Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([OH:12])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[OH:13][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:23]=1[N:22]=[C:21](C)[CH:20]=[CH:19]2.[NH3:25]>>[NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([O:12][CH2:6][CH2:5][CH2:4][CH:9]([CH3:8])[O:13][C:14]3[CH:15]=[CH:16][CH:17]=[C:18]4[C:23]=3[N:22]=[C:21]([NH2:25])[CH:20]=[CH:19]4)[CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: Cc1ccc2cccc(O)c2n1
Reactant: N
Reactant: Nc1ccc2cccc(O)c2n1
Product: CC(CCCOc1cccc2ccc(N)nc12)Oc1cccc2ccc(N)nc12

Procedure:
The title compound was prepared according to the procedure described in Example 86 substituting 2-aminoquinolin-8-ol for 8-hydroxyquinaldine. 1H NMR (500 MHz, CDCl3) δ ppm 7.99 (m, 2H), 7.33 (m, 3H), 7.22 (m, 2H), 7.14 (m, 2H), 7.08 (m, 1H), 4.69 (m, 1H), 4.23 (m, 2H), 1.88 (m, 4H), 1.46 (d, 3H); MS (DCI/NH3) m/z 389 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[C:5]([F:12])=[CH:4][C:3]=1[NH:13][C@H:14]1[CH2:18][CH2:17][N:16]([CH:19]2[CH2:24][CH2:23][N:22](C(OCC3C=CC=CC=3)=O)[CH2:21][CH2:20]2)[C:15]1=[O:35].[H][H]>C(O)C.[Pd]>[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[C:5]([F:12])=[CH:4][C:3]=1[NH:13][C@H:14]1[CH2:18][CH2:17][N:16]([CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[C:15]1=[O:35]
Reactant: [H][H]
Reactant: CS(=O)(=O)c1cc(F)c(N[C@H]2CCN(C3CCN(C(=O)OCc4ccccc4)CC3)C2=O)cc1F
Agent: [Pd]
Solvent: CCO
Product: CS(=O)(=O)c1cc(F)c(N[C@H]2CCN(C3CCNCC3)C2=O)cc1F
Yield: 105.9 %

Procedure:
A solution of (S)-benzyl 4-(3-(2,5-difluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (2.6 g, 5.1 mmol) in ethanol (20 mL) was hydrogenated using a double balloon of hydrogen with 10% Degussa type Pd/C (650 mg) for 18 hours. The mixture was filtered through celite and the solids were washed with MeOH (200 mL) The combined organic layers were concentrated in vacuo to yield (S)-3-(2,5-difluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (2.0 g, 5.4 mmol, >95%). Mass spectrum (apci) m/z=374.2 (M+H).
Reaction SMILES: [CH3:1][C:2]([CH3:5])([O-:4])C.[K+].[OH2:7]>CS(C)=O>[C:2]([OH:7])(=[O:4])[CH3:5].[C:2]([OH:4])(=[O:7])[CH3:1].[C:2]([OH:7])(=[O:4])[CH3:5].[CH:1]#[CH:2]
Reactant: CC(C)(C)[O-]
Reactant: O
Agent: [K+]
Solvent: CS(C)=O
Product: C#C
Product: CC(=O)O
Temperature: 50 °C
Reaction time: 0.17 h

Procedure:
Separetely, 16 g of potassium t-butoxide was dissolved in 21 ml of dry dimethyl sulfoxide (hereinafter "DMSO"), and a solution of 1.9 g of the above prepared dibromide in 5 ml of DMSO was added thereto over 10 minutes, followed by heating at 50° C. for 1 hour. The reaction mixture was poured into 100 ml of water and extracted with diethyl ether. The extract was washed successively with water and a saturated sodium chloride aqueous solution, and dried. After filtration, the filtrate was concentrated under reduced pressure to obtain 1.5 g of an acetylene triacetate compound.
Reaction SMILES: [C:1]1([CH:7]([CH:12](OS(C)(=O)=O)[CH2:13][CH2:14]CC)C=S(=O)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>CO.[Na].[Hg]>[CH3:3][CH:2]=[CH:1][CH2:7][CH2:12][CH2:13][CH3:14].[CH2:7]=[CH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCC(OS(C)(=O)=O)C(C=S(=O)=O)c1ccccc1
Agent: [Hg]
Agent: [Na]
Solvent: CO
Product: C=CCCCCC
Product: CC=CCCCC
Temperature: -30 °C
Reaction time: 8 h

Procedure:
Following the procedure of Example 1, 0.850 g of phenylethyl sulphone and 0.430 g of valeric aldehyde were condensed with n-butyl lithium. Methyl sulphonic acid chloride was then added and, after standing overnight at -30°C, the reaction mixture was treated in the usual way, giving 1.72 g of a yellow oil which was 2-phenyl sulphonyl-3-mesyloxy heptane. 282 mg of this product in solution in methanol were then reduced by the addition of 1.5 g of 6 % sodium amalgam, followed by stirring overnight at -30°C. The upper decanted layer was analysed by vapour-phase chromatography. 2-Heptene was obtained in a yield of 80 % without any traces either of 1-heptene or of 3-heptene.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[C:9]([S:11][C:12]([S:15][C:16]2[CH:21]=[C:20]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:19]([O:26][CH2:27][CH2:28][CH:29]3[CH:33]([CH2:34][CH2:35][OH:36])[O:32]C(OCC)[O:30]3)=[C:18]([C:40]([CH3:43])([CH3:42])[CH3:41])[CH:17]=2)([CH3:14])[CH3:13])[CH:8]=[C:7]([C:44]([CH3:47])([CH3:46])[CH3:45])[C:6]=1[OH:48])([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.O>CO>[C:40]([C:18]1[CH:17]=[C:16]([S:15][C:12]([S:11][C:9]2[CH:10]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[C:6]([OH:48])=[C:7]([C:44]([CH3:47])([CH3:46])[CH3:45])[CH:8]=2)([CH3:14])[CH3:13])[CH:21]=[C:20]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:19]=1[O:26][CH2:27][CH2:28][CH:29]([OH:30])[CH:33]([OH:32])[CH2:34][CH2:35][OH:36])([CH3:43])([CH3:42])[CH3:41]
Reactant: CCOC1OC(CCO)C(CCOc2c(C(C)(C)C)cc(SC(C)(C)Sc3cc(C(C)(C)C)c(O)c(C(C)(C)C)c3)cc2C(C)(C)C)O1
Solvent: CC(=O)O
Solvent: CO
Solvent: O
Product: CC(C)(Sc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1)Sc1cc(C(C)(C)C)c(OCCC(O)C(O)CCO)c(C(C)(C)C)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 59.5 %

Procedure:
2,6-Di-tert-butyl-4-[1-(3,5-di-tert-butyl-4-{2-[2-ethoxy-5-(2-hydroxy-ethyl)-[1,3]dioxo-lan-4-yl]-ethoxy}-phenylsulfanyl)-1-methyl-ethylsulfanyl]-phenol (Ex-13D, 4.0 g, 5.7 mmol) was dissolved in methanol (60 mL). Acetic acid (2.8 mL) and water (2.8 mL) were added and the resultant mixture was stirred at reflux for 3 h. The reaction mixture was concentrated under reduced pressure and the residue was diluted with water (100 mL) and extracted with dichloromethane (3×100 mL). The combined organic extracts were dried over sodium sulfate and concentrated to an off-white foam. The residue was dissolved in methanol (60 mL) and potassium carbonate (1.6 g) was added. The mixture was stirred at room temperature for 1.5 h and concentrated under reduced pressure and the residue was diluted with water (100 mL). The solution was extracted with dichloromethane (3×100 mL), dried over sodium sulfate, and concentrated to a white foam. Following silica gel chromatography (2:1 ethyl acetate:hexanes) gave 2.2 g (65%) of 6-{2,6-di-tert-butyl-4-[1-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-1-methyl-ethylsulfanyl]-phenoxy}-hexane-1,3,4-triol as a white solid, mp 75–77° C. 1H-NMR (300 MHz, CDCl3) δ7.54 (s, 2H), 7.45 (s, 2H), 5.36 (s, 1H), 3.92–3.99 (m, 4H), 3.78 (brs, 2H), 2.99 (d, 1H, J=3.8 Hz, 2.78 (d, 1H, J=3.8 Hz), 2.15 (t, 1H, J=4.6 Hz), 2.02–2.11 (m, 2H), 1.83–1.85 (m, 2H), 1.43–1.44 (m, 42H). HRMS (ESI) calcd for C37H60O5S2 (M+Na), 671.3780; found, 671.3775. Anal. calcd. for C37H60O5S2: C, 68.47, H, 9.32, S, 9.88; Found: C, 68.62, H, 9.49, S, 9.59.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[C:5]([F:15])[CH:4]=1)[CH3:2].[Cl-].[Cl-].[Cl-].[Al+3].[CH2:20]([C@H:25]1[CH2:30][CH2:29][C@H:28]([CH2:31][C:32](Cl)=[O:33])[CH2:27][CH2:26]1)[CH2:21][CH2:22][CH2:23][CH3:24].Cl>ClCCl>[CH2:20]([C@H:25]1[CH2:26][CH2:27][C@H:28]([CH2:31][C:32]([C:12]2[CH:11]=[CH:10][C:9]([C:6]3[CH:7]=[CH:8][C:3]([CH2:1][CH3:2])=[CH:4][C:5]=3[F:15])=[CH:14][CH:13]=2)=[O:33])[CH2:29][CH2:30]1)[CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: CCc1ccc(-c2ccccc2)c(F)c1
Reactant: CCCCC[C@H]1CC[C@H](CC(=O)Cl)CC1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CCCCC[C@H]1CC[C@H](CC(=O)c2ccc(-c3ccc(CC)cc3F)cc2)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
4-Ethyl-2-fluorobiphenyl (13.0 gram) was added in one portion to a stirred suspension of aluminium trichloride (9.54 gram) in dichloromethane (30 ml), followed by a solution of trans-4-n-pentylcyclohexyl acetyl chloride (15 gram) in dichloromethane (30 ml), added dropwise over 30 minutes. After stirring at room temperature for 31/2 hours, the reaction mixture was poured onto ice (250 gram) and hydrochloric acid (25 ml) and the product was extracted with 350 ml and 250 ml portions of petroleum ether (boiling point 60°-80° C.). The combined extracts were washed with water (150 ml), dried over anhydrous sodium sulphate and evaporated to dryness. The residue (26.8 gram) was crystallised from industrial methylated spirits at 0° C. to give 13.2 gram (51.5% yield) 4-(trans-4-n-pentylcyclohexylacetyl)-2'-fluoro-4'-ethylbiphenyl, melting point 72°-73° C.
Reaction SMILES: [Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13](Cl)=[O:14])=[CH:11][C:10]([C:16]([F:19])([F:18])[F:17])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[NH2:20][C:21]1[N:29]=[CH:28][CH:27]=[CH:26][C:22]=1[C:23](O)=[O:24].C(N(CC)CC)C.CS(Cl)(=O)=O>C(#N)C>[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]3[O:14][C:23](=[O:24])[C:22]4[CH:26]=[CH:27][CH:28]=[N:29][C:21]=4[N:20]=3)=[CH:11][C:10]([C:16]([F:19])([F:18])[F:17])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(Cl)c1cc(C(F)(F)F)nn1-c1ncccc1Cl
Reactant: Nc1ncccc1C(=O)O
Agent: CS(=O)(=O)Cl
Solvent: CC#N
Solvent: CCN(CC)CC
Product: O=c1oc(-c2cc(C(F)(F)F)nn2-c2ncccc2Cl)nc2ncccc12
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 65 %

Procedure:
5-Trifluoromethyl-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid chloride (example 2, step 3) (800 mg) was added to a mixture of 2-aminonicotinic acid (356 mg) in acetonitrile (20 mL). The mixture was stirred for 10 minutes at room temperature and triethylamine (360 μL) was added and stirred for 15 minutes, before a second portion of triethylamine (720 μL) was added. After the mixture was stirred for further 15 minutes at room temperature, methanesulfonyl chloride (220 μL) was added. After stirring for 1.5 hours at room temperature, the reaction was quenched with water and extracted 2× with ethyl acetate, washed with brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate=1:1, Rf=0.40) to afford 660 mg of the title compound of the formula
Reaction SMILES: [C:1]1([NH:7][C:8](=[O:14])/[CH:9]=[CH:10]\[C:11](O)=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:15](OC(=O)C)(=O)[CH3:16].C(N(CC)CC)C>CC(C)=O.O.O.O.O.C([O-])(=O)C.[Ni+2].C([O-])(=O)C>[CH:15]1[C:4]2[CH:3]=[CH:2][C:1]([N:7]3[C:8](=[O:14])[CH:9]=[CH:10][C:11]3=[O:12])=[CH:6][C:5]=2[CH:16]=1
Reactant: O=C(O)/C=C\C(=O)Nc1ccccc1
Reactant: CC(=O)OC(C)=O
Agent: [Ni+2]
Agent: CC(=O)[O-]
Solvent: O
Solvent: CC(C)=O
Solvent: CCN(CC)CC
Product: O=C1C=CC(=O)N1c1ccc2c(c1)C=C2
Temperature: 25 °C
Reaction time: 48 h

Procedure:
N-phenyl-maleamic acid (6.00 g, 27.62 mmol) was partially dissolved in about 100 ml of acetone in a 250 ml round-bottomed flask. To this stirred heterogeneous mixture was added solid nickel acetate tetrahydrate (0.25 g), followed by the mixture of acetic anhydride (6.27 g. 61.42 mmol) and triethylamine (1.82 g, 23.0 mmol). Gradually, almost all the solids dissolved and the resultant reaction mixture was stirred at room temperature for two days. After all the solvent had been removed by rotary evaporation, the residual oil (smell of acetic acid) was mixed with a small amount of methylene chloride. The solution was passed through a small column containing silica gel saturated with hexane. The column was eluted with hexane until the yellow band developed reached its bottom. Then, it was eluted with methylene chloride. The second yellow fraction collected was then subjected to rotary evaporation and hexane was then added slowly to the concentrated solution to precipitate the product as a yellow solid. The product was collected, washed with hexane and air-dried overnight. Yield: 4.34 g (78.9%). Anal Calc. for C12H9NO2 : C, 72.35; H, 4.55; N, 7.03. Found: C, 71.84; H, 4.54; N, 6.90. Mass Spectroscopy: M+ , 199 (100%). Proton NMR (CDCl3),δ(ppm): 3.23 (singlet, 4H, alicyclic protons); 6.87 (singlet, 2H, olefinic protons); 7.03-7.33 (complex, 3H, aromatic protons). IR (KBr): ν(maleimide): 1710 cm-1, vs; 1772 cm-1, W.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([Cl:9])[C:3]=1[NH2:4].[C:10]([N:13]1[C:17]([NH2:18])=[N:16][C:15]([S:19](Cl)(=[O:21])=[O:20])=[N:14]1)(=[O:12])[CH3:11]>N1C=CC=CC=1>[C:10]([N:13]1[C:17]([NH2:18])=[N:16][C:15]([S:19]([NH:4][C:3]2[C:2]([Cl:1])=[CH:8][CH:7]=[CH:6][C:5]=2[Cl:9])(=[O:20])=[O:21])=[N:14]1)(=[O:12])[CH3:11]
Reactant: Nc1c(Cl)cccc1Cl
Reactant: CC(=O)n1nc(S(=O)(=O)Cl)nc1N
Solvent: c1ccncc1
Product: CC(=O)n1nc(S(=O)(=O)Nc2c(Cl)cccc2Cl)nc1N
Temperature: 60 °C
Reaction time: 12 h

Procedure:
42.63 g (0.26 mol) 2,6-dichloroaniline in 350 ml pyridine was treated with 54 g (0.24 mol) of 1-acetyl-5-amino-1,2,4-triazole-3-sulphonyl chloride and stirred at 60° C. for 12 hours. After cooling, the crystals were separated, washed with a small amount of pyridine and ether and dried in vacuo.
Reaction SMILES: C[Si](C)(C)[N-][Si](C)(C)C.[K+].C1COCC1.[CH3:16][O:17][C:18]1[CH:35]=[CH:34][C:21]([CH2:22][O:23][C:24]2[CH:29]=[CH:28][C:27]([C:30](=[O:33])[CH2:31][CH3:32])=[CH:26][CH:25]=2)=[CH:20][CH:19]=1.[C:36]([Si:40]([CH3:43])([CH3:42])Cl)([CH3:39])([CH3:38])[CH3:37]>O>[C:36]([Si:40]([O:33]/[C:30](/[C:27]1[CH:28]=[CH:29][C:24]([O:23][CH2:22][C:21]2[CH:34]=[CH:35][C:18]([O:17][CH3:16])=[CH:19][CH:20]=2)=[CH:25][CH:26]=1)=[CH:31]\[CH3:32])([CH3:43])[CH3:42])([CH3:39])([CH3:38])[CH3:37]
Reactant: CCC(=O)c1ccc(OCc2ccc(OC)cc2)cc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: C/C=C(\O[Si](C)(C)C(C)(C)C)c1ccc(OCc2ccc(OC)cc2)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 95 %

Procedure:
With cooling with ice, potassium hexamethyldisilazide (0.5 M toluene solution, 89 mL) was dropwise added to a stirring THF (100 mL) solution of the compound (10.0 g, 37.0 mmol) synthesized in the above (1) and t-butyldimethylchlorosilane (6.13 g, 40.7 mmol), and then the reaction solution was stirred at room temperature for 12 hours. The reaction solution was poured into water, extracted with ethyl acetate, the organic layer was washed with saturated saline, and dried with magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel flash column chromatography (hexane) to obtain the entitled compound (13.5 g, 95%) as a white solid.
Reaction SMILES: [F:1][C:2]([F:9])([C:5]([F:8])([F:7])[F:6])[CH2:3][OH:4].N1C=CC=CC=1.[S:16](Cl)([C:19]1[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=1)(=[O:18])=[O:17].C([O-])([O-])=O.[K+].[K+]>C(Cl)(Cl)Cl>[S:16]([C:19]1[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=1)([O:4][CH2:3][C:2]([F:9])([F:1])[C:5]([F:8])([F:7])[F:6])(=[O:18])=[O:17]
Reactant: OCC(F)(F)C(F)(F)F
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OCC(F)(F)C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 83.6 %

Procedure:
To a solution of 2,2,3,3,3-pentafluoropropanol (5.0 mL, 50 mmol) and pyridine (8.1 mL, 100 mmol) in chloroform (100 mL), cooled at 0° C. and under argon, tosyl chloride (14.29 g, 75 mmol) was slowly added. The resulting mixture was allowed to warm up to room temperature and was stirred at this temperature overnight. Then, 10% aqueous K2CO3 solution was added and the mixture was vigorously stirred for 30 min. The layers were separated, and the organic layer was treated again with K2CO3. After that, it was washed with 2 N HCl, dried over Na2SO4 and the solvent was removed, yielding 12.72 g of the desired compound (84% yield).
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[N:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:13]=1.CO.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl>[CH2:22]([O:21][C:19](=[O:20])[CH2:18][C:14]1[CH:13]=[N+:12]([O-:9])[CH:17]=[CH:16][CH:15]=1)[CH3:23]
Reactant: CCOC(=O)Cc1cccnc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: ClC(Cl)Cl
Product: CCOC(=O)Cc1ccc[n+]([O-])c1
Temperature: 25 °C
Reaction time: 5 h
Yield: 124.9 %

Procedure:
m-Chloro perbenzoic acid (6.2 g, 36.06 mmol) in CHCl3 (30 mL) was added drop wise to a solution of ethyl 2-(pyridin-3-yl)acetate (3.5 g, 21.21 mmol) in CHCl3 (30 mL) at room temperature under nitrogen atmosphere and the resulting reaction mass was stirred at room temperature for 5 hours. The reaction was monitored by TLC (10% methanol in chloroform). The reaction mass was basified using aqueous NaHCO3 solution to pH 7 and extracted using CHCl3. The organic layer was dried over sodium sulphate and concentrated under reduced pressure to afford 4.8 g of the crude product. LCMS: 60.09%, m/z=182.0 (M+1)
Reaction SMILES: I[C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[CH:3]=1.[N:13]1[CH:18]=[CH:17][CH:16]=[C:15](B(O)O)[CH:14]=1.N>>[N:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[C:4]1[CH:3]=[C:2]([C:15]2[CH:14]=[N:13][CH:18]=[CH:17][CH:16]=2)[O:6][N:5]=1
Reactant: Ic1cc(-c2ccccn2)no1
Reactant: OB(O)c1cccnc1
Agent: N
Product: c1ccc(-c2cc(-c3cccnc3)on2)nc1

Procedure:
The titled compound was prepared as the bishydrochloride salt according to Method CC using 5-iodo-3-(pyridin-2-yl)isoxazole [prepared as described by Ku, Y.-Y.; Grieme, T.; Sharma, P.; Pu, Y.-M.; Raje, P.; Morton, H.; King, S. Org. Lett. 2001, 3, 4185-4187] (136 mg, 0.5 mmol) and pyridin-3-ylboronic acid (Aldrich, 92 mg, 0.750 mmol). 1H NMR (300 MHz, DMSO-d6) d ppm 7.52-7.64 (m, 1H), 7.75-7.83 (m, 1H), 7.86 (s, 1H), 8.03 (td, J=7.7, 1.6 Hz, 1H), 8.11 (dt, J=7.9, 1.2 Hz, 1 H), 8.58 (dt, J=8.0, 1.9 Hz, 1H), 8.75-8.79 (m, 1H), 8.81 (dd, J=5.2, 1.6 Hz, 1H), 9.32 (d, J=2.4 Hz, 1H) ppm; MS (DCI/NH3) m/z 224 (M+H)+.
Reaction SMILES: [Na].[C:2]([O:8]CC)(=O)[CH2:3][C:4]([CH3:6])=O.Cl.[C:12]([NH2:15])(=[NH:14])[CH3:13].Cl>C(O)C>[CH3:13][C:12]1[N:15]=[C:2]([OH:8])[CH:3]=[C:4]([CH3:6])[N:14]=1
Reactant: CC(=N)N
Reactant: CCOC(=O)CC(C)=O
Agent: Cl
Agent: [Na]
Solvent: CCO
Product: Cc1cc(O)nc(C)n1
Temperature: 25 °C

Procedure:
Sodium (3.6 g) was added by portions to ethanol (92 ml) over 2 hours, while the solution was stirred at room temperature. Thereafter, ethyl acetoacetate (10 ml) and acetamidine hydrochloride (7.42 g) were added to the reaction solution, and the obtained mixture was stirred at 70° C. for 16 hours. Thereafter, the reaction mixture was stirred at 100° C. for 9 hours, and the temperature of the reaction solution was returned to room temperature. Concentrated hydrochloric acid was added to the reaction solution, so that the pH value was adjusted to around 5. The obtained mixture was concentrated under reduced pressure, so as to obtain a crude title compound (25.6 g).
Reaction SMILES: CCOCC.[CH3:6][C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][C:8]=1[OH:14].[N+:15]([O-])([OH:17])=[O:16]>O>[CH3:13][C:10]1[C:9]([N+:15]([O-:17])=[O:16])=[C:8]([OH:14])[C:7]([CH3:6])=[CH:12][CH:11]=1
Reactant: O=[N+]([O-])O
Reactant: Cc1ccc(C)c(O)c1
Solvent: O
Solvent: CCOCC
Product: Cc1ccc(C)c([N+](=O)[O-])c1O
Temperature: 25 °C

Procedure:
To a stirred mixture of 130 ml of water, 130 ml of ether and 10.0 g of 2,5-dimethylphenol was added dropwise 5.2 ml of 70% nitric acid while cooling with ice. The temperature of the mixture was raised to room temperature and the reaction was continued for a day. After 500 ml of water was added, the reaction mixture was extracted with 500 ml of ethyl acetate, washed with water and a brine successively, and dried with anhydrous sodium sulfate. The drying agent was filtered off and the solvent was distilled away under reduced pressure. The residue was purified by subjecting to silica-gel column-chromatography [eluent:chloroform] to give 3.83 g of 3,6-dimethyl-2-nitrophenol.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]=[CH2:10].[I-:11].[Na+].O>CC(C)=O>[I:11][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]=[CH2:10]
Reactant: [I-]
Reactant: C=Cc1ccccc1CCl
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: C=Cc1ccccc1CI
Yield: 95 %

Procedure:
Dissolve 1-chloromethyl-2-vinyl-benzene (4.0 g, 26 mmol) in acetone (100 mL) and add sodium iodide (4.5 g, 30 mmol). Heat at gentle reflux for 30 minutes. Cool, add water (150 mL) and extract with pentane (200 mL). Dry (MgSO4) and evaporate the solvent in vacuo to give the title compound (95%).
Reaction SMILES: [OH:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([C:9]([CH3:25])([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:10][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:12])=[CH:4][CH:3]=1.[CH2:26]([N:28]([CH2:33][CH3:34])[CH:29]([Cl:32])[CH2:30][CH3:31])[CH3:27].[NH2-].[Na+]>C1(C)C=CC=CC=1>[ClH:32].[CH2:26]([N:28]([CH2:29][CH2:30][CH2:31][O:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([C:9]([CH3:25])([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:10][C:11]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:12])=[CH:4][CH:3]=1)[CH2:33][CH3:34])[CH3:27]
Reactant: Cc1cc(C(C)(CC(=O)c2ccccc2)c2ccccc2)ccc1O
Reactant: CCC(Cl)N(CC)CC
Agent: [NH2-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CCN(CC)CCCOc1ccc(C(C)(CC(=O)c2ccccc2)c2ccccc2)cc1C
Product: Cl
Reaction time: 48 h

Procedure:
Fifty-three grams of 4-hydroxy-3,5-dimethyl-β,β-diphenylpropiophenone (prepared as in Example 5) are dissolved in 300 mls of dry toluene. Thirty-eight and four-tenths grams (100% excess) of 1-diethylamino-propylchloride, dissolved in 100 mls of toluene, are added to this solution dropwise. At that time, 13.8 grams sodium amide, 50% in toluene suspension, are added dropwise with stirring. This mixture is boiled for two days under reflux. The precipitate is filtered and the toluene is evaporated in vacuo. The residue is taken up in ether and washed several times with water. After drying with sodium sulfate, the hydrochloride is precipitated with ethereal hydrochloric acid and it is filtered over active carbon and recrystallized from acetone/ether. 4-[3-(N,N-diethylamino)-propoxy]-3,5-dimethyl-β,β-diphenylpropiophenone hydrochloride (Melting point = 179° C.) is obtained.
Reaction SMILES: I(O)(=O)(=O)=O.C[S:7]([C:9]1[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=1[C:11]([NH2:13])=[O:12])=O.S(Cl)(Cl)=O>>[S:7]1[C:9]2[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=2[C:11](=[O:12])[NH:13]1
Reactant: CS(=O)c1ccccc1C(N)=O
Agent: [O-][I+3]([O-])([O-])O
Solvent: O=S(Cl)Cl
Product: O=c1[nH]sc2ccccc12

Procedure:
In this method, 2-(methylthio)benzamide is produced from 2-(methylthio)benzoyl chloride; oxidized with periodic acid to 2-(methylsulfinyl)benzamide; and cyclized in the presence of thionyl chloride to yield a 1,2-benzisothiazol-3-one. ##STR1## (B) Org. Prep. Proced. Int., 15, 315-319(1983)
Reaction SMILES: Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[CH:15]=[C:16]([C:20]2[C:24]([Br:25])=[CH:23][N:22]([CH3:26])[N:21]=2)[CH:17]=[CH:18][CH:19]=1.C(N(CC)CC)C.[F:34][C:35]([F:46])([F:45])[O:36][C:37]1[CH:44]=[CH:43][C:40]([CH2:41][NH2:42])=[CH:39][CH:38]=1>C(Cl)Cl>[Br:25][C:24]1[C:20]([C:16]2[CH:15]=[C:14]([NH:13][C:2]([NH:42][CH2:41][C:40]3[CH:43]=[CH:44][C:37]([O:36][C:35]([F:45])([F:46])[F:34])=[CH:38][CH:39]=3)=[O:4])[CH:19]=[CH:18][CH:17]=2)=[N:21][N:22]([CH3:26])[CH:23]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: NCc1ccc(OC(F)(F)F)cc1
Reactant: Cn1cc(Br)c(-c2cccc(N)c2)n1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cn1cc(Br)c(-c2cccc(NC(=O)NCc3ccc(OC(F)(F)F)cc3)c2)n1
Reaction time: 1 h
Yield: 202.4 %

Procedure:
To a stirred solution of triphosgene (12 mg, 0.04 mmol) in CH2Cl2 (0.5 mL) was added dropwise a solution of 3-(3-aminophenyl)4-bromo-1-methylpyrazole (30 mg, 0.12 mmol) and triethylamine (33 μL, 0.24 mmol) in CH2Cl2 (0.5 mL). After 1 h, 4-(trifluoromethoxy)benzylamine (23 mg, 0.12 mmol) was added. The reaction mixture was stirred for 16 h and concentrated. Chromatography on flash silica (75% EtOAc/hexane) gave the title compound as a colourless solid (38 mg, 68%), m.p. 144.6-145.8° C. (EtOAc/hexane).