Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[C:2](C)([O-:4])C.[K+].[C:7]1([N:13]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:14]2[CH:19]=[CH:18][C:17]([C:20]3[S:24][C:23]4[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=4[C:21]=3[C:29]3[CH:36]=[CH:35][CH:34]=[CH:33][C:30]=3C=O)=[CH:16][CH:15]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C1COCC1>O1CCCC1.[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:37]1([N:13]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:14]2[CH:15]=[CH:16][C:17]([C:20]3[S:24][C:23]4[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=4[C:21]=3[C:29]3[CH:30]=[CH:33][C:34]([CH:2]=[O:4])=[CH:35][CH:36]=3)=[CH:18][CH:19]=2)[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1
Reactant: O=Cc1ccccc1-c1c(-c2ccc(N(c3ccccc3)c3ccccc3)cc2)sc2ccccc12
Reactant: CC(C)(C)[O-]
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [K+]
Solvent: C1CCOC1
Product: O=Cc1ccc(-c2c(-c3ccc(N(c4ccccc4)c4ccccc4)cc3)sc3ccccc23)cc1

Procedure:
A solution of 4-(2-(4-(diphenylamino)phenyl)benzo[b]thiophen-3-yl)benzaldehyde (1.1 g, 0.0023 mol) was prepared in anhydrous tetrahydrofuran (75 mL). To a dry round bottom flask equipped with an addition funnel, methyltriphenylphosphonium bromide (1.22 g, 0.003 mol) was added. Tetrahydrofuran (75 mL) was added to this reaction flask and allowed to stir. Potassium tert-butoxide (0.40 g, 0.0035 mol) was then added. The solution of (2-(4-(diphenylamino)phenyl)benzo[b]thiophen-3-yl)benzaldehyde/THF was then transferred to the addition funnel via cannula. This solution was then added to the reaction flask from the addition funnel drop-wise. The reaction solution was allowed to stir for approximately 1 hour and completion was then monitored via thin-layer chromatography. Following confirmation of completion, the reaction solution was filtered through a celite/silica gel (treated with triethylamine) plug. Solvent was removed by rotary evaporation. And the resulting solids were placed under vacuum. Crude mixture was purified by chromatography. Precipitation from a minimum amount of ethyl acetate into methanol yielded 1H NMR pure product. Product obtained: 0.7 g
Reaction SMILES: [NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:4]([C:13]2[CH:18]=[CH:17][C:16]([S:19]([NH2:22])(=[O:21])=[O:20])=[CH:15][CH:14]=2)[N:3]=1.[F:23][C:24]([F:35])([F:34])[C:25]1[CH:26]=[C:27]([N:31]=[C:32]=[O:33])[CH:28]=[CH:29][CH:30]=1.C(N(CC)CC)C.O>CN(C=O)C>[C:7]1([C:5]2[N:4]([C:13]3[CH:18]=[CH:17][C:16]([S:19]([NH2:22])(=[O:20])=[O:21])=[CH:15][CH:14]=3)[N:3]=[C:2]([NH:1][C:32]([NH:31][C:27]3[CH:28]=[CH:29][CH:30]=[C:25]([C:24]([F:23])([F:34])[F:35])[CH:26]=3)=[O:33])[CH:6]=2)[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: O=C=Nc1cccc(C(F)(F)F)c1
Reactant: Nc1cc(-c2ccccc2)n(-c2ccc(S(N)(=O)=O)cc2)n1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: NS(=O)(=O)c1ccc(-n2nc(NC(=O)Nc3cccc(C(F)(F)F)c3)cc2-c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 81 %

Procedure:
To a solution of amine 6 (0.1 g, 0.32 mmol) in 5 mL of DMF was added 3-(trifluoromethyl)phenyl isocyanate (0.12 g, 0.62 mmol) followed by triethylamine (0.05 mL, 0.32 mmol) at 0° C. The reaction mixture was warmed up to room temperature and stirred overnight. The reaction mixture was poured into water, and the resulting precipitates were collected and washed with water. The crude product was purified by column chromatography by dry loading method to give the titled compound (0.13 g, 81% yield). mp 195.1-197.0° C. 1H NMR (300 MHz, DMSO-d6): δ 9.48 (s, 1H), 9.21 (s, 1H), 8.07 (s, 1H), 7.80 (d, J=9 Hz, 2H), 7.61-7.26 (m, 12H), 6.81 (s, 1H). MS (ESI) m/z: 502.12 (M+H+). Anal. Calcd for C23H18F3N5O3S.0.36CH4O: C, 54.69; H, 3.82; N, 13.65. Found: C, 54.69; H, 3.70; N, 13.44.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:9])[C:7]=1[NH2:8].C(N(C(C)C)C(C)C)C.[C:19](Cl)(Cl)=[S:20]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:9])[C:7]=1[N:8]=[C:19]=[S:20]
Reactant: S=C(Cl)Cl
Reactant: Nc1c(Cl)cncc1Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: S=C=Nc1c(Cl)cncc1Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 20.3 %

Procedure:
To a solution of 3,5-dichloropyridin-4-amine (4.0 g, 24.53 mmol) in DCM (20 mL), was added N-ethyl di-isopropyl amine (6.3 g, 48.83 mmol). The reaction mixture was stirred at RT for 30 minutes. The reaction mixture was cooled at 0° C. and thiophosgene (2.76 g, 24.00 mmol) was added drop wise. The reaction mixture was stirred at 0° C. to RT for 3-4 h. The reaction mixture was diluted with DCM and the obtained crude was purified by column chromatography to afford 1.0 g of the desired product. 1HNMR (DMSO-d6): δ 8.77 (s, 2H); MS [M+H]+: 205.20.
Reaction SMILES: [NH2:1][C:2]1[C:7]([CH2:8]O)=[CH:6][C:5]([Br:10])=[CH:4][N:3]=1.[BrH:11]>>[BrH:10].[NH2:1][C:2]1[C:7]([CH2:8][Br:11])=[CH:6][C:5]([Br:10])=[CH:4][N:3]=1
Reactant: Nc1ncc(Br)cc1CO
Agent: Br
Product: Nc1ncc(Br)cc1CBr

Procedure:
A solution of 2-amino-5-bromo-3-hydroxymethylpyridine (5.00 g. 24.6 mmole), from Preparation 14 (b), in 48% aqueous HBr (50 mL), was heated at reflux for 12 hrs. The reaction was concentrated and toluene was used to azeotrope the residual H2O. The resulting light brown solid was placed under high vacuum overnight and used directly.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:15])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.C1C(=O)N(Br)C(=O)C1.BrC(C(C1C=CC(Br)=CC=1)=O)C(OCC)=O.[C:40]([N:47]1[CH2:54][CH2:53][CH2:52][C@H:48]1[C:49]([OH:51])=[O:50])([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41].CCN(C(C)C)C(C)C>C(Cl)Cl.C(#N)C>[N:47]1([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:54][CH2:53][CH2:52][CH:48]1[C:49]([O:51][C@H:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:8]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=1)=[O:15])=[O:50]
Reactant: CCOC(=O)CC(=O)c1ccc(Br)cc1
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)O
Agent: CCOC(=O)C(Br)C(=O)c1ccc(Br)cc1
Agent: O=C1CCC(=O)N1Br
Solvent: CC#N
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)[C@@H](OC(=O)C1CCCN1C(=O)OC(C)(C)C)C(=O)c1ccc(Br)cc1
Reaction time: 18 h

Procedure:
The ethyl 3-(4-bromophenyl)-3-oxopropanoate (15 g, 55 mmol) was dissolved in CH2Cl2 (600 mL) and freshly recrystallized NBS (9.8 g, 55 mmol) was added and the solution stirred 18 hr. The reaction mixture was washed with NaHCO3 solution, brine, and dried (MgSO4), filtered, and concentrated to give a residue which was not purified. Ethyl 2-bromo-3-(4-bromophenyl)-3-oxopropanoate (16.5 g, 48 mmol) and N-Boc-L-proline (10 g, 48 mmol) were taken up in acetonitrile (450 mL) and Hunig's base (16 mL, 95 mmol) was added and the solution stirred 18 hr. The solvent was removed by rotary evaporation and the residue taken up in ethyl acetate, washed with 0.1 N HCl, and brine. 1H NMR (300 MHz, DMSO-d6) δ 7.95 (d, J=8.4 Hz, 2H), 7.79 (d, J=8.4 Hz, 2H), 6.68-6.65 (m, 1H), 4.39-4.30 (m, 1H), 4.21-4.12 (m, 2H), 2.27-2.21 (m, 1H), 2.0-1.95 (m, 1H), 1.90-1.76 (m, 2H), 1.39 (s, 2H), 1.31 (s, 9H), 1.11 (t, J=7.3 Hz, 3H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9](=[N:11][OH:12])[CH3:10])[CH:3]=1.[H-].[Na+].[CH3:15][O:16][C:17]1[CH:24]=[CH:23][CH:22]=[C:21]([CH3:25])[C:18]=1[CH2:19]Br>CN(C)C=O>[CH3:15][O:16][C:17]1[CH:24]=[CH:23][CH:22]=[C:21]([CH3:25])[C:18]=1[CH2:19][O:12][N:11]=[C:9]([C:4]1[CH:3]=[C:2]([CH3:1])[CH:7]=[C:6]([CH3:8])[N:5]=1)[CH3:10]
Reactant: COc1cccc(C)c1CBr
Reactant: CC(=NO)c1cc(C)cc(C)n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cccc(C)c1CON=C(C)c1cc(C)cc(C)n1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
On the other hand, 0.50 g (3.05 mmol) of 1-(4,6-dimethyl-2-pyridinyl)ethanone oxime was dissolved in 10 ml of N,N-dimethylformamide, and the resultant solution was added with 0.12 g (3.00 mmol) of sodium hydride (60%, oiliness) under cooling with ice. The solution was then stirred for 30 min. at a temperature below 0° C. and then added with the whole amount of the crude product of 2-methoxy-6-methylbenzyl bromide prepared previously under cooling with ice. The resultant solution was stirred for an hour at a room temperature to complete a reaction, and the reacted solution was poured into ice water and subjected to an extraction with diethyl ether. The resultant nonaqueous layer was separated, and the separated layer was washed with water and then dried with anhydrous magnesium sulfate. The dried nonaqueous layer was then condensed under reduced pressure to produce a crude product. The crude product was then purified by means of silica gel column chromatography (eluate; hexane:ethyl acetate=7:3 (v/v)) and recrystallized in hexane to obtain the target compound in an amount of 0.30 g.
Reaction SMILES: [Cl-].[Ce+3].[Cl-].[Cl-].C[Mg]Br.[CH2:8](OCC)C.[CH:13]([C@H:16]1[C:20](=[O:21])[CH2:19][CH2:18][N:17]1[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23])([CH3:15])[CH3:14]>>[OH:21][C@@:20]1([CH3:8])[CH2:19][CH2:18][N:17]([C:22]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[O:23])[C@H:16]1[CH:13]([CH3:15])[CH3:14]
Reactant: CC(C)[C@H]1C(=O)CCN1C(=O)OCc1ccccc1
Reactant: CCOCC
Agent: C[Mg]Br
Agent: [Ce+3]
Agent: [Cl-]
Product: CC(C)[C@@H]1N(C(=O)OCc2ccccc2)CC[C@]1(C)O

Procedure:
By an operation in the same manner as in Reference Example 3 and using cerium chloride (6.35 g), 3 mol/L methylmagnesium bromide-diethyl ether solution (7.55 mL) and benzyl (2S)-2-isopropyl-3-oxopyrrolidine-1-carboxylate (2.7 g), the title compound was obtained as pale-yellow oil (yield: 1.78 g, yield: 62%).
Reaction SMILES: [C:1]([O:5][CH3:6])(=[O:4])[CH:2]=[CH2:3].[CH3:7][N:8]([CH3:12])[CH2:9]CO>>[C:1]([O:5][CH2:6][CH2:7][N:8]([CH3:12])[CH3:9])(=[O:4])[CH:2]=[CH2:3]
Reactant: CN(C)CCO
Reactant: C=CC(=O)OC
Product: C=CC(=O)OCCN(C)C

Procedure:
The mass of 2-dimethylaminoethyl acrylate thus obtained was 693 g, wherein 0.0122 wt % of methyl acrylate and 0.0134 wt % of 2-dimethylamino ethanol, that is 0.0256 wt % of the total, were contained, therefore, 2-dimethylaminoethyl acrylate with a small amount of raw components could be obtained. The concentrations of the raw components were obtained by gas chromatography (detector: TCD).
Reaction SMILES: [CH2:1]([NH:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([C:15]2[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=2[CH3:23])=[N:7][CH:6]=1)[CH2:2][CH3:3].CC(C)([O-])C.[K+].Br[CH2:31][CH:32]1[CH2:34][CH2:33]1.[NH4+].[Cl-]>CS(C)=O>[CH:34]1([CH2:33][N:4]([CH2:1][CH2:2][CH3:3])[C:5]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]([C:15]3[C:16]([CH3:23])=[CH:17][C:18]([CH3:22])=[CH:19][C:20]=3[CH3:21])=[N:7][CH:6]=2)[CH2:32][CH2:31]1
Reactant: CCCNc1cnc(-c2c(C)cc(C)cc2C)c2ccccc12
Reactant: BrCC1CC1
Agent: CC(C)(C)[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: CS(C)=O
Product: CCCN(CC1CC1)c1cnc(-c2c(C)cc(C)cc2C)c2ccccc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 57.6 %

Procedure:
To a solution of the product of step E (72 mg, 9.24 mmol) in DMSO (0.7 mL) was added potassium t-butoxide (40 mg, 0.36 mmol), followed by slow dropwise addition of bromomethylcyclopropane (0.028 mL, 0.3 mmol). The mixture was stirred at room temperature for 1 h, diluted by aqueous NH4Cl, and extracted twice with 50% ethyl ether in hexane. Combined organics were dried over Na2SO4, filtered, concentrated, and chromatographed on silica gel (6% to 10% ethyl acetate in hexane) to give 62 mg of the title compound as an oil 1H NMR (CDCl3): δ0.10 (m, 2H), 0.50 (m,2H), 0.78 (t,3H), 1.00 (m, 1H), 1.50 (q,2H), 186 (s, 6H), 2.38 (s, 3H), 2.45 (d, 2H), 2.56 (t, 2H), 4.07 (s, 2H), 6.98 (s, 2H), 7.42 (5, 1H), 7.52 (d,1H), 7.66 (t, 1H), 8.48 (d, 1H), 8.53 (s 1H)ppm.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH:7]([NH:9][C:10]1[CH:15]=[C:14]([CH3:16])[CH:13]=[CH:12][C:11]=1[OH:17])=O.C(OCC)(=O)C.Cl>CCOCC.O>[CH3:16][C:14]1[CH:13]=[CH:12][C:11]([OH:17])=[C:10]([NH:9][CH3:7])[CH:15]=1
Reactant: Cc1ccc(O)c(NC=O)c1
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CCOCC
Product: CNc1cc(C)ccc1O

Procedure:
To a suspension of lithium aluminium hydride (3.56 g, 94 mmol) in dry ether (100 ml) was added dropwise a solution of the compound (1) (10.9 g, 72 mmol) in dry ether (600 ml) under ice-cooling. The mixture was stirred under ice-cooling for 30 minutes, and thereto was added ethyl acetate and water in that order. The aqueous layer was neutralized with diluted hydrochloric acid and extracted with ether. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel to give the title compound (2). Yield 7.63 g (77%).
Reaction SMILES: [S-2].[Na+].[Na+].S(C1C=CC(C)=CC=1)([O-])(=O)=O.[Cl:15][C:16]1[CH:37]=[CH:36][C:19]([O:20][CH:21]([O:28][C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)[CH:22](O)[C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:18][CH:17]=1.O>CS(C)=O>[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([O:20][C:21]([O:28][C:29]2[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=2)=[CH:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:36][CH:37]=1
Reactant: CC(C)(C)C(O)C(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: [Na+]
Agent: [S-2]
Solvent: CS(C)=O
Solvent: O
Product: CC(C)(C)C=C(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1
Temperature: 120 °C

Procedure:
39 g (0.5 mole) of sodium sulfide are added to 47.8 g (0.1 mole) of the tosylate of 1,1-bis-(4-chlorophenoxy)-3,3-dimethylbutan-2-ol in 200 ml of dry dimethylsulfoxide, and the mixture is stirred at 120° C. until starting material is no longer detectable by high pressure liquid chromatography (HPLC). Thereafter, the mixture is cooled, water is added and the mixture is extracted twice with the same volume of ethyl acetate, the organic phase is dried and the solvent is distilled off under reduced pressure.
Reaction SMILES: [CH2:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[CH2:4][CH2:3][N:2]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].Br[C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[N:21]1[CH:22]=[CH:23][CH:24]=[C:19]([N:8]2[CH2:7][CH2:6][C:5]3([CH2:1][N:2]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:3][CH2:4]3)[CH2:10][CH2:9]2)[CH:20]=1
Reactant: Brc1cccnc1
Reactant: CC(C)(C)OC(=O)N1CCC2(CCNCC2)C1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCC2(CCN(c3cccnc3)CC2)C1
Temperature: 120 °C
Yield: 69 %

Procedure:
Sodium t-butylate (5.4 mmol, 3.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (1.8 mmol, 1.0 eq.) and 3-bromopyridine (1.8 mmol, 1.0 eq.) in toluene (30 ml) and the reaction mixture was degassed with N2. BINAP (0.108 mmol, 0.06 eq.) and Pd(OAc)2 (0.036 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo. The crude product was purified by column chromatography (silica gel, 30% ethyl acetate in hexane) in order to obtain the desired product. Yield: 69%
Reaction SMILES: [CH3:1][C:2]1[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[C:3]=1[CH2:4][C:5]1[N:6]=[CH:7][NH:8][CH:9]=1.[CH3:15]I.[OH-].[Na+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[C:3]=1[CH2:4][C:5]1[N:6]=[CH:7][N:8]([CH3:15])[CH:9]=1
Reactant: Cc1cccc(C)c1Cc1c[nH]cn1
Reactant: CI
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Product: Cc1cccc(C)c1Cc1cn(C)cn1
Temperature: 70 °C
Reaction time: 2 h

Procedure:
3.0 g of 4-(2',6'-dimethylbenzyl)-imidazole, 40 ml of toluene, 3.0 g of methyliodide, 0.14 g of tetrabutylammoniumhydrogensulfate and 40 ml of 48% sodium hydroxide are mixed. The mixture is stirred vigorously for 2 hours at 70° C., after which the mixture is cooled and filtered. The toluene layer is separated from the mother liquid, after which it is washed with water and evaporated to dryness. The residue is a mixture of 4-(2',6'-dimethylbenzyl)-3-methylimidazole and 4-(2',6'-dimethylbenzyl)-1-methylimidazole. These two components are separated column chromatographically, eluting the column with a mixture of chloroform and methanol.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([OH:11])=[C:4]([O:12][CH3:13])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:20](Cl)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>S1(CCCC1)(=O)=O.O>[CH2:20]([O:11][C:5]1[C:4]([O:12][CH3:13])=[CH:3][C:2]([Br:1])=[CH:7][C:6]=1[N+:8]([O-:10])=[O:9])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: ClCc1ccccc1
Reactant: COc1cc(Br)cc([N+](=O)[O-])c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=S1(=O)CCCC1
Solvent: O
Product: COc1cc(Br)cc([N+](=O)[O-])c1OCc1ccccc1
Reaction time: 24 h
Yield: 80.7 %

Procedure:
A mixture of 4-bromo-2-methoxy-6-nitrophenol (7.0 g), anhydrous potassium carbonate (2.12 g) and benzyl chloride (3.93 g) in dry sulpholane (70 ml) was stirred at 90°-95° C. for 24 hours. The mixture was then diluted with water (300 ml) and the resulting oil was extracted with diethyl ether (3×50 ml). The combined ethereal extracts were washed with aqueous sodium carbonate solution (2 N; 2×50 ml) and then with water (3×20 ml), dried over anhydrous sodium sulphate and evaporated in vacuo to give a solid, which was recrystallised from ethanol to give 2-benzyloxy-5-bromo-3-methoxynitrobenzene (7.7 g), m.p. 74°-76° C.
Reaction SMILES: [C:1]1([C:7]2[CH2:8][CH:9]3[CH2:25][CH:24]=[CH:23][CH:10]3[N:11]([S:13]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[N:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>[Pd].C(O)C>[C:1]1([C:7]2[CH2:8][CH:9]3[CH2:25][CH2:24][CH2:23][CH:10]3[N:11]([S:13]([C:16]3[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=3)(=[O:15])=[O:14])[N:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Cc1ccc(S(=O)(=O)N2N=C(c3ccccc3)CC3CC=CC32)cc1
Agent: [Pd]
Solvent: CCO
Product: Cc1ccc(S(=O)(=O)N2N=C(c3ccccc3)CC3CCCC32)cc1
Reaction time: 3 h

Procedure:
A catalytic amount of palladium on carbon was added to a solution of 3-phenyl-1-(4-tolylsulfonyl)-4,4a,5,7a-tetrahydro-1H-cyclopenta[c]pyridazine (0.5 g) in ethanol. The suspension was placed in a Parr Shaker apparatus under a H2 atmosphere (40 PSI) and shaken for 3 hours. The mixture was filtered through celite and concentrated. The resulting residue was purified by recrystallization from ethyl acetate to give the title compound as a solid: mp 171°-176° C.
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:17](Cl)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C=O)C>[CH2:17]([N:8]1[C:4]2[N:5]=[CH:6][N:7]=[C:2]([Cl:1])[C:3]=2[CH:10]=[CH:9]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: ClCc1ccccc1
Reactant: Clc1ncnc2[nH]ccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Clc1ncnc2c1ccn2Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 80.1 %

Procedure:
To a stirred solution of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (250 mg/1.63 mmol) in 12 mL of DMF was added 676 mg (4.89 mmol) of potassium carbonate and the resulting mixture stirred at room temperature for 20 min. Benzylchloride (310 mg/2.45 mmol) was added and the new mixture stirred at room temperature for 24 h then filtered, concentrated and the residue purified by silica gel chromatography (3:1 hexanes/ethyl acetate) affording 318 mg (80%) of the title compound. LRMS: 244.1 (M+1).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N+:12]([O-:14])=[O:13])[N:8]([CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C:7](=[O:21])[C:6](=[O:22])[NH:5]2.CO[CH:25]1[CH2:29][CH2:28][CH:27](OC)O1>C(O)(=O)C.O>[CH:15]1([N:8]2[C:9]3[C:4](=[CH:3][C:2]([N:1]4[CH:25]=[CH:29][CH:28]=[CH:27]4)=[C:11]([N+:12]([O-:14])=[O:13])[CH:10]=3)[NH:5][C:6](=[O:22])[C:7]2=[O:21])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: Nc1cc2[nH]c(=O)c(=O)n(C3CCCCC3)c2cc1[N+](=O)[O-]
Reactant: COC1CCC(OC)O1
Solvent: O
Solvent: CC(=O)O
Product: O=c1[nH]c2cc(-n3cccc3)c([N+](=O)[O-])cc2n(C2CCCCC2)c1=O
Yield: 6.8 %

Procedure:
3.0 g (99 mmol) of 6-amino-1-cyclohexyl-7-nitro-2,3(1H,4H)-quinoxalinedione and 1.3 g (99 mmol) of 2,5-dimethoxytetrahydrofuran were refluxed in 70 ml of acetic acid for 30 minutes. The mixture was then diluted with water, and the precipitate was filtered off with suction to yield 2.4 g (69%) of the product. Melting point 197° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]2[S:17][C:18]([CH:21]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)O)=[CH:19][N:20]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1.C(Cl)Cl>>[CH2:21]([C:18]1[S:17][C:16]([NH:15][C:5]2[CH:6]=[CH:7][C:8]([N:9]3[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]3)=[C:3]([O:2][CH3:1])[CH:4]=2)=[N:20][CH:19]=1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: COc1cc(Nc2ncc(C(O)c3ccccc3)s2)ccc1-n1cnc(C)c1
Solvent: ClCCl
Product: COc1cc(Nc2ncc(Cc3ccccc3)s2)ccc1-n1cnc(C)c1
Temperature: 25 °C
Reaction time: 6 h
Yield: 97.4 %

Procedure:
To a solution of 35 mg (0.09 mmol) {2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-thiazol-5-yl}-phenyl-methanol in methylene chloride (2 ml) 12 mg (0.1 mmol) triethylsilane was added at room temperature and trifluoro acetate (2 ml) was added. The reaction was stirred at room temperature for 6 hours and the solvent was evaporated under reduced pressure. The residue was suspended in saturated aqueous sodium hydrogen carbonate solution and extracted twice with methylene chloride. The combined organic layers were washed with brine, dried over sodium sulphate, filtered and the solvent was evaporated under reduced pressure to yield 33 mg (98%) (5-benzyl-thiazol-2-yl)-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine as a brown solid. MS ISP (m/e): 377.4 (100) (M+H)+. 1H NMR (CDCl3, 250 MHz): δ (ppm)=7.64 (s, 1H), 7.53 (s, 1H), 7.35-7.22 (m, 7H), 7.07 (s, 1H), 7.01 (s, 1H), 4.03 (s, 2H), 3.77 (s, 3H), 2.13 (s, 3H).
Reaction SMILES: C(OC(CCCCC(O[C:18]1[C:27](=[O:28])[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[O:20][C:19]=1[C:29]1[CH:34]=[CH:33][C:32](OC(CCCCC(OCC2C=CC=CC=2)=O)=O)=[CH:31][CH:30]=1)=O)=O)C1C=CC=CC=1.[H][H].C1COCC1>CCOC(C)=O.[OH-].[OH-].[Pd+2]>[O:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:27](=[O:28])[CH:18]=[C:19]1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: [H][H]
Reactant: O=C(CCCCC(=O)Oc1ccc(-c2oc3ccccc3c(=O)c2OC(=O)CCCCC(=O)OCc2ccccc2)cc1)OCc1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=c1cc(-c2ccccc2)oc2ccccc12
Yield: 130.9 %

Procedure:
A mixture of 3,4′-di-(benzyloxycarbonylbutylcarbonyloxy)flavone (435 mg, 0.629 mmol) and Pd(OH)2 (50 mg) in EtOAc (5 mL) was treated with hydrogen for 2 h resulting in a grey precipitate. THF was added to dissolve the precipitate and the mixture was filtered (Celite). The pad washed with THF, and the filtrate concentrated. The solid residue was recrystallised from THF/petrol to afford the bis(hemiadipate) as a colourless solid (183 mg, 50%); mp 133° C.; 1H NMR (500 MHz, d6-DMSO) δ 1.55-1.70 (m, 8H, CH2CH2), 2.24 (t, 2H, J=7.0 Hz, CH2CO), 2.27 (t, 2H, J=7.0 Hz, CH2CO), 2.63 (t, 2H, J=7.0 Hz, CH2CO), 2.64 (t, 2H, J=7.0 Hz, CH2CO), 7.37 app. d, 2H, J=9.0 Hz, H3′,5′), 7.55 (dd, 1H, J5,6=8.5, J6,7=7.5, Hz, H6), 7.80 (d, 1H, J7,8=8.5 Hz, H8), 7.88 (ddd, 1H, J6,7=7.5, J7,8=8.5, J5,7=1.5 Hz, H7), 7.96 (app. d, 2H, J=9.0 Hz, H2′,6′), 8.08 (dd, 1H, J5,6=8.5, J5,7=1.5 Hz, H5); 13C NMR (125 MHz, d6-DMS) δ 23.77, 23.82, 32.6, 33.2, 33.3; 44.3 (CH2), 118.7, 122.5, 122.6, 122.7, 125.1, 126.8, 129.7, 132.9, 134.8, 152.7, 154.9, 155.1 (Ar), 170.4, 171.1, 171.4, 174.3, 174.3 (5C, C═O); IR 3059, 2940, 2873, 1768, 1706, 1504, 759 cm−1; HRMS (ESI−) m/z 509.1441, C27H25O10 [M−H]− requires 509.1442.