Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][C:11](=[N:16]O)[CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>O1CCCC1>[CH2:1]([N:8]1[CH:9]2[CH2:15][CH2:14][CH:13]1[CH2:12][CH:11]([NH2:16])[CH2:10]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: ON=C1CC2CCC(C1)N2Cc1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: NC1CC2CCC(C1)N2Cc1ccccc1
Yield: 113.8 %

Procedure:
A suspension of 8-benzyl-8-azabicyclo[3.2.1]octan-3-one oxime (230 mg, 0.999 mmol) in tetrahydrofuran (4 ml) was added dropwise to a suspension of lithium aluminum hydride (152 mg, 4.01 mmol) in tetrahydrofuran (3 ml) at room temperature, and the resulting mixture was refluxed for 8 hours. The reaction mixture was cooled on an ice-water bath, and water (0.2 ml), a 2N-aqueous sodium hydroxide solution (0.4 ml) and water (0.2 ml) were added thereto in that order and stirred. Subsequently, the resulting mixture was filtered and the solvent of the filtrate was distilled off to obtain 8-benzyl-8-azabicyclo[3.2.1]octan-3-amine (246 mg) containing a small amount of impurities.
Reaction SMILES: [CH3:1][N:2]1[CH2:14][CH2:13][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[CH3:15][C:16]1[CH:24]=[CH:23][C:19]([CH:20]2[O:22][CH2:21]2)=[CH:18][CH:17]=1.[H-].[Na+].FC(F)(F)C([O-])=O>CN(C=O)C>[CH3:1][N:2]1[CH2:14][CH2:13][C:5]2[N:6]([CH2:21][CH:20]([C:19]3[CH:23]=[CH:24][C:16]([CH3:15])=[CH:17][CH:18]=3)[OH:22])[C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=3[C:4]=2[CH2:3]1
Reactant: CN1CCc2[nH]c3ccccc3c2C1
Reactant: Cc1ccc(C2CO2)cc1
Agent: O=C([O-])C(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1ccc(C(O)Cn2c3c(c4ccccc42)CN(C)CC3)cc1
Yield: 11.1 %

Procedure:
Preparation of the title compound was carried out according to General Method 6. 2,3,4,5-Tetrahydro-2-methyl-1H-pyrido[4,3-b]indole (See Example 3) (400 mg, 2.1 mmol), 4-methylstyrene oxide (2.1 g, 15.7 mmol) and NaH (252 mg, 6.3 mmol) were heated in DMF (5 mL) at 120° C. for 16 h to obtain 75 mg of racemic-2-(1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-1-p-tolylethanol as a trifluoroacetate salt after purification by reverse-phase chromatography (C-18, 500 mm×50 mm, Mobile Phase A=0.05% TFA in water, B=0.05% TFA in acetonitrile, Gradient: 10% B to 80% B in 30 min, injection vol. 5 mL).
Reaction SMILES: O.O.[Sn](Cl)(Cl)(Cl)Cl.[CH3:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[C:13]([N+:18]([O-])=O)[CH:12]=1)=[O:10].[OH-].[Na+]>O.Cl>[CH3:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[C:13]([NH2:18])[CH:12]=1)=[O:10]
Reactant: CC(=O)c1ccc(F)c([N+](=O)[O-])c1
Agent: Cl
Agent: Cl[Sn](Cl)(Cl)Cl
Agent: [Na+]
Solvent: O
Product: CC(=O)c1ccc(F)c(N)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
At 0° C., a solution of 11.1 g (89 mmol) of tin chloride dihydrate in 12 ml of water was added dropwise over a period of 15 min to a solution of 3 g (16.4 mmol) of 4-fluoro-3-nitroacetophenone in 7.8 ml of 12 N hydrochloric acid. The reaction mixture was then heated at reflux for 15 min and subsequently stirred at RT overnight. The reaction mixture was then poured on ice, adjusted to pH 12 using 50% strength aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried over magnesium sulphate and concentrated. This gave 2.47 g (purity 90%, 87% of theory) of the target compound.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][C:3]=1[N+:11]([O-])=O>C(O)C.[Pt]>[NH2:11][C:3]1[CH:4]=[C:5]([C:8](=[O:10])[CH3:9])[CH:6]=[CH:7][C:2]=1[F:1]
Reactant: CC(=O)c1ccc(F)c([N+](=O)[O-])c1
Agent: [Pt]
Solvent: CCO
Product: CC(=O)c1ccc(F)c(N)c1
Reaction time: 3 h
Yield: 79.9 %

Procedure:
A mixture of 1-(4-fluoro-3-nitrophenyl)-ethanone (4.94 g) and 5% Pt(S)/C (500 mg) in ethanol (50 mL) was hydrogenated at 50 psi for 3 hours. After filtration and concentration, the residue was purified by silica gel flash chromatography over silica gel (elution with 30% ethyl acetate in hexane) to give 3.3 g of the title compound as a solid.
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[CH:5][CH:6]=1.C([Li])CCC.CCCCCC.[CH:18](=[O:25])[C:19]1[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=1>C1COCC1>[N:22]1[CH:23]=[CH:24][C:19]([CH:18]([C:2]2[S:3][CH:4]=[CH:5][CH:6]=2)[OH:25])=[CH:20][CH:21]=1
Reactant: O=Cc1ccncc1
Reactant: Brc1cccs1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: OC(c1ccncc1)c1cccs1
Reaction time: 0.5 h
Yield: 34.1 %

Procedure:
To a stirred solution of 2-bromothiophene (10 g, 61.34 mmol) in dry THF (42 ml) was dropwise added a solution of n-butyl lithium in n-hexane (1.6M, 42.0 ml, 67.48 mmol) at −78° C. The resulting suspension was stirred at the same temperature for 30 min. After 30 min, a solution of isonicotinaldehyde (6.56 g, 61.34 mmol) in dry THF (30 ml) was dropwise added and continued the stirring at −78° C. for another 2 h. The progress of the reaction was monitored by TLC. The reaction was quenched with NH4Cl solution (10 ml) and diluted with diethyl ether (500 ml). The organic layer was washed with water (50 ml), brine (50 ml), dried over anhydrous Na2SO4 and evaporated. The crude compound was triturated with hexane and diethyl ether to get the desired compound as an off-white solid (4.0 g, 34%). 1H NMR (400 MHz, DMSO-d6) δ 8.52 (dd, J=4.9, 1.5 Hz, 2H), 7.45-7.38 (m, 3H), 6.97-6.93 (m, 2H), 6.45 (d, J=4.4 Hz, 1H), 5.97 (d, J=4.4 Hz, 1H).
Reaction SMILES: [C:1](N1C=CN=C1)([N:3]1[CH:7]=[CH:6][N:5]=[CH:4]1)=[O:2].[CH3:13][O:14][CH:15]([O:18][CH3:19])[CH2:16][NH2:17]>CCOC(C)=O>[CH3:13][O:14][CH:15]([O:18][CH3:19])[CH2:16][NH:17][C:1]([N:3]1[CH:7]=[CH:6][N:5]=[CH:4]1)=[O:2]
Reactant: COC(CN)OC
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: CCOC(C)=O
Product: COC(CNC(=O)n1ccnc1)OC
Reaction time: 0.25 h
Yield: 69.5 %

Procedure:
A mixture of 1,1′-carbonylbis[1H-imidazole] (2 mol) in EtOAc (800 ml) was stirred and cooled on an ice-bath, resulting in a suspension. 2,2-dimethoxyethanamine (2 mol) was added dropwise while the temperature was kept below 25 ° C. The resulting reaction mixture was stirred for 2 hours at RT, then for 30 minutes while cooling on an ice-bath. The precipitate was filtered off, stirred in EtOAc (400 ml) during 15 minutes, and on an ice-bath during 15 minutes. The precipitate was filtered off, washed with DIPE (2×50 ml), and dried, yielding 277 g (70%) of N-(2,2-dimethoxyethyl)-1H-imidazole-1-carboxamide (interm. 5).
Reaction SMILES: [F:1][C:2]1[C:14]([F:15])=[C:13]([F:16])[CH:12]=[CH:11][C:3]=1[NH:4][C@H:5]([CH3:10])[C:6]([O:8][CH3:9])=[O:7].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[F:1][C:2]1[C:14]([F:15])=[C:13]([F:16])[CH:12]=[CH:11][C:3]=1[NH:4][CH:5]([CH3:10])[C:6]([O:8][CH3:9])=[O:7]
Reactant: COC(=O)[C@@H](C)Nc1ccc(F)c(F)c1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)C(C)Nc1ccc(F)c(F)c1F
Temperature: 110 °C
Reaction time: 19 h
Yield: 85 %

Procedure:
Methyl (2R)-2-(2,3,4-trifluoroanilino)propionate (50 mg, 57% ee) was dissolved in N,N-dimethylformamide (DMF; 1 ml) and potassium carbonate (63.2 mg) was added thereto at room temperature. Then the liquid reaction mixture was stirred at 110° C. for 19 hours. After adding water to the liquid reaction mixture, the aqueous layer was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. After evaporating the solvent, the obtained residue was subjected to silica gel column chromatography (ethyl acetate-normal hexane=1:4) to thereby give the title compound (42.5 mg) as colorless crystals. The optical purity of this product was 0% ee. The 1H-NMR and IR spectral data of this product was identical with those of the compound obtained in Example 5.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)([C:14]([OH:16])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:23][N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>ClCCl.C(OCC)(=O)C>[CH3:23][N:24]1[CH2:29][CH2:28][N:27]([C:6]([NH2:8])=[O:5])[CH2:26][CH2:25]1.[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)([C:14]([OH:16])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CN1CCNCC1
Agent: CC(C)(C)OC(=O)N1CCC(C(=O)O)(c2ccccc2)CC1
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: ClCCCl
Solvent: CCOC(C)=O
Product: CN1CCN(C(N)=O)CC1
Reaction time: 18 h

Procedure:
Combine 1-tert-butoxycarbonyl-4-phenyl-piperidine-4-carboxylic acid (14.5 g, 47.5 mmol) and N-methylpiperazine (12 mL, 108 mmol) in dichloromethane (450 mL), Add HOBt (8.0 g), EDC (11.2 g). After 18 hours, evaporate in vacuo to give a residue, dissolve the residue in ethyl acetate, and extract repeatedly with water. Dry the organic layer over MgSO4, filter, and concentrate in vacuo to give 1-tert-butoxycarbonyl-4-phenyl-piperidine-4-carboxylic acid 4-methylpiperazine-amide: Rf =0.33 (6% methanol/dichloromethane).
Reaction SMILES: [C:1]([C:4]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8](=[O:22])[NH:9]2)(=[O:3])[CH3:2].CO.I([Cl:28])(=O)=O.I(Cl)(=O)=O.C([N+](C)(C)C)C1C=CC=CC=1>ClCCCl>[CH2:15]([O:14][C:11]1[CH:12]=[CH:13][C:4]([C:1](=[O:3])[CH2:2][Cl:28])=[C:5]2[C:10]=1[NH:9][C:8](=[O:22])[CH:7]=[CH:6]2)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CC(=O)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Reactant: O=I(=O)Cl
Agent: C[N+](C)(C)Cc1ccccc1
Solvent: CO
Solvent: ClCCCl
Product: O=C(CCl)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12

Procedure:
A solution of 5-acetyl-8-benzyloxycarbostyril (1.75 g, 6 mMol) in 1,2-dichloroethane (60 ml)/methanol (40 ml) and benzyltrimethylammonium dichloroiodate (4.2 g, 12 mMol) was heated at 60° C. under an argon atmosphere for 2 hours.
Reaction SMILES: [O:1]=[C:2]([CH2:9][CH2:10][CH3:11])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[N+:12]([C:15]1[CH:22]=[CH:21][C:18]([CH2:19]Br)=[CH:17][CH:16]=1)([O-:14])=[O:13].[Cl-].[Li+].C(N(C(C)C)CC)(C)C.C(OC(C)C)(C)C>O1CCCC1>[N+:12]([C:15]1[CH:22]=[CH:21][C:18]([CH2:19][CH:3]([C:2](=[O:1])[CH2:9][CH2:10][CH3:11])[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[CH:17][CH:16]=1)([O-:14])=[O:13]
Reactant: CCCC(=O)CC(=O)OCC
Reactant: O=[N+]([O-])c1ccc(CBr)cc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CC(C)OC(C)C
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CCCC(=O)C(Cc1ccc([N+](=O)[O-])cc1)C(=O)OCC
Temperature: 25 °C
Yield: 73.5 %

Procedure:
127.7 g of ethyl 3-oxohexanoate are dissolved in 700 ml of tetrahydrofuran. 174.5 g of 4-nitrobenzyl bromide and 35 g of lithium chloride are added and the mixture is stirred at room temperature. 286 ml of diisopropylethylamine are then introduced dropwise, which causes a slight exothermic effect. The mixture is then stirred for 3 hours at room temperature and thereafter for 10 hours under reflux. The solvents are evaporated off under vacuum and the residue is taken up with water and then extracted with chloroform. The organic phase is separated after settling has taken place and then washed with dilute hydrochloric acid solution, dried over magnesium sulphate and evaporated under vacuum. The oily residue obtained is taken up with isopropyl ether and the crystals formed are filtered off. The mother liquors are concentrated under vacuum and the residue is heated to 130° C. at 20 mm of mercury in order to remove the residual starting materials. 174 g of ethyl 2-(4-nitrobenzyl)-3-oxohexanoate are thereby obtained in the form of an oil, which is used without further purification for the next step.
Reaction SMILES: [CH3:1][S:2][CH2:3][CH2:4][CH:5]=[O:6].[CH2:7](O)[CH2:8][OH:9].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[CH3:1][S:2][CH2:3][CH2:4][CH:5]1[O:9][CH2:8][CH2:7][O:6]1
Reactant: CSCCC=O
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Product: CSCCC1OCCO1

Procedure:
A solution of 3-(methylthio)propanal (5.2 g, 0.05 mol) and ethyleneglycol (3.4g. 0.055 mol) in 100 mL of benzene was treated with 300 mg p-toluenesulfonic acid and heated at reflux for 4 hrs. The solution was cooled and decanted. Concentration and drying in vacuo provided the title compound as a light yellow oil. 1H NMR (300 MHz, CDCl3) δ ppm:4.93 (1 H, t, J=4.76 Hz) 3.74-4.03 (4 H, m) 2.46-2.68 (2 H, m) 2.08 (3 H, s) 1.83-2.00 (2 H, m).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C.C(OCC)(=O)C>C(O)CCC.O>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=2)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: O
Solvent: CCN(CC)CC
Solvent: CCCCO
Product: CC(C)(C)OC(=O)N1CCN(c2ccc([N+](=O)[O-])cn2)CC1
Temperature: 120 °C
Yield: 58.6 %

Procedure:
Place 2-chloro-5-nitro-pyridine (1.0 g, 6.31 mmol), piperazine-1-carboxylic acid tert-butyl ester (1.76 g, 9.45 mmol), and triethylamine (1.76 mL, 12.6 mmol) in n-butanol (20 mL). Heat to 120° C. for 17 hours. Cool to room temperature and add ethyl acetate and water. Separate organic layer and wash with water and saturated aq. sodium chloride. Collect organic layer, dry over Mg2SO4, filter, and concentrate under reduced pressure. Subject residue to silica gel chromatography eluting with 20% EtOAc:hexane to yield 1.14 g (58%) of 4-(5-nitro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester. MS(ES): m/z=309 [M+H].
Reaction SMILES: [C:1]1([C:7]2[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[N:9]([CH2:24][CH2:25][CH2:26][CH2:27][OH:28])[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClCl.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C(Cl)Cl>[C:1]1([C:7]2[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:10]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:9]([CH2:24][CH2:25][CH2:26][CH:27]=[O:28])[N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: OCCCCn1nc(-c2ccccc2)c(-c2ccccc2)c1-c1ccccc1
Agent: O=[Cr](=O)([O-])Cl
Agent: ClCl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: O=CCCCn1nc(-c2ccccc2)c(-c2ccccc2)c1-c1ccccc1
Reaction time: 3 h

Procedure:
3,4,5-Triphenyl-lH-pyrazol-1-butanol (4 g, 10.9 mmol) in dry CH 0.12. Cl2 (10 mL) was added to a stirred suspension of pyridinium chlorochromate (7.03 g, 32.6 mmol) in dry CH2Cl2 (370 mL). After 3 hours, the CH2Cl2 was removed in vacuo and the residue diluted with diethyl ether (800 mL) and filtered through diatomateous earth. The organic phase was washed twice with water and once with saturated sodium chloride solution, dried over sodium sulfate and concentrated to furnish 3,4,5-triphenyl-lH-pyrazol-1-butanal as a viscous oil. MS(CI): m/e =367 (MH+)
Reaction SMILES: Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.[F:22][C:23]([F:35])([F:34])[O:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C(O)C.C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:18]([C:15]1[CH:16]=[CH:17][C:12]([CH2:11][N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([C:28]4[CH:27]=[CH:26][C:25]([O:24][C:23]([F:22])([F:34])[F:35])=[CH:30][CH:29]=4)[CH:10]=3)[CH:6]=[CH:7]2)=[CH:13][CH:14]=1)([CH3:21])([CH3:20])[CH3:19]
Reactant: OB(O)c1ccc(OC(F)(F)F)cc1
Reactant: CC(C)(C)c1ccc(Cn2ccc3ccc(Br)cc32)cc1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Solvent: O
Product: CC(C)(C)c1ccc(Cn2ccc3ccc(-c4ccc(OC(F)(F)F)cc4)cc32)cc1
Yield: 61.4 %

Procedure:
Following the procedure described in Step 2 of Example 5, 6-bromo-1-[4-(tert-butyl)benzyl]-1H-indole (0.488 g, 1.43 mmol) was coupled to 4-trifluoromethoxybenzene boronic acid (0.329 g, 1.60 mmol), using tetrakis(triphenylphosphine) palladium (0.0574 g, 0.0496 mmol) and sodium carbonate (0.617 g, 5.82 mmol) in water (2.8 mL), ethanol (1.4 mL) and toluene (10 mL). Purification by flash chromatography using hexane as an eluant yielded 1-[4-(tert-butyl)benzyl]-6-[4-(trifluoromethoxy)phenyl]-1H-indole as a white solid (0.372 g, 61%), mp 100-102° C. 1HNMR (200 MHz, DMSO-d6): δ7.8 (d, 3H, J=8.5 Hz), 7.65 (d, 1H, J=8.5 Hz), 7.55 (d, 1H, J=3.5 Hz), 7.3-7.5 (m, 5H), 7.15 (d, 2H, J=7.5 Hz), 6.5 (d, 1H, J=3.5 Hz), 5.45 (s, 2H), and 1.2 ppm (s, 9H).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]2[N:8]=C[S:10][C:6]=2[CH:5]=1)([O-:3])=[O:2].NN>>[NH2:8][C:7]1[CH:11]=[CH:12][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][C:6]=1[SH:10]
Reactant: O=[N+]([O-])c1ccc2ncsc2c1
Agent: NN
Product: Nc1ccc([N+](=O)[O-])cc1S

Procedure:
Commercially available 6-nitrobenzothiazole can be treated with hydrazine to obtain the 2-amino-5-nitro-benzenethiol, which can subsequently be reacted with chloroacetoacetate to give the (7-nitro-4H-benzo[1,4]thiazin-3-yl)-acetic acid ethyl ester. Reduction of the nitro group to the amino group can be accomplished by reaction with tin (II) chloride. Subsequent reaction with methansulfonyl chloride can be used to obtain the corresponding sulfonamide. Protection of both nitrogens with a suitable protecting group such as a Boc group can be achieved by using standard methods for protecting amino groups. The sulfide can be oxidized using a suitable oxidizing reagent (e.g., MCPBA) to give the sulfone. Finally, deprotection of the amino groups using trifluoroacetic acid can be used to afford the desired (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-3-yl)-acetic acid ethyl ester intermediate.
Reaction SMILES: [F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:36]=[CH:35][CH:34]=[C:33]2[C:29]=1[CH:30]=[CH:31][NH:32]2>O>[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:24][CH2:25][CH2:26][O:27][C:28]4[CH:36]=[CH:35][CH:34]=[C:33]5[C:29]=4[CH:30]=[CH:31][NH:32]5)[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1
Reactant: ClCCCOc1cccc2[nH]ccc12
Reactant: Fc1ccc2c(C3CCNCC3)noc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: Fc1ccc2c(C3CCN(CCCOc4cccc5[nH]ccc45)CC3)noc2c1
Reaction time: 68 h
Yield: 103.5 %

Procedure:
A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.5 g, 16 mmol), K2CO3 (2.2 g, 16 mmol), KI (200 mg), 4-(3-chloropropoxy)indole (3.0 g, 14 mmol) CH3CN (100 ml) was stirred at reflux under N2 for 7 hours and then at ambient temperature for 68 hours. Reflux was resumed for an additional 6 hours whereupon a TLC revealed incomplete reaction. K2CO3 (0.5 g, 4 mmol) was added and the reaction was stirred at reflux for 17 hours. The cooled reaction was poured into H2O and the aqueous mixture was extracted with EtOAc. The organic extract was washed with H2O and saturated NaCl and after drying over MgSO4 the solvent was removed to afford 5.7 g of a beige solid. The product was purified by preparative HPLC (Water's Associates Prep LC/System 500 using 2 silica gel columns and 4% MeOH-CH2Cl2 as eluent) to yield 3.4 g (61%) of a beige solid. Two consecutive recrystallizations from EtOH provided 2.3 g (41%) of a white powder, m.p.=129°-131° C.
Reaction SMILES: C[O:2][CH:3]=[CH:4][C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]2[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.O>O1CCCC1>[C:15]([C:14]1[CH:17]=[CH:18][C:11]([C@H:8]2[CH2:9][CH2:10][C@H:5]([CH2:4][CH:3]=[O:2])[CH2:6][CH2:7]2)=[CH:12][CH:13]=1)#[N:16]
Reactant: COC=C[C@H]1CC[C@H](c2ccc(C#N)cc2)CC1
Solvent: O
Solvent: C1CCOC1
Product: N#Cc1ccc([C@H]2CC[C@H](CC=O)CC2)cc1

Procedure:
A solution of 10.1 g of p-[trans-4-(2-methoxyvinyl)cyclohexyl]benzonitrile in 200 ml of tetrahydrofuran/2N hydrochloric acid (vol. 4:1) was heated to reflux for 1 hour. The reaction mixture was subsequently poured into 200 ml of water and extracted three times with 150 ml of diethyl ether each time. The organic phases were washed twice with 100 ml of water each time, dried over magnesium sulphate and concentrated, whereby 9.8 g of [trans-4-(p-cyanophenyl)cyclohexyl]acetaldehyde were obtained as light yellowish crystals (purity 98.7%). Recrystallization of a sample from hexane/t-butyl methyl ether (vol. 1:1) gave pure aldehyde with m.p. 43.4° C.
Reaction SMILES: [CH:1](=[O:7])[C:2]1[O:6][CH:5]=[CH:4][CH:3]=1.CC(C)=O.CCCCCCCC.[CH:20](=[O:26])[CH:21]1[O:25][CH2:24][CH2:23][CH2:22]1>CCCCCCCCCCCCCCCC.O1CCCC1>[CH:4]1[CH:3]=[C:2]([CH:1]([OH:7])[C:20]([C:21]2[O:25][CH:24]=[CH:23][CH:22]=2)=[O:26])[O:6][CH:5]=1
Reactant: O=CC1CCCO1
Reactant: O=Cc1ccco1
Solvent: C1CCOC1
Solvent: CC(C)=O
Solvent: CCCCCCCC
Product: O=C(c1ccco1)C(O)c1ccco1
Yield: 71 %

Procedure:
This has as a consequence that if stoichiometric ratios are used, which means 2 moles of furfural and 1 mole of acetone (since acetone can react by both ends), between 16% and 37% of components with only 5 carbon atoms would be obtained, having a very limited interest as components for gasoline (Appl. Catal. B Environ. 2006, 66, 111-118). A second product with 8 carbon atoms which tends to be one-third of the mixture appears under other conditions. This condensation product is hydrogenated to n-octane which does not have an interesting application in gasoline since it has linear chain, nor in diesel because of the low molecular weight. To increase selectivity to 85% with a 71% yield, the condensation has to be carried out in an aqueous phase and hydrogenation in hexadecane as a solvent at 120° C. thereby making the process more expensive (Appl. Catal. B Environ. 2006, 66, 111-118). The authors themselves realized the disadvantages caused by selectivity and proposed as an alternative the hydrogenation of the furan ring to tetrahydrofuran since these derivatives are capable of carrying out an aldol condensation with themselves and this would ensure a high selectivity. However, chemoselective hydrogenation of, for example, furfural to tetrahydrofurfural in one step is still a challenge and it is currently carried out in several stages. In any case, if a multistage process is accepted, molecules with a total of 10 carbon atoms can be obtained (Science 2005, 308, 1446-1450) as well as by the formation of furoin.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[CH3:9][O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[O:10][CH3:9])[N:5]=[CH:4][N:3]=1
Reactant: COc1ccccc1B(O)O
Reactant: Clc1cc(Cl)ncn1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: COc1ccccc1-c1cc(Cl)ncn1
Temperature: 25 °C
Yield: 83.7 %

Procedure:
A solution of 4,6-dichloropyrimidine (2.0 g, 13 mmol), 2-methoxyphenylboronic acid (2.0 g, 13 mmol), and sodium carbonate (4.4 g, 42 mmol, dissolved in minimal amount of water) was degassed with argon. To the degassed solution Pd(Ph3)4 was added and the resultant reaction mixture was refluxed for 18 hours. The reaction mixture was cooled to room temperature and diluted with dichloromethane. The organics were washed with water and the aqueous layer was extracted with additional dichloromethane. The combined organics were washed with brine and dried over sodium sulfate. Following filtration, the organics were dried in vacuo and the residue was purified by Si gel chromatography (1:10 ethyl acetate:hexanes) to yield 2.4 g (80%) of the title compound.
Reaction SMILES: [Br:1]Br.[C:3]([C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][CH:13]=1)[C:9]#[N:10])(=[O:5])[CH3:4]>C(OCC)C>[Br:1][CH2:4][C:3]([C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][CH:13]=1)[C:9]#[N:10])=[O:5]
Reactant: BrBr
Reactant: CC(=O)c1cccc(C#N)c1
Solvent: CCOCC
Product: N#Cc1cccc(C(=O)CBr)c1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Bromine (5.50 g, 34.4 mmol) was slowly added dropwise to a solution of 3-acetylbenzonitrile (5.00 g, 34.4 mmol) in diethyl ether (100 ml), and the mixture was stirred at room temperature for 4 hours. The reaction mixture was distilled off under reduced pressure to give the desired product as an oil.