Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]([CH2:4][C@@H:5]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:6][C@H:7]1[CH2:12][CH2:11][CH2:10][O:9][CH2:8]1)=[N+:2]=[N-:3].[Li+].[CH3:22][Si]([N-][Si](C)(C)C)(C)C.CI>C1COCC1>[N:1]([CH2:4][C@@H:5]([N:13]([CH3:22])[C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:19])[CH3:18])[CH2:6][C@H:7]1[CH2:12][CH2:11][CH2:10][O:9][CH2:8]1)=[N+:2]=[N-:3]
Reactant: CC(C)(C)OC(=O)N[C@H](CN=[N+]=[N-])C[C@H]1CCCOC1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CI
Product: CN(C(=O)OC(C)(C)C)[C@H](CN=[N+]=[N-])C[C@H]1CCCOC1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 100 %

Procedure:
To a solution of tert-butyl (S)-1-azido-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamate (30 mg, 0.11 mmol) in anhydrous THF (4 mL) at −78° C. was added 1.0 M LHMDS solution in THF (253 μL, 0.25 mmol), then stirred at this temperature for 30 min. To this mixture was added MeI (125 μL, 0.22 mmol), then the temperature was allowed to warm to 0° C., and stand for 12 hr in the refrigerator. The reaction mixture was quenched with saturated aq. NH4Cl, extracted with EtOAc (30 mL), the separated organic phase was washed with H2O (2×10 mL), brine, and dried (Na2SO4), and filtered. The filtrate was concentrated, the resulting slurry was purified through flash chromatography on silica gel (eluted with gradient system, 0-30% EtOAc in hexane) to afford tert-butyl (S)-1-azido-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-yl(methyl)carbamate 31 mg, yield 100%. MS ESI+ve m/z 321 (M+Na).
Reaction SMILES: [C:1]([O:5][C:6](=[O:34])[NH:7][C:8]([CH3:33])([CH3:32])[CH2:9][NH:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:19]=2)[N:14]=[CH:13][C:12]=1[N+:29]([O-])=O)([CH3:4])([CH3:3])[CH3:2].[H][H]>[Pt].C(#N)C>[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]([CH3:33])([CH3:32])[CH2:9][NH:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:19]=2)[N:14]=[CH:13][C:12]=1[NH2:29])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(CNc1c([N+](=O)[O-])cnc2ccc(OCc3ccccc3)cc12)NC(=O)OC(C)(C)C
Reactant: [H][H]
Agent: [Pt]
Solvent: CC#N
Product: CC(C)(CNc1c(N)cnc2ccc(OCc3ccccc3)cc12)NC(=O)OC(C)(C)C
Yield: 103.7 %

Procedure:
tert-Butyl[2-(6-benzyloxy-3-nitroquinolin-4-ylamino)-1,1-dimethylethyl]carbamate (13.75 g), 5% platinum on carbon (1.03 g), and acetonitrile (250 mL) were combined. The mixture was shaken overnight under 50 psi (3.4×105 Pa) of hydrogen. The reaction was filtered through CELITE filter agent, and the filter pad was rinsed with acetonitrile. The filtrate was concentrated under reduced pressure. Residual water was removed by an azeotrope with toluene. Removal of all volatiles under reduced pressure provided 13.34 g of crude tert-butyl[2-(3-amino-6-benzyloxyquinolin-4-ylamino)-1,1-dimethylethyl]carbamate as a brown foam.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12](=[O:16])[CH:13]([CH3:15])[CH3:14])=[C:5]2[NH:17][C@H:18]1[CH2:23][CH2:22][C@H:21]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:20][CH2:19]1.[N:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1>>[CH:13]1([C:12]([C:6]2[CH:7]=[N:8][C:9]3[C:4]([C:5]=2[NH:17][C@H:18]2[CH2:23][CH2:22][C@H:21]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:28])([CH3:30])[CH3:29])[CH2:20][CH2:19]2)=[CH:3][C:2]([C:35]2[CH:36]=[CH:37][N:32]=[CH:33][CH:34]=2)=[CH:11][CH:10]=3)=[O:16])[CH2:14][CH2:15]1
Reactant: CC(C)C(=O)c1cnc2ccc(Br)cc2c1N[C@H]1CC[C@H](NC(=O)OC(C)(C)C)CC1
Reactant: OB(O)c1ccncc1
Product: CC(C)(C)OC(=O)N[C@H]1CC[C@H](Nc2c(C(=O)C3CC3)cnc3ccc(-c4ccncc4)cc23)CC1

Procedure:
Following general procedure D, tert-butyl trans-4-(6-bromo-3-isobutyrylquinolin-4-ylamino)cyclohexylcarbamate (49 mg, 0.100 mmol) was reacted with pyridin-4-ylboronic acid (25 mg, 0.200 mmol) to afford the crude product (50 mg) as an off-white solid: ESI MS m/z 487 [C29H34N4O3+H]+.
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]([OH:9])=O)=[C:5]([N+:10]([O-:12])=[O:11])[CH:4]=[N:3]1.[NH:13]1[CH2:16][CH2:15][CH2:14]1.C(N(C(C)C)CC)(C)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>C(OCC)(=O)C>[N:13]1([C:7]([C:6]2[N:2]([CH3:1])[N:3]=[CH:4][C:5]=2[N+:10]([O-:12])=[O:11])=[O:9])[CH2:16][CH2:15][CH2:14]1
Reactant: C1CNC1
Reactant: Cn1ncc([N+](=O)[O-])c1C(=O)O
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: Cn1ncc([N+](=O)[O-])c1C(=O)N1CCC1
Temperature: 25 °C
Reaction time: 40 h
Yield: 73.1 %

Procedure:
To a suspension of 2-methyl-4-nitro-2H-pyrazole-3-carboxylic acid (300 mg, 1.75 mmol), azetidine (354 μl, 5.25 mmol) and diisopropylethylamine (920 μl, 5.26 mmol) in ethyl acetate (7.5 ml) was added 1-propanephosphonic acid cyclic anhydride (3.68 ml, 6.13 mmol; 50% in ethyl acetate) at 0° C. The ice bath was removed and stirring at r.t. was continued for 40 h. The reaction mixture was poured into ethyl acetate (100 ml) and extracted with sodium bicarbonate (saturated aqueous solution) water and brine. The aqueous layer was back-extracted with ethyl acetate, the combined organic phases were dried, evaporated, and the product was purified by silica gel chromatography using an amine phase and a heptane/ethyl acetate gradient to yield a white solid (269 mg, 73%).
Reaction SMILES: [H-].[Na+].[C:3]([C:5]1[CH:21]=[C:20]([C:22]#[N:23])[CH:19]=[CH:18][C:6]=1[NH:7][S:8]([C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1)(=[O:10])=[O:9])#[N:4].[CH:24](I)([CH3:26])[CH3:25].O>CN(C=O)C>[C:3]([C:5]1[CH:21]=[C:20]([C:22]#[N:23])[CH:19]=[CH:18][C:6]=1[N:7]([CH:24]([CH3:26])[CH3:25])[S:8]([C:11]1[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=1)(=[O:10])=[O:9])#[N:4]
Reactant: Cc1ccc(S(=O)(=O)Nc2ccc(C#N)cc2C#N)cc1
Reactant: CC(C)I
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc(S(=O)(=O)N(c2ccc(C#N)cc2C#N)C(C)C)cc1
Temperature: 25 °C
Yield: 12.5 %

Procedure:
To a suspension of sodium hydride (65%, 0.12 g (3.30 mmol)) in 6.0 ml of DMF, 2′,4′-dicyano-p-toluenesulfonanilide (0.49 g (1.65 mmol)) was added with stirring at room temperature. To the resulting mixture, after 10 minutes' stirring at room temperature, isopropyl iodide (0.50 ml (4.94 mmol)) was added and the mixture was heated at 130° C. for 6 hours with stirring. The reaction mixture was then cooled to room temperature, poured into water and extracted with diethyl ether. The extract was washed with 1% aqueous sodium hydroxide solution and with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography with ethyl acetate-hexane (3:7) as eluent, to give 0.07 g (13%) of the title compound as white crystals.
Reaction SMILES: [Si:1]([O:8][CH2:9][CH:10]1[CH2:14][CH:13]([OH:15])[CH2:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].[NH2:18][C:19]1[C:24]([N+:25]([O-:27])=[O:26])=[C:23](Cl)[CH:22]=[CH:21][N:20]=1>C1COCC1>[Si:1]([O:8][C@@H:11]1[C@H:10]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:14][C@@H:13]([O:15][C:23]2[CH:22]=[CH:21][N:20]=[C:19]([NH2:18])[C:24]=2[N+:25]([O-:27])=[O:26])[CH2:12]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: Nc1nccc(Cl)c1[N+](=O)[O-]
Reactant: CC(C)(C)[Si](C)(C)OCC1CCC(O)C1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OC[C@@H]1C[C@@H](Oc2ccnc(N)c2[N+](=O)[O-])C[C@@H]1O[Si](C)(C)C(C)(C)C
Reaction time: 1 h
Yield: 70.5 %

Procedure:
To a solution of (1R,3S,4S)-3-f[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentanol (0.782 g, 0.00217 mol) in THF (30.0 mL) was added NaH (0.156 g, 0.00650 mol) and the mixture was stirred for 1 h. To this was added 2-amino-4-chloro-3-nitropyridine (0.376 g, 0.00217 mol) and the mixture was stirred overnight. The solution was concentrated and the residue was purified by flash chromatography (25% EtOAc/hexanes) to afford the title compound (0.381 g, 35%) as a yellow solid.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:4]([C:5](O)=[O:6])[C:3]=1[NH2:11].[NH2:12][C:13](N)=[O:14].C1(O)C=CC=CC=1>C(O)C>[CH3:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:4]2[C:3]=1[NH:11][C:13](=[O:14])[NH:12][C:5]2=[O:6]
Reactant: NC(N)=O
Reactant: Cc1cccc(C(=O)O)c1N
Solvent: Oc1ccccc1
Solvent: CCO
Product: Cc1cccc2c(=O)[nH]c(=O)[nH]c12
Temperature: 100 °C
Yield: 75 %

Procedure:
3-Methylanthranilic acid (15 g., 0.1 mole), urea (36 g., 0.6 mole) and phenol (86 g.) were mixed together and heated to reflux for three hours. The reaction was then allowed to cool to 100° C. and ethanol (75 ml.) added dropwise. The resulting solid was filtered and washed twice with cold ethanol to afford 13.2 g. (75% yield); m.p. 170° C.
Reaction SMILES: [CH:1]1([CH2:6][C@H:7]([CH2:11][NH:12][O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)[C:8]([OH:10])=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.CC1SC(=S)N([CH:27]=[O:28])N=1>CC(C)=O>[CH:1]1([CH2:6][C@H:7]([CH2:11][N:12]([CH:27]=[O:28])[O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)[C:8]([OH:10])=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cc1nn(C=O)c(=S)s1
Reactant: O=C(O)[C@@H](CNOC1CCCCO1)CC1CCCC1
Solvent: CC(C)=O
Product: O=CN(C[C@@H](CC1CCCC1)C(=O)O)OC1CCCCO1
Reaction time: 0.17 h
Yield: 115.7 %

Procedure:
To a solution of (2R)-3-cyclopentyl-2-{[(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acid (97.05 g, 358 mmol) in acetone (1.1 L) at room temperature was added 5-methyl-2-thioxo-[1,3,4]thiadiazole-3-carbaldehyde (57.3 g, 358 mmol) (Tetrahedron Lett. 1985, 26, 3703-3706). When the reaction was deemed complete, the acetone was removed in vacuo. The residue was suspended in a mixture of hexanes (320 mL) and methyl-t-butyl ether (180 mL), then sonicated. After 10 min, the white solid (presumably 5-methyl-3H-[1,3,4]thiadiazole-2-thione) was filtered off, and the filtrate was evaporated in vacuo to give (2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acid as a pale yellow gum (124 g, >100%). NMR shows the product contains a small amount of MTBE and 5-methyl-3H-[1,3,4]thiadiazole-2-thione.
Reaction SMILES: [Br:1][C:2]1[N:3]=[C:4]([CH:33]2[CH2:36][CH2:35][CH2:34]2)[N:5](COCC[Si](C)(C)C)[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([NH:17]C(=O)OC(C)(C)C)[CH3:16])[N:8]=1>Cl.CO>[Br:1][C:2]1[N:3]=[C:4]([CH:33]2[CH2:36][CH2:35][CH2:34]2)[NH:5][C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([NH2:17])[CH3:16])[N:8]=1
Reactant: C[C@@H](CNc1nccc(-c2c(Br)nc(C3CCC3)n2COCC[Si](C)(C)C)n1)NC(=O)OC(C)(C)C
Agent: Cl
Solvent: CO
Product: C[C@H](N)CNc1nccc(-c2[nH]c(C3CCC3)nc2Br)n1
Temperature: 80 °C
Yield: 151.4 %

Procedure:
A mixture of ((S)-tert-butyl 1-(4-(4-bromo-2-cyclobutyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (0.27 g, 0.47 mmol) in concentrated HCl (0.14 mL) and MeOH (4 mL) was heated to 80° C. for 5 hours. The reaction mixture was allowed to cool to room temperature and concentrated to a yellow solid to afford the crude (S)—N1-(4-(4-bromo-2-cyclobutyl-1H-imidazol-5-yl)pyrimidin-2-yl)propane-1,2-diamine (0.25 g) as the HCl salt which is used in next step without purification: LCMS(m/z) 351.0 (MH+), tR=0.45 minute.
Reaction SMILES: [NH3:1].[C:2]([C:4](=[C:7](SC)[S:8][CH3:9])[C:5]#[N:6])#[N:3]>C(O)C>[NH2:1][C:7]([S:8][CH3:9])=[C:4]([C:5]#[N:6])[C:2]#[N:3]
Reactant: N
Reactant: CSC(SC)=C(C#N)C#N
Solvent: CCO
Product: CSC(N)=C(C#N)C#N
Temperature: 25 °C

Procedure:
At 15°, 650 ml of ethanol was saturated with gaseous ammonia. Seventy-three and three-tenths grams of 2-cyano-3,3-bis(methylthio)propenenitrile were added portionwise during 10 minutes. The reaction mixture was heated to 78° during 15 minutes. The slurry was allowed to cool to ambient temperature, then cooled to 10°. The solid was collected by filtration and washed with cold ethanol to give, when dried, m.p. 228°-229° (Literature m.p. 229°-230°, R. Gompper and W. Topel, Ber. 95, 2871 (1902)).
Reaction SMILES: Cl[C:2]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=1)=[O:5].[CH3:20][CH:21]1[CH2:26][CH2:25][CH2:24][NH:23][CH2:22]1.C(=O)([O-])[O-].[Ca+2]>C(O)C>[CH3:20][CH:21]1[CH2:26][CH2:25][CH2:24][N:23]([C:2]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:3]=2[C:4]([C:6]2[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=2)=[O:5])[CH2:22]1
Reactant: CC1CCCNC1
Reactant: O=C(c1ccc(Cl)cc1)c1cc([N+](=O)[O-])ccc1Cl
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: CCO
Product: CC1CCCN(c2ccc([N+](=O)[O-])cc2C(=O)c2ccc(Cl)cc2)C1

Procedure:
Proceeding as in example 2, with 0.035 mole (10.4 g) of 2,4'-dichloro-5-nitro-benzophenone, 0.07 mole (7 cm3) of 3-methylpiperidine and 0.035 mole (5 g) of calcium carbonate mixed in ethanol, 12 g (Yield : 96%) of the expected product are obtained. M.P. 112° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[NH:7][CH:8]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[Br-:19].[Br-].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.O>C1COCC1>[C:1]([O:5][C:6](=[O:18])[NH:7][CH:8]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([Br:19])[CH:15]=2)[NH:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)NC1CNc2ccccc2C1
Reactant: [Br-]
Agent: c1cc[nH+]cc1
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)NC1CNc2ccc(Br)cc2C1
Yield: 1863.5 %

Procedure:
To a solution of XXIII (2.7 g, 10.9 mmol) in THF was added dropwise a solution of pyridinium tribromide (3.83, 0.41 mmol) in 50 mL of THF at rt. The reaction mixture was stirred for 15 min before 60 mL of water was added into the flask. The aqueous phase was extracted with EtOAc. The combined organic phase was washed with saturated NaCl, dried over Na2SO4 and concentrated. The residue was purified by flash silica gel chromatography to give (6-bromo-1,2,3,4-tetrahydro-quinoline-3-yl)-carbamic acid tert-butyl ester XXIV (2.5 g, 70%) as white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[N+:9]([O-:12])([OH:11])=[O:10].[N:13]#[C:14][NH2:15]>CCO>[N+:9]([O-:12])([OH:11])=[O:10].[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:14]([NH2:15])=[NH:13])=[CH:4][CH:3]=1
Reactant: N#CN
Reactant: Nc1ccc(Cl)cc1
Solvent: CCO
Solvent: O=[N+]([O-])O
Product: N=C(N)Nc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 44 %

Procedure:
A solution of 4-chloroaniline (70 mmol, 8.88 g) in EtOH (5 mL) on an ice bath was treated with nitric acid (69% aq soln.; 5 mL). To this mixture cyanamide (50% aq. soln.; 5.4 mL) was added. The reaction mixture was stirred at r.t. for 10 min and then refluxed under N2 for a further 22 h. The solvent was evaporated. The dark brown solid residue was washed with EtOH and was dried under high vacuum to afford the title compound as a white powder (7.16 g, 44%). 1H-NMR (300 MHz, d6-DMSO) δ7.27-7.54 (m, 4H, Ph-H), 9.65 (br. s, 2H, NH).
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[C:15]2[C:6](=[CH:7][C:8]3[C:9]([CH3:19])([CH3:18])[CH2:10][CH2:11][C:12]([CH3:17])([CH3:16])[C:13]=3[CH:14]=2)[CH2:5][CH2:4][CH2:3]1.CC(O)=[O:23]>[O-2].[O-2].[O-2].[Cr+6]>[CH3:1][C:2]1([CH3:20])[C:15]2[C:6](=[CH:7][C:8]3[C:9]([CH3:19])([CH3:18])[CH2:10][CH2:11][C:12]([CH3:17])([CH3:16])[C:13]=3[CH:14]=2)[C:5](=[O:23])[CH2:4][CH2:3]1
Reactant: CC(=O)O
Reactant: CC1(C)CCCc2cc3c(cc21)C(C)(C)CCC3(C)C
Agent: [Cr+6]
Agent: [O-2]
Product: CC1(C)CCC(=O)c2cc3c(cc21)C(C)(C)CCC3(C)C
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A solution of chromium trioxide (13.55 mL of a 10% CrO3 /AcOH solution) was slowly added to a solution of finely ground 1,1,5,5,8,8-hexamethyl-1,2,3,4,5,6,7,8-octahydroanthracene (861 mg, 3.18 mmol) in AcOH (12 mL) at 25° C. The mixture was stirred for 30 min. Ice water (100 mL) was added, and the mixture was extracted with EtOAc (3×50 mL). The organic extracts were combined and twice treated with Et3N (10 mL), and washed and with sat. NaHCO3 (20 mL), water (2×20 mL) and brine (2×20 mL). The solvent was evaporated and the crude residue was purified by silica gel chromatography (hexanes:EtOAc 9:1) to give 831 mg of pure 3,4,5,6,7,8-hexahydro-4,4,5,5,8,8-hexamethyl-2H-anthracen-1-one (structure 1 where R1, R2, R3, and R4 are methyl, R5, R6, R7, R8, R9, and R10 are hydrogen, X and Y are carbon, Z is C(CH3)2 and m=n=1): 1H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H, Ar), 7.31 (s, 1H, Ar), 2.68 (t, J=8.0 Hz, 2H), 1.98 (t, J=6.0 Hz, 2H), 1.68 (s, 4H) 1.37 (s, 3H), 1.30 (s, 3H), 1.29 (s, 3H). The above ketone was transformed to the title compound as outlined in Scheme II.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH:17]([CH3:23])[C:18]([O:20][CH2:21][CH3:22])=[O:19]>CN(C=O)C>[CH2:21]([O:20][C:18](=[O:19])[CH:17]([O:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=1)[CH3:23])[CH3:22]
Reactant: COc1cccc(O)c1
Reactant: CCOC(=O)C(C)Br
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)Oc1cccc(OC)c1
Temperature: 90 °C
Reaction time: 16 h

Procedure:
3-Methoxyphenol (0.30 mol), Cs2CO3 (197.0 g, 0.61 mol), and ethyl 2-bromopropionate (54.3 g, 0.30 mol) were combined in anhydrous DMF (1000 mL) and stirred at 90° C. under an atmosphere of nitrogen. After 16 h, the DMF was removed in vacuo. The residue was dissolved in ethyl acetate (300 mL) and washed twice with water and once with brine. The organic layer was dried over Na2SO4 and concentrated in vacuo to produce an oil.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=[O:10].O.[CH3:13]C1C=CC(S(O)(=O)=O)=CC=1>CO>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([O:11][CH3:13])=[O:10]
Reactant: O=C(O)Cc1ccccc1Br
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: O
Product: COC(=O)Cc1ccccc1Br
Yield: 93.9 %

Procedure:
To a solution of 2-(2-bromophenyl)acetic acid (2 g, 9.3 mmol) in anhydrous methanol (20 mL) was added 4-methylbenzenesulfonic acid hydrate (1.767 g, 9.3 mmol). The mixture was heated to reflux for 3 hr. The solvent was removed in vacuum. Ethyl ether and water was added. The organic phase was washed with water and brine, then dried over Na2SO4, filtered and concentrated to give methyl 2-(2-bromophenyl)acetate (2 g, 80%), which was used for next step without purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5](O)=[O:6].S(Cl)([Cl:14])=O>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5]([Cl:14])=[O:6]
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1ccc(Cl)c(Cl)c1
Product: O=C(Cl)c1ccc(Cl)c(Cl)c1
Yield: 91 %

Procedure:
A solution of 3,4-dichlorobenzoic acid (20 g, 105.26 mmol) in thionyl chloride (200 ml) was stirred overnight at 90° C. The resulting mixture was concentrated under vacuum to afford 3,4-dichlorobenzoyl chloride as light yellow oil (20 g, 91%).
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[NH4+].[Cl-].[N-:12]=[N+:13]=[N-:14].[Na+]>CN(C=O)C>[NH:12]1[C:6]([C:5]2[CH:8]=[CH:9][C:2]([NH2:1])=[CH:3][CH:4]=2)=[N:7][N:14]=[N:13]1
Reactant: [N-]=[N+]=[N-]
Reactant: N#Cc1ccc(N)cc1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Nc1ccc(-c2nnn[nH]2)cc1
Temperature: 120 °C
Yield: 44.4 %

Procedure:
To a stirred solution of 4-amino-benzonitrile (300 mg, 2.53 mmol; CAS Reg. No. 873-74-5) in dry DMF (6 ml) was added NH4Cl (547 mg, 10.2 mmol) and NaN3 (660 mg, 10.2 mmol) at room temperature. The reaction mixture was then heated at 120° C. for 12 h. After cooling, TLC shows formation of new spot, filtered the solid material by sintered funnel and washed the solid residue by EtOAc (4×5 ml). Combined organic layers were reduced under pressure at 60° C. and diluted the residue with EtOAc (25 mL). Organic layer was washed with H2O (15 ml), brine (12 ml) and dried over Na2SO4; which was then concentrated under reduced pressure to give the crude material (300 mg). Crude product was then purified by column chromatography [SiO2 (230-400 mesh), MeOH:DCM 5:95] to give the title compound (180 mg, 44.4%) as light yellow solid.
Reaction SMILES: Cl.[CH2:2]([O:9][NH2:10])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:11](Br)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[CH2:11]([N:10]([CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[O:9][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: BrCc1ccccc1
Reactant: NOCc1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: c1ccc(CON(Cc2ccccc2)Cc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 96 h

Procedure:
A mixture of 13.04 g of benzyloxyaminehydrochloride, 20.0 ml of benzylbromide, and 32.0 g of sodium carbonate in 85 ml of dimethylformamide is stirred at room temperature for four days. The reaction mixture is worked up as in Example I and the crude product is distilled under reduced pressure to afford the title compound as a clear colorless liquid.
Reaction SMILES: C([O-])(=O)C.[Na+].[NH2:6][C:7]([NH2:9])=[S:8].Cl[CH2:11][C:12](=O)/[C:13](=[N:17]/[O:18][CH2:19][C:20]([O:22][CH3:23])=[O:21])/[C:14]([OH:16])=[O:15].Cl>O>[NH2:6][C:7]1[S:8][CH:11]=[C:12](/[C:13](=[N:17]/[O:18][CH2:19][C:20]([O:22][CH3:23])=[O:21])/[C:14]([OH:16])=[O:15])[N:9]=1
Reactant: COC(=O)CO/N=C(\C(=O)O)C(=O)CCl
Reactant: NC(N)=S
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: COC(=O)CO/N=C(\C(=O)O)c1csc(N)n1
Temperature: 12 °C
Reaction time: 3 h
Yield: 87.1 %

Procedure:
Sodium acetate (120 gm) is added to water (400 ml) and thiourea (41.6 gm) at 25-30° C., cooled to 12° C. and then (Z)-4-chloro-2-[[(methoxycarbonyl)methoxy]imino]acetoacetic acid (100 gm) Is added at 12° C. The contents are stirred for 3 hours at 25-30° C., cooled to 5° C., pH is adjusted to 3.0 with conc. hydrochloric acid at 5-0° C. Then the reaction mass is cooled to 0° C. and stirred for 1 hour at 0-5° C. The resulting solid is filtered, washed two times with chilled water (each time 100 ml) and dried at 100-105° C. to give 95 gm of (Z)-2-(2-aminothiazol-4-yl)-(methoxycarbonyl)methoxyimino acetic acid (High Performance Liquid Chromatographic (HPLC) purity: 99.5%). B) 2,2′-Dithiobis(benzothiazole) (117.75 gm) and acetonitrile (580 ml) are added to (Z)-2-(2-aminothiazol-4-yl)-(methoxycarbonyl)methoxyimino acetic acid (75 gm) at 25-30° C. and then distilled off 50 ml of acetonitrile under vacuum at 45-50° C. The contents are cooled to 25° C. under N2 atmosphere, flushed with 20 ml of acetonitrile and cooled to 13° C. Triethylamine (30 gm) is added to the contents at 13° C., stirred for 30 minutes at 13° C. under N2 atmosphere and then cooled to 0° C. Triphenylphosphine (96 gm) is added to the reaction mass at 0° C., stirred for 1 hour at 0-2° C. and cooled to −10° C. Then the reaction mass is stirred for 4 to 5 hours at −10° C., filtered the mass and washed with chilled methanol. Methanol (470 ml) is added to the reaction mass at 25° C., cooled to −5° C. under N2 atmosphere, the wet cake is added for 5 minutes at −5° C. and stirred for 1 hour at −5° C. Filtered the mass, washed with methanol (100 ml) and dried to yield 93.75 gm of 2-mercapto-1,3-benzothiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-(methoxycarbonyl)-methoxyimino acetate (HPLC purity 98.2%).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][C:6]=1[OH:14])(=[O:3])[CH3:2].[K].CN(C)C=O.[CH2:21]([N:23]([CH2:26][CH2:27]Cl)[CH2:24][CH3:25])[CH3:22]>O>[CH2:21]([N:23]([CH2:26][CH2:27][O:14][C:6]1[CH:7]=[CH:8][C:9]([N+:11]([O-:13])=[O:12])=[CH:10][C:5]=1[NH:4][C:1](=[O:3])[CH3:2])[CH2:24][CH3:25])[CH3:22]
Reactant: CC(=O)Nc1cc([N+](=O)[O-])ccc1O
Reactant: CCN(CC)CCCl
Agent: [K]
Solvent: O
Solvent: CN(C)C=O
Product: CCN(CC)CCOc1ccc([N+](=O)[O-])cc1NC(C)=O
Temperature: 60 °C

Procedure:
117 g (0.5 mol) of 2-acetylamino-4-nitrophenol, in the form of the potassium salt, are introduced into 350 ml of dimethylformamide and the mixture is then heated to 60° C., whilst stirring. 88.2 g (0.65 mol) of diethylaminoethyl chloride are then added; the reaction medium is heated at 95° C. for 150 minutes and is then poured into 1,500 ml of iced water; the expected product precipitates. This product is filtered off and washed with a 0.5 N sodium carbonate solution and then with water. After filtration, the product is finally dried in vacuo at 45° C. It melts at 117° C.