Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[Br:2][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:12]2[CH2:16][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[O:14][N:13]=2)[CH:11]=1)[C:6]([OH:8])=O.Cl.[F:24][C:25]1[CH:26]=[CH:27][C:28]([C@H:31]([NH2:33])[CH3:32])=[N:29][CH:30]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>CN(C)C=O>[Br:2][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:12]2[CH2:16][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[O:14][N:13]=2)[CH:11]=1)[C:6]([NH:33][C@@H:31]([C:28]1[CH:27]=[CH:26][C:25]([F:24])=[CH:30][N:29]=1)[CH3:32])=[O:8]
Reactant: C[C@@H](N)c1ccc(F)cn1
Reactant: O=C(O)c1cc(Br)cc(C2=NO[C@H](c3ccccn3)C2)c1
Agent: Cl
Agent: O=C([O-])O
Agent: On1nnc2cccnc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: ClCCCl
Product: C[C@@H](NC(=O)c1cc(Br)cc(C2=NO[C@H](c3ccccn3)C2)c1)c1ccc(F)cn1
Temperature: 25 °C
Reaction time: 18 h
Yield: 94 %

Procedure:
To a solution of 3-bromo-5-[(5S)-5-(2-pyridinyl)-4,5-dihydro-3-isoxazolyl]benzoic acid hydrochloride (0.476 g, 1.24 mmol) in N,N-dimethylformamide (6 mL) were added (1R)-1-(5-fluoropyridin-2-yl)ethanamine hydrochloride (0.330 g, 1.55 mmol), EDC (416 mg, 2.17 mmol), HOAT (0.051 g, 0.372 mmol) and triethylamine (0.865 mL, 6.20 mmol). The reaction mixture was stirred at ambient temperature for 18 h. Saturated aqueous sodium bicarbonate was added. The mixture was extracted with dichloromethane (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (50% hexanes/ethyl acetate→0% hexanes/ethyl acetate) gave the title compound (547 mg). MS 468.9 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([S:15]([NH:18][C:19]2[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=2)[C:22]([OH:24])=O)(=[O:17])=[O:16])=[CH:11][CH:10]=1.C(Cl)(=O)C([Cl:31])=O.CN(C=O)C>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([S:15]([NH:18][C:19]2[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=2)[C:22]([Cl:31])=[O:24])(=[O:17])=[O:16])=[CH:11][CH:10]=1
Reactant: O=C(O)c1cccc(NS(=O)(=O)c2ccc(-c3ccc(Cl)cc3Cl)cc2)c1
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(Cl)c1cccc(NS(=O)(=O)c2ccc(-c3ccc(Cl)cc3Cl)cc2)c1
Temperature: 0 °C

Procedure:
A suspension of 3-(2′,4′-dichlorobiphenyl-4-ylsulfonamido)benzoic acid (1.50 g, 3.56 mmol) in DCM (35 mL) was stirred at 0° C. and oxalyl chloride (340 μL, 3.9 mmol) was added, followed by a catalytic amount of DMF (<50 μL). The mixture was allowed to warm to room temperature and stirred for two days, during which time the solid dissolved to form a light yellow clear solution. The mixture was evaporated under reduced pressure and the residue was azeotroped with toluene (3 mL), then hexane (10 mL) and the title compound obtained as a light brown, slightly gummy, solid (1.5 g) which was used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.OO.NC(N)=[O:13].FC(F)(F)C(O)=O.S(S([O-])=O)([O-])=O.[Na+].[Na+].Cl>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N+:3]=1[O-:13]
Reactant: NC(N)=O
Reactant: Cc1ccc(Cl)nc1
Agent: Cl
Agent: O=S([O-])S(=O)[O-]
Agent: OO
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1ccc(Cl)[n+]([O-])c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 73 %

Procedure:
Into a mixture of 2-chloro-5-methylpyridine (27.4 g, 215 mmol), urea hydrogen peroxide addition compound (42.5 g, 452 mmol), dichloromethane (250 ml) was added dropwise anhydrous trifluoroacetic acid (60.7 ml and 430 mmol) at 0° C., and the reaction mixture was stirred at 0° C. for 1 hour. Then, after stirring for 45 minutes while elevating the reaction temperature to room temperature, an aqueous solution (450 ml) of sodium hydrosulfite (45 g) was added, and the reaction mixture was stirred for 15 minutes. 0.5N hydrochloric acid (400 ml) was added and the mixture was extracted with dichloromethane (400 ml), and after washed with sodium bicarbonate solution, the mixture was dried over magnesium sulfate and the solvent was evaporated, thereby yielding the title compound (22.5 g, 157 mmol, 73%) as a beige solid.
Reaction SMILES: [F:1][C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[CH2:4][NH:5][CH2:6][CH3:7].[CH3:12][O:13][C:14]([C:16]1[CH:33]=[CH:32][CH:31]=[CH:30][C:17]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27](O)=[O:28])=[CH:22][CH:21]=1)=[O:15].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>CN(C=O)C.CCOC(C)=O>[CH2:6]([N:5]([CH2:4][C:3]1[CH:8]=[CH:9][CH:10]=[CH:11][C:2]=1[F:1])[C:27](=[O:28])[CH2:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][O:18][C:17]2[CH:30]=[CH:31][CH:32]=[CH:33][C:16]=2[C:14]([O:13][CH3:12])=[O:15])=[CH:21][CH:22]=1)[CH3:7]
Reactant: CCNCc1ccccc1F
Reactant: COC(=O)c1ccccc1OCc1ccc(CC(=O)O)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCN(Cc1ccccc1F)C(=O)Cc1ccc(COc2ccccc2C(=O)OC)cc1
Temperature: 0 °C
Reaction time: 8 h
Yield: 67.1 %

Procedure:
N-(2-Fluorobenzyl)ethanamine (0.077 g, 0.500 mmol) was dissolved in DMF (10 ml), (4-{[2-(methoxycarbonyl)phenoxy]methyl}phenyl)acetic acid (0.150 g, 0.500 mmol) was added and the mixture was cooled to 0° C. N-[(1H-1,2,3-benzotriazol-1yloxy)(dimethylamino)methylene]-N-methylmethanaminium tetrafluoroborate (0.176 g, 0.549 mmol) and N-ethyl-N,N-diisopropylamine (0.136 g, 1.049 mmol) was added. The solution was stirred overnight at room temperature. EtOAc (20 ml) was added and the organic phase was washed with two portions of Na2CO3 (2×20 ml, aq). The organic layer was dried (MgSO4) and the solvent was removed by evaporation. The crude was purified by preparative HPLC (started with isocratic acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product containing fractions were pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4) and the solvent was removed by evaporation to give 0.146 g of methyl 2-[(4-{2-[ethyl(2-fluorobenzyl)amino]-2-oxoethyl}benzyl)oxy]benzoate (yield 67.1%).
Reaction SMILES: C(N(CC)CC)C.[NH2:8][N:9]1[CH:13]=[CH:12][CH:11]=[C:10]1[C:14]([NH2:16])=[O:15].Cl[C:18]([C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][CH:21]=1)=[O:19]>C(#N)C.ClCCl>[C:14]([C:10]1[N:9]([NH:8][C:18]([C:20]2[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][CH:21]=2)=[O:19])[CH:13]=[CH:12][CH:11]=1)(=[O:15])[NH2:16]
Reactant: COC(=O)c1ccc(C(=O)Cl)cc1
Reactant: NC(=O)c1cccn1N
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CC#N
Product: COC(=O)c1ccc(C(=O)Nn2cccc2C(N)=O)cc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Triethylamine (554 μl, 4.00 mmol) is added to a suspension of 1-amino-1H-pyrrole-2-carboxylic acid amide (501 mg, 4.00 mmol) in acetonitrile (8.0 ml). Then a suspension of methyl 4-chlorocarbonylbenzoate (264 μl, 2.00 mmol) in dichloromethane (4.0 ml) is added slowly. The reaction mixture is stirred at room temperature for 18 hours. The solvents are evaporated and the residue is triturated with water. The solid is filtered off, washed with water and dried under vacuum to give methyl 4-[(2-carbamoylpyrrol-1-yl)carbamoyl]benzoate as white crystals; HPLC/MS 1.45 min (C), [M+H] 288.
Reaction SMILES: O=[C:2]1[C:6]2([CH2:10][CH2:9][CH2:8][CH2:7]2)[CH2:5][N:4]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:3]1.[BH4-].[Na+].[NH3:20]>>[NH2:20][CH:2]1[C:6]2([CH2:10][CH2:9][CH2:8][CH2:7]2)[CH2:5][N:4]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:3]1
Reactant: CC(C)(C)OC(=O)N1CC(=O)C2(CCCC2)C1
Reactant: N
Agent: [BH4-]
Agent: [Na+]
Product: CC(C)(C)OC(=O)N1CC(N)C2(CCCC2)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 58 %

Procedure:
To a solution of tert-butyl 4-oxo-2-azaspiro[4.4]nonane-2-carboxylate (8.56 g, 35.77 mmol) in ammonia (7M in methanol, 100 mL) was added Ti(Oi-Pr)4 (22.37 g, 78.6 mmol) and the reaction mixture was stirred at rt overnight. Then NaBH4 (2.71 g, 71.54 mmol) was added portion-wise and the resulting mixture was stirred at rt for another 2 h and concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=10/1) to give the product as yellow oil (5 g, 58%).
Reaction SMILES: [O-]CC.[Na+].[NH2:5][C:6]([NH2:8])=[O:7].C([O:11][C:12](=O)[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][C:25]([CH:28]([C:36](=[O:40])[N:37]([CH3:39])[CH3:38])[CH2:29][C:30]3[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=3)=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)C.FC(F)(F)C(O)=O>O.C(OCC)(=O)C>[CH3:39][N:37]([CH3:38])[C:36](=[O:40])[CH:28]([C:25]1[CH:26]=[CH:27][C:22]([O:21][C:18]2[CH:17]=[CH:16][C:15]([CH2:14][CH2:13][C:12](=[O:11])[NH:5][C:6]([NH2:8])=[O:7])=[CH:20][CH:19]=2)=[CH:23][CH:24]=1)[CH2:29][C:30]1[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=1
Reactant: CCOC(=O)CCc1ccc(Oc2ccc(C(Cc3cccnc3)C(=O)N(C)C)cc2)cc1
Reactant: NC(N)=O
Agent: CC[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: CN(C)C(=O)C(Cc1cccnc1)c1ccc(Oc2ccc(CCC(=O)NC(N)=O)cc2)cc1
Temperature: 80 °C

Procedure:
A mixture of sodium ethoxide (21% w/w, 8.10 mL, 21.8 mmol) and ethyl acetate (0.6 mL) was refluxed for 30 min. Urea (1.30 g, 21.8 mmol) was added and heated till it dissolved completely. 3-{4-[4-(1-Dimethylcarbamoyl-2-pyridin-3-ylethyl)-phenoxy]-phenyl}-propionic acid ethyl ester, 80 (1.74 g, 3.80 mmol) was added and heated for 5 min at 80° C. Reaction mixture was cooled to room temperature, neutralized by trifluoroacetic acid and water (50 mL) was added and extracted with ethyl acetate (3×50 mL). Organic layer was washed with water (2×20 mL) and brine (50 mL). The compound was purified by silica gel chromatography and product was eluted with chloroform-methanol (97:3). Yield: 0.30 g (16.7%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][CH2:10][CH2:9][C:8](=[O:12])[NH:7][C:6]=2[CH:13]=1.Cl[C:15]1[N:20]=[C:19]([NH:21][C:22]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:23]=2[C:24]([NH2:26])=[O:25])[C:18]([Cl:32])=[CH:17][N:16]=1>>[Cl:32][C:18]1[C:19]([NH:21][C:22]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:23]=2[C:24]([NH2:26])=[O:25])=[N:20][C:15]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[CH2:11][CH2:10][CH2:9][C:8](=[O:12])[NH:7][C:6]=3[CH:13]=2)=[N:16][CH:17]=1
Reactant: Nc1ccc2c(c1)NC(=O)CCC2
Reactant: NC(=O)c1cccc(F)c1Nc1nc(Cl)ncc1Cl
Product: NC(=O)c1cccc(F)c1Nc1nc(Nc2ccc3c(c2)NC(=O)CCC3)ncc1Cl

Procedure:
Title compound was prepared from 8-Amino-1,3,4,5-tetrahydro-benzo[b]azepin-2-one and 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-benzamide in an analogous manner to Example 1221d. Title compound isolated as a moss green solid (86 mg, 69%). HPLC purity 90%, LCMS 443.03 (M+H), HNMR (DMSO) 9.92 (bs, 1H), 9.82 (bs, 1H), 9.32 (s, 1H), 8.30 (d, J=1.9 Hz, 1H), 8.03 (s, 1H), 7.71 (s, 1H), 7.54 (s, 1H), 7.47-7.38 (m, 3H), 7.15-7.13 (m, 1H), 6.99-6.90 (m, 2H). 2.60-2.56 (m, 2H), 2.07-2.03 (m, 4H).
Reaction SMILES: [O:1]1[C@H:5]([C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([O:14][CH3:15])=[O:13])[CH:7]=2)[C@H:2]1[CH2:3][OH:4].C(Cl)Cl>CCCCCC.C(OCC)(=O)C>[O:1]1[C@H:5]([C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([O:14][CH3:15])=[O:13])[CH:7]=2)[C@H:2]1[CH:3]=[O:4]
Reactant: COC(=O)c1cccc([C@H]2O[C@@H]2CO)c1
Solvent: CCCCCC
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: COC(=O)c1cccc([C@H]2O[C@@H]2C=O)c1

Procedure:
The title compound is prepared analogously to Example 5a) from (2R,3R)-2,3-epoxy-3-(3-methoxycarbonylphenyl)-propanol; light-yellow oil; IR (methylene chloride): 2950, 2820, 1725, 1610, 1590, 1430, 1290, 1255 cm-1 ; Rf =0.33 (hexane/ethyl acetate 3:2).
Reaction SMILES: [Br:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][NH:7][C@@H:8]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:9]([OH:11])=O)=[CH:4][CH:3]=1.C1CN([P+](O[N:35]2N=[N:42][C:37]3C=CC=C[C:36]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl.NCC#N.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C@@H:8]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:9]([NH:42][CH2:37][C:36]#[N:35])=[O:11])=[CH:16][CH:17]=1
Reactant: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Reactant: CC(C)C[C@H](NCc1ccc(Br)cc1)C(=O)O
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Agent: N#CCN
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)C[C@H](NCc1ccc(Br)cc1)C(=O)NCC#N
Reaction time: 4 h

Procedure:
To (2S)-2-[(4-bromobenzyl)amino]-4-methylpentanoic acid (1.343 g, 4.62 mmol), PyBOP (2.65 g, 5.08 mmol), aminoacetonitrile hydrochloride (940 mg, 10.16 mmol) in dry DMF (30 mL) under dry nitrogen was added triethylamine (2.2 mL, 15.71 mmol) dropwise and the reaction was stirred for 4 hours. Aqueous sat. NaHCO3 was added and the product extracted with Et2O (2×), dried on Na2SO4, concentrated in vacuo, and purified by flash chromatography over silica gel (EtOAc/Hex, 4/6 then 1/1) to afford (2S)-2-[(4-bromobenzyl)amino]-N-(cyanomethyl)-4-methylpentanamide.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[N:7]1([C:13]2[CH:18]=[CH:17][C:16]([CH2:19][C:20](OC)=[O:21])=[C:15]([CH3:24])[CH:14]=2)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.O.[OH-].[Na+]>O1CCCC1>[N:7]1([C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][OH:21])=[C:15]([CH3:24])[CH:14]=2)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1
Reactant: COC(=O)Cc1ccc(N2CCCCC2)cc1C
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1cc(N2CCCCC2)ccc1CCO
Temperature: 0 °C
Reaction time: 2 h
Yield: 87.8 %

Procedure:
To a mixture of lithium aluminum hydride (2.53 g, 66.7 mmol) in tetrahydrofuran (100 ml) was added dropwise methyl (4-piperidin-1-yl-methyl-phenyl)acetate (5.50 g, 22.2 mmol) at 0° C. under nitrogen atmosphere. The mixture was stirred at 0° C. for 2 hours. Water (2.5 ml), 15 wt % aqueous solution of sodium hydroxide (2.5 ml) and water (7.5 ml) was added to the mixture sequentially at 0° C. The mixture was filtrated through a pad of Celite, and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent; ethyl acetate/methanol=90/10 to 80/20) to afford 2-(4-piperidin-1-yl-methyl-phenyl)ethanol as a colorless oil (4.27 g, 19.5 mmol, 88%).
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:14])[CH2:5][CH:6]([NH2:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:15]1([CH:23]=O)[C:16]([CH:21]=[O:22])=[CH:17][CH:18]=[CH:19][CH:20]=1>ClCCl>[CH3:2][O:3][C:4](=[O:14])[CH2:5][CH:6]([N:13]1[CH2:23][C:15]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:21]1=[O:22])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: O=Cc1ccccc1C=O
Reactant: COC(=O)CC(N)c1ccccc1
Agent: Cl
Solvent: ClCCl
Product: COC(=O)CC(c1ccccc1)N1Cc2ccccc2C1=O

Procedure:
3-Amino-3-phenyl-propionic acid methyl ester hydrochloride (1.3 mmol, 1 eq), benzene-1,2-dicarbaldehyde (0.8 eq) and glacial acid (15 eq) are dissolved in dichloromethane and refluxed for 2 h (J. Chem. Soc., Chem Commun 1985, 1183). The mixture is concentrated in vacuo and partitioned between dichloromethane and water. The organic phase is dried over Na2SO4, filtered and concentrated in vacuo. 3-(1-Oxo-1,3-dihydro-isoindole-2-yl)-3-phenyl-propionic acid methyl ester is obtained as a brown solid (83% yield); ES-MS (MH+)=296.2; 1H-NMR (DMSO-d6, 400 MHz): δ [ppm] 7.73-7.30 (m, 9H), 5.82-5.78 (m, 1H), 4.54 (d, 1H, 17.4 Hz), 4.14 (d, 1H, 17.4 Hz), 3.57 (s, 3H), 3.31-3.28 (m, 2H).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[C:12](=[N:15][NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19](Br)[C:18]=3[O:24][CH3:25])[C:11]([CH3:26])=[N:10]2)[CH:5]=[CH:6][C:7]=1[CH3:8].[C:27]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)([OH:29])=[O:28].[OH-].[K+].O>C(O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH3:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[C:12](=[N:15][NH:16][C:17]3[C:18]([O:24][CH3:25])=[C:19]([C:34]4[CH:33]=[CH:32][CH:31]=[C:30]([C:27]([OH:29])=[O:28])[CH:35]=4)[CH:20]=[CH:21][CH:22]=3)[C:11]([CH3:26])=[N:10]2)[CH:5]=[CH:6][C:7]=1[CH3:8]
Reactant: O=C(O)c1cccc(B(O)O)c1
Reactant: COc1c(Br)cccc1NN=C1C(=O)N(c2ccc(C)c(C)c2)N=C1C
Agent: Cl[Pd]Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: COc1c(NN=C2C(=O)N(c3ccc(C)c(C)c3)N=C2C)cccc1-c1cccc(C(=O)O)c1
Reaction time: 24 h

Procedure:
A mixture of 1-(3,4-dimethylphenyl)-3-methyl-4-(3-bromo-2-methoxyphenyl)hydrazono-5-pyrazolone (5 g) prepared as in Example 2, and 3-carboxyphenylboronic acid (2.99 g), bis(triphenylphosphine)palladium(II)chloride [PdCl2(PPh3)2] (0.42 g), potassium hydroxide (1.74 g) in ethanol. (250 mL) and water (30 mL) was heated to about reflux temperature and stirred for about 24 hours. The hot mixture was filtered to remove the catalyst. The clear filtrate was concentrated under vacuum. To the residue, water (100 mL) was added; acidified to pH 3-5 using hydrochloric acid and stirred for about 30 minutes at about room temperature. The slurry was filtered to give a yellowish orange solid product, which was washed with water (50 mL) and dried in an oven at about 55° C. to about 60° C. for about 12 hours.