Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:3]1[N:7]([CH3:8])[C:6]2[CH:9]=[C:10]([N:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][C:14]3=[O:20])[CH:11]=[CH:12][C:5]=2[N:4]=1)[CH3:2].[Cl:21][C:22]1[S:26][CH:25]=[C:24]([CH2:27]O)[CH:23]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1.O>[Cl:21][C:22]1[S:26][CH:25]=[C:24]([CH2:27][O:19][C:16]2[CH:17]=[CH:18][N:13]([C:10]3[CH:11]=[CH:12][C:5]4[N:4]=[C:3]([CH2:1][CH3:2])[N:7]([CH3:8])[C:6]=4[CH:9]=3)[C:14](=[O:20])[CH:15]=2)[CH:23]=1
Reactant: OCc1csc(Cl)c1
Reactant: CCc1nc2ccc(-n3ccc(O)cc3=O)cc2n1C
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: O
Solvent: C1CCOC1
Product: CCc1nc2ccc(-n3ccc(OCc4csc(Cl)c4)cc3=O)cc2n1C
Temperature: 60 °C
Reaction time: 2 h
Yield: 31 %

Procedure:
To a solution of 1-(2-ethyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one (2.5 g), (5-chloro-3-thienyl)methanol (2.48 g) and tributylphosphine (5.63 g) in THF (150 ml) was added 1,1′-(azodicarbonyl)dipiperidine (7.03 g), and the reaction mixture was stirred at 60° C. for 2 h. The reaction mixture was cooled to room temperature. The mixture was poured into water and extracted with EtOAc. The extract was washed With brine, dried over MgSO4, concentrated and purified by NH silica gel column chromatography (hexane/EtOAc then ETOAc/MeOH). The resulting solid was recrystallized from EtOH-hexane to give the title compound (1.15 g) as a white solid.
Reaction SMILES: O.ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.[CH3:23][N:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([CH3:33])=[C:25]1[C:34]([NH:36][C@H:37]([C:41]([OH:43])=O)[CH:38]([CH3:40])[CH3:39])=[O:35].[NH2:44][CH:45]([CH:54]([OH:66])[CH2:55][O:56][CH2:57][C:58]1[C:63]([Cl:64])=[CH:62][CH:61]=[CH:60][C:59]=1[Cl:65])[CH2:46][C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48]>C(OCC)(=O)C.CCCCCC.C(Cl)Cl>[CH3:23][N:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([CH3:33])=[C:25]1[C:34]([NH:36][C@H:37]([C:41]([NH:44][CH:45]([CH:54]([OH:66])[CH2:55][O:56][CH2:57][C:58]1[C:59]([Cl:65])=[CH:60][CH:61]=[CH:62][C:63]=1[Cl:64])[CH2:46][C:47]([O:49][C:50]([CH3:52])([CH3:51])[CH3:53])=[O:48])=[O:43])[CH:38]([CH3:39])[CH3:40])=[O:35]
Reactant: Cc1c(C(=O)N[C@H](C(=O)O)C(C)C)n(C)c2ccccc12
Reactant: CC(C)(C)OC(=O)CC(N)C(O)COCc1c(Cl)cccc1Cl
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1c(C(=O)N[C@H](C(=O)NC(CC(=O)OC(C)(C)C)C(O)COCc2c(Cl)cccc2Cl)C(C)C)n(C)c2ccccc12
Temperature: 0 °C
Reaction time: 1 h
Yield: 41 %

Procedure:
1-Hydroxybenzotriazole hydrate (153 mg, 1.0 mmol) and EDAC (268 mg, 1.4 mmol) were added to a methylene chloride solution of N-(1,3-dimethylindole-2-carbonyl)valine (288 mg, 1.0 mmol, in 3 mL of methylene chloride). The resultant mixture was stirred for 10 minutes under a nitrogen atmosphere at room temperature. A methylene chloride solution of 3-amino-5-(2′,6′-dichlorobenzyloxy)-4-hydroxypentanoic acid, t-butyl ester (364 mg, 1.0 mmol, in 2 mL of methylene chloride) was added to the reaction mixture and the mixture was first stirred for one hour under a nitrogen atmosphere at 0° C., and then for 16 hours at room temperature. The reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution and the aqueous solution was back-extracted with ethyl acetate. The combined ethyl acetate solutions were washed with 5% KHSO4 solution, saturated sodium bicarbonate solution (2×) and brine, dried over sodium sulfate, and concentrated to give crude product (583 mg). The crude product was subjected to flash chromatography on silica gel with ethyl acetate/hexane (2/3) to give the title product as a white solid (260 mg). TLC: (ethyl acetate/hexanes 1:1): Rf=0.38.
Reaction SMILES: II.Br[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH:20]([O:22][CH3:23])=O.[BH4-].[Na+].Cl>C1COCC1.O>[CH2:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH:11]([OH:12])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:20][O:22][CH2:23][C:19]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: BrCCCCCCCCOCc1ccccc1
Reactant: COC=O
Agent: Cl
Agent: II
Agent: [BH4-]
Solvent: C1CCOC1
Solvent: O
Product: OC(CCCCCCCCOCc1ccccc1)CCCCCCCCOCc1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 48.5 %

Procedure:
To freshly activated Mg turnings (24.08 g, 1.003 mol) was added 200 mL anhydrous THF was added followed by the addition of pinch of iodine into the mixture under inert atmosphere. After initiation of the Grignard formation a solution of Compound 3 (150 g, 0.5016 mol) in 1 L of dry THF was added slowly controlling the exothermic reaction. After complete addition reaction was refluxed for 1 h and then cooled to room temperature. (60.24 g, 1.0033 mol) methyl formate was then added slowly and reaction was continued for 2 h. After completion, the reaction was quenched by slow addition of 10% HCl followed by water (1 L) and extracted with Ethyl Acetate (3×1 L). Organic layer was taken in 5 lit beaker, diluted with 500 mL of methanol and cooled to 0° C. To this solution excess of NaBH4 (˜5 eq) was added in portions to ensure the hydrolysis of formate ester which was not cleaved by addition of HCl. Resulting solution was stirred for an hour and then volatilites were stripped off under vacuum. Residue was taken in water (1 L) and acidified by 10% HCl solution (PH 4). Product was then extracted out with ethyl acetate (3×1 L). Organic phase was then dried and concentrated on rotary evaporator to get the desired compound 4 (57 g, 24%) as solid. H1 NMR (400 MHz, CDCl3): δ=7.35-7.32 (m, 8H), 7.29-7.24 (m, 2H), 4.49 (s, 4H), 3.56 (m, 1H), 3.46-3.43 (m, 4H), 1.63-1.56 (m, 4H), 1.44-1.34 (m, 28H). C13 NMR (100 MHz, CDCl3): δ=138.56, 128.21, 127.49, 127.34, 72.72, 71.76, 70.37, 37.37, 29.64, 29.56, 29.47, 29.33, 26.07, 25.54.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH2:11][C@@H:10]([O:12][S:13]([CH3:16])(=[O:15])=[O:14])[C@H:9]([O:17][S:18]([CH3:21])(=[O:20])=[O:19])[C@H:8](OS(C)(=O)=O)[CH:7]=1)=[O:5])[CH3:2].CS(C)=O.[N-:31]=[N+:32]=[N-:33].[Na+]>CCOC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[CH2:11][C@@H:10]([O:12][S:13]([CH3:16])(=[O:15])=[O:14])[C@@H:9]([O:17][S:18]([CH3:21])(=[O:20])=[O:19])[C@H:8]([N:31]=[N+:32]=[N-:33])[CH:7]=1)=[O:5])[CH3:2]
Reactant: [N-]=[N+]=[N-]
Reactant: CCOC(=O)C1=C[C@@H](OS(C)(=O)=O)[C@@H](OS(C)(=O)=O)[C@H](OS(C)(=O)=O)C1
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CCOC(=O)C1=C[C@@H](N=[N+]=[N-])[C@H](OS(C)(=O)=O)[C@H](OS(C)(=O)=O)C1
Reaction time: 2.5 h
Yield: 70.5 %

Procedure:
A 5 mL round-bottom flask equipped with a magnetic stirrer and an inert gas supply was charged with 436.3 mg of 12 and 0.83 mL DMSO. To the clear colorless solution at RT was added 71.5 mg sodium azide and the reaction mixture was stirred for 2.5 h, then an additional 13.7 mg of sodium azide were added and stirring continued at RT for 19 h. The reaction mixture was diluted with 5 mL of EtOAc and extracted three times with a 1 M solution of NaHCO3. The organic phase was separated, dried (Na2SO4), filtered and evaporated at 20° C./140-10 mbar to obtain 0.33 g of the crude product as light yellow oil. The crude product was purified by SiO2 column chromatography eluting with a ½ mixture of EtOAc and n-hexane. The combined fractions were evaporated and dried on a rotary evaporator to obtain 0.27 g of 14 as a colorless oil
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([C:12]([OH:14])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.ON1C2C=CC=CC=2N=N1.Cl.[CH3:27][NH:28][CH3:29].Cl.CN(C)CCCN=C=NCC.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([C:12](=[O:14])[N:28]([CH3:29])[CH3:27])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CNC
Reactant: CC(C)(C)OC(=O)N1CC(C(=O)O)C1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CN(C)C(=O)C1CN(C(=O)OC(C)(C)C)C1
Reaction time: 0.5 h

Procedure:
To 300 mg (1.49 mmol) azetidine-1,3-dicarboxylic acid mono-tert-butyl ester and 241.6 mg (1.79 mmol) 1-hydroxybenzotriazole hydrate in 20 mL DMF at 0° C., was added 364.5 mg (4.47 mmol) dimethylamine hydrochloride, and the reaction was stirred for 30 minutes. 342.8 mg (1.79 mmol) N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, followed by 1.5 mL (8.94 mmol) DIPEA were added, and the reaction was stirred at room temperature for 3 hours. After evaporation of the solvent, the crude was diluted with 100 mL DCM. The organic phase was washed with a 2 M solution of HCl (2×50 mL), a saturated solution of NaHCO3 (2×50 mL), brine (2×50 mL), and dried over Na2SO4. After filtration, the solvent was evaporated to give the desired product which was used for the next step without further purification.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([S:8]([NH2:11])(=[O:10])=[O:9])[CH2:4][CH2:3]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:53]1[CH:58]=[C:57]([O:59][C@H:60]([CH3:82])[CH2:61][O:62][C:63]([C:76]2[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=2)([C:70]2[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=2)[C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)[N:56]=[C:55]([S:83][CH2:84][C:85]2[CH:90]=[CH:89][CH:88]=[C:87]([F:91])[C:86]=2[F:92])[N:54]=1>O1CCOCC1.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:92][C:86]1[C:87]([F:91])=[CH:88][CH:89]=[CH:90][C:85]=1[CH2:84][S:83][C:55]1[N:54]=[C:53]([NH:11][S:8]([N:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)(=[O:10])=[O:9])[CH:58]=[C:57]([O:59][C@H:60]([CH3:82])[CH2:61][O:62][C:63]([C:76]2[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=2)([C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)[C:70]2[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=2)[N:56]=1
Reactant: C[C@H](COC(c1ccccc1)(c1ccccc1)c1ccccc1)Oc1cc(Cl)nc(SCc2cccc(F)c2F)n1
Reactant: CN1CCN(S(N)(=O)=O)CC1
Agent: [Pd]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Solvent: ClCCl
Product: C[C@H](COC(c1ccccc1)(c1ccccc1)c1ccccc1)Oc1cc(NS(=O)(=O)N2CCN(C)CC2)nc(SCc2cccc(F)c2F)n1
Temperature: 100 °C

Procedure:
A mixture of 4-Methylpiperazine-1-sulfonamide (the product from step i) (0.64 g), tris(dibenzylideneacetone)dipalladium (0) (50 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (50 mg), cesium carbonate (0.55 g) and 4-chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-methyl-2-(triphenylmethoxy)ethoxy]-pyrimidine ((the product of example 13 step iii), 0.50 g) in dioxane (40 mL) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 1 h. The reaction mixture was diluted with DCM, filtered through arbocel and the filtrate evaporated. The residue was purified by reverse phase HPLC using a TFA (0.2%)/MeCN system to give the subtitle compound as a yellow solid. Yield: 0.22 g.
Reaction SMILES: N[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5](SC2C=CC(S(O)(=O)=O)=C(N)C=2)=[CH:4][C:3]=1C(O)=O.N1C(Cl)=NC(Cl)=NC=1Cl>>[CH:9]1[C:8]2[C:7](=[O:17])[C:6]3[C:15](=[CH:2][CH:3]=[CH:4][CH:5]=3)[C:14](=[O:16])[C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: Nc1cc(Sc2cc(C(=O)O)c(N)c3c2C(=O)c2ccccc2C3=O)ccc1S(=O)(=O)O
Agent: Clc1nc(Cl)nc(Cl)n1
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
Example 13 was repeated, except that the compounds described in 1st, 2nd and 3rd columns of the following table were used in place of the 1-amino-2-carboxy-4-(3'-amino-4'-sulfophenylthio)anthraquinone, cyanuric chloride and 1-aminobenzene-3-β-sulfatoethylsulfone, respectively, thereby obtaining a corresponding anthraquinone compound. The color shade obtained by dyeing cotton with the anthraquinone compound is as shown in a 4th column of the table.
Reaction SMILES: [C:1]1(/[CH:9]=[CH:10]/[C:11]2[CH:17]=[CH:16][C:14]([OH:15])=[CH:13][CH:12]=2)[CH:8]=[C:6]([OH:7])[CH:5]=[C:3]([OH:4])[CH:2]=1.C([O-])(O)=O.[Na+]>C(O)C>[C:1]1([CH:9]=[CH:10][C:11]2[CH:17]=[CH:16][C:14]([OH:15])=[CH:13][CH:12]=2)[CH:8]=[C:6]([OH:7])[CH:5]=[C:3]([OH:4])[CH:2]=1
Reactant: Oc1ccc(/C=C/c2cc(O)cc(O)c2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: Oc1ccc(C=Cc2cc(O)cc(O)c2)cc1

Procedure:
700 mg of trans-resveratrol (manufactured by Tokyo Chemical Industry Co., Ltd.) was dissolved in 14 ml of ethanol, and then 14 mL of a 2.5% NaHCO3 aqueous solution was added thereto to obtain a resveratrol containing solution (pH 9.9). The resveratrol containing solution was heated at 130° C. for 20 minutes in an autoclave (“SANYO LABO AUTOCLAVE” manufactured by SANYO Electric Co., Ltd., which was used in the following Examples). Subsequently, 14 ml of ethanol and 14 mL of a 5.0% NaHCO3 aqueous solution were added to the reaction solution obtained by the first autoclave treatment, and then heated again at 130° C. for 20 minutes in the autoclave. Then, 1 mL of the obtained reaction solution was diluted with methanol in a measuring cylinder to 50 mL, and then 10 L, thereof was analyzed by HPLC.
Reaction SMILES: C[O-].[Na+].[C:4]1([SH:10])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:11]1(=[O:16])[O:15][CH2:14][CH2:13][CH2:12]1>C(O)C>[C:4]1([S:10][CH2:14][CH2:13][CH2:12][C:11]([OH:16])=[O:15])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: O=C1CCCO1
Reactant: Sc1ccccc1
Agent: C[O-]
Agent: [Na+]
Solvent: CCO
Product: O=C(O)CCCSc1ccccc1
Temperature: 25 °C
Yield: 52 %

Procedure:
Sodium methoxide (1.2 equivalent) was added to 60 ml of ethanol, in one portion, and the suspension was stirred at room temperature. Thiophenol (1 equivalent) was added to the above suspension and stirred at room temperature for 30 minutes. Butyrolactone (1.1 equivalent) was added to the reaction mixture and the resulting mixture was stirred at reflux temperature for 6 hours, cooled to room temperature and concentrated in vacuo. The resulting solid was washed with 200 ml hexane/ether 2:1, v/v. The solid was suspended into ice cold 2N HCl solution and stirred for 15 minutes. The resulting solid was filtered, washed with 100 ml hexane/ether and dried under reduced pressure at room temperature to give 4-(phenylsulfanyl)butanoic acid as tan solid: 52% yield; 1H NMR (CDCl3) δ 7.32-7.12 (m, 5H), 2.94 (t, 2H, J=7.2 Hz), 2.41 (t, 2H, J=7.2 Hz), 1.85 (p, 2H, J=7.2 Hz); Anal. Calc. For C10H12S1O2 : C, 61.22; H, 6.12. Found: C, 61.16; H, 6.28.
Reaction SMILES: [OH-].[Na+].C[O:4][C:5]([C:7]1[C:8]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][C:19]=2[Cl:25])=[C:9]([Cl:16])[C:10]2[N:11]([CH:13]=[CH:14][N:15]=2)[CH:12]=1)=[O:6]>CO>[Br:24][C:21]1[CH:22]=[CH:23][C:18]([NH:17][C:8]2[C:7]([C:5]([OH:6])=[O:4])=[CH:12][N:11]3[CH:13]=[CH:14][N:15]=[C:10]3[C:9]=2[Cl:16])=[C:19]([Cl:25])[CH:20]=1
Reactant: COC(=O)c1cn2ccnc2c(Cl)c1Nc1ccc(Br)cc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1cn2ccnc2c(Cl)c1Nc1ccc(Br)cc1Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Sodium hydroxide (1.0 M aqueous solution, 14.6 mL, 14.6 mmol) was added to a solution of 7-(4-bromo-2-chlorophenylamino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylic acid methyl ester (29) in methanol (30 mL) and the solution allowed to stir at room temperature overnight. Methanol was removed by rotary evaporation and the solution diluted with water and acidified to pH 2 by addition of 1.0 M HCl. The aqueous suspension was extracted with 4:1 ethyl acetate/THF. The organic extracts were washed with brine, dried over NaSO4, filtered, and concentrated in vacuo to provide the desired product as a light orange solid (30). MS (APCI+) m/z 400, 402, 404 (M+: Cl, Br pattern) detected. 1H NMR (400 MHz, methanol-d4) δ 9.01 (s, 1H), 7.83 (s, 1H), 7.51 (s, 2H), 7.25 (d, 1H), 6.60 (d, 1H).
Reaction SMILES: C1C(=O)N([Br:8])C(=O)C1.[CH3:9][C:10]1[N:11]([S:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)(=[O:21])=[O:20])[C:12]2[C:17]([CH:18]=1)=[CH:16][CH:15]=[CH:14][N:13]=2.O>CC#N>[Br:8][C:18]1[C:17]2[C:12](=[N:13][CH:14]=[CH:15][CH:16]=2)[N:11]([S:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)(=[O:20])=[O:21])[C:10]=1[CH3:9]
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cc2cccnc2n1S(=O)(=O)c1ccccc1
Solvent: O
Solvent: CC#N
Product: Cc1c(Br)c2cccnc2n1S(=O)(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 72.1 %

Procedure:
72 mg of NBS in 2 ml of CH3CN are added to a solution of 100 mg of 2-methyl-1-(benzenesulfonyl)-7-azaindole in 3 ml of CH3CN. The mixture is stirred at room temperature for 20 h, poured into water, the precipitate which has precipitated out is separated off and dried, giving 93 mg of 3-bromo-2-methyl-1-(benzenesulfonyl)-7-azaindole, M˜351.22 g/mol, M+H found 351.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13][C:12]3[CH:14]=[C:15]([O:18][CH3:19])[CH:16]=[CH:17][C:11]=3[CH:10]=2)=[CH:5][CH:4]=1.[CH3:20][O:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](Cl)=[O:27])=[CH:24][CH:23]=1.[Al+3].[Cl-].[Cl-].[Cl-].O>C(Cl)Cl.CCOC(C)=O>[CH3:20][O:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([C:10]2[C:11]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:12]=3[S:13][C:9]=2[C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[O:27])=[CH:24][CH:23]=1
Reactant: COc1ccc(C(=O)Cl)cc1
Reactant: COc1ccc(-c2cc3ccc(OC)cc3s2)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: COc1ccc(C(=O)c2c(-c3ccc(OC)cc3)sc3cc(OC)ccc23)cc1
Reaction time: 1.3 h
Yield: 77.9 %

Procedure:
To a well stirred solution of 2-(4′-methoxyphenyl)-6-methoxybenzo[b]thiophene (0.305 g, 1.13 mmol) and 4-methoxybenzoyl chloride (0.378 g, 2.22 mmol) in CH2Cl2 (45 ml) was added AlCl3 (0.550 g, 4.12 mmol) portion-wise over a 15 minute period. After 1.3 hours, water was added, and the product was isolated initially by extraction with CH2Cl2 and subsequently by extraction with EtOAc. The organic layers were separately washed with brine and then combined and dried over MgSO4. Purification by flash chromatography (silica gel, 70:30 EtOAc/hexanes) afforded the title compound (0.3576 g, 0.88 mmol, 78%) as a pale yellow solid. Recrystallization (EtOAc/hexanes) afforded a highly pure, crystalline sample with mp 119-120° C. 1H-NMR (CDCl3, 360 MHz): δ=7.77 (d, J=9.0 Hz, 2H, ArH), 7.52 (d, J=8.9 Hz, 1H, ArH), 7.35 (d, J=8.9 Hz, 2H, ArH), 7.31 (d, J=2.3 Hz, 1H, ArH), 6.95 (dd, J=8.9, 2.4 Hz, 1H, ArH), 6.76 (d, J=9.0, 2H, ArH), 6.75 (d, J=8.9, 2H, ArH), 3.87 (s, 3H, —OCH3), 3.79 (s, 3H,—OCH3), 3.74 (s, 3H, —OCH3); 13C-NMR (CDCl3, 90 MHz): δ=193.2, 193,7, 159.7, 157.6, 142.4, 140.0,134.0, 132.2, 130.5, 130.4, 130.2,126.0,124.0, 114.7, 114.0, 113.6, 104.5, 55.6, 55.4, 55.2. HRMS (EI) M+ calcd for C24H20O4S, 404.1082, found 404.1059. Anal. Calcd for C24H20O 4S: C, 71.27; H, 4.98; S, 7.93. Found: C, 71.39; H, 4;98; S, 7.90.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:24]=[C:25]([N:27]2[CH2:32][CH2:31][CH:30]([CH3:33])[CH2:29][CH2:28]2)[CH:26]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][CH2:19][C:20]([NH:22][NH2:23])=O)=[CH:10][CH:9]=1)=[O:6].[CH2:34]([N:36]=[C:37]=[O:38])[CH3:35]>>[CH2:34]([N:36]1[C:37](=[O:38])[NH:23][N:22]=[C:20]1[CH2:19][O:18][C:11]1[C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]([NH:7][C:5](=[O:6])[C:4]2[CH:24]=[C:25]([N:27]3[CH2:32][CH2:31][CH:30]([CH3:33])[CH2:29][CH2:28]3)[CH:26]=[C:2]([F:1])[CH:3]=2)=[CH:9][CH:10]=1)[CH3:35]
Reactant: CC1CCN(c2cc(F)cc(C(=O)Nc3ccc(OCC(=O)NN)c4ccccc34)c2)CC1
Reactant: CCN=C=O
Product: CCn1c(COc2ccc(NC(=O)c3cc(F)cc(N4CCC(C)CC4)c3)c3ccccc23)n[nH]c1=O
Temperature: 25 °C
Reaction time: 15 h
Yield: 87.7 %

Procedure:
To a solution of 3-fluoro-N-(4-hydrazinocarbonylmethoxy-naphthalen-1-yl)-5-(4-methyl-piperidin-1-yl)-benzamide (0.35 g, 0.77 mmol) tetrahydrofuran (10 ml) is added ethylisocyanate (60 mg, 1.1 eq). The mixture is stirred at room temperature for 15 hours before being evaporated to dryness to give the urea intermediate as a solid (0.34 g). MS: 522 (M+1). Urea intermediate (0.1 g, 0.19 mmol) in 5% NaOH (2 ml) is heated at 100° C. for five hours. The mixture is then extracted with ethyl acetate, washed with water, dried over Na2SO4 and evaporated to dryness. The residue is purified by column chromatography on silica gel eluted with ethyl acetate then ethyl acetate containing a few drops of ammonium hydroxide to give N-[4-(4-ethyl-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-ylmethoxy)-naphthalen-1-yl]-3-fluoro-5-(4-methyl-piperidin-1-yl)-benzamide as a white solid (21 mg). Mp: 240-241° C. 1H NMR (300 MHz, DMSO-d6) δ 11.88 (s, 1H), 10.27 (s, 1H), 8.16 (d, J=5.1 Hz, 1H), 7.88 (d, J=4.5 Hz, 1H), 7.57-6.95 (m, 7H), 5.27 (s, 2H), 3.78 (m, 4H), 2.77 (t, J=11.4 Hz, 2H) 1.68 (m, 3H), 1.20 (brs, 6H), 0.95 (brs, 3H). MS: 504 (M+1).
Reaction SMILES: [C:1]([OH:8])(=[O:7])[CH2:2][CH2:3][C:4]([CH3:6])=[O:5].C(O)=O.OS(C(F)(F)F)(=O)=O.[CH2:20]=[CH:21][CH2:22][CH3:23]>>[C:1]([O:8][CH2:20][CH2:21][CH2:22][CH3:23])(=[O:7])[CH2:2][CH2:3][C:4]([CH3:6])=[O:5]
Reactant: CC(=O)CCC(=O)O
Reactant: C=CCC
Agent: O=S(=O)(O)C(F)(F)F
Solvent: O=CO
Product: CCCCOC(=O)CCC(C)=O
Temperature: 100 °C

Procedure:
A 5 cc autoclave is charged with 2 cc of an aqueous solution containing 2 mmoles of levulinic acid and 0.5 mmoles of formic acid. 2 wt. % triflic acid is added as a catalyst. The reactor is pressurized to 0.69 MPa with 1-butene and heated to 100° C. for 0.5 hours while maintaining a constant pressure of 1-butene. After cooling, the organic phase is separated. A mixture of butyl formate and butyl levulinate is formed as product.
Reaction SMILES: N1CCCC1.[H-].COCCO[Al+]OCCOC.[Na+].[H-].CC(C)([O-])C.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH:34]=[CH:35][C:36]=1[N:37]1[CH:41]=[C:40]([CH3:42])[N:39]=[CH:38]1)[C:30](OC)=[O:31].[OH-].[Na+]>C(OCC)(=O)C.C1COCC1.C1(C)C=CC=CC=1>[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH:34]=[CH:35][C:36]=1[N:37]1[CH:41]=[C:40]([CH3:42])[N:39]=[CH:38]1)[CH:30]=[O:31]
Reactant: COC(=O)c1ccc(-n2cnc(C)c2)c(OC)c1
Agent: CC(C)(C)[O-]
Agent: COCCO[Al+]OCCOC
Agent: [H-]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: COc1cc(C=O)ccc1-n1cnc(C)c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 40.4 %

Procedure:
A THF (45 mL) solution of pyrrolidine (18 mL) was added dropwise to a THF (60 mL) solution of sodium bis(2-methoxyethoxy)aluminium hydride (a 65% toluene solution, 56 mL) at −5° C. or lower over a period of 15 minutes. The reaction liquid was stirred at room temperature for one hour, to which a THF (15 mL) suspension of tertiary-butoxide (2.10 g) was then dropwise added at room temperature, followed by stirring the reaction liquid for 15 minutes. The reaction liquid was added dropwise to a THF (50 mL) solution of methyl 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzoate (20 g) under cooling with ice over a period of 30 minutes. The reaction liquid was stirred at room temperature for 2 hours, to which a 5N sodium hydroxide aqueous solution (150 mL) was then added dropwise. Ethyl acetate was added to the reaction liquid to separate an organic layer. The organic layer was washed with a saturated ammonium chloride aqueous solution and saturated saline in that order. The organic layer was dried with anhydrous magnesium sulfate and filtered on a silica gel pad, followed by concentrating the filtrate under reduced pressure. The residue was diluted with ethyl acetate, followed by collecting the precipitated solid by filtration. The resultant solid was air-dried overnight to provide 7.10 g of the title compound. In addition, the crystallizing mother liquor was concentrated under reduced pressure, followed by purifying the residue using silica gel column chromatography (elution solvent: a heptane-ethyl acetate-2-propanol system) to provide 2.65 g of the title compound.