Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2](N(C)C)=[O:3].C1(C)C=CC=CC=1.[OH:14][CH2:15][C:16]([CH2:21][OH:22])([CH2:19][OH:20])[CH2:17]O.[C:23]1([C:31]2[CH:36]=[CH:35]C=[CH:33][CH:32]=2)[C:24](C=O)=[CH:25][CH:26]=[CH:27][CH:28]=1>O>[C:31]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:32]=[CH:33][C:1]([CH:2]2[O:3][CH2:17][C:16]([CH2:21][OH:22])([CH2:19][OH:20])[CH2:15][O:14]2)=[CH:35][CH:36]=1
Reactant: OCC(CO)(CO)CO
Reactant: CC(=O)N(C)C
Reactant: O=Cc1ccccc1-c1ccccc1
Solvent: O
Solvent: Cc1ccccc1
Product: OCC1(CO)COC(c2ccc(-c3ccccc3)cc2)OC1
Temperature: 100 °C
Yield: 90 %

Procedure:
A 5,000 ml flask was charged with 2,000 ml of DMAc, 1,400 ml of toluene, 200 g (1.47 mol) of pentaerythritol, 134 g (0.74 mol) of biphenylaldehyde and 20 g of paratoluenesulfonic acid dihydrate, and the mixture was stirred at 100° C. Then, it heated up to 145° C. A distillate containing water was separated, and the reaction was finished in a reaction time of 5 hours. 5 L of water was put into the reaction liquid, and white crystals were deposited. They were filtrated, washed with water and then concentrated to thereby obtain white crystals (yield: 90%). It was identified from chemical shift values of 1H-NMR that the compound obtained in the present example was the same compound as the compound obtained in Example 1.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[N:12]3[N:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[N:16][C:11]3=[N:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[N:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:21]1[CH:26]=[CH:25][C:24]([C:2]2[CH:3]=[C:4]([C:8]3[N:12]4[N:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[N:16][C:11]4=[N:10][CH:9]=3)[CH:5]=[CH:6][CH:7]=2)=[CH:23][CH:22]=1
Reactant: FC(F)(F)c1cnn2c(-c3cccc(Br)c3)cnc2n1
Reactant: OB(O)c1ccncc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: COCCOC
Product: FC(F)(F)c1cnn2c(-c3cccc(-c4ccncc4)c3)cnc2n1
Temperature: 65 °C
Reaction time: 12 h
Yield: 44.9 %

Procedure:
A mixture of 7-(3-bromophenyl)-3-trifluoromethylimidazo[1,2-b][1,2,4]triazine (21 mg, 0.06 mmol), 4-pyridylboronic acid (11 mg, 0.09 mmol) and 2 M Na2CO3 (0.09 ml) in 1,2-dimethoxyethane (1.5 ml) was degassed with a stream of nitrogen for 10 min. Tetrakis(triphenylphosphine)palladium(0) (4 mg, 0.003 mmol) was added and the mixture was stirred under nitrogen at 65° C. for 12 h. After allowing to cool to room temperature, the mixture was diluted with ethyl acetate and partitioned between water (20 ml) and ethyl acetate (30 ml). The organic extracts were dried (MgSO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 5% MeOH/CH2Cl2) and triturated with diethyl ether to give 9.2 mg (44%) of the title compound: 1H NMR (400 MHz, CDCl3) δ 7.58 (2H, m), 7.70 (1H, t, J 7.3 Hz), 7.74-7.77 (1H, m), 8.13 (1H, dt, J 7.3, 1.6 Hz), 8.39 (1H, t, J 1.6 Hz), 8.68 (1H, s), 8.72 (2H, m), 8.83 (1H, s); MS (ES+) m/z 342 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.[CH2:21]([O:23][C:24]1[CH:29]=[CH:28][C:27]([N:30]=[C:31]=[O:32])=[CH:26][CH:25]=1)[CH3:22]>CN(C=O)C>[CH2:21]([O:23][C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31]([N:18]2[CH2:19][CH2:20][CH:15]([C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][N:7]=3)[CH2:16][CH2:17]2)=[O:32])=[CH:26][CH:25]=1)[CH3:22]
Reactant: CCOc1ccc(N=C=O)cc1
Reactant: COc1cc2ncnc(C3CCNCC3)c2cc1OC
Solvent: CN(C)C=O
Product: CCOc1ccc(NC(=O)N2CCC(c3ncnc4cc(OC)c(OC)cc34)CC2)cc1
Yield: 20.2 %

Procedure:
A solution of 6,7-dimethoxy-4-piperidin-4-yl-quinazoline (30 mg, 0.110 mmol), as prepared in Example 1d, in DMF (1 mL) was treated with 1-ethoxy-4-isocyanato-benzene (26.8 mg, 0.164 mmol) at RT overnight. The reaction was then partitioned between EtOAc (10 mL) and H2O (10 mL). The organic phase was dried over Na2SO4 and concentrated in vacuo. Purification by prep tlc (1:9 MeOH/DCM) afforded the title compound as a light brown solid (9.7 mg, 20%). 1H NMR (300 MHz, CDCl3) δ 9.09 (s, 1H), 7.41 (m, 1H), 7.26 (m, 3H), 6.87 (m, 2H), 6.29 (br s, NH), 4.30-4.25 (m, 2H), 4.08 (s, 6H), 4.01 (q, 2H), 3.61 (m, 1H), 3.17 (m, 2H), 2.17 (m, 2H), 2.02-2.01 (m, 2H), 1.40 (t, 3H); LC/MS (ESI): calcd mass 436.2, found 437.3 [M+1]+.
Reaction SMILES: Cl[C:2]1[C:3](=[O:12])[N:4]([CH3:11])[N:5]=[CH:6][C:7]=1[N:8]([CH3:10])[CH3:9].[CH:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1B(O)O)=[O:14].C([O-])([O-])=O.[Na+].[Na+].C(Cl)(Cl)Cl.CC(C)=O>C(COC)OC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:9][N:8]([CH3:10])[C:7]1[CH:6]=[N:5][N:4]([CH3:11])[C:3](=[O:12])[C:2]=1[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[CH:13]=[O:14]
Reactant: O=Cc1ccccc1B(O)O
Reactant: CN(C)c1cnn(C)c(=O)c1Cl
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: CC(C)=O
Solvent: ClC(Cl)Cl
Product: CN(C)c1cnn(C)c(=O)c1-c1ccccc1C=O
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
4-Chloro-5-(dimethylamino)-2-methylpyridazin-3(2H)-one (50.00 mmol) was dissolved in dimethoxyethane (155 ml), and Pd(PPh3)4 (1.60 g, 1.38 mmol) was added under argon. After stirring at room temperature for 10 min, 2-formylbenzeneboronic acid (10.50 g, 70.00 mmol) and 2M Na2CO3 solution (49.5 ml) were added. Subsequently, the reaction mixture was refluxed (oil bath temperature: 110° C.) for 15 h. The reaction was followed by TLC (eluent: chloroform:acetone (9:1)). Upon cooling the reaction mixture was poured onto ice (375 g), filtered over Celite and washed with chloroform (130 ml). The two layers were separated and the aqueous phase was extracted with chloroform (3×380 ml). The combined organic layers were washed with water (1×100 ml), dried over MgSO4, filtered and purified by flash column chromatography with a mixture of diisopropyl ether and acetone (8:1) as the eluent and crystallized from a mixture of ethyl acetate and hexane (2.3:1).
Reaction SMILES: Cl[C:2]1[C:6]2[CH:7]=[C:8]([N:11]3[C:16](=[O:17])[CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[N:13]([CH3:22])[C:12]3=[O:23])[CH:9]=[CH:10][C:5]=2[S:4][N:3]=1.[C:24](#[N:28])[CH2:25][C:26]#[N:27].C(N(CC)CC)C.Cl>CS(C)=O.O.[Cl-].[Na+].O>[CH3:22][N:13]1[C:14]([C:18]([F:21])([F:20])[F:19])=[CH:15][C:16](=[O:17])[N:11]([C:8]2[CH:9]=[CH:10][C:5]3[S:4][N:3]=[C:2]([CH:25]([C:24]#[N:28])[C:26]#[N:27])[C:6]=3[CH:7]=2)[C:12]1=[O:23]
Reactant: Cn1c(C(F)(F)F)cc(=O)n(-c2ccc3snc(Cl)c3c2)c1=O
Reactant: N#CCC#N
Agent: Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Solvent: CCN(CC)CC
Product: Cn1c(C(F)(F)F)cc(=O)n(-c2ccc3snc(C(C#N)C#N)c3c2)c1=O
Temperature: 60 °C
Reaction time: 0.25 h

Procedure:
A mixture of 3-(3-chloro-1,2-benzisothiazol-5-yl)-1-methyl-6-(trifluoromethyl)-2,4(1H,3H)-pyrimidinedione (0.500 g), malononitrile (0.270 g) and triethylamine (1.50 g) in methyl sulfoxide is stirred at 60° C. for 15 minutes, cooled to room temperature, and diluted with water. The resultant aqueous mixture is extracted with ethyl acetate. The organic extract is washed with water, dried over anhydrous magnesium sulfate, and concentrated in vacuo to obtain a brown oil. The extracted aqueous phase is diluted with brine, acidified with concentrated hydrochloric acid, and extracted with ethyl acetate. The organic extract is dried over anhydrous magnesium sulfate and concentrated in vacuo to obtain a brown oil. Flash column chromatography of the combined oils using silica gel and an ethyl acetate/hexanes/methanol/acetic acid solution (10:10:4:1) gives the title product as an oil which is identified by NMR spectral analyses.
Reaction SMILES: [OH-].[Na+].C[O:4][C:5]([C:7]1[C:15]2[S:14][CH:13]=[N:12][C:11]=2[CH:10]=[CH:9][CH:8]=1)=[O:6].C1COCC1.O>CO>[S:14]1[C:15]2[C:7]([C:5]([OH:6])=[O:4])=[CH:8][CH:9]=[CH:10][C:11]=2[N:12]=[CH:13]1
Reactant: COC(=O)c1cccc2ncsc12
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1cccc2ncsc12
Reaction time: 4 h

Procedure:
At 0° C. an aqueous NaOH solution (50%, 6.0 mL) is added to a solution of benzothiazole-7-carboxylic acid methyl ester in a mixture of MeOH (39 mL), THF (11.7 mL) and water (3.0 mL). The mixture is stirred for 4 h and concentrated in vacuo. At 0° C. water (60 mL) is added and the mixture is made acidic (pH 5) by addition of conc. hydrochloric acid. After 30 min the precipitate is filtered off, washed with water and dried in vacuo to give the desired product. LC-MS: tR=0.77 min; [M+CH3CN+H]+=221.1.
Reaction SMILES: [C:1]1([C:7]2[CH:16]=[CH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C(O)(=O)C.C(OCC)(=O)C>[C:1]1([CH:7]2[CH2:16][CH2:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[NH:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: c1ccc(-c2ccc3ccccc3n2)cc1
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: c1ccc(C2CCc3ccccc3N2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 97.5 %

Procedure:
A solution of 2-phenylquinoline, (0.248 g, 1.21 mmol) [Aldrich, cat. #299650] in acetic acid (6.0 mL) was treated with borane-pyridine complex (0.605 mL, 5.99 mmol) and stirred at room temperature for 18 h. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with 3 M sodium hydroxide solution (70 mL), water (20 mL), and brine (20 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated to give a crude oil. Purification by flash column chromatography (100% hexanes to 25% ethyl acetate/hexanes) gave the desired product (0.247 g, 98%) as a racemic mixture. LCMS calculated for C15H16N (M+H)+: m/z=210.1. found: 210.1.
Reaction SMILES: [C:1]([OH:6])(=[O:5])[C:2]([CH3:4])=[CH2:3].C[O:8][C:9]1C=CC(O)=C[CH:10]=1.C1OC1>[Cr]>[OH:8][CH2:9][CH2:10][O:5][C:1](=[O:6])[C:2]([CH3:4])=[CH2:3]
Reactant: COc1ccc(O)cc1
Reactant: C=C(C)C(=O)O
Agent: [Cr]
Solvent: C1CO1
Product: C=C(C)C(=O)OCCO
Temperature: 80 °C

Procedure:
Following the procedure according to U.S. Pat. No. 3,875,211, 60 parts by weight of methacrylic acid, 0.16 parts by weight of hydroquinone monomethyl ether (MEHQ), and 0.24 parts by weight of chromium silicylate were placed in an autoclave under nitrogen atmosphere. 36 Parts by weight of ethylene oxide were added in the gas phase. The contents of the autoclave were heated to 80° C. for three hours. Ethylene oxide was removed under vacuum and the reaction mixture cooled to ambient temperature. The reaction mixture was then distilled under vacuum at 60° C. to obtain a 2-hydroxyethylmethacrylate-rich solution with a characteristic composition according to Table 3. There was a clear correlation between the purity of the methacrylic acid used and the optical properties of the hydroxyester as well as the diester content. This is relevant for the further processing of the hydroxyester, for example polymerisation for biomedical products, such as soft, oxygen-permeable contact lenses.
Reaction SMILES: [CH2:1]([C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].Cl[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N+:21]([O-:23])=[O:22].[H-].[Na+].[C:26]([OH:29])(=O)[CH3:27]>C1COCC1>[CH2:1]([C:7]1[CH:8]=[CH:9][C:10]([O:13][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[N+:21]([O-:23])=[O:22])=[CH:11][CH:12]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[CH2:1]([C:7]1[CH:12]=[CH:11][C:10]([O:29][C:26]2[CH:27]=[CH:3][C:2]([CH2:15][CH2:20][CH2:19][CH2:18][CH2:17][CH3:16])=[CH:1][CH:7]=2)=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CC(=O)O
Reactant: O=[N+]([O-])c1ccccc1Cl
Reactant: CCCCCCc1ccc(O)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCCCCc1ccc(Oc2ccc(CCCCCC)cc2)cc1
Product: CCCCCCc1ccc(Oc2ccccc2[N+](=O)[O-])cc1
Yield: 34 %

Procedure:
The plasticizer 2-nitrophenyl 4-hexylphenyl ether (NPHPE) is synthesized by reacting p-hexylphenol (available from Kodak Lab. Chem., catalog No. 14,319) with 2-chloronitrobenzene (available from Aldrich Chem. Co., catalog No. C5,910-6). 1.44 g (0.06 mol) of sodium hydride is suspended in 75 ml of THF under N2. 9.01 g (0.05 mol) of p-hexylphenol are dissolved in 25 ml of THF and added dropwise to the suspension. 7.86 (0.05 mol) of 2-chloronitrobenzene are dissolved in 25 ml of THF and added dropwise to the reaction mixture; the resultant mixture is refluxed for 88 hours. Following reflux 3 ml of acetic acid are added, and the reaction is filtered through filter cel, concentrated, chromatographed twice on silical gel, and Kugelrohr distilled at 0.01 mm Hg, 140°-150° C., to yield 4.7 g (34% yield) of 2-nitrophenl 4-hexylphenyl ether as an orange oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Br[CH2:12][C:13]1[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=1[C:15]#[N:16].O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[O:8][CH2:12][C:13]1[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=1[C:15]#[N:16]
Reactant: N#Cc1ccccc1CBr
Reactant: Oc1cccc(Cl)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: N#Cc1ccccc1COc1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.4 %

Procedure:
A solution of 3-chlorophenol (9.26 g) in DMF (25 ml) was added dropwise to a stirred suspension of sodium hydride (1.44 g) in DMF (50 ml) (effervescence) and the resulting mixture was stirred at room temperature for 1 hour. A solution of 2-(bromomethyl)benzonitrile (11.76 g) in DMF (25 ml) was then added to the stirred reaction mixture and after a further hour at room temperature the mixture was poured into water and extracted with ether. The extracts were washed successively with water, dilute aqueous sodium hydroxide and brine, then dried and concentrated to give crude 2-(3-chlorophenoxymethyl)-benzonitrile (13.95 g) as an orange-brown oil which crystallised on standing. An analytical sample, recrystallised from petrol, had m.p. 56° C.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:17]2[CH:21]=[CH:20][O:19][C:18]=2[CH3:22])O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:17]2[CH:21]=[CH:20][O:19][C:18]=2[CH3:22])[CH:5]=[CH:4][N:3]=1
Reactant: Cc1occc1B1OC(C)(C)C(C)(C)O1
Reactant: Clc1ccnc(Cl)n1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: Cc1occc1-c1ccnc(Cl)n1
Temperature: 25 °C
Yield: 52.5 %

Procedure:
2,4-Dichloropyrimidine (1.0 g, 6.71 mmol), 4,4,5,5-tetramethyl-2-(2-methyl-3-furanyl)-1,3,2-dioxaborolane (1.397 g, 6.71 mmol), sodium carbonate (1.067 g, 10.07 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.388 g, 0.336 mmol) were added together in 1,4-dioxane (42 mL) and water (7.00 mL) and the resulting mixture was heated at 85° C. under argon for 4 hours. The reaction mixture was allowed to cool to room temperature, diluted with water and extracted with ethyl acetate (×3). The ethyl acetate layers were combined, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by Biotage SP4 column chromatography eluting with a gradient of 0-30% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure to give the title compound (686 mg, 3.52 mmol, 52.5 yield) as a white solid. LC/MS [M+H]+=195/197.
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8]([C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)[CH:7]=[CH:6][C:3]=1[CH:4]=O.[C:15]([C:18]1[CH:26]=[CH:25][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=1)(=[O:17])[CH3:16]>>[F:1][C:2]1[CH:9]=[C:8]([C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)[CH:7]=[CH:6][C:3]=1/[CH:4]=[CH:16]/[C:15]([C:18]1[CH:26]=[CH:25][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=1)=[O:17]
Reactant: CC(=O)c1ccc(C(=O)O)cc1
Reactant: O=Cc1ccc(-c2cccs2)cc1F
Product: O=C(O)c1ccc(C(=O)/C=C/c2ccc(-c3cccs3)cc2F)cc1
Yield: 71 %

Procedure:
The title compound was prepared by condensing 2-fluoro-4-thiophen-2-yl-benzaldehyde (Ex-30A) and 4-acetylbezoic acid in a similar manner as described in Ex-3. Yellow solid, 71% yield, m.p.>260° C. 1H-NMR (300 MHz, d6-DMSO): 8.19 (d, 2H, J=8.4 Hz), 8.12 (d, 1H, J=8 Hz), 8.06 (d, 2H, J=8 Hz), 7.95 (d, 1H, J=16 Hz), 7.80 (d, 1H, J=16 Hz), 7.71 (d, 1H, J=3.5 Hz), 7.62 (m, 2H), 7.56 (d, 1H, J=8 Hz), 7.15 (m, 1H). MS m/z=352 ([M]+, 100%). HRMS (EI) Calcd. for C20H13NO3S: 352.0569. Found: 352.0560.
Reaction SMILES: [CH2:1]([Mg]Br)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].C(OC(=O)[O:17][CH2:18][CH3:19])C.[CH2:21]([Mg]Br)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34].Cl>C(OCC)C>[CH2:1]([C:18]([CH2:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9])([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[OH:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCOC(=O)OCC
Reactant: CCCCCCCCCC[Mg]Br
Reactant: CCCCCCCCCCCCCC[Mg]Br
Agent: Cl
Solvent: CCOCC
Product: CCCCCCCCCCCCCCC(O)(CCCCCCCCCC)CCCCCCCCCC
Temperature: 30 °C
Reaction time: 1 h

Procedure:
Decylmagnesium bromide (0.66 mole) in ethyl ether is slowly added to 0.33 moles of diethylcarbonate in 100 ml ethyl ether and stirred for one hour at 30° C. (nitrogen atmosphere). Tetradecylmagnesium bromide (0.33 moles) is slowly added to the solution and stirred for one hour at 30° C. The mixture is then slowly poured into 600 ml of a cold 10% HCl solution. The organic layer is dried with magnesium sulfate and the ethyl ether evaporated off to give di-n-decyl-n-tetradecylcarbinol.
Reaction SMILES: C(N[C:6]1[S:7][C:8]2[CH:14]=[C:13]([O:15][S:16]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)(=[O:18])=[O:17])[CH:12]=[CH:11][C:9]=2[N:10]=1)(=O)CC.[NH2:26]C1SC2C=C(OS(C3C=CC(F)=CC=3)(=O)=O)C=CC=2N=1.[C:47]([OH:51])(=O)[CH2:48][CH3:49]>>[C:47]([C:6]1[S:7][C:8]2[CH:14]=[C:13]([O:15][S:16]([C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)(=[O:17])=[O:18])[CH:12]=[C:11]([NH2:26])[C:9]=2[N:10]=1)(=[O:51])[CH2:48][CH3:49]
Reactant: Nc1nc2ccc(OS(=O)(=O)c3ccc(F)cc3)cc2s1
Reactant: CCC(=O)O
Reactant: CCC(=O)Nc1nc2ccc(OS(=O)(=O)c3ccc(F)cc3)cc2s1
Product: CCC(=O)c1nc2c(N)cc(OS(=O)(=O)c3ccc(F)cc3)cc2s1
Yield: 93 %

Procedure:
According to the method of intermediate 46, 4-fluorobenzenesulfonic acid 2-propionylaminobenzothiazol-6-yl ester is prepared via the action of 4-fluorobenzenesulfonic acid 2-aminobenzothiazol-6-yl ester (intermediate 16, brevetbenzothiazole_V2) with propionic acid. The product, 0.397 g, is obtained in a yield of 93%.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.F[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[N+:22]([C:19]1[CH:20]=[CH:21][C:16]([O:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:7]=2)=[CH:17][CH:18]=1)([O-:24])=[O:23]
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: CCOC(=O)CCc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCc1ccc(Oc2ccc([N+](=O)[O-])cc2)cc1
Temperature: 80 °C
Reaction time: 1 h

Procedure:
To a solution of ethyl 3-(4-hydroxyphenyl)-propionate (6.00 g, 30.9 mmol) in DMF (60 mL) were added 4-fluoronitrobenzene (6.54 g, 46.3 mmol) and potassium carbonate (5.12 g, 37.1 mmol). The resulting reaction solution was stirred for 1 hour at 80° C. To the reaction solution was added water and extracted with ethyl acetate. The resulting ethyl acetate layer was washed with water and then with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1), to thereby yield 9.64 g of the title compound.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[C:12]([F:29])=[C:13]([NH:17][S:18]([C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])(=[O:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)=O)[CH:5]=[CH:4][N:3]=1.C1C(=O)N(Br)C(=O)C1.[CH3:38][C:39]([CH3:44])([CH3:43])[C:40](=[S:42])[NH2:41]>CC(N(C)C)=O.O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:42][C:40]([C:39]([CH3:44])([CH3:43])[CH3:38])=[N:41][C:9]=2[C:11]2[C:12]([F:29])=[C:13]([NH:17][S:18]([C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])(=[O:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)[CH:5]=[CH:4][N:3]=1
Reactant: CC(C)(C)C(N)=S
Reactant: O=C(Cc1ccnc(Cl)n1)c1cccc(NS(=O)(=O)c2c(F)cccc2F)c1F
Agent: O=C1CCC(=O)N1Br
Solvent: O
Solvent: CC(=O)N(C)C
Product: CC(C)(C)c1nc(-c2cccc(NS(=O)(=O)c3c(F)cccc3F)c2F)c(-c2ccnc(Cl)n2)s1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of N-{3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (2.0 g, 4.53 mmol) in 40 mL DMA, 1.0 eq. NBS (0.806 g, 4.53 mmol) was added and the solution was allowed to stir 15 min at rt. 2,2-dimethylpropanethioamide (0.531 g, 4.53 mmol) was then added at rt. The reaction was heated to 60° C. for 2 hours. The reaction was not complete by LC-MS. The reaction mixture was then heated to 80° C. for an additional hour. The reaction mixture was diluted with water and extracted×2 with EtOAc. The combined EtOAc washings were washed with water×3 to remove DMA, dried over MgSO4, filtered and concentrated onto silica gel. The crude material was chromatographed in 10-80% EtOAc in Hexanes to give the desired product, 1.6 g (64%). MS (ESI): 539.1 [M+H]+.
Reaction SMILES: [C:1](O)(=O)[CH2:2][C:3]1[CH:12]=[CH:11][C:8]([O:9][CH3:10])=[C:5]([O:6][CH3:7])[CH:4]=1.C(OC(Cl)=O)C(C)C.[CH3:23][O:24][C:25]1[CH:26]=[C:27]([C:33]2([CH2:39][CH2:40][CH2:41][NH:42][CH3:43])[S:38][CH2:37][CH2:36][CH2:35][S:34]2)[CH:28]=[CH:29][C:30]=1[O:31][CH3:32].ClCCCC1(C2C=CC(OC)=C(OC)C=2)SCCCS1.CN>O1CCCC1.C(N(CC)CC)C>[CH3:7][O:6][C:5]1[CH:4]=[C:3]([CH:12]=[CH:11][C:8]=1[O:9][CH3:10])[CH2:2][CH2:1][N:42]([CH3:43])[CH2:41][CH2:40][CH2:39][C:33]1([C:27]2[CH:28]=[CH:29][C:30]([O:31][CH3:32])=[C:25]([O:24][CH3:23])[CH:26]=2)[S:38][CH2:37][CH2:36][CH2:35][S:34]1
Reactant: CNCCCC1(c2ccc(OC)c(OC)c2)SCCCS1
Reactant: COc1ccc(CC(=O)O)cc1OC
Agent: CC(C)COC(=O)Cl
Agent: CN
Agent: COc1ccc(C2(CCCCl)SCCCS2)cc1OC
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COc1ccc(CCN(C)CCCC2(c3ccc(OC)c(OC)c3)SCCCS2)cc1OC
Reaction time: 1 h

Procedure:
1 g of homoveratric acid is dissolved in 15 ml of absolute tetrahydrofuran and treated with 0.15 g of triethylamine. 0.72 g of chloroformic acid isobutyl ester are then slowly added dropwise at 0°-5° C. and the mixture is stirred for 1 hour at 5°-10° C. There is then added dropwise a solution of 1.63 g of 2-(3,4-dimethoxyphenyl)-N-methyl-m-dithiane-2-propylamine [prepared in a manner analogous to that described in Example 15 from 2-(γ-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane and methylamine] in 5 ml of tetrahydrofuran. The resulting mixture is left to stand at room temperature overnight. After evaporation of the solvent, the residue is partitioned between 1-M hydrochloric acid and ether. The organic extracts are washed with 5% sodium carbonate solution and water. After drying over magnesium sulphate, the solvent is removed by evaporation. The oily residue (1.5 g) is dissolved in 15 ml of tetrahydrofuran and added dropwise to a suspension of 0.15 g of lithium aluminium hydride under reflux and under argon. The mixture is boiled for 2 hours and then treated slowly with a concentrated sodium sulphate solution in water and then with 10 ml of methylene chloride. The mixture is filtered under suction and then concentrated. The residue is chromatographed on silica gel and there is obtained N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithiane-2-propylamine in the form of a thick oil.