Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH2:7][C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=1[C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=O>>[Cl:18][C:15]1[CH:14]=[C:13]2[C:12](=[CH:17][CH:16]=1)[NH:11][C:8](=[O:10])[C:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)=[C:19]2[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: O=C(O)Cc1ccccc1
Reactant: Nc1ccc(Cl)cc1C(=O)c1ccccc1
Product: O=c1[nH]c2ccc(Cl)cc2c(-c2ccccc2)c1-c1ccccc1
Yield: 53 %

Procedure:
from phenylacetic acid and (2-amino-5-chloro-phenyl)-phenyl-methanone according to general procedure 2. Yield 53%.
Reaction SMILES: [NH2:1][C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5].[NH:10]([C:19]([O:21][CH2:22][CH:23]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]2[C:24]1=[CH:25][CH:26]=[CH:27][CH:28]=2)=[O:20])[C@H:11]([C:16](O)=[O:17])[C@H:12]([CH2:14][CH3:15])[CH3:13].C(N(C(C)C)CC)(C)C>CN(C)C=O>[NH:10]([C:19]([O:21][CH2:22][CH:23]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]2[C:24]1=[CH:25][CH:26]=[CH:27][CH:28]=2)=[O:20])[C@H:11]([C:16]([NH:1][C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5])=[O:17])[C@H:12]([CH2:14][CH3:15])[CH3:13]
Reactant: CC[C@H](C)[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Reactant: CC(C)C[C@H](N)C(=O)O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC[C@H](C)[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)N[C@@H](CC(C)C)C(=O)O

Procedure:
Acylation of the Leu resin with Fmoc-Ile (1.42 g, 4 mmole) activated with O-(benzotriazol-1-yl),1,1,3,3,-tetramethyluronium hexafluorophosphate (HBTU) (1.52 g, 4 mmole) and diisopropylethylamine (1.4 ml, 8 mmole) in dimethylformamide (8 ml) for 30 minutes. After the reaction, the resin was washed five times (as above) with dimethylformamide to remove the excess reagents and dried. Only half of the Fmoc-Ile-Leu resin thus obtained was used in the next step.
Reaction SMILES: [C:1]([O:4][CH:5]1[O:18][C@H:17]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[C@H:12]([O:13][C:14](=[O:16])[CH3:15])[C@H:11]([N:24]=[N+:25]=[N-:26])[C@H:6]1[O:7][C:8](=[O:10])[CH3:9])(=[O:3])[CH3:2].[C:27]([O:31][CH3:32])(=[O:30])[C:28]#[CH:29].C(N(C(C)C)CC)(C)C>[Cu](I)I.C1(C)C=CC=CC=1>[C:1]([O:4][CH:5]1[O:18][C@H:17]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[C@H:12]([O:13][C:14](=[O:16])[CH3:15])[C@H:11]([N:24]2[CH:29]=[C:28]([C:27]([O:31][CH3:32])=[O:30])[N:26]=[N:25]2)[C@H:6]1[O:7][C:8](=[O:10])[CH3:9])(=[O:3])[CH3:2]
Reactant: C#CC(=O)OC
Reactant: CC(=O)OC[C@H]1OC(OC(C)=O)[C@H](OC(C)=O)[C@@H](N=[N+]=[N-])[C@H]1OC(C)=O
Agent: I[Cu]I
Solvent: Cc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1cn([C@H]2[C@@H](OC(C)=O)[C@@H](COC(C)=O)OC(OC(C)=O)[C@@H]2OC(C)=O)nn1
Temperature: 25 °C
Reaction time: 12 h
Yield: 93 %

Procedure:
A mixture of 1,2,4,6-tetra-O-acetyl-3-azido-3-deoxy-D-galactopyranose 22 (Lowary and Hindsgaul, 1994) (10 mg, 0.027 mmol), methyl propiolate (2.4 μL, 1 eq.), copper iodide (0.6 mg, 0.1 eq.), diisopropylethylamine (1 eq.), and toluene (1 mL) were stirred together for 12 h at r.t. The solvent was evaporated and the product was purified by column chromatography (SiO2, heptane:EtOAc 2:1) to give 23 (12.2 mg, 93%).
Reaction SMILES: Cl[CH2:2][C@@H:3]([CH3:13])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1.[CH3:14][CH:15]([CH3:31])[C:16]([NH:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH:20]=1)=[O:17]>>[F:12][C:9]1[CH:10]=[CH:11][C:6]([O:5][CH2:4][C@H:3]([CH3:13])[CH2:2][N:28]2[CH2:29][CH2:30][CH:25]([C:21]3[CH:20]=[C:19]([NH:18][C:16](=[O:17])[CH:15]([CH3:14])[CH3:31])[CH:24]=[CH:23][CH:22]=3)[CH2:26][CH2:27]2)=[CH:7][CH:8]=1
Reactant: C[C@H](CCl)COc1ccc(F)cc1
Reactant: CC(C)C(=O)Nc1cccc(C2CCNCC2)c1
Product: CC(C)C(=O)Nc1cccc(C2CCN(C[C@@H](C)COc3ccc(F)cc3)CC2)c1

Procedure:
Prepared by Procedure G and Scheme B1 using 1-{[(2S)-3-chloro-2-methylpropyl]oxy}-4-fluorobenzene and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 413.8 (M+H)+.
Reaction SMILES: [NH:1]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[C:5](=[O:12])[CH2:4][CH2:3][C:2]1=[O:13].[CH3:14][N:15]([CH3:18])[CH:16]=O>C(OCC)C>[CH3:14][N:15]([CH:18]=[C:3]1[CH2:4][C:5](=[O:12])[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[NH:1][C:2]1=[O:13])[CH3:16]
Reactant: O=C1CCC(=O)c2ccccc2N1
Reactant: CN(C)C=O
Solvent: CCOCC
Product: CN(C)C=C1CC(=O)c2ccccc2NC1=O
Temperature: 90 °C
Yield: 79 %

Procedure:
A mixture of 0.250 g (1.43 mmol) of 3,4-dihydro-1H-1benzazepine-2,5-dione and 5.5 ml (4.93 g, 41.5 mmol) of N,N-dimethylformamide, dimethylacetal is heated at 90° C. for 1.5 hour. The mixture is cooled, diluted with diethylether and filtered. The solid is washed well with diethylether and dried to give 0.26 g of tan crystals, m.p. 203°-205° C.
Reaction SMILES: Br[CH2:2][C:3](=O)[C:4](=[N:10][O:11][CH2:12][CH2:13][CH3:14])[C:5]([O:7][CH2:8][CH3:9])=[O:6].[NH2:16][C:17]([NH2:19])=[S:18].O>C(O)C>[NH2:19][C:17]1[S:18][CH:2]=[C:3]([C:4](=[N:10][O:11][CH2:12][CH2:13][CH3:14])[C:5]([O:7][CH2:8][CH3:9])=[O:6])[N:16]=1
Reactant: NC(N)=S
Reactant: CCCON=C(C(=O)CBr)C(=O)OCC
Solvent: O
Solvent: CCO
Product: CCCON=C(C(=O)OCC)c1csc(N)n1
Reaction time: 1 h
Yield: 58.3 %

Procedure:
85 g of ethyl 4-bromo-2-propoxyimino-acetoacetate are added dropwise to 23 g (0.3 mole) of thiourea in 155 ccs of water and 75 ccs of ethanol at 25°, while stirring. After one hour, the hydrobromide which has precipitated in the meantime is decomposed by adding concentrated ammonia up to pH 6. After filtering off the product, washing with water and diisopropyl ether and drying, 45 g of ethyl 2-(2-aminothiazol-4-yl)-2-propoxyimino-acetate are obtained.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10](=O)[O:11][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:13][CH:14]=1.CO.[CH3:22][NH2:23]>C(O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10](=[O:11])[N:23]([CH3:22])[C:12]([C:15]([F:18])([F:17])[F:16])=[CH:13][CH:14]=1
Reactant: O=c1oc(C(F)(F)F)ccc1-c1ccc(F)cc1F
Reactant: CN
Solvent: CCO
Solvent: CO
Product: Cn1c(C(F)(F)F)ccc(-c2ccc(F)cc2F)c1=O
Temperature: 0 °C
Reaction time: 6 h
Yield: 26 %

Procedure:
13.8 g (50 mmol) of 3-(2,4-difluorophenyl)-6-trifluoromethyl-2H-pyran-2-one was dissolved in 150 ml of ethanol, and 5.5 g (70 mmol) of a 40% methylamine methanol solution was added, followed by stirring for 6 hours under heating and refluxing. The reaction solution was poured into ice water and extracted with ethyl acetate. After washing with 1N hydrochloric acid and water, the organic layer was dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and then, the obtained residue was purified by silica gel column chromatography to obtain 3.8 g (yield: 26%) of the desired product. Melting point: 123-124° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:39][CH2:40][CH3:41])=[C:24]([NH:27][C:28](=[O:38])[CH2:29]P(OCC)(OCC)=O)[CH:25]=3)[N:20]=[CH:19][C:18]=2[C:42]#[N:43])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1(C)C=CC=CC=1.[CH:61]([C@@H:63]1[CH2:67][CH2:66][CH2:65][N:64]1[C:68]([O:70][C:71]([CH3:74])([CH3:73])[CH3:72])=[O:69])=O>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:39][CH2:40][CH3:41])=[C:24]([NH:27][C:28](=[O:38])/[CH:29]=[CH:61]/[C@@H:63]4[CH2:67][CH2:66][CH2:65][N:64]4[C:68]([O:70][C:71]([CH3:72])([CH3:74])[CH3:73])=[O:69])[CH:25]=3)[N:20]=[CH:19][C:18]=2[C:42]#[N:43])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1
Reactant: CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)CP(=O)(OCC)OCC
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C=O
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/[C@@H]1CCCN1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 96.2 %

Procedure:
N-[4-[[3-Chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-2-diethoxyphosphoryl-acetamide 1d (156 mg, 0.25 mmol) was dissolved in 3 mL of tetrahydrofuran in a dry ice bath, followed by dropwise addition of a solution of lithium bis(trimethylsilyl)amide (1 M) in toluene (375 μL, 0.38 mmol). After the reaction mixture was stirred for 45 minutes, a solution of tert-butyl (2S)-2-formylpyrrolidine-1-carboxylate 2c (100 mg, 0.50 mmol) in 2 mL of tetrahydrofuran was added. The reaction mixture was stirred for another 1 hour, then warmed up to room temperature and stirred for 12 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography with elution system A to obtain the title compound tert-butyl (2S)-2-[(E)-3-[[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]amino]-3-oxo-prop-1-enyl]pyrrolidine-1-carboxylate 2d (161 mg, yield 96.2%) as a light yellow solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[C:7](=O)[CH2:6][C:5](=[O:9])[C:4]([CH3:11])([CH3:10])[O:3]1.P(Cl)(Cl)(Cl)(Cl)[Cl:14]>C(Cl)(Cl)Cl>[Cl:14][C:7]1[C:2]([CH3:12])([CH3:1])[O:3][C:4]([CH3:11])([CH3:10])[C:5](=[O:9])[CH:6]=1
Reactant: CC1(C)OC(C)(C)C(=O)CC1=O
Reactant: ClP(Cl)(Cl)(Cl)Cl
Solvent: ClC(Cl)Cl
Product: CC1(C)OC(C)(C)C(Cl)=CC1=O
Yield: 84.9 %

Procedure:
To a suspension of 2,2,6,6-tetramethylpyran-3,5-dione (741 mg, 4.35 mmol) in chloroform (10 ml) is added phosphorus pentachloride (454 mg, 2.18 mmol), and the reaction is heated to reflux for 5 hours. Silica gel is added to the cooled crude reaction mixture, the solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel to give 5-chloro-2,2,6,6-tetramethyl-6H-pyran-3-one (349 mg).
Reaction SMILES: CI.C(=O)([O-])[O-].[K+].[K+].O1CCOC[CH2:10]1.[F:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([N+:25]([O-:27])=[O:26])[CH:23]=2)[NH:18][N:17]=1>C(OCC)(=O)C>[F:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([N+:25]([O-:27])=[O:26])[CH:23]=2)[N:18]([CH3:10])[N:17]=1
Reactant: O=[N+]([O-])c1ccc2[nH]nc(F)c2c1
Reactant: C1COCCO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CI
Product: Cn1nc(F)c2cc([N+](=O)[O-])ccc21
Temperature: 100 °C
Reaction time: 2 h

Procedure:
Methyl iodide (41 μl) and potassium carbonate (114 mg) were added to a 1,4-dioxane (2.5 ml) solution containing 3-fluoro-5-nitro-1H-indazole (100 mg), followed by stirring at 100° C. for 2 hours. Ethyl acetate was added to the reaction solution. An insoluble precipitate was removed by filtration, the solvent was distilled away under reduced pressure, and the obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=1:0 to 1:1). 3-Fluoro-1-methyl-5-nitro-1H-indazole was thus obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[O:9][N:10]=[C:11]3[CH:16]=[CH:15][C:14]([CH:17]([C:19]4[S:20][CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[N:23]=4)[OH:18])=[CH:13][C:12]=23)[CH:5]=[CH:6][CH:7]=1>O1CCOCC1.O=[Mn]=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[O:9][N:10]=[C:11]3[CH:16]=[CH:15][C:14]([C:17]([C:19]4[S:20][CH:21]=[C:22]([C:24]5[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=5)[N:23]=4)=[O:18])=[CH:13][C:12]=23)[CH:5]=[CH:6][CH:7]=1
Reactant: OC(c1ccc2noc(-c3cccc(Cl)c3)c2c1)c1nc(-c2ccccc2)cs1
Agent: O=[Mn]=O
Solvent: C1COCCO1
Product: O=C(c1ccc2noc(-c3cccc(Cl)c3)c2c1)c1nc(-c2ccccc2)cs1
Temperature: 80 °C
Reaction time: 3 h
Yield: 99.8 %

Procedure:
A mixture of intermediate (14) (0.0656 mol) and MnO2 (27.5 g) in 1,4-dioxane (275 ml) was stirred at 80° C. for 3 hours, then cooled to room temperature, filtered over celite and pasted up with CH2Cl2/CH3OH. The solvent was evaporated till dryness, yielding 27.3 g (100%) of [3-(3-chlorophenyl)-2,1-benzisoxazol-5-yl](4-phenyl-2-thiazolyl)-methanone (intermediate 15).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[CH2:7]OS(C1C=CC(C)=CC=1)(=O)=O.[CH:19]1([NH2:22])[CH2:21][CH2:20]1>>[CH:19]1([NH:22][CH2:7][CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][O:1]2)[CH2:21][CH2:20]1
Reactant: Cc1ccc(S(=O)(=O)OCC2CCCCO2)cc1
Reactant: NC1CC1
Product: C1CCC(CNC2CC2)OC1
Temperature: 110 °C

Procedure:
A mixture of toluene-4-sulfonic acid tetrahydro-pyran-2-ylmethyl ester (500 mg, 1.85 mmol) and cyclopropylamine (2 mL, 15 mmol) is heated overnight at 110° C. in a sealed tube. The crude mixture is concentrated and taken up in CH2Cl2. Water is added, the layers are separated and the aqueous one back extracted twice with CH2Cl2. The combined organic extracts are washed with brine, dried over Na2SO4, filtered and concentrated. TLC, Rf (CH2Cl2/MeOH 95:5)=0.3, MS (LC-MS): 156.2 [M+H]+.
Reaction SMILES: [CH3:1][NH:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[C:8]([Cl:13])[CH:7]=1)=[S:4].[C:14]([C:19]([OH:21])=[O:20])#[C:15][C:16](O)=[O:17]>>[Cl:13][C:8]1[CH:7]=[C:6]([N:5]=[C:3]2[N:2]([CH3:1])[C:16](=[O:17])[C:15](=[CH:14][C:19]([OH:21])=[O:20])[S:4]2)[CH:11]=[CH:10][C:9]=1[Cl:12]
Reactant: O=C(O)C#CC(=O)O
Reactant: CNC(=S)Nc1ccc(Cl)c(Cl)c1
Product: CN1C(=O)C(=CC(=O)O)SC1=Nc1ccc(Cl)c(Cl)c1
Yield: 64.7 %

Procedure:
Prepared by the method described in Example 1 from N-methyl-N'-(3,4-dichlorophenyl)thiourea (4.9 g, 21 mmoles) and acetylenedicarboxylic acid (2.6 g, 22 mmoles). Recrystallization from ethyl acetate gave the product (4.5 g), mp 225°-226° C.
Reaction SMILES: S=[C:2]1[CH:8]([NH:9][C:10](=[O:19])[O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:7][CH2:6][C:5]2[CH:20]=[CH:21][CH:22]=[CH:23][C:4]=2[NH:3]1.[CH3:24][O:25][CH:26]([O:29][CH3:30])[CH2:27][NH2:28]>ClCCl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:24][O:25][CH:26]([O:29][CH3:30])[CH2:27][NH:28][C:2]1[CH:8]([NH:9][C:10](=[O:19])[O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:7][CH2:6][C:5]2[CH:20]=[CH:21][CH:22]=[CH:23][C:4]=2[N:3]=1
Reactant: O=C(NC1CCc2ccccc2NC1=S)OCc1ccccc1
Reactant: COC(CN)OC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: ClCCl
Product: COC(CNC1=Nc2ccccc2CCC1NC(=O)OCc1ccccc1)OC
Temperature: 25 °C
Reaction time: 36 h
Yield: 112.8 %

Procedure:
Dissolve Benzyl N-(2-thioxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl)carbamate (1.78 Kg, 5.13 mol) and para-toluene sulfonic acid monohydrate (48.8 g, 256 mmol) in dichloromethane (12 L). Add aminoacetaldehyde dimethyl acetal (2.70 Kg, 25 mole) dropwise over 1 hour and stir for 36 hours at ambient temperature. Add additional aminoacetaldehyde dimethyl acetal (1.40 Kg, 13 mol) and stir for 12 hours at ambient temperature. Add water (5.0 L), separate the organic layer, and extract the aqueous with dichloromethane (2.0 L). Combine the organic layers and wash with water, saturated ammonium chloride (6.0 L), and brine (4.0 L). Filter the organic through diatomaceous earth and concentrate under reduced pressure to give the title compound (2.30 kg, 118%) as a yellow oil: MS (m/z): 398 (M+1).
Reaction SMILES: [CH2:1]([O:5][C:6]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[C:12]2[C:7]=1[CH:8]=[CH:9][CH:10]=[CH:11]2)[CH2:2][CH2:3][CH3:4].CN([CH:23]=[O:24])C>>[CH2:1]([O:5][C:6]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]([CH:23]=[O:24])=[C:12]2[C:7]=1[CH:8]=[CH:9][CH:10]=[CH:11]2)[CH2:2][CH2:3][CH3:4]
Reactant: CN(C)C=O
Reactant: CCCCOc1c2ccccc2cc2ccccc12
Product: CCCCOc1c2ccccc2c(C=O)c2ccccc12

Procedure:
10-Butoxyanthracene was formylated using DMF as both solvent and electrophile by the procedure of E. Campaigne and W. L. Archer, J. Amer. Chem. Soc. 75 989 (1953), affording 10-butoxy-9-anthracenecarbaldehyde mp 65°-67°, (pentane), (C, H).
Reaction SMILES: Cl.[NH:2]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)[NH2:3].[CH:14]12[CH2:23][CH:18]3[CH2:19][CH:20]([CH2:22][CH:16]([CH2:17]3)[CH:15]1[NH:24][C:25](=[O:38])/[C:26](/[C:31]([CH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1)=O)=[CH:27]\N(C)C)[CH2:21]2>C(O)C.C(O)(=O)C>[CH:16]12[CH2:17][CH:18]3[CH2:19][CH:20]([CH2:21][CH:14]([CH2:23]3)[CH:15]1[NH:24][C:25]([C:26]1[CH:27]=[N:3][N:2]([C:4]3[CH:5]=[CH:6][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:12][CH:13]=3)[C:31]=1[CH:33]1[CH2:34][CH2:35][CH2:36][CH2:37]1)=[O:38])[CH2:22]2
Reactant: CN(C)/C=C(\C(=O)NC1C2CC3CC(C2)CC1C3)C(=O)C1CCCC1
Reactant: COC(=O)c1ccc(NN)cc1
Agent: Cl
Solvent: CCO
Solvent: CC(=O)O
Product: COC(=O)c1ccc(-n2ncc(C(=O)NC3C4CC5CC(C4)CC3C5)c2C2CCCC2)cc1
Temperature: 80 °C
Reaction time: 2 h
Yield: 39.4 %

Procedure:
Methyl 4-hydrazinylbenzoate hydrochloride (Intermediate#123) (0.712 g, 3.51 mmol) was added in one portion to (Z)—N-(2-adamantyl)-2-(cyclopentanecarbonyl)-3-dimethylamino-prop-2-enamide (Intermediate#67), 1.21 g, 3.51 mmol) in ethanol (30 mL). 5 drops of acetic acid were added and the resulting solution was stirred at 80° C. for 2 hours and then cooled to ambient giving a precipitate. The reaction mixture was filtered and the product recovered, washed with ethanol (10 mL) and water (10 mL) before being dried under vacuum to give methyl 4-[4-(2-adamantylcarbamoyl)-5-cyclopentyl-pyrazol-1-yl]benzoate (0.620 g, 39.4%) as a white solid.
Reaction SMILES: [H-].[Na+].C(OP([CH:11]([CH3:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH:24]=O.O>O1CCCC1>[CH3:17][C:11](=[CH:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][N:18]=1)[C:12]([O:14][CH2:15][CH3:16])=[O:13]
Reactant: CCOC(=O)C(C)P(=O)(OCC)OCC
Reactant: O=Cc1ccccn1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)C(C)=Cc1ccccn1
Reaction time: 0.5 h
Yield: 87.3 %

Procedure:
Sodium hydride (ca. 60%, 2.0 g, 50.0 mmol) was suspended in tetrahydrofuran (20 ml), and a solution of ethyl 2-(diethylphosphono)propionate (11.7 g, 49.1 mmol) in tetrahydrofuran (8 ml) was added thereto under ice cooling condition. The mixture was stirred for 0.5 hr. Successively, a solution of 2-pyridinecarbaldehyde (5.0 g, 46.7 mmol) in tetrahydrofuran (8 ml) was added to the mixture. The mixture was stirred at 0° C. for 14 hrs, combined with water, concentrated under reduced pressure to the half amount and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was subjected to a silica gel (80 g) column chromatography. The fractions eluted with hexane-ethyl acetate (3:1, v/v) were collected and concentrated to give the titled compound (7.8 g, 87%).
Reaction SMILES: Cl.[F:2][C:3]([F:17])([F:16])[C:4]1[CH:5]=[C:6]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH:7]=[CH:8][CH:9]=1.[CH2:18]([Cl:21])[C:19]#[CH:20].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[ClH:21].[F:17][C:3]([F:2])([F:16])[C:4]1[CH:5]=[C:6]([N:10]2[CH2:15][CH2:14][N:13]([CH2:20][C:19]#[CH:18])[CH2:12][CH2:11]2)[CH:7]=[CH:8][CH:9]=1
Reactant: C#CCCl
Reactant: FC(F)(F)c1cccc(N2CCNCC2)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: C#CCN1CCN(c2cccc(C(F)(F)F)c2)CC1
Reaction time: 15 h

Procedure:
3.2 g (0.012 mol) of N-(3-trifluoromethyl-phenyl)-piperazine hydrochloride, 0.9 g (0.012 mol) of propargyl chloride and 2.5 g (0.024 mol) of sodium carbonate were heated at 60° C. in 50 ml of absolute acetonitrile while stirring. Over a period of 15 hours, an additional 0.34 g (0.0046 mol) of propargyl chloride and 0.5 g (0.0046 mol) of sodium carbonate were added. The inorganic salts were removed by suction filtration, and the filtrate was evaporated under reduced pressure. The evaporation residue was dissolved in toluene, and the product solution was extracted with the calculated quantity of dilute hydrochloric acid. The aqueous phase was made alkaline with soda, and the base was extracted with ether. After drying with sodium sulfate, the organice phase was evaporated under reduced pressure, and the base was converted into its hydrochloride in conventional manner. White crystals from acetonitrile, melting point 218°-219° C. (decomposition). Yield: 2.7 g (73.8% of theory). The existence of these compounds was confirmed by elemental and spectrum analysis.
Reaction SMILES: [CH2:1]([O:8][C:9]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]#[C:21][CH2:22][N:23]([CH3:25])[CH3:24])[CH:18]=2)[NH:13][C:12]=1[CH3:26])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)C.[Pd].CC([O-])=O.CC([O-])=O.[Pb+2]>[CH2:1]([O:8][C:9]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17](/[CH:20]=[CH:21]\[CH2:22][N:23]([CH3:25])[CH3:24])[CH:18]=2)[NH:13][C:12]=1[CH3:26])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1[nH]c2ccc(C#CCN(C)C)cc2c1C(=O)OCc1ccccc1
Agent: [Pd]
Agent: CC(=O)[O-]
Agent: [Pb+2]
Solvent: CCO
Product: Cc1[nH]c2ccc(/C=C\CN(C)C)cc2c1C(=O)OCc1ccccc1
Temperature: 25 °C

Procedure:
5-(3-Dimethylamino-prop-1-ynyl)-2-methyl-1H-indole-3-carboxylic acid benzyl ester (0.160 g, 0.428 mmol, 1 eq, Example 53) was dissolved in ethanol (30 mL). Lindlar's catalyst (0.05 mg) was added, and the reaction was hydrogenated at room temperature under a hydrogen atmosphere, 35 PSI. The reaction mixture was shaken at room temperature and followed by LC-MS. After one week, the reaction was loaded on silica gel and chromatographed, (ethyl acetate/methanol/triethylamine 87/10/3). The resulting indole-alkene product (0.019 g, 12%) was converted to the —HCl salt, obtained as a brown semisolid: LC/MS (ESI+) 377 (M+1), Anal. (C24H28N2O2.HCl.1.0H2O) C, H, N.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:6]([O-:10])(=[O:9])(=[O:8])=[O:7].CS[C:13]1[S:17][CH:16]=[CH:15][S+:14]=1>>[Cl:6]([O-:10])(=[O:9])(=[O:8])=[O:7].[S:14]1[CH:15]=[CH:16][S:17][C:13]1=[N+:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C1CCNC1
Reactant: CSc1scc[s+]1
Agent: [O-][Cl+3]([O-])([O-])[O-]
Product: c1csc(=[N+]2CCCC2)s1

Procedure:
0.9 ml of pyrrolidine and 2.5 g of 2-methylthio-1,3-dithiolium perchlorate were treated in the same manner as in Example 26, and the product was recrystallized from acetone-ethyl ether, whereby 1.5 g (yield: 55.3%) of 1-(1,3-dithiol-2-ylidene)pyrrolidinium perchlorate (Compound No. 35) was obtained as crystals having a melting point of 216° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.[C:11]1([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[NH2:24])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(N=C=NC(C)C)(C)C.C(N(CC)CC)C>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([NH:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[NH:17][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:9]
Reactant: Nc1ccccc1Nc1ccccc1
Reactant: O=C(O)c1cncc(Br)c1
Agent: CC(C)N=C=NC(C)C
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(Nc1ccccc1Nc1ccccc1)c1cncc(Br)c1
Temperature: 50 °C
Yield: 83.2 %

Procedure:
A mixture of 5-bromonicotinic acid (20.0 g, 99 mmol), N-phenyl-o-phenylenediamine (19.32 g, 105 mmol), diisopropylcarbodiimide (DIC) (26.5 g, 210 mmol), and triethylamine (Et3N)(2.65 g, 27 mmol) in DCM (anhydrous, 350 mL) was heated to about 50° C. and degassed overnight under argon. After cooling to RT, the solids were then filtered off. The filtrate was washed with water (2×200 mL), dried over sodium sulfate and loaded onto silica gel. A flash column (gradient of 3% to 10% ethyl acetate in DCM) gave 30.32 g of 1E; 83% yield, pure by HNMR.