Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:30])[NH:6][CH:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:4](=[O:13])[N:3]1[C@@H:14]1[C:28](=[O:29])[N:16]2[C:17]([C:22]([O:24]COC)=[O:23])=[C:18]([Cl:21])[CH2:19][S:20][C@H:15]12>CO>[CH3:1][C:2]1([CH3:30])[NH:6][CH:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:4](=[O:13])[N:3]1[C@@H:14]1[C:28](=[O:29])[N:16]2[C:17]([C:22]([OH:24])=[O:23])=[C:18]([Cl:21])[CH2:19][S:20][C@H:15]12
Reactant: COCOC(=O)C1=C(Cl)CS[C@@H]2[C@H](N3C(=O)C(c4ccccc4)NC3(C)C)C(=O)N12
Solvent: CO
Product: CC1(C)NC(c2ccccc2)C(=O)N1[C@@H]1C(=O)N2C(C(=O)O)=C(Cl)CS[C@H]12
Reaction time: 0.5 h
Yield: 88.6 %

Procedure:
A solution of 0.5 g of methoxymethyl 7β-(2,2-dimethyl-5-oxo-4-phenylimidazolidin-1-yl)-3-chloro-3-cephem-4-carboxylate in 10 ml of methanol is refluxed for 1 hour, and the reaction mixture is concentrated to a third volume and stirred for 30 minutes under ice-cooling. The resulting precipitate is collected by filtration and dried under reduced pressure to yield 0.4 g of 7β-(2,2-dimethyl-5oxo-4-phenylimidazolidin-1-yl)-3-chloro-3-cephem-4-carboxylic acid.
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](=[O:13])[NH:7]2.[H-].[Na+].CS(O[CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][C@H:26]([N:29]([CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C@H:25]([O:44][CH3:45])[CH2:24]1)(=O)=O>CN(C=O)C>[CH2:37]([N:29]([CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[C@H:26]1[CH2:27][CH2:28][N:23]([CH2:22][CH2:21][N:7]2[C:8]3[C:3](=[C:2]([F:1])[CH:11]=[C:10]([F:12])[CH:9]=3)[CH:4]=[CH:5][C:6]2=[O:13])[CH2:24][C@H:25]1[O:44][CH3:45])[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1
Reactant: O=c1ccc2c(F)cc(F)cc2[nH]1
Reactant: CO[C@@H]1CN(CCOS(C)(=O)=O)CC[C@@H]1N(Cc1ccccc1)Cc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CO[C@@H]1CN(CCn2c(=O)ccc3c(F)cc(F)cc32)CC[C@@H]1N(Cc1ccccc1)Cc1ccccc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 27 %

Procedure:
A solution of 5,7-difluoroquinolin-2(1H)-one (Intermediate 25, 300 mg, 1.70 mmol) in dry DMF (10 mL) was treated with sodium hydride (60% in oil, 80 mg, 2.00 mmol) with cooling in an ice bath. The reaction was stirred at room temperature for 90 min. The reaction was again cooled in an ice bath and treated with a solution of cis(±)2-[4-(dibenzylamino)-3-methoxypiperidin-1-yl]ethyl methanesulfonate in dry DMF (10 mL) (Intermediate 169, 1.2 eq, 2.00 mmol). The reaction was stirred at room temperature overnight. It was quenched with a small amount of water and concentrated to dryness. Residual DMF was removed by co-evaporating with toluene and the residue was partitioned between ethyl acetate (50 mL) and water (20 mL). The biphasic mixture was filtered, the phases separated and the aqueous phase was back extracted two times with ethyl acetate (2×50 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to dryness. Chromatography on silica gel with a gradient of 10-20% acetone in hexanes gave 240 mg (27%) of product as a colorless solid.
Reaction SMILES: [CH:1]1([CH2:7][C@H:8]2[C@H:12]([CH:13]=[O:14])[O:11][C:10]([CH3:16])([CH3:15])[N:9]2[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[CH:25]1[CH2:28][CH2:27][CH2:26]1.[Mg].[Cl-].[NH4+]>O1CCCC1>[CH:1]1([CH2:7][C@H:8]2[C@H:12]([C@H:13]([CH:25]3[CH2:28][CH2:27][CH2:26]3)[OH:14])[O:11][C:10]([CH3:16])([CH3:15])[N:9]2[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: BrC1CCC1
Reactant: CC(C)(C)OC(=O)N1[C@@H](CC2CCCCC2)[C@H](C=O)OC1(C)C
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1[C@@H](CC2CCCCC2)[C@H]([C@@H](O)C2CCC2)OC1(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 28.8 %

Procedure:
A solution of 7.23 g (22.2 mmol) of t-butyl (4S,5R)-4-(cyclohexylmethyl)-5-formyl-2,2-dimethyl-3-oxazolidinecarboxylate in 150 ml of tetrahydrofuran is added dropwise within 40 minutes at 30° to a solution of the Grignard compound prepared from 15 g (111 mmol) of bromocyclobutane and 2.7 g (111 mgram atom) of magnesium shavings in 150 ml of tetrahydrofuran and the reaction mixture is subsequently stirred at room temperature overnight. Thereafter, the reaction mixture is poured into 300 ml of a saturated ammonium chloride solution and extracted three times with 600 ml of ether each time. The ether extracts are washed with ammonium chloride solution, dried, filtered and evaporated. The crude product (9.34 g) is chromatographed on 500 g of silica gel with a 92.5:7.5 mixture of toluene and ethyl acetate as the eluting agent, whereby there are obtained 2.44 g of t-butyl (4S,5R)-4-(cyclohexylmethyl)-5-[(S)-cyclobutylhydroxymethyl]-2,2-dimethyl-3-oxazolidinecarboxylate as an oil; MS: 381 (M)+, and 2.9 g of the epimeric compound t-butyl (4S,5R)-4-(cyclohexylmethyl)-5-[(R)-cyclobutylhydroxymethyl]-2,2-dimethyl-3-oxazolidinecarboxylate, likewise as an oil, MS: 381 (M)+.
Reaction SMILES: NC1C=CNN=1.O/[CH:8]=[C:9]1\[C:10](=[O:18])[NH:11][C:12]2[C:17]\1=[CH:16][CH:15]=[CH:14][CH:13]=2.[C:19]([C:23]1[O:27][N:26]=[C:25]([NH2:28])[CH:24]=1)([CH3:22])([CH3:21])[CH3:20]>O1CCCC1>[C:19]([C:23]1[O:27][N:26]=[C:25]([NH:28][CH:8]=[C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]2=[O:18])[CH:24]=1)([CH3:22])([CH3:21])[CH3:20]
Reactant: CC(C)(C)c1cc(N)no1
Reactant: O=C1Nc2ccccc2/C1=C/O
Agent: Nc1cc[nH]n1
Solvent: C1CCOC1
Product: CC(C)(C)c1cc(NC=C2C(=O)Nc3ccccc32)no1

Procedure:
The named compound is prepared by substituting 5-tert-butyl-isoxazol-3-ylamine for 3-aminopyrazole in the reaction of Example 1. Specifically, E & Z-3-[(hydroxy)-methylene]-1,3-dihydro-indol-2-one (0.100 gms.) is reacted with 0.1742 gms. 5-tert-butyl-isoxazol-3-ylamine by refluxing in tetrahydrofuran (2.7 mL).
Reaction SMILES: Cl.BrC1C=CN=CC=1.N1C=CC([NH:15][C@H:16]2[CH2:20][CH2:19][N:18]([C:21]3[CH:33]=[CH:32][C:24]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[CH:23][CH:22]=3)[CH2:17]2)=CC=1>>[NH2:15][C@H:16]1[CH2:20][CH2:19][N:18]([C:21]2[CH:33]=[CH:32][C:24]([C:25]([O:27][C:28]([CH3:29])([CH3:31])[CH3:30])=[O:26])=[CH:23][CH:22]=2)[CH2:17]1
Reactant: CC(C)(C)OC(=O)c1ccc(N2CC[C@H](Nc3ccncc3)C2)cc1
Agent: Brc1ccncc1
Agent: Cl
Product: CC(C)(C)OC(=O)c1ccc(N2CC[C@H](N)C2)cc1
Yield: 77 %

Procedure:
Staring from 4-bromopyridine hydrochloride (16) (356 mg, 1.83 mmol) and compound 17 (400 mg, 1.52 mmol) title compound 18 was obtained (398 mg, 77% yield) according to the known procedure (Harris, M. C.; Geis, O.; Buchwald, S. L.*; J. Org. Chem., 1999, 64, 6019-6022). 1H NMR: (DMSO-d6) δ(ppm): 8.58 (d, J=6.5 Hz, 1H), 8.18 (d, J=6.5 Hz, 2H), 7.72 (d, J=8.8 Hz, 2H), 6.91 (d, J=6.8 Hz, 2H), 6.58 (d, J=9.0 Hz, 2H), 4.46-4.40 (m, 1H), 3.71 (dd, J=10.6, 6.3 Hz, 1H), 3.48 (dt, J=9.6, 7.6 Hz, 1H), 4.42 (td, J=9.8, 4.9 Hz, 1H), 3.27 (dd, J=10.4, 3.3 Hz, 1H), 2.35 (sext, J=7.2 Hz, 1H), 2.05-1.98 (m, 1H), 1.50 (s, 9H). LRMS (ESI): (calc) 339.19 (found) 340.2 (MH+).
Reaction SMILES: C(N(C(C)C)CC)(C)C.[C:10]([Si:14]([CH3:42])([CH3:41])[O:15][CH:16]([C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=1)[CH2:17][CH2:18][CH2:19][C:20]([N:22]1[CH:26]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:25][O:24][C:23]1=[O:33])=[O:21])([CH3:13])([CH3:12])[CH3:11].[F:43][C:44]1[CH:49]=[CH:48][C:47]([N:50]=[CH:51][C:52]2[CH:53]=[C:54]([CH:57]=[CH:58][CH:59]=2)[C:55]#[N:56])=[CH:46][CH:45]=1.C[Si](Cl)(C)C.C(O)(=O)C(C(C(O)=O)O)O.S([O-])(O)=O.[Na+]>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl.C(O)(=O)C>[Si:14]([O:15][CH:16]([C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=1)[CH2:17][CH2:18][CH:19]([C:20]([N:22]1[CH:26]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:25][O:24][C:23]1=[O:33])=[O:21])[CH:51]([C:52]1[CH:53]=[C:54]([CH:57]=[CH:58][CH:59]=1)[C:55]#[N:56])[NH:50][C:47]1[CH:46]=[CH:45][C:44]([F:43])=[CH:49][CH:48]=1)([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:42])[CH3:41]
Reactant: CC(C)(C)[Si](C)(C)OC(CCCC(=O)N1C(=O)OCC1c1ccccc1)c1ccc(F)cc1
Reactant: N#Cc1cccc(C=Nc2ccc(F)cc2)c1
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: C[Si](C)(C)Cl
Agent: O=C(O)C(O)C(O)C(=O)O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(=O)O
Product: CC(C)(C)[Si](C)(C)OC(CCC(C(=O)N1C(=O)OCC1c1ccccc1)C(Nc1ccc(F)cc1)c1cccc(C#N)c1)c1ccc(F)cc1
Temperature: -10 °C
Reaction time: 1 h

Procedure:
At 10° C., 24 ml of diisopropylethylamine are added to 14 g of 3-[5-(tert-butyidimethyl-silanyloxy)-5-(4-fluorophenyl)pentanoyl]-4-phenyloxazolidin-2-one (10) and 12.5 g of 3-[(4-fluorophenylimino)methyl]benzonitrile 11 in 200 ml of methylene chloride, and 7.1 ml of trimethylsilyl chloride are added dropwise. After 1 h, 3.4 ml of titanium tetrachloride are added dropwise at −10° C. The mixture is stirred at −10° C. for 3 h and then allowed to stand at −30° C. for another 12 h. 8 ml of acetic acid and 140 ml of a 7% strength aqueous tartaric acid solution are then added, and stirring is continued at room temperature for another 2 h. 50 ml of 20% strength aqueous sodium hydrogen sulfite solution are added, and the mixture is then stirred for another hour and extracted with methylene chloride. The organic phase is dried over magnesium sulfate, concentrated and purified by silica gel chromatography (ethyl acetate/heptane=1/3→1/1). This gives 12
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.[H-].[Na+].Cl.[CH3:13][N:14]([CH3:18])[CH2:15][CH2:16]Cl>CN(C=O)C>[CH3:13][N:14]([CH3:18])[CH2:15][CH2:16][N:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1
Reactant: CN(C)CCCl
Reactant: c1cnc2[nH]ccc2c1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN(C)CCn1ccc2cccnc21
Reaction time: 16 h
Yield: 81 %

Procedure:
A stirred solution of 1H-pyrrolo[2,3-b]pyridine (5.00 g, 42.3 mmol) in DMF at ambient temperature is treated with 95% sodium hydride in oil (3.78 g, 150 mmol). After gas evolution subsides, the reaction mixture is treated with 2-(dimethylamino)-ethyl chloride hydrochloride (6.40 g, 44.4 mmol), stirred for 16 h and concentrated in vacuo. The resultant residue is partitioned between EtOAc and water. The organic phase is separated, dried over MgSO4 and concentrated in vacuo to afford the title compound as an oil, 6.50 g (81% yield), identified by HNMR and mass spectral analyses.
Reaction SMILES: O=P(Cl)(Cl)[Cl:3].[CH2:6]([O:13][CH:14]1[CH2:17][CH:16]([S:18]([O-:21])(=O)=[O:19])[CH2:15]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[K+].C(N(C(C)C)CC)(C)C.C(OCC)(=O)C>C(Cl)Cl.CCCCCC>[CH2:6]([O:13][CH:14]1[CH2:17][CH:16]([S:18]([Cl:3])(=[O:21])=[O:19])[CH2:15]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: O=S(=O)([O-])C1CC(OCc2ccccc2)C1
Reactant: O=P(Cl)(Cl)Cl
Agent: [K+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: O=S(=O)(Cl)C1CC(OCc2ccccc2)C1
Yield: 32.3 %

Procedure:
POCl3 (0.34 mL, 3.558 mmol) was added to a cooled solution of potassium 3-(benzyloxy)cyclobutane-1-sulfonate (0.5 g, 1.779 mmol) in dry DCM (10 mL) at 0° C. This was followed by the slow addition of diisopropyl ethyl amine (0.65 mL, 3.558 mmol) and stirred the resulting reaction mixture at 0° C. for 2 hours. The reaction was monitored by TLC (20% ethyl acetate in hexane). The reaction mixture was extracted with DCM. The organic layer was washed with water, brine solution, dried over Na2SO4 and concentrated. Purification by column chromatography on silica gel (8% ethyl acetate in hexane) afforded 0.15 g of the product (38% yield).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)(=[O:12])=[O:11])=[CH:6][CH:5]=1)([O-])=O>CO.[Rh]>[F:19][C:16]1[CH:17]=[CH:18][C:13]([S:10]([C:7]2[CH:8]=[CH:9][C:4]([NH2:1])=[CH:5][CH:6]=2)(=[O:12])=[O:11])=[CH:14][CH:15]=1
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)c2ccc(F)cc2)cc1
Agent: [Rh]
Solvent: CO
Product: Nc1ccc(S(=O)(=O)c2ccc(F)cc2)cc1

Procedure:
A mixture of 4-fluorophenyl 4-nitrophenyl sulfone (1.89 g, 6.72 mmol) in methanol (80 mL) is treated with Rhodium on carbon (5%, 95 mg) and hydrogenated at 20 psi for 24 hr. The mixture is filtered, rinsing with methylene chloride (2×100 mL) and methanol (100 mL). The filtrate is concentrated to near dryness and refiltered, rinsing with minimal methanol. The solid is dried in the vacuum oven at 500 to give the desired amine, mp=204–205°: IR (drift) 3473, 3373, 1638, 1592, 1489, 1303, 1294, 1285, 1231, 1159, 1144, 1107, 834, 713 and 689 cm−1; NMR (300 MHz, CDCl3) 7.80–7.95, 7.60–7.75, 7.13, 6.60–6.75 and 4.17 δ; MS (EI) m/z 251 (M+), 140, 108, 95, 92, 80, 65, 65, 63 and 51.
Reaction SMILES: [OH:1][C:2]1[C:3]([C:13]([O:15][CH3:16])=[O:14])=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([OH:12])[CH:6]=2.[CH2:17](Cl)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH3:16][O:15][C:13]([C:3]1[C:2]([OH:1])=[CH:11][C:10]2[C:5](=[CH:6][C:7]([O:12][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:8][CH:9]=2)[CH:4]=1)=[O:14]
Reactant: ClCc1ccccc1
Reactant: COC(=O)c1cc2cc(O)ccc2cc1O
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)c1cc2cc(OCc3ccccc3)ccc2cc1O
Temperature: 25 °C
Yield: 38.9 %

Procedure:
A suspension of methyl 3,7-dihydroxy-2-naphthoate (2.2 g; 10 mmole), benzylchloride (Merck) (1.26 mL; 11.0 mmole), potassium iodide (1.8 g; 11.0 mmole) and potassium carbonate (2.0 g; 15 mmole) in acetone (30 mL) was refluxed for 7 hours and then cooled to room temperature. The inorganic precipitate was filtered off and washed with acetone, whereas the filtrate was evaporated to dryness The solid residue was dissolved in ethyl acetate and the resulting solution was washed with 1M hydrochloric acid. After drying with sodium sulfate the organic layer was evaporated and the dry residue was recrystallized from methanol, whereat 1.2 g (39%) of methyl-7-benzyloxy-3-hydroxy-2-naphthoate were obtained.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][C:13]([O:19]C)=[CH:14][CH:15]=3)[O:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.Br>O>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[CH:14][CH:15]=3)[O:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc2c(=O)c(-c3cccc(F)c3)coc2c1
Agent: Br
Solvent: O
Product: O=c1c(-c2cccc(F)c2)coc2cc(O)ccc12

Procedure:
3-(3-Fluorophenyl)-7-methoxychromen-4-one (320 mg) was refluxed with 47% HBr (18 ml) until disappearance of the starting material. The mixture was poured into water and the precipitate was filtrated and dried yielding 3-(3-fluorophenyl)-7-hydroxychromen-4-one. 1H NMR (400 MHz, d6-DMSO) δ: 10.87 (s, 1H), 8.49 (s, 1H), 7.99 (d, 1H, J 8.7 Hz), 7.43-7.49 (m, 3H), 7.20-7.24 (m, 1H), 6.97 (dd, 1H, J 8.7, 2.2 Hz), 6.90 (d, 1H, J 2.2 Hz).
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH:13]=[C:12]([C:14]#[N:15])[N:11]=[CH:10]1.C[NH:19]O.Cl.CCN(CC)CC>CCO>[F:17][C:2]([F:16])([F:1])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH:13]=[C:12]([C:14](=[NH:19])[NH2:15])[N:11]=[CH:10]1
Reactant: N#Cc1cn(-c2ccccc2C(F)(F)F)cn1
Reactant: CNO
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: N=C(N)c1cn(-c2ccccc2C(F)(F)F)cn1
Temperature: 80 °C
Reaction time: 2 h

Procedure:
A mixture of 1-(3′-methylsulfonyl)biphenyl-4-yl)-2-(2-(trifluoromethyl)phenyl-1H-imidazole-4-carbonitrile (374 mg, 0.8 mmol), MeNHOH.HCl (167 mg, 2 mmol), Et3N (0.5 mL), and dry EtOH in a sealed vial was stirred at 80° C. for 2 h, the volatiles were removed in vacuo to give N-hydroxy-N-methyl-1-(3′-methylsulfonyl)biphenyl-4-yl)-2-(2-(trifluoromethyl)phenyl-1H-imidazole-4-carboximidamide as a white solid, which was used in next reaction without further purification.
Reaction SMILES: [C:1]1([NH:7][CH2:8][C:9]2[CH:16]=[CH:15][C:12]([CH:13]=O)=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N+:17]([CH3:20])([O-:19])=[O:18].C([O-])(=O)C.[NH4+]>C(O)(=O)C>[N+:17](/[CH:20]=[CH:13]/[C:12]1[CH:15]=[CH:16][C:9]([CH2:8][NH:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:10][CH:11]=1)([O-:19])=[O:18]
Reactant: O=Cc1ccc(CNc2ccccc2)cc1
Reactant: C[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CC(=O)O
Product: O=[N+]([O-])/C=C/c1ccc(CNc2ccccc2)cc1
Temperature: 100 °C
Reaction time: 4 h
Yield: 36.2 %

Procedure:
A mixture of 4-phenylaminomethyl-benzaldehyde (3.5 g, 16.6 mmol) described in Manufacturing Example 73-1-3, nitromethane (4.46 mL, 83 mmol), ammonium acetate (2.56 g, 33.2 mmol) and acetic acid (30 mL) was stirred for 4 hours at 100° C. This mixture was cooled to room temperature, concentrated under a reduced pressure, and diluted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=10:1-4:1) to obtain the title compound (1.53 g, 36%).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[C:5]([NH:12][NH2:13])=[N:4][N:3]=1.[C:14](O)(=O)[CH2:15][CH3:16]>>[Cl:1][C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[C:5]2=[N:12][N:13]=[C:14]([CH2:15][CH3:16])[N:4]2[N:3]=1
Reactant: NNc1nnc(Cl)c2c1CCCC2
Reactant: CCC(=O)O
Product: CCc1nnc2c3c(c(Cl)nn12)CCCC3
Yield: 89.6 %

Procedure:
A solution of 98.5 grams (0.496 mole) of 1-chloro-4-hydrazino-5,6,7,8-tetrahydrophthalazine in 300 milliliters of propionic acid was heated at reflux for 18 hours, then concentrated by evaporation to half the original volume. The solution was diluted with aqueous sodium carbonate until neutral (pH 7). The resulting precipitate was collected, air-dried at ambient temperature, then dried in a drying over to produce 105 grams (0.444 mol) of 6-chloro-3-ethyl-7,8,9,10-tetrahydro-1,2,4-triazolo[3,4-a]phthalazine, melting at 93°-94° C. (89.6% yield). Calculated for C11H13ClN4 : C, 55.81; H, 5.53; N, 23.67. Found: C, 56.00; H, 5.63; N, 23.87.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]([CH2:18][CH2:19][O:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=1)[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[S:29]1[CH2:33][C:32](=[O:34])[NH:31][C:30]1=[O:35].N1CCCCC1.C(O)(=O)C1C=CC=CC=1>C1(C)C=CC=CC=1>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]([CH2:18][CH2:19][O:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]=[C:33]2[S:29][C:30](=[O:35])[NH:31][C:32]2=[O:34])=[CH:23][CH:22]=1)[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=C1CSC(=O)N1
Reactant: O=Cc1ccc(OCCN(Cc2ccccc2)c2nc3ccccc3s2)cc1
Agent: O=C(O)c1ccccc1
Solvent: Cc1ccccc1
Solvent: C1CCNCC1
Product: O=C1NC(=O)C(=Cc2ccc(OCCN(Cc3ccccc3)c3nc4ccccc4s3)cc2)S1

Procedure:
4-(2-(N-(2-Benzothiazolyl)-N-benzylamino)ethoxy)benzaldehyde (3 g) and 2,4-thiazolidinedione (1 g) were dissolved in toluene (200 ml) containing piperidine (0.2 ml) and benzoic acid (0.2 g) and heated to reflux for 4 h. in a Dean and Stark apparatus. On cooling, the solution was concentrated under vacuum to 50% of its volume and the title compound, which crystallised, was collected by filtration and dried in vacuo (m.p. 185-188° C.). It was used in Example 27 without further purification.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1[N:13]1[C:35](=[O:36])[C:32]2[C:33]3[C:34]4[C:29](=[CH:30][CH:31]=2)[C:28]2[C:37]5[C:24]([C:25]([C:38]#[C:39][CH2:40][CH2:41][CH2:42][CH2:43][OH:44])=[CH:26][CH:27]=2)=[CH:23][CH:22]=[CH:21][C:20]=5[C:19]=4[CH:18]=[CH:17][C:16]=3[C:14]1=[O:15])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:52](Cl)(=[O:56])[C:53]([CH3:55])=[CH2:54].O>O1CCOCC1>[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1[N:13]1[C:35](=[O:36])[C:32]2[C:33]3[C:34]4[C:29](=[CH:30][CH:31]=2)[C:28]2[C:37]5[C:24]([C:25]([C:38]#[C:39][CH2:40][CH2:41][CH2:42][CH2:43][O:44][C:52](=[O:56])[C:53]([CH3:55])=[CH2:54])=[CH:26][CH:27]=2)=[CH:23][CH:22]=[CH:21][C:20]=5[C:19]=4[CH:18]=[CH:17][C:16]=3[C:14]1=[O:15])([CH3:2])[CH3:3]
Reactant: CC(C)c1cccc(C(C)C)c1N1C(=O)c2ccc3c4cccc5c(C#CCCCCO)ccc(c6ccc(c2c36)C1=O)c54
Reactant: C=C(C)C(=O)Cl
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Solvent: O
Product: C=C(C)C(=O)OCCCCC#Cc1ccc2c3ccc4c5c(ccc(c6cccc1c62)c53)C(=O)N(c1c(C(C)C)cccc1C(C)C)C4=O
Temperature: 45 °C
Reaction time: 4 h
Yield: 78 %

Procedure:
A solution of 1 g (1.72 mmol) of N-(2,6-diisopropylphenyl)-9-(6-hydroxy-1-hexynyl)perylene-3,4-dicarboximide in 100 ml of dry dioxane was heated to 45° C. under nitrogen, admixed with 0.4 ml of triethylamine and 0.28 ml of methacryloyl chloride, stirred at 45° C. for 4 h, admixed with 0.28 ml of methacryloyl chloride, stirred at 45° C. for a further 12 h, cooled to room temperature, again admixed with 200 ml of water and extracted with a total of 400 ml of methylene chloride. The solvent was distilled off under reduced pressure and the residue was chromatographed on silica gel using methylene chloride as eluent. Following removal of the solvent under reduced pressure, 800 mg (78%) of the desired product were isolated as a red, finely crystalline solid.
Reaction SMILES: [CH3:1][C:2]1[N:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:15])=[CH:9][CH:8]=2)[O:4][N:3]=1.[H-].[Na+].[CH2:24](Br)[CH:25]=[CH:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CN(C=O)C>[CH3:1][C:2]1[N:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH:13]([CH2:24]/[CH:25]=[CH:26]/[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:15])=[CH:11][CH:12]=2)[O:4][N:3]=1
Reactant: BrCC=Cc1ccccc1
Reactant: Cc1noc(-c2ccc(CC(=O)c3ccccc3)cc2)n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1noc(-c2ccc(C(C/C=C/c3ccccc3)C(=O)c3ccccc3)cc2)n1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 2-[4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]-1-phenyl 1-ethanone (0.2 g, 0.72 mmole) in DMF (3 mL) was added NaH (0.022 g, 0.7 mmole) at 0° C. The reaction was stirred for 15 min. Then a solution of cinnamyl bromide (0.16 g, 0.84 mmol) in 1 mL DMF was added. The reaction was warmed to room temperature, and was then quenched with saturated NH4Cl solution and extracted with ethyl acetate. The organic phase was then dried (Na2SO4), filtered, and evaporated to give the title compound.
Reaction SMILES: [CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[C:12](=O)[C:11]=3[C:20]([O:22]CC)=[O:21])=[CH:4][C:3]=2[O:2]1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([Mg]Br)=[CH:28][CH:27]=1>C1COCC1>[F:25][C:26]1[CH:31]=[CH:30][C:29]([CH:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:10]([C:5]3[CH:6]=[CH:7][C:8]4[O:9][CH2:1][O:2][C:3]=4[CH:4]=3)[CH:11]2[C:20]([OH:22])=[O:21])=[CH:28][CH:27]=1
Reactant: CCOC(=O)C1=C(c2ccc3c(c2)OCO3)c2ccccc2C1=O
Reactant: Fc1ccc([Mg]Br)cc1
Solvent: C1CCOC1
Product: O=C(O)C1C(c2ccc(F)cc2)c2ccccc2C1c1ccc2c(c1)OCO2
Reaction time: 0.75 h
Yield: 38.6 %

Procedure:
To a solution of ethyl 3-(3,4-methylenedioxyphenyl)-1-oxoindene-2-carboxylate (100 mg, 0.31 mmol) in THF (5 ml) under an argon atmosphere at 0° C. was added a solution of freshly prepared 4-fluorophenyl magnesium bromide (0.62 mmol). After stirring for 45 min, the mixture was partitioned between 3M HCl and EtOAc. The organic extract was washed successively with H2O, 5% aqueous NaHCO3 and saturated aqueous NaCl. The solvent was removed in vacua, and the residue was purified by flash chromatography, eluting with 15% EtOAc/hexanes to afford the title compound (45 mg, 35%).