Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][N:2]=[C:3](Cl)[C:4]1[CH:15]=[CH:14][C:7]2[B:8]([OH:13])[O:9][C:10]([CH3:12])([CH3:11])[C:6]=2[CH:5]=1.[Br:17][C:18]1[CH:23]=[C:22]([C:24]([C:26]([F:29])([F:28])[F:27])=[CH2:25])[CH:21]=[C:20]([Br:30])[C:19]=1[Cl:31].CC(=O)OCC>CN(C=O)C>[Br:17][C:18]1[CH:23]=[C:22]([C:24]2([C:26]([F:29])([F:28])[F:27])[O:1][N:2]=[C:3]([C:4]3[CH:15]=[CH:14][C:7]4[B:8]([OH:13])[O:9][C:10]([CH3:12])([CH3:11])[C:6]=4[CH:5]=3)[CH2:25]2)[CH:21]=[C:20]([Br:30])[C:19]=1[Cl:31]
Reactant: C=C(c1cc(Br)c(Cl)c(Br)c1)C(F)(F)F
Reactant: CC1(C)OB(O)c2ccc(C(Cl)=NO)cc21
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC1(C)OB(O)c2ccc(C3=NOC(c4cc(Br)c(Cl)c(Br)c4)(C(F)(F)F)C3)cc21
Temperature: 25 °C
Reaction time: 12 h
Yield: 23.9 %

Procedure:
To a solution of N,1-dihydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborole-5-carbimidoyl chloride (68 mg, 0.28 mmol) in DMF was added 1,3-dibromo-2-chloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene (132 mg, 0.36 mmol) and TEA (31 mg, 0.36 mmol) at rt. The mixture was stirred at 25° C. for 12 h, quenched with water, extracted with EA (3×10 mL). The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography eluted with PE:EA=5:1 to give the final title compound 5-(5-(3,5-dibromo-4-chlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethyl-benzo[c][1,2]oxaborol-1(3H)-ol (38 mg; yield 22%) as solid. 1H NMR (400 MHz, DMSO-d6): δ 9.21 (s, 1H), 7.96 (s, 2H), 7.76-7.69 (m, 3H), 4.45-4.30 (q, 2H), 1.48 (s,6H) ppm; MS: m/z=568 (M+1, ESI+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[C:11]([N+:13]([O-])=O)[CH:12]=1)[N:9]=[C:8]([CH:16]=[CH2:17])[CH:7]=[CH:6]2.O.NN>[Ni].C1(C)C=CC=CC=1>[NH2:13][C:11]1[CH:12]=[C:3]([O:2][CH3:1])[CH:4]=[C:5]2[C:10]=1[N:9]=[C:8]([CH2:16][CH3:17])[CH:7]=[CH:6]2
Reactant: C=Cc1ccc2cc(OC)cc([N+](=O)[O-])c2n1
Agent: [Ni]
Agent: NN
Solvent: O
Solvent: Cc1ccccc1
Product: CCc1ccc2cc(OC)cc(N)c2n1

Procedure:
To a mixture of 9.6 g (0.04 mole) of 6-methoxy-8-nitro-2-vinylquinoline, 5 g (wet weight, washed with ethanol) of Raney nickel catalyst and 250 ml of toluene-95% ethanol (1:1) was added 25 ml of 85% hydrazine hydrate in portions, and after the vigorous reaction was over the mixture was heated under reflux for 5 hr. The condensor was removed and the mixture heated (ethanol added) until the vapors were faintly alkaline. The mixture was cooled, filtered over diatomaceous earth, and the filtrate concentrated in vacuo. The oily residue was dissolved in anhydrous ether and treated with HBr gas. The hydrobromide precipitated as a yellow powder and was recrystallized from ethanol-chloroform. The yield was 6.6 g (56%) of the desired 8-amino-2-ethyl-6-methoxyquinoline hydrobromide, mp 239°-241°. Rf : 0.62 (19.2 ethyl acetate-diethylamine), 0.67 (19:1 ethanol-diethylamine), 0.74 (19:1 methanol-diethylamine).
Reaction SMILES: [NH2:1][NH2:2].[CH3:3][O:4][C:5]1[N:10]=[CH:9][C:8]([C:11]([C:13]2[CH:21]=[CH:20][CH:19]=[CH:18][C:14]=2[C:15](O)=[O:16])=O)=[CH:7][CH:6]=1>C(O)C>[CH3:3][O:4][C:5]1[N:10]=[CH:9][C:8]([C:11]2[C:13]3[C:14](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:15](=[O:16])[NH:2][N:1]=2)=[CH:7][CH:6]=1
Reactant: NN
Reactant: COc1ccc(C(=O)c2ccccc2C(=O)O)cn1
Solvent: CCO
Product: COc1ccc(-c2n[nH]c(=O)c3ccccc23)cn1
Temperature: 60 °C
Reaction time: 4 h
Yield: 78 %

Procedure:
24 ml (121 mmol) of hydrazine was added to an ethanol solution (200 ml) of 28.0 g of 2-[(6-methoxypyridin-3-yl)carbonyl]benzoic acid, and the reaction liquid was stirred at 60° C. for 4 hours. The reaction liquid was concentrated under reduced pressure, and the resulting solid was washed with diethyl ether to obtain 21.50 g (yield: 77%) of 4-(6-methoxypyridin-3-yl)-2H-phthalazin-1-on as a white solid.
Reaction SMILES: [F:1][C:2]([F:8])([F:7])[S:3](Cl)(=[O:5])=[O:4].Cl.[CH3:10][O:11][C:12](=[O:17])[CH2:13][CH2:14][CH2:15][NH2:16].C(N(CC)CC)C.Cl>ClCCl>[CH3:10][O:11][C:12](=[O:17])[CH2:13][CH2:14][CH2:15][NH:16][S:3]([C:2]([F:8])([F:7])[F:1])(=[O:5])=[O:4]
Reactant: COC(=O)CCCN
Reactant: O=S(=O)(Cl)C(F)(F)F
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)CCCNS(=O)(=O)C(F)(F)F
Temperature: 25 °C
Reaction time: 18 h
Yield: 86 %

Procedure:
Trifluoromethanesulfonyl chloride (0.23 mL, 2.16 mmol) was added dropwise to a solution of 4-amino-butyric acid methyl ester hydrochloride (0.30 g, 1.96 mmol) and triethylamine (0.68 mL, 4.90 mmol) in dichloromethane and stirred at room temperature for 18 hours. 1N HCl was added and the product was extracted with dichloromethane, dried with magnesium sulfate and evaporated to give the title compound (0.42 g, 85%). 1H-NMR (CDCl3): δ 4.89 (s, 1H), 3.12 (t, 2H, J=7.2 Hz), 2.94 (s, 3H), 2.41 (t, 2H, J=7.2 Hz), 1.84 (m, 2H, J=7.2 Hz).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([C:12](O)=[O:13])[CH:11]=1)[NH:8][CH:7]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:16]=1)[CH2:6][C:5]2([CH3:27])[CH3:26].[CH:28]1([S:31]([NH2:34])(=[O:33])=[O:32])[CH2:30][CH2:29]1>CN(C)C1C=CN=CC=1.ClCCl>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([C:12]([NH:34][S:31]([CH:28]3[CH2:30][CH2:29]3)(=[O:33])=[O:32])=[O:13])[CH:11]=1)[NH:8][CH:7]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:16]=1)[CH2:6][C:5]2([CH3:27])[CH3:26]
Reactant: NS(=O)(=O)C1CC1
Reactant: CC1(C)CC(c2cccc(N3CCCC3)c2)Nc2c(C(=O)O)cc(F)cc21
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CC1(C)CC(c2cccc(N3CCCC3)c2)Nc2c(C(=O)NS(=O)(=O)C3CC3)cc(F)cc21
Yield: 25.6 %

Procedure:
A mixture of 6-fluoro-4,4-dimethyl-2-(3-pyrrolidin-1-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid (150 mg, 0.32 mmol), 1-3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride (91 mg, 0.48 mmol), 4-dimethylaminopyridine (59 mg, 0.48 mmol), cyclopropane sulfonic acid amide (149 mg, 1.23 mmol) in dichloromethane (10 mL) was refluxed for 12 h. Removal of the solvent to afford the oil residue. Purification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% formic acid in water) afforded cyclopropanesulfonic acid [6-fluoro-4,4-dimethyl-2-(3-pyrrolidin-1-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-8-carbonyl]-amide (38.6 mg, 20%) as a light yellow solid: MS (ESI) M+1=472.3.
Reaction SMILES: Br[CH2:2][CH2:3][N:4]1[C:8]([CH2:9]Br)=[CH:7][C:6]([N+:11]([O-:13])=[O:12])=[N:5]1.[CH2:14]([NH2:16])[CH3:15]>C1COCC1>[CH2:14]([N:16]1[CH2:2][CH2:3][N:4]2[N:5]=[C:6]([N+:11]([O-:13])=[O:12])[CH:7]=[C:8]2[CH2:9]1)[CH3:15]
Reactant: CCN
Reactant: O=[N+]([O-])c1cc(CBr)n(CCBr)n1
Solvent: C1CCOC1
Product: CCN1CCn2nc([N+](=O)[O-])cc2C1
Temperature: 25 °C
Reaction time: 12 h
Yield: 97.2 %

Procedure:
In a 100 mL round-bottomed flask, 1-(2-bromoethyl)-5-(bromomethyl)-3-nitro-1H-pyrazole (0.7 g, 2.24 mmol, Eq: 1.00) was combined with THF (25 ml) to give a light yellow solution. To this ethylamine (7.83 ml of 2M in THF, 15.7 mmol, Eq: 7) was added dropwise and the reaction mixture was stirred at ambient temperature for 12 hr. The reaction mixture was concentrated and the resulting solid was stirred with a mixture of EtOAc (250 mL) and 10% aqueous K2CO3 (200 mL). The layers were separated and aqueous layer was back extracted with EtOAc (2×100 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 1% to 4% MeOH in DCM). Fractions containing product were combined and concentrated to afford the desired product (427 mg). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.20 (t, J=7.18 Hz, 3 H) 2.68 (q, J=7.18 Hz, 2 H) 3.01 (t, J=5.48 Hz, 2 H) 3.72 (s, 2 H) 4.29 (t, J=5.67 Hz, 2 H) 6.64 (s, 1 H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1.C([O-])(=O)C.[Na+].[Br:14]Br.[OH-].[Na+]>C(O)(=O)C.O>[Br:14][C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[N:4][CH:5]=1
Reactant: BrBr
Reactant: COc1ccccn1
Agent: CC(=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Product: COc1ccc(Br)cn1
Reaction time: 3 h
Yield: 51.3 %

Procedure:
To a suspension of 2-methoxypyridine (10.00 g, 0.09 mol) and sodium acetate (8.27 g, 0.10 mmol) in 30 mL of glacial acetic acid was added a solution of bromine in 20 mL glacial acetic acid while maintaining the reaction temperature below 50° C. After 3 hours, 100 mL of H2O was added and the resulting solution neutralized with cold 2.5 M NaOH. The suspension was extracted with ether (2×200 mL), the combined organics were dried over MgSO4, filtered and evaporated. The crude material was purified on silica gel (eluent: hexane to hexane:ethyl acetate 97:3) and distilled (34-36.5° C./0.05 mm Hg) to give 8.84 g (51.3%) of 5-bromo-2-methoxy-pyridine as a clear colorless liquid.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15](=[O:23])[C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[C:9]=1[O:24][C:25](=[O:33])[C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=1.[C:34]1([CH2:40][O:41][C:42](=[O:54])[C:43]2[CH:48]=[CH:47][C:46]([OH:49])=[C:45]([CH2:50][CH2:51][CH3:52])[C:44]=2[OH:53])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[C:34]1([CH2:40][O:41][C:42](=[O:54])[C:43]2[CH:48]=[CH:47][C:46]([O:49][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15](=[O:23])[C:16]4[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=4)[C:9]=3[O:24][C:25](=[O:33])[C:26]3[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=3)=[C:45]([CH2:50][CH2:51][CH3:52])[C:44]=2[OH:53])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
Reactant: Cc1ccc(C(=O)Oc2cccc(CCCCCCBr)c2OC(=O)c2ccc(C)cc2)cc1
Reactant: CCCc1c(O)ccc(C(=O)OCc2ccccc2)c1O
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCc1c(OCCCCCCc2cccc(OC(=O)c3ccc(C)cc3)c2OC(=O)c2ccc(C)cc2)ccc(C(=O)OCc2ccccc2)c1O
Yield: 31.7 %

Procedure:
A mixture of 1.91 g (3.75 mmol) of 1-(6-bromohexyl)-2,3-bis[(4-methylbenzoyl)oxy]benzene, 1.07 g (3.75 mmol) 2,4-dihydroxy-3-propylbenzoic acid phenylmethyl ester, 0.94 g (5.63 mmol) of potassium iodide and 0.75 g (5.63 mol) of potassium carbonate in 40 mL of acetone was stirred at reflux for 26 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressue. The crude product was purified by HPLC using 5% ethyl acetate-hexane to give 0.85 g (32% yield) of 2-hydroxy-4-[6-[2,3-bis[(4-methylbenzoyl)oxy]phenyl]hexyloxy]-3-propylbenzoic acid phenylmethyl ester as an oil.
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[C:11](Cl)[N:10]=[N:9][C:8]=2[Cl:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:15]1[CH:20]=[CH:19][CH:18]=[C:17](B(O)O)[CH:16]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O>[Cl:14][C:8]1[N:9]=[N:10][C:11]([C:17]2[CH:16]=[N:15][CH:20]=[CH:19][CH:18]=2)=[CH:12][C:7]=1[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Clc1cc(-c2ccccc2)c(Cl)nn1
Reactant: OB(O)c1cccnc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: Clc1nnc(-c2cccnc2)cc1-c1ccccc1
Temperature: 110 °C

Procedure:
4-Phenyl-3,6-dichloropyridazine (1-1; 113 mg, 0.5 mmol) was dissolved in dry dioxane (2 mL). Then pyridine-3-boronic acid (99 mg, 0.8 mmol), 2 M aqueous Na2CO3 (0.75 mL) and palladium(0) tetrakis-triphenylphosphine (60 mg, 0.04 mmol) were added. This mixture was degassed, the vessel sealed and heated at 110° C. for 9 hours. The cooled reaction was diluted with water and the product mixture extracted into ethyl acetate, the extract dried over anhydrous NaSO4, filtered and evaporated. The product was purified by chromatography on silica gel and elution with a 20-70% ethyl acetate/hexane gradient to give 3-chloro-4-phenyl-6-pyridin-3-ylpyridazine (3-1). NMR (CDCl3): δ9.26 (1H, s), 8.78 (1H, d, J=4.6 Hz), 8.51 (1H, d, J=8 Hz), 7.86 (1H, s), 7.55-7.58 (5H, m), 7.51 (1H, dd, J=8 Hz, J=4.5 Hz); m/e (m+1): 268.1.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])=[CH:10][C:9]=1[NH:21][C:22](=[O:39])[CH2:23][C:24](C1C=CC=C(C2C=CN=C(C)C=2)C=1)=O)(C)(C)C.[C:41](O)([C:43](F)(F)F)=O>C(Cl)Cl>[F:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[C:11]1[CH:12]=[CH:13][C:8]2[N:7]=[C:24]([C:16]3[CH:17]=[CH:18][CH:19]=[C:14]([C:11]4[CH:10]=[CH:9][N:21]=[C:41]([CH3:43])[CH:12]=4)[CH:15]=3)[CH2:23][C:22](=[O:39])[NH:21][C:9]=2[CH:10]=1
Reactant: O=C(O)C(F)(F)F
Reactant: Cc1cc(-c2cccc(C(=O)CC(=O)Nc3cc(-c4ccccc4F)ccc3NC(=O)OC(C)(C)C)c2)ccn1
Solvent: ClCCl
Product: Cc1cc(-c2cccc(C3=Nc4ccc(-c5ccccc5F)cc4NC(=O)C3)c2)ccn1

Procedure:
The title compound was prepared from (2′-fluoro-3-{3-[3-(2-methyl-pyridin-4-yl)-phenyl]-3-oxo-propionylamino}-biphenyl-4-yl)-carbamic acid tert-butyl ester (Example M65) (0.47 g, 0.87 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (305 mg, 83%).
Reaction SMILES: [CH3:1][C:2]1[CH:28]=[CH:27][C:5]([NH:6][C:7]2[CH:15]=[C:14]([C:16]([OH:18])=O)[C:13]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=3)=[CH:12][C:8]=2[C:9](O)=[O:10])=[CH:4][CH:3]=1.CO>O.[Fe]>[CH3:1][C:2]1[CH:28]=[CH:27][C:5]2[NH:6][C:7]3[C:8]([C:9](=[O:10])[C:4]=2[CH:3]=1)=[CH:12][C:13]1[NH:19][C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][C:21]=2[C:16](=[O:18])[C:14]=1[CH:15]=3
Reactant: Cc1ccc(Nc2cc(C(=O)O)c(Nc3ccc(C)cc3)cc2C(=O)O)cc1
Agent: [Fe]
Solvent: O
Solvent: CO
Product: Cc1ccc2[nH]c3cc4c(=O)c5cc(C)ccc5[nH]c4cc3c(=O)c2c1
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
To 320 g of polyphosphoric acid (111.8% phosphoric acid) heated at 80°-95° C. was added 0.89 g (3.2 mmole) of ferrous sulfate heptahydrate followed by 72 g (0.1915 mole) of essentially iron-free 2,5-di(4-methylanilino)terephthalic acid. The iron content, relative to 2,5-di(4-methylanilino)terephthalic acid, was about 1.7 mole percent. The mixture was heated at 120°-125° C. for two hours. The viscous solution was cooled to 90°-95° C. and then slowly poured into a mixture of 470 g of methanol and 50 g of water at 40° C. The temperature of the resultant slurry was allowed to rise during the addition to about 64° C., with the temperature being controlled during addition by external cooling and adjustment of melt addition rate. The slurry was heated at reflux (68°-72° C.) for one hour, cooled to 60° C., and diluted with 600 g of water. After the slurry was stirred at 60° C. for 30 minutes, the solid component was collected by filtration and washed with water until acid-free. The resultant presscake was reslurried in 800 g of water and 33 g of 50% sodium hydroxide, then heated for 90°-95° C. for two hours. After being cooled to 70° C., the slurry was filtered and washed with water until free of alkali. The resultant presscake was reslurried in 700 g water and heated to 110°-115° C. for two hours in a closed system (e.g., a pressure reactor). After the slurry was cooled to 60°-70° C., the pH was adjusted to 3.5 with phosphoric acid and an emulsion of 2.5 g of sodium dioctyl sulfosuccinate (available as AEROSOL OT from American Cyanamid Co.), 35 g of VM&P Naphtha (available from Unocal Chemicals), and 75 g of water was added. The mixture was stirred at 30°-35° C. for three hours, collected by filtration, and washed with water. The wet cake can be oven dried or used as is for specific applications. Here, the wet cake was dried in an oven at 60° C. to give about 55 g of 2,9-dimethylquinacridone as a brilliant magenta solid. Based on a rub-out test in linseed oil (as described above), the pigment of Example 5 is significantly bluer in undertone (tint) and deeper in masstone than a comparison pigment that did not contain an iron salt in the ring closure melt or water in the drown solvent.
Reaction SMILES: [CH2:1]([CH:3]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][OH:5])[CH3:2].[SH:10][C:11]1[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=1[C:13](O)=[O:14].S(=O)(=O)(O)O>O.C1(C)C=CC=CC=1>[SH:10][C:11]1[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=1[C:13]([O:5][CH2:4][CH:3]([CH2:1][CH3:2])[CH2:6][CH2:7][CH2:8][CH3:9])=[O:14]
Reactant: CCCCC(CC)CO
Reactant: O=C(O)c1ccccc1S
Agent: O=S(=O)(O)O
Solvent: Cc1ccccc1
Solvent: O
Product: CCCCC(CC)COC(=O)c1ccccc1S
Temperature: 25 °C
Reaction time: 6 h
Yield: 95.4 %

Procedure:
2-Ethyl-1-hexanol (21.0 g, 0.161 mol), 2-mercaptobenzoic acid (25.0 g, 0.162 mol), toluene (200 mL), and concentrated sulfuric acid (0.2 mL) were placed in a 500-mL three-neck round-bottom flask equipped with a magnetic stirring bar, a water separator, and a reflux condenser. After the mixture had been heated under reflux with stirring for 6 h, the solid 2-mercaptobenzoic acid had disappeared, and 2.90 mL (0.161 mol) of water had been collected by the water separator. The mixture was allowed to cool to room temperature and washed in succession with 20 mL of saturated NaHCO3 solution and two 50-mL portions of brine. Then the organic layer was dried over anhydrous MgSO4 and freed of solvent by rotary evaporation under vacuum to give 40.9 g (95%) of residual 2-ethylhexyl 2-mercaptobenzoate as a mobile straw-colored oil; 1H NMR (400 MHz, in CDCl3 w/TMS, ppm) 0.88-0.97 (m, 6H, 2CH3), 1.3-1.5 (m, 8H, 4CH2), 1.68-1.78 (m, 1H, CH), 4.21-4.29 (m, 2H, OCH2), 4.73 (s, 1H, SH), 7.1-7.3 [m, 3H, H-4 and H-5 with d (J=3.2 Hz) for H-3 at 7.29], 8.01 (d, J=7.6 Hz, H-6); {1H}13C NMR (100 MHz, in CDCl3 w/TMS, ppm) 166.99 (C═O), 138.49 and 126.39 (C-1 and C-2), 132.53, 131.77, 131.12, and 124.82 (C-3, -4, -5, and -6), 67.86, 39.19, 30.92, 29.33, 24.34, 23.35, 14.44, and 11.46 (8 aliphatic Cs).
Reaction SMILES: [CH2:1]([N:3]([CH2:12][CH3:13])[C:4]1[CH:9]=[CH:8][C:7]([N:10]=O)=[CH:6][CH:5]=1)[CH3:2].[C:14]1([N:20]2[C:24]([NH2:25])=[CH:23][C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[N:21]2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C(O)(=O)C>[CH2:1]([N:3]([CH2:12][CH3:13])[C:4]1[CH:9]=[C:8]2[C:7]([N:10]=[C:23]3[C:22]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[N:21][N:20]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:24]3=[N:25]2)=[CH:6][CH:5]=1)[CH3:2]
Reactant: CCN(CC)c1ccc(N=O)cc1
Reactant: Nc1cc(-c2ccccc2)nn1-c1ccccc1
Solvent: CC(=O)O
Product: CCN(CC)c1ccc2nc3c(-c4ccccc4)nn(-c4ccccc4)c3nc2c1
Yield: 40.7 %

Procedure:
1.78 g N,N-diethyl-p-nitrosoaniline and 2.65 g 1,3-diphenyl-5-aminopyrazole were refluxed for 2 hrs in acetic acid. The mixture was concentrated to half volume. Water was added to get a precipitate, then filtered. The solid was purified by chromatograph column on silica gel. After removing the solvent, 1.6 g pure 7-diethylamino-1,3-diphenyl-1H-pyrazolo[3,4-b]quinoxaline (DEDPPQ) was obtained as a brown solid.
Reaction SMILES: [O:1]1[C:3]2([CH2:8][CH2:7][N:6]([C:9]3[CH:14]=[CH:13][C:12]([N:15]4[CH2:19][C@H:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]4=[O:25])=[CH:11][C:10]=3[F:26])[CH2:5][CH2:4]2)[CH2:2]1.B(F)(F)F.[NH:31]1[CH:35]=[CH:34][N:33]=[CH:32]1>CN(C)C=O>[NH:31]1[CH:35]=[CH:34][N:33]=[C:32]1[CH2:2][C:3]1([OH:1])[CH2:4][CH2:5][N:6]([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:19][C@H:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]3=[O:25])=[CH:11][C:10]=2[F:26])[CH2:7][CH2:8]1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(N3CCC4(CC3)CO4)c(F)c2)C(=O)O1
Reactant: c1c[nH]cn1
Agent: FB(F)F
Solvent: CN(C)C=O
Product: CC(=O)NC[C@H]1CN(c2ccc(N3CCC(O)(Cc4ncc[nH]4)CC3)c(F)c2)C(=O)O1
Yield: 66 %

Procedure:
The compound was obtained by reacting (S)-N-{3-[4-(1-oxa-6-aza-spiro[2.5]oct-6-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1.40 mmol), BF3 etherate (catalytic) and imidazole (1.80 mmol) in dimethylformamide (10 ml) at 80° C. for 8 hours, followed by silica gel column chromatographic separation to provide title compound in 66% yield. M.P. 130-132° C. and MS (M+1)=432 (MH+, 100%) for M.F.=C21H26FN5O4.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([S:10]([N:13]1[CH2:18][CH2:17][CH:16]([C:19]2[C:27]3[C:22](=[C:23]([C:42]([NH2:44])=[O:43])[CH:24]=[C:25]([C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([CH2:34][NH:35][CH2:36]C5SC=CC=5)[CH:29]=4)[CH:26]=3)[NH:21][CH:20]=2)[CH2:15][CH2:14]1)(=[O:12])=[O:11])[CH3:9].S1[CH:49]=[CH:48][CH:47]=C1CN>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:2][C:48]([CH3:47])([CH3:49])[CH2:36][NH:35][CH2:34][C:30]1[CH:29]=[C:28]([C:25]2[CH:26]=[C:27]3[C:22](=[C:23]([C:42]([NH2:44])=[O:43])[CH:24]=2)[NH:21][CH:20]=[C:19]3[CH:16]2[CH2:15][CH2:14][N:13]([S:10]([CH2:8][CH3:9])(=[O:11])=[O:12])[CH2:18][CH2:17]2)[CH:33]=[CH:32][CH:31]=1
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cccc(CNCc5cccs5)c4)cc23)CC1
Reactant: NCc1cccs1
Solvent: O=C(O)C(F)(F)F
Product: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cccc(CNCC(C)(C)C)c4)cc23)CC1
Yield: 59.5 %

Procedure:
The title compound was prepared according to the general procedure of 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(3-{[(2-thienylmethyl)amino]methyl}phenyl)-1H-indole-7-carboxamide trifluoroacetate, substituting 2,2-dimethyl-1-propanamine (30.6 mg, 0.6 mmol) for 1-(2-thienyl)methanamine to afford 30.4 mg of the title compound (59.5%).
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][C:5](=[O:13])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1I.C(=O)([O-])O.[Na+].[CH:19]1([C:25]2[C:33]3[C:28](=[CH:29][C:30]([C:34]([O:36][CH3:37])=[O:35])=[CH:31][CH:32]=3)[NH:27][C:26]=2B2OC(C)(C)C(C)(C)O2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:19]1([C:25]2[C:33]3[C:28](=[CH:29][C:30]([C:34]([O:36][CH3:37])=[O:35])=[CH:31][CH:32]=3)[NH:27][C:26]=2[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[C:5](=[O:13])[NH:4][CH2:3][CH2:2][OH:1])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1
Reactant: COC(=O)c1ccc2c(C3CCCCC3)c(B3OC(C)(C)C(C)(C)O3)[nH]c2c1
Reactant: O=C(NCCO)c1ccccc1I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: COC(=O)c1ccc2c(C3CCCCC3)c(-c3ccccc3C(=O)NCCO)[nH]c2c1
Reaction time: 1 h
Yield: 100.6 %

Procedure:
To a suspension of N-(2-hydroxyethyl)-2-iodobenzamide (5.12 g, 17.5 mmol), sodium hydrogen carbonate (5.80 g, 69.8 mmol) and tetrakis(triphenylphosphine)palladium (2.00 g, 1.73 mmol) in 1,2-dimethoxyethane (70 ml) and water (35 ml) was added methyl 3-cyclohexyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-6-carboxylate (7.50 g, 19.5 mmol) in five divided portions at 90° C., and the mixture was stirred for 1 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was successively washed with water and saturated brine and dried over anhydrous sodium is sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform:methanol=30:1-20:1) to give methyl 3-cyclohexyl-2-[2-(2-hydroxyethylcarbamoyl)phenyl]-1H-indole-6-carboxylate (7.40 g, yield 100%).