Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([OH:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1)#[CH:2].Br[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28]>>[C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O-:29])=[O:28])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1)#[CH:2].[C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1)#[CH:2]
Reactant: C#Cc1cccc(Nc2ncnc3ccc(O)cc23)c1
Reactant: CCOC(=O)CCCCCBr
Product: C#Cc1cccc(Nc2ncnc3ccc(OCCCCCC(=O)OCC)cc23)c1
Product: C#Cc1cccc(Nc2ncnc3ccc(OCCCCCC(=O)[O-])cc23)c1
Yield: 64 %

Procedure:
The title compound ethyl 6-(4-(3-ethynylphenylamino)quinazolin-6-yloxy)hexanoate (0212-23) (0.3 g, 64%) was prepared from compound 4-(3-ethynylphenylamino)quinazolin-6-ol (0211) and ethyl 6-bromohexanoate using a procedure similar to that described for compound 0210-13 (Example 9): LC-MS m/z 404 [M+1].
Reaction SMILES: Cl[CH2:2][CH2:3][C:4]([NH:6][C:7]1[C:8]([Cl:18])=[N:9][N:10]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[CH:11]=1)=[O:5].CO.[OH-].[K+].[F:23][C:24]([F:29])([F:28])[CH2:25][CH2:26][SH:27]>O.C(OCC)(=O)C>[Cl:18][C:8]1[C:7]([NH:6][C:4](=[O:5])[CH2:3][CH2:2][S:27][CH2:26][CH2:25][C:24]([F:29])([F:28])[F:23])=[CH:11][N:10]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[N:9]=1
Reactant: FC(F)(F)CCS
Reactant: O=C(CCCl)Nc1cn(-c2cccnc2)nc1Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: O
Product: O=C(CCSCCC(F)(F)F)Nc1cn(-c2cccnc2)nc1Cl
Temperature: 20 °C
Yield: 92.4 %

Procedure:
A 100 mL, 3-neck round bottom flask was charged with 3-chloro-N-(3-chloro-1-(pyridine-3-yl)-1H-pyrazol-4-yl)propanamide (570 mg, 2.00 mmol) and methanol (10 mL), potassium hydroxide (135 mg, 2.40 mmol) was added, followed by 3,3,3-trifluoropropane-1-thiol (312 mg, 2.40 mmol) The mixture was heated at 50° C. for 4 hours, at which point thin layer chromatography analysis [Eluent: ethyl acetate] indicated the reaction was complete to give exclusively a new product. It was cooled to 20° C. and diluted with water (20 mL) and ethyl acetate (20 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (20 mL). The organics were dried over sodium sulfate and concentrated to dryness to afford a light yellow oil, which solidified upon standing to give a light yellow solid (700 mg, 92%): mp 99-102° C.; 1H NMR (400 MHz, DMSO-d6) δ 9.92 (s, 1H), 9.05 (d, J=2.7 Hz, 1H), 8.86 (s, 1H), 8.54 (dd, J=4.5, 1.4 Hz, 1H), 8.21 (ddd, J=8.4, 2.7, 1.4 Hz, 1H), 7.54 (dd, J=8.4, 4.7 Hz, 1H), 2.86 (t, J=7.3 Hz, 2H), 2.74 (td, J=6.5, 5.6, 4.2 Hz, 4H), 2.59 (ddd, J=11.7, 9.7, 7.4 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) δ 169.32, 147.49, 139.44, 135.47, 133.40, 126.60 (q, J=296 Hz), 125.49, 124.23, 122.30, 120.00, 35.18, 33.42 (q, J=27.2 Hz), 26.77, 23.05 (q, J=3.3 Hz); EIMS m/z 378 ([M]+).
Reaction SMILES: P(Br)(Br)[Br:2].[Br:5][C:6]1[C:7]([O:15][CH3:16])=[CH:8][C:9]([F:14])=[C:10]([CH2:12]O)[CH:11]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Br:5][C:6]1[CH:11]=[C:10]([CH2:12][Br:2])[C:9]([F:14])=[CH:8][C:7]=1[O:15][CH3:16]
Reactant: BrP(Br)Br
Reactant: COc1cc(F)c(CO)cc1Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: COc1cc(F)c(CBr)cc1Br
Temperature: 25 °C
Reaction time: 3 h
Yield: 94.5 %

Procedure:
PBr3 (4.7 g, 17.4 mmol) was added drop-wise to a solution of (5-bromo-2-fluoro-4-methoxyphenyl)methanol (4.1 g, 17.4 mmol) in anhydrous CH2Cl2 (40 mL) at 0° C. The mixture was stirred at room temperature for 3 h and poured into ice water. The pH was adjusted to 8 with saturated aqueous NaHCO3. Extractive work up with CH2Cl2 gave the title compound (4.9 g, 94.8%) as a white solid which was carried on without purification. 1H NMR (DMSO-d6, 400 MHz) δ 7.56 (d, J=8.0 Hz, 1H), 6.65 (d, J=11.6 Hz, 1H), 4.46 (s, 2H), 3.89 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[N:3]=1.[CH2:9](N(CC)CC)C.C([Li])CCC.CI>CCCCCC.O1CCCC1>[CH2:1]([C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[N:3]=1)[CH3:9]
Reactant: Cc1cccc(C)n1
Reactant: CCN(CC)CC
Agent: [Li]CCCC
Solvent: CI
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCc1cccc(C)n1
Temperature: -40 °C
Reaction time: 1 h

Procedure:
In a 250-ml 3-neck jacketed reactor flask, 4.3 g (40.2 mmol) of 2,6-dimethylpyridine and 4.06 g (40.2 mmol) of triethylamine were dissolved by addition of 50 ml of anhydrous tetrahydrofuran, and the solution was cooled to −40° C., after which 28.7 ml (46 mmol) of 1.6 M butyllithium in hexane was added dropwise thereto. At the same time, the solution changed to deep red. Next, the solution was stirred for 1 hour, and then warmed to 0° C., after which 5.7 g (40.2 mmol) of methyl iodide was added dropwise thereto, followed by stirring for 1 hour. Then, the reaction product was concentrated, and the concentrate was dissolved in ethyl acetate, washed with water and saline, dried with anhydrous magnesium sulfate, and then concentrated again, thereby obtaining crude 2-ethyl-6-methylpyridine. Subsequently, 3.2 g of the obtained 2-ethyl-6-methylpyridine was placed in a 250-ml 3-neck jacketed reactor flask and dissolved by addition of 4.06 g (40.2 mmol) of triethylamine and 50 ml of anhydrous tetrahydrofuran. The solution was cooled to −40° C., and 28.7 ml (46 mmol) of 1.6 M n-butyllithium in hexane was added dropwise. At this time, the solution changed to deep red. Next, the solution was stirred for 1 hour, and then cooled to 0° C., after which 6.0 g (42 mmol) of methyl iodide was added thereto dropwise. Then, the cooling bath was removed, and the solution was stirred at room temperature for 1 hour, and then concentrated. The concentrate was dissolved in ethyl acetate, washed with water and saline, dried with anhydrous magnesium sulfate, and then concentrated again. The concentrate was purified by column chromatography (stationary phase: silicagel; eluent: n-hexane/ethyl acetate (6/1), thereby obtaining 2 g of 2,6-diethyl pyridine as liquid. The obtained 2,6-diethyl pyridine was analyzed by NMR.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2[CH2:21][CH2:20][C:19]3[C:14](=[CH:15][C:16]([C:22]4[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=4)=[CH:17][CH:18]=3)[CH:13]=2)=[O:11])=[CH:5][CH:4]=1.[CH3:29][O:30][C:31]1[CH:32]=[C:33]([CH:41]=[C:42]([O:46][CH3:47])[C:43]=1[O:44][CH3:45])[CH2:34][N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[CH3:47][O:46][C:42]1[CH:41]=[C:33]([CH:32]=[C:31]([O:30][CH3:29])[C:43]=1[O:44][CH3:45])[CH2:34][N:35]1[CH2:40][CH2:39][N:38]([CH2:2][C:3]2[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]3[CH2:21][CH2:20][C:19]4[C:14](=[CH:15][C:16]([C:22]5[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=5)=[CH:17][CH:18]=4)[CH:13]=3)=[O:11])=[CH:5][CH:4]=2)[CH2:37][CH2:36]1
Reactant: Cc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CCl)cc2)CC3)cc1
Reactant: COc1cc(CN2CCNCC2)cc(OC)c1OC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc(CN2CCN(Cc3ccc(NC(=O)C4=Cc5cc(-c6ccc(C)cc6)ccc5CC4)cc3)CC2)cc(OC)c1OC
Temperature: 25 °C
Reaction time: 48 h
Yield: 64.9 %

Procedure:
In DMF (3 ml) was dissolved N-[4-(chloromethyl)phenyl]-7-(4-methylphenyl)-3,4-dihydronaphthalene-2-carboxamide (150 mg), and to the solution were added 1-(3,4,5-trimethoxybenzyl)piperazine (138 mg) and potassium carbonate (268 mg). The mixture was stirred at room temperature for 48 hours, and to the mixture was added water (50 ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-diisopropylether to give N-[4-[1-(3,4,5-trimethoxybenzyl)-4-piperazinylmethyl]-phenyl]-7-(4-methylphenyl)-3,4-dihydronaphthalene-2-carboxamide (Compound 45) (155 mg) as pale yellow crystals.
Reaction SMILES: [S:1]([N:11]1[C:15]2=[N:16][CH:17]=[C:18]([CH2:20][NH:21][C:22]([C:24]34[CH2:31][CH2:30][C:27]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])([CH2:28][CH2:29]3)[CH2:26][CH2:25]4)=O)[N:19]=[C:14]2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].O(C1C=CC(P2(=S)SP(=S)(C3C=CC(OC4C=CC=CC=4)=CC=3)S2)=CC=1)C1C=CC=CC=1>C1COCC1.CCOC(C)=O.C(O[Hg]OC(=O)C)(=O)C>[S:1]([N:11]1[C:15]2[N:16]=[CH:17][C:18]3[N:19]([C:22]([C:24]45[CH2:29][CH2:28][C:27]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:36])([CH3:38])[CH3:37])([CH2:30][CH2:31]4)[CH2:26][CH2:25]5)=[N:21][CH:20]=3)[C:14]=2[CH:13]=[CH:12]1)([C:4]1[CH:5]=[CH:6][C:7]([CH3:8])=[CH:9][CH:10]=1)(=[O:3])=[O:2]
Reactant: Cc1ccc(S(=O)(=O)n2ccc3nc(CNC(=O)C45CCC(NC(=O)OC(C)(C)C)(CC4)CC5)cnc32)cc1
Agent: CC(=O)O[Hg]OC(C)=O
Agent: S=P1(c2ccc(Oc3ccccc3)cc2)SP(=S)(c2ccc(Oc3ccccc3)cc2)S1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cc1ccc(S(=O)(=O)n2ccc3c2ncc2cnc(C45CCC(NC(=O)OC(C)(C)C)(CC4)CC5)n23)cc1
Reaction time: 15 h
Yield: 88.3 %

Procedure:
To a solution of tert-butyl 4-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamoyl)-bicyclo[2.2.2]octan-1-ylcarbamate (0.205 g, 0.370 mmol) in THF (5 mL) was added 2,4-bis(4-phenoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide (0.215 g, 0.407 mmol, TCI America). After about 15 h at ambient temperature, diacetoxymercury (0.295 g, 0.926 mmol) was added to the reaction mixture. After about 2 h, the reaction mixture was diluted with EtOAc (30 mL) and filtered through Celite®. The filtrate was concentrated under reduced pressure and the crude mixture was purified by chromatography on silica gel eluting with a gradient of 20-80% EtOAc in DCM to provide tert-butyl 4-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)bicyclo[2.2.2]octan-1-ylcarbamate as a tan solid (0.175 g, 84%). LC/MS (Table 2, Method a) Rt=2.84 min; MS m/z: 536 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1Cl.[NH:10]1[CH:14]=[CH:13][N:12]=[CH:11]1.CC[O-].[Na+]>C(O)C.C1COCC1>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[N:10]1[CH:14]=[CH:13][N:12]=[CH:11]1
Reactant: c1c[nH]cn1
Reactant: Cc1ccc(Cl)c(C)c1
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Solvent: C1CCOC1
Product: Cc1ccc(-n2ccnc2)c(C)c1
Temperature: 110 °C
Yield: 48 %

Procedure:
30 mmol of 2,4-dimethylchlorobenzene (4.2 g), 40 mmol of imidazole (2.7 g), 35 mmol of NaOEt solution in ethanol (10% by weight) and 230 mg of trans-di-μ-chlorobis[2-[bis(1,1-dimethylethyl)phosphino]-2-methylpropyl-C,P]dipalladium(II) (1.0 mol %) are suspended in 50 ml of THF and heated at 110° C. in a pressure tube for 9 hours. After removal of the salts by filtration, the solvent is removed under reduced pressure. This gives crude 1-(2,4-dimethylphenyl)imidazole as a brown liquid which can be purified by distillation (boiling point: 122° C./12 torr); yield: 48%.
Reaction SMILES: Cl.[CH2:2]([NH:9][NH2:10])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH:11](=O)[C:12]([CH3:14])=[O:13]>O.C(Cl)Cl>[CH2:2]([NH:9][N:10]=[CH:11][C:12](=[O:13])[CH3:14])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: NNCc1ccccc1
Reactant: CC(=O)C=O
Agent: Cl
Solvent: ClCCl
Solvent: O
Product: CC(=O)C=NNCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100.4 %

Procedure:
To a solution of benzylhydrazine hydrochloride (11.1 g, 57.1 mmol) in water (100 mL) was added dropwise a solution of pyruvaldehyde (10.3 g, 9.3 mL, 57.1 mmol) in water (500 mL). The mixture was stirred at room temperature overnight. The reaction mixture was diluted with CH2Cl2 (4×150 mL). The combined organic extracts were washed with saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated to provide 2-oxopropanal benzylhydrazone (10.1 g, 100%).
Reaction SMILES: [C:1]([C:4]1[O:5][C:6]2[C:12]([N:13]3[C:18](=[O:19])[CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[N:15]([CH3:24])[C:14]3=[O:25])=[C:11]([F:26])[CH:10]=[C:9]([Cl:27])[C:7]=2[CH:8]=1)([OH:3])=[O:2].[C:28](=O)([O-])[O-].[K+].[K+].CI.O>CN(C)C=O>[Cl:27][C:9]1[C:7]2[CH:8]=[C:4]([C:1]([O:3][CH3:28])=[O:2])[O:5][C:6]=2[C:12]([N:13]2[C:18](=[O:19])[CH:17]=[C:16]([C:20]([F:21])([F:23])[F:22])[N:15]([CH3:24])[C:14]2=[O:25])=[C:11]([F:26])[CH:10]=1
Reactant: Cn1c(C(F)(F)F)cc(=O)n(-c2c(F)cc(Cl)c3cc(C(=O)O)oc23)c1=O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Solvent: O
Product: COC(=O)c1cc2c(Cl)cc(F)c(-n3c(=O)cc(C(F)(F)F)n(C)c3=O)c2o1
Temperature: 25 °C
Reaction time: 3 h
Yield: 99.8 %

Procedure:
0.21 g (0.5 mmol) of 3-(2-carboxy-4-chloro-6-fluorobenzofuran-7-yl)-1-methyl-6-trifluoromethyluracil and 0.16 g (1.1 mmol) of potassium carbonate were suspended in 10 ml of N,N-dimethylformamide, and 0.15 g (1.1 mmol) of methyl iodide was added thereto at room temperature, followed by stirring at room temperature for 3 hours. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed sequentially with water and a saturated sodium chloride aqueous solution, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. Then, the obtained residue was purified by silica gel column chromatography to obtain 0.21 g (yield: 96.8%) of the desired product as yellowish brown crystals. Melting point: 194-196° C.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[Cl:6][C:7]1[CH:8]=[C:9]([C:13]2[O:17][N:16]=[C:15]([CH:18]([OH:20])[CH3:19])[N:14]=2)[CH:10]=[CH:11][CH:12]=1>C(Cl)Cl>[CH3:1][S:2]([O:20][CH:18]([C:15]1[N:14]=[C:13]([C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([Cl:6])[CH:8]=2)[O:17][N:16]=1)[CH3:19])(=[O:4])=[O:3]
Reactant: CS(=O)(=O)Cl
Reactant: CC(O)c1noc(-c2cccc(Cl)c2)n1
Solvent: ClCCl
Product: CC(OS(C)(=O)=O)c1noc(-c2cccc(Cl)c2)n1
Reaction time: 0.25 h
Yield: 99.1 %

Procedure:
Methane sulfonyl chloride (40 ml, 0.49 mmol) was added to a mixture of TEA (95 ml, 0.67 mmol) and 1-[5-(3-Chloro-phenyl)-1,2,4-oxadiazol-3-yl]-ethanol (100 mg, 0.45 mmol) in DCM (5 ml). After stirring for 15 min the mixture was washed with water and brine, dried and concentrated to yield the title compound (135 mg). 1H NMR: 1.9 (d, 3 H) 3.1 (s, 3 H) 5.9 (q, 1 H) 7.5 (t, 1 H) 7.6 (m, 1 H) 8.0 (m, 1 H) 8.1 (t, 1 H)
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=4)[C:24](O)=[O:25])=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.Cl.[CH3:42][S:43]([NH2:46])(=[O:45])=[O:44]>CN(C1C=CN=CC=1)C.CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:29]=[CH:28][CH:27]=[C:23]([C:24](=[O:25])[NH:46][S:43]([CH3:42])(=[O:45])=[O:44])[CH:22]=4)=[CH:17][C:11]=3[C:12]=2[C:13]([NH:14][CH3:15])=[O:16])=[CH:4][CH:3]=1
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2ccc(-c3cccc(C(=O)O)c3)cc12
Reactant: CS(N)(=O)=O
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CN(C)C=O
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2ccc(-c3cccc(C(=O)NS(C)(=O)=O)c3)cc12
Yield: 71.5 %

Procedure:
In a 1 dram vial with stir bar were combined 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoic acid (35 mg, 0.090 mmol), DMAP (33 mg, 0.27 mmol), EDC hydrochloride (26 mg, 0.14 mmol), and methanesulfonamide (25 mg, 0.26 mmol). DMF (0.5 mL) was added, the vial was capped, and the reaction was stirred at r.t. overnight. The reaction was filtered, purified by prep HPLC, and concentrated to give 30 mg (72% yield) of the title compound as a white powder. 1H NMR (500 MHz, DMSO-d6) δ ppm 12.36 (br. s., 1H) 8.53 (d, J=4.58 Hz, 1H) 8.27 (s, 1H) 7.97-8.05 (m, 2H) 7.84-7.96 (m, 3H) 7.77-7.82 (m, 1H) 7.71-7.76 (m, 1H) 7.56 (t, J=7.78 Hz, 1H) 7.40 (t, J=8.85 Hz, 2H) 3.17 (s, 3H) 2.86 (d, J=4.58 Hz, 3H). LC/MS was performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters MICROMASS®. LC/MS method: solvent A=10% CH3CN/90% H2O/0.1% TFA, solvent B=90% CH3CN/10% H2O/0.1% TFA, start % B=0, final % B=100, gradient time=2 min, stop time=3 min, flow rate=4 ml/min, column: Sunfire C18 5 μm 4.6×50 mm; HPLC Rt=1.56 min, (ES+) m/z (MH+)=467. Analytical HPLC were performed using a Shimadzu-VP instrument with UV detection at 220 nm and 254 nm. Analytical HPLC method: solvent A=5% CH3OH/95% H2O/10 mM NH4HCO3, solvent B=95% CH3OH/5% H2O/10 mM NH4HCO3, start % B=10, final % B=100, gradient time=15 min, stop time=18 min, flow rate=1 ml/min. Column: PHENOMENEX® Gemini C18, 4.6 mm, 3 μm, Rt=11.93 min, purity=100%; column: Waters XBridge phenyl 4.6×150 mm, 3.5 μm, Rt=13.97 min, purity=99%.
Reaction SMILES: [CH3:1][N:2]([CH2:26][CH2:27][OH:28])[C:3](=[O:25])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24].[C:29](Cl)(=[O:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>>[CH3:1][N:2]([CH2:26][CH2:27][O:28][C:29](=[O:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:3](=[O:25])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: O=C(Cl)c1ccccc1
Reactant: CCCCCCCC/C=C\CCCCCCCCCCCC(=O)N(C)CCO
Product: CCCCCCCC/C=C\CCCCCCCCCCCC(=O)N(C)CCOC(=O)c1ccccc1

Procedure:
N-methyl-N-(2-benzoyloxyethyl)erucamide was prepared by the procedure of example 1 from 39.5 gms. (0.1 mole) of N-methyl-N-(2-hydroxyethyl)erucamide and 14 gms. (0.1 mole) of benzoyl chloride. The structure of the final product was characterized on the basis of IR and NMR spectral analyses as described in example 1.
Reaction SMILES: [C:1]([NH:4][NH:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:7]=1[Cl:13])(=O)[CH3:2].P(Cl)(Cl)([Cl:16])=O>C1(C)C=CC=CC=1>[Cl:13][C:7]1[CH:8]=[C:9]([Cl:12])[CH:10]=[CH:11][C:6]=1[NH:5][N:4]=[C:1]([Cl:16])[CH3:2]
Reactant: CC(=O)NNc1ccc(Cl)cc1Cl
Reactant: O=P(Cl)(Cl)Cl
Solvent: Cc1ccccc1
Product: CC(Cl)=NNc1ccc(Cl)cc1Cl
Temperature: 110 °C
Reaction time: 0.5 h
Yield: 78.5 %

Procedure:
A solution of 25.0 grams (0.1142 mole) of 1-acetyl-2-(2,4-dichlorophenyl)-hydrazine (2) in 120 grams of toluene was stirred, and 17.7 grams (0.1142 mole) of phosphorus oxychloride was added portionwise. Upon completion of addition the reaction mixture was warmed to about 110° C. where it stirred for about 30 minutes. GC analysis of the reaction mixture after this time indicated the reaction was complete. An additional 100 grams of toluene was added to the reaction mixture, and the solution was decanted into a separatory funnel. A residue in the reaction vessel was washed with about 40 grams of toluene, and the wash was also decanted into the separatory funnel. The toluene solution was then washed with an aqueous solution of 10% potassium carbonate. The aqueous layer was back-washed with two 75 gram portions of toluene. The combined toluene layer and washes was dried with magnesium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure, yielding 21.3 grams (78.5% yield) of N-(2,4-dichlorophenyl)-ethanehydrazonoyl chloride (A).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([Br:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[O:10][CH3:11].[Br:12]Br>ClC(Cl)(Cl)Cl.C(OOCC1C=CC=CC=1)C1C=CC=CC=1>[Br:1][C:2]1[CH:7]=[C:6]([Br:8])[CH:5]=[C:4]([CH2:9][Br:12])[C:3]=1[O:10][CH3:11]
Reactant: BrBr
Reactant: COc1c(C)cc(Br)cc1Br
Agent: c1ccc(COOCc2ccccc2)cc1
Solvent: ClC(Cl)(Cl)Cl
Product: COc1c(Br)cc(Br)cc1CBr
Temperature: 25 °C
Yield: 71.5 %

Procedure:
A solution of the product of stage (b) (200 g) and benzyl peroxide (1 g) in tetrachloromethane (600 ml) was heated to reflux with stirring. Bromine (114 g) was added dropwise, and the mixture was stirred until it cooled to room temperature. Evaporation of the solvent gave an oil, distillation of which gave the title compound (183 g) as an oil, bp 115°-116° C./0.3 mm Hg.
Reaction SMILES: [CH2:1]([N:3]([CH2:23][CH2:24][OH:25])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[C:12](=[N:21]O)[CH:11]=2)=[CH:6][CH:5]=1)[CH3:2].[CH3:26][N:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]([CH3:37])([CH3:36])[C:28]1=[CH2:38]>C(O)C>[CH2:1]([N:3]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]3[O:20][C:28]4([C:29]([CH3:37])([CH3:36])[C:30]5[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=5)[N:27]4[CH3:26])[CH:38]=[N:21][C:12]=3[CH:11]=2)=[CH:6][CH:5]=1)[CH2:23][CH2:24][OH:25])[CH3:2]
Reactant: C=C1N(C)c2ccccc2C1(C)C
Reactant: CCN(CCO)c1ccc(C2=CC(=NO)C(=O)c3ccccc32)cc1
Solvent: CCO
Product: CCN(CCO)c1ccc(-c2cc3c(c4ccccc24)OC2(C=N3)N(C)c3ccccc3C2(C)C)cc1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
A suspension of 4-(4-(ethyl(2-hydroxyethyl)amino)phenyl)-2-(hydroxyimino)naphthalen-1(2H)-one (4.0 g, 11.89 mmol) in ethanol (100 ml) was treated with 1,3,3-trimethyl-2-methyleneindoline (2.68 g, 15.46 mmol) in one portion and heated to 100° C. in a sealed tube for 4 hrs. The mixture was then cooled to RT and left to stand overnight. The resulting suspension was evaporated in vacuo to approx 25 ml total volume, MeOH added (25 ml) and the mixture stored in the freezer for 3 hrs. After this time the product was collected by filtration and washed with a little methanol to give the product, 2-(ethyl(4-(1,3,3-trimethylspiro[indoline-2,2′-naphtho[1,2-b][1,4]oxazine]-6′yl)phenyl)amino)ethanol, as pale green fibres (4.15 g, 71%). Analysis of the product by 1H NMR gave a spectrum consistent with the structure.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.[C:12]([OH:16])(=[O:15])[CH:13]=O.[BH3-]C#N.[Na+].[C:21](#N)[CH3:22]>>[N:8]1[C:9]2[C:4](=[CH:3][C:2]([NH:1][CH2:13][C:12]([O:16][CH2:21][CH3:22])=[O:15])=[CH:11][CH:10]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: Nc1ccc2ncccc2c1
Reactant: CC#N
Reactant: O=CC(=O)O
Agent: [BH3-]C#N
Agent: [Na+]
Product: CCOC(=O)CNc1ccc2ncccc2c1
Temperature: 25 °C
Reaction time: 48 h
Yield: 87 %

Procedure:
To a stirred solution of 6-aminoquinoline (compound IV, FIG. 3B) (0.72 g, 5 mmol) in acetonitrile (20 ml) was added 33% aqueous glyoxylic acid (1.85 g, 20 mmole) solution. A solution of NaBH3CN (0.64 g, 10.2 mmol) in acetonitrile (20 ml) was then added at 3° C. over 20 minutes and the reaction mixture was warmed to room temperature and stirred for 48 hours. Acetonitrile was evaporated under vacuum, water (20 ml) was added to the residue, the solution was alkalinized to pH 9.5, and unreacted amine was extracted with ether. Concentrated HCl (25 ml) was added to the aqueous solution and the mixture was stirred at 25° C. for 1 hour. Solvent was evaporated under vacuum. The resultant residue of N-(6-quinolinyl)glycine was dissolved in dry ethanol (50 ml) saturated with dry HCl, stirred overnight and then refluxed for 3 hours. Ethanol was evaporated, the ester hydrochloride was suspended in dry ether, and ammonia gas was bubbled. The ammonium chloride was filtered and ether was removed by evaporation to give ethyl N-(6-quinolinyl)glycinate (0.5 g, 87%, mp 122-123° C.). N-(6-quinolinyl)glycine hydrazide (compound VI, FIG. 3B), synthesized by hydrazinolysis of the above ester, was reacted with 3,5-dibromo-2,4-dihydroxybenzaldehyde to give GlyH-126. Similar procedures were used for synthesis of GlyH-127.