Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS([C:5]1[N:6]=[N:7][C:8]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:10]=1)(=O)=O.[OH-:24].[K+].Cl>O.C1COCC1>[C:11]1([C:9]2[C:8]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=3)=[N:7][NH:6][C:5](=[O:24])[N:10]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: [OH-]
Reactant: Cc1ccc(-c2nnc(S(C)(=O)=O)nc2-c2ccccc2)cc1
Agent: Cl
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: Cc1ccc(-c2n[nH]c(=O)nc2-c2ccccc2)cc1
Yield: 92.1 %

Procedure:
To a solution of 3-(methylsulfonyl)-5-phenyl-6-p-tolyl-1,2,4-triazine (98.9 mg, 0.304 mmol) in a 1:1 mixture of H2O/THF (6.0 mL) was added potassium hydroxide (109.1 mg, 1.945 mmol). The mixture was heated at reflux for 1 h. The reaction mixture was cooled to room temperature and neutralized with 1 M HCl, then extracted with CH2Cl2. The combined organic phases were washed with H2O and brine, dried over MgSO4, and concentrated to give the title compound as a yellow solid (73.7 mg). LCMS m/z=264.1 [M+H]+.
Reaction SMILES: [N:1]([O-])=O.[Na+].[CH]Cl.[F:7][C:8]1[CH:9]=[C:10]([C:14]2[C:18]([C:19]#[C:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[C:17]([NH2:27])[NH:16][N:15]=2)[CH:11]=[CH:12][CH:13]=1.[Na+].[Cl-:29]>C(Cl)Cl>[Cl:29][C:19]1[C:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[N:1][N:27]=[C:17]2[NH:16][N:15]=[C:14]([C:10]3[CH:11]=[CH:12][CH:13]=[C:8]([F:7])[CH:9]=3)[C:18]=12
Reactant: Nc1[nH]nc(-c2cccc(F)c2)c1C#Cc1ccccc1
Reactant: [Cl-]
Reactant: O=N[O-]
Agent: [CH]Cl
Agent: [Na+]
Solvent: ClCCl
Product: Fc1cccc(-c2n[nH]c3nnc(-c4ccccc4)c(Cl)c23)c1
Temperature: 50 °C
Reaction time: 0.25 h
Yield: 42.8 %

Procedure:
Sodium nitrite (740 mg, 10.7 mmol) was added portionwise to cHCl (24 mL) at −15° C. and stirred for 15 min. 3-(3-fluorophenyl)-4-(2-phenylethynyl)-1H-pyrazol-5-amine (1 g, 3.6 mmol) was added as a solid, followed by the addition of CH2Cl2 (10 mL). The reaction mixture was allowed to warm up and stirred at room temperature for 1.5 h. The reaction mixture was diluted with CH2Cl2 (20 mL) and NaCl (0.5 g) was added. The reaction mixture was heated to 50° C. for 1 d. The layers were separated and the organic layer was washed with water, dried (phase separator cartridge) and concentrated in vacuo. The residue was purified by column chromatography (silica gel, ethyl acetate/isohexane 0:1 to 7:3) yielding the title compound as a solid (500 mg).
Reaction SMILES: [CH3:1][O:2][CH:3]=[CH:4][C:5]#[N:6].[N:7](Cl)=[O:8].N([O-])=O.[Na+].Cl.[CH3:15][OH:16]>>[CH3:1][O:2][CH:3]([O:16][CH3:15])[C:4](=[N:7][OH:8])[C:5]#[N:6]
Reactant: O=NCl
Reactant: CO
Reactant: COC=CC#N
Agent: Cl
Agent: O=N[O-]
Agent: [Na+]
Product: COC(OC)C(C#N)=NO
Temperature: -10 °C
Yield: 80.1 %

Procedure:
To a flask having an inner volume of 300 ml and equipped with a stirring device, a thermometer, a condenser and a gas inlet tube were charged 42.83 g (0.5 mol) of 3-methoxyacrylonitrile with a purity of 97% by weight and 125 ml of methanol, and the mixture was cooled to −10° C. under stirring. Then, the reaction solution was maintained to −10 to 0° C., and while feeding nitrosyl chloride generated by reacting 170.5 g (1.0 mol) of 41% by weight aqueous sodium nitrite solution and 320 ml (3.5 mol) of conc. hydrochloric acid (the above-mentioned method (2)) in a separate apparatus to the reaction solution, the resulting mixture was reacted at −10 to 0° C. for 3 hours and at room temperature for 2 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, the concentrate was washed in the order of n-hexane and toluene, dried under reduced pressure at 40° C. to obtain 61.6 g of 3,3-dimethoxy-2-hydroxyiminopropionitrile (Isolation yield: 80.1%) as a pale yellowish solid with a purity of 93.7% by weight (absolute calibration curve method by high performance liquid chromatography).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]#[C:8][CH2:9][CH2:10][CH2:11][OH:12].[H][H]>C(O)C.[Pd]>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][OH:12]
Reactant: [H][H]
Reactant: OCCCC#Cc1ccccn1
Agent: [Pd]
Solvent: CCO
Product: OCCCCCc1ccccn1
Yield: 93.1 %

Procedure:
5-(2-pyridinyl)-4-pentyn-1-ol (8.8 g) was hydrogenated over 1.0 g of 10% Pd/C in 125 mL of ethanol at room temperature and atmospheric pressure. After the uptake of hydrogen had stopped, the catalyst was removed by filtration and the solvent was removed under reduced pressure. The residual oil was distilled on a Kugelrohr apparatus (115°-120° C./0.1 mm) to yield 8.4 g of 2-pyridinepentanol.
Reaction SMILES: [C:1]([O:4][C:5](=O)[CH3:6])(=[O:3])[CH3:2].CC([O-])=O.[Na+].[N+:13](CCO)([O-:15])=[O:14].C(Cl)(Cl)Cl>N1C=CC=CC=1.O>[C:1]([O:4][CH2:5][CH2:6][N+:13]([O-:15])=[O:14])(=[O:3])[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: O=[N+]([O-])CCO
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: O
Solvent: c1ccncc1
Product: CC(=O)OCC[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 73.2 %

Procedure:
This compound was prepared according to M. E. Flaugh, T. A. Crowell, J. A. Clemens, B. D. Sawyer J. Med. Chem., 1979, 22, pp. 63-68. Acetic anhydride (8.06 g, 79.0 mmol) and NaOAc (1.45 g, 17.7 mmol) were mixed and heated. Two drops of pyridine were added. 2-nitroethanol (6.45 g, 70.8 mmol) was carefully added to the suspension at 30-35° C. during 30 min. Thereafter the mixture was stirred overnight at room temperature. The next morning the mixture contained undissolved NaOAc and a new orange precipitate. The reaction mixture was taken up between CHCl3 and water, washed 1× with water, 1× with brine and dried with MgSO4. Thereafter the solvent was evaporated under reduced pressure at 40° C. The remaining orange oil was co-evaporated first with chloroform and then five times with toluene and finally with chloroform to get the 6.90 g of pure compound.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C:4](=[CH:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=1)[C:5]([CH3:7])=O.[C:19]1([N:25]2[C:29]([NH2:30])=[CH:28][C:27]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[N:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(O)C>[CH3:1][O:2][C:3]([C:4]1[CH:8]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)[C:28]2[C:27]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[N:26][N:25]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:29]=2[NH:30][C:5]=1[CH3:7])=[O:18]
Reactant: Nc1cc(-c2ccccc2)nn1-c1ccccc1
Reactant: COC(=O)C(=Cc1cccc([N+](=O)[O-])c1)C(C)=O
Solvent: CCO
Product: COC(=O)C1=C(C)Nc2c(c(-c3ccccc3)nn2-c2ccccc2)C1c1cccc([N+](=O)[O-])c1
Temperature: 25 °C

Procedure:
Methyl-2-(3-nitrobenzyliden)acetoacetate is added to 1,3-diphenyl-5-pyrazolamine (0.010 mol) in ethanol (16 ml) and refluxed for 90 minutes under nitrogen. After cooling to room temperature, the solvent is evaporated under reduced pressure, the residue is taken up in ethyl ether, discarding the insolubles, and then the solvent is evaporated. Upon crystallization from methanol, the product of the title is obtained. M.p. 186°-189° C.
Reaction SMILES: [CH3:1][N:2]([CH3:10])[C:3]1[CH:8]=[CH:7][C:6](Br)=[CH:5][CH:4]=1.[Mg].[S:12](Cl)(Cl)=[O:13]>C1COCC1>[CH3:1][N:2]([CH3:10])[C:3]1[CH:8]=[CH:7][C:6]([S:12]([C:6]2[CH:7]=[CH:8][C:3]([N:2]([CH3:10])[CH3:1])=[CH:4][CH:5]=2)=[O:13])=[CH:5][CH:4]=1
Reactant: O=S(Cl)Cl
Reactant: CN(C)c1ccc(Br)cc1
Agent: [Mg]
Solvent: C1CCOC1
Product: CN(C)c1ccc(S(=O)c2ccc(N(C)C)cc2)cc1
Yield: 33 %

Procedure:
A Grignard reagent was conventionally prepared using 4-dimethylaminophenyl bromide, magnesium, and THF and further reacted with thionyl chloride, obtaining bis(4-dimethylaminophenyl) sulfoxide in a yield of 33%. A solution of 7.0 g (0.024 mol) of the thus obtained bis(4-dimethylaminophenyl) sulfoxide in 100 g of methylene chloride was cooled at -70° C. in a dry ice/methanol bath whereupon with stirring, 6.0 g (0.027 mol) of trimethylsilyl triflate was added dropwise thereto at less -60° C.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:4][C:5](Cl)=[C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].C(N(CC)CC)C>[Pd].C(OCC)(=O)C>[NH2:1][C:2]1[C:3]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[N:4][CH:5]=[C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9]
Reactant: CCOC(=O)c1c(Cl)nc(-c2ccccc2)c(N)c1C(=O)OCC
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CCOC(=O)c1cnc(-c2ccccc2)c(N)c1C(=O)OCC

Procedure:
A mixture of 100 mg of 3-amino-6-chloro-4,5-diethoxycarbonyl-2-phenylpyridine, 0.08 ml (2.0 eq.) of triethylamine amd 8 ml of ethyl acetate was subjected to catalytic reduction for 7 hours with 100 mg of 10% Pd-C (50% wet). The catalyst was removed by filtration, and the solvent was distilled off. Yield: 86 mg(95.4%).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[OH:9].[C:10](=S)=[S:11].[OH-].[K+]>C(O)C>[Cl:8][C:6]1[CH:5]=[CH:4][C:3]2[O:9][C:10]([SH:11])=[N:1][C:2]=2[CH:7]=1
Reactant: Nc1cc(Cl)ccc1O
Reactant: S=C=S
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: Sc1nc2cc(Cl)ccc2o1

Procedure:
A 2 g portion of 2-amino-4-chlorophenol was dissolved in 150 ml of ethanol, and the solution was mixed with 80 ml of carbon disulfide and 937 mg of potassium hydroxide and heated under reflux for 8 hours. The solvent was evaporated under a reduced pressure, and the residual oily mixture was mixed with 50 ml of 1 N hydrochloric acid aqueous solution and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried with magnesium sulfate and then the solvent was evaporated under a reduced pressure. By recrystallizing the thus obtained mixture from ethyl acetate, the title compound (1.3 g) in light yellow color was obtained.
Reaction SMILES: [C:1]1([CH2:7][C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC([O-])(C)C.[K+].[C:23](=[S:25])=[S:24].Br[CH2:27]Br>C1COCC1>[S:24]1[CH2:27][S:25][C:23]1=[C:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:8]([C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=1)=[O:9]
Reactant: BrCBr
Reactant: Cc1ccc(C(=O)Cc2ccccc2)cc1
Reactant: S=C=S
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: Cc1ccc(C(=O)C(=C2SCS2)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 2-phenyl-1-p-tolylethanone (3.00 g, 14.27 mmol) in THF (50.0 mL) was added KOtBu (30.0 mL, 30.0 mmol), CS2 (0.862 mL, 14.27 mmol) and dibromomethane (0.994 mL, 14.27 mmol). The reaction was stirred at 25° C. for 12 h, quenched with water (40.0 mL) and extracted with EtOAc (3×50.0 mL). The combined organics were dried over MgSO4, filtered, and concentrated to give the title compound as a brown oil without further purification. LCMS m/z=299.2 [M+H]+.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:22]=[CH:21][CH:20]=[C:19]4[C:15]=3[C:16]([CH2:31][CH3:32])=[N:17][N:18]4[CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=3)=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[SH:33][CH2:34][CH2:35][NH:36][C:37](=[O:39])[CH3:38].CC(C)([O-])C.[K+]>O1CCOCC1>[C:37]([NH:36][CH2:35][CH2:34][S:33][C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:22]=[CH:21][CH:20]=[C:19]4[C:15]=3[C:16]([CH2:31][CH3:32])=[N:17][N:18]4[CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=3)=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1)(=[O:39])[CH3:38]
Reactant: CC(=O)NCCS
Reactant: CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(F)ccn34)c12
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: CCc1nn(Cc2cccc(C)n2)c2cccc(NC(=O)c3cnc4cc(SCCNC(C)=O)ccn34)c12
Temperature: 95 °C
Yield: 58.3 %

Procedure:
N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-fluoroimidazo[1,2-a]pyridine-3-carboxamide (0.028 g, 0.065 mmol) (Example 74, Step A), N-(2-mercaptoethyl)acetamide (0.078 g, 0.65 mmol), and potassium tert-butoxide (0.022 g, 0.20 mmol) were added to a minimal amount of deoxygenated 1,4-dioxane in a sealed tube and heated for 18 hours at 95° C. The reaction mixture was cooled, concentrated under reduced pressure and purified by silica gel chromatography eluting with methanol (containing 6% ammonium hydroxide) and dichloromethane (1:9), to yield the product (20 mg) as a white powder. MS ESI (+) m/z 528 (M+1) detected.
Reaction SMILES: [Na].[O:2]([C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br[CH:17]([CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)[C:18]([O:20][CH2:21][CH3:22])=[O:19].C(N)=O>C(O)C>[O:2]([C:9]1[CH:10]=[CH:11][C:12]([O:15][CH:17]([CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:13][CH:14]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CCOC(=O)C(Br)C1CCCCC1
Reactant: Oc1ccc(Oc2ccccc2)cc1
Agent: [Na]
Solvent: CCO
Solvent: NC=O
Product: CCOC(=O)C(Oc1ccc(Oc2ccccc2)cc1)C1CCCCC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 44.4 %

Procedure:
Into 15 ml of anhydrous ethanol, 205 mg (0.0089 mole) of methallic sodium was dissolved and then, 1.8 g (0.0089 mole) of p-phenoxyphenol was added. The mixture was stirred at room temperature for about 30 minutes. Ethanol was distilled off under a reduced pressure and 5 ml of dimethyl formamide was added to the residue and dimethyl formamide was distilled off under a reduced pressure and then, 15 ml of dimethyl formamide was added to the residue to dissolve it. Into the solution, 2.5 g (0.010 mole) of ethyl α-bromo-α-cyclohexylacetate was added. The mixture was refluxed for 8 hours and then diemethyl formamide was distilled off under a reduced pressure. The residue was admixed with 50 ml of water and extracted twice with 50 ml of benzene. The benzene layers were combined and washed three times with 30 ml of 5% NaOH aq.sol. and then with water and dehydrated over sodium sulfate and distilled in vacuum to obtain 1.4 g of ethyl α-(p-phenoxyphenoxy)α-cyclohexylacetate (yield: 42.6%).
Reaction SMILES: Cl[CH:2]1[C:8]2[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:7]=2[S:6][C:5]2[CH:14]=[CH:15][C:16]([CH3:18])=[CH:17][C:4]=2[CH2:3]1.[N:19]1([CH2:25][CH2:26][N:27]2[CH2:31][CH2:30][O:29][C:28]2=[O:32])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>C(Cl)(Cl)Cl>[F:13][C:10]1[CH:11]=[CH:12][C:7]2[S:6][C:5]3[CH:14]=[CH:15][C:16]([CH3:18])=[CH:17][C:4]=3[CH2:3][CH:2]([N:22]3[CH2:23][CH2:24][N:19]([CH2:25][CH2:26][N:27]4[CH2:31][CH2:30][O:29][C:28]4=[O:32])[CH2:20][CH2:21]3)[C:8]=2[CH:9]=1
Reactant: O=C1OCCN1CCN1CCNCC1
Reactant: Cc1ccc2c(c1)CC(Cl)c1cc(F)ccc1S2
Solvent: ClC(Cl)Cl
Product: Cc1ccc2c(c1)CC(N1CCN(CCN3CCOC3=O)CC1)c1cc(F)ccc1S2

Procedure:
17.6 g of 10-chloro-8-fluoro-10,11-dihydro-2-methyl-dibenzo[b,f]thiepin are heated for 20 hours under reflux conditions together with 27.3 g of 3-[2-(1-piperazinyl)-ethyl]-2-oxazolidinone in 100 ml of chloroform. After evaporation of the chloroform, the residue is mixed with ice, benzene and aqueous sodium hydroxide solution and again mixed well. The benzene phase is acidified with 6 N aqueous hydrochloric acid and maintained in an ice bath for 30 minutes. The precripitate, which is formed, is filtered, made alkaline with aqueous sodium hydroxide solution and taken up in benzene. The benzene phase is dried over sodium sulphate and evaporated, whereby 3-{2-[4-(8-fluoro-10,11-dihydro-2-methyl-dibenzo [b,f]thiepin-10-yl)-1-piperazinyl]-ethyl}-2-oxazolidinone is obtained, which is converted into the corresponding dihydrochloride by reaction with ethanolic hydrochloric acid. The dihydrochloric melts at 210° (dec;).
Reaction SMILES: C(N(CC)CC)C.C(O[CH:11]=[C:12]([C:18]#[N:19])[C:13]([O:15][CH2:16][CH3:17])=[O:14])C.C(O)(=O)C(O)=O.[CH2:26]([NH:28][NH2:29])[CH3:27]>C(O)C>[CH2:16]([O:15][C:13]([C:12]1[CH:11]=[N:29][N:28]([CH2:26][CH3:27])[C:18]=1[NH2:19])=[O:14])[CH3:17]
Reactant: CCOC=C(C#N)C(=O)OCC
Reactant: CCNN
Agent: O=C(O)C(=O)O
Solvent: CCO
Solvent: CCN(CC)CC
Product: CCOC(=O)c1cnn(CC)c1N
Yield: 80.1 %

Procedure:
Triethylamine (19.6 ml, 144 mmol) was added cautiously to a solution of ethyl (ethoxymethylene)cyanoacetate (10.1 g, 60 mmol) and ethyl hydrazine oxalate (9.9 g, 66 mmol) in ethanol (200 ml). The mixture was heated at reflux for 24 h then concentrated in vacuo. The residue was redissolved in EtOAc, washed with 5% KHCO3 solution then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 25% pet. ether:75% EtOAc) to yield the title compound (8.8 g, 80%).
Reaction SMILES: [CH2:1]([NH2:4])[CH:2]=[CH2:3].[Cl:5][C:6]1[N:11]=[C:10](Cl)[N:9]=[C:8]([N:13]([CH:39]2[CH2:44][C:43]([CH3:46])([CH3:45])[NH:42][C:41]([CH3:48])([CH3:47])[CH2:40]2)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][N:20]([C:31]2[N:36]=[C:35]([Cl:37])[N:34]=[C:33](Cl)[N:32]=2)[CH:21]2[CH2:26][C:25]([CH3:28])([CH3:27])[NH:24][C:23]([CH3:30])([CH3:29])[CH2:22]2)[N:7]=1.[OH-].[Na+]>C1(C)C=CC=CC=1.O>[Cl:5][C:6]1[N:11]=[C:10]([NH:4][CH2:1][CH:2]=[CH2:3])[N:9]=[C:8]([N:13]([CH:39]2[CH2:40][C:41]([CH3:47])([CH3:48])[NH:42][C:43]([CH3:45])([CH3:46])[CH2:44]2)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][N:20]([C:31]2[N:36]=[C:35]([Cl:37])[N:34]=[C:33]([NH:4][CH2:1][CH:2]=[CH2:3])[N:32]=2)[CH:21]2[CH2:22][C:23]([CH3:29])([CH3:30])[NH:24][C:25]([CH3:28])([CH3:27])[CH2:26]2)[N:7]=1
Reactant: CC1(C)CC(N(CCCCCCN(c2nc(Cl)nc(Cl)n2)C2CC(C)(C)NC(C)(C)C2)c2nc(Cl)nc(Cl)n2)CC(C)(C)N1
Reactant: C=CCN
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: O
Product: C=CCNc1nc(Cl)nc(N(CCCCCCN(c2nc(Cl)nc(NCC=C)n2)C2CC(C)(C)NC(C)(C)C2)C2CC(C)(C)NC(C)(C)C2)n1
Reaction time: 19 h

Procedure:
17.2 g (0.3 mole) of anhydrous allylamine are added dropwise, in the course of one hour, at 30°-40° and while stirring, to a solution of 103.6 g (0.15 mole) of N,N'-bis-(2,4-dichloro-1,3,5-triazin-6-yl)-N,N'-bis-(2,2,6,6-tetramethylpiperid-4-yl)-hexamethylenediamine in 500 ml of toluene. A solution of 12.0 g (0.3 mole) of sodium hydroxide in 100 ml of water is then added at approx. 30°, and stirring is continued for a further 19 hours at 50°. The mixture is worked up by separating off the aqueous phase in a separating funnel, washing the organic phase with three times 200 ml of water, drying it over sodium sulfate and removing the solvent by vacuum distillation. The solid residue is recrystallised from ethyl methyl ketone, which gives pure N,N'-bis-(2-chloro-4-allylamino-1,3,5-triazin-6-yl)-N,N'-bis-(2,2,6,6-tetramethylpiperid-4-yl)-hexamethylenediamine of melting point 210°-211°.
Reaction SMILES: C[O:2][CH:3]=[CH:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1.Cl.CCOC(C)=O.CCCCCC>C1COCC1>[F:18][C:17]([F:19])([F:20])[C:14]1[CH:13]=[CH:12][C:11]([C:8]2[CH:9]=[CH:10][C:5]([CH2:4][CH:3]=[O:2])=[CH:6][CH:7]=2)=[CH:16][CH:15]=1
Reactant: COC=Cc1ccc(-c2ccc(C(F)(F)F)cc2)cc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: O=CCc1ccc(-c2ccc(C(F)(F)F)cc2)cc1
Temperature: 25 °C
Yield: 96.1 %

Procedure:
To a 0° C. solution of 4′-(2-methoxy-vinyl)-4-trifluoromethyl-biphenyl (464 mg, 1.67 mmol) in THF (17 mL) is added dropwise concentrated hydrochloric acid (2.98 mL) and the reaction is warmed to room temperature. After 1 h TLC (30% EtOAc/hexane) indicates complete consumption of starting material. The reaction mixture is diluted with water and the pH is adjusted to 8 with solid NaHCO3. The reaction mixture is concentrated and the aqueous layer extracted with EtOAc (3×50 mL). The combined organic layers are washed with brine, dried (MgSO4), filtered, concentrated and chromatographed (40 g SiO2, 5% EtOAc/Hexanes) to yield the title compound (424 mg, 96%). 1NMR (400 MHz, CDCl3) δ ppm: 9.81 (t, 1H, J=2.2 Hz), 7.69 (s, 4H), 7.61 (d, 2H, J=8.4 Hz), 7.33 (d, 2H, J=8.4 Hz), 3.78 (d, 2H, J=1.8 Hz).
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6](O)=[O:7])=[O:2].[CH3:12][S:13]([NH2:16])(=[O:15])=[O:14].CN(C1C=CC=CN=1)C.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1.ClCCl>[CH3:12][S:13]([NH:16][C:6]([C:5]1[CH:4]=[C:3]([CH:11]=[CH:10][CH:9]=1)[CH:1]=[O:2])=[O:7])(=[O:15])=[O:14]
Reactant: CS(N)(=O)=O
Reactant: O=Cc1cccc(C(=O)O)c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccccn1
Solvent: C1CCOC1
Solvent: ClCCl
Product: CS(=O)(=O)NC(=O)c1cccc(C=O)c1
Temperature: 25 °C
Yield: 26 %

Procedure:
A mixture of 10.18 g of 3-formylbenzoic acid, 6.99 g of methanesulfonamide, 200 ml of dichloromethane, 8.95 g of dimethylaminopyridine, 15.22 g of dicyclohexylcarbodiimide and 100 ml of tetrahydrofuran was stirred at room temperature. The reaction solution was concentrated under reduced pressure, dissolved in ethyl acetate, a 1 N aqueous sodium hydroxide solution was added, and the layers were separated. To the aqueous layer was added 2 N hydrochloric acid to adjust to pH 1, this was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and then concentrated to obtain 4.01 g of 3-[(methanesulfonyl)aminocarbonyl]benzaldehyde [Compound No. (j)] as a white solid.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=O)([O-:3])=[O:2].[N+](C(Br)C1C=CC=CC=1)([O-])=O.[C:23]1(=[O:33])[NH:27][C:26](=[O:28])[C:25]2=[CH:29][CH:30]=[CH:31][CH:32]=[C:24]12.[K]>>[N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH2:7][N:27]1[C:26](=[O:28])[C:25]2=[CH:29][CH:30]=[CH:31][CH:32]=[C:24]2[C:23]1=[O:33])([O-:3])=[O:2]
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Reactant: O=C1NC(=O)c2ccccc21
Agent: O=[N+]([O-])C(Br)c1ccccc1
Agent: [K]
Product: O=C1c2ccccc2C(=O)N1Cc1cccc([N+](=O)[O-])c1

Procedure:
A process wherein from m-nitrobenzaldehyde is derived nitrobenzylbromide, which is then reacted with potassium phthalimide to obtain N-(m-nitrobenzyl)-phthalimide which is then subjected to a two-stage reduction to obtain m-aminobenzylamine (yield: Ca. 20%) (N. Kornblum et al., J.Am. Chem. Co., 71, 2137(1949)).
Reaction SMILES: [OH:1][N:2]1[CH:6]=[CH:5][CH:4]=[N:3]1.[F:7][C:8]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:9]=1[CH2:10]Br>C(Cl)(Cl)Cl>[F:7][C:8]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:9]=1[CH2:10][N:3]1[CH2:4][CH:5]=[CH:6][N:2]1[OH:1]
Reactant: On1cccn1
Reactant: Fc1cccc(F)c1CBr
Solvent: ClC(Cl)Cl
Product: ON1C=CCN1Cc1c(F)cccc1F
Temperature: 80 °C
Yield: 68.9 %

Procedure:
1-Hydroxypyrazole (49.3 mg, 0.59 mmol, 1.0 eq) was mixed with 165.8 mg (0.80 mmol, 1.36 eq) of 2,6-difluorobenzyl bromide in ˜1-2 mL of anhydrous CHCl3 under argon. The mixture was heated at 80° C. for 18 h under inert atmosphere in a sealed flask without condenser. The residue was partitioned between 37 weight percent aqueous HCl and toluene. The aqueous layer was collected and the toluene fraction extracted again with 37 weight percent aqueous HCl. The combined aqueous HCl fractions were neutralized with 5N aqueous NaOH to pH˜11-12 and then back-extracted with 3×30 mL of CHCl3. The organic layers were combined, washed with brine, dried over Na2SO4 and concentrated under reduced pressure to yield 86.3 mg (70.1% yield) of 2-(2,6-difluorobenzyl)-1-hydroxy-1H-pyrazole as a tan brown solid. 1H NMR (CDCl3 300 MHz) δ 7.37 (m, 1H), 7.18 (d, 1H), 6.95 (t, 2H), 6.85 (d, 1H), 6.11 (t, 1H), 5.43 (s, 2.00 H). LC/MS (ES) M+1=211.2