Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]([O-])=O.[Na+].[F:5][C:6]1([F:16])[O:10][C:9]2[CH:11]=[CH:12][C:13]([NH2:15])=[CH:14][C:8]=2[O:7]1.[Sn](Cl)[Cl:18]>O.Cl>[ClH:18].[F:16][C:6]1([F:5])[O:10][C:9]2[CH:11]=[CH:12][C:13]([NH:15][NH2:1])=[CH:14][C:8]=2[O:7]1
Reactant: Cl[Sn]Cl
Reactant: O=N[O-]
Reactant: Nc1ccc2c(c1)OC(F)(F)O2
Agent: Cl
Agent: [Na+]
Solvent: O
Product: NNc1ccc2c(c1)OC(F)(F)O2
Yield: 25.8 %

Procedure:
Add slowly a solution of sodium nitrite (1.40 g, 20.3 mmol) in water (11 mL) to a flask containing 2,2-difluoro-benzo[1,3]dioxol-5-ylamine (3.41 g, 19.7 mmol), water (14 mL), and concentrated hydrochloric acid (5 mL) at −5° C. Cool the reaction to −10° C. then add tin(II) chloride (11.20 g, 49.6 mmol) in concentrated hydrochloric acid (9 mL). Stir the reaction for one hour and collect the resultant solid by filtration. Dissolve the solid in methylene chloride (20 mL) and treat with acetone (5 mL). Wash the resultant organic solution with water (50 mL), dry over magnesium sulfate, filter, and evaporate under reduced pressure. Stir the resultant oil with 2N hydrochloric acid (100 mL) for 12 h. Collect a solid by filtration, wash with water and dry in a vacuum oven at 40° C. overnight to give the subtitled compound (1.14 g, 26%) as a red powder. 1H NMR (300 MHz, DMSO-d6): δ 10.32 (br s, 3H), 8.45 (br s, 1H), 7.34 (d, J=8.7 Hz, 1H), 7.11 (d, J=2.3 Hz, 1H), 6.79 (dd, J=8.7, 2.3 Hz, 1H).
Reaction SMILES: CCN(C(C)C)C(C)C.[CH3:10][O:11][C:12]([NH:14][C@H:15]([C:19]([OH:21])=O)[CH:16]([CH3:18])[CH3:17])=[O:13].[B-](F)(F)(F)F.CN(C(ON1C(=O)C=CC=C1)=[N+](C)C)C.Cl.[CH2:43]([N:45]([C:48]1[CH:53]=[CH:52][C:51]([CH2:54][N:55]([NH2:80])[CH2:56][C@H:57]([OH:79])[C@@H:58]([NH:66][C:67](=[O:78])[C@H:68]([C:74]([CH3:77])([CH3:76])[CH3:75])[NH:69][C:70]([O:72][CH3:73])=[O:71])[CH2:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)=[CH:50][CH:49]=1)[CH2:46][CH3:47])[CH3:44]>CN(C=O)C>[CH2:43]([N:45]([C:48]1[CH:53]=[CH:52][C:51]([CH2:54][N:55]([NH:80][C:19](=[O:21])[C@H:15]([CH:16]([CH3:17])[CH3:18])[NH:14][C:12]([O:11][CH3:10])=[O:13])[CH2:56][C@H:57]([OH:79])[C@@H:58]([NH:66][C:67](=[O:78])[C@H:68]([C:74]([CH3:76])([CH3:75])[CH3:77])[NH:69][C:70]([O:72][CH3:73])=[O:71])[CH2:59][C:60]2[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=2)=[CH:50][CH:49]=1)[CH2:46][CH3:47])[CH3:44]
Reactant: CCN(CC)c1ccc(CN(N)C[C@H](O)[C@H](Cc2ccccc2)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)cc1
Reactant: COC(=O)N[C@H](C(=O)O)C(C)C
Agent: CN(C)C(On1ccccc1=O)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCN(CC)c1ccc(CN(C[C@H](O)[C@H](Cc2ccccc2)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)NC(=O)[C@@H](NC(=O)OC)C(C)C)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
In analogy with Example 2, 0.42 ml of Hünig's base is added to 0.193 g (1.1 mmol) of N-methoxycarbonyl-(L)-valine and 0.327 g (1.1 mmol) of TPTU in 3 ml of DMF and the whole is stirred at RT for 10 min. After that, 0.63 g (1 mmol) of 1-[p-(N,N-diethylamino)-phenyl]-4(S)-hydroxy-2-amino-5(S)-[N-(N-methoxycarbonyl-(L)-tert-leucyl)amino]-6-phenyl-2-azahexane hydrochloride (Example 2f), dissolved in 2 ml of DMF, is added and the mixture is stirred at RT for 21 h. After working-up in the same way as described for Example 2, the residue is digested in DIPE and the title compound is filtered off. The suction filter residue is washed once again with DIPE and dried in a heated desiccator at 45° C. TLC: Rf0.50 (ethyl acetate). HPLC20-100: tret=10.93; FAB MS (M+H)+=685.
Reaction SMILES: S1CCCS[C:2]1=[CH:7][CH:8]1[C:13]2([CH3:17])[CH2:14][CH2:15][CH2:16][C:9]1([CH3:19])[CH2:10][N:11]([CH3:18])[CH2:12]2.C[OH:21].O.[C:23](=O)([O-])[O-:24].[K+].[K+]>C(OCC)(=O)C>[CH3:23][O:24][C:2](=[O:21])[CH2:7][CH:8]1[C:13]2([CH3:17])[CH2:14][CH2:15][CH2:16][C:9]1([CH3:19])[CH2:10][N:11]([CH3:18])[CH2:12]2
Reactant: CN1CC2(C)CCCC(C)(C1)C2C=C1SCCCS1
Reactant: CO
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)CC1C2(C)CCCC1(C)CN(C)C2

Procedure:
To a solution of 1.78 g of 9-(1,3-dithian-2-ylidenemethyl)-1,3,5-trimethyl-3-azabicyclo[3.3.1]nonane in a solvent mixture of methanol (27 ml) with water (3 ml) was added 3.53 g of mercuric chloride under stirring and the resulting mixture was then refluxed for 20 hours. Next, the reaction mixture was poured into ethyl acetate/an aqueous solution of potassium carbonate and filtered through celite. After. distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate) to thereby give 0.23 g of the title compound as a colorless oily substance.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH2:8]Cl)=[CH:6][CH:5]=[C:4]([Cl:10])[N:3]=1.[C:11]([O-:14])(=[O:13])[CH3:12].[Na+]>C(O)(=O)C>[Cl:1][C:2]1[C:7]([CH2:8][O:14][C:11](=[O:13])[CH3:12])=[CH:6][CH:5]=[C:4]([Cl:10])[N:3]=1
Reactant: CC(=O)[O-]
Reactant: ClCc1ccc(Cl)nc1Cl
Agent: [Na+]
Solvent: CC(=O)O
Product: CC(=O)OCc1ccc(Cl)nc1Cl

Procedure:
840 g (4.28 mols) of 2,6-dichloro-3-chloromethylpyridine, 700 g (8.5mols) of sodium acetate and 1,600 ml of anhydrous acetic acid are heated together for 4 hours under reflux. The reaction product is then freed from solvent by distilling the latter off, is made alkaline (pH 8-10) with aqueous sodium hydroxide solution and is suspended in water. The reaction product is extracted with diethyl ether and the organic phase is dried over magnesium sulphate and evaporated. After distilling the crude product, colourless 2,6-dichloro-3-acetoxymethylpyridine is obtained.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[C:5]([Cl:14])=[C:4]([C:15]#[N:16])[N:3]=1.[CH3:17][C:18]1[N:19]=[CH:20][NH:21][CH:22]=1.C(O)(C)C>CC(=O)OCC.CO>[CH3:8][OH:12].[NH3:3].[Cl:14][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[C:8]([O:12][CH3:13])[CH:7]=2)[C:2]([N:21]2[CH:22]=[C:18]([CH3:17])[N:19]=[CH:20]2)=[N:3][C:4]=1[C:15]#[N:16]
Reactant: COc1ccc2c(Cl)nc(C#N)c(Cl)c2c1
Reactant: Cc1c[nH]cn1
Solvent: CC(C)O
Solvent: CCOC(C)=O
Solvent: CO
Product: COc1ccc2c(-n3cnc(C)c3)nc(C#N)c(Cl)c2c1
Product: N
Temperature: 150 °C

Procedure:
1,4-dichloro-6-methoxyisoquinoline-3-carbonitrile (0.25 g, 0.988 mmol) and 4-methylimidazole (0.324 g 3.951 mmol) and 4 mL isopropanol were taken in a sealed tube and heated at 150° C. for 2 h The resulting white solid was dissolved in hot EA-MeOH and dry loaded on a flash column. Flash chromatography (0% to 6% MeOH—NH3 in EA) gave the titled compound as a white solid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:9])[CH:7]=[CH2:8])(=O)[CH:2]=[CH2:3].[CH2:10](O)CCC>>[C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:10])(=[O:9])[CH:7]=[CH2:8]
Reactant: C=CC(=O)OC(=O)C=C
Reactant: CCCCO
Product: C=CC(=O)OCCCC
Reaction time: 3.5 h
Yield: 91.2 %

Procedure:
According to another embodiment of the invention, the olefin acid anhydrides are reacted with alcohols to give high yields of the acrylate esters at room temperature. In particular, acrylic anhydride has been reacted with a series of alcohols ranging from C-1 to C-18 to give high yields of the acrylate esters at room temperature. The synthesis of acrylate esters by the reaction of alcohols with acrylic anhydride were found to proceed essentially to completion at room temperature to yield only the desired acrylate esters. The following mechanism is proposed for this reaction: ##STR3## No significant competing reactions were observed, such as the Michael addition reactions that often accompany the production of acrylate esters under reflux conditions. The following are representative of this embodiment: (1) the reaction of n-butyl alcohol with acrylic anhydride was completed in 3.5 hours and yielded 91.2% of n-butyl acrylate; (2) the reaction of n-octyl alcohol with acrylic anhydride was completed in 4 hours to obtain an 81.3% yield of n-octyl acrylate; and (3) the reaction of cis-12,13-epoxy-cis-9-octadecenol with acrylic anhydride was completed in 55 hours to give an 88.4% yield of cis-12, 13-epoxy-cis-9-octadecenyl acrylate.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1([NH:10][C:11]([CH:13]2[CH2:17][CH:16]([OH:18])[CH2:15][N:14]2[C:19](=[O:34])[CH:20]([NH:25][C:26]([O:28][CH:29]2[CH2:33][CH2:32][CH2:31][CH2:30]2)=[O:27])[C:21]([CH3:24])([CH3:23])[CH3:22])=[O:12])[CH2:7][CH:6]1[CH:8]=[CH2:9])=[O:4].C1N=CN([C:40]([N:42]2[CH:46]=N[CH:44]=[CH:43]2)=[O:41])C=1.[F:47][C:48]1C=[CH:55][CH:54]=[C:53]2[C:49]=1CNC2>C(Cl)Cl>[CH:29]1([O:28][C:26]([NH:25][CH:20]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:19]([N:14]2[CH:13]([C:11](=[O:12])[NH:10][C:5]3([C:3]([O:2][CH3:1])=[O:4])[CH2:7][CH:6]3[CH:8]=[CH2:9])[CH2:17][CH:16]([O:18][C:40]([N:42]3[CH2:43][C:44]4[C:55](=[CH:54][CH:53]=[CH:49][C:48]=4[F:47])[CH2:46]3)=[O:41])[CH2:15]2)=[O:34])=[O:27])[CH2:30][CH2:31][CH2:32][CH2:33]1
Reactant: Fc1cccc2c1CNC2
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: C=CC1CC1(NC(=O)C1CC(O)CN1C(=O)C(NC(=O)OC1CCCC1)C(C)(C)C)C(=O)OC
Solvent: ClCCl
Product: C=CC1CC1(NC(=O)C1CC(OC(=O)N2Cc3cccc(F)c3C2)CN1C(=O)C(NC(=O)OC1CCCC1)C(C)(C)C)C(=O)OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 78.9 %

Procedure:
1-{[1-(2-Cyclopentyloxycarbonylamino-3,3-dimethyl-butyryl)-4-hydroxy-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid methyl ester (530 mg, 1.11 mmol) was dissolved in CH2Cl2 (11 mL) and treated with CDI (234 mg, 1.44 mmol). After stirring overnight at room temperature, 4-fluoro-2,3-dihydro-1H-isoindole (762 mg, 5.56 mmol) was added and the reaction mixture was stirred overnight. The reaction was then diluted with CH2Cl2 and sequentially washed with 1N HCl, saturated aqueous NaHCO3, H2O and saturated aqueous NaCl. The organic phase was then dried over sodium sulfate. After removal of solvent, the crude product was purified by column chromatography on silica (40-60% EtOAc/Hexanes) to provide 4-fluoro-1,3-dihydro-isoindole-2-carboxylic acid 1-(2-cyclopentyloxycarbonylamino-3,3-dimethyl-butyryl)-5-(1-methoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-pyrrolidin-3-yl ester (563 mg, 79% yield). 1H NMR (CDCl3, 300 MHz) δ 7.77 (bd, 1H), 6.92-7.27 (m, 3H), 5.75 (m, 1H), 5.29 (m, 2H), 5.15 (m, 2H), 4.55-4.85 (m, 5H), 4.26 (m, 2H), 3.70 (m, 1H), 3.67 (s, 3H), 2.82 (m, 1H), 2.56 (m, 1H), 2.10 (m, 1H), 1.87 (m, 1H), 1.40-1.65 (m, 5H), 1.02 (s, 9H). LCMS found 643.3 [M+H]+.
Reaction SMILES: [NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]([CH3:19])[C:3]1=[O:20].[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]=[C:30]=[O:31])=[CH:25][CH:24]=1>O1CCCC1>[CH3:19][N:4]1[C:5]2[CH:18]=[CH:17][CH:16]=[CH:15][C:6]=2[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:8][CH:2]([NH:1][C:30]([NH:29][C:26]2[CH:27]=[CH:28][C:23]([O:22][CH3:21])=[CH:24][CH:25]=2)=[O:31])[C:3]1=[O:20]
Reactant: COc1ccc(N=C=O)cc1
Reactant: CN1C(=O)C(N)N=C(c2ccccc2)c2ccccc21
Solvent: C1CCOC1
Product: COc1ccc(NC(=O)NC2N=C(c3ccccc3)c3ccccc3N(C)C2=O)cc1
Reaction time: 8 h

Procedure:
Equimolar amounts of 3(R,S)-amino-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one and 4-methoxyphenylisocyanate were mixed in 8 ml of dry tetrahydrofuran at room temperature. The reaction mixture was allowed to stand for 8 hours and was then filtered. The collected solids were washed with tetrahydrofuran and dried in vacuo over P2O5 to give the analytical product: m.p. 261°-263° C.
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH:8][NH2:9])=[N:4][CH:5]=[CH:6][CH:7]=1.C(O)CCCC.[C:16]([O:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])(=[O:22])/[CH:17]=[CH:18]\[C:19]([O-])=[O:20]>C(O)(=O)C>[Cl:1][C:2]1[C:3]([N:8]2[CH:17]([C:16]([O:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[O:22])[CH2:18][C:19](=[O:20])[NH:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCCCCOC(=O)/C=C\C(=O)[O-]
Reactant: NNc1ncccc1Cl
Solvent: CCCCCO
Solvent: CC(=O)O
Product: CCCCCOC(=O)C1CC(=O)NN1c1ncccc1Cl
Temperature: 75 °C
Yield: 23.8 %

Procedure:
0.75 g of sodium hydroxide was added to a mixed solution comprising 15 ml of 1-pentanol and 30 ml of toluene, followed by dehydration using an azeotropic dehydrator under reflux with heating, and then toluene was distilled off. Further, 20 ml of toluene was added to the reaction system and then toluene was distilled off with heating again, to obtain a 1-pentanol solution of sodium pentaoxide. 2.5 g of 3-chloro-2-hydrazinylpyridine was added to the reaction liquid at from 70 to 80° C. little by little over a period of 5 minutes, and then 5 ml of 1-pentanol was added, followed by heating at from 70 to 80° C. for 25 minutes. Then, a mixed solution comprising 5.1 g of pentyl maleate and 5 ml of 1-pentanol was dropwise added over a period of 15 minutes, followed by reaction at from 70 to 80° C. further for 2 hours. After the reaction liquid was stood to cool, acetic acid was added to the reaction liquid for neutralization, followed by concentration under reduced pressure. Water was added to the residue, followed by extraction with ethyl acetate, and the organic layer was washed with diluted hydrochloric acid and a sodium chloride aqueous solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=6/4 to 0/1) to obtain 1.29 g of the desired product (melting point: 66 to 68° C.) in the form of brown crystals.
Reaction SMILES: [CH2:1]([N:3]1[C:7]2=[N:8][CH:9]=[C:10]([C:19]([O:21]CC)=[O:20])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[OH-].[Na+]>C(O)C.O>[CH2:1]([N:3]1[C:7]2=[N:8][CH:9]=[C:10]([C:19]([OH:21])=[O:20])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]
Reactant: CCOC(=O)c1cnc2c(cnn2CC)c1NC1CCOCC1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCn1ncc2c(NC3CCOCC3)c(C(=O)O)cnc21
Temperature: 50 °C
Yield: 86 %

Procedure:
A solution of Intermediate 16 (37.8 g) in ethanol:water (4:1, 375 ml) was treated with sodium hydroxide (18.9 g). The mixture was heated at 50° C. for 5 hours, then concentrated in vacuo, dissolved in water and acidified to pH 2 with aqueous hydrochloric acid (2M). The resultant white solid was removed by filtration and dried under vacuum to afford Intermediate 17 as an off-white solid (29.65 g). LCMS showed MH+=291; TRET=2.17 min.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][C:14]([OH:16])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:17]([CH2:19][C:20]([O:22][CH3:23])=[O:21])#[C-:18].C(P(C#N)(CC)=O)C.N12CCCN=C1CCCCC2>CN(C)C=O.C(N(CC)CC)C>[CH3:23][O:22][C:20]([C:19]1[N:17]=[CH:18][O:16][C:14]=1[CH2:13][CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])=[O:21]
Reactant: O=C(O)CCNC(=O)OCc1ccccc1
Reactant: [C-]#[N+]CC(=O)OC
Agent: CCP(=O)(C#N)CC
Solvent: C1CCC2=NCCCN2CC1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COC(=O)c1ncoc1CCNC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 49.5 %

Procedure:
A mixture of 33.5 g of N-benzyloxycarbonyl-β-alanine, 15 g of methyl isocyanoacetate, 31.8 g of diethylphosphorylcyanide, 23 g of 1,8-diazabicyclo[5.4.0]undec-7-ene, 42 ml of triethylamine and 300 ml of dimethylformamide was stirred at room temperature overnight. Then, the solvent was removed, and ethyl acetate was added to the mixture. The mixture was washed and dried, and then the solvent was removed. The residue was purified by silica gel chromatography and crystallized from isopropyl ether, followed by recrystallization from an ethyl acetate-isopropyl ether mixed solution, to obtain 22.6 g of 4-methoxycarbonyl-5-{2-(benzyloxycarbonylamino)ethyl}oxazole.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[S:11](Cl)(=[O:13])=[O:12].[CH:15]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)=[O:16].C(N(CC)CC)C>C1COCC1>[CH:15]([N:17]1[CH2:22][CH2:21][N:20]([S:11]([C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=2)(=[O:13])=[O:12])[CH2:19][CH2:18]1)=[O:16]
Reactant: O=CN1CCNCC1
Reactant: O=S(=O)(Cl)c1ccc2ccccc2c1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=CN1CCN(S(=O)(=O)c2ccc3ccccc3c2)CC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A THF (10 ml) solution of 2-naphthalenesulfonylchloride (23 g, 101 mmol) was added dropwise to a THF (100 ml) solution of 1-formylpiperazine (11.4 g, 100 mmol) and triethylamine (15 g, 150 mmol) under ice-cooling. The solution was stirred at room temperature for 30 minutes, and concentrated. The residue was washed with water and diisopropylether and dried under reduced pressure to give 1-formyl-4-(2-naphthalenesulfonyl)piperazine.
Reaction SMILES: [OH:1][C:2]1[C:9](O)=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[CH2:11](Cl)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[C:19](=[O:22])([O-])[O-].[K+].[K+]>C(O)C>[CH2:11]([O:1][C:2]1[C:9]([O:22][CH2:19][C:2]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:3]=2)=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: ClCc1ccccc1
Reactant: O=C([O-])[O-]
Reactant: O=Cc1cccc(O)c1O
Agent: [K+]
Solvent: CCO
Product: O=Cc1cccc(OCc2ccccc2)c1OCc1ccccc1

Procedure:
13.8 g of 2,3-dihydroxybenzaldehyde, 30.4 g of benzyl chloride and 17.3 g of powdered anhydrous potassium carbonate in 160 ml of anhydrous ethanol are boiled under reflux with exclusion of moisture for 6 hours. The reaction solution is filtered, washing with ethanol, and the filtrate is evaporated in vacuo. On digestion of the residue with diisopropyl ether the known desired compound crystallizes and as white needles (M.p. 89°-91° C.).
Reaction SMILES: C([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]=[CH2:10])=C.BrBr.[CH:13]1C=CC=C[CH:14]=1>>[CH:9]([C:4]1[CH:3]=[CH:8][C:7]([CH:13]=[CH2:14])=[CH:6][CH:5]=1)=[CH2:10]
Reactant: C=Cc1ccccc1C=C
Reactant: c1ccccc1
Agent: BrBr
Product: C=Cc1ccc(C=C)cc1
Temperature: 0 °C
Yield: 80 %

Procedure:
Pure 1,4-divinylbenzene (1,4-DVB) monomer was isolated from commercially available divinylbenzene mixture (Aldrich Chemical Co.), containing about 60 wt. % divinylbenzene and having a mole ratio between the 1,3- and 1,4-isomer of about 1 to 2.5, by a bromination-debromination method. In a 1 L flask equipped with a magnetic stirring bar, 230 ml of the commercial divinylbenzene mixture was mixed with 500 ml of benzene. Under stirring and cooling at 0° C., 120 ml of bromine was dropwised into the mixed solution for a period of 6 hours. During the bromine addition, the color of solution changed from deep red through brown yellow to light yellow. At the last stage, the tetrabromided 1,4-divinylbenzene was crystallized and the solution became gray white. The crystals were filtered and washed with methanol until complete decoloration. The resulting crystals were recrystallized twice from chloroform, filtered and dried. About 95 g of the tetrabromided 1,4-divinylbenzene, i.e. 1,4-bis(1,2-dibromoethyl)benzene, was obtained. The crystals were analyzed by DSC and NMR. DSC showed a melting point at 163° C. 1H NMR spectra showed the expected chemical shifts: 67 =7.45 (singlet, 4H, C6H4), 5.15 (multiplet, 2H, CHBrCH2Br), and 4.10 (multiplet, 4H, CHBrCH2Br).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10](F)[CH:9]=2)[CH:5]=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH:19]([C:23]3[NH:24][C:25]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[C:26]([CH3:28])[N:27]=3)[CH2:18]2)[N:3]=1.[NH2:35][NH2:36]>C(O)C>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]3[C:11]([C:12]([NH2:13])=[N:35][NH:36]3)=[CH:14][CH:15]=2)[CH:5]=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH:19]([C:23]3[NH:24][C:25]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)=[C:26]([CH3:28])[N:27]=3)[CH2:18]2)[N:3]=1
Reactant: Cc1nc(C2CN(c3cc(-c4ccc(C#N)c(F)c4)nc(N)n3)CCO2)[nH]c1-c1ccccc1
Reactant: NN
Solvent: CCO
Product: Cc1nc(C2CN(c3cc(-c4ccc5c(N)n[nH]c5c4)nc(N)n3)CCO2)[nH]c1-c1ccccc1
Reaction time: 1 h
Yield: 87.5 %

Procedure:
A mixture of 4-{2-amino-6-[2-(4-methyl-5-phenyl-1H-imidazol-2-yl)-4-morpholinyl]-4-pyrimidinyl}-2-fluorobenzonitrile (100 mg, 0.220 mmol) and hydrazine (0.348 mL, 10.98 mmol) in ethanol (2 mL) was heated under microwave conditions with stirring for 1 hour. The mixture was concentrated, and the crude product was purified by RPHPLC to afford the title compound (90 mg) as a pale yellow solid. LC-MS (ES) m/z=468 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 2.35 (s, 3H), 3.04-3.22 (m, 2H), 3.66-3.75 (m, 1H), 4.04 (d, J=11.2 Hz, 1H), 4.32 (d, J=12.8 Hz, 1H), 4.52-4.58 (m, 1H), 4.70 (s, 1H), 5.38 (s, 2H), 6.20 (s, 2H), 6.70 (s, 1H), 7.17-7.28 (m, 1H), 7.34-7.46 (m, 2H), 7.52-7.66 (m, 3H), 7.71 (d, J=8.4 Hz, 1H), 7.96 (s, 1H), 11.52 (s, 1H), 12.20 (s, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[O:9][C:8]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][N:11]=2)=[CH:7][CH:6]=1)=[O:4].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[H-].[Na+]>C1COCC1>[CH2:19]([N:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]([C:8]2[O:9][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=2)=[N:11]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: COC(=O)c1ccc(-c2n[nH]c3ccccc23)o1
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)c1ccc(-c2nn(Cc3ccccc3)c3ccccc23)o1

Procedure:
A solution of 3-(5-methoxycarbonyl-2-furyl)-1H-indazole (2.0 g, 8.3 mmol) and benzyl bromide (2.5 mL, 21.0 mmol) in THF (100 mL) was added dropwise via dropping funnel to a suspension of sodium hydride (60% dispersion in oil: 0.50 g, 12.5 mmol) in THF (200 mL). The resultant mixture was stirred at room temperature for 20 h. The mixture was poured onto brine and the layers separated. The aqueous layer was extracted three times with ether and then the combined organic material was washed with saturated aqueous NaHCO3 solution, dried (MgSO4) and concentrated under reduced pressure. The residue was chromatographed on silica (EtOAc:cyclohexane 1:4) and then the product was recrystallised (EtOAc/hexane) to give a yellow solid: mp 137–138° C.; MS (EI) M+ 332; 1H-NMR (CDCl3) 3.97 (s, 3H), 5.67 (s, 2H), 7.03 (d, 1H, J=3.7 Hz), 7.22–7.43 (m, 9H), 8.27 (d, 1H, J=8.1 Hz); Anal. (C20H16N2O3) C, calcd 72.28; found 71.92, H, calcd 4.85; found 4.75, N, calcd 8.43; found 8.39.