Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[C:3]1([C:9]2[NH:10][CH:11]=[CH:12][N:13]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:14]([NH:18][C:19]1[CH:24]=[C:23](F)[CH:22]=[CH:21][C:20]=1[N+:26]([O-:28])=[O:27])[CH:15]([CH3:17])[CH3:16]>CN(C)C=O.C(OCC)(=O)C>[CH2:14]([NH:18][C:19]1[CH:24]=[C:23]([N:13]2[CH:12]=[CH:11][N:10]=[C:9]2[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:22]=[CH:21][C:20]=1[N+:26]([O-:28])=[O:27])[CH:15]([CH3:17])[CH3:16]
Reactant: CC(C)CNc1cc(F)ccc1[N+](=O)[O-]
Reactant: c1ccc(-c2ncc[nH]2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)CNc1cc(-n2ccnc2-c2ccccc2)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 56.7 %

Procedure:
Add sodium hydride (60% oil dispersion, 94 mg, 2.36 mmol) to a solution of 2-phenylimidazole (340 mg, 2.36 mmol) in 8 mL dimethylformamide. Stir at room temperature for 15 minutes and then add N-[isobutyl]2-nitro-5-fluoroaniline (500 mg, 2.36 mmol). Stir at 60° C. over night under a nitrogen atmosphere. Dilute the reaction mixture with ethyl acetate and wash with dilute aqueous sodium bicarbonate. Dry the organic phase over sodium sulfate, filter, and concentrate under reduced pressure. Subject the residue to radial silica gel chromatography, eluting with a gradient of 0.1%-5% methanol in dichloromethane to provide the desired compound as a yellow solid (450 mg, 57%).
Reaction SMILES: [F:1][C:2]1[C:9]([N+:10]([O-:12])=[O:11])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[NH2:13]/[C:14](/[CH3:20])=[CH:15]\[C:16]([O:18][CH3:19])=[O:17].[C:21]([O:27][CH2:28][C:29]([CH3:33])([CH3:32])[CH2:30][Cl:31])(=[O:26])[CH2:22][C:23]([CH3:25])=O>C(O)(C)C>[CH3:25][C:23]1[NH:13][C:14]([CH3:20])=[C:15]([C:16]([O:18][CH3:19])=[O:17])[CH:4]([C:3]2[CH:6]=[CH:7][CH:8]=[C:9]([N+:10]([O-:12])=[O:11])[C:2]=2[F:1])[C:22]=1[C:21]([O:27][CH2:28][C:29]([CH3:33])([CH3:32])[CH2:30][Cl:31])=[O:26]
Reactant: COC(=O)/C=C(/C)N
Reactant: O=Cc1cccc([N+](=O)[O-])c1F
Reactant: CC(=O)CC(=O)OCC(C)(C)CCl
Solvent: CC(C)O
Product: COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)(C)CCl)C1c1cccc([N+](=O)[O-])c1F
Yield: 46 %

Procedure:
To a solution of 1.70 g of 2-fluoro-3-nitrobenzaldehyde in 10 ml of isopropanol were added 1.15 g of methyl 3-aminocrotonate and 2.10 g of 3-chloro-2,2-dimethylpropyl acetoacetate. The mixture was refluxed for 5 hours. Solvent was distilled off under reduced presoure to leave a residue. The residue was chromatographed on silica gel to give 2.09 g of 3-chloro-2,2-dimethylpropyl methyl 2,6-dimethyl-4-(2-fluoro-3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].[Br:14][CH2:15][CH2:16][CH2:17][CH2:18]Br>C1(=O)CCCC1>[Br:14][CH2:15][CH2:16][CH:17]([O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH3:18]
Reactant: BrCCCCBr
Reactant: Oc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=C1CCCC1
Product: CC(CCBr)Oc1ccccc1
Yield: 49.3 %

Procedure:
A mixture of 329 g of phenol, 484 g of dry potassium carbonate, 756 g of 1,4-dibromobutane and 1,000 ml of cyclopentanone is refluxed for 24 hours, whilst stirring. The solid constituents are filtered off and the filtrate is then concentrated under reduced pressure; the oily residue is taken up in 1,500 ml of methylene chloride and this solution is extracted ten times with 200 ml of 15 percent strength aqueous sodium hydroxide solution at a time. The organic phase is then extracted twice with 300 ml of water at a time, dried over magnesium sulate, filtered and concentrated under reduced pressure. Distillation of the residue gives, at 92°-98° C./0.4 mbar, 395 g of colorless 1-bromo-3-phenoxybutane, which solidifies in the receiver; melting point 33°-36° C.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][C@H:5]1[C@H:9]([NH:10][S:11]([C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=2)(=[O:13])=[O:12])[CH2:8][N:7]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:6]1.Br[CH2:31][CH2:32][CH:33]([CH3:35])[CH3:34].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[OH:1][CH2:2][CH2:3][CH2:4][C@H:5]1[C@H:9]([N:10]([CH2:31][CH2:32][CH:33]([CH3:35])[CH3:34])[S:11]([C:14]2[CH:15]=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)(=[O:13])=[O:12])[CH2:8][N:7]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:6]1
Reactant: CC(C)CCBr
Reactant: CC(C)(C)OC(=O)N1C[C@@H](CCCO)[C@H](NS(=O)(=O)c2ccc([N+](=O)[O-])cc2)C1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)CCN([C@@H]1CN(C(=O)OC(C)(C)C)C[C@H]1CCCO)S(=O)(=O)c1ccc([N+](=O)[O-])cc1
Temperature: 85 °C
Reaction time: 3.5 h

Procedure:
To a mixture of tert-butyl (3R*,4S*)-3-(3-hydroxypropyl)-4-{[(4-nitrophenyl)sulfonyl]amino}pyrrolidine-1-carboxylate (0.82 g, 1.91 mmol) and 1-bromo-3-methylbutane (0.30 g, 2.0 mmol) in 8 mL DMF, Cs2CO3 (0.93 g, 2.86 mmol) was added and the mixture was stirred at 3.5 hours at 85° C. The mixture was diluted with H2O, extracted with CH2Cl2, the combined organic extracts were dried with Na2SO4 and evaporated. The residue was purified by column chromatography on silica gel eluting with 1→5% MeOH in CH2Cl2 giving the title compound.
Reaction SMILES: [NH2:1][C:2]1[C:10]([C:11]([F:14])([F:13])[F:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH3:15][NH2:16].[CH:17]1([N:21]2[CH2:26][CH2:25][CH:24]([O:27][C:28]3[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=3)[CH2:23][CH2:22]2)[CH2:20][CH2:19][CH2:18]1>>[CH:17]1([N:21]2[CH2:26][CH2:25][CH:24]([O:27][C:28]3[CH:35]=[CH:34][C:31]([C:32]4[N:16]([CH3:15])[C:4](=[O:6])[C:3]5[C:2](=[C:10]([C:11]([F:14])([F:13])[F:12])[CH:9]=[CH:8][CH:7]=5)[N:1]=4)=[CH:30][CH:29]=3)[CH2:23][CH2:22]2)[CH2:20][CH2:19][CH2:18]1
Reactant: CN
Reactant: Nc1c(C(=O)O)cccc1C(F)(F)F
Reactant: O=Cc1ccc(OC2CCN(C3CCC3)CC2)cc1
Product: Cn1c(-c2ccc(OC3CCN(C4CCC4)CC3)cc2)nc2c(C(F)(F)F)cccc2c1=O

Procedure:
The entitled compound was obtained according to the method of Example 15 but starting from 2-amino-3-trifluoromethylbenzoic acid, methylamine and 4-[(1-cyclobutyl-4-piperidinyl)oxy]benzaldehyde.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1.[CH2:12]=[O:13].[OH-].[K+].Cl>CS(C)=O.C(O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:12][OH:13])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1
Reactant: C=O
Reactant: Cc1ccc(F)cc1[N+](=O)[O-]
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: CCO
Solvent: O
Product: O=[N+]([O-])c1cc(F)ccc1CCO
Temperature: 25 °C
Reaction time: 144 h
Yield: 23.8 %

Procedure:
To a solution of 4-fluoro-1-methyl-2-nitrobenzene (73.2 g, 0.47 mole) in DMSO (75 mL) was added paraformaldehyde (14.1 g, 0.47 mole), followed by potassium hydroxide (0.75 g) in ethanol (5 mL). The resulting reaction mixture was stirred at room temperature for six days and water (2 L) was added and the mixture neutralized with hydrochloric acid (2 N). The mixture was extracted with ethyl acetate (1 L) and the combined organic layers were washed with water (1 L), saturated sodium chloride (500 mL), dried (sodium sulfate) and concentrated to a yellow solid. Purification by flash column chromatography (silica gel, 1:1 methylene chloride:hexanes to methylene chloride) provided 20.7 g of the title compound as a light yellow oil. 1H NMR (CDCl3): 7.63 δ (dd, 1H); 7.40 δ (dd, 1H); 7.28 δ (dd, 1H); 3.90 δ (t, 3H); 3.10 δ (t, 2H); 1.55 δ (broad, 1H).
Reaction SMILES: [CH:1]1([NH:4][C:5]([C:7]2[N:8]=[N:9][N:10]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([NH:20][CH2:21][C:22](F)(F)F)=[O:19])=[CH:14][C:13]=3[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]O)[CH:11]=2)=[O:6])[CH2:3][CH2:2]1.[F:32]C1(F)N(C)CCN1C>C(#N)C>[CH:1]1([NH:4][C:5]([C:7]2[N:8]=[N:9][N:10]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([NH:20][CH2:21][CH3:22])=[O:19])=[CH:14][C:13]=3[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][F:32])[CH:11]=2)=[O:6])[CH2:2][CH2:3]1
Reactant: O=C(NCC(F)(F)F)c1ccc(-n2cc(C(=O)NC3CC3)nn2)c(CCCCCO)c1
Reactant: CN1CCN(C)C1(F)F
Solvent: CC#N
Product: CCNC(=O)c1ccc(-n2cc(C(=O)NC3CC3)nn2)c(CCCCCF)c1
Temperature: 60 °C
Reaction time: 1 h
Yield: 53.2 %

Procedure:
To a suspension of N-cyclopropyl-1-(2-(5-hydroxypentyl)-4-{[(2,2,2-trifluoroethyl)amino]carbonyl}phenyl)-1H-1,2,3-triazole-4-carboxamide (50.0 mg, 0.13 mmol) obtained in Example 394 in acetonitrile (3.0 ml) was added 2,2-difluoro-1,3-dimethylimidazolidine (20 μl, 0.16 mmol) and the mixture was stirred at 60° C. for 1 hr. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column (ethyl acetate/hexane=1/4 to ethyl acetate) and recrystallized from ethyl acetate-hexane to give the title compound as a colorless powder (26.8 mg, 53%).
Reaction SMILES: [OH-].[Na+].C[O:4][C:5]([C:7]1([NH:13][C:14]([C:16]2[CH:20]=[CH:19][O:18][CH:17]=2)=[O:15])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:6].CCOCC>O1CCCC1>[O:18]1[CH:19]=[CH:20][C:16]([C:14]([NH:13][C:7]2([C:5]([OH:6])=[O:4])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)=[O:15])=[CH:17]1
Reactant: COC(=O)C1(NC(=O)c2ccoc2)CCCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCOCC
Product: O=C(NC1(C(=O)O)CCCCC1)c1ccoc1
Yield: 96.7 %

Procedure:
450 ml of 2N aqueous sodium hydroxide solution was added to a solution of 75.4 g (300 mmol) of 1-[(3-furanylcarbonyl)amino]cyclohexanecarboxylic acid methyl ester in 450 ml of tetrahydrofuran, and the mixture was heated under reflux for 3 hours. After ether was added to the reaction solution to wash it, the aqueous layer was neutralized by concentrated hydrochloric acid, it was extracted with ethyl acetate. After the obtained organic layer was washed with saturated brine, it was dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 68.8 g (97%) of the title compound.
Reaction SMILES: [F:1][C:2]([F:22])([F:21])[C:3]1[CH:4]=[C:5]([C:9]2[S:13][N:12]=[N:11][C:10]=2[S:14]CCC(OC)=O)[CH:6]=[CH:7][CH:8]=1.C[O-].[Na+]>CO>[F:22][C:2]([F:1])([F:21])[C:3]1[CH:4]=[C:5]([C:9]2[S:13][N:12]=[N:11][C:10]=2[SH:14])[CH:6]=[CH:7][CH:8]=1
Reactant: COC(=O)CCSc1nnsc1-c1cccc(C(F)(F)F)c1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: FC(F)(F)c1cccc(-c2snnc2S)c1
Reaction time: 1 h
Yield: 77.9 %

Procedure:
A solution of 11.6 g of 3-[[5-[3-(trifluoromethyl)phenyl]-1,2,3-thiadiazol-4-yl]thio]propanoic acid, methyl ester in 100 ml of dry methanol was treated with 32 ml of 1M methanolic sodium methoxide. After standing one hour, the solvent was removed in vacuo, the residue taken up in dry methanol, filtered and then concentrated. The oil was triturated with ether giving a solid which was collected and dried in vacuo, giving 6.8 g of 5-[3-(trifluoromethyl)phenyl]-1,2,3-thiadiazole-4-thiol, monosodium salt as a yellow powder, mp>200° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:23])[CH2:5][NH:6][CH2:7][CH2:8][CH:9]=[C:10]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:2].Br[CH2:25][CH3:26].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>>[CH2:1]([O:3][C:4](=[O:23])[CH2:5][N:6]([CH2:7][CH2:8][CH:9]=[C:10]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH2:25][CH3:26])[CH3:2]
Reactant: CCBr
Reactant: CCOC(=O)CNCCC=C(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Product: CCOC(=O)CN(CC)CCC=C(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 66.4 %

Procedure:
A mixture of 0.158 g (0.5 mmol) of N-[(4,4-diphenyl)but-3-enyl]glycine ethyl ester (Compound A26), 0.234 g (2.1 mmol) bromoethane, 0.281 g (2 mmol) potassium carbonate and 0.068 g (0.4 mmol) potassium iodide was stirred under argon for 20 hours at room temperature. The reaction mixture was filtered, the solvent evaporated, and the residue chromatographed on a silica gel column with 20% ethyl acetate in hexanes to yield 0.112 g (66%) N-[(4,4-diphenyl)but-3-enyl]-N-ethylglycine ethyl ester (Compound A16) as an oil. NMR spectra showed: 1H NMR (CDCl3, 300 MHz) 7.60-7.00 (m, 10 H), 6.09 (t, 1 H), 4.13 (q, 2 H), 3.27 (s, 2 H), 2.72 (t, 2 H), 2.61 (q, 2 H), 2.28 (dt, 2 H), 1.23 (t, 3 H), 1.01 (t, 3 H); 13C NMR (CDCl3, 75 MHz) 171.77, 142.96, 142.86, 140.33, 130.09, 128.49, 128.35, 127.48, 127.27, 127.19, 60.58, 54.90, 53.98, 48.20, 28.19, 14.57, 12.70.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([CH:12]=[CH2:13])=[C:7]([O:14][CH3:15])[CH:6]=[CH:5]2.C([Li])CCC.[NH:21]1[CH:25]=[C:24]([C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[N:23]=[CH:22]1.[Cl-].[NH4+]>C1COCC1.CCCCCC.O>[CH2:12]([C:8]1[C:7]([O:14][CH3:15])=[CH:6][CH:5]=[C:4]2[C:9]=1[CH:10]=[CH:11][C:2]([C:26]([C:24]1[N:23]=[CH:22][NH:21][CH:25]=1)([OH:30])[CH:27]([CH3:29])[CH3:28])=[CH:3]2)[CH3:13]
Reactant: C=Cc1c(OC)ccc2cc(Br)ccc12
Reactant: CC(C)C(=O)c1c[nH]cn1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: O
Product: CCc1c(OC)ccc2cc(C(O)(c3c[nH]cn3)C(C)C)ccc12
Reaction time: 0.5 h
Yield: 86.5 %

Procedure:
6-Bromo-1-ethenyl-2-methoxynaphthalene (1.20 g) was dissolved in THF (12 ml). To the solution was added dropwise a solution of n-butyllithium in hexane (1.6M: 3.4 ml) at −70° C., and the mixture was stirred for 30 min. A solution of 1-(1H-imidazol-4-yl)-2-methyl-1-propanone (1.73 g) in THF (10 ml) was stirred for 40 min, and the temperature of the mixture was elevated to room temperature. To the reaction mixture were added an aqueous solution of ammonium chloride (10 ml) and water (10 ml), and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried and concentrated. The residue was crystallized from ethyl acetate to give the titled compound (1.28 g) as a colorless powder. Mother liquor was purified by silica gel column chromatography (eluent, hexane-ethyl acetate=1:1) followed by recrystallization from ethyl acetate-diisopropyl ether to give the titled compound (0.23 g).
Reaction SMILES: C(SC1SC2=NC(C3C=CC=CC=3)=CN2N=1)C1C=CC=CC=1.[NH2:23][N:24]1[CH:28]=[C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:26]=[C:25]1[SH:35].[CH3:36][C:37]1[CH:45]=[CH:44][CH:43]=[CH:42][C:38]=1[C:39](Cl)=[O:40]>>[CH3:36][C:37]1[CH:45]=[CH:44][CH:43]=[CH:42][C:38]=1[C:39]([NH:23][N:24]1[CH:28]=[C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:26]=[C:25]1[SH:35])=[O:40]
Reactant: Cc1ccccc1C(=O)Cl
Reactant: Nn1cc(-c2ccccc2)nc1S
Agent: c1ccc(CSc2nn3cc(-c4ccccc4)nc3s2)cc1
Product: Cc1ccccc1C(=O)Nn1cc(-c2ccccc2)nc1S

Procedure:
4.4 g of 1-(2-methylbenzoylamino)-2-mercapto-4-phenylimidazole (obtained by hydrazinolysis of 2-benzylmercapto-6-phenyl-imidazo[2,1-b]-1,3,4-thiadiazole and subsequent acylation of the 1-amino-2-mercapto-4-phenyl-imidazole with 2-methylbenzoyl chloride), melting point 268°-270° C., were heated to the boil in 30 ml of POCl3 for 20 minutes. The mixture is cooled and mixed with ice and the product is filtered off and then recrystallised from alcohol. 2.6 g, corresponding to 67% of theory, of colourless crystals of melting point 159°-160° C. are obtained.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:20]=[CH:19][C:11]3[NH:12][C:13](=O)[O:14][C:15]([CH3:17])([CH3:16])[C:10]=3[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:30])=CC=1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:20]=[CH:19][C:11]3[NH:12][C:13](=[S:30])[O:14][C:15]([CH3:17])([CH3:16])[C:10]=3[CH:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CC1(C)OC(=O)Nc2ccc(-c3cccc(Br)c3)cc21
Solvent: Cc1ccccc1
Product: CC1(C)OC(=S)Nc2ccc(-c3cccc(Br)c3)cc21
Temperature: 110 °C
Yield: 122.9 %

Procedure:
A mixture of 6-(3-bromo-phenyl)-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one(3 g, 9.04 mmol) and Lawesson's Reagent (1.83 g, 4,51 mmol) in toluene (30 ml) was heated to 110° C. for 24 hours. The reaction was cooled, the toluene moved removed in vacuo and the residue purified via flash chromatography (silica gel, 20% ethyl acetate/hexane) to give 6-(3-bromophenyl)-4,4-dimethyl-1,4-dihydro-2H-3,1-benzoxazine-2-thione (1.93 g, 61%) as a yellow solid: mp 191-193° C.; 1H-NMR (DMSO-d6) (12.3 (s, 1H), 7.92 (s, 1H), 7.72-7.65 (m, 3H), 7.57-7.54 (m, 1H); 7.45-7.39 (m, 1H), 7.14-7.11 (m, 1H), 1.7 (s, 6H); MS (ES) m/z 347 ([M−H]−, 100%); Anal. Calc. For C16H14BrNOS: C, 55.18; H, 4.05; N, 4.02; Found: C, 55.17; H, 3.93; N, 3.97.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([NH:9][CH:10]1[C:39](=[O:40])[N:12]2[CH:13]([C:23]([O:25][CH:26]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[O:24])[C:14]([CH:17]([O:19][C:20](=[O:22])[CH3:21])[CH3:18])=[CH:15][S:16][C@H:11]12)=[O:8].ClC1C=CC=C(C(OO)=[O:49])C=1>C(Cl)(Cl)Cl>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([NH:9][CH:10]1[C:39](=[O:40])[N:12]2[C:13]([C:23]([O:25][CH:26]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[O:24])=[C:14]([CH:17]([O:19][C:20](=[O:22])[CH3:21])[CH3:18])[CH2:15][S:16](=[O:49])[C@H:11]12)=[O:8]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(=O)OC(C)C1=CS[C@@H]2C(NC(=O)Cc3cccs3)C(=O)N2C1C(=O)OC(c1ccccc1)c1ccccc1
Solvent: ClC(Cl)Cl
Product: CC(=O)OC(C)C1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)C(NC(=O)Cc3cccs3)[C@H]2S(=O)C1
Temperature: 5 °C

Procedure:
To a cooled (5° C.), stirred solution of 0.897 g. of benzhydryl 7-(2-thienylacetamido)-3-(1-acetoxyethyl)-2-cephem-4-carboxylate in 80 ml. of chloroform was added a solution of 0.348 g. of 85 percent m-chloroperbenzoic acid in 3 ml. of chloroform. The reaction mixture was allowed to stir with cooling for 30 minutes after which time it was transferred to a separatory funnel with the aid of additional chloroform and washed successively with sodium bicarbonate solution (2X), and brine (2X) and dried over anhydrous sodium sulfate. The residue obtained by evaporation in vacuo to a froth which was chromatographed on a silica gel column using a toluene-ethyl acetate gradient to give 0.243 g. (26 percent) of what was labeled diastereoisomer I and 0.514 g. (55 percent) of what was labeled diastereoisomer II of the title product; isomer I coming off the column first.
Reaction SMILES: [C:1]([NH:5][C:6]1[C:7]([NH:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=2[O:35][CH3:36])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13](B1OC(C)(C)C(C)(C)O1)[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:45]2[NH:53][C:52]3[CH2:51][CH2:50][NH:49][C:48](=[O:54])[C:47]=3[CH:46]=2)O1>O1CCOCC1.O.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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[C:1]([NH:5][C:6]1[C:7]([NH:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=2[O:35][CH3:36])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:45]1[NH:53][C:52]3[CH2:51][CH2:50][NH:49][C:48](=[O:54])[C:47]=3[CH:46]=1)[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1ccc(CNc2nc3cccc(B4OC(C)(C)C(C)(C)O4)c3nc2NC(C)(C)C)c(OC)c1
Reactant: CC1(C)OB(c2cc3c([nH]2)CCNC3=O)OC1(C)C
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: ClCCl
Solvent: C1COCCO1
Solvent: O
Product: COc1ccc(CNc2nc3cccc(-c4cc5c([nH]4)CCNC5=O)c3nc2NC(C)(C)C)c(OC)c1
Temperature: 105 °C
Reaction time: 3 h
Yield: 125 %

Procedure:
A mixture of N3-(tert-butyl)-N2-(2,4-dimethoxybenzyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxaline-2,3-diamine (304c; 109.6 mg, 0.09 mmol), 2-bromo-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (608) (80 mg, 0.37 mmol), K2PO4 (59 mg, 0.28 mmol), X-Phos (Strem Chemicals, Inc.) (4.46 mg, 9.35 μmol), and Pd2dba3 (Aldrich) (4.28 mg, 4.67 μmol) in a mixture of dioxane (1.0 mL) and water (0.20 mL) was stirred under argon at 105° C. for 3 h. Additional Pd2dba3 (4.28 mg, 4.67 μmol) and dicyclohexyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (4.46 mg, 9.35 μmol) were added, and the resulting mixture was stirred under argon at 105° C. for 15 h. The reaction mixture was subsequently diluted with DCM (10 mL) and concentrated onto silica gel. Chromatographic purification (silica gel, 0-100% EtOAc/hexanes, then 0-10% MeOH/DCM) furnished 2-(3-(tert-butylamino)-2-((2,4-dimethoxybenzyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (56.3 mg) as a yellow solid: m/z (ESI, +ve) 501.2 (M+H)+.
Reaction SMILES: Cl.[CH2:2]([C:9]1[CH:14]=[C:13]([CH3:15])[N:12]=[C:11]([NH:16][CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[N:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Br:23][C:24]1[N:28]=[C:27](Cl)[S:26][N:25]=1.C(N(CC)C(C)C)(C)C>O1CCCC1.O>[CH2:2]([C:9]1[CH:14]=[C:13]([CH3:15])[N:12]=[C:11]([NH:16][CH:17]2[CH2:22][CH2:21][N:20]([C:27]3[S:26][N:25]=[C:24]([Br:23])[N:28]=3)[CH2:19][CH2:18]2)[N:10]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: Clc1nc(Br)ns1
Reactant: Cc1cc(Cc2ccccc2)nc(NC2CCNCC2)n1
Agent: Cl
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: Cc1cc(Cc2ccccc2)nc(NC2CCN(c3nc(Br)ns3)CC2)n1

Procedure:
A solution of (4-benzyl-6-methyl-pyrimidin-2-yl)-piperidin-4-yl-amine hydrochloride (125 mg, 0.39 mmol), 3-bromo-5-chloro-[1,2,4]thiadiazol (39 mg, 0.19 mmol) and N,N-diisopropylethyl amine (66 L, 0.39 mmol) in tetrahydrofurane (3 mL) was heated to 95° C. 4.5 hours. The reaction was diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with saturated aqueous NaCl solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using a gradient from CH2Cl2 to CH2Cl2/MeOH 19:1 (v/v) as eluent. The title compound was obtained as a colorless oil (84 mg, 96%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][C:4]=1[S:10]([N:13]1[C:21]2[C:16](=[C:17]([CH:22]=C)[CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14]1)(=[O:12])=[O:11].I([O-])(=O)(=O)=[O:25].[Na+]>O1CCOCC1.O.O=[Os](=O)(=O)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][C:4]=1[S:10]([N:13]1[C:21]2[CH:20]=[CH:19][CH:18]=[C:17]([CH:22]=[O:25])[C:16]=2[CH:15]=[CH:14]1)(=[O:12])=[O:11]
Reactant: C=Cc1cccc2c1ccn2S(=O)(=O)c1cc(C)ccc1OC
Reactant: [O-][I+3]([O-])([O-])[O-]
Agent: O=[Os](=O)(=O)=O
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: COc1ccc(C)cc1S(=O)(=O)n1ccc2c(C=O)cccc21
Reaction time: 0.5 h

Procedure:
OsO4 (10 mg, 0.05 mmol) was added to a stirred mixture of 1-[(2-methoxy-5-methylphenyl)sulfonyl]-4-vinyl-1H-indole (262 mg, 0.80 mmol; Intermediate 7) and 2,6-2,6-lutidine (186 μL, 0.46 mmol) in dioxane (9 mL). The mixture turned from colorless to black in 1 minute. Sodium periodate (0.684 g, 3.2 mmol) in water (3 mL, warmed to dissolve) was added. A grey precipitation was immediately formed. The mixture was stirred for 30 min. and partitioned between 2M aqueous HCl (25 mL) and DCM (25 mL). The organic layer was dried, filtered and concentrated to give the title compound (290 mg, 110%, still some dioxane according to HNMR) as a black solid. MS (ESI+) for C17H15NO4S m/z 330 (M+H)+.