Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][N:5]([CH3:17])[C:6]=1[C:7]1[CH:8]=[C:9]([C:13]([O:15][CH3:16])=[O:14])[S:10][C:11]=1[CH3:12].C(=O)([O-])[O-].[K+].[K+].O1CCO[CH2:26][CH2:25]1>O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:25]([C:2]1[CH:3]=[N:4][N:5]([CH3:17])[C:6]=1[C:7]1[CH:8]=[C:9]([C:13]([O:15][CH3:16])=[O:14])[S:10][C:11]=1[CH3:12])=[CH2:26]
Reactant: C1COCCO1
Reactant: COC(=O)c1cc(-c2c(Br)cnn2C)c(C)s1
Agent: CC(C)(C)[P]([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: C=Cc1cnn(C)c1-c1cc(C(=O)OC)sc1C
Yield: 81 %

Procedure:
A solution of methyl 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxylate (200 mg, 0.64 mmol) [prepared in Example 99], potassium carbonate (438 mg, 3.17 mmol), bis(tri-t-butylphosphine)palladium(0) (324 mg, 0.64 mmol) and 2,4,6-trivinylcycloboroxane-pyridine complex (77 mg, 0.32 mmol) in 1,4-dioxane (5.3 ml) and H2O (1 ml) was stirred at 80° C. in a sealed tube for 12 h. The reaction contents were partitioned between H2O-DCM and the aqueous phase was washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (10-50% EtOAc in hexanes) affording methyl 4-(4-ethenyl-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxylate (135 mg, 0.515 mmol, 81% yield) as a yellow oil: LCMS (ES) m/z=250 (M+H)+.
Reaction SMILES: Br[CH2:2][CH:3]1[CH2:5][CH2:4]1.[Br:6][C:7]1[CH:12]=[C:11]([OH:13])[CH:10]=[CH:9][C:8]=1[CH2:14][C:15]([OH:17])=[O:16].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Br:6][C:7]1[CH:12]=[C:11]([O:13][CH2:2][CH:3]2[CH2:5][CH2:4]2)[CH:10]=[CH:9][C:8]=1[CH2:14][C:15]([O:17][CH2:2][CH:3]1[CH2:5][CH2:4]1)=[O:16]
Reactant: O=C(O)Cc1ccc(O)cc1Br
Reactant: BrCC1CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C(Cc1ccc(OCC2CC2)cc1Br)OCC1CC1
Temperature: 25 °C
Yield: 89.6 %

Procedure:
A solution of (bromomethyl)cyclopropane (10.52 g), (2-bromo-4-hydroxyphenyl)acetic acid (6.0 g) and potassium carbonate (7.18 g) in DMF (200 mL) was stirred at 80° C. for 8 hr. The reaction mixture was allowed to cool to room temperature, and the solvent was evaporated under reduced pressure. The residue was diluted with diethyl ether and water, and the organic layer was separated. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (7.89 g).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([NH2:10])=[N:8][CH:9]=1)([O-:3])=[O:2].[CH2:11]([O:13][C:14](=[O:28])[CH:15]([CH2:19][C:20](=O)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:16](=O)[CH3:17])[CH3:12].CC1C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH2:11]([O:13][C:14]([C:15]1[CH:19]=[C:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:10]([C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][N:8]=2)[C:16]=1[CH3:17])=[O:28])[CH3:12]
Reactant: CCOC(=O)C(CC(=O)c1ccccc1)C(C)=O
Reactant: Nc1ccc([N+](=O)[O-])cn1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCO
Product: CCOC(=O)c1cc(-c2ccccc2)n(-c2ccc([N+](=O)[O-])cn2)c1C

Procedure:
5-Nitro-pyridin-2-ylamine (5 mmol, 0.7 g), 3-oxo-2-(2-oxo-2-phenyl-ethyl)-butyric acid ethyl ester (5 mmol, 1.2 g), and tosic acid (0.1 g) were combined in ethanol, then heated under reflux. The resulting solid was triturated with chloroform, the filtrate was further purified over silica gel to yield the named product, 1H-NMR (CDCl3, ppm) 1.35 t (3H), 2.54 s (3H), 4.30 q (2H), 6.78 s (1H), 6.96-7.25 bm (6H), 8.33 dd (1H), 9.39 sd (1H)
Reaction SMILES: [C:1]([C:9]1[CH:41]=[CH:40][C:12]([CH2:13][N:14]2[CH2:18][CH2:17][C@@H:16]([N:19]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C:20]3[N:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28]([O:30]CC)=[O:29])=[CH:22][CH:21]=3)[CH2:15]2)=[CH:11][CH:10]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].O.[ClH:45]>O1CCOCC1>[ClH:45].[ClH:45].[C:1]([C:9]1[CH:10]=[CH:11][C:12]([CH2:13][N:14]2[CH2:18][CH2:17][C@@H:16]([N:19]([C:33]([O:35][C:36]([CH3:37])([CH3:39])[CH3:38])=[O:34])[C:20]3[N:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29])=[CH:22][CH:21]=3)[CH2:15]2)=[CH:40][CH:41]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)/C=C/c1ccc(N(C(=O)OC(C)(C)C)[C@@H]2CCN(Cc3ccc(C(=O)c4ccccc4)cc3)C2)nc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: CC(C)(C)OC(=O)N(c1ccc(/C=C/C(=O)O)cn1)[C@@H]1CCN(Cc2ccc(C(=O)c3ccccc3)cc2)C1
Temperature: 60 °C
Reaction time: 2 h

Procedure:
To a solution of ethyl (2E)-3-{6-[[(3R)-1-(4-benzoylbenzyl)-3-pyrrolidinyl](tert-butoxycarbonyl)amino]-3-pyridyl}acrylate (111 mg) in dioxane (2 mL) was added 1N sodium hydroxide (0.6 mL). After stirring at 60° C. for 2 hours, the reaction mixture was added H2O (10 mL) and acidified with 1N hydrochloric acid (to pH 1). A resulting mixture was extracted with CHCl3, and the organic layer was dried over MgSO4, filtered, and evaporated in vacuo to give (2E)-3-{6-[[(3R)-1-(4-benzoylbenzyl)-3-pyrrolidinyl](tert-butoxycarbonyl)amino]-3-pyridyl}acrylic acid dihydrochloride (97 mg).
Reaction SMILES: [CH3:1][Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH:11]([C@H:13]1[CH2:18][CH2:17][CH2:16][CH2:15][N:14]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=O>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[CH:11]([C@H:13]1[CH2:18][CH2:17][CH2:16][CH2:15][N:14]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH2:1]
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: CC(C)(C)OC(=O)N1CCCC[C@@H]1C=O
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [Na+]
Solvent: C1CCOC1
Product: C=C[C@H]1CCCCN1C(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 77.4 %

Procedure:
NaHMDS (1.0 M in THF, 18.6 mL, 18.6 mmol) was slowly added over 15 min to a 0° C. solution of methyltriphenylphosphonium bromide (7.19 gm, 20.1 mmol) in THF (65 mL). The yellow mixture was stirred at 0° C. for 45 min and then cooled to −78° C. A solution of (R)-tert-butyl 2-formylpiperidine-1-carboxylate (3.30 gm, 15.5 mmol) in THF (10 mL) was added dropwise. The reaction mixture was then stirred at 0° C. for 1 hr. The reaction was quenched by the addition of saturated aqueous NH4Cl. The solution was partitioned between EtOAc and water. The aqueous phase was isolated and extracted with EtOAc. All organic phases were combined, dried over MgSO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/Hex to give (R)-tert-butyl 2-vinylpiperidine-1-carboxylate (2.53 gm, 12.0 mmol, 77% yield) as an orange oil. Anal. Calcd. for C12H21N0 m/z 211.3. found: 212.0 (M+H)+.
Reaction SMILES: Cl[C:2]1[C:6]2[CH:7]=[CH:8][C:9]([O:11][CH3:12])=[CH:10][C:5]=2[O:4][N:3]=1.[CH3:13][NH:14][CH2:15][CH2:16][NH2:17]>>[CH3:12][O:11][C:9]1[CH:8]=[CH:7][C:6]2[C:2]([NH:17][CH2:16][CH2:15][NH:14][CH3:13])=[N:3][O:4][C:5]=2[CH:10]=1
Reactant: CNCCN
Reactant: COc1ccc2c(Cl)noc2c1
Product: CNCCNc1noc2cc(OC)ccc12
Temperature: 140 °C

Procedure:
To a sealed tube was added 3-chloro-6-methoxy-1,2-benzisoxazole (2.0 g) and N-methylethylenediamine (4.8 g). The reaction was heated to 140° C. over 48 hours and then cooled to room temperature. The residue was partitioned between EtOAc and brine, washed with brine (4×) and the organic phase was dried over MgSO4 and concentrated in vacuo. Flash chromatography (silica gel) eluting with 5% acetone/CH2Cl2 provided a residue upon evaporation (0.4 g) m.p. 136°-137° C.
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:5]=1F.O.[NH2:16][NH2:17]>C(O)C>[N+:10]([C:7]1[CH:6]=[C:5]2[C:4]([C:3]([OH:2])=[N:16][NH:17]2)=[CH:9][CH:8]=1)([O-:12])=[O:11]
Reactant: NN
Reactant: COC(=O)c1ccc([N+](=O)[O-])cc1F
Solvent: O
Solvent: CCO
Product: O=[N+]([O-])c1ccc2c(O)n[nH]c2c1
Yield: 30.9 %

Procedure:
2-Fluoro-4-nitrobenzoic acid methyl ester (5 g, 25.11 mmol) and hydrazine hydrate (1.34 ml, 27.62 mmol) were dissolved in 250 ml of ethanol and heated under reflux for 11 h. A further 0.26 ml of hydrazine hydrate were added and heated under reflux for a further 6 h, and the mixture was concentrated and ethyl acetate and water were added. The precipitated residue was filtered off with suction and dried. Purification by preparative HPLC (PR18, acetonitrile/water 0.1% TFA) resulted in 1.39 g of product, M+H+: 180.05.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[CH:4][N:5]=[C:6]2[C:13]=1[C:12]1[C@@H:11]([CH2:14][CH:15]([O:18][Si](C)(C)C)[C:16]#[N:17])[CH2:10][CH2:9][C:8]=1[S:7]2.Cl.C(=O)(O)[O-].[Na+]>CO.C(Cl)Cl>[Cl:1][C:2]1[N:3]=[CH:4][N:5]=[C:6]2[C:13]=1[C:12]1[C@@H:11]([CH2:14][CH:15]([OH:18])[C:16]#[N:17])[CH2:10][CH2:9][C:8]=1[S:7]2
Reactant: C[Si](C)(C)OC(C#N)C[C@H]1CCc2sc3ncnc(Cl)c3c21
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: N#CC(O)C[C@H]1CCc2sc3ncnc(Cl)c3c21
Temperature: 25 °C
Reaction time: 1 h
Yield: 89.4 %

Procedure:
To a solution of 3-[(3R)-12-chloro-7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(12),2(6),8,10-tetraen-3-yl]-2-[(trimethylsilyl)oxy]propanenitrile (240 mg, 0.68 mmol, 1.00 equiv) in methanol (5 mL) was added 1 mL of concentrated hydrochloric acid at 0° C. After stirring for 1 h at room temperature, the pH value of the solution was adjusted to 10 with saturated aqueous sodium bicarbonate, diluted with DCM, washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum to give 170 mg (89%) of 3-[(3R)-12-chloro-7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(12),2(6),8,10-tetraen-3-yl]-2-hydroxypropanenitrile as a white solid. MS: m/z 280 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:23])[CH2:15][N:16]2[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[N:17]2)[CH2:10][CH2:9]1.C(N(C(C)C)CC)(C)C.[C:33](Cl)(=[O:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>C(Cl)Cl>[CH3:22][C:18]1[CH:19]=[C:20]([CH3:21])[N:16]([CH2:15][C:14]([N:11]2[CH2:12][CH2:13][N:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[NH:1][C:33](=[O:40])[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:9][CH2:10]2)=[O:23])[N:17]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Cc1cc(C)n(CC(=O)N2CCN(c3ccccc3N)CC2)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1cc(C)n(CC(=O)N2CCN(c3ccccc3NC(=O)c3ccccc3)CC2)n1
Reaction time: 60 h
Yield: 100 %

Procedure:
The 1-[4-(2-amino-phenyl)-piperazin-1-yl]-2-(3,5-dimethyl-pyrazol-1-yl)-ethanone (0.042 g, 0.136 mmol) is dissolved in 1.5 mL of CH2Cl2. To this is added diisopropylethyl amine (0.046 mL, 0.250 mmol) and benzoyl chloride (0.018 mL, 0.150). The mixture is stirred for 60 h. The reaction is quenched with 2 mL of saturated NH4Cl and extracted in the reaction vial with 2×2 mL of CH2Cl2. The organic phase is concentrated. The residue is purified using a SiO2 prep plate eluting with (75% EtOAc/hexanes) to give 58.1 mg of N-(2-{4-[2-(3,5-dimethyl-pyrazol-1-yl)-acetyl]-piperazin-1-yl}-phenyl)-benzamide in 100% Yield. MS: MH+=418.2.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]2[OH:21])=[CH:4][CH:3]=1.Br[CH2:23][C:24]1[CH:25]=[C:26]([C:30]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:31])[CH:27]=[CH:28][CH:29]=1>>[C:30]([C:26]1[CH:25]=[C:24]([CH:29]=[CH:28][CH:27]=1)[CH2:23][O:21][CH:9]1[CH:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:10]1)(=[O:31])[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1
Reactant: O=C(c1ccccc1)c1cccc(CBr)c1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(F)cc2)C(O)C1
Product: CC(C)(C)OC(=O)N1CCC(c2ccc(F)cc2)C(OCc2cccc(C(=O)c3ccccc3)c2)C1

Procedure:
(jj) In an analogous manner to that described in Example 1(g), by alkylating tert-butyl (3RS,4RS)-4-(4-fluoro-phenyl)-3-hydroxy-piperidine-1-carboxylate [Example 3(b)] with (3-bromomethyl-phenyl)-phenyl-methanone [J.Med.Chem. 1984, 27 (12), 1682-1690] there was obtained tert-butyl (3RS,4RS)-3-(3-benzoyl-benzyloxy)-4-(4-fluoro-phenyl)-piperidine-1-carboxylate as a yellowish liquid; MS: 490 (M+H)+.
Reaction SMILES: [CH:1]([C:3]1[O:4][C:5]([CH3:18])=[CH:6][C:7](=[O:17])[C:8]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:2].S(=O)(=O)([OH:21])N.Cl([O-])=O.[Na+]>CC(C)=O.O>[C:1]([C:3]1[O:4][C:5]([CH3:18])=[CH:6][C:7](=[O:17])[C:8]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([OH:21])=[O:2]
Reactant: NS(=O)(=O)O
Reactant: Cc1cc(=O)c(OCc2ccccc2)c(C=O)o1
Agent: [Na+]
Agent: [O-][Cl+][O-]
Solvent: O
Solvent: CC(C)=O
Product: Cc1cc(=O)c(OCc2ccccc2)c(C(=O)O)o1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2-Formyl-3-benzyloxy-6-methyl-pyran-4(1H)-one (3.67 g, 15.03 mmol, 1 eq) was dissolved in acetone (50 ml) and the solution diluted with water (50 ml). To the reaction mixture was added sulfamic acid (2.04 g, 21.04 mmol, 1.4 eq) and 80% sodium chlorite (1.78 g, 15.8 mmol, 1.05 eq) and allowed to stir for 1 hour at room temperature in an open vessel. Removal of acetone in vacuo yielded crude product as a precipitate in the remaining aqueous solution. The solid was collected, washed with absolute ethanol and dried (3.32 g, 85%). m.p. 173-175° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH2:15])[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1.C(N(CC)CC)C.[N:23]1[C:30]([Cl:31])=[N:29][C:27](Cl)=[N:26][C:24]=1[Cl:25]>CO>[Cl:25][C:24]1[N:23]=[C:30]([Cl:31])[N:29]=[C:27]([NH:15][C:5]2[CH:6]=[CH:7][C:8]([N:9]3[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]3)=[C:3]([O:2][CH3:1])[CH:4]=2)[N:26]=1
Reactant: Clc1nc(Cl)nc(Cl)n1
Reactant: COc1cc(N)ccc1-n1cnc(C)c1
Solvent: CCN(CC)CC
Solvent: CO
Product: COc1cc(Nc2nc(Cl)nc(Cl)n2)ccc1-n1cnc(C)c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 65.9 %

Procedure:
A solution of 3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamine (1.0 g, 4.92 mmol) and triethylamine (0.75 ml, 5.42 mmol) in 15 ml of methanol was cooled in an ice-bath and cyanuric chloride (889 mg, 4.82 mmol) added portionwise. The mixture was stirred for 1 hour at 0° C. Filtration of the precipitate gave the title compound (1.115 g, 65%) as a slightly brownish solid.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH:11]4[CH2:17][CH2:16][N:14]([CH2:15][C:5]=3[C:4]=2[CH:3]=1)[CH2:13][CH2:12]4.Br[C:19]1[CH:28]=[C:27]2[C:22]([CH:23]=[CH:24][N:25]=[CH:26]2)=[CH:21][CH:20]=1>>[CH:26]1[C:27]2[C:22](=[CH:21][CH:20]=[C:19]([N:7]3[C:8]4[CH:9]=[CH:10][C:2]([CH3:1])=[CH:3][C:4]=4[C:5]4[CH2:15][N:14]5[CH2:13][CH2:12][CH:11]([C:6]3=4)[CH2:17][CH2:16]5)[CH:28]=2)[CH:23]=[CH:24][N:25]=1
Reactant: Cc1ccc2[nH]c3c(c2c1)CN1CCC3CC1
Reactant: Brc1ccc2ccncc2c1
Product: Cc1ccc2c(c1)c1c(n2-c2ccc3ccncc3c2)C2CCN(CC2)C1

Procedure:
The reaction of 9-methyl-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole (226 mg, 1.0 mmol; Example 2B) and 7-bromoisoquinoline (312 mg, 1.5 mmol; Frontier) was performed as described in Example 68 to afford the title compound: 1H NMR (300 MHz, methanol-d4) δ ppm 1.94-2.20 (m, 4H) 2.42 (s, 3H) 2.91-2.98 (m, 1H) 3.08-3.29 (m, 4H) 4.32 (s, 2H) 6.90-6.96 (m, 1H) 6.98-7.04 (m, 1H) 7.22 (s, 1H) 7.73 (dd, J=8, 2 Hz, 1H) 7.94 (d, J=6 Hz, 1H) 8.09 (d, J=2 Hz, 1H) 8.15 (d, J=9 Hz, 1H) 8.53 (d, J=6 Hz, 1H) 9.33 (s, 1H); MS (DCI/NH3) m/z 354 (M+H)+.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][C:7]3[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=3[CH:9]=2)[C:4](=O)[NH:3][CH:2]=1.C=CC1C=CC=CC=1.[Cl:24]C(Cl)C>C(Cl)(Cl)(Cl)Cl>[Cl:24][C:4]1[C:5]2[C:10](=[CH:9][C:8]3[CH:11]=[CH:12][CH:13]=[CH:14][C:7]=3[CH:6]=2)[N:1]=[CH:2][N:3]=1
Reactant: CC(Cl)Cl
Reactant: O=c1[nH]cnc2cc3ccccc3cc12
Solvent: C=Cc1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: Clc1ncnc2cc3ccccc3cc12
Temperature: 22.5 °C

Procedure:
A mixture of 3H-benzo[g]quinazolin-4-one (1.00 g, 5.07 mmol) and styrene-bound triphenylphosphine (2.53 g (approx. 3 mmoles/g), 7.61 mmol) in 15 mL dichloroethane and 15 mL carbon tetrachloride was heated to reflux for 1 hour, cooled to ambient temperature (20-25° C.) and filtered. Solvents were removed in vacuo to give 4-Chloro-benzo[g]quinazoline: 0.3881 g (36%); 1H NMR (DMSO-d6) δ7.63-7.71 (2H,m), 8.10 (1H, d, J=10 Hz), 8.28 (1H, d, J=10 Hz), 8.32 (1H, s), 8.69 (1H, s), 8.82 (1H, s).
Reaction SMILES: Br[C:2]1[O:11][C:5]2[N:6]=[CH:7][NH:8][C:9](=[O:10])[C:4]=2[C:3]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CC1(C)C(C)(C)OB([C:26]2[CH:39]=[CH:38][C:29]([O:30][CH2:31][CH2:32][N:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)=[CH:28][CH:27]=2)O1.C(=O)([O-])[O-].[K+].[K+].COCCOC>O>[C:12]1([C:3]2[C:4]3[C:9](=[O:10])[NH:8][CH:7]=[N:6][C:5]=3[O:11][C:2]=2[C:26]2[CH:27]=[CH:28][C:29]([O:30][CH2:31][CH2:32][N:33]3[CH2:34][CH2:35][CH2:36][CH2:37]3)=[CH:38][CH:39]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CC1(C)OB(c2ccc(OCCN3CCCC3)cc2)OC1(C)C
Reactant: O=c1[nH]cnc2oc(Br)c(-c3ccccc3)c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: COCCOC
Product: O=c1[nH]cnc2oc(-c3ccc(OCCN4CCCC4)cc3)c(-c3ccccc3)c12
Temperature: 75 °C

Procedure:
Into a 16×100 mm vial sparged with argon was placed 6-bromo-5-phenylfuro[2,3-d]pyrimidin-4 (3H)-one 45 (250 mg, 0.859 mmol), 1-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethyl)pyrrolidine (409 mg, 1.29 mmol), palladiumtetrakistriphenylphosphine (100 mg, 0.086 mmol), potassium carbonate (1.18 g, 8.59 mmol), DME (4 mL), and water (1 mL). The vial was capped and heated to 75° C. for 20 hours.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11](Cl)=O.C=[CH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(N(CCCC)CCCC)CCC>C(OCC)(=O)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:11]([C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:1]=1)=[CH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: C=Cc1ccccc1
Reactant: O=C(Cl)c1ccc2ccccc2c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CCCCN(CCCC)CCCC
Solvent: CCCC(=O)OCC
Product: C(=Cc1ccc2ccccc2c1)c1ccccc1
Yield: 44.5 %

Procedure:
The procedure described in Example 1 is followed, except that 19.1 g (0.1 mol) of 2-naphthoyl chloride, 13.1 g (0.125 mol) of styrene, 23.2 g (0.125 mol) of tri-n-butylamine and 0.225 g (0.001 mol) of palladium acetate are used. After a reaction time of 2 hours at 130° C., in 100 ml of ethyl butyrate, 10.2 g (0.0445 mol) of 2-styrylnaphthalene, corresponding to a yield of 44.5% of theory, are obtained; melting point 143°-145° C.
Reaction SMILES: [C:1]1([O:7][CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:9]1(=[O:15])[O:14][C:12](=[O:13])[CH2:11][CH2:10]1.ClC(Cl)C(Cl)Cl.[N+](C1C=CC=CC=1)([O-])=O.[Cl-].[Cl-].[Cl-].[Al+3].Cl>>[CH3:8][O:7][C:1]1[CH:6]=[CH:5][C:4]([C:9](=[O:15])[CH2:10][CH2:11][C:12]([OH:14])=[O:13])=[CH:3][CH:2]=1
Reactant: O=C1CCC(=O)O1
Reactant: COc1ccccc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClC(Cl)C(Cl)Cl
Solvent: O=[N+]([O-])c1ccccc1
Product: COc1ccc(C(=O)CCC(=O)O)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 46.7 %

Procedure:
A 500 mL round bottom flask equipped with a magnetic stirrer bar and an inert atmosphere (nitrogen gas) was charged with 5.25 mL (48.3 mmol) of anisole, 4.83 g (48.3 mmol) of succinic anhydride, 125 mL 1,1,2,2-tetrachloroethane and 125 mL of nitrobenzene. The reaction vessel was cooled with an external ice bath and stirred for 30 minutes. Aluminum trichloride (14.2 g, 106.4 mmol) was added to the pale yellow solution, which then turned to a dark reddish brown color. The ice bath was removed, and the reaction was allowed to stir at room temperature for 36 hours. Reaction was again cooled with an external ice bath. Prepared acidic solution by pouring 1N hydrogen chloride solution into a 100 mL beaker filled with ice. This solution was added to the reaction mixture carefully, drop-wise at first until reaction became clear with white precipitate. After that point a 10 mL portion was carefully added to test for reactivity, and then the remained of the ice/acid mixture was added. A second 100 mL of ice/acid mixture was added, the external ice bath removed and the pale emulsion was stirred for 2 hours. A white precipitate was collected form the emulsion by suction filtration. This solid was dissolved in 300 mL of 0.3 M sodium hydroxide, washed with 100 mL of ethyl acetate, and acidified to ˜pH 1 with 1 M hydrochloric acid. The white precipitate that was collected upon vacuum filtration was washed with 3×100 mL de-ionized water and dried. The product (4.7 g, 47%) was isolated as a white solid, mp 149-150° C. Combustion analysis: Found: C, 63.52; H, 5.78%; C11H12O4 requires C, 63.45; H, 5.81%; 1H NMR (d6-DMSO): δ 12.2, s, 1H (COOH); δ 7.9 d, 2H (aryl H's); δ 7.0, d, 2H, (aryl H's); δ 3.8, s, 3H (OMe H's); δ 3.2, t, 2H (CH2 α to carbonyl); δ 2.5, t, 2H (CH2 α to COOH).
Reaction SMILES: Br[C:2]1[C:3](=[O:20])[N:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[CH:7]=1.[CH:21]1([Mg]Cl)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.O>O1CCCC1.Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1>[CH:21]1([C:2]2[C:3](=[O:20])[N:4]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:5]=[C:6]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=3)[CH:7]=2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: O=c1c(Br)cc(-c2ccccn2)cn1-c1ccccc1
Reactant: Cl[Mg]C1CCCCC1
Agent: Cl[Ni]1(Cl)[P](c2ccccc2)(c2ccccc2)CCC[P]1(c1ccccc1)c1ccccc1
Solvent: C1CCOC1
Solvent: O
Product: O=c1c(C2CCCCC2)cc(-c2ccccn2)cn1-c1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
34 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one was dissolved in 10 ml of tetrahydrofuran, followed by adding 1 mg of [1,3-bis(diphenylphosphino)propane]nickel (II) chloride. Under stirring in nitrogen atmosphere, 0.1 ml of cyclohexyl magnesium chloride (2.0M ether solution) was added dropwise thereinto. The mixture was stirred at room temperature in nitrogen atmosphere for 1 hour, followed by heating under reflux for 72 hours. After cooling to room temperature, water was added thereto, followed by extracting with ethyl acetate. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (chloroform/methanol system), to give 5 mg of the title compound.
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH:3]=[CH:2]1.[Cl-].[Al+3].[Cl-].[Cl-].[CH3:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[O:20][CH3:21].Cl>ClC1C=CC=CC=1>[CH3:12][O:13][C:14]1[CH:19]=[C:18]([C:4](=[O:5])/[CH:3]=[CH:2]/[C:1]([OH:6])=[O:7])[CH:17]=[CH:16][C:15]=1[O:20][CH3:21]
Reactant: COc1ccccc1OC
Reactant: O=C1C=CC(=O)O1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: Clc1ccccc1
Product: COc1ccc(C(=O)/C=C/C(=O)O)cc1OC
Temperature: 10 °C
Reaction time: 24 h
Yield: 62.1 %

Procedure:
Into a 500 ml four-neck flask were charged 66.9 g (0.682 mol) of maleic anhydride and 150 ml of chlorobenzene under a nitrogen atmosphere. Then, the whole was cooled to 10° C. or lower and 67.6 g (0.507 mol) of aluminum chloride was added thereto. While temperature was maintained at 10 to 15° C., 25 ml (0.195 mol) of 1,2-dimethoxybenzene was added dropwise, followed by 48 hours of reaction at 20 to 30° C. After termination of the reaction was confirmed by HPLC analysis, the reaction solution was added dropwise to 200 ml of a 1N hydrochloric acid aqueous solution cooled to 0° C. to decompose excess aluminum chloride. The resulting mixture was extracted with 400 ml of ethyl acetate and washing was conducted twice with 200 ml of a 1N hydrochloric acid aqueous solution. The organic layer was washed three times with 200 ml of a saturated sodium hydrogen carbonate aqueous solution to extract (E)-4-(3,4-dimethoxyphenyl)-4-oxo-2-butenoic acid into the aqueous layer, followed by adjusting the aqueous layer to pH 2.0. After 24 h of stirring at 5° C., filtration was carried out to obtain 28.6 g (yield 62.1%) of the aimed compound as light yellow crystals. As a result of HPLC analysis, the purity was found to be 96.5%.