30][O:29][CH2:28]4)[C:14]3=[O:15])=[C:11]([CH3:21])[C:10]=2[CH3:22])=[CH:23][CH:24]=1
Reactant: COC(=O)c1cc(Cc2ccc(OC(F)F)cc2)c(C)c(C)c1C=O
Reactant: N[C@H]1COCC[C@@H]1O
Solvent: C1CCOC1
Product: Cc1c(Cc2ccc(OC(F)F)cc2)cc2c(c1C)CN([C@H]1COCC[C@@H]1O)C2=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 56.1 %

Procedure:
To a solution of methyl 5-(4-(difluoromethoxy)benzyl)-2-formyl-3,4-dimethylbenzoate (0.04 g) in THF (2.00 mL) was added (3S,4S)-3-aminotetrahydro-2H-pyran-4-ol (0.01 g) under argon atmosphere, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated, and the residue was diluted with acetic acid (2.00 mL). Sodium triacetoxyborohydride (0.03 g) was added thereto under argon atmosphere, and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with saturated aqueous sodium bicarbonate solution, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate/hexane) to give the title compound (0.02 g).
Reaction SMILES: C(OC(N1C[CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C@@H:21]3[O:30][C:25]4=[N:26][CH:27]=[CH:28][CH:29]=[C:24]4[O:23][CH2:22]3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.N1CC[CH:34]([CH2:37][NH:38][C:39](=[O:41])[CH3:40])[CH2:33]C1>>[O:23]1[C:24]2[C:25](=[N:26][CH:27]=[CH:28][CH:29]=2)[O:30][C@@H:21]([C:18]2[CH:17]=[CH:16][C:15]([CH2:14][N:11]3[CH2:10][CH2:9][CH:34]([CH2:37][NH:38][C:39](=[O:41])[CH3:40])[CH2:33][CH2:12]3)=[CH:20][CH:19]=2)[CH2:22]1
Reactant: CC(C)(C)OC(=O)N1CCN(Cc2ccc([C@H]3COc4cccnc4O3)cc2)CC1
Reactant: CC(=O)NCC1CCNCC1
Product: CC(=O)NCC1CCN(Cc2ccc([C@H]3COc4cccnc4O3)cc2)CC1

Procedure:
Compound 279 is synthesized from Intermediate C and N-piperidin-4-ylmethyl-acetamide according to General Method H. (LC/MS method 16: ES+ m/z 382.4 [M+H]+, Rt=2.50 min)
Reaction SMILES: [NH2:1][C:2]1[CH:6]=[CH:5][NH:4][N:3]=1.[CH3:7][C:8](=O)[CH2:9][CH2:10][C:11](=O)[CH3:12].O>C(O)(=O)C>[CH3:12][C:11]1[N:1]([C:2]2[CH:6]=[CH:5][NH:4][N:3]=2)[C:8]([CH3:7])=[CH:9][CH:10]=1
Reactant: Nc1cc[nH]n1
Reactant: CC(=O)CCC(C)=O
Solvent: O
Solvent: CC(=O)O
Product: Cc1ccc(C)n1-c1cc[nH]n1
Temperature: 25 °C
Reaction time: 2.4 h

Procedure:
To a solution of 3-aminopyrazole (100 g) in acetic acid (1000 ml) was added 2,5-hexanedione (148 ml), and the mixture was stirred for 2.4 hours at reflux. This reaction solution was cooled to room temperature, water (1000 ml) was added thereto, and the precipitated solid was collected by filtration. The resulting solid was washed with water (1000 ml), and dried under reduced pressure to give the titled compound (183 g).
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:19][N:18]=[C:17]([C:20]3[CH:32]=[CH:31][C:23]([O:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=4)=[CH:22][CH:21]=3)[N:16]=2)=[CH:11][CH:10]=1)C1C=CC=CC=1.C1COCC1>CO.[Pd]>[N:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[O:24][C:23]1[CH:31]=[CH:32][C:20]([C:17]2[N:16]=[C:15]([C:12]3[CH:11]=[CH:10][C:9]([OH:8])=[CH:14][CH:13]=3)[O:19][N:18]=2)=[CH:21][CH:22]=1
Reactant: c1ccc(COc2ccc(-c3nc(-c4ccc(Oc5ccccn5)cc4)no3)cc2)cc1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: Oc1ccc(-c2nc(-c3ccc(Oc4ccccn4)cc3)no2)cc1
Temperature: 55 °C
Reaction time: 22 h
Yield: 5.6 %

Procedure:
2-(4-(5-(4-(Benzyloxy)phenyl)-1,2,4-oxadiazol-3-yl)phenoxy)pyridine (310 mg, 376 μmol) was placed in a single neck round bottom flask, suspended in methanol (5.0 mL) and THF (5.0 mL) and 10% Pd/C (0.5 mg, 5.0 μmol) was added. A condenser was placed on top of the flask and then sealed. The solution was stirred under H2 at 55° C. for 22 hours. While hot, the solution was filtered through Celite washed with additional methanol and the solvent was removed under reduced pressure. The solid residue was purified by silica gel column chromatography (EtOAc/Hex 1:2) to give the product as a white solid (7 mg, 3%). 1H NMR (500 MHz, CDCL3) δ(ppm): 7.00 (2H, d, J=8.8 Hz), 7.14 (1H, d, J=8.2 Hz), 7.05 (1H, ddd, J=7.3, 5.0, 1.0 Hz), 7.32 (2H, d, J=8.8 Hz), 7.92 (1H, ddd, J=8.8, 8.2, 2.0 Hz), 8.03 (2H, d, J=8.8 Hz), 8.11 (2H, d, J=8.8 Hz), 8.21 (1H, ddd, J=5.0, 2.0, 1.0 Hz). 13C NMR (125 MHz, CDCL3) δ(ppm): 112.2 (CH), 114.1, 116.3 (CH), 119.7 (CH), 121.5 (CH), 122.4, 128.7 (CH), 130.1 (CH), 140.5 (CH), 147.6 (CH), 156.6, 162.1, 162.4 167.6, 175.5. MS (FAB+): 332 (MH+). HRMS for C19H13N3O3 (MH+): calculated: 332.1035; found 332.1049.
Reaction SMILES: [Na].[Cl:2][C:3]1[NH:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[Cl-].[Cl-].[Ca+2].[O:15]1[CH:17]([CH2:18][CH3:19])[CH2:16]1>>[OH:15][CH:17]([CH2:18][CH3:19])[CH2:16][N:4]1[C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=[C:3]1[Cl:2]
Reactant: CCC1CO1
Reactant: Clc1nc2ccccc2[nH]1
Agent: [Ca+2]
Agent: [Cl-]
Agent: [Na]
Product: CCC(O)Cn1c(Cl)nc2ccccc21
Reaction time: 15 h

Procedure:
5 g of the sodium salt of 2-chlorobenzimidazole are suspended in 50 ml of epoxybutane in a flask provided with a reflux condenser and a CaCl2 plug. The mixture is boiled for 15 hours, the epoxybutane is then evaporated under vacuum and the residue is taken up with water and made alkaline with 10% sodium hydrate. After agitation for about 1 hour it is filtered and the residue obtained is crystallised twice from benzene. A white product is obtained which melts at 126°.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][N:7]([CH2:12][CH2:13][CH2:14][NH2:15])[CH:6]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[CH2:5]2.[CH3:24][O:25][C:26]1[CH:27]=[C:28]([N:32]=[C:33]=[O:34])[CH:29]=[CH:30][CH:31]=1>>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][N:7]([CH2:12][CH2:13][CH2:14][NH:15][C:33]([NH:32][C:28]1[CH:29]=[CH:30][CH:31]=[C:26]([O:25][CH3:24])[CH:27]=1)=[O:34])[CH:6]([CH2:16][C:17]1[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=1)[CH2:5]2
Reactant: COc1cccc(N=C=O)c1
Reactant: NCCCN1Cc2ccc(F)cc2CC1Cc1ccc(F)cc1
Product: COc1cccc(NC(=O)NCCCN2Cc3ccc(F)cc3CC2Cc2ccc(F)cc2)c1

Procedure:
The reaction and treatment were carried out in the same manner as in Example 208 using 3-[6-fluoro-3-(4-fluorobenzyl)-3,4-dihydroisoquinolin-2(1H)-yl]propanamine obtained in Example 238-b) as a starting material, and using 3-methoxyphenyl isocyanate instead of phenyl isocyanate to obtain a title compound as a pale yellow amorphous substance.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([C:11]([OH:13])=O)=[CH:7][C:6]=12.C(Cl)(=O)C(Cl)=O.[O:20]1[CH2:23][CH:22]([NH:24][C:25]2[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][N:26]=2)[CH2:21]1.[H-].[Na+]>ClCCl.CN(C)C=O>[Br:1][C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([C:11]([N:24]([C:25]3[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][N:26]=3)[CH:22]3[CH2:21][O:20][CH2:23]3)=[O:13])=[CH:7][C:6]=12
Reactant: O=C(O)c1ccn2ncc(Br)c2c1
Reactant: N#Cc1ccc(NC2COC2)nc1
Agent: O=C(Cl)C(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: N#Cc1ccc(N(C(=O)c2ccn3ncc(Br)c3c2)C2COC2)nc1
Reaction time: 0.5 h
Yield: 18.8 %

Procedure:
To a solution of 3-bromopyrazolo[1,5-a]pyridine-5-carboxylic acid (I-7, 240 mg, 1 mmol) in dichloromethane (10 mL) was added oxalyl chloride (0.25 mL) and catalytic amounts of anhydrous dimethylformamide at rt. The reaction mixture was stirred for 30 minutes and subsequently the solvent was removed under reduced pressure. To the residual acid chloride was added a solution of 6-(oxetan-3-ylamino)nicotinonitrile (I-25, 175 mg, 1 mmol) in dichloromethane (10 mL). The resulting reaction mixture was quickly transferred to a microwave vial and NaH (60% in mineral oil) (191 mg, 5 mmol) was added. The vial was heatedin a microwave oven at 80° C. for 3 h. The reaction mixture was diluted with dichloromethane (15 mL) and subsequently washed with water, sat. NaHCO3 solution and brine. The organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure. The resulting crude product was purified by column chromatography over silica gel (chloroform/MeOH, 0-10% EtOAc) to afford 75 mg (20%) of 3-bromo-N-(5-cyanopyridin-2-yl)-N-(oxetan-3-yl)pyrazolo[1,5-a]pyridine-5-carboxamide (I-26) as a brown solid. 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J=7.0 Hz, 1H), 8.16 (s, 1H), 8.02 (t, J=7.90 Hz, 1H), 7.53 (d, J=0.8 Hz, 1H), 7.33-7.31 (m, 1H), 6.90-6.87 (m, 1H), 6.43 (d, J=10.1 Hz, 1H), 4.67-4.62 (m, 1H), 4.52-4.43 (m, 2H), 4.25-4.19 (m, 1H), 4.03-3.98 (m, 1H); ESI-LC/MS (m/z): [M+H]+ 398.13, [(M+2)+H]+ 400.08, RT 1.25 min.
Reaction SMILES: C([O:4][CH2:5][CH3:6])(=O)C.[NH2:7][CH2:8][C:9]([NH2:12])([CH3:11])[CH3:10]>>[CH3:10][C:9]([NH2:12])([CH3:11])[CH2:8][NH:7][C:5](=[O:4])[CH3:6]
Reactant: CCOC(C)=O
Reactant: CC(C)(N)CN
Product: CC(=O)NCC(C)(C)N
Temperature: 100 °C
Yield: 57.4 %

Procedure:
A mixture of 26.4 g (0.3 mol) of ethyl acetate and 79.2 g (0.9 mole) of 1,2-diamino-2-methylpropane was heated at 100° C. in a pressured bomb for 36 hours. The reaction mixture was evaporated in vacuo and distilled to give 22.4 g (57.4%) of product which had a boiling point of 100° C. at 0.1 mmHg. This product was identified by NMR and IR spectroscopy.
Reaction SMILES: [I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[CH3:9][O:10][N:11]([CH3:30])[C:12](=[O:29])/[CH:13]=[CH:14]/[C:15]1[CH:24]=[CH:23][C:22]2[C:21]([CH3:26])([CH3:25])[CH2:20][CH2:19][C:18]([CH3:28])([CH3:27])[C:17]=2[CH:16]=1.O>CS(C)=O>[CH3:9][O:10][N:11]([CH3:30])[C:12]([CH:13]1[CH2:2][CH:14]1[C:15]1[CH:24]=[CH:23][C:22]2[C:21]([CH3:25])([CH3:26])[CH2:20][CH2:19][C:18]([CH3:28])([CH3:27])[C:17]=2[CH:16]=1)=[O:29]
Reactant: CON(C)C(=O)/C=C/c1ccc2c(c1)C(C)(C)CCC2(C)C
Reactant: C[S+](C)(C)=O
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CON(C)C(=O)C1CC1c1ccc2c(c1)C(C)(C)CCC2(C)C

Procedure:
660 mg (3.3 mmol) of trimethylsulphoxonium iodide and 3 ml of DMSO are introduced into a three-necked flask under a stream of nitrogen. 100 mg (4.12 mmol) of sodium hydride (80% in oil) are added portionwise and the mixture is stirred until the evolution of gas has ceased. A solution of 900 mg (3 mmol) of (E)-N-methoxy-N-methyl-3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)acrylamide in 15 ml of DMSO is then added dropwise and the mixture is stirred at room temperature for two hours. The reaction medium is poured into water and extracted with ethyl acetate, and the organic phase is separated out after settling has taken place, dried over magnesium sulphate and evaporated. The residue obtained is purified by chromatography on a column of silica eluted with a mixture of heptane and ethyl acetate (80/20). After evaporating the solvents, 400 mg (43%) of N-methoxy-N-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)cyclopropanecarboxamide are collected in the form of an oil.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[CH:11][C:12]([O:17][CH2:18][CH3:19])=[C:13]([CH:16]=1)[C:14]#[N:15])C1C=CC=CC=1>CO.[Pd]>[CH2:18]([O:17][C:12]1[CH:11]=[CH:10][C:9]([OH:8])=[CH:16][C:13]=1[C:14]#[N:15])[CH3:19]
Reactant: CCOc1ccc(OCc2ccccc2)cc1C#N
Agent: [Pd]
Solvent: CO
Product: CCOc1ccc(O)cc1C#N
Reaction time: 4 h

Procedure:
40.02 g of 5-benzyloxy-2-ethoxybenizonitrile (158 mmol) (example 32A) and 5% Pd/C (4.0 g) are initially charged in 1 l of methanol. The mixture is then hydrogenated under an atmosphere of hydrogen (1 atm) for about 4 h. The mixture is filtered through kieselguhr and evaporated and the crystalline residue is dried under reduced pressure.
Reaction SMILES: Cl.[CH3:2][C:3]1([CH3:15])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][CH:4]1[C:12]([OH:14])=[O:13].C(N(CC)CC)C.[C:23]([S:31][CH2:32][CH:33]([CH3:37])[C:34](Cl)=[O:35])(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(Cl)Cl>[C:23]([S:31][CH2:32][CH:33]([CH3:37])[C:34]([N:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:3]([CH3:15])([CH3:2])[CH:4]1[C:12]([OH:14])=[O:13])=[O:35])(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: CC(CSC(=O)c1ccccc1)C(=O)Cl
Reactant: CC1(C)c2ccccc2NC1C(=O)O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(CSC(=O)c1ccccc1)C(=O)N1c2ccccc2C(C)(C)C1C(=O)O
Reaction time: 1 h

Procedure:
To the suspension of 1.0 g of 3,3-dimethylindoline-2-carboxylic acid hydrochloride in 25 ml of methylene chloride, 1.33 g of triethylamine are added and the resulting solution cooled to -10°. The solution of 1.065 g of 3-benzoylthio-2-methylpropanoyl chloride in 5 ml of methylene chloride is added dropwise and the mixture stirred at -5° for 1 hour, and then at room temperature for 2 hours. It is evaporated, 10 ml of 3N hydrochloric acid are added to the residue and the mixture is extracted with methylene chloride. The extract is dried and evaporated, to give the 1-(3-benzoylthio-2-methylpropanoyl)-3,3-dimethylindoline-2-carboxylic acid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9][C:10]2[N:14]([CH3:15])[C:13]([CH2:16][CH2:17][OH:18])=[N:12][C:11]=2[CH:19]([CH3:21])[CH3:20])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:22][O:23][C:24]1(OC)[C:36]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:30]2[C:25]1=[CH:26][CH:27]=[CH:28][CH:29]=2>>[Cl:8][C:6]1[CH:5]=[C:4]([S:9][C:10]2[N:14]([CH3:15])[C:13]([CH2:16][CH2:17][O:18][C:24]3([O:23][CH3:22])[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][C:30]=4[C:31]4[C:36]3=[CH:35][CH:34]=[CH:33][CH:32]=4)=[N:12][C:11]=2[CH:19]([CH3:21])[CH3:20])[CH:3]=[C:2]([Cl:1])[CH:7]=1
Reactant: COC1(OC)c2ccccc2-c2ccccc21
Reactant: CC(C)c1nc(CCO)n(C)c1Sc1cc(Cl)cc(Cl)c1
Product: COC1(OCCc2nc(C(C)C)c(Sc3cc(Cl)cc(Cl)c3)n2C)c2ccccc2-c2ccccc21
Yield: 21.1 %

Procedure:
The compound 22 (345 mg, 1 mmol) was converted to the acetal with 9,9-dimethoxyfluorene (2.26 g, 10 mmol) in the same manner as the example 20 to give the compound 43 (114 mg, 21.2%). Mp 130-131° C. PMR (CDCl3 -0.1% d5 -Py): δH1.24 (6 H, d, J 7 Hz, (CH3)2C), 3.20 (3 H, s, CH3O), 3.02 (2 H, m, CH2 -Im), 3.11 (1 H, m, (CH3)2CH), 3.42 (3 H, s, NCH3), 3.85 (2 H, t, J 6.2 Hz, OCH2), 6.8-7.6 (8 H, m, arom-H) Elementary analysis (for C29H28N2O2Cl2S) Calcd.: C, 64.56% H, 5.23% N, 5.19% S, 5.94% Cl, 13.14% Found: C, 64.65% H, 5.25% N, 5.10% S, 5.95% Cl, 12.89%
Reaction SMILES: [CH3:1][N:2]1[C:6]([SH:7])=[N:5][C:4]([N+:8]([O-:10])=[O:9])=[N:3]1.CN(C=O)C.C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:24][C:25]1[N:29]([CH2:30][CH2:31][CH3:32])[CH:28]=[N:27][CH:26]=1>O>[CH3:1][N:2]1[C:6]([S:7][CH2:24][C:25]2[N:29]([CH2:30][CH2:31][CH3:32])[CH:28]=[N:27][CH:26]=2)=[N:5][C:4]([N+:8]([O-:10])=[O:9])=[N:3]1
Reactant: Cn1nc([N+](=O)[O-])nc1S
Reactant: CCCn1cncc1CCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCn1cncc1CSc1nc([N+](=O)[O-])nn1C
Temperature: 25 °C
Reaction time: 18 h
Yield: 47.3 %

Procedure:
1-methyl-3-nitro-1,2,4-triazol-5-thiol (0.66 g) was dissolved in. DMF (13.2 ml), potassium carbonate (1.7 g) and 5-chloromethyl-1-propylimidazole hydrochloride (1.1 g) were added to the mixture, and the mixture was stirred for 18 hours at room temperature. The reaction solution was added to water and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure, and the obtained residue was washed, to give 1-methyl-3-nitro-5-[[(1-propylimidazol-5-yl)methyl]thio]-1,2,4-triazole (0.55 g).
Reaction SMILES: [C:1]1([S:7]([C:10]2[C:15](=[NH:16])[N:14]3[CH:17]=[CH:18][CH:19]=[CH:20][C:13]3=[N:12][C:11]=2[S:21][CH3:22])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.[C:29](Cl)(=[O:31])[CH3:30]>C(Cl)Cl>[C:1]1([S:7]([C:10]2[C:15](=[N:16][C:29](=[O:31])[CH3:30])[N:14]3[CH:17]=[CH:18][CH:19]=[CH:20][C:13]3=[N:12][C:11]=2[S:21][CH3:22])(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CSc1nc2ccccn2c(=N)c1S(=O)(=O)c1ccccc1
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CSc1nc2ccccn2c(=NC(C)=O)c1S(=O)(=O)c1ccccc1
Reaction time: 8 h

Procedure:
3-Benzenesulfonyl-2-methylsulfanyl-pyrido[1,2-a]pyrimidin-4-ylideneamine (100 mg, 0.30 mmol) was dissolved in anhydrous methylenechloride (2 ml) to which pyridine (48 mg, 0.6 mmol) was added. Acetylchloride was then added at room temperature and the reaction mixture was stirred overnight. The reaction was quenched with saturated aqueous NaHCO3, extracted with methylene chloride, and purified by flash chromatography to yield 79 mg of a yellow solid product.
Reaction SMILES: [N:1](OCCC(C)C)=[O:2].[CH3:9][N:10]1[C:14](=[O:15])[CH:13]=[C:12]([CH3:16])[NH:11]1.C[O-].[Na+]>C(O)C>[CH3:9][N:10]1[C:14](=[O:15])[C:13](=[N:1][OH:2])[CH:12]([CH3:16])[NH:11]1
Reactant: CC(C)CCON=O
Reactant: Cc1cc(=O)n(C)[nH]1
Agent: C[O-]
Agent: [Na+]
Solvent: CCO
Product: CC1NN(C)C(=O)C1=NO
Temperature: 0 °C
Reaction time: 24 h
Yield: 72.5 %

Procedure:
183 g (1.56 mol) of isopentyl nitrite are added dropwise to 175 g (1.56 mol) of 1,3-dimethyl-pyrazolin-5-one and 84.4 g (1.56 mol) of sodium methylate in 1 L of absolute ethanol, while stirring and cooling with ice so that the internal temperature does not rise above 25° C. to 30° C. When the addition has ended, stirring is continued at room temperature for 24 hours and the sodium salt of 1,3-dimethyl-4-hydroximino-pyrazolin-5-one which has precipitated is filtered off with suction. The crystalline product is dissolved in 1 L of water and the solution is acidified with glacial acetic acid. For complete precipitation, the mixture is cooled at 0° C. for several hours, and the product is then filtered off with suction. 162 g (74% of theory) of 1,3-dimethyl-4-hydroximino-pyrazolin-5-one of melting point 93° C. are obtained.
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:18]=[CH:17][C:13]([C:14](O)=[O:15])=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)[CH2:2][CH3:3].S(Cl)([Cl:21])=O>C(Cl)Cl>[CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:18]=[CH:17][C:13]([C:14]([Cl:21])=[O:15])=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)[CH2:2][CH3:3]
Reactant: O=S(Cl)Cl
Reactant: CCCc1ccc(-c2ccc(C(=O)O)cc2)cc1
Solvent: ClCCl
Product: CCCc1ccc(-c2ccc(C(=O)Cl)cc2)cc1

Procedure:
A mixture of 2.0 g of 4-(4-propylphenyl]benzoic acid and 30 ml of thionyl chloride is stirred at reflux for 45 minutes. The reaction mixture is evaporated in vacuo to a residue which is evaporated from carbon tetrachloride (2×50 ml) to give a residue which is dissolved in methylene chloride.
Reaction SMILES: [C:1]1([NH:7][C:8]([C:10]2[C:14]([N+:15]([O-])=O)=[CH:13][NH:12][N:11]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.O.[Sn](Cl)Cl>C(O)C>[C:1]1([NH:7][C:8]([C:10]2[C:14]([NH2:15])=[CH:13][NH:12][N:11]=2)=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(Nc1ccccc1)c1n[nH]cc1[N+](=O)[O-]
Agent: Cl[Sn]Cl
Solvent: O
Solvent: CCO
Product: Nc1c[nH]nc1C(=O)Nc1ccccc1
Yield: 17.3 %

Procedure:
4-Nitro-1H-pyrazole-3-carboxylic acid phenylamide (100 mg; 0.43 mmol) was dissolved in ethanol (5 ml), treated with tin (II) chloride dihydrate (500 mg; 2.15 mmol) then heated at reflux overnight. The reaction mixture was cooled and evaporated. The residue was partitioned between ethyl acetate and brine, and the ethyl acetate layer was separated, dried (MgSO4), filtered and evaporated. The crude product was purified by flash column chromatography eluting with 1:1 ethyl acetate/petroleum ether then 5% methanol/dichloromethane. Evaporation of product containing fractions followed by preparative LC/MS gave 15 mg of the product as an off white solid. (LC/MS: Rt 1.40, [M+H]+ 202.95).
Reaction SMILES: [CH:1]1([C:7]2[CH:30]=[CH:29][C:10]([C:11]([N:13]([CH3:28])[C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH2:24][CH:23]([NH:25][CH3:26])[CH2:22][C:21]4=[O:27])=[CH:16][CH:15]=3)=[O:12])=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:31](OC(=O)C)(=[O:33])[CH3:32]>N1C=CC=CC=1>[C:31]([CH2:26][NH:25][CH:23]1[CH2:24][N:20]([C:17]2[CH:18]=[CH:19][C:14]([N:13]([CH3:28])[C:11](=[O:12])[C:10]3[CH:29]=[CH:30][C:7]([CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]4)=[CH:8][CH:9]=3)=[CH:15][CH:16]=2)[C:21](=[O:27])[CH2:22]1)(=[O:33])[CH3:32]
Reactant: CNC1CC(=O)N(c2ccc(N(C)C(=O)c3ccc(C4CCCCC4)cc3)cc2)C1
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)CNC1CC(=O)N(c2ccc(N(C)C(=O)c3ccc(C4CCCCC4)cc3)cc2)C1

Procedure:
4-Cyclohexyl-N-methyl-N-[4-(4-methylamino-2-oxo-pyrrolidin-1-yl)phenyl]benzamide (101 mg) was mixed with pyridine (20 mg) and acetic anhydride (25 mg) and, after 3 hours, volatile fractions were removed in vacuo. This resulted in the product with the molecular weight of 447.58 (C27H33N3O3); MS (ESI): 448 (M+H+).