Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C@:2]12[C:11]3=[CH:12][CH2:13][C@@:14]([CH:17]=[CH2:18])([CH3:16])[CH2:15][CH:10]3[CH2:9][CH2:8][CH:7]1[C@@:6]([C:20](O)=[O:21])([CH3:19])[CH2:5][CH2:4][CH2:3]2.C(Cl)(=O)C(Cl)=O.[CH2:29]([N:31](CC)[CH2:32][CH3:33])[CH3:30].N1CCCC1>C(Cl)Cl.CN(C=O)C>[CH3:19][C@@:6]1([C:20]([N:31]2[CH2:32][CH2:33][CH2:30][CH2:29]2)=[O:21])[CH:7]2[C@@:2]([CH3:1])([C:11]3[CH:10]([CH2:9][CH2:8]2)[CH2:15][C@:14]([CH3:16])([CH:17]=[CH2:18])[CH2:13][CH:12]=3)[CH2:3][CH2:4][CH2:5]1
Reactant: C=C[C@@]1(C)CC=C2C(CCC3[C@](C)(C(=O)O)CCC[C@@]23C)C1
Reactant: CCN(CC)CC
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: C1CCNC1
Solvent: CN(C)C=O
Product: C=C[C@]1(C)CC=C2C(CCC3[C@@](C)(C(=O)N4CCCC4)CCC[C@]23C)C1
Temperature: 25 °C
Reaction time: 3 h
Yield: 71 %

Procedure:
A solution of acanthoic acid 1 (30 mg, 0.10 mmol) in CH2Cl2 (3.0 ml) was treated with oxalyl chloride (0.013 ml, 0.15 mmol) in the presence of a catalytic amount of DMF at room temperature. The reaction mixture was stirred for 3 h at room temperature, distilled under reduced pressure, and then 3 ml of CH2Cl2 was added. Triethylamine (0.03 ml, 0.20 mmol) and pyrrolidine (0.02 ml, 0.20 mmol) were added to the reaction mixture. The reaction mixture was stirred for 30 min., quenched with water and extracted with 5 ml of CH2Cl2. The organic layer was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:10) to afford 25 mg of the analog 2 (71%).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[N+:8]([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][N+:16]#[C-:17])#[C-:9].[CH:18](=O)[C:19]1[O:23][CH:22]=[CH:21][CH:20]=1>Cl(O)(=O)(=O)=O>[O:23]1[CH:22]=[CH:21][CH:20]=[C:19]1[C:18]1[N:1]=[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]2[C:9]=1[NH:8][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][N+:16]#[C-:17]
Reactant: [C-]#[N+]CCCCCC[N+]#[C-]
Reactant: O=Cc1ccco1
Reactant: Nc1ccccn1
Agent: [O-][Cl+3]([O-])([O-])O
Product: [C-]#[N+]CCCCCCNc1c(-c2ccco2)nc2ccccn12

Procedure:
Compound (2) was prepared in accordance with general instructions 1 from 1.0 ml 2-aminopyridine solution (0.1 M, MC), 0.575 ml 1,6-diisocyanohexane solution (0.2 M, MC), 0.500 ml furfural solution (0.3 M, MC), and 10 μl perchloric acid (w=20%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:32])[C@@H:4]([NH:14][C:15]([C:17]1[CH:26]=[C:25]([O:27][CH2:28][C:29](O)=[O:30])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]=1)=[O:16])[CH2:5][CH2:6][C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH2:33](Cl)CCl.FC1C(O)=C(F)C(F)=C(F)C=1F.FC(F)(F)C(O)=O.[CH:56]1([NH:59][C:60]([C@@H:62]2[CH2:66][CH2:65][CH2:64][NH:63]2)=[O:61])[CH2:58][CH2:57]1>C(Cl)Cl.O>[CH3:1][O:2][C:3](=[O:32])[C@@H:4]([NH:14][C:15]([C:17]1[CH:26]=[C:25]([O:27][CH2:28][C:29]([N:63]2[CH2:64][CH2:65][CH2:66][C@H:62]2[C:60](=[O:61])[NH:59][CH:56]2[CH2:58][CH2:57][CH2:33]2)=[O:30])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]=1)=[O:16])[CH2:5][CH2:6][C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8]
Reactant: COC(=O)[C@H](CCC(=O)OC(C)(C)C)NC(=O)c1cc(OCC(=O)O)c2ccccc2n1
Reactant: ClCCCl
Reactant: O=C(NC1CC1)[C@@H]1CCCN1
Agent: Oc1c(F)c(F)c(F)c(F)c1F
Solvent: O=C(O)C(F)(F)F
Solvent: O
Solvent: ClCCl
Product: COC(=O)[C@H](CCC(=O)OC(C)(C)C)NC(=O)c1cc(OCC(=O)N2CCC[C@H]2C(=O)NC2CCC2)c2ccccc2n1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 4 g of (S)-2-[(4-Carboxymethoxy-quinoline-2-carbonyl)-amino]-pentanedioic acid 5-tert-butyl ester 1-methyl ester in 30 ml of DCM, 3.4 g of EDC and 3.2 g of pentafluorophenol was added and the reaction mixture was stirred for 2 h at RT. Then, 5 g of (S)-Pyrrolidine-2-carboxylic acid cyclopropylamide trifluoroacetate salt and 2 g of NEM in 10 ml of DCM was added. After 3 h the reaction mixture was diluted with water and extracted with DCM (3×150 ml). The combined organic phases were dried over MgSO4 and the solvents were removed under reduced pressure. The crude product was purified by chromatography on silica gel eluting with a gradient of n-heptane/ethyl acetate. The fractions containing the product were combined and the solvent evaporated under reduced pressure. Yield: 1.8 g.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([C:11]2[C:16]([NH2:17])=[CH:15][CH:14]=[C:13]([CH3:18])[N:12]=2)=[O:10])=[N:6][CH:7]=1.Br[C:20]1[CH:21]=[N:22][CH:23]=[N:24][CH:25]=1>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([C:11]2[C:16]([NH:17][C:20]3[CH:21]=[N:22][CH:23]=[N:24][CH:25]=3)=[CH:15][CH:14]=[C:13]([CH3:18])[N:12]=2)=[O:10])=[N:6][CH:7]=1
Reactant: Brc1cncnc1
Reactant: Cc1ccc(N)c(C(=O)Nc2ccc(F)cn2)n1
Product: Cc1ccc(Nc2cncnc2)c(C(=O)Nc2ccc(F)cn2)n1

Procedure:
The title compound, MS (ISP): m/e=325.0 (M+H+), was prepared from 3-Amino-6-methyl-pyridine-2-carboxylic acid (5-fluoro-pyridin-2-yl)-amide in accordance with the general method of example 20 using 5-bromopyrimidine instead of 3-Bromopyridine.
Reaction SMILES: [Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[C:16](I)[CH:17]=3)[N:12]([CH:22]3[CH2:24][CH2:23]3)[CH:11]=2)=[O:9])=[CH:4][CH:3]=1.C(NCC)C.[CH2:32]([OH:35])[C:33]#[CH:34]>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:34]#[C:33][CH2:32][OH:35])[CH:17]=3)[N:12]([CH:22]3[CH2:24][CH2:23]3)[CH:11]=2)=[O:9])=[CH:4][CH:3]=1
Reactant: O=C(NCc1ccc(Cl)cc1)c1cn(C2CC2)c2ccc(I)cc2c1=O
Reactant: C#CCO
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCNCC
Solvent: CN(C)C=O
Product: O=C(NCc1ccc(Cl)cc1)c1cn(C2CC2)c2ccc(C#CCO)cc2c1=O
Reaction time: 8 h

Procedure:
To a dry flask under an atmosphere of argon gas containing 0.24 g of N-(4-chlorobenzyl)-1-cyclopropyl-6-iodo-4-oxo-1,4-dihydro-3-quinolinecarboxamide from Preparation No. 20, 0.01 g of copper (I) iodide and 0.04 g of dichlorobis(triphenylphosphine)palladium (II) is added diethylamine (1.5 mL) and propargyl alcohol (0.04 mL). After 3 hours reaction is diluted with DMF (0.5 mL) and left to stir overnight. The reaction is concentrated under reduced pressure, diluted with dichloromethane containing a small amount of methanol, and partioned against water. The organic layer is washed with brine, dried and concentrated under reduced pressure. The residue is adsorbed onto silica and chromatographed on silica eluting with 2% to 6% methanol in dichloromethane . The product-containing fractions are combined and concentrated under reduced pressure to afford 0.17 g of the title compound as a solid.
Reaction SMILES: [CH3:1][C:2]1[C:6]2[C:7](=[O:18])[N:8]([CH2:11][CH2:12][N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[CH2:9][CH2:10][C:5]=2[NH:4][C:3]=1[CH:19]=O.[Cl:21][C:22]1[C:23]([F:38])=[C:24]([C:28]2[CH:36]=[CH:35][CH:34]=[C:33]3[C:29]=2[CH2:30][C:31](=[O:37])[NH:32]3)[CH:25]=[CH:26][CH:27]=1>>[Cl:21][C:22]1[C:23]([F:38])=[C:24]([C:28]2[CH:36]=[CH:35][CH:34]=[C:33]3[C:29]=2[C:30](=[CH:19][C:3]2[NH:4][C:5]4[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][N:13]5[CH2:14][CH2:15][CH2:16][CH2:17]5)[C:7](=[O:18])[C:6]=4[C:2]=2[CH3:1])[C:31](=[O:37])[NH:32]3)[CH:25]=[CH:26][CH:27]=1
Reactant: Cc1c(C=O)[nH]c2c1C(=O)N(CCN1CCCC1)CC2
Reactant: O=C1Cc2c(cccc2-c2cccc(Cl)c2F)N1
Product: Cc1c(C=C2C(=O)Nc3cccc(-c4cccc(Cl)c4F)c32)[nH]c2c1C(=O)N(CCN1CCCC1)CC2
Yield: 28.5 %

Procedure:
The title compound was prepared under the same conditions as described in Example 13 with 3-methyl-4-oxo-5-(2-pyrrolidin-1-yl-ethyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde and 4-(3-chloro-2-fluoro-phenyl)-1,3-dihydro-indol-2-one (prepared according to WO2002055517) as starting materials to give 2-[4-(3-chloro-2-fluoro-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidenemethyl]-3-methyl-5-(2-pyrrolidin-1-yl-ethyl)-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (24 mg, 28.5%) as a yellow solid.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[H-].[Na+].C([O:15][C:16](=O)[C:17]([C:29]#[N:30])=[CH:18][C:19]1[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[C:21]([O:27][CH3:28])[CH:20]=1)C>C1COCC1>[CH3:28][O:27][C:21]1[CH:20]=[C:19]([C:18]2[CH:17]([C:29]#[N:30])[C:16](=[O:15])[O:1][C:2]3[C:10]=2[CH:9]=[CH:8][C:7]2=[N:6][CH:5]=[CH:4][C:3]=32)[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=1
Reactant: Oc1cccc2[nH]ccc12
Reactant: CCOC(=O)C(C#N)=Cc1cc(OC)cc(OC)c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1cc(OC)cc(C2=c3ccc4c(c3OC(=O)C2C#N)C=CN=4)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 1.1 %

Procedure:
To a solution of 3,5-dimethoxybenzaldehyde (1.35 g, 8.12 mmol) and ethyl cyanoacetate (0.92 ml, 8.1 mmol) in ethanol (10 mL) was added piperidine (0.4 mL, 4 mmol). The mixture was stirred at room temperature for approximately 2 h. A precipitate formed, which was collected by filtration and dried to yield approximately 2.12 g of a white solid, which was used directly in the next step. To a solution of 4-hydroxyindole (250 mg, 1.91 mmol) in THF (10 mL) was added sodium hydride (153 mg, 3.80 mmol, 60%) and the mixture was stirred at room temperature for approximately 10 min. To the mixture was added a solution of 3-(3,5-dimethoxyphenyl)-2-cyano-acrylic acid ethyl ester (500 mg, 1.91 mmol, prepared as described above) in THF (2 mL). The mixture was heated at approximately 60° C. overnight. The solvent was evaporated and the residue was purified by flash column chromatography (silica gel, EtOAc:hexane, 1:2), yielding 7 mg (1.1%) of the title compound. 1H NMR (CDCl3): 8.64 (brs, 1H), 7.35-7.24 (m, 2H), 7.19-7.16 (m, 1H), 7.04 (s, 1H), 6.65-6.59 (m, 3H), 3.85 (s, 6H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][CH:14]3[CH2:17][N:16]([C:18]([CH:20]4[CH2:22][CH2:21]4)=[O:19])[CH2:15]3)=[N:11][NH:10][C:9]2=[O:23])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[CH:34][C:35]3[O:39][CH:38]=[CH:37][C:36]=3[CH:40]=2)O1.C(=O)([O-])[O-].[K+].[K+].Cl>O1CCOCC1.O>[O:39]1[C:35]2[CH:34]=[CH:33][C:32]([C:2]3[CH:7]=[CH:6][C:5]([N:8]4[C:12]([CH2:13][CH:14]5[CH2:17][N:16]([C:18]([CH:20]6[CH2:22][CH2:21]6)=[O:19])[CH2:15]5)=[N:11][NH:10][C:9]4=[O:23])=[CH:4][CH:3]=3)=[CH:40][C:36]=2[CH:37]=[CH:38]1
Reactant: O=C(C1CC1)N1CC(Cc2n[nH]c(=O)n2-c2ccc(Br)cc2)C1
Reactant: CC1(C)OB(c2ccc3occc3c2)OC1(C)C
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: O=C(C1CC1)N1CC(Cc2n[nH]c(=O)n2-c2ccc(-c3ccc4occc4c3)cc2)C1
Temperature: 100 °C
Reaction time: 22 h
Yield: 40.6 %

Procedure:
In a microwave vial purged with nitrogen, a mixture of 4-(4-bromophenyl)-5-{[1-(cyclopropylcarbonyl)-3-azetidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (83 mg, 0.220 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (9 mg, 11 μmol), and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (59 mg, 0.242 mmol) in 1,4-dioxane (2 mL) and 2M aq potassium carbonate (0.5 mL, 1.00 mmol) was stirred at 100° C. in an oil bath for 22 h. Additional 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (59 mg, 0.242 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (9 mg, 11 μmol) were added and the reaction mixture was heated at 100° C. in an oil bath for 20 h. The reaction was cooled to room temperature, poured into water (50 mL), and adjusted to pH˜4.5 with 1N aq HCl. The aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification of the residue by flash chromatography (ethyl acetate, then 0-10% methanol/ethyl acetate) followed by a second purification by reverse phase HPLC (20-70% acetonitrile/water+0.1% NH4OH) provided the title compound as an ivory solid (37 mg, 38%). MS(ES)+ m/e 415.2 [M+H]+.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:13])[CH:7]=[C:8]([CH3:12])[O:9]2)=[CH:4][CH:3]=1.Br[CH2:15][CH2:16][CH2:17][Cl:18].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.C(OCC)C>[Cl:18][CH2:17][CH2:16][CH2:15][O:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:13])[CH:7]=[C:8]([CH3:12])[O:9]2)=[CH:4][CH:3]=1
Reactant: ClCCCBr
Reactant: Cc1cc(=O)c2ccc(O)cc2o1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CCOCC
Product: Cc1cc(=O)c2ccc(OCCCCl)cc2o1
Yield: 94.2 %

Procedure:
3.9 g (20 mmole) of 7-hydroxy-2-methylchromen-4-one, 4.4 ml (40 mmole) of 1-bromo-3-chloropropane and 6.1 g (40 mmole) of anhydrous potassium carbonate in 100 ml of acetone were mixed and refluxed under heating for 16 hours. The mixture was allowed to cool and the insoluble solid was separated by filtration. The filtrate was evaporated to dryness, and the residue obtained was suspended in ethyl ether, filtered, washed with ether and dried at vaccum to yield 4.76 g (85%) of the product, melting point 113°-115° C.
Reaction SMILES: CCO[C:4]([C:6]1[C:12](C)=[CH:11][C:9](=[O:10])[O:8][C:7]=1C)=O.[OH-:15].[Na+].Cl>O>[CH3:4][CH:6]1[C:7](=[O:15])[O:8][C:9](=[O:10])[CH:11]=[CH:12]1
Reactant: CCOC(=O)c1c(C)cc(=O)oc1C
Reactant: [OH-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CC1C=CC(=O)OC1=O

Procedure:
The procedure found in J. Am. Chem. Soc. 75, 2377-9 (1953) was generally followed. Ethyl isodehydroacetate (100 g, 0.51 mol) was added to a warm solution of sodium hydroxide (68.5 g., 0.71 mol) in water (500 mL) and stirred for an hour until the mixture became clear. The solution was acidified with concentrated hydrochloric acid (200 mL) and was extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated by evaporation under reduced pressure. The residue was mixed with acetic anhydride (250 mL) and the resulting mixture was heated at reflux for 20-30 min. The solvent was removed by evaporation under reduced pressure and the residue obtained was crystallized from ether to obtain 60.8 g (94 percent of theory) of the title compound as a tan powder melting at 70°-72° C.
Reaction SMILES: Cl.Cl.[NH2:3][C:4]1[CH:36]=[CH:35][C:7]([O:8][C:9]2[CH:10]=[CH:11][C:12]3[N:16]=[C:15]([CH2:17][O:18][C:19]4[CH:32]=[CH:31][C:22]([CH2:23][CH:24]5[S:28][C:27](=[O:29])[NH:26][C:25]5=[O:30])=[CH:21][CH:20]=4)[N:14]([CH3:33])[C:13]=3[CH:34]=2)=[CH:6][CH:5]=1.[C:37]([C:41]1[CH:42]=[C:43]([CH:47]=[C:48]([C:51]([CH3:54])([CH3:53])[CH3:52])[C:49]=1[OH:50])[C:44](O)=[O:45])([CH3:40])([CH3:39])[CH3:38].C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O>[C:51]([C:48]1[CH:47]=[C:43]([CH:42]=[C:41]([C:37]([CH3:40])([CH3:39])[CH3:38])[C:49]=1[OH:50])[C:44]([NH:3][C:4]1[CH:36]=[CH:35][C:7]([O:8][C:9]2[CH:10]=[CH:11][C:12]3[N:16]=[C:15]([CH2:17][O:18][C:19]4[CH:32]=[CH:31][C:22]([CH2:23][CH:24]5[S:28][C:27](=[O:29])[NH:26][C:25]5=[O:30])=[CH:21][CH:20]=4)[N:14]([CH3:33])[C:13]=3[CH:34]=2)=[CH:6][CH:5]=1)=[O:45])([CH3:54])([CH3:53])[CH3:52]
Reactant: Cn1c(COc2ccc(CC3SC(=O)NC3=O)cc2)nc2ccc(Oc3ccc(N)cc3)cc21
Reactant: CC(C)(C)c1cc(C(=O)O)cc(C(C)(C)C)c1O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cn1c(COc2ccc(CC3SC(=O)NC3=O)cc2)nc2ccc(Oc3ccc(NC(=O)c4cc(C(C)(C)C)c(O)c(C(C)(C)C)c4)cc3)cc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 34.1 %

Procedure:
To a mixture of 5-[4-[6-(4-aminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride (400 mg) and 3,5-di-t-butyl-4-hydroxybenzoic acid (204 mg) in anhydrous N,N-dimethylformamide (8 ml) were added triethylamine (0.32 ml) and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (153 mg). The mixture was stirred at room temperature for 1 hour and then allowed to stand at room temperature overnight. To the reaction mixture was further added triethylamine (0.10 ml) and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (134 mg) and this mixture was stirred at room temperature for 8 hours and allowed to stand at room temperature overnight. The reaction mixture was concentrated under reduced pressure and partitioned between ethyl acetate and water. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated. The residue was chromatographed on a silica gel column using ethyl acetate:n-hexane=2:1→3:1 as the eluant to afford the title compound (176 mg, mp 160-162° C.).
Reaction SMILES: I[C:2]1[CH:3]=[N:4][O:5][C:6]=1[CH3:7].[CH3:8][O:9][C:10]1[N:15]=[C:14]([CH3:16])[C:13](B(O)O)=[CH:12][CH:11]=1.C(=O)(O)[O-].[Na+].O>COCCOC>[CH3:16][C:14]1[C:13]([C:2]2[CH:3]=[N:4][O:5][C:6]=2[CH3:7])=[CH:12][CH:11]=[C:10]([O:9][CH3:8])[N:15]=1
Reactant: Cc1oncc1I
Reactant: COc1ccc(B(O)O)c(C)n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: COc1ccc(-c2cnoc2C)c(C)n1
Temperature: 25 °C
Yield: 40.2 %

Procedure:
A mixture of 4-iodo-5-methylisoxazole (18.2 g, 87 mmol), 6-methoxy-2-methylpyridine-3-boronic acid (14.6 g, 87 mmol), sodium bicarbonate (22.0 g, 262 mmol), water (150 mL) and DME (150 mL) was degassed three times with stirring by the application of a vacuum and then introduction of a nitrogen atmosphere. [1,1-Bis(diphenylphosphino)ferrocene]-dichloropalladium (II) (2.14 g, 2.6 mmol) was added in one portion. The reaction mixture was degassed as before. The reaction mixture was then stirred at 80° C. for 4 h, then it was cooled to ambient temperature. Three extractions with EtOAc, drying the combined organic layers over MgSO4, filtration and removal of solvent in vacuo afforded an oil. Flash chromatography (EtOAc:hexane::1:9) and removal of solvent in vacuo from the desired fractions gave the product (7.15 g): 1H-NMR(CDCl3, 300 MHz): δ 8.16 (s, 1H), 7.33 (d, 1H, J=8), 6.63 (d, 1H, J=8), 3.95 (s, 3H), 2.35 (s, 6H); APCI+−MS: 205 (M++H).
Reaction SMILES: [CH:1]([CH:3]([CH:9]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:4]([O:6]CC)=O)=O.[C:21]([NH:25][S:26]([C:29]1[CH:30]=[N:31][C:32]([NH:35][NH2:36])=[CH:33][CH:34]=1)(=[O:28])=[O:27])([CH3:24])([CH3:23])[CH3:22].C(NS(C1C=CC(N2C(=O)C(C(C3C=CC=CC=3)C(OC)=O)=CN2)=NC=1)(=O)=O)(C)(C)C>>[C:21]([NH:25][S:26]([C:29]1[CH:34]=[CH:33][C:32]([N:35]2[C:4](=[O:6])[C:3]([CH:9]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:1][NH:36]2)=[N:31][CH:30]=1)(=[O:28])=[O:27])([CH3:24])([CH3:22])[CH3:23]
Reactant: CC(C)(C)NS(=O)(=O)c1ccc(NN)nc1
Reactant: CCOC(=O)C(C=O)C(C(=O)OCC)c1ccccc1
Agent: COC(=O)C(c1ccccc1)c1c[nH]n(-c2ccc(S(=O)(=O)NC(C)(C)C)cn2)c1=O
Product: CCOC(=O)C(c1ccccc1)c1c[nH]n(-c2ccc(S(=O)(=O)NC(C)(C)C)cn2)c1=O

Procedure:
According to the process described in Example 27.2, starting with 2 g (7.19 mmol) of diethyl 2-formyl-3-phenylbutanedioate and 1.75 g (7.19 mmol) of N-tert-butyl-6-hydrazinylpyridine-3-sulfonamide, 3.1 g of methyl {2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-3-oxo-2,3-dihydro-1H-pyrazol-4-yl}(phenyl)acetate are obtained in the form of a powder.
Reaction SMILES: [C:1]1([C:7]([CH:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])[OH:10])=[CH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Mn]([O-])([O-])(=O)=O.[Ba+2]>C1(C)C=CC=CC=1>[Cl:18][C:12]1[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:11]=1[C:9](=[O:10])[C:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)=[CH2:8]
Reactant: C=C(c1ccccc1)C(O)c1ccc(Cl)cc1Cl
Agent: O=[Mn](=O)([O-])[O-]
Agent: [Ba+2]
Solvent: Cc1ccccc1
Product: C=C(C(=O)c1ccc(Cl)cc1Cl)c1ccccc1

Procedure:
To a solution of α-(1-phenylethenyl)-2,4-dichlorobenzenemethanol (4 g) in toluene (100 ml) was added barium manganate (5 g) and the resulting mixture heated at reflux under an atmosphere of nitrogen for a period of 12 hours. The reaction mixture was cooled, filtered and concentrated under reduced pressure to yield 1-(2,4-dichlorophenyl)-2-phenylpropen-1-one, (δ (CDCl3), 5.75 (1H,s), 6.3 (1H,s) and 7.25-7.60 (8H,m)) as a gum (4.3 g) having the formula: ##STR27##
Reaction SMILES: [C:1]([CH2:3][NH:4][C:5]([C:7]1([NH2:13])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:6])#[N:2].Cl.[CH:15]([N:18]1[CH2:23][CH2:22][N:21]([C:24]2[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][CH:25]=2)[CH2:20][CH2:19]1)([CH3:17])[CH3:16].C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C>[C:1]([CH2:3][NH:4][C:5]([C:7]1([NH:13][C:28](=[O:29])[C:27]2[CH:26]=[CH:25][C:24]([N:21]3[CH2:20][CH2:19][N:18]([CH:15]([CH3:16])[CH3:17])[CH2:23][CH2:22]3)=[CH:32][CH:31]=2)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:6])#[N:2]
Reactant: CC(C)N1CCN(c2ccc(C(=O)O)cc2)CC1
Reactant: N#CCNC(=O)C1(N)CCCCC1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)N1CCN(c2ccc(C(=O)NC3(C(=O)NCC#N)CCCCC3)cc2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1-Amino-cyclohexanecarboxylic acid cyanomethyl-amide (0.6 mmol), 4-(4-isopropyl-piperazin-1-yl)-benzoic acid hydrochloride (0.6 mmol), HOBT (0.6 mmol), WSCD (0.6 mmol) and triethylamine (0.6 mmol) are dissolved in DMF (2 ml) and stirred overnight at rt. After evaporation of the solvent, the residue is dissolved in a mixture of water and sodium carbonate (to ensure slightly basic conditions) and extracted three times with ethyl acetate. The combined extract is dried over sodium sulfate and evaporated. The residue is suspended in ethyl acetate/diethylether and the solid filtered of and dried (vacuum). A white powder with mp. 218-220° C., Rf=0.28 (CH2Cl2/MeOH=9:1) is obtained.
Reaction SMILES: [C:1]1([CH3:10])[CH:6]=[CH:5][C:4]([N:7]=[C:8]=[O:9])=[CH:3][CH:2]=1.[NH2:11][N:12]1[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][C:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[NH:22][CH:21]=2)[CH2:14][CH2:13]1.C(Cl)Cl>CCOCC>[NH:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:20]([CH2:19][CH2:18][N:15]2[CH2:16][CH2:17][N:12]([NH:11][C:8]([NH:7][C:4]3[CH:5]=[CH:6][C:1]([CH3:10])=[CH:2][CH:3]=3)=[O:9])[CH2:13][CH2:14]2)=[CH:21]1
Reactant: Cc1ccc(N=C=O)cc1
Reactant: NN1CCN(CCc2c[nH]c3ccccc23)CC1
Solvent: ClCCl
Solvent: CCOCC
Product: Cc1ccc(NC(=O)NN2CCN(CCc3c[nH]c4ccccc34)CC2)cc1
Reaction time: 3 h

Procedure:
4.0 G of p-tolylisocyanate are added dropwise to a stirred solution of 6.13 g of 3-[2-(4-aminopiperazin-1-yl)-ethyl]indole in 100 ml. of dry methylene chloride while maintaining the reaction temperature below 35°C. After 3 hours at ambient temperature, ether is added to promote precipitation. The precipitate is filtered, washed with ether, and dried. The resulting solid is recrystallized twice from a methanol and water mixture to give 1-[1-(indol-3-ylethyl)piperazin-4-yl]-3-p-tolylurea, m.p. 201°-203° C.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[C:7]([OH:9])[CH:6]=[CH:5][C:3]=1[NH2:4].[C:10](O)(=O)[CH3:11].C([C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1)=C>CO>[N:19]1[CH:20]=[CH:21][CH:16]=[CH:17][C:18]=1[CH2:10][CH2:11][NH:4][C:3]1[CH:5]=[CH:6][C:7]([OH:9])=[CH:8][C:2]=1[CH3:1]
Reactant: CC(=O)O
Reactant: Cc1cc(O)ccc1N
Reactant: C=Cc1ccncc1
Solvent: CO
Product: Cc1cc(O)ccc1NCCc1ccccn1
Temperature: 25 °C
Yield: 338.7 %

Procedure:
A mixture of 50.0 g (0.4 mole) of 2-methyl-4-hydroxyaniline, 2.4 g of glacial acetic acid and 125.0 ml of anhydrous methyl alcohol was heated to reflux with stirring and 63.1 g (0.6 mole) of 4-vinylpyridine was added dropwise. The resulting reaction mixture was refluxed approximately seventy-two hours. After cooling the reaction mixture to ambient temperature, the solid was collected by filtration, washed twice with fresh methanol, and dried in vacuo to obtain 30.9 g of N-2-[2-(4-pyridyl)ethyl]-2-methyl-4-hydroxyaniline (Formula VI: R1 =R9 =H; R2 =CH3 ; R11 =OH), a solid which melted at 146° to 148.5° C. A significant infrared maximum appeared at 3410 cm-1 (OH;m). The nuclear magnetic resonance spectrum was in accord with the assigned structure.