Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:15]2[C:16]3=[C:17]4[C:12](=[CH:13][CH:14]=2)[CH:11]=[CH:10][CH:9]=[C:8]4[CH:7]=[CH:6][C:5]3=[CH:4][CH:3]=1.[C:18]([C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)([CH3:21])([CH3:20])[CH3:19].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C)C=O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:18]([C:22]1[CH:27]=[CH:26][C:25]([C:9]2[C:8]3[C:17]4=[C:16]5[C:5](=[CH:6][CH:7]=3)[CH:4]=[CH:3][CH:2]=[C:15]5[CH:14]=[CH:13][C:12]4=[CH:11][CH:10]=2)=[CH:24][CH:23]=1)([CH3:21])([CH3:20])[CH3:19]
Reactant: CC(C)(C)c1ccc(B(O)O)cc1
Reactant: Brc1ccc2ccc3cccc4ccc1c2c34
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)c1ccc(-c2ccc3ccc4cccc5ccc2c3c45)cc1
Temperature: 130 °C
Reaction time: 2 h
Yield: 79.9 %

Procedure:
A mixed solution of 2.0 g of 1-bromopyrene, 1.9 g of 4-t-butylphenylboronic acid, 3.1 g of tripotassium phosphate, 0.46 g of tetrabutylammonium bromide, 70 mg of palladium acetate and 70 mL of dimethylformamide was heated and stirred under a nitrogen gas stream at 130° C. for 2 hours. The solution was cooled to room temperature and poured into 350 mL of water, and then the precipitated solid was collected by filtration. The resulting solid was dissolved in dichloromethane, washed with water, dried over magnesium sulfate and then concentrated. The resulting crude product was purified by column chromatography and then vacuum-dried to obtain 1.9 g of 1-(4-t-butylphenyl)pyrene.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9](Cl)(=[O:11])=[O:10])=[CH:5][N:4]=1.C(N(CC)CC)C.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([OH:32])[CH:25]=[C:26]([O:30][CH3:31])[C:27]=1[O:28][CH3:29]>ClCCl.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[N:4]=[CH:5][C:6]([S:9]([O:32][C:24]2[CH:25]=[C:26]([O:30][CH3:31])[C:27]([O:28][CH3:29])=[C:22]([O:21][CH3:20])[CH:23]=2)(=[O:11])=[O:10])=[CH:7][CH:8]=1
Reactant: COc1ccc(S(=O)(=O)Cl)cn1
Reactant: COc1cc(O)cc(OC)c1OC
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: COc1ccc(S(=O)(=O)Oc2cc(OC)c(OC)c(OC)c2)cn1
Temperature: 25 °C
Reaction time: 18 h
Yield: 83.3 %

Procedure:
A solution of 2-methoxypyridine-5-sulfonylchloride (314 mg, 1.51 mmol) in dichloromethane (15 mL) was treated with triethylamine (0.63 mL) and 3,4,5-trimethoxyphenol (279 mg, 1.51 mmol), stirred for 18 hours at room temperature, diluted with ethyl acetate, washed three times with 1M Na2CO3, dried (MgSO4), filtered, and concentrated to provide 447 mg of the desired product.
Reaction SMILES: F[C:2]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH2:16]([N:18]([CH2:22][CH3:23])[CH2:19][CH2:20][OH:21])[CH3:17].[H-].[Na+]>CN(C=O)C>[CH2:16]([N:18]([CH2:22][CH3:23])[CH2:19][CH2:20][O:21][C:2]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH3:17]
Reactant: CCOC(=O)c1cc([N+](=O)[O-])ccc1F
Reactant: CCN(CC)CCO
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1cc([N+](=O)[O-])ccc1OCCN(CC)CC
Temperature: 0 °C
Reaction time: 0.75 h

Procedure:
1.06 g (5.00 mmol) of ethyl 2-fluoro-5-nitrobenzoate and 0.58 mL (5.00 mmol) of 2-diethylaminoethanol are dissolved in 20 mL of DMF and at 0° C. 0.36 g (7.45 mmol) of sodium hydride (50%) is added. The mixture is stirred for 45 minutes at 0° C., poured onto ice water, and finally extracted three times with ethyl acetate. The organic phase is dried over sodium sulfate, the solvent is eliminated and the residue is purified through a silica gel column with petroleum ether/ethyl acetate (4:1) as eluant. Yield: 0.30 g (19% of theory); C15H22N2O5 (M=310.35); calc.: molecular ion peak (M+H)+: 311; found: molecular ion peak (M+H)+: 311; Rf value: 0.1 (silica gel, petroleum ether/ethyl acetate (4:1)).
Reaction SMILES: N[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[C:16]([F:19])([F:18])[F:17].OS(O)(=O)=O.N([O-])=O.[Na+].[BrH:29]>O>[Br:29][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[C:16]([F:19])([F:18])[F:17]
Reactant: Br
Reactant: Nc1ccc(C(=O)N2CCOCC2)cc1C(F)(F)F
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Product: O=C(c1ccc(Br)c(C(F)(F)F)c1)N1CCOCC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture of EXAMPLE 144B (8.3 g) was added water (75 mL) and H2SO4 (25 mL). The mixture was stirred at 0° C. while NaNO2 (3.13 g) in water (30 mL) was added. After stirring for 1 hour, the mixture was added to CuBr (5.45 g) in 48% HBr (200 mL). This mixture was stirred at 60° C. for 3 hours, cooled to room temperature, and partitioned between water and ethyl acetate. The organic layer was washed with aqueous Na2CO3 and dried (Na2SO4), filtered and concentrated.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:10]=[CH:9][N:8]([CH:11]([CH3:13])[CH3:12])[N:7]=1)=O)C.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.[OH-].[Na+]>C1COCC1.CCOC(C)=O>[CH:11]([N:8]1[CH:9]=[CH:10][C:6]([CH2:4][OH:3])=[N:7]1)([CH3:13])[CH3:12]
Reactant: CCOC(=O)c1ccn(C(C)C)n1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: CC(C)n1ccc(CO)n1
Reaction time: 8 h

Procedure:
A solution of 1-Isopropyl-1H-pyrazole-3-carboxylic acid ethyl ester (41.1 g, 226 mmol) in THF (678 mL) was cooled to 0° C. under N2. LiAlH4 (1M in THF, 226 mL, 226 mmol) was added dropwise to this solution over 20 min. The reaction was stirred for 1 h, at which point the ester starting material was not detectable by LCMS. H2O (8.58 mL) was added to the reaction dropwise, followed by dropwise addition of 15% NaOH (8.58 mL), followed by H2O (8.57 mL). Celite was then added to the solution and this was allowed to stir overnight. The mixture was then filtered through celite, washing the filter cake to remove all the product (1× with EtOAc, then 2× with 90:10 CH2Cl2:MeOH, then 2× with 1:1 CH2Cl2:MeOH, then 1× with MeOH.) The solvent was then concentrated to give a mixture of solid and oil. The oil was dissolved in EtOAc and filtered through celite, then concentrated. The resulting oil was a mixture of ˜1:1 product with aluminum complexed product. The oil was dissolved in THF (400 mL), 15% NaOH (300 mL) was added and this solution was stirred vigorously for 3 h. The layers were separated, and the aqueous was extracted with EtOAc (6×200 mL) then 2:1 CHCl3:iPrOH (2×300 mL). The combined organic was dried over MgSO4, filtered, and concentrated. The resulting oil was carried on without further purification.
Reaction SMILES: O.Cl.[NH:3]1[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]1.[OH-].[Na+].[CH:12]([O:15][C:16]1[CH:24]=[CH:23][C:19]([C:20](Cl)=[O:21])=[CH:18][C:17]=1[O:25][CH3:26])([CH3:14])[CH3:13].C(Cl)Cl>C1(C)C=CC=CC=1.O>[CH:12]([O:15][C:16]1[CH:24]=[CH:23][C:19]([C:20]([N:3]2[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]2)=[O:21])=[CH:18][C:17]=1[O:25][CH3:26])([CH3:14])[CH3:13]
Reactant: COc1cc(C(=O)Cl)ccc1OC(C)C
Reactant: O=C1CCNCC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Solvent: Cc1ccccc1
Product: COc1cc(C(=O)N2CCC(=O)CC2)ccc1OC(C)C
Yield: 29.9 %

Procedure:
Piperidin-4-one hydrochloride hydrate (29.2 g, 190 mmol) was dissolved in an aqueous solution of sodium hydroxide (95 mL of 2.0 M, 190 mmol). The resulting clear solution was then stirred under nitrogen in an ice water bath. 4-isopropoxy-3-methoxy-benzoyl chloride (43.5 g, 190 mmol) was dissolved in toluene (90 mL) to provide a final volume of 100 mL. This solution was added dropwise in 2 mL portions followed by addition of 1 mL of an aqueous sodium hydroxide (48 mL of 4.0 M, 192 mmol) solution. This process was repeated until both reagents were completely added. When complete, the reaction mixture was allowed to stir at 0° C. for an additional 30 minutes. To the mixture was added CH2Cl2 (250 mL) followed by water (200 mL). The mixture was mixed well in a separatory funnel, and the aqueous layer was further extracted with CH2Cl2 (2×100 mL). Organic layers were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to provide a dark brown oil. Purification was performed by column chromatography to provide 1-(4-isopropoxy-3-methoxy-benzoyl)piperidin-4-one (16.56 g) as a clear light brown oil that crystallized to a slightly tan white solid upon standing. 1H NMR (400 MHz, CDCl3) δ 7.06 (d, J=1.9 Hz, 1H), 7.02 (dd, J=8.2, 2.0 Hz, 1H), 6.90 (d, J=8.3 Hz, 1H), 4.59 (dt, J=12.2, 6.1 Hz, 1H), 3.90-3.88 (br s, 4H), 3.88 (s, 3H), 2.51 (s, 4H), 1.40 (d, J=6.1 Hz, 6H). ESI-MS m/z calc. 291.15, found 292.0 (M+1)+; Retention time: 0.94 minutes (3 minute run).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([NH:7][C:8](=[NH:11])[O:9][CH3:10])[CH2:3][CH2:2]1.[Cl:12][CH2:13][C:14](Cl)=[O:15].C(N(CC)CC)C>O1CCCC1>[O:1]1[CH2:6][CH2:5][N:4]([NH:7][C:8](=[N:11][C:14](=[O:15])[CH2:13][Cl:12])[O:9][CH3:10])[CH2:3][CH2:2]1
Reactant: COC(=N)NN1CCOCC1
Reactant: O=C(Cl)CCl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COC(=NC(=O)CCl)NN1CCOCC1
Yield: 98.4 %

Procedure:
Following the procedure of Example IB, 7.2 g (0.05 mole) of the above isourea, 5.65 g (0.05 mole) of chloroacetyl chloride, 5.05 g (0.05 mole) of triethyl amine and 150 ml of tetrahydrofuran were combined to yield 11.6 g of N-morpholino-N'-(chloroacetyl)-O-methylisourea, nD30 1.4853.
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[Br:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1>[Br:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:2]2[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:3]=2[C:4]([OH:6])=[O:5])=[CH:16][CH:15]=1
Reactant: COc1ccc(Br)c(C(=O)O)c1
Reactant: Oc1ccc(Br)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: COc1ccc(Oc2ccc(Br)cc2)c(C(=O)O)c1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A RBF equipped with a reflux condenser was charged with 2-bromo-5-methoxy benzoic acid (430 g, 1.8614 mol), 4-bromo phenol (322 g, 1.8614 mol, 1 eq), potassium carbonate (514.5 g, 3.7 228 mol, 2.0 eq) and CuOTf-toluene complex (24.08 g, 0.04653 mol, 0.025 eq). Ethyl acetate (9.0 ml 0.09679 mol, 0.052) and toluene (1.3 L) was carefully added portion wise. After stirring at RT for 10 min, the mixture was heated to 50° C. and stirred for 30 min. The mixture was then heated to 110° C. for 20 hrs. The reaction was monitored by TLC. After 20 hrs, TLC showed total consumption of starting materials. The reaction mixture was cooled to RT, diluted with water and acidified by 2N HCl. The reaction mixture was extracted with ethyl acetate (3.0×2 liter) followed by filteration of the extract through celite bed and washing with ethyl acetate (1.0 liter). Combined extracts were dried over sodium sulfate and concentrated to yield a crude mass of 590 g. (Dark brown solid). This mass was used directly in step 2.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([F:14])=[CH:11][CH:12]=2)[CH:7]=[C:6]1[CH3:15].[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([S:24]([C:27]2[C:32]([CH:33]=O)=[CH:31][CH:30]=[CH:29][N:28]=2)(=[O:26])=[O:25])=[CH:20][CH:19]=1>>[CH3:1][O:2][C:3](=[O:16])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([F:14])=[CH:11][CH:12]=2)[C:7]([CH2:33][C:32]2[C:27]([S:24]([C:21]3[CH:22]=[CH:23][C:18]([Cl:17])=[CH:19][CH:20]=3)(=[O:26])=[O:25])=[N:28][CH:29]=[CH:30][CH:31]=2)=[C:6]1[CH3:15]
Reactant: COC(=O)Cn1c(C)cc2cc(F)ccc21
Reactant: O=Cc1cccnc1S(=O)(=O)c1ccc(Cl)cc1
Product: COC(=O)Cn1c(C)c(Cc2cccnc2S(=O)(=O)c2ccc(Cl)cc2)c2cc(F)ccc21

Procedure:
The title compound was prepared by the method of Preparation 1c using (5-fluoro-2-methylindol-1-yl)acetic acid methyl ester and 2-(4-chlorobenzenesulfonyl)pyridine-3-carbaldehyde.
Reaction SMILES: O1CCCCC1[O:7][CH2:8][CH2:9][O:10][C:11]1[C:12]([CH2:17][O:18][CH2:19][CH2:20][N:21]([CH3:23])[CH3:22])=[N:13][CH:14]=[CH:15][CH:16]=1>CC(O)=O>[CH3:22][N:21]([CH3:23])[CH2:20][CH2:19][O:18][CH2:17][C:12]1[C:11]([O:10][CH2:9][CH2:8][OH:7])=[CH:16][CH:15]=[CH:14][N:13]=1
Reactant: CN(C)CCOCc1ncccc1OCCOC1CCCCO1
Solvent: CC(=O)O
Product: CN(C)CCOCc1ncccc1OCCO
Yield: 91.8 %

Procedure:
A solution of N-(2-{[3-(2-(tetrahydro-2H-pyran-2-yloxy)ethoxy)pyridin-2-yl]methoxy}ethyl)-N,N-dimethylamine (from Step 3; 0.69 g, 2.13 mmol) in 2 M HOAc (20 mL) was stirred at 50° C. for two days. The reaction mixture was washed with CHCl3 (×3), saturated with sodium chloride, made basic by addition of 8 M NaOH, and extracted with CHCl3 (×3). The solvent from the combined organic phases was removed under reduced pressure to give 0.47 g (92%) of the title compound as a light brown oil. HRMS m/z calcd for C12H20N2O3 (M)+ 240.1474. found 240.1476.
Reaction SMILES: [I:1][C:2]1[C:3](N)=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([O:12][CH3:13])[CH:6]=2.N([O-])=O.[Na+].[ClH:19]>O.Cl[Cu]>[Cl:19][C:3]1[C:2]([I:1])=[CH:11][C:10]2[C:5]([CH:4]=1)=[CH:6][C:7]([O:12][CH3:13])=[CH:8][CH:9]=2
Reactant: Cl
Reactant: COc1ccc2cc(I)c(N)cc2c1
Agent: Cl[Cu]
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: COc1ccc2cc(I)c(Cl)cc2c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 85 %

Procedure:
To a solution of 3-iodo-7-methoxynaphthalen-2-amine (see Intermediate 6, product of step 3) (1.0 g, 3.34 mmol) in water (20 mL) and conc. HCl (20 mL) was added a solution of NaNO2 (230 mg, 3.34 mmol) in water (10 mL) dropwise at 0° C. and the reaction was stirred at 0° C. for 1 hour. Then CuCl (400 mg, 4.04 mmol) was added and the mixture was stirred at 20° C. for 2 hours. An aqueous/EtOAc workup was followed by purification by silica gel column (PE/EtOAc=100/1) to give 3-chloro-2-iodo-6-methoxynaphthalene (900 mg, yield 85%) as off-white solid. 1H NMR (CDCl3 300 MHz TMS): δ 8.29 (s, 1H), 7.84 (s, 1H), 7.60 (d, J=9.0 Hz, 1H), 7.13 (dd, J=9.0, 2.7 Hz, 1H), 6.99 (d, J=2.4 Hz, 1H), 3.91 (s, 3H).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH:10]=[C:11]([N+]([O-])=O)[CH3:12])([O-:3])=[O:2].C1CCN2C(=NCCC2)CC1.[N+:27]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])#[C-:28].Cl>C1COCC1.C(O)(C)(C)C.CCOC(C)=O>[CH3:12][C:11]1[C:10]([C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N+:1]([O-:3])=[O:2])=[C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[NH:27][CH:28]=1
Reactant: [C-]#[N+]CC(=O)OCC
Reactant: CC(=Cc1ccccc1[N+](=O)[O-])[N+](=O)[O-]
Agent: Cl
Solvent: C1CCC2=NCCCN2CC1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCOC(=O)c1[nH]cc(C)c1-c1ccccc1[N+](=O)[O-]
Temperature: 70 °C
Reaction time: 1 h
Yield: 59.2 %

Procedure:
A solution of 1-nitro-2-[2-nitroprop-1-en-1-yl]benzene (4.1 g, 19.7 mmol) in a mixture of THF (131 mL) and tert-BuOH (66 mL) was treated with DBU (4.45 mL, 29.5 mmol) and ethyl isocyanoacetate (2.67 g, 2.58 mL) added. The resulting solution was stirred for 1 h then heated to 70° C. for 4 h. The mixture was cooled and concentrated in vacuo to give a residue was taken up in EtOAc and aqueous HCl (1 N). The organic layer was separated and washed with brine then dried over Na2SO4. Filtration and solvent removal afforded a residue that was purified on silica gel (gradient elution, 0-40% EtOAc/hexanes) to afford the title compound (3.2 g, 59%) as solid. LCMS (ES+) m/z 275 (M+H)+
Reaction SMILES: [CH3:1][O:2][C:3](=[O:27])[C@H:4]([NH:16][C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])[CH2:5][C:6]1[CH:15]=[CH:14][C:9]2[NH:10][C:11]([CH3:13])=[N:12][C:8]=2[CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:34][Si:35]([CH3:43])([CH3:42])[CH2:36][CH2:37][S:38](Cl)(=[O:40])=[O:39]>C(#N)C>[CH3:1][O:2][C:3](=[O:27])[C@H:4]([NH:16][C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])[CH2:5][C:6]1[CH:15]=[CH:14][C:9]2[N:10]([S:38]([CH2:37][CH2:36][Si:35]([CH3:43])([CH3:42])[CH3:34])(=[O:40])=[O:39])[C:11]([CH3:13])=[N:12][C:8]=2[CH:7]=1
Reactant: C[Si](C)(C)CCS(=O)(=O)Cl
Reactant: COC(=O)[C@@H](Cc1ccc2[nH]c(C)nc2c1)NC(=O)OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: COC(=O)[C@@H](Cc1ccc2c(c1)nc(C)n2S(=O)(=O)CC[Si](C)(C)C)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of (R)-2-benzyloxycarbonylamino-3-(2-methyl-1H-benzoimidazol-5-yl)-propionic acid methyl ester (533 mg, 1.96 mmol), and sodium carbonate in acetonitrile (20 mL) was added neat 2-trimethylsilanylethanesulfonyl chloride all at once. The mixture was stirred at room temperature overnight. Solvents were removed and the residue was purified by chromatography on silica gel using ethyl acetate/hexanes (1:2) as eluent to afford the title compound as a waxy solid (1:1 mixture of N1 and N3 isomers, 66%). 1H-NMR (CDCl3, 500 MHz) δ 7.68 (d, J=8.5 Hz, 0.5H), 7.55 (d, J=8.5 Hz, 0.5H), 7.53 (s, 0.5H), 7.41 (s, 0.5H), 7.34-7.29 (m, 5H), 7.06-7.04 (m, 1H), 5.22 (d, J=8.0 Hz, 0.5H), 5.17 (d, J=7.5 Hz, 0.5H), 5.11-5.07 (m, 2H), 4.72-4.69 (m, 1H), 3.75 (s, 1.5H), 3.72 (s, 1.5H), 3.24-3.17 (m, 2H), 2.79 (s, 3H), 0.92-0.83 (m, 2H), −0.02 (s, 4.5H), −0.05 (s, 4.5H). Mass spec.: 532.26 (MH)+.
Reaction SMILES: OO.FC(F)(F)C(OC(=O)C(F)(F)F)=[O:6].[CH2:16]([C:18]1[N:19]=[N+:20]([O-:34])[C:21]2[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]([CH3:33])[CH3:32])=[CH:24][C:22]=2[N:23]=1)[CH3:17].FC(F)(F)C(O)=O>C(Cl)Cl.N>[CH2:16]([C:18]1[N:19]=[N+:20]([O-:34])[C:21]2[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]([CH3:32])[CH3:33])=[CH:24][C:22]=2[N+:23]=1[O-:6])[CH3:17]
Reactant: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Reactant: CCc1nc2cc(OCCN(C)C)ccc2[n+]([O-])n1
Agent: N
Agent: OO
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCc1n[n+]([O-])c2ccc(OCCN(C)C)cc2[n+]1[O-]
Temperature: 20 °C
Reaction time: 0.17 h
Yield: 32.4 %

Procedure:
Hydrogen peroxide (70%; 0.30 mL, ca. 6.1 mmol) was added dropwise to a stirred solution of trifluoroacetic anhydride (0.85 mL, 6.1 mmol) in DCM (15 mL) at 5° C. The solution was stirred at 20° C. for 10 min, then cooled to 5° C., added to a solution of 1-oxide 29 (160 mg, 0.61 mmol) and trifluoroactic acid (0.10 mL, 1.31 mmol) in DCM (15 mL) at 5° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (40 mL) and extracted with CHCl3 (4×40 mL). The combined organic fraction was dried (Na2SO4) and the solvent evaporated. The residue was purified by column chromatography, eluting with a gradient (0-8%) MeOH/CH2Cl2 to give 1,4-dioxide 30 (55 mg, 32%) as a bright yellow solid, mp (MeOH, EtOAc) 146-149° C.; 1H NMR δ 8.33 (d, J=9.6 Hz, 1 H, H-8), 7.78 (d, J=2.6 Hz, 1 H, H-5), 7.42 (dd, J=9.6, 2.6 Hz, 1 H, H-7), 4.30 (t, J=5.4 Hz, 2 H, OCH2), 3.21 (q, J=7.5 Hz, 2 H, CH2), 2.83 (t, J=5.4 Hz, 2 H, NCH2), 2.37 [s, 6 H N(CH3)2], 1.43 (t, J=7.4 Hz, 3 H, CH3); 13C δ 164.9, 157.1, 141.5, 129.7, 124.7, 123.4, 98.0, 67.9, 57.7, 45.8 (2), 24.1, 9.3. Anal. Calcd for C13H18N4O3.¼MeOH: C, 55.6; H, 6.7; N, 19.6. Found: C, 55.5; H, 6.4; N, 19.5%.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][N:7]([CH2:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=1)[CH2:8][C:9]1[NH:10][CH:11]=[CH:12][N:13]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[CH:46]1([N:52]([CH3:58])[CH2:53][CH2:54][CH2:55][CH2:56][NH2:57])[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1>CN(C=O)C>[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][N:7]([CH2:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([NH:57][CH2:56][CH2:55][CH2:54][CH2:53][N:52]([CH:46]2[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]2)[CH3:58])=[O:21])=[CH:17][CH:16]=1)[CH2:8][C:9]1[NH:13][CH:12]=[CH:11][N:10]=1
Reactant: CN(CCCCN)C1CCCCC1
Reactant: O=C(O)c1ccc(CN(Cc2ncc[nH]2)Cc2ncc[nH]2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: CN(CCCCNC(=O)c1ccc(CN(Cc2ncc[nH]2)Cc2ncc[nH]2)cc1)C1CCCCC1
Reaction time: 18 h

Procedure:
The compound (120 mg) obtained in Example 2-2 was dissolved in anhydrous DMF (3.0 ml) and added with WSCI hydrochloride (103.3 mg) and HOBt (72.8 mg). Then, the solution was added with a solution of the compound (76.0 mg) obtained in Example 98-2 in DMF and stirred for 18 hours. After the reaction, the solvent was distilled off and the residue was then added with a 1 mol/l sodium hydroxide aqueous solution, followed by extraction with chloroform. The extract was washed with saturated saline solution and dried with magnesium sulfate, followed by distilling the solvent off. Subsequently, the residue was purified through silica gel column chromatography (chloroform/methanol) and then treated with hydrochloric acid, thereby obtaining hydrochloride (20.4 mg) of the subject compound as a white solid.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[C:6](=[O:15])[CH:7]=[CH:8][C:9]2=[O:14])([O-])=O.[CH2:16]=[CH:17][CH:18]=[CH2:19]>[Pd].COCCO>[NH2:1][C:4]1[C:5]2[C:6](=[O:15])[C:7]3[C:8](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:9](=[O:14])[C:10]=2[CH:11]=[CH:12][CH:13]=1
Reactant: C=CC=C
Reactant: O=C1C=CC(=O)c2c1cccc2[N+](=O)[O-]
Agent: [Pd]
Solvent: COCCO
Product: Nc1cccc2c1C(=O)c1ccccc1C2=O

Procedure:
122 Grams of 5-nitro-1,4-naphthoquinone which contained 10% of the 6-nitro compound, 2800 grams of methyl cellosolve and 48 grams of 1,3-butadiene were charged into an autoclave and reacted at 90° C. for 2 hours. The reaction solution was allowed to stand for cooling and 1.2 grams of a 5% palladium on carbon catalyst was added thereto. Thereafter, the procedure of Example 4 was repeated to obtain 104 grams of 1-aminoanthraquinone containing therein 7% of 2-aminoanthraquinone.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH:6]([NH:8]S(C(C)(C)C)=O)[CH3:7].[ClH:15]>CO>[ClH:15].[ClH:15].[O:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH:6]([NH2:8])[CH3:7]
Reactant: CC(NS(=O)C(C)(C)C)c1ncco1
Agent: Cl
Solvent: CO
Product: CC(N)c1ncco1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 114.4 %

Procedure:
In a round-bottomed flask, 2-methyl-propane-2-sulfinic acid (1-oxazol-2-yl-ethyl)-amide (449 mg, 1.97 mmol) was dissolved in methanol (3.5 ml) and hydrogen chloride (4.0 M in 1,4-dioxane, 1.0 ml, 4.0 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 15 min then concentrated to give 417 mg of 1-oxazol-2-yl-ethylamine dihydrochloride as an orange waxy solid which was used without further purification.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:21](=[O:22])[N:20]([CH2:23][CH3:24])[C:9]2[N:10]=[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:12]=[CH:13][C:8]=2[C:7]=1Cl)=[O:5])[CH3:2].[CH2:26]([NH:28][CH2:29][CH3:30])[CH3:27]>C(O)C>[CH2:1]([O:3][C:4]([C:6]1[C:21](=[O:22])[N:20]([CH2:23][CH3:24])[C:9]2[N:10]=[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:12]=[CH:13][C:8]=2[C:7]=1[N:28]([CH2:29][CH3:30])[CH2:26][CH3:27])=[O:5])[CH3:2]
Reactant: CCNCC
Reactant: CCOC(=O)c1c(Cl)c2cnc(-c3ccccc3)nc2n(CC)c1=O
Solvent: CCO
Product: CCOC(=O)c1c(N(CC)CC)c2cnc(-c3ccccc3)nc2n(CC)c1=O

Procedure:
Two grams (0.0056 mole) of 5-chloro-7,8-dihydro-8-ethyl-7-oxo-2-phenylpyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (prepared by the method of Example 3, first paragraph) and 0.82 g. (0.11 mole) of diethylamine were added together in ethanol in an autoclave and heated on a steam bath for 2 hours. The reaction mixture was then filtered and the filtrate chilled in ice. The precipitate which formed was collected on a suction filter. Recrystallization from ethyl acetate gave 0.8 g. of product m.p. 110°-115° C.