Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][CH2:12][CH2:13][C:14]([OH:16])=O)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].Cl.Cl.[NH2:19][CH:20]1[CH2:25][CH2:24][N:23]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([Cl:34])[CH:28]=2)[CH2:22][CH2:21]1.C(N(CC)CC)C.CCN=C=NCCCN(C)C.Cl>ClCCl>[C:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:10][CH2:11][CH2:12][CH2:13][C:14]([NH:19][CH:20]2[CH2:25][CH2:24][N:23]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([Cl:34])[CH:28]=3)[CH2:22][CH2:21]2)=[O:16])=[CH:8][CH:9]=1)(=[O:3])[CH3:2]
Reactant: NC1CCN(Cc2ccc(Cl)c(Cl)c2)CC1
Reactant: CC(=O)c1ccc(CCCCC(=O)O)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)c1ccc(CCCCC(=O)NC2CCN(Cc3ccc(Cl)c(Cl)c3)CC2)cc1
Reaction time: 12 h
Yield: 55.7 %

Procedure:
5-(4-Acetylphenyl)valeric acid (996 mg) and 4-amino-1-(3,4-dichlorobenzyl)piperidine dihydrochloride (1.50 g) were suspended in dichloromethane (40 mL), and triethylamine (1.26 mL) and EDC hydrochloride (953 mg) were added to the suspension. The suspension was stirred for 12 hrs. The reaction mixture was washed with water and then saturated brine and dried, and the solvent was evaporated under reduced pressure. Diethyl ether was added to the residue to crystallize to give the title compound (1.16 g) as a white solid.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].C(N(CC)CC)C.[C:13]1([C:19]2[C:20]3[N:21]([CH2:36][CH2:37][N:38]=3)[C:22]3[C:27]([N+:28]=2[O-:29])=[CH:26][CH:25]=[C:24]([N:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH:23]=3)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>ClCCl>[CH3:1][S:2]([N:33]1[CH2:34][CH2:35][N:30]([C:24]2[CH:23]=[C:22]3[C:27]([N+:28]([O-:29])=[C:19]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[C:20]4[N:21]3[CH2:36][CH2:37][N:38]=4)=[CH:26][CH:25]=2)[CH2:31][CH2:32]1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)Cl
Reactant: [O-][N+]1=C(c2ccccc2)C2=NCCN2c2cc(N3CCNCC3)ccc21
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)N1CCN(c2ccc3c(c2)N2CCN=C2C(c2ccccc2)=[N+]3[O-])CC1
Temperature: 25 °C
Yield: 62.7 %

Procedure:
A solution of methanesulfonyl chloride (0.33 g, 0.003 mol) in dichloromethane (20 ml) was cooled in an ice-bath. To this solution was added dropwise with stirring, a solution of triethylamine (0.29 g, 0.003 mol) and 1,2-dihydro-4-phenyl-8-piperazinylimidazo[1,2-a]quinoxaline 5-oxide (1 g, 0.003 mol) in dichloromethane (10 ml). The reaction mixture was stirred for an additional 15 minutes and then was allowed to warm to room temperature. The reaction mixture was washed with water, dried over anhydrous magnesium sulphate and then evaporated to dryness under reduced pressure to yield a yellow solid. Recrystallization from ethyl acetate yielded 1,2-dihydro-8-(4-(methylsulphonyl)piperazinyl)-4-phenylimidazo[1,2-a]quinoxaline 5-oxide (0.8 g), as yellow crystals, m.p. 252°-253° C. (Found: C,59.19; H,5.35; N,16.33%; C21H23N5O3S requires C,59.29; H,5.41; N,16.47%) having the formula: ##STR31##
Reaction SMILES: [F:1][C:2]([F:24])([F:23])[CH2:3][O:4][C:5]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:6]=1[CH2:7][S:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N+:12]=1[O-:17])(=[O:10])=[O:9].[H-].[Na+].[CH3:27]I>CN(C)C=O>[F:24][C:2]([F:1])([F:23])[CH2:3][O:4][C:5]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:6]=1[CH:7]([S:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N+:12]=1[O-:17])(=[O:9])=[O:10])[CH3:27]
Reactant: O=S(=O)(Cc1cc(Cl)ccc1OCC(F)(F)F)c1cccc[n+]1[O-]
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(c1cc(Cl)ccc1OCC(F)(F)F)S(=O)(=O)c1cccc[n+]1[O-]

Procedure:
In the same manner as Example 1, 2.00 g of 2-[2-(2,2,2-trifluoroethoxy)-5-chlorobenzylsulfonyl]pyridine-N-oxide, 230 mg of 55% sodium hydride and 740 mg of methyl iodide were mixed with 50 ml of dimethylformamide and the mixture was reacted, followed by the same after-treatment as in Example 1, whereby 1.43 g of Compound No. 27 of the present invention was obtained. The product was white crystals having a melting point of from 119° to 121° C.
Reaction SMILES: [NH2:1][CH2:2][CH:3]([C:9]1([CH3:14])[O:13][CH2:12][CH2:11][O:10]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH3:15][C:16]1[CH:26]=[CH:25][CH:24]=[C:18]2[C:19]([O:21][C:22](=O)[C:17]=12)=[O:20]>>[CH3:15][C:16]1[CH:26]=[CH:25][CH:24]=[C:18]2[C:17]=1[C:22](=[O:21])[N:1]([CH2:2][CH:3]([C:9]1([CH3:14])[O:10][CH2:11][CH2:12][O:13]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:19]2=[O:20]
Reactant: CCOC(=O)C(CN)C1(C)OCCO1
Reactant: Cc1cccc2c1C(=O)OC2=O
Product: CCOC(=O)C(CN1C(=O)c2cccc(C)c2C1=O)C1(C)OCCO1

Procedure:
Ethyl 3-(4-methyl-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(2-methyl-[1,3]dioxolan-2-yl)propionate was prepared (0.57 g, 76%) in the same manner as described in the above example 5 (20) from ethyl 3-amino-2-(2-methyl-[1,3]dioxolan-2-yl)propionate (0.60 g, 3.25 mmol) and 3-methylphthalic anhydride (0.79 g, 4.87 mmol), and the obtained product was identified with the following NMR data.
Reaction SMILES: CO[C:3]([N:5]([CH2:16][CH2:17][CH3:18])[CH:6](NCCC)[C:7]([O:9]CC)=[O:8])=O.[CH2:19](NC(NCCC)C(OCC)=O)[CH2:20]C.[ClH:33]>>[ClH:33].[CH2:16]([N:5]([CH2:3][CH2:19][CH3:20])[CH2:6][C:7]([OH:9])=[O:8])[CH2:17][CH3:18]
Reactant: CCCNC(NCCC)C(=O)OCC
Reactant: CCCNC(C(=O)OCC)N(CCC)C(=O)OC
Agent: Cl
Product: CCCN(CCC)CC(=O)O
Yield: 80 %

Procedure:
The amino acid di-n-propylglycine can be obtained in the form of its hydrochloride by combining the ethyl N-methoxycarbonyl-2,2-di-n-propylaminoacetate and the ethyl 2,2-di-n-propylaminoacetate and refluxing the mixture with concentrated hydrochloric acid for 12 hours. After cooling, the solution is extracted with MTBE, and the aqueous solution is evaporated to dryness. The residue is taken up again in water, and the solution is evaporated under reduced pressure in order to remove excess hydrochloric acid to leave 43.8 g (80%) of di-n-propylglycine hydrochloride. This can be used to obtain the free amino acid in accordance with known methods.
Reaction SMILES: O[N:2]=[C:3]1[CH2:8][CH2:7][CH:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:5][CH2:4]1.[ClH:15]>[Ni].C(O)C>[ClH:15].[C:9]1([CH:6]2[CH2:5][CH2:4][CH:3]([NH2:2])[CH2:8][CH2:7]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: ON=C1CCC(c2ccccc2)CC1
Agent: [Ni]
Agent: Cl
Solvent: CCO
Product: NC1CCC(c2ccccc2)CC1
Yield: 100 %

Procedure:
A mixture of 1-(hydroxyimino)-4-phenylcyclohexane (17.4 mmol) and Raney Nickel (300 mg) in ethanol was hydrogenated (90 psi) at 50° C. for 40 hours. The mixture was filtered through a pad of Celite, washed with MeOH, and concentrated. The residue was dissolved in MeOH, treated with HCl (4 N in dioxane, 20 mmol), and concentrated to give 4-phenylcyclohexylamine hydrochloride (100%).
Reaction SMILES: P(Cl)(Cl)(Cl)(Cl)Cl.[C:7]([NH:26][C:27]1[S:28][CH:29]=[C:30]([C:32](=[N:36][O:37][CH2:38][C:39]2[CH:43]=[CH:42][N:41]([C:44]([C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)([C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)[C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[N:40]=2)[C:33](O)=[O:34])[N:31]=1)([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)([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(N(CC)CC)C.Cl.[NH2:71][C@@H:72]1[C:89](=[O:90])[N:74]2[C:75]([C:82]([O:84][C:85]([CH3:88])([CH3:87])[CH3:86])=[O:83])=[C:76]([CH2:80][Br:81])[CH2:77][S:78](=[O:79])[C@H:73]12>C(Cl)(Cl)Cl.C(Cl)Cl>[C:7]([NH:26][C:27]1[S:28][CH:29]=[C:30]([C:32](=[N:36][O:37][CH2:38][C:39]2[CH:43]=[CH:42][N:41]([C:44]([C:51]3[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=3)([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)[N:40]=2)[C:33]([NH:71][C@@H:72]2[C:89](=[O:90])[N:74]3[C:75]([C:82]([O:84][C:85]([CH3:86])([CH3:87])[CH3:88])=[O:83])=[C:76]([CH2:80][Br:81])[CH2:77][S:78](=[O:79])[C@H:73]23)=[O:34])[N:31]=1)([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=C(O)C(=NOCc1ccn(C(c2ccccc2)(c2ccccc2)c2ccccc2)n1)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Reactant: CC(C)(C)OC(=O)C1=C(CBr)CS(=O)[C@@H]2[C@H](N)C(=O)N12
Agent: Cl
Agent: ClP(Cl)(Cl)(Cl)Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: CC(C)(C)OC(=O)C1=C(CBr)CS(=O)[C@@H]2[C@H](NC(=O)C(=NOCc3ccn(C(c4ccccc4)(c4ccccc4)c4ccccc4)n3)c3csc(NC(c4ccccc4)(c4ccccc4)c4ccccc4)n3)C(=O)N12
Reaction time: 0.5 h
Yield: 87 %

Procedure:
420 mg of phosphorus pentachloride was dissolved in 70 ml of chloroform and the mixture was cooled to -25° to -30° C. 1.51 g of 2-(2-tritylaminothiazol-4-yl)-2-((N-tritylpyrazol-3-yl)methoxyimino)acetic acid was added to the mixture and the resulting mixture was stirred for 30 minutes at the same temperature. 0.5 ml of triethylamine was added to the mixture and, after 3 minutes, a mixture of 810 mg of tertiary butyl 7β-amino-3-bromomethyl-3-cephem-4-carboxylate 1-oxide hydrochloride, 0.28 ml of triethylamine and methylene chloride was added to the mixture. The resulting mixture was stirred for 40 minutes at the same temperature. 50 ml of chloroform cooled in an ice-bath was added to the reaction mixture and the mixture was washed with water, a 3% aqueous solution of sodium bicarbonate and SSC and dried with sodium sulfate and then concentrated to dryness. The residue was purified by silica gel column chromatography using chloroform and nextly a mixture of chloroform and ethyl acetate (4:1 by volume) as an eluent solvent to give 1.92 g of tertiary butyl 7β-(2-(2-tritylaminothiazol-4-yl)-2-((N-tritylpyrazol-3-yl)methoxyimino)acetamido)-3-bromomethyl-3-cephem-4-carboxylate 1-oxide (syn isomer).
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C@H:10]([N:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([NH:25][CH:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)[N:20]=3)=[CH:15][C:14]2=[O:32])[CH2:11][OH:12])=[CH:6][C:5]=1[F:33].[I-].[Na+].[CH3:36][S:37][CH2:38]Cl>CN(C=O)C>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C@H:10]([N:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([NH:25][CH:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)[N:20]=3)=[CH:15][C:14]2=[O:32])[CH2:11][O:12][CH2:36][S:37][CH3:38])=[CH:6][C:5]=1[F:33]
Reactant: CSCCl
Reactant: O=c1cc(-c2ccnc(NC3CCOCC3)n2)ccn1[C@H](CO)c1ccc(Cl)c(F)c1
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CSCOC[C@H](c1ccc(Cl)c(F)c1)n1ccc(-c2ccnc(NC3CCOCC3)n2)cc1=O
Temperature: 0 °C
Yield: 99.9 %

Procedure:
Sodium hydride (44 mg, 1.10 mmol) was added to 1-[(1S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl]-4-[2-(tetrahydropyran-4-ylamino)pyrimidin-4-yl]pyridine-2-one (0.49 g, 1.10 mmol) in DMF (10 mL) at 0° C., which was left to stir at 0° C. In a separate vial, sodium iodide (0.17 g, 1.10 mmol) and chlorodimethyl sulfide (0.11 g, 1.10 mmol) were transferred, which was then added to the reaction mixture. The reaction mixture was stirred overnight at room temperature. The mixture was quenched carefully with water before diluting with ethyl acetate. The phases were separated. The organic phase was washed with saturated sodium bicarbonate, water, and followed by brine. The mixture was dried over sodium sulfate before removing the solvent to leave an oil. The oil was purified by CombiFlash (24 g column, 0-10% MeOH/DCM over 20 minutes) to furnish (S)-1-(1-(4-chloro-3-fluorophenyl)-2-((methylthio)methoxy)ethyl)-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (555 mg) as a solid (M+1=506).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[O:11])=[CH:2]1.[H-].[Na+].[CH2:14]([O:21][CH2:22][C:23](Cl)=[O:24])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1COCC1>[CH2:14]([O:21][CH2:22][C:23]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[O:11])=[CH:2]1)=[O:24])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: O=C(Cl)COCc1ccccc1
Reactant: O=Cc1c[nH]c2ccccc12
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=Cc1cn(C(=O)COCc2ccccc2)c2ccccc12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of indole-3-carboxaldehyde (2 g, 13.8 mmol) in THF (70 mL) at 5° C., was added NaH (60% in mineral oil, 551 mg, 13.8 mmol) under nitrogen atmosphere. The mixture was stirred at 5° C. for 30 min before dropwise addition of benzyloxyacetyl chloride (2.6 mL, 16.53 mmol) over 20 min maintaining the internal temperature between 5° C. and 10° C. The resulting dark solution was further stirred at RT for 1 h. As the reaction was not completed benzyloxyacetyl chloride (1 mL, 6.44 mmol, 0.5 eq) and NaH (60% in mineral oil, 551 mg, 13.8 mmol) were added and the mixture was further stirred at RT for 3 days. The reaction mixture was concentrated, and the residue taken up in CH2Cl2 and washed with water. The organic layer was dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 4-1) corresponding to the desired compound. TLC, Rf (c-hexane/EtOAc 1:1)=0.61; MS (LC/MS): 294.1 [M+H]+, 316.1 [M+Na]+; tR (HPLC conditions a): 3.87 min.
Reaction SMILES: [OH:1][CH2:2][C@H:3]1[C@H:7]([C:8]2[C:9]([O:26]C)=[CH:10][C:11]([O:24]C)=[C:12]3[C:17]=2[O:16][C:15]([C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)=[CH:14][C:13]3=[O:23])[CH2:6][CH2:5][N:4]1[CH3:28].Cl.N1C=CC=CC=1>>[OH:24][C:11]1[CH:10]=[C:9]([OH:26])[C:8]([C@@H:7]2[CH2:6][CH2:5][N:4]([CH3:28])[C@H:3]2[CH2:2][OH:1])=[C:17]2[C:12]=1[C:13](=[O:23])[CH:14]=[C:15]([C:18]1[S:19][CH:20]=[CH:21][CH:22]=1)[O:16]2
Reactant: COc1cc(OC)c2c(=O)cc(-c3cccs3)oc2c1[C@@H]1CCN(C)[C@H]1CO
Agent: Cl
Solvent: c1ccncc1
Product: CN1CC[C@@H](c2c(O)cc(O)c3c(=O)cc(-c4cccs4)oc23)[C@@H]1CO

Procedure:
Compound of example 67 (0.29 g, 0.72 mmol) of was subjected to demethylation using pyridine hydrochloride (2.9 g, 25.11 mmol) as described in example 17 to obtain the title compound.
Reaction SMILES: [O:1]1[CH2:6][C:5](=O)[NH:4][C:3](=[O:8])[NH:2]1.[CH3:9][O:10][C:11]1[CH:17]=[CH:16][C:14]([NH2:15])=[CH:13][CH:12]=1.C[Si](C)(C)N[Si](C)(C)C>S([O-])([O-])(=O)=O.[NH4+].[NH4+].O1CCOCC1>[CH3:9][O:10][C:11]1[CH:17]=[CH:16][C:14]([NH:15][C:5]2[CH2:6][O:1][NH:2][C:3](=[O:8])[N:4]=2)=[CH:13][CH:12]=1
Reactant: O=C1CONC(=O)N1
Reactant: COc1ccc(N)cc1
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: O=S(=O)([O-])[O-]
Agent: [NH4+]
Solvent: C1COCCO1
Product: COc1ccc(NC2=NC(=O)NOC2)cc1
Yield: 58.8 %

Procedure:
A solution of 1.16 g (0.010 mole) of 6H-1,2,4-oxadiazin-3,5(2H,4H)-dione, 5 mg ammonium sulfate, 1.47 g (0.012 mole) of p-methoxyaniline and 20 ml hexamethyldisilazane in 40 ml of freshly distilled dry dioxane is refluxed for 17 hours. After cooling, the dioxane and hexamethyldisilazane are removed in vacuo and the syrupy residue is dried on a vacuum pump for 2 hours. The resulting semi-solid residue is triturated with 100 ml of petroleum ether and filtered to give a yield of 1.3 g (59 percent) of 5-((4-methoxyphenyl)amino)-6H-1,2,4-oxadiazin-3(2H)-one.
Reaction SMILES: [CH3:1][C:2]1([CH3:8])[CH2:6][CH2:5][CH2:4][C@H:3]1[NH2:7].[C:9]([C:12]1[CH:17]=[N:16][N:15]2[CH:18]=[C:19]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:20]=[C:14]2[C:13]=1Cl)(=[O:11])[NH2:10].ClC1C2N(C=C(Cl)C=2)N=CC=1C(N)=O>>[C:9]([C:12]1[CH:17]=[N:16][N:15]2[CH:18]=[C:19]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:20]=[C:14]2[C:13]=1[NH:7][C@@H:3]1[CH2:4][CH2:5][CH2:6][C:2]1([CH3:8])[CH3:1])(=[O:11])[NH2:10]
Reactant: CC1(C)CCC[C@H]1N
Reactant: CCOC(=O)c1cc2c(Cl)c(C(N)=O)cnn2c1
Agent: NC(=O)c1cnn2cc(Cl)cc2c1Cl
Product: CCOC(=O)c1cc2c(N[C@@H]3CCCC3(C)C)c(C(N)=O)cnn2c1

Procedure:
Prepared by reacting (R)-2,2-dimethylcyclopentylamine with ethyl 3-carbamoyl-4-chloropyrrolo[1,2-b]pyridazine-6-carboxylate (Preparation 4) according to the procedure described in Step 5 of Intermediate 4. HPLC (condition B): retention time=3.67 min. LCMS (condition E): m/z 345+ve. 1H NMR (400 MHz, MeOD) δ ppm 10.86 (1 H, br. s.), 8.20 (1 H, s), 8.01 (1 H, d, J=1.76 Hz), 7.38 (1 H, d, J=1.54 Hz), 4.27-4.43 (2 H, m), 4.13-4.29 (1 H, m), 2.29-2.46 (1 H, m), 1.58-1.92 (5 H, m), 1.38 (3 H, t, J=7.15 Hz), 1.13 (3 H, s), 1.10 (3 H, s).
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:16]([CH3:17])=[CH:15][C:12]([CH:13]=[O:14])=[CH:11][C:10]=1[CH2:18][CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O-:20][Mn](=O)(=O)=O.[K+]>CC(C)=O>[CH2:1]([O:8][C:9]1[C:16]([CH3:17])=[CH:15][C:12]([C:13]([OH:20])=[O:14])=[CH:11][C:10]=1[CH2:18][CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=[Mn](=O)(=O)[O-]
Reactant: CCc1cc(C=O)cc(C)c1OCc1ccccc1
Agent: [K+]
Solvent: CC(C)=O
Product: CCc1cc(C(=O)O)cc(C)c1OCc1ccccc1
Temperature: 45 °C
Reaction time: 16 h
Yield: 72.3 %

Procedure:
To a solution of 4-benzyloxy-3-ethyl-5-methyl-benzaldehyde (25.0 g, 98.3 mmol) in acetone (500 mL), KMnO4 (20.2 g, 127.8 mmol) is added. The mixture becomes warm (45° C.). The mixture is stirred at rt for 16 h before it is filtered over glass filters. The clear, colourless filtrate is concentrated, diluted with water and acidified with 2N aq. HCl, then extracted twice with EA. The combined org. extracts are dried over MgSO4, filtered, concentrated and dried to give 4-benzyloxy-3-ethyl-5-methyl-benzoic acid as a pale yellow solid (19.2 g). LC-MS: tR=1.00 min; 1H NMR (D6-DMSO): δ 1.13-1.22 (m, 3H), 2.32 (s, 3H), 2.64-2.72 (m, 2H), 4.87 (s, 2H), 7.34-7.56 (m, 5H), 7.69 (m, 2H), 12.66 (br s, 1H).
Reaction SMILES: C(OC(=O)[NH:7][C@@H:8]([C:10]1[N:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:13]2[CH:21]=[CH:22][CH:23]=[C:24]([CH3:25])[C:12]=2[N:11]=1)[CH3:9])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:25][C:24]1[C:12]2[N:11]=[C:10]([C@H:8]([NH2:7])[CH3:9])[N:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:13]=2[CH:21]=[CH:22][CH:23]=1
Reactant: Cc1cccc2c1nc([C@@H](C)NC(=O)OC(C)(C)C)n2-c1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1cccc2c1nc([C@@H](C)N)n2-c1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 94.5 %

Procedure:
To a solution of [(R)-1-(4-methyl-1-phenyl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tertbutyl ester (404 mg, 1.15 mmol) in DCM (5 mL) was added TFA (1 mL) and the mixture was stirred at RT for 3 h. Additional TFA (0.5 mL) was added and stirring was continued for 30 min. Volatiles were then removed under reduced pressure and the residue was dissolved in a small amount of DCM and loaded onto an SCX-2 cartridge. The cartridge was initially washed with 10% MeOH in DCM and the product was eluted with 2M NH3/MeOH affording (R)-1-(4-Methyl-1-phenyl-1H-benzoimidazol-2-yl)ethylamine as a brown solid (273 mg, 94%). LCMS: RT 2.14 [M-NH2]+ 235.1
Reaction SMILES: C([O-])([O-])=O.[Ca+2:5].[B:6]1([O-:9])[O:8][O:7]1.O.O.O.O.[Na+:14].[N:15]#[C:16][NH2:17].N#CN.[Ca]>O>[B:6]([O:7][O-:8])=[O:9].[Na+:14].[N:15]#[C:16][NH2:17].[Ca:5]
Reactant: [O-]B1OO1
Reactant: [Ca+2]
Agent: N#CN
Agent: O=C([O-])[O-]
Agent: [Ca]
Solvent: O
Product: O=BO[O-]
Temperature: 48.888888888888886 °C

Procedure:
Five hundred (500) ml of deionized water was added to a U.S. Testing, Inc. Terg-O-Tometer bath maintained at a temperature of 120° F and the hardness level of the water adjusted to 150 ppm as CaCO3 (Ca/Mg = 3/2 on a molar basis). The peroxide-based bleach (sodium perborate tetrahydrate) and metal cyanamide activator (crude calcium cyanamide) were then added to the wash water in the concentrations shown in Table I, and the water agitated to avoid localized concentrations of any one additive. The pH of the water in the bath was maintained in the general range of 10-11.5 throughout the test. Although sodium perborate and calcium cyanamide give alkaline solutions, a detergent was used to simulate home laundry conditions. In this example Tide containing 12.3 percent phosphorus (Tide, 12.3%P) was employed as the detergent. Finally, four swatches, measuring 4 × 4, of EMPA 115 cloth (a standard cotton bleach test cloth soiled with sulfur black dye) were introduced into the wash water and the agitator run for 10 minutes at 100 rpm. At the conclusion of the wash cycle, the swatches were removed and rinsed by squeezing under a tap. The test cloths were then dried and the reflectance values measured on a Gardner Reflectometer, Model UX-2, utilizing a G (green) filter. The change that occurred as a result of the bleach/wash cycle was reported as the change in percent reflectance value (ΔR), which equals the difference between the reflectance of the swatch after bleaching and the reflectance of the same swatch before bleaching. Thus the larger the ΔR value, the more effective the bleaching action.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[C:6]2[CH:9]=[C:10]([N+:12]([O-])=O)[S:11][C:5]=2[N:4]=[N:3]1.Cl.[Cl-].[NH4+]>CO.O.[Fe]>[NH2:12][C:10]1[S:11][C:5]2[N:4]=[N:3][N:2]([CH3:1])[C:7](=[O:8])[C:6]=2[CH:9]=1
Reactant: Cn1nnc2sc([N+](=O)[O-])cc2c1=O
Agent: [Fe]
Agent: Cl
Agent: [Cl-]
Solvent: CO
Solvent: O
Product: Cn1nnc2sc(N)cc2c1=O
Temperature: 25 °C
Yield: 7.4 %

Procedure:
To a solution of 3-methyl-6-nitrothiopheno[2,3-d]1,2,3-triazin-4-one (1.25 g, 5.9 mmol) in methanol (50 mL) was added conc. Hydrochloric acid (0.6 mL). To the above solution was added iron powder (1.67 g, 29.5 mmol) followed by a solution of ammonium chloride (1.57 g, 29.5 mmol) in water (10 mL) at rt. The reaction mixture was stirred and warmed to 70 for 1 h and was then allowed to cool to rt. The solution was filtered and basified with saturated sodium bicarbonate solution. The solution was extracted with ethyl acetate (4×100 mL). The combined organic layer was dried over sodium sulfate and filtered. Solvent was evaporated and the residue was chromatographed over silica gel column using hexane-ethyl: acetate (60:40) as eluents to give the product as a pale yellow color solid (80 mg, 7.5%), mp 190-194° C. 1H NMR (400 MHz, DMSO-d6): δ 7.40 (2H, s), 6.11 (1H, s), 3.82 (3H, s); LC-MS (negative ion mode): m/z 181 (M−H)−.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[N:9]([CH2:20][CH:21]([CH3:23])[CH3:22])[S:10]([C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)(=[O:12])=[O:11].[N:24]1[CH:29]=[CH:28][C:27]([CH2:30]O)=[CH:26][CH:25]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[N:9]([CH2:20][CH:21]([CH3:23])[CH3:22])[S:10]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:30][C:27]2[CH:28]=[CH:29][N:24]=[CH:25][CH:26]=2)=[CH:15][CH:14]=1)(=[O:12])=[O:11]
Reactant: Cc1ccc(N(CC(C)C)S(=O)(=O)c2ccc(O)cc2)c(C)c1
Reactant: OCc1ccncc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1ccc(N(CC(C)C)S(=O)(=O)c2ccc(OCc3ccncc3)cc2)c(C)c1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
N-(2,4-dimethylphenyl)-4-hydroxy-N-isobutylbenzenesulfonamide (33 mg, 0.099 mmol), pyridine-4ylmethanol (2.52 mg, 0.148 mmol), triphenylphosphine (39 mg, 0.149 mmol) were pre-weighed into a 4 mL glass vial. Tetrahydrofuran (THF) (0.6 mL) was added followed by diisopropyl diazene-1,2-dicarboxylate (DIAD) (0.029 mL, 0.148 mmol). The vial was capped and stirred at RT for 2 days. The reaction mixture was filtered to remove any insoluble materials. The sample was purified by mass directed autoprep on an Xbridge column using acetonitrile:water with an ammonium carbonate modifier. The solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus to give the required product.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.C([SiH](CC)CC)C>FC(F)(F)C(O)=O>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][NH:6]2
Reactant: Clc1cccc2[nH]ccc12
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: Clc1cccc2c1CCN2
Yield: 90.5 %

Procedure:
A solution of 4-chloroindole (3.15 g) and triethylsilane (8.30 ml) in trifluoroacetic acid (32 ml) was stirred at 50° C. for 30 minutes. The solvent was evaporated under reduced pressure, and the residue was basified with a saturated aqueous sodium hydrogen carbonate solution. The mixture was extracted with ethyl acetate twice, and the combined organic layer was dried over magnesium sulfate. The insoluble materials were filtered off, and the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0-80:20) to give the titled compound (2.89 g) as colorless oil. APCI-Mass m/Z 154/156 (M+H). 1H-NMR (DMSO-d6) δ 2.94 (t, J=8.7 Hz, 2H), 3.46 (t, J=8.7 Hz, 2H), 5.83 (s, 1H), 6.40 (d, J=7.7 Hz, 1H), 6.50 (d, J=8.0 Hz, 1H), 6.90 (t, J=7.9 Hz, 1H).