Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:3]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:7][CH:6]=2.[N:22]1([C:28]2[N:33]=[CH:32][CH:31]=[CH:30][N:29]=2)[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.CCN(C(C)C)C(C)C>CN(C)C=O>[C:16]1([C:3]2[C:2]([N:25]3[CH2:26][CH2:27][N:22]([C:28]4[N:29]=[CH:30][CH:31]=[CH:32][N:33]=4)[CH2:23][CH2:24]3)=[N:11][C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:12]([O:14][CH3:15])=[O:13])[CH:9]=3)[N:4]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: c1cnc(N2CCNCC2)nc1
Reactant: COC(=O)c1ccc2nc(-c3ccccc3)c(Br)nc2c1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc2nc(-c3ccccc3)c(N3CCN(c4ncccn4)CC3)nc2c1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
Into a 8-mL sealed tube, was placed methyl 3-bromo-2-phenylquinoxaline-6-carboxylate (150 mg, 0.44 mmol, 1.00 equiv), 2-(piperazin-1-yl)pyrimidine (144.3 mg, 0.88 mmol, 2.00 equiv), DIEA (170.3 mg, 1.32 mmol, 3.00 equiv), N,N-dimethylformamide (3 mL). The resulting solution was stirred overnight at 100° C. in an oil bath. The resulting solution was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:50). This resulted in 192 mg (95%) of methyl 2-phenyl-3-(4-(pyrimidin-2-yl)piperazin-1-yl)quinoxaline-6-carboxylate as a yellow solid.
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[OH:12][CH2:13][CH:14]1[O:18][C:17](=[O:19])[CH2:16][CH2:15]1.N1C=CC=CC=1>C(Cl)Cl>[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([O:12][CH2:13][CH:14]2[O:18][C:17](=[O:19])[CH2:16][CH2:15]2)(=[O:9])=[O:8])=[CH:3][CH:2]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: O=C1CCC(CO)O1
Solvent: c1ccncc1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)OCC2CCC(=O)O2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 76.1 %

Procedure:
p-Toluenesulfonyl chloride (23.65 g, 124.03 mmol) was added portion wise to a solution of (±)-dihydro-5-hydroxymethyl-2(3H)-furanone (example 56) (11.07 g, 95.43 mmol) and pyridine (15.4 mL, 190.86 mmol) in methylene chloride (300 mL) at 0° C. The solution was allowed to warm to rt and stirred overnight. The solution was then washed with water (2×100 mL), 0.5 n HCl until the washings were acidic and finally with saturated NaHCO3. After drying and concentrating, the residue was triturated with toluene to give the title compound as a white solid (19.63 g, 76%).
Reaction SMILES: [C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]\[C:4]([OH:6])=[O:5].C[OH:10].[CH3:11][NH:12][C@@H:13]1[CH2:22][C:21]2[C:16]3=[C:17]([NH:23][C:24](=[S:25])[N:15]3[CH2:14]1)[CH:18]=[CH:19][CH:20]=2>C(Cl)Cl>[C:1]([OH:8])(=[O:7])[CH:2]([CH2:3][C:4]([OH:6])=[O:5])[OH:10].[CH3:11][NH:12][C@@H:13]1[CH2:22][C:21]2[C:16]3=[C:17]([NH:23][C:24](=[S:25])[N:15]3[CH2:14]1)[CH:18]=[CH:19][CH:20]=2
Reactant: O=C(O)/C=C\C(=O)O
Reactant: CO
Agent: CN[C@@H]1Cc2cccc3[nH]c(=S)n(c23)C1
Solvent: ClCCl
Product: O=C(O)CC(O)C(=O)O

Procedure:
A mixture of maleic acid (0.317 g, 2.36 mmol) in a minimal amount of methanol (1 mL) is added to a mixture of (5R)-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione (EXAMPLE 8, 0.493 g, 2.25 mmol) in methylene chloride. The resulting solid is collected by filtration to give the title compound, mp=195-1960; [α]25D=−600 (c 0.93, methanol); IR (drift) 3140, 3112, 3060, 2969, 1627, 1619, 1568, 1481, 1455, 1398, 1389, 1361, 1220, 868 and 747 cm−1; NMR (300 MHz, CD3OD) 7.20-7.30, 7.10-7.20, 6.26, 4.49, 4.31, 4.05-4.20, 3.47, 3.28 and 2.83 δ; CMR (100 MHz, DMSO-d6+CD3OD) 170.4, 169.4, 136.6, 131.1, 130.9, 125.1, 122.1, 116.2, 109.6, 53.9, 43.1, 31.9 and 27.2 δ; MS (ESI, m/z) 220.1 (MH+).
Reaction SMILES: C([O:5][C:6](=[O:26])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][O:18][C:19]2[CH:24]=[CH:23][C:22](Br)=[CH:21][N:20]=2)[N:15]=1)([CH3:9])[CH3:8])(C)(C)C.[F:27][C:28]([F:40])([F:39])[C:29]1[CH:34]=[CH:33][C:32](OB(O)O)=[CH:31][CH:30]=1.[ClH:41].C(OCC)(=O)C>>[ClH:41].[CH3:9][C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][O:18][C:19]2[CH:24]=[CH:23][C:22]([C:32]3[CH:33]=[CH:34][C:29]([C:28]([F:40])([F:39])[F:27])=[CH:30][CH:31]=3)=[CH:21][N:20]=2)[N:15]=1)([CH3:8])[C:6]([OH:5])=[O:26]
Reactant: OB(O)Oc1ccc(C(F)(F)F)cc1
Reactant: CC(C)(C)OC(=O)C(C)(C)Sc1nc(CCOc2ccc(Br)cn2)cs1
Agent: Cl
Solvent: CCOC(C)=O
Product: CC(C)(Sc1nc(CCOc2ccc(-c3ccc(C(F)(F)F)cc3)cn2)cs1)C(=O)O

Procedure:
A compound obtained using 2-[(4-{2-[(5-bromopyridin-2-yl)oxy]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester synthesized in Example 100-1 and 4-(trifluoromethyl)phenylboric acid as starting materials by operations similar to those of Example 100-2 and Example 100-3 was reacted with 4 mol/L hydrochloric acid-ethyl acetate to give the title compound.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[C:4]=1[OH:10])[CH3:2].C1N2CN3CN(C2)CN1C3.[C:21](O)(=[O:23])C>O>[CH2:1]([C:3]1[CH:8]=[C:7]([CH:6]=[C:5]([CH3:9])[C:4]=1[OH:10])[CH:21]=[O:23])[CH3:2]
Reactant: CCc1cccc(C)c1O
Reactant: CC(=O)O
Agent: C1N2CN3CN1CN(C2)C3
Solvent: O
Product: CCc1cc(C=O)cc(C)c1O
Temperature: 25 °C

Procedure:
A solution of 2-ethyl-6-methyl-phenol (8.40 g, 61.7 mmol) and hexamethylene tetraamine (12.97 g, 92.5 mmol) in acetic acid (60 mL) and water (14 mL) is heated to 115° C. The water is distilled off at 117° C. and collected with a Dean-Stark apparatus. Then the water separator is replaced by a reflux condenser and the mixture is refluxed for 3 h. The mixture is cooled to rt, diluted with water (100 mL) and extracted with EA. The org. extract is washed with sat. aq. NaHCO3, dried over MgSO4 and evaporated. The remaining solid is dissolved in EA and treated with heptane to initialize crystallisation. The solid material is collected and dried to give 3-ethyl-4-hydroxy-5-methyl-benzaldehyde (3.13 g) as a colourless crystalline powder, 1H NMR (CDCl3): δ 9.83 (s, 1H), 7.58-7.53 (m, 2H), 5.30 (s br, 1H), 2.69 (q, J=7.6 Hz, 2H), 2.32 (s, 3H), 1.28 (t, J=7.6 Hz, 3H).
Reaction SMILES: Cl[C:2]1[C:11]([O:12][CH:13]([C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[C:14]([F:17])([F:16])[F:15])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.CS(C)=O.[F:28][C:29]([F:35])([F:34])[S:30]([NH2:33])(=[O:32])=[O:31].C(=O)([O-])[O-].[K+].[K+]>C(O)(=O)C>[F:28][C:29]([F:35])([F:34])[S:30]([NH:33][C:2]1[C:11]([O:12][CH:13]([C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[C:14]([F:17])([F:16])[F:15])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1)(=[O:32])=[O:31]
Reactant: FC(F)(F)C(Oc1nc2ccccc2nc1Cl)c1cccnc1
Reactant: NS(=O)(=O)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CC(=O)O
Product: O=S(=O)(Nc1nc2ccccc2nc1OC(c1cccnc1)C(F)(F)F)C(F)(F)F
Temperature: 25 °C
Yield: 13.7 %

Procedure:
According to Example 132, by use of 2-chloro-3-[2,2,2-trifluoro-1-(pyridin-3-yl)ethoxy]-quinoxaline (Compound BJ) (70 mg, 0.21 mmol), dimethyl sulfoxide (2 mL), trifluoromethanesulfonamide (31 mg, 0.21 mmol) and potassium carbonate (28 mg, 0.21 mmol), the mixture was stirred and reacted at 150° C. for 1.5 hours. The reaction mixture was allowed to cool down to room temperature, a 1% aqueous acetic acid solution was added thereto, and extraction with ethyl acetate was performed. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and then the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=1/0 to 20/1). Further, slurry purification was performed using isopropyl ether, to give 1,1,1-trifluoro-N-{3-[2,2,2-trifluoro-1-(pyridin-3-yl)-ethoxy]quinoxalin-2-yl}methanesulfonamide (Compound 149) (13 mg, 14%).
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH2:11][CH2:10][C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:14]1([NH2:21])[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[NH2:20]>>[CH2:1]([NH:8][CH2:12][CH2:11][CH2:10][C:9]1[NH:20][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:21]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1CCCN1Cc1ccccc1
Reactant: Nc1ccccc1N
Product: c1ccc(CNCCCc2nc3ccccc3[nH]2)cc1

Procedure:
By the procedure of Example 2 N-benzylpyrrolidone was reacted with o-phenylenediamine to yield 2-(3-benzylaminopropyl)benzimidazole.
Reaction SMILES: C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.[C:47]([O:51][C:52]([N:54]1[CH2:59][CH2:58][C:57]2([CH2:64][CH2:63][NH:62][CH2:61][CH2:60]2)[CH2:56][CH2:55]1)=[O:53])([CH3:50])([CH3:49])[CH3:48].Br[C:66]1[CH:71]=[CH:70][C:69]([F:72])=[CH:68][CH:67]=1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:47]([O:51][C:52]([N:54]1[CH2:59][CH2:58][C:57]2([CH2:64][CH2:63][N:62]([C:66]3[CH:71]=[CH:70][C:69]([F:72])=[CH:68][CH:67]=3)[CH2:61][CH2:60]2)[CH2:56][CH2:55]1)=[O:53])([CH3:50])([CH3:48])[CH3:49]
Reactant: Fc1ccc(Br)cc1
Reactant: CC(C)(C)OC(=O)N1CCC2(CCNCC2)CC1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCC2(CC1)CCN(c1ccc(F)cc1)CC2
Reaction time: 0.25 h
Yield: 43 %

Procedure:
BINAP (350 mg, 0.47 mmol) and Pd2 dba3 (317 mg, 1.57 mmol) was added to a mixture of 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (2 g, 7.87 mmol), 1-bromo-4-fluoro-benzene (1.3 g, 7.87 mmol) and sodium tert-butylate (2.26 g, 23.61 mmol) in toluene (25 ml) and the reaction mixture was degassed under argon for 20 minutes and heated under reflux for 4 h. The mixture was then diluted with ethyl acetate, stirred for 15 minutes and filtered over Celite. The reaction mixture was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 43%
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]=[C:12]=[O:13])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:14][C:15]1[CH:20]=[C:19]([Br:21])[CH:18]=[CH:17][N:16]=1>C(Cl)Cl>[Br:21][C:19]1[CH:18]=[CH:17][N:16]=[C:15]([NH:14][C:12]([NH:11][S:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)(=[O:9])=[O:10])=[O:13])[CH:20]=1
Reactant: O=C=NS(=O)(=O)c1ccc(Cl)cc1
Reactant: Nc1cc(Br)ccn1
Solvent: ClCCl
Product: O=C(Nc1cc(Br)ccn1)NS(=O)(=O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 41.2 %

Procedure:
4-Chlorbenzenesulfonyl isocyanate (150 mg) was dissolved in CH2Cl2 (2 mL). 2-Amino-4-brompyridine (132 mg) was added to the mixture. After that the mixture was stirred for 18 h at 25° C. The obtained white precipitate was filtered off and washed with CH2Cl2 and dried in vacuo to yield N-[(4-bromopyridin-2-yl)carbamoyl]-4-chlorobenzenesulfonamide (111 mg; 41%) as a white solid.
Reaction SMILES: Cl[C:2]1[CH:11]=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:12])[CH:8]=2)[N:3]=1.[C:13]1([CH2:19][NH2:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.O>CS(C)=O>[CH2:19]([NH:20][C:2]1[CH:11]=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:12])[CH:8]=2)[N:3]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: NCc1ccccc1
Reactant: Clc1ccc2nc(Cl)cnc2c1
Solvent: O
Solvent: CS(C)=O
Product: Clc1ccc2nc(NCc3ccccc3)cnc2c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
2,6-Dichloroquinoxaline (0.500 g, 2.5 mmol) was dissolved in DMSO (10 mL) at RT and phenylmethanamine (1.3 g, 12.56 mmol) was added. The reaction mixture was stirred at RT for 16 h. After completion of reaction (confirmed by TLC), water (100 mL) was added to the reaction mixture and this layer was extracted with ethyl acetate (50 mL×3). The organic layer was washed with water (15 mL), brine (15 mL) and dried over Na2SO4. The organic layer was concentrated under vacuum to give crude product.
Reaction SMILES: [C:1]1([O:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.[NH:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]([CH2:26][CH:27]([NH2:29])[CH3:28])=[CH:18]1>C(Cl)Cl>[C:1]1([O:7][C:8](=[O:9])[NH:29][CH:27]([CH3:28])[CH2:26][C:19]2[C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[NH:17][CH:18]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(N)Cc1c[nH]c2ccccc12
Reactant: O=C(Cl)Oc1ccccc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(Cc1c[nH]c2ccccc12)NC(=O)Oc1ccccc1
Reaction time: 24 h

Procedure:
Chloroformic acid phenyl ester (760 μl, 6.03 mmol.) and pyridine (510 μl, 6.31 mmol.) were added to a solution of rac. 2-(1H-indol-3-yl)-1-methylethylamine (1.0 g, 5.74 mmol.) in abs. DCM (20 ml), and stirring was carried out for 24 h at RT. For working up, the mixture was washed with water (2×20 ml), with 1M HCl (2×20 ml) and with 1M NaOH (2×20 ml), then dried, filtered and concentrated. [2-(1H-Indol-3-yl)-1-methylethyl]carbamic acid phenyl ester was obtained in the form of a white solid in a yield of 1.35 g.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:18]=[CH:17][C:8]2[CH2:9][N:10]3[CH:16]=[CH:15][CH:14]=[C:11]3[CH2:12][NH:13][C:7]=2[CH:6]=1)=[O:4].[F:19][C:20]([F:38])([F:37])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]1[CH:35]=[CH:34][C:30]([C:31](Cl)=[O:32])=[CH:29][C:28]=1[CH3:36].C(N(CC)CC)C>ClCCCl>[CH3:36][C:28]1[CH:29]=[C:30]([C:31]([N:13]2[C:7]3[CH:6]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:18]=[CH:17][C:8]=3[CH2:9][N:10]3[CH:16]=[CH:15][CH:14]=[C:11]3[CH2:12]2)=[O:32])[CH:34]=[CH:35][C:27]=1[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[C:20]([F:19])([F:37])[F:38]
Reactant: COC(=O)c1ccc2c(c1)NCc1cccn1C2
Reactant: Cc1cc(C(=O)Cl)ccc1-c1ccccc1C(F)(F)F
Solvent: ClCCCl
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc2c(c1)N(C(=O)c1ccc(-c3ccccc3C(F)(F)F)c(C)c1)Cc1cccn1C2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-8-carboxylic acid methyl ester of Step B (1.64 g) in 1,2-dichloroethane (25 mL) was added 4-(2-trifluoromethylphenyl)-3-methylbenzoyl chloride (2.0 g, 1.1 eq) prepared in the manner of Example 1, Step D and triethylamine (1.0 g) and the mixture was stirred at room temperature overnight. The solvent was then removed in vacuo and the residue chromatographed on silica gel eluting with 10% ethyl acetate in petroleum ether to provide the title compound as a white crystalline solid, m.p. 180–182° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[CH2:8][C:7](=[O:9])[O:6][C:4](=[O:5])[CH2:3]1.[CH3:11][C:12]([CH3:15])([O-:14])[CH3:13].[K+]>O1CCCC1>[C:12]([O:14][C:7](=[O:9])[CH2:8][C:2]([CH3:10])([CH3:1])[CH2:3][C:4]([OH:6])=[O:5])([CH3:15])([CH3:13])[CH3:11]
Reactant: CC1(C)CC(=O)OC(=O)C1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(C)(CC(=O)O)CC(=O)OC(C)(C)C
Yield: 25.9 %

Procedure:
3,3 Dimethylglutaric anhydride (455 mg, 3.2 mmol) in tetrahydrofuran (THF, 5 mL) was treated with sublimed potassium t butoxide (395 mg, 3.5 mmol). After 30 min the solution was concentrated, poured into saturated NaHCO3 solution and washed with ether. The aqueous phase was acidified to pH 4 with 0.5M H3PO4 and extracted with chloroform which was dried over Na2SO4 and evaporated to afford 179 mg (26%) of the desired product as an oil. NMR (300 MHz, CDCl3, ppm), 1.13 (s,6H), 1.47 (s,9H), 2.33 (s,2H), 2.45 (s,2H).
Reaction SMILES: [CH2:1]([CH:4]1[N:7]([C:8]([C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])=P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[C:6](=[O:38])[CH:5]1[CH3:39])[CH:2]=C.FC(F)(F)C(O)=O>C(OCC)(=O)C>[CH3:39][CH:5]1[C:6](=[O:38])[N:7]2[CH:4]1[CH2:1][CH:2]=[C:8]2[C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29]
Reactant: C=CCC1C(C)C(=O)N1C(C(=O)OCc1ccccc1)=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: CCOC(C)=O
Product: CC1C(=O)N2C(C(=O)OCc3ccccc3)=CCC12
Reaction time: 0.17 h
Yield: 57.2 %

Procedure:
A solution of 4-allyl-3-methyl-1-(1-benzyloxycarbonyl-1-triphenylphosphoranylidenemethyl)azetidine-2-one (38) (0.29 g) in ethyl acetate (25 ml) was treated with trifluoroacetic acid (0.4 ml) and then cooled to -78°. Ozone was bubbled through the solution until it just became pale blue in colour. The excess ozone was blown off in a stream of argon and an ethyl acetate solution of triphenylphosphine (0.14 g) was then added. After a further 10 minutes the reaction flask was transferred to an ice bath and saturated aqueous sodium bicarbonate (45 ml) was added with vigorous stirring. This was continued for 30 minutes and the ethyl acetate solution was then separated, washed with brine and dried over sodium sulphate. The solution was concentrated and chromatographed on silica gel 60 (<230 mesh) eluting with ethyl acetate/60°-80° petroleum ether mixtures grading from 3:7 to 6:4. This gave the trans-isomer of benzyl 6-methyl-7-oxo-1-azabicyclo[3,2,0]hept-2-ene- 2-carboxylate (39) (0.08 g, 55%); νmax (CHCl3) 3000, 1780, 1725 and 1615 cm-1 ; δppm ((CD3)2CO) 1.34 (3H, d, J 7 Hz, CH3), 2.85 (2H, dd, J 9 and 2 Hz, C4--H2), 3.24 (1H, dq, J 3 and 7 Hz, C6--H), 3.91 (1H, dt, J 3 and 9 Hz, C5--H), 5.20 (2H, s, benzyl CH2), 6.45 (1H, t, J 2 Hz, C3--H) and 7.2-7.5 (5H, m, phenyl); (M+ at m/e 257.1052 C15H15NO3 requires 257.1051).
Reaction SMILES: Br[CH2:2][C:3]1[N:8]=[C:7]([NH:9]C(=O)C(C)(C)C)[CH:6]=[CH:5][CH:4]=1.C(OC([N:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[N:25]=[C:24]1[CH2:32][NH:33][CH:34]1[C:43]2[N:42]=[CH:41][CH:40]=[CH:39][C:38]=2[CH2:37][CH2:36][CH2:35]1)=O)(C)(C)C.C(N(CC)C(C)C)(C)C.[I-].[K+]>CC#N>[NH2:9][C:7]1[N:8]=[C:3]([CH2:2][N:33]([CH2:32][C:24]2[NH:23][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=3[N:25]=2)[CH:34]2[C:43]3[N:42]=[CH:41][CH:40]=[CH:39][C:38]=3[CH2:37][CH2:36][CH2:35]2)[CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)(C)C(=O)Nc1cccc(CBr)n1
Reactant: CC(C)(C)OC(=O)n1c(CNC2CCCc3cccnc32)nc2ccccc21
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: Nc1cccc(CN(Cc2nc3ccccc3[nH]2)C2CCCc3cccnc32)n1
Temperature: 60 °C
Reaction time: 3.75 h
Yield: 85.5 %

Procedure:
Using the general N-alkylation procedure: To a stirred solution of N-[6-(bromomethyl)-2-pyridyl]pivalamide (prepared as described by Harata, M.; Hasegawa, K.; Jitsukawa, K.; Masuda, H.; Einaga, H. Bull. Chem. Soc. Jpn 1998, 71, 1031-1038) (0.129 g, 0.45 mmol) in dry CH3CN (10 mL) was added (1-tert-butoxycarbonyl-1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine (0.176 g, 0.47 mmol), N,N-diisopropylethylamine (0.20 mL, 1.15 mmol) and potassium iodide (12 mg, 0.048 mmol). The mixture was stirred under an argon atmosphere at 60° C. for 3.75 h. Purification of the crude material by column chromatography on silica gel (CH2Cl2/MeOH, 98:2 followed by 96:4) gave the alkylated product (0.148 g, 54%) as a brown oil.
Reaction SMILES: [CH2:1]([C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][NH2:19])=[O:17])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[C:20](O)(=O)C.C(N)=N.O>CN(C)C=O>[CH2:1]([C:9]1[CH:10]=[CH:11][C:12]([N:15]2[CH:20]=[N:19][NH:18][C:16]2=[O:17])=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CC(=O)O
Reactant: CCCCCCCCc1ccc(NC(=O)NN)cc1
Agent: N=CN
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCCCc1ccc(-n2cn[nH]c2=O)cc1

Procedure:
N-(4-octylphenyl)-N′-aminourea, Formamidine acetate (12.76 g) and N-carbazoyl-4-octylaniline (6.458 g) in N,N-dimethylformamide (19.4 ml) were stirred at 150° C. for 6 hours. The reaction mixture was pulverized with water. The precipitate was collected by filtration and washed with water to give 4-(4-Octylphenyl)-2,3-dihydro-4H-1,2,4-triazol-3-one (4.27 g).
Reaction SMILES: [Cl:1][C:2]1[C:3](F)=[C:4]([F:19])[CH:5]=[C:6]2[C:11]=1[N:10]([CH:12]1[CH2:14][CH2:13]1)[CH:9]=[C:8]([C:15]([OH:17])=[O:16])[C:7]2=[O:18].[C:21]([O:25][C:26]([NH:28][C@H:29]1[C@H:33]([CH3:34])[CH2:32][NH:31][CH2:30]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].C1CCN2C(=NCCC2)CC1>C(#N)C>[C:21]([O:25][C:26]([NH:28][C@H:29]1[C@H:33]([CH3:34])[CH2:32][N:31]([C:3]2[C:2]([Cl:1])=[C:11]3[C:6]([C:7](=[O:18])[C:8]([C:15]([OH:17])=[O:16])=[CH:9][N:10]3[CH:12]3[CH2:14][CH2:13]3)=[CH:5][C:4]=2[F:19])[CH2:30]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]
Reactant: C[C@@H]1CNC[C@H]1NC(=O)OC(C)(C)C
Reactant: O=C(O)c1cn(C2CC2)c2c(Cl)c(F)c(F)cc2c1=O
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Product: C[C@@H]1CN(c2c(F)cc3c(=O)c(C(=O)O)cn(C4CC4)c3c2Cl)C[C@H]1NC(=O)OC(C)(C)C
Yield: 102.7 %

Procedure:
A mixture of 8-chloro-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (2.2 g), anhydrous acetonitrile (22 ml), trans-3-t-butoxycarbonylamino-4-methylpyrrolidine (reference example 5; 2.4 g) and DBU (1.22 g) was refluxed for 5 hours. The reacting mixture was concentrated under reduced pressure, the resulting residue was dissolved in chloroform and washed with 10% aqueous citric acid solution. The chloroform layer was further washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in hot methanol (20 ml) and, after cooling, the resulting precipitate was collected by filtration to give 7-(trans-3-t-butoxycarbonylamino-4-methyl-1-pyrrolidinyl)-8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (3.62 g) as yellow needle, mp 210°-213° C. (decompd.).
Reaction SMILES: [NH2:1][C:2]1[S:6][N:5]=[C:4]([CH3:7])[C:3]=1[C:8]#[N:9].[N:10]([O-])=[O:11].[Na+].O>C(O)=O.N([O-])=O.[Na+]>[C:8]([C:3]1[C:4]([CH3:7])=[N:5][S:6][C:2]=1[NH:1][N:10]=[O:11])#[N:9]
Reactant: Cc1nsc(N)c1C#N
Reactant: O=N[O-]
Agent: [Na+]
Solvent: O=CO
Solvent: O
Product: Cc1nsc(NN=O)c1C#N
Yield: 51533.2 %

Procedure:
First, 4 g (0.028 mol) of 5-amino-4-cyano-3-methylisothiazole was dissolved in 40 mL of 98% formic acid. While the mixture was stirred, an aqueous sodium nitrite solution (containing 2.1 g (0.03 mmol) of sodium nitrite in 6 mL of water) was added dropwise at 0° C. or less. After completion of dropwise addition, the mixture was continuously stirred at 0° C. further for one hour. To the solution, 100 mL of water was added to precipitate crystals, which were collected by filtration and washed with ice cold water. The crystals were dried in the air at room temperature overnight to obtain 2.6 g (56% in yield) of 4-cyano-3-methyl-5-nitrosoaminoisothiazole. To 2 g (0.012 mol) of the obtained nitrosoaminoisothiazole, 20 mL of methanol was added, stirred while heating to an inner temperature of 55 to 60° C. for one hour and cooled to room temperature to precipitate crystals, which were collected by filtration. The crystals were recrystallized from methanol to obtain 0.66 g (41% in yield) of triazene dissociative direct dye D-34.
Reaction SMILES: C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:11](=[C:12](OS(C(F)(F)F)(=O)=O)[N:13]([CH:18]3[CH2:21][CH2:20][CH2:19]3)[N:14]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[F:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1>>[CH:18]1([N:13]2[C:12]([C:34]3[CH:35]=[CH:36][C:31]([F:30])=[CH:32][CH:33]=3)=[C:11]3[C:15]([CH2:16][CH2:17][NH:8][CH2:9][CH2:10]3)=[N:14]2)[CH2:19][CH2:20][CH2:21]1
Reactant: OB(O)c1ccc(F)cc1
Reactant: CC(C)(C)OC(=O)N1CCc2nn(C3CCC3)c(OS(=O)(=O)C(F)(F)F)c2CC1
Product: Fc1ccc(-c2c3c(nn2C2CCC2)CCNCC3)cc1
Yield: 94.9 %

Procedure:
The title compound (122 mg) was prepared according to Example 263 using 198 mg of 2-cyclobutyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 276, Step A) and 88 mg of 4-fluorophenylboronic acid. MS (ESI): exact mass calculated for C17H20FN3, 285.16. found, m/z 286.4 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.35-7.27 (m, 4H), 4.65-4.59 (m, 2H), 3.95-3.3.40 (m, 2H), 3.32-3.05 (m, 3H), 3.00-2.75 (m, 2H), 2.67-2.59 (m, 2H), 2.29-2.23 (m, 2H), 1.84-1.73 (m, 2H).