Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][C:9](=[O:28])[C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[O:24]C(=O)C)[CH2:6]1)(=O)C.[O-]S([O-])(=O)=O.[Mg+2].C1C(I)=C(I)C(C(O)=O)=CC=1I>CCCCC>[OH:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][C@H:9]([OH:28])[C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[OH:24])[CH2:6]1
Reactant: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC(=O)[C@H]3[C@@H]4CC[C@H](OC(C)=O)[C@@]4(C)CC[C@@H]32)C1
Agent: O=C(O)c1cc(I)cc(I)c1I
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Solvent: CCCCC
Product: C[C@]12CC[C@H]3[C@@H]([C@@H](O)C=C4C[C@@H](O)CC[C@@]43C)[C@@H]1CC[C@@H]2O
Temperature: 25 °C
Reaction time: 1 h
Yield: 86 %

Procedure:
A solution of 3β,17β diacetoxyandrost-5-en-7-one (0.9581 g, 2.466 mmol) and pentane (30 mL), dried over MgSO4) were mixed under a nitrogen atmosphere. TIBA (9.5 mL, 9.5 mmol, 1M in toluene) was then added dropwise by syringe. The solution was stirred at room temperature for about 1 hour. The reaction was terminated by the addition of diluted hydrochloric acid (approximately 5mL). This solution was added to water (100 mL) and extracted with ethyl acetate (3 times with 50 mL). The organic layers were combined and then washed several times with saturated sodium bicarbonate solution (50 ml), saturated sodium chloride solution (two times with 50 mL,) and water (50 mL). The organic layer was dried over magnesium sulfate and the solvent removed by rotary evaporation to yield 86% crude product. 1H NMR indicated that the crude product contained 3β,17β,-diacetoxy-7-β-hydroxyandrost-5-en-7-one (86%) and 3β,17β-diacetoxy- 7-α-hydroxyandrost-5-ene.
Reaction SMILES: [CH:1]([O:11][CH3:12])=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[C:13]([O:18][CH2:19][CH3:20])(=[O:17])[CH:14]([CH3:16])[OH:15]>Cl>[CH3:12][O:11][CH:1]([O:15][CH:14]([CH3:16])[C:13]([O:18][CH2:19][CH3:20])=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCOC(=O)C(C)O
Reactant: CCCCCCCCC=COC
Agent: Cl
Product: CCCCCCCCCC(OC)OC(C)C(=O)OCC
Temperature: 40 °C
Reaction time: 2.3 h

Procedure:
Into a 50 ml. round-bottom flask equipped with a static nitrogen acid, thermometer, mantle, and magnetic stirrer, was charged 10.2 g. of methyl decenyl ether and 3.5 g. of ethyl lactate. One drop of HCl was added after heating the mixture to 40° C., whereupon an exotherm to 63° C. was experienced. Stirring was continued for 2.3 hours at between 40° and 53° C. The mixture was quenched with solid sodium carbonate. Another run made with 20.4 g. of the methyl decenyl ether and 7.1 g. of ethyl lactate was performed in a similar manner and combined with the above run for workup. The product was distilled on a one-foot micro-vigreaux column:
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11](=[O:26])[C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]([C:22]([F:25])([F:24])[F:23])[CH:13]=2)[C@H:7]([CH2:27][C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[NH:30][CH:29]=2)[CH2:6]1.[CH2:37]([N:39]([CH2:42]C)CC)C.[Cl:44]C(OC1C=CC([N+]([O-])=O)=CC=1)=[O:46]>O1CCCC1>[ClH:44].[F:24][C:22]([F:23])([F:25])[C:14]1[CH:13]=[C:12]([CH:17]=[C:16]([C:18]([F:20])([F:19])[F:21])[CH:15]=1)[C:11]([N:8]1[CH2:9][CH2:10][N:5]([CH2:4][CH2:3][CH2:2][NH:1][C:37]([NH:39][CH3:42])=[O:46])[CH2:6][C@H:7]1[CH2:27][C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[NH:30][CH:29]=1)=[O:26]
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: CCN(CC)CC
Reactant: NCCCN1CCN(C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@H](Cc2c[nH]c3ccccc23)C1
Solvent: C1CCOC1
Product: CNC(=O)NCCCN1CCN(C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@H](Cc2c[nH]c3ccccc23)C1
Product: Cl
Reaction time: 0.58 h

Procedure:
To a stirred mixture of (2R)-4-(3-aminopropyl)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-yl-methyl)-piperazine (0.20 g) and triethylamine (0.06 ml) in tetrahydrofuran (10 ml) was added 4-nitrophenyl chloroformate (0.08 g) under ice-cooling. After 35 minutes, the resulting precipitate was filtered off. To the filtrate were added triethylamine (0.06 ml) and 30% methylamine in ethanol (0.05 ml) at room temperature. After stirring for 1 hour and 40 minutes, additional 30% methylamine in ethanol (0.05 ml) was added to the reaction mixture and then stirred for 45 minutes. The reaction mixture was concentrated in vacuo and the residue was partitioned between dichloromethane and water. The organic layer was separated, washed with aqueous saturated sodium chloride solution and dried over magnesium sulfate. After evaporation of the solvent in vacuo, the residue was purified by column chromatography on silica gel eluting with a mixed solvent of dichloromethane and methanol (100:3). The eluate was treated with 4N hydrogen chloride in dioxane solution to afford (2R)-1-[3,5-bis(trifluoromethyl)-benzoyl]-2-(1H-indol-3-yl-methyl)-4-[3-(3-methylureido)propyl]piperazine hydrochloride (0.08 g).
Reaction SMILES: C([O:3][C:4](=[O:25])[CH2:5][C:6]1[C:7](=[O:24])[O:8][C:9]2[C:14]([C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[CH:13][C:12]([CH3:22])=[C:11]([Cl:23])[CH:10]=2)C.[Br:26]N1C(=O)CCC1=O.Cl>C(OCC)(=O)C.C(O)(=O)C>[Br:26][CH2:22][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][C:11]=1[Cl:23])[O:8][C:7](=[O:24])[C:6]([CH2:5][C:4]([OH:3])=[O:25])=[C:15]2[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)Cc1c(-c2ccccc2)c2cc(C)c(Cl)cc2oc1=O
Agent: Cl
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: O=C(O)Cc1c(-c2ccccc2)c2cc(CBr)c(Cl)cc2oc1=O

Procedure:
A solution of ethyl(7-chloro-6-methyl-2-oxo-4-phenyl-2H-chromen-3-yl)acetate (3.5 g) in ethyl acetate (50 ml) was combined with N-bromosuccinimide (2.1 g) and 2,2′-azoisobutyronitrile (48.3 mg), and heated under reflux for 1 hour. After cooling, the reaction solution was washed with water followed by a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by a silica gel column chromatography (eluent: ethyl acetate-hexane=1:4) to obtain the crude crystal (approximately 2.6 g) of ethyl 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetate. The crude crystal was dissolved in acetic acid (50 ml) and concentrated hydrochloric acid (25 ml), and heated under reflux for 30 minutes. The reaction solution was concentrated under reduced pressure, and the resultant residue was dissolved in a solvent mixture of THF (10 ml) and ethyl acetate (50 ml), and then washed with water followed by a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was washed with ethyl acetate to obtain a crude crystal (1.78 g, yield: 44%) of the title compound. The compound was used in the next reaction without further purification. NMR (CDCl3) δ: 3.43 (2H, s), 4.58 (2H, s), 7.11 (1H, s), 7.20-7.30 (2H, m), 7.48 (1H, s), 7.50-7.65 (3H, m).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16](I)[S:17][C:13]=2[N:12]2[C:19]([CH3:22])=[N:20][N:21]=[C:11]2[CH2:10][N:9]=1.FC1C=CC2N(CC#C)C(=O)COC=2C=1.C(O)C>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[CH:16][S:17][C:13]=2[N:12]2[C:19]([CH3:22])=[N:20][N:21]=[C:11]2[CH2:10][N:9]=1
Reactant: Cc1nnc2n1-c1sc(I)cc1C(c1ccccc1Cl)=NC2
Agent: C#CCN1C(=O)COc2cc(F)ccc21
Solvent: ClCCl
Solvent: CCO
Product: Cc1nnc2n1-c1sccc1C(c1ccccc1Cl)=NC2

Procedure:
The title compound was prepared by reacting 4-(2-chlorophenyl)-2-iodo-9-methyl-6H-thieno-[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine with 7-fluoro-4-(2-propynyl)-2H-1,4-benzoxazin-3(4H)-one under the conditions used in Example 37. The product was isolated by chromatography over the 50 fold amount of silica gel using 4 % (v/v) of ethanol in methylene chloride. The good fractions were combined and evaporated and the residue was crystallized from ethyl acetate to give colorless crystals of 4-{3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin.2.2-propynyl}-7-fluoro-2H-1,4-benzoxazin-3(4H)-one with m.p. 215°-217°.
Reaction SMILES: [N:1]1([C:7]2[N:12]=[CH:11][NH:10][C:9](=[O:13])[CH:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH3:14][O:15][C:16]1[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[CH:21]=[C:18]([CH:19]=O)[C:17]=1[OH:27]>>[OH:27][C:17]1[C:16]([O:15][CH3:14])=[CH:23][C:22]([N+:24]([O-:26])=[O:25])=[CH:21][C:18]=1[CH2:19][N:4]1[CH2:5][CH2:6][N:1]([C:7]2[N:12]=[CH:11][NH:10][C:9](=[O:13])[CH:8]=2)[CH2:2][CH2:3]1
Reactant: COc1cc([N+](=O)[O-])cc(C=O)c1O
Reactant: O=c1cc(N2CCNCC2)nc[nH]1
Product: COc1cc([N+](=O)[O-])cc(CN2CCN(c3cc(=O)[nH]cn3)CC2)c1O

Procedure:
6-[4-(2-Hydroxy-3-methoxy-5-nitro-benzyl)-piperazin-1-yl]-3H-pyrimidin-4-one was prepared using Procedure B from 6-piperazin-1-yl-3H-pyrimidin-4-one (Intermediate 4) and 3-methoxy-5-nitrosalicylaldehyde (available from Aldrich). 1H NMR (400 MHz, CDCl3) δ 2.65-2.70 (m, 4H), 3.59-3.66 (m, 4H), 3.85 (s, 2H), 3.99 (s, 3H), 5.40 (s, 1H), 7.67 (s, 1H), 7.72 (s, 1H), 7.85 (s, 1H), 12.20 (br s, 1H). Mass spectrum (ES) MH+=362.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][N:6]=[CH:5]2.[CH3:12]C([O-])(C)C.[K+].CI>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[N:7]([CH3:12])[N:6]=[CH:5]2
Reactant: CC(C)(C)[O-]
Reactant: Fc1cc2[nH]ncc2cc1Br
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: Cn1ncc2cc(Br)c(F)cc21
Reaction time: 0.67 h
Yield: 43.7 %

Procedure:
To a solution of 5-bromo-6-fluoro-1H-indazole (4 g, 18.60 mmol) in DMF (20 ml) was added potassium 2-methylpropan-2-olate (2.087 g, 18.60 mmol). The resulting mixture was stirred for 40 min. CH3I (3.17 g, 22.32 mmol) was added dropwise. After stirring overnight, the reaction mixture was quenched with NH4Cl(aq), extracted with EtOAc, washed with NH4Cl(aq), dried over Na2SO4, filtered and concentrated in vacuo to give crude product. The crude product was purified with silica gel column chromatography with gradient Hexanes:EA to give light yellow solid 5-bromo-6-fluoro-1-methyl-1H-indazole (1.86 g, 42%).
Reaction SMILES: [CH3:1][N:2]1[C:6]([S:7][CH3:8])=[CH:5][C:4]([CH:9]([CH2:14][CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:10]([O:12]C)=[O:11])=[N:3]1.[OH-].[Na+].O1CCCC1.Cl>CO>[CH3:1][N:2]1[C:6]([S:7][CH3:8])=[CH:5][C:4]([CH:9]([CH2:14][CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:10]([OH:12])=[O:11])=[N:3]1
Reactant: COC(=O)C(CC1CCOCC1)c1cc(SC)n(C)n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CSc1cc(C(CC2CCOCC2)C(=O)O)nn1C
Temperature: 50 °C
Reaction time: 3 h

Procedure:
A mixture of methyl 2-[1-methyl-5-(methylsulfanyl)-1H-pyrazol-3-yl]-3-(tetrahydro-2H-pyran-4-yl)propanoate (2.52 g), 2N aqueous sodium hydroxide solution (6.3 ml), tetrahydrofuran (6 mL) and methanol (6 mL) was stirred at 50° C. for 3 hr. To the reaction mixture was added 1N hydrochloric acid (13 mL), and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4), and concentrated. The obtained residue was subjected to silica gel column chromatography to give the title compound (2.47 g, quantitatively) as a colorless oil from the fraction eluted with ethyl acetate. MS: 285 (MH+).
Reaction SMILES: [CH3:1][C:2]12[CH2:12][CH:6]3[CH2:7][C:8]([CH3:11])([CH2:10][C:4](Br)([CH2:5]3)[CH2:3]1)[CH2:9]2.[CH2:14](Br)[CH:15]=[CH2:16].CC1(C)C2CC3CC(CC1(Br)C3)C2.[Cl:31][Si:32]([Cl:39])([Cl:38])[CH2:33][CH2:34][SiH:35]([Cl:37])[Cl:36]>CCCCC.[Zn]>[Cl:31][Si:32]([Cl:39])([Cl:38])[CH2:33][CH2:34][Si:35]([Cl:37])([Cl:36])[CH2:14][CH2:15][CH2:16][C:6]12[CH2:12][C:2]3([CH3:1])[CH2:3][CH:4]([CH2:10][C:8]([CH3:11])([CH2:9]3)[CH2:7]1)[CH2:5]2
Reactant: Cl[SiH](Cl)CC[Si](Cl)(Cl)Cl
Reactant: CC12CC3CC(C)(C1)CC(Br)(C3)C2
Reactant: C=CCBr
Agent: CC1(C)C2CC3CC(C2)CC1(Br)C3
Agent: [Zn]
Solvent: CCCCC
Product: CC12CC3CC(C)(C1)CC(CCC[Si](Cl)(Cl)CC[Si](Cl)(Cl)Cl)(C3)C2
Temperature: 25 °C
Reaction time: 3 h

Procedure:
81.71 g (0.336 mol) 3,5-dimethyladamantylbromide was dissolved in 500 ml pentane. The solution was cooled to below −10° C. by ice/acetone bath. 51.40 g (0.425 mol) allylbromide was added followed by 410 mg FeBr3. The solution was then stirred for three hours at −20 . . . 10° C. after which analysis by GC-MS was carried out, indicating that some unreacted starting materials remained. 420 mg FeBr3 was added and solution was stirred for an additional two hours after which GC-MS showed that all the dimethyladamantyl bromide had reacted. The solution was warmed up to room temperature and it was washed twice with 500 ml water. The organic layer was collected and pentane was evaporated. Remaining material was dissolved to 700 ml ethanol and a small amount of water was added followed by 25 g (0.382 mol) metallic zinc. The solution was then heated up to reflux and it was stirred for 15 h. After cooling down to room temperature the solution was filtered. 300 ml water was added and the product was extracted by washing twice with 500 ml pentane. Pentane layers were collected and washed once with water. The organic layer were collected, dried with anhydrous magnesium sulfate and filtered. Pentane was evaporated and remaining crude 1-allyl-3,5-dimethyladamantane was purified by distillation, yield 45.90 g (67%). 1-allyl-3,5-dimethyladamantane was moved to a 100 ml vessel followed by 50 μl H2PtCl6/IPA solution. The solution was heated up to 85° C. and 59.50 g (0.227 mol) 1,1,1,4,4-pentachloro-1,4-disilabutane was added slowly during 30 min. After addition, the solution was heated up to 100° C. and it was stirred for an hour. The product thus obtained was then purified by distillation yielding 53.54 g (51%), bp. 157-158° C./<0.5 mbar.
Reaction SMILES: CS(O[CH2:6][CH:7]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8][O:9][CH2:10][CH3:11])(=O)=O.[N-:20]=[N+:21]=[N-:22].[Na+]>CN(C=O)C.O>[N:20]([CH2:6][CH:7]([NH:12][C:13](=[O:14])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:8][O:9][CH2:10][CH3:11])=[N+:21]=[N-:22]
Reactant: CCOCC(COS(C)(=O)=O)NC(=O)OC(C)(C)C
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOCC(CN=[N+]=[N-])NC(=O)OC(C)(C)C
Temperature: 50 °C
Reaction time: 24 h

Procedure:
To a solution of 2-[(tert-butoxycarbonyl)amino]-3-ethoxypropyl methanesulfonate (1.6 g, 5.4 mmol) in DMF (20 mL) was added sodium azide (1.10 g, 16.2 mmol) and then the reaction mixture was heated to 50° C. After 24 hours, the reaction mixture was diluted with water and the aqueous layer was extracted with ethyl acetate. The combined organic layers were concentrated under reduced pressure and the resulting residue was purified via silica chromatography to give tert-butyl (1-azido-3-ethoxypropan-2-yl)carbamate. MS ESI calc'd. for C10H21N4O3 [M+H]+ 245. found 245.
Reaction SMILES: [CH3:1][N:2]([CH3:19])[CH2:3][CH2:4][NH:5][C:6]1[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:8][C:7]=1[N+:16]([O-])=O.[H][H].[C:22](OCC)(=[O:24])C>[Pd]>[CH3:1][N:2]([CH3:19])[CH2:3][CH2:4][N:5]1[C:6]2[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:8][C:7]=2[NH:16][C:22]1=[O:24]
Reactant: CN(C)CCNc1cc(C(F)(F)F)ccc1[N+](=O)[O-]
Reactant: [H][H]
Reactant: CCOC(C)=O
Agent: [Pd]
Product: CN(C)CCn1c(=O)[nH]c2ccc(C(F)(F)F)cc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In ethyl acetate (20 ml) was dissolved N,N-dimethyl-N'-(2-nitro-5-trifluoromethylphenyl)ethylenediamine (0.24 g) followed by addition of a catalytic amount of 10% palladium-on-carbon, and the mixture was stirred under a hydrogen atmosphere at atmospheric pressure and room temperature until the absorption of hydrogen was ceased (for about 1 hour). The insoluble matter was filtered off and the solvent was distilled off under reduced pressure. The residue was dissolved in N,N-dimethylformamide (2 ml) followed by addition of N,N'-disuccinimidyl carbonate (DSC) (0.23 g). The reaction mixture was stirred at room temperature overnight, after which it was diluted with 1N hydrochloric acid and washed with ethyl acetate. The aqueous layer was alkalized with sodium hydroxide and the product was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was then distilled off under reduced pressure and the residue was purified by column chromatography (eluent:chloroform:methanol=5:1) to give 0.11 g of 1,3-dihydro-1-(2-dimethylaminoethyl)-6-trifluoromethyl-2H-benzimidazol-2-one.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][CH:15]=2)[N:8]=1)(=O)=O.[Cl:24][C:25]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([Cl:35])[C:26]=1[NH2:36]>O1CCOCC1>[Cl:24][C:25]1[CH:30]=[C:29]([C:31]([F:34])([F:32])[F:33])[CH:28]=[C:27]([Cl:35])[C:26]=1[NH:36][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]#[N:21])=[CH:18][CH:19]=2)[N:8]=1
Reactant: Nc1c(Cl)cc(C(F)(F)F)cc1Cl
Reactant: N#Cc1ccc(Nc2nccc(OS(=O)(=O)C(F)(F)F)n2)cc1
Solvent: C1COCCO1
Product: N#Cc1ccc(Nc2nccc(Nc3c(Cl)cc(C(F)(F)F)cc3Cl)n2)cc1
Temperature: 170 °C
Yield: 9.2 %

Procedure:
4-[(4-chloro-2-pyrimidinyl)amino]benzonitrile (0.003 mol), 2,6-dibromo-4-methyl-benzenamine (0.006 mol) and 1 M HCl in diethyl ether (4.5 ml) in 1,4-dioxane (10 ml) were combined in a tube and heated under Ar until all diethyl ether had evaporated. The tube was sealed and heated at 170° C. for 2.5 days. Silica gel was added, and the solvent was evaporated. The residue was purified by flash column chromatography over silica gel (eluent gradient: CH2Cl2:CH3OH:NH4OH 100:0:0 to 99:0.9:0.1). The desired fractions were collected and the solvent was evaporated. The residue was recrystallized from acetonitrile, filtered off and dried, yielding 0.22 g (15.9%) of 4-[[4-[(2,6-dibromo-4-methylphenyl)amino]-2-pyrimidinyl]amino]benzonitrile. b) 4-[[4-[(4-chloro-5-methyl-2-pyrimidinyl]amino]benzonitrile (0.01541 mol), 4-amino-3,5-dimethyl-benzonitrile (0.00219 mol), 1-methyl-2-pyrrolidinone (4 ml), 1,4-dioxane (15 ml) and diisopropylethylamine (0.0154 mol) were combined in a flask under a stream of argon and heated at 160–230° C. for 16 hours. CH2Cl2 and 1N NaOH were added, and the mixture was stirred 1 hour and filtered to give a brown solid (!). The CH2Cl2 filtrate was separated and was evaporated and purified by flash column chromatography (eluent: 2% CH3OH/CH2Cl2). The desired fractions were combined, evaporated and the residue was stirred in CH2Cl2. The solid precipitate was filtered off, combined with the brown solid (!) and recrystallized from CH3CN. The precipitate was filtered off and dried, yielding 1.57 g (29%) of 4-[[2-[(4-cyanophenyl)amino]-5-methyl-4-pyrimidinyl]amino]-3,5-dimethylbenzonitrile (comp. 52). c) 2-[(4-cyanophenyl)amino]4-pyrimidinyl trifluoromethanesulfonate (0.0022 mol) and 2,6-dichloro-4-(trifluoromethyl)-benzenamine (0.0044 mol) were combined in 1,4-dioxane (2.5 ml) and heated in a sealed tube under Ar at 170° C. for 40 hours. The reaction mixture was allowed to cool to room temperature. Silica gel was added, and the solvent was evaporated. The residue was purified by flash column chromatography over silica gel (eluent gradient: CH2Cl2:CH3OH:NH4OH 100:0:0 to 97:2.7:0.3). The desired fractions were collected and the solvent was evaporated. The residue was recrystallized from CH3CN, filtered off and dried, yielding 0.086 g (9.2%) of 4-[[4-[[2,6-dichloro-4-(trifluoromethyl)-phenyl]amino]-2-pyrimidinyl]amino]benzonitrile (comp. 23).
Reaction SMILES: [O:1]=[CH:2][C:3](=[CH2:5])[CH3:4].[O:6]=O.[OH2:8]>C(O)(=O)C>[C:2]([OH:6])(=[O:1])[C:3]([CH3:4])=[CH2:5].[C:2]([OH:1])(=[O:8])[CH:3]=[CH2:4]
Reactant: O
Reactant: O=O
Reactant: C=C(C)C=O
Solvent: CC(=O)O
Product: C=C(C)C(=O)O
Product: C=CC(=O)O
Temperature: 0 °C

Procedure:
For each of the catalysts described herein, 3-6 cc of catalyst were mixed with sufficient quartz chips to make a total volume of 15 cc, which was placed into a downflow reactor having an internal diameter of 0.40 inches. A gas stream consisting of 3.8% methacrolein, 8.0% oxygen, 30% water and the balance as nitrogen was passed over the catalyst bed in the reactor. The volumetric flow rates were varied between 50 and 100 seem. The internal reactor temperature was varied between 275° C. and 295° C. The reactor pressure was maintained at about 1 atmosphere. The catalyst loading, flow rates and reactor temperature were adjusted such that methacrolein conversions between 70% and 95% were obtained. Reaction products were condensed into a glass trap maintained at 0° C. for a period of one to three hours. The yields of methacrylic acid, acetic acid, and acrylic acid were determined from this liquid. The amount of methacrolein, carbon dioxide, carbon monoxide, and the other byproducts were determined from on-line analysis or the reaction product stream by gas chromatography. The stability of catalysts made with these binders is shown in FIG. 1.
Reaction SMILES: O.NN.C1(=O)[N:8]([CH2:9]/[CH:10]=[CH:11]\[CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])C(=O)C2=CC=CC=C12>C(O)C.O>[NH2:8][CH2:9]/[CH:10]=[CH:11]\[CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16]
Reactant: O=C(O)CCC/C=C\CN1C(=O)c2ccccc2C1=O
Agent: NN
Solvent: O
Solvent: CCO
Product: NC/C=C\CCCC(=O)O
Yield: 112.7 %

Procedure:
Hydrazine hydrate (0.19 ml) was added to a solution of (Z)-7-phtalimidohept-5-enoic acid (1.05 g) in ethanol (25 ml) and water (5 ml). The solution was refluxed for 3 hours and then the solvent was removed. The residue was suspended in water and the pH of the solution was adjusted to 5. The resulting precipitate was collected by filtration. The filtrate was evaporated to dryness and extracted with ethanol. The ethanol extracts were evaporated to dryness to give the title compound as an oil (0.62 g).
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:19]([NH2:21])=O)=[N:4][C:5]([C:9]2[CH:14]=[CH:13][C:12](=[O:15])[N:11]([CH:16]([CH3:18])[CH3:17])[CH:10]=2)=[CH:6][N+:7]=1[O-].P(Cl)(Cl)([Cl:24])=O.O.[OH-].[Na+]>CN(C=O)C>[NH2:1][C:2]1[C:3]([C:19]#[N:21])=[N:4][C:5]([C:9]2[CH:14]=[CH:13][C:12](=[O:15])[N:11]([CH:16]([CH3:18])[CH3:17])[CH:10]=2)=[C:6]([Cl:24])[N:7]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: CC(C)n1cc(-c2c[n+]([O-])c(N)c(C(N)=O)n2)ccc1=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)n1cc(-c2nc(C#N)c(N)nc2Cl)ccc1=O
Temperature: -30 °C
Reaction time: 1 h
Yield: 59 %

Procedure:
3-Amino-6-(1-isopropyl-6-oxo-1,6-dihydro-3-pyridyl)-2-pyrazinecarboxamide 4-oxide (29.1 g) was dissolved in DMF (290 ml). The solution was cooled to −30° C. To the cooled solution was added phosphoryl chloride (46.3 g) dropwise at −30˜−40° C. After addition of phosphoryl chloride, the temperature of the reaction mixture was raised to 40-45° C. The mixture was stirred at 40-45° C. for 1 hour. To the reaction mixture was added water (1160 ml). The suspension was stirred at 30-35° C. for 15 hours. The pH of the suspension was adjusted to 7 with 12% aq. NaOH (400 ml). The suspension was cooled to 0-5° C. and stirred at the same temperature for 2 hours. The precipitate was collected by filtration and washed with water, and dried in vacuo at 40-50° C., to give 3-amino-5-chloro-6-(1-isopropyl-6-oxo-1,6-dihydro-3-pyridyl)-2-pyrazinecarbonitrile (17.2 g).