Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1)=[CH2:2].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(OC=C)C.O>O1CCOCC1>[CH:2]#[C:1][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1
Reactant: C=Cc1ccc(O)cc1
Agent: C=COCC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: C1COCCO1
Product: C#Cc1ccc(O)cc1
Reaction time: 5 h

Procedure:
Into a 500 ml four-necked flask purged with nitrogen were charged 25 g of poly (p-vinylphenol) ["VP-5000" manufactured by Nippon Soda K.K.] having a weight average molecular weight (Mw) of 8400 and a dispersion degree (Mw/Mn) of 1.19 (208 mmol as p-vinylphenol unit) and 0.024 g (0.125 mmol) of p-toluenesulfonic acid, and they were dissolved in 250 g of 1,4-dioxane. To this solution was added dropwise 9.0 g (125 mmol) of ethylvinyl ether, and then reaction was carried out for 5 hours at 25° C. This reaction solution was added dropwise into 1500 ml of ion-exchanged water, then separated by filtration to obtain a white wet cake. This wet cake was dissolved again in 200 g of 1,4-dioxane, and the resulting solution was added dropwise into 1500 ml of ion-exchanged water. The resulting mixture was separated by filtration. The wet cake thus obtained was washed by being stirred with 600 g of ion-exchanged water, followed by being filtered to obtain a wet cake. The washing operation with this ion-exchanged water was further repeated twice. The resulting white wet cake was dried under reduced pressure to obtain a resin in which the hydroxyl group of poly (p-vinylphenol) was partially 1-ethoxyethyl etherized. This resin was analyzed by 1H-NMR to find that 40% of the hydroxyl group was protected by a 1-ethoxylethyl group. This resin has a weight average molecular weight of 12300 and a dispersion degree of 1.23.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[CH:11]=[CH:10][NH:9][C:5]2=[C:6]([Cl:8])[N:7]=1.[H-].[Na+].I[CH3:15]>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]2[CH:11]=[CH:10][N:9]([CH3:15])[C:5]2=[C:6]([Cl:8])[N:7]=1
Reactant: CI
Reactant: Clc1nc(Br)cc2cc[nH]c12
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cn1ccc2cc(Br)nc(Cl)c21
Reaction time: 0.25 h
Yield: 82.1 %

Procedure:
A solution of 5-bromo-7-chloro-1H-pyrrolo[2,3-c]pyridine (Aldrich, 0.86 g, 3.72 mmol) in tetrahydrofuran (37.2 mL) was treated with sodium hydride (0.297 g, 7.43 mmol) at ambient temperature, stirred for 15 minutes, treated with iodomethane (0.348 mL, 5.57 mmol), stirred for 1 hour at ambient temperature and quenched with saturated aqueous ammonium chloride. The mixture was partitioned with ethyl acetate and the organic layer was washed with saturated aqueous sodium chloride, dried (anhydrous Na2SO4), filtered, and concentrated. Purification by chromatography (silica gel, 0-40% ethyl acetate in heptanes) afforded the title compound (0.75 g, 82%).
Reaction SMILES: S(Cl)([Cl:3])=O.[CH2:5]([CH:13]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:22]([OH:24])=O)[CH:19]=2)[CH2:14]1)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]>>[CH2:5]([CH:13]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:22]([Cl:3])=[O:24])[CH:19]=2)[CH2:14]1)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: O=S(Cl)Cl
Reactant: CCCCCCCCC1Cc2ccc(C(=O)O)cc2C1
Product: CCCCCCCCC1Cc2ccc(C(=O)Cl)cc2C1

Procedure:
4.8 g of thionyl chloride was added to 1.10 g (4.00 mM) of 2-octylindan-5-carboxylic acid, followed by refluxing for 1 hour. After the refluxing, an excessive thionyl chloride was distilled off under reduced pressure, followed by further distillation with benzene to obtain 2-octylindan-5-carbonyl chloride.
Reaction SMILES: [OH:1][C:2]1([CH2:21][C:22](=[O:32])[CH2:23][C:24]([C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)=O)[CH2:7][CH2:6][N:5]([C:8](=[O:20])[C:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]([CH3:18])[CH3:17])=[C:11]([CH3:19])[CH:10]=2)[CH2:4][CH2:3]1.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1.O>ClCCl>[CH:16]([O:15][C:12]1[CH:13]=[CH:14][C:9]([C:8]([N:5]2[CH2:6][CH2:7][C:2]3([O:1][C:24]([C:26]4[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=4)=[CH:23][C:22](=[O:32])[CH2:21]3)[CH2:3][CH2:4]2)=[O:20])=[CH:10][C:11]=1[CH3:19])([CH3:18])[CH3:17]
Reactant: Cc1cc(C(=O)N2CCC(O)(CC(=O)CC(=O)c3cccnc3)CC2)ccc1OC(C)C
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: O
Product: Cc1cc(C(=O)N2CCC3(CC2)CC(=O)C=C(c2cccnc2)O3)ccc1OC(C)C
Temperature: 120 °C

Procedure:
To a solution of 4-[4-hydroxy-1-(4-isopropoxy-3-methyl-benzoyl)-4-piperidyl]-1-(3-pyridyl)butane-1,3-dione (1 mmol) in dichloromethane (5 mL) was added PPTS (251 mg, 1.00 mmol). The mixture was heated in microwave at 120° C. for 45 min. Water was added. The aqueous layer was extracted with dichloromethane (2×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated to dryness. The residue was purified by column chromatography (40-50% ethyl acetate-Hex) to provide 3-(4-isopropoxy-3-methyl-benzoyl)-10-(3-pyridyl)-11-oxa-3-azaspiro[5.5]undec-9-en-8-one.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:13][CH:14]([S:27][CH3:28])[C:15]([NH:17][C:18]([CH3:26])([CH2:21][O:22][CH2:23][C:24]#[CH:25])[CH2:19][OH:20])=[O:16])=[CH:8][CH:7]=2)#[CH:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl>[C:1]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:13][CH:14]([S:27][CH3:28])[C:15]([NH:17][C:18]([CH3:26])([CH2:21][O:22][CH2:23][C:24]#[CH:25])[CH:19]=[O:20])=[O:16])=[CH:8][CH:7]=2)#[CH:2]
Reactant: C#CCOCC(C)(CO)NC(=O)C(Oc1ccc2ncc(C#C)cc2c1)SC
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: C#CCOCC(C)(C=O)NC(=O)C(Oc1ccc2ncc(C#C)cc2c1)SC
Temperature: 25 °C
Reaction time: 2 h
Yield: 110.6 %

Procedure:
2-(3-Ethynyl-quinolin-6-yloxy)-N-(2-hydroxy-1-methyl-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide (1.0 g) from Stage 3 above in dichloromethane (40 ml) was treated with Dess-Martin periodinane (1.277 g). The reaction mixture was stirred at R.T. for 2 h 30 and then, quenched with sat. aqueous NaHCO3 and sat. aqueous sodium thiosulphate. The reaction mixture was vigorously stirred at rt. for 30 minutes after which time the two phases were separated. The organic layer was washed with sat. aqueous. NaHCO3. After separation, the organic phase was dried over sodium sulphate, filtered and evaporated to yield 1.10 g of 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-methyl-2-oxo-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl acetamide as a crude product (along with minor impurities. The crude mixture was used in the next step without any further purification.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([O:8][CH3:9])[CH:5]=[CH:6][CH:7]=1.[C:10]1(B(O)O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[F-].[Cs+]>COCCOC>[C:10]1([C:2]2[CH:3]=[C:4]([O:8][CH3:9])[CH:5]=[CH:6][CH:7]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: OB(O)c1ccccc1
Reactant: COc1cccc(Cl)c1
Agent: [Cs+]
Agent: [F-]
Solvent: COCCOC
Product: COc1cccc(-c2ccccc2)c1
Temperature: 25 °C
Yield: 93.9 %

Procedure:
A 100 mL of reactor equipped with magnetic stir bar was charged with 150 mg (0.161 mmol) of {[(t-Bu)2P(OH)]2PdCl}2 (from Experiment 7), 1.43 g (10.0 mmol) of 3-chloroanisole, 1.83 g (15.0 mmol) of PhB(OH)2 and 4.56 g (30.0 mmol) of CsF in 30.0 mL of DME. The resulting mixture was refluxed for 12 h until the starting material was completely consumed as judged by TLC. The reaction was cooled to room temperature, transferred to a separatory funnel, and diluted with 300 mL of diethyl ether. The layers were separated, and organic layer was washed with H2O (2×100 mL), brine (100 mL), and dried over mgSO4, filtered, and the ether and dioxane removed from the filtrate by rotary evaporation. The resulting residue was chromatographed on silicon gel using 2% EtOAc/hexane as eluant. The eluate was concentrated by rotary evaporation followed by high vacuum to give 1.73 g (94% yield) of 3-phenylanisole.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH:10]([C:12]1[C:13]([CH3:24])=[N:14][O:15][C:16]=1[C:17]1[CH:22]=[CH:21][C:20](Br)=[CH:19][CH:18]=1)[OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:25]([O:27][C:28]([C:30]1([C:33]2[CH:38]=[CH:37][C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][CH:34]=2)[CH2:32][CH2:31]1)=[O:29])[CH3:26]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:25]([O:27][C:28]([C:30]1([C:33]2[CH:38]=[CH:37][C:36]([C:20]3[CH:21]=[CH:22][C:17]([C:16]4[O:15][N:14]=[C:13]([CH3:24])[C:12]=4[CH:10]([OH:11])[CH2:9][O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:18][CH:19]=3)=[CH:35][CH:34]=2)[CH2:31][CH2:32]1)=[O:29])[CH3:26]
Reactant: Cc1noc(-c2ccc(Br)cc2)c1C(O)COCc1ccccc1
Reactant: CCOC(=O)C1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4C(O)COCc4ccccc4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 3, Step 5, using dichlorobis(triphenylphosphine)palladium(II) as the catalyst and using 2-benzyloxy-1-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-ethanol (Enantiomer B) and 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarboxylic acid ethyl ester.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Si:8](Cl)(Cl)(Cl)[Cl:9]>>[Cl:9][Si:8].[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Cl[Si](Cl)(Cl)Cl
Solvent: Oc1ccccc1
Product: [Si]Cl
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
About 1 mol of hydrated silicon acid, 0.25 mol of phenol and 1 mol of silicon tetrachloride are slowly added simultaneously while agitating at ambient temperature for 1 to 2 hours; the reaction is complete in 2 to 8 hours, thereby producing a phenol chlorosilicon acid resinous product. To this resinous product, about 0.25 to 6 mols of an organic diene, isoprene, are added while agitating at a temperature between the liquid state and the boiling temperature of the diene for 1 to 2 hours; the reaction is complete in 2 to 8 hours, thereby producing a vinyl phenol silicon acid resinous product.
Reaction SMILES: [C:1]([C:3](=[C:9](SC)[S:10][CH3:11])[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].Cl.[NH2:15][NH2:16].C([O-])(=O)C.[Na+]>C(O)C>[NH2:2][C:1]1[NH:16][N:15]=[C:9]([S:10][CH3:11])[C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5]
Reactant: CCOC(=O)C(C#N)=C(SC)SC
Reactant: NN
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)c1c(SC)n[nH]c1N
Temperature: 25 °C
Yield: 47 %

Procedure:
A solution of ethyl 2-cyano-3,3-bis(methylthio)-acrylate (40 g), hydrazine hydrochloride (12.6 g) and sodium acetate (22.6 g) in ethanol was stirred at 90° C. for 2 hour. After cooling to room temperature, the reaction mixture was concentrated in vacuo, and to the residue were added water and ethyl acetate. The organic layer was separated, dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo, and to the residue was added ethyl acetate and hexane. The precipitates were collected by filtration and dried to give 5-amino-4-ethoxycarbonyl-3-methylthio-1H-pyrazole (17.4 g, yield: 47%) as a colorless solid.
Reaction SMILES: [C:1]([C:3]1[CH:29]=[CH:28][C:6]([O:7][CH2:8][C@@H:9]([OH:27])[CH2:10][N:11]2[CH2:18][CH:17]3[O:19][CH:13]([CH2:14][N:15](C(OC(C)(C)C)=O)[CH2:16]3)[CH2:12]2)=[CH:5][CH:4]=1)#[N:2].FC(F)(F)C(O)=O>ClCCl>[OH:27][C@@H:9]([CH2:10][N:11]1[CH2:18][CH:17]2[O:19][CH:13]([CH2:14][NH:15][CH2:16]2)[CH2:12]1)[CH2:8][O:7][C:6]1[CH:28]=[CH:29][C:3]([C:1]#[N:2])=[CH:4][CH:5]=1
Reactant: CC(C)(C)OC(=O)N1CC2CN(C[C@H](O)COc3ccc(C#N)cc3)CC(C1)O2
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: N#Cc1ccc(OC[C@@H](O)CN2CC3CNCC(C2)O3)cc1
Reaction time: 3 h
Yield: 97.1 %

Procedure:
A 3 L, three-necked flask equipped with a magnetic stirrer, a thermometer and an addition funnel was charged with unpurified tert-butyl 7-[(2S)-3-(4-cyanophenoxy)-2-hydroxypropyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate (100 g, from step (ii) above) and dichloromethane (1.15 L). Trifluoroacetic acid (0.352 L) was added slowly at room temperature and the resulting solution was stirred for three hours, at which point TLC analysis showed complete reaction. The contents were transferred to a single-necked flask and concentrated under vacuum. The residue was dissolved in dichloromethane (1.2 L) and washed with saturated sodium bicarbonate. The aqueous layer was separated and extracted with dichloromethane (2×0.2 L). The combined organic layers were washed with brine (0.25 L), dried over magnesium sulfate and concentrated under vacuum to afford 73 g (>100% yield) of sub-title compound as an off-white solid. The unpurified material was used in the next step.
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([Br:10])=[CH:6][C:5]=1[CH2:11]Br.[NH3:14]>>[Br:10][C:7]1[CH:6]=[C:5]2[C:4](=[CH:9][CH:8]=1)[C:3](=[O:2])[NH:14][CH2:11]2
Reactant: N
Reactant: COC(=O)c1ccc(Br)cc1CBr
Product: O=C1NCc2cc(Br)ccc21
Temperature: 25 °C
Yield: 65 %

Procedure:
4-Bromo-2-bromomethyl-benzoic acid methyl ester (0.5 g, 16.2 mmol) is treated with methanolic ammonia (10 mL, 7 N NH3 in MeOH) for 5 minutes at 90° C. After cooling to room temperature a precipitate is formed, collected by filtration and washed with a small amount of methanol to afford the title compound as a colourless solid (224 mg, 65%). 1H-NMR (400 MHz, d6-DMSO) δ(ppm) 4.41 (2H, s), 7.64 (1H, d), 7.70 (1H, d), 7.87 (1H, s), 8.67 (1H, br s). LCMS: Rt 2.49 min, (99.6%), m/z (APCI) 212 (M+H)+.
Reaction SMILES: [F:1][C:2]1[C:8]([OH:9])=[C:7]([F:10])[CH:6]=[CH:5][C:3]=1[OH:4].[Cl:11][CH2:12][C:13](=O)[CH2:14][C:15](OCC)=[O:16]>CS(O)(=O)=O.O>[Cl:11][CH2:12][C:13]1[C:5]2[C:3](=[C:2]([F:1])[C:8]([OH:9])=[C:7]([F:10])[CH:6]=2)[O:4][C:15](=[O:16])[CH:14]=1
Reactant: Oc1ccc(F)c(O)c1F
Reactant: CCOC(=O)CC(=O)CCl
Agent: CS(=O)(=O)O
Solvent: O
Product: O=c1cc(CCl)c2cc(F)c(O)c(F)c2o1

Procedure:
A solution of 2,4-difluororesorcinol (Compound 4, 0.20 g, 1.37 mmol) and ethyl 4-chloroacetoacetate (0.29 g, 1.75 mmol) in 2 mL methanesulfonic acid is kept at room temperature for 2.5 hours, then diluted with 25 mL water. The resulting precipitate is collected on a Buchner funnel and dried to give 134 mg of dimly fluorescent Compound 28 as a colorless powder. This product is purified further by chromatography (silica gel, ethyl acetate/hexanes): Rf =0.45 (EtOAc/hexanes 3:2); 1H NMR (CDCl3 -CD3OD) δ 7.13 (dd, 1H), 6.41 (s, 1H), 4.52 (s, 2H); 19F NMR (CDCl3 -CD3OD) Φ 136.38 (t, 1F), 153.26 (d, 1F).
Reaction SMILES: [C:1]([CH:3]([C:8]1([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[CH2:13][C:12]2([CH2:18][CH2:17][CH2:16]C[CH2:14]2)[O:11][CH2:10][CH2:9]1)C(OC)=O)#[N:2].C(C(C1(C2C=CC(F)=CC=2)CC2(CCCC2)OCC1)C(OC)=O)#N.FC1C=CC(C2(CC#N)CC3(CCCCC3)OCC2)=CC=1>>[F:25][C:22]1[CH:21]=[CH:20][C:19]([C@@:8]2([CH2:3][C:1]#[N:2])[CH2:13][C:12]3([CH2:14][CH2:16][CH2:17][CH2:18]3)[O:11][CH2:10][CH2:9]2)=[CH:24][CH:23]=1
Reactant: COC(=O)C(C#N)C1(c2ccc(F)cc2)CCOC2(CCCCC2)C1
Agent: COC(=O)C(C#N)C1(c2ccc(F)cc2)CCOC2(CCCC2)C1
Agent: N#CCC1(c2ccc(F)cc2)CCOC2(CCCCC2)C1
Product: N#CC[C@@]1(c2ccc(F)cc2)CCOC2(CCCC2)C1

Procedure:
By the procedure described in the preparation of intermediate 10 substituting methyl 2-cyano-2-[4-(4-fluorophenyl)-1-oxaspiro[5.5]undecan-4-yl]acetate for methyl 2-cyano-2-[9-(4-fluorophenyl)-6-oxaspiro[4.5]decan-9-yl]acetate, 2-[4-(4-fluorophenyl)-1-oxaspiro[5.5]undecan-4-yl]acetonitrile was prepared (m/z 287.2 [M+H]+ observed).
Reaction SMILES: [CH3:1][N:2]1[N:6]=[N:5][C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([N+:13]([O-])=O)[CH:8]=2)=[N:3]1>C(O)C.[Pd]>[NH2:13][C:9]1[CH:8]=[C:7]([C:4]2[N:5]=[N:6][N:2]([CH3:1])[N:3]=2)[CH:12]=[CH:11][CH:10]=1
Reactant: Cn1nnc(-c2cccc([N+](=O)[O-])c2)n1
Agent: [Pd]
Solvent: CCO
Product: Cn1nnc(-c2cccc(N)c2)n1
Yield: 78.9 %

Procedure:
2-Methyl-5-(3-nitrophenyl)tetrazole (2.30 g) was hydrogenated at 20 psi in ethanol (50 ml) using 10% palladium on carbon (230 mg) for 15 minutes. The mixture was filtered then evaporated to dryness in vacuo to give the title compound as a colourless solid (1.55 g), mp 97° C. Rf 0.40 in dichloromethane/methanol (5:1) on silica plates. 1H NMR (360 MHz, CDCl3) δ3.80 (2H, broad resonance), 4.38 (3H, s), 6.78 (1H, ddd, J1 =J2 =8 Hz, J3 =8 Hz), 7.26 (1H, dd, J1 =J2 =8 Hz), 7.47 (1H, dd, J1 =J2 =2 Hz), 7.51 (1H, dd, J1 =2 Hz, J2 =8 Hz).
Reaction SMILES: [CH:1]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6](Cl)=[S:7])([CH3:3])[CH3:2].[OH:13][CH:14]1[CH2:17][O:16][CH2:15]1.N1C=CC=CC=1>C1(C)C=CC=CC=1>[CH:1]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]([O:13][CH:14]1[CH2:17][O:16][CH2:15]1)=[S:7])([CH3:3])[CH3:2]
Reactant: OC1COC1
Reactant: CC(C)c1ccccc1C(=S)Cl
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CC(C)c1ccccc1C(=S)OC1COC1
Reaction time: 3 h
Yield: 89 %

Procedure:
##STR16## A mixture of 12.9 g of 2-isopropylthiobenzoyl chloride and 20 ml of absolute toluene is added dropwise to a mixture of 4.44 g of 3-hydroxyoxetane, 6.64 g of pyridine and 60 ml of absolute toluene at a temperature of 15° to 20° C. The suspension formed is stirred at a temperature of 20°-25° C. for 2 hours and at a temperature of 40°-45° C. for a further 3 hours. Adding water to the reaction mixture, washing the organic phase with water and drying and evaporating it gives 12.6 g of oxetan-3-yl 2-isopropylthiobenzoate as a pale yellow oil.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][C:7]([OH:11])=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.[C:18](Cl)(=[O:20])[CH3:19]>C(Cl)Cl>[C:18]([O:11][C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[N:1]=[CH:2][CH:3]=[CH:4]2)(=[O:20])[CH3:19]
Reactant: CC(=O)Cl
Reactant: Oc1ccc2ncccc2c1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(=O)Oc1ccc2ncccc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 86.2 %

Procedure:
To a solution of quinolin-6-ol (4.5 g, 31.0 mmol) and pyridine (3.01 ml, 37.2 mmol) in DCM (50 ml) was added acetyl chloride (2.65 ml, 37.2 mmol) at 0° C. The mixture was then stirred at rt for 8 h. The reaction was quenched with saturated NaHCO3 and the mixture was extracted with DCM (30 ml) three times. The combined organic phase was washed with brine and dried over anhydrous MgSO4, filtered and concentrated to give the title compound (5.0 g, 68.9% yield), which was used directly in next step. LCMS (method B): [M+H]+=188, tR=1.64 min.
Reaction SMILES: [Si]([O:8][CH:9]([CH2:37][CH2:38][CH2:39][O:40][Si](C(C)(C)C)(C)C)/[CH:10]=[CH:11]/[CH:12]=[C:13]1[C:17](=[O:18])[C:16]([S:19][CH3:20])=[CH:15][C:14]1([CH2:26][CH2:27][CH2:28][CH2:29][O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[O:21][Si](C)(C)C)(C(C)(C)C)(C)C.C(O)(=O)C.O1CCCC1>O>[OH:8][CH:9]([CH2:37][CH2:38][CH2:39][OH:40])/[CH:10]=[CH:11]/[CH:12]=[C:13]1[C:17](=[O:18])[C:16]([S:19][CH3:20])=[CH:15][C:14]1([OH:21])[CH2:26][CH2:27][CH2:28][CH2:29][O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: CSC1=CC(CCCCOc2ccccc2)(O[Si](C)(C)C)C(=C/C=C/C(CCCO[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C)C1=O
Solvent: O
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: CSC1=CC(O)(CCCCOc2ccccc2)C(=C/C=C/C(O)CCCO)C1=O
Yield: 63.3 %

Procedure:
To 255 mg of 5-[(E)-4,7-bis(t-butyldimethylsilyloxy)-2-heptenylidene]-2-methylthio-4-(4-phenoxybutyl)-4-trimethylsilyloxy-2-cyclopentenone obtained in Example 75 was added 20 ml of a mixture of acetic acid:tetrahydrofuran:water=3:1:1, and the mixture was stirred at room temperature for 26 hours. After concentration with an addition of toluene, saturated aqueous sodium hydrogencarbonate was added, and the mixture was extracted 3 times with ethyl acetate. The organic layers were combined, washed successively with saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate. After filtration and concentration, the concentrate was subjected to silica gel column chromatography to give 94 mg (yield 63%) of 5-[(E)-4,7-dihydroxy-2-heptenylidene]-4-hydroxy-2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone.
Reaction SMILES: F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[C:3]=1[N+:10]([O-:12])=[O:11].C([O-])([O-])=O.[K+].[K+].CS(C)=O.[NH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>CCOC(C)=O>[F:9][C:4]1[C:3]([N+:10]([O-:12])=[O:11])=[C:2]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH:7]=[C:6]([F:8])[CH:5]=1
Reactant: C1COCCN1
Reactant: O=[N+]([O-])c1c(F)cc(F)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: O=[N+]([O-])c1c(F)cc(F)cc1N1CCOCC1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
1,3,5-Trifluoro-2-nitro-benzene (5.30 g, 29.9 mmol) and K2CO3 (4.96 g, 35.9 mmol) were mixed in DMSO (40.0 mL, 564 mmol) and morpholine (2.74 mL, 31.4 mmol) was added. The reaction was stirred at rt for 48 h, diluted with EtOAc and washed twice with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Title compound isolated as a yellow oil (4.26 g, 58%). LCMS (m/e) 245 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 6.67-6.58 (m, 2H), 3.80 (t, 4H, J=4.2 Hz), 3.06 (t, 4H, J=4.2 Hz), 19F-NMR (CDCl3, 400 MHz) δ −102, −118. Also obtained in this reaction, 4-(3,5-difluoro-4-nitro-phenyl)-morpholine as a yellow solid (2.85 g, 39%). m.p.=112-114° C.; LCMS (m/e) 245 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 6.45-6.37 (m, 2H), 3.86 (t, 4H, J=4.5 Hz), 3.33 (t, 4H, J=4.5 Hz); 19F-NMR (CDCl3, 400 MHz) δ −115.
Reaction SMILES: [CH3:1][N:2]([CH3:22])[C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]2[CH:16]=[CH:15][C:14](/[CH:17]=[CH:18]/[C:19](O)=[O:20])=[CH:13]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[C:45]([NH:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[NH2:59])([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46]>CN(C=O)C.C(N(CC)CC)C.O>[C:48]([O:47][C:45](=[O:46])[NH:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[NH:59][C:19](=[O:20])/[CH:18]=[CH:17]/[C:14]1[CH:15]=[CH:16][N:12]([S:9]([C:6]2[CH:5]=[CH:4][C:3]([N:2]([CH3:1])[CH3:22])=[CH:8][CH:7]=2)(=[O:11])=[O:10])[CH:13]=1)([CH3:51])([CH3:50])[CH3:49]
Reactant: CN(C)c1ccc(S(=O)(=O)n2ccc(/C=C/C(=O)O)c2)cc1
Reactant: CC(C)(C)OC(=O)Nc1ccccc1N
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CN(C)c1ccc(S(=O)(=O)n2ccc(/C=C/C(=O)Nc3ccccc3NC(=O)OC(C)(C)C)c2)cc1

Procedure:
Starting materials: (E)-3-[1-(4-dimethylamino-benzenesulfonyl)-1H-pyrrol-3-yl)-acrylic acid (compound B3) (0.150 g), HOBt.H2O (0.072 g), triethylamine (259 μl), DMF (10 ml), EDC.HCl (0.269 g), N-BOC-1,2-phenylenediamine (0.049 g). Reaction conditions: room temperature, 1 hour; room temperature, 21 hours.
Reaction SMILES: [C:1]([NH:4][C:5]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)(SC)[C:6]([O:8][CH3:9])=[O:7])(=[O:3])[CH3:2].C1(S)C=CC=CC=1.C(N(CC)CC)C.C(Cl)Cl>CO>[C:1]([NH:4][CH:5]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]([O:8][CH3:9])=[O:7])(=[O:3])[CH3:2]
Reactant: COC(=O)C(NC(C)=O)(SC)c1ccccc1
Agent: Sc1ccccc1
Solvent: CO
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)C(NC(C)=O)c1ccccc1
Yield: 99 %

Procedure:
113 Milligrams of methyl α-acetylamino-α-methylthiophenylacetate and 41 mg of thiophenol were dissolved in 5 ml of methanol, and to the solution 0.5 ml of triethylamine was added, followed by an hour's refluxing. After a reduced pressure concentration of the reaction mixture, the residue was parted by a column chromatography (silica gel and methylene chloride). Thus 92 mg of methyl α-acetylaminophenylacetate was obtained. The yield was 99%.