Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si](O[CH2:9][CH2:10][C:11]([C:14]1[NH:15][C:16]2[C:21]([CH:22]=1)=[CH:20][C:19]([N+:23]([O-:25])=[O:24])=[C:18]([F:26])[CH:17]=2)([CH3:13])[CH3:12])(C(C)(C)C)(C)C.CC1C=CC(S(OC[C@@H]2COC(C)(C)O2)(=O)=O)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>>[F:26][C:18]1[C:19]([N+:23]([O-:25])=[O:24])=[CH:20][C:21]2[CH:22]=[C:14]3[C:11]([CH3:13])([CH3:12])[CH2:10][CH2:9][N:15]3[C:16]=2[CH:17]=1
Reactant: CC(C)(CCO[Si](C)(C)C(C)(C)C)c1cc2cc([N+](=O)[O-])c(F)cc2[nH]1
Agent: Cc1ccc(S(=O)(=O)OC[C@@H]2COC(C)(C)O2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: CC1(C)CCn2c1cc1cc([N+](=O)[O-])c(F)cc12
Temperature: 90 °C
Yield: 48.3 %

Procedure:
To a solution of 2-(4-(tert-butyldimethylsilyloxy)-2-methylbutan-2-yl)-6-fluoro-5-nitro-1H-indole (1.9 g, 5.0 mmol) and (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (2.86 g, 10.0 mmol) DMF (10 mL) was added Cs2CO3 (4.88 g, 15.0 mmol). The mixture was heated at 90° C. for 24 hours. The reaction was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine and dried over MgSO4. After the removal of solvent, the residue was purified by column chromatography (10-50% ethyl acetate-hexane) to afford 6-fluoro-1,1-dimethyl-7-nitro-2,3-dihydro-1H-pyrrolo[1,2-a]indole (600 mg, 48%). ESI-MS m/z calc. 248.1, found 249.2 (M+1)+. Retention time 2.00 minutes; 2-(4-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-2-methylbutan-2-yl)-1-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1H-indole (270 mg, containing some (R)-2-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-2-methylbutan-2-yl)-6-fluoro-5-nitro-1H-indole). ESI-MS m/z calc. 494.2 and 380.2, found 495.4 and 381.4 (M+1)+. Retention time 2.12 and 1.92 minutes; (R)-3-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1H-indol-2-yl)-3-methylbutan-1-01 (1.0 g, containing some 3-(6-fluoro-5-nitro-1H-indol-2-yl)-3-methylbutan-1-ol). ESI-MS m/z calc. 380.2 and 266.1, found 381.2 and 267.2 (M+1)+. Retention time 1.74 and 1.48 minutes.
Reaction SMILES: [C:1]([N:20]=[N+:21]=[N-:22])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23]([O:27][CH3:28])(=[O:26])[C:24]#[CH:25]>CC(C)=O.CCOCC>[CH3:28][O:27][C:23]([C:24]1[N:22]=[N:21][N:20]([C:1]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:25]=1)=[O:26]
Reactant: [N-]=[N+]=NC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: C#CC(=O)OC
Solvent: CCOCC
Solvent: CC(C)=O
Product: COC(=O)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)nn1
Temperature: 25 °C
Yield: 62 %

Procedure:
To a suspension of sodium azide (19.0 g : 0.283 Mol.) in dimethyl- formamide (130 ml) is added trityl chloride (76.0 g : 0.273 Mol.), and the mixture is stirred at room temperature for 5 hours. The reaction mixture is diluted with water and extracted with ether. The extract is washed with brine, dried over sodium sulfate, and concentrated to give trityl azide. To a solution of this azide in acetone (300 ml) is added methyl propiolate (24 ml : 0.27 Mol.), and the mixture is heated under reflux for 6 days. The reaction mixture is cooled to the room temperature and diluted with ether. The separating crystals are collected by filtration to give 1-trityl-1,2,3-triazol-4-ylcarboxylic acid methyl ester (62.0 g) as colorless crystals. Yield: 62%. mp. 189° to 190° C. NMR δ (CDCl3) ppm: 3.93(s, 3H), 7.05-7.15(m, 6H), 7.3-7.4(m, 9H), 8.02(s, 1H).
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([O-:10])(=[O:9])=[O:8])=[CH:3][CH:2]=1.[Cl:12][C:13]1[CH:14]=[CH:15][C:16]2[S:20][C:19]([CH3:21])=[N+:18]([CH2:22][CH3:23])[C:17]=2[CH:24]=1.[CH3:25]O.[CH3:27][C:28](C)=[O:29]>C(OCC)(=O)C>[C:1]1([CH3:11])[CH:2]=[CH:3][C:4]([S:7]([O-:10])(=[O:8])=[O:9])=[CH:5][CH:6]=1.[Cl:12][C:13]1[CH:14]=[CH:15][C:16]2[S:20][C:19]([CH:21]=[C:28]3[CH:27]=[C:11]([CH3:25])[C:1]4[C:6](=[CH:5][CH:4]=[CH:3][CH:2]=4)[O:29]3)=[N+:18]([CH2:22][CH3:23])[C:17]=2[CH:24]=1
Reactant: CO
Reactant: CC[n+]1c(C)sc2ccc(Cl)cc21
Reactant: CC(C)=O
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Solvent: CCOC(C)=O
Product: CC[n+]1c(C=C2C=C(C)c3ccccc3O2)sc2ccc(Cl)cc21
Temperature: 150 °C
Reaction time: 0.33 h
Yield: 52 %

Procedure:
11.1 g of 5-chloro-3-ethyl-2-methylbenzothiazolium p-toluenesulfonate and 5.5 g of 4-methylcoumarin-2-thione were reacted under heat at 150° C. for 23 hours, and then 25 ml of methanol, 50 ml of acetone and 150 ml of ethyl acetate were added to the reaction mixture in the order listed. After cooling to room temperature, crystals precipitated out from the reaction solution, and the crystals were separated by filtration and washed with a small amount of acetone. Afterwards, the crystals were placed in a mixed solvent comprising 25 ml of methanol, 50 ml of acetone, and 150 ml of ethyl acetate at room temperature, and stirred for 20 minutes, and then the crystals was again separated by filtration and washed with acetone, to finally obtain 7.9 g of the desired p-toluenesulfonate product. Yield: 52%. Appearance: brown crystal. M.p.: 282°-283° C. (decomposition).
Reaction SMILES: [CH:1]1([C:7]2[N:11]([CH2:12][C:13]3[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=3)[N:10]=[C:9]([C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=3)[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl.[CH2:53]([O:55][C:56](=[O:61])[C@H:57]([CH2:59][NH2:60])N)[CH3:54]>CN(C=O)C.C(Cl)CCl>[CH:1]1([C:7]2[N:11]([CH2:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH:60][CH2:59][CH2:57][C:56]([O:55][CH2:53][CH3:54])=[O:61])=[O:18])=[CH:15][CH:14]=3)[N:10]=[C:9]([C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:30])([F:31])[F:32])=[CH:24][CH:23]=3)[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(O)c1ccc(Cn2nc(-c3ccc(OC(F)(F)F)cc3)cc2C2CCCCC2)cc1
Reactant: CCOC(=O)[C@@H](N)CN
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: CCOC(=O)CCNC(=O)c1ccc(Cn2nc(-c3ccc(OC(F)(F)F)cc3)cc2C2CCCCC2)cc1
Reaction time: 16 h

Procedure:
A solution of 177.8 mg product from Step D Example 1, 92.0 mg EDC, 64.9 mg HOBt in 1.5 mL DMF was stirred at room temperature for 30 minutes. Diisopropylethylamine (DIEA, 84 μL) and β-amino-alanine ethyl ester hydrochloride (73.7 mg) were added and the mixture stirred for additional 16 hours. The solvent was removed under reduced pressure. Some crystalline product precipitated after dissolving the residue in 14 mL 3:2 MeCN and water with 0.1% TFA. More title compound was isolated by preparative HPLC of the filtrate using 60˜80% MeCN gradient over 10 minutes at 8.0 mL per minute with 0.1% TFA on a 9.4×250 mm SB-C18 Zorbax column. 1H NMR (CD3OD, 600 MHz) δ 7.84˜7.87 (m, 2H), 7.75 (d, J=8.4 Hz, 2H), 7.28 (d, J=8.3 Hz, 2H), 7.18 (d, J=8.2 Hz, 2H), 6.56 (s, 1H), 5.46 (s, 2H), 4.12 (q, J=7.1 Hz, 2H), 3.60 (t, J=6.8 Hz, 2H), 2.62 (t, J=6.8 Hz, 2H), 2.60 (tt, J=11.7 & 3.3 Hz, 1H), 1.73˜1.77 (m, 4H), 1.68˜1.71 (m, 1H), 1.37˜1.43 (m, 2H), 1.24˜1.35 (m, 3H), 1.21 (t, J=7.1 Hz, 3H). LC-MS: 2.47 min. (M+H=544.4).
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[C:6](Cl)[CH:5]=[C:4]([CH3:10])[C:3]=1[OH:11].[Cr](O)(O)(=O)=[O:13]>C(O)(=O)C>[CH3:1][C:2]1[C:3](=[O:11])[C:4]([CH3:10])=[CH:5][C:6](=[O:13])[C:7]=1[CH3:8]
Reactant: O=[Cr](=O)(O)O
Reactant: Cc1cc(Cl)c(C)c(C)c1O
Solvent: CC(=O)O
Product: CC1=CC(=O)C(C)=C(C)C1=O
Yield: 83.9 %

Procedure:
17.0 g (0.1 mole) of 2,3,6-trimethyl-4-chlorophenol obtained in Example 1 (A) was oxidized with a solution prepared by dissolving 15 g of chromic acid in 20 g of acetic acid. The reaction solution was treated in the same manner as in Example 1 to obtain 12.6 g of 2,3,6-trimethyl-p-benzoquinone (84% in yield).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([C:11]([F:14])([F:13])[F:12])[CH:3]=1.[C@H:15]1([OH:22])[CH2:20][CH2:19][C@H:18]([OH:21])[CH2:17][CH2:16]1.[H-].[Na+].O>CS(C)=O>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([O:21][CH:18]2[CH2:19][CH2:20][CH:15]([OH:22])[CH2:16][CH2:17]2)=[CH:3][C:4]=1[C:11]([F:14])([F:13])[F:12])([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1ccc(F)cc1C(F)(F)F
Reactant: O[C@H]1CC[C@H](O)CC1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: O=[N+]([O-])c1ccc(OC2CCC(O)CC2)cc1C(F)(F)F
Temperature: 50 °C
Reaction time: 3 h
Yield: 36 %

Procedure:
4-Fluoro-1-nitro-2-trifluoromethyl-benz ene (11.5 mmol), trans-cyclohexane-1,4-diol (17.2 mmol), and sodium hydride (60% in oil, 11.5 mmol) are suspended in dry dimethylsulfoxide (20 mL) and the resulting mixture is reacted under stirring for 3 hours at 50° C. The reaction is allowed to reach room temperature and is then further reacted at this temperature overnight. The reaction is treated with water (20 mL), the precipitate formed is removed by filtration and the filtrate is extracted with dichloromethane (50 mL). The organic phase is washed with aqueous saturated ammonium chloride (10 mL), dried over magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure. The precipitate is triturated with diethylether (20 mL), filtered and the filtrate concentrated under reduced pressure. Both fractions of crude product are combined, dissolved in dichloromethane and filtered trough a short pad of silica gel to afford the desired product (36% yield).
Reaction SMILES: [CH3:1][OH:2].[CH3:3][C:4]1[C:10]([OH:11])=[CH:9][CH:8]=[CH:7][C:5]=1[OH:6].O[CH2:13][C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([CH2:21]O)[C:15]=1[OH:23].Cl>O>[OH:6][C:5]1[C:4]([CH3:3])=[C:10]([OH:11])[CH:9]=[CH:8][C:7]=1[CH2:13][C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([CH2:21][C:4]2[CH:10]=[CH:9][C:1]([OH:2])=[C:7]([CH3:8])[C:5]=2[OH:6])[C:15]=1[OH:23]
Reactant: CO
Reactant: Cc1c(O)cccc1O
Reactant: Cc1cc(CO)c(O)c(CO)c1
Agent: Cl
Solvent: O
Product: Cc1cc(Cc2ccc(O)c(C)c2O)c(O)c(Cc2ccc(O)c(C)c2O)c1
Temperature: 25 °C

Procedure:
To a one liter flask was added 500 ml of methanol, 102.6 g of 2-methylresorcinol, 17 g of 2,6-bis(hydroxymethyl)-4-methylphenol and 10 ml of concentrated hydrochloric acid. The mixture was heated at reflux for 24 hours, cooled and slowly poured into 3 L of de-mineralized water to precipitate the crude product. After the product was collected by filtration it was washed with a copious amount of water, dissolved into 3.5 L of hot water, and the mixture filtered while hot. The filtrate was cooled to ambient temperature and the crystals collected by filtration and dried. The filtrant was extracted with hot water four more times to give a total of 23.2 g of product having a purity greater than 94% as determined by HPLC.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][N:18]=[C:17](Cl)[CH:16]=3)[CH:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:22][CH:23]([CH3:27])[CH2:24][O:25][CH3:26]>O1CCOCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH:22][CH:23]([CH3:27])[CH2:24][O:25][CH3:26])[CH:16]=3)[CH:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: Clc1cccc(Nc2nccc(-c3ccnc(Cl)c3)n2)c1
Reactant: COCC(C)N
Solvent: C1COCCO1
Product: COCC(C)Nc1cc(-c2ccnc(Nc3cccc(Cl)c3)n2)ccn1
Temperature: 195 °C

Procedure:
A mixture of (3-chloro-phenyl)-[4-(2-chloro-pyridin-4-yl)-pyrimidin-2-yl]-amine (10.0 g, 0.03 mol) and 2-amino-1-methoxypropane (14.0 g, 0.16 mol) in dioxane (75 ml) is heated in an autoclave at 195° C. for 12 hours. The reaction mixture is partitioned between ethyl acetate and water. The organic phase is separated, dried over magnesium sulfate, filtered and evaporated under reduced presssure. The residue is purified by silicagel chromatography to give the title compound, m.p. 143–144° C.
Reaction SMILES: [Si:1]([O-])([O-:4])([O-:3])[O-:2].[Na+:6].[Na+].[Na+].[Na+].O=[Al-:11]=O.[Na+]>>[O-:3][Si:1]([O-:4])=[O:2].[O-:3][Si:1]([O-:4])=[O:2].[Na+:6].[Al+3:11]
Reactant: O=[Al-]=O
Reactant: [O-][Si]([O-])([O-])[O-]
Agent: [Na+]
Product: O=[Si]([O-])[O-]
Product: [Al+3]

Procedure:
In a stainless steel vessel having an inner volume of about 2 l, 780 g of a dilute solution of sodium silicate was gradually mixed with 730 g of a dilute solution of sodium aluminate with stirring to obtain a sodium aluminosilicate gel which was homogeneous as a whole.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([O:14][C:15]3[S:16][C:17]4[CH:23]=[C:22]([CH:24]5[CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25]5)[CH:21]=[CH:20][C:18]=4[N:19]=3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([O:14][C:15]3[S:16][C:17]4[CH:23]=[C:22]([CH:24]5[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]5)[CH:21]=[CH:20][C:18]=4[N:19]=3)[CH2:10][CH2:9]2)=[N:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc3nc(OC4CCN(c5ncc(Cl)cn5)CC4)sc3c2)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Clc1cnc(N2CCC(Oc3nc4ccc(C5CCNCC5)cc4s3)CC2)nc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 94.4 %

Procedure:
To a solution of tert-butyl 4-(2-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)benzo[d]thiazol-6-yl)piperidine-1-carboxylate (133 mg, 0.251 mmol) in CH2Cl2 (2.5 mL) was added TFA (0.2 mL, 2.5 mmol). The reaction mixture was stirred at rt for 3 h. The reaction mixture was diluted with CH2Cl2 (5 mL) and washed with aq. NaOH (1 N, 3 mL) and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to afford 2-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)-6-(piperidin-4-yl)benzo[d]thiazole (102 mg, 0.237 mmol, 95% yield) as a pale yellow solid. LCMS (m/z)=430 (M+H)+.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10]N)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:12]1(=O)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.Cl.O>C(O)(=O)C>[N+:1]([C:4]1[CH:9]=[C:8]2[C:7](=[CH:6][CH:5]=1)[NH:10][C:13]1[CH2:14][CH2:15][CH2:16][CH2:17][C:12]2=1)([O-:3])=[O:2]
Reactant: NNc1ccc([N+](=O)[O-])cc1
Reactant: O=C1CCCCC1
Agent: Cl
Solvent: CC(=O)O
Solvent: O
Product: O=[N+]([O-])c1ccc2[nH]c3c(c2c1)CCCC3
Temperature: 60 °C
Reaction time: 0.33 h
Yield: 80.3 %

Procedure:
The mixture of p-nitrophenylhydrazine (12) (15.0 g, 97.9 mmol) and cyclohexanone (10.15 ml, 97.9 mmol) in acetic acid (45 ml) was heated and stirred for 20 minutes at 60° C. To the reaction mixture was added conc. hydrochloric acid (15 ml) and the resulting mixture was heated for 1.5 h at reflux. To the reaction mixture was added water (50 ml), heated for 10 minutes at reflux, and allowed to cool to room temperature. The precipitated crystal was filtered off, washed with water, and recrystallized from ethanol-water to give 6-nitrotetrahydrocarbazole (13) (17.0 g; yield 80%).
Reaction SMILES: Br[CH2:2][C:3]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[O:7][C:6]2[CH:14]=[CH:15][CH:16]=[CH:17][C:5]=2[CH:4]=1.[CH3:18][NH:19][CH2:20][CH2:21][CH3:22].[S:23]([C:27]1[CH:33]=[CH:32][C:30]([CH3:31])=[CH:29][CH:28]=1)([O-:26])(=[O:25])=[O:24].C1(C)C=CC(S(O)(=O)=O)=CC=1>C(OCC)(=O)C>[S:23]([C:27]1[CH:33]=[CH:32][C:30]([CH3:31])=[CH:29][CH:28]=1)([OH:26])(=[O:25])=[O:24].[CH:17]1[C:5]2[CH:4]=[C:3]([CH2:2][N:19]([CH3:18])[CH2:20][CH2:21][CH3:22])[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=3[O:7][C:6]=2[CH:14]=[CH:15][CH:16]=1
Reactant: Cc1ccc(S(=O)(=O)[O-])cc1
Reactant: CCCNC
Reactant: BrCC1=Cc2ccccc2Oc2ccccc21
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOC(C)=O
Product: CCCN(C)CC1=Cc2ccccc2Oc2ccccc21
Yield: 68 %

Procedure:
Preparation analogous to Example 2 from 10-bromomethyl-dibenz[b,f]oxepine and N-methyl-N-propylamine. Tosylate prepared with 1 equivalent of p-toluenesulfonic acid in ethyl acetate, crystallised from dichloromethane/tert-butyl methyl ether. Yield: 68%; melting point: 179°-180° C.; 1H-NMR (CD3OD, 200 MHz): 0.97 (t, 3H); 1.78 (m, 2H); 2.36 (s, 3H); 2.85 (s, 3H); 3.15 (mbr, 2H); 4.50 (mbr, 2H); 7.17°-7.75 (m, ca. 13H); MS: 279 (M+, free base), 250, 207.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH3:12]/[C:13](=[CH:21]\[CH2:22][CH2:23][C:24](=[CH2:27])[CH:25]=[CH2:26])/[CH2:14][CH2:15][C:16]([O:18]CC)=[O:17].C(Cl)Cl.C(=O)([O-])[O-].[K+].[K+]>CO.O>[OH:9][CH:21]([C:13]1([CH3:12])[CH2:14][CH2:15][C:16](=[O:18])[O:17]1)[CH2:22][CH2:23][C:24](=[CH2:27])[CH:25]=[CH2:26]
Reactant: C=CC(=C)CC/C=C(\C)CCC(=O)OCC
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Solvent: ClCCl
Product: C=CC(=C)CCC(O)C1(C)CCC(=O)O1
Temperature: 0 °C
Reaction time: 2 h
Yield: 58.2 %

Procedure:
m-Chloroperbenzoic acid (36 g, 0.175 M) is added in five portions to a mixture of ethyl 4-methyl-8-methylene-(E)-4,9-decadienoate (40 g, 0.18 M) and methylene chloride (1 l), at -8° C. under nitrogen and the resulting mixture is stirred for two hours. The precipitate is filtered and the filtrate dried in vacuo to give crude ethyl 4-methyl-8-methylene-4,5-oxido-9-decenoate. This material is dissolved in methanol (200 ml) and the resulting solution is treated with saturated potassium carbonate solution (50 ml) and water (50 ml) and stirred overnight. Most of the methanol is removed in vacuo, the residue is cooled to 0° C. and slowly treated with conc. hydrochloric acid (150 ml). The resulting mixture is extracted with ether (3×350 ml). The combined organic layers are dried (Na2SO4), the solvent is removed in vacuo, and the residue (52 g) is purified by column chromatography on silica gel (400 g) with ether-petroleum ether (4:1) to give 2-(1-hydroxy-4-methylene-5-hexenyl)-2-methyl-5-oxo-tetrahydrofuran as a colorless liquid (22 g, 58%).
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:8]([C:12]([F:15])([F:14])[F:13])[O:9]2)=[CH:4][CH:3]=1.[Br:21]Br.C(OCC)(=O)C>ClC(Cl)(Cl)Cl>[Br:21][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[F:1])[O:9][CH:8]([C:12]([F:14])([F:15])[F:13])[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:6]2
Reactant: BrBr
Reactant: CCOC(=O)C1=Cc2ccc(F)cc2OC1C(F)(F)F
Solvent: ClC(Cl)(Cl)Cl
Solvent: CCOC(C)=O
Product: CCOC(=O)C1=Cc2cc(Br)c(F)cc2OC1C(F)(F)F
Reaction time: 24 h
Yield: 44.6 %

Procedure:
To the solution of ethyl 7-fluoro-2-(trifluoromethyl)-2H chromene-3-carboxylate (5 g, 34 mmol) in 100 mL of tetrachloromethane was added dropwise at room temperature a solution of bromine(10.5 mL, 204 mmol) in 20 mL of tetrachloromethane. The resulting solution was stirred for 24 hrs. To the reaction was added 500 mL of ethyl acetate. The resulting organic phase was then washed with aqueous sodium thiosulfite to remove excess bromine, and brine, then dried over anhydrous magnesium sulfate. After removing the volatiles, the residue was purified on silica gel column with 1:9 EtOAc/hexane. It gave 5.6 g product. A small fraction of the product was further purified on reverse phase HPLC for analytica characterization. It gave a white solid. m.p.=98.5-100.0° C. 1H NMR(CDCl3/300 MHz) 7.67(s, 1H), 7.46(d, J=7.5 Hz, 1H), 6.83(d, J=9 Hz, 1H), 5.74(q, J=6.6 Hz, 1H), 4.36(m, 2H), 1.39(t, J=7.2 Hz, 3H). 19F NMR(CDCl3/300 MHz): −78.82(d, J=6.5 Hz), −98.7(t, J=7.9 Hz). 13C NMR(CDCl3/300 MHz): 163.6, 163.1, 159.7,154.0(d, J=11.5 Hz), 135.1, 133.4, 123.4(q, J=287.3 Hz), 117.3, 105.6(d, J=26.7 Hz), 102.2(d, J=22.3 Hz), 71.1(q, J=33.3 Hz), 61.9, 14.4. LC-MS(ES+): 369.2(M+1, 100). HRMS (EI+): m/z calc. For C13H9BrF4O3: 367.9671(M+), found: 367.9675.
Reaction SMILES: [NH2:1][CH2:2][C:3]1([N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.[C:16](OC(=O)C)(=[O:18])[CH3:17]>>[C:16]([NH:1][CH2:2][C:3]1([N:9]2[CH2:10][CH2:11][N:12]([CH3:15])[CH2:13][CH2:14]2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)(=[O:18])[CH3:17]
Reactant: CC(=O)OC(C)=O
Reactant: CN1CCN(C2(CN)CCCCC2)CC1
Product: CC(=O)NCC1(N2CCN(C)CC2)CCCCC1
Reaction time: 0.25 h
Yield: 65 %

Procedure:
1-[1-(Aminomethyl)cyclohexyl]-4-methyl piperazine (10.57 g.,) was added slowly to stirred acetic anhydride (40 ml) cooled in ice and the stirring was continued for 15 mins. The mixture was heated under reflux for 1 hr.. The solution was evaporated to dryness and re-evaporated with ethanol/benzene (X2). The residue was dissolved in water, the solution made alkaline with 5NNaOH (pH = 14), extracted with chloroform (X3), dried (anhyd.Na2SO4) and evaporated. The residue was dissolved in hot petroleum ether (80°-100°) decolourised with charcoal and allowed to cool. The crystalline solid which formed was recrystallised from petroleum ether (b.p. 80°-100°) to give 1-[1-(acetamidomethyl)cyclohexyl]-4-methyl piperazine (8.3 g; 65%) m.p. 110°-111°.
Reaction SMILES: [F:1][C:2]([F:26])([F:25])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:13][C:12]([C:14]3[CH:24]=[CH:23][CH:22]=[CH:21][C:15]=3[C:16]([O:18]CC)=[O:17])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[OH-].[Na+].O1CCCC1.Cl>O.C(O)C>[F:25][C:2]([F:1])([F:26])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[O:13][C:12]([C:14]3[CH:24]=[CH:23][CH:22]=[CH:21][C:15]=3[C:16]([OH:18])=[O:17])=[CH:11][CH:10]=2)=[CH:7][CH:8]=1
Reactant: CCOC(=O)c1ccccc1-c1ccc(-c2ccc(C(F)(F)F)cc2)o1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)c1ccccc1-c1ccc(-c2ccc(C(F)(F)F)cc2)o1
Temperature: 60 °C
Reaction time: 1 h
Yield: 53 %

Procedure:
A mixture of ethyl 2-[5-(4-trifluoromethylphenyl)-2-furyl]benzoate (1.80 g), 1 M aqueous sodium hydroxide solution (20 ml), tetrahydrofuran (35 ml) and ethanol (35 ml) was stirred at 60° C. for 1 hr. After cooling, the reaction mixture was poured into water and 1 M hydrochloric acid (30 ml) was added. The mixture was extracted with ethyl acetate-tetrahydrofuran (1:1, volume ratio). The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was recrystallized from hexane-ethanol to give 2-[5-(4-trifluoromethylphenyl)-2-furyl]benzoic acid (1.15, yield 53%) as colorless plate crystals. melting point: 182–183° C.
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[C:5]([C:7](=[O:9])[CH3:8])[N:6]=1.C[C:11]([N:13]([CH3:15])[CH3:14])=O.[CH3:16]N(C=O)C>>[CH3:11][N:13]([CH3:15])[CH:14]=[CH:8][C:7]([C:5]1[N:6]([CH3:16])[C:2]([CH3:1])=[N:3][CH:4]=1)=[O:9]
Reactant: CC(=O)c1c[nH]c(C)n1
Reactant: CC(=O)N(C)C
Reactant: CN(C)C=O
Product: Cc1ncc(C(=O)C=CN(C)C)n1C
Temperature: 25 °C
Yield: 57 %

Procedure:
2-Methyl-4-acetylimidazole (Tetrahedron letters 1985, 26 (29), 3423-3426; 129 g, 1.04 mol) was dissolved in a mixture of DMF (900 ml) and DMF.DMA (1.51) and the mixture heated under reflux, under an atmosphere of nitrogen, for 18 hours. The reaction mixture was allowed to cool to ambient temperature the product crystallised. The solid product was collected by filtration, washed with DMF.DMA and then ether and dried under vacuum at 40° C. to give the title compound (115 g, 57%) as a pale brown crystalline solid. NMR: 2.13 (s, 3H), 2.95 (s, 6H), 3.78 (s, 3H), 5.56 (d, 1H), 7.50 (d, 1H), 7.53 (s, 1H); m/z 194.
Reaction SMILES: O([C:8]([C:10]1[CH:19]=[CH:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]=1[OH:20])=[O:9])C1C=CC=CC=1.[S:21]([OH:31])(=[O:30])([C:23]1[CH:28]=[CH:27][C:26]([NH2:29])=[CH:25][CH:24]=1)=[O:22].C[N:33](C=O)C>C(N(CC)CC)C>[S:21]([C:23]1[CH:24]=[CH:25][C:26]([NH:29][NH:33][C:8]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]=2[OH:20])=[O:9])=[CH:27][CH:28]=1)([OH:31])(=[O:30])=[O:22]
Reactant: Nc1ccc(S(=O)(=O)O)cc1
Reactant: CN(C)C=O
Reactant: O=C(Oc1ccccc1)c1ccc2ccccc2c1O
Solvent: CCN(CC)CC
Product: O=C(NNc1ccc(S(=O)(=O)O)cc1)c1ccc2ccccc2c1O
Temperature: 170 °C
Reaction time: 5 h

Procedure:
To 13.2 g of 2-phenoxycarbonyl-1-naphthol, 8.6 g of sulfanilic acid, 20 ml of DMF and 14 ml of triethylamine were added. The mixture was stirred at 170° C. for 5 hours. The mixture was concentrated at reduced pressure and methanol was added to the residue. The crystals thus-precipitated were collected by filtration.