Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[C:7]([NH2:12])=[N:8][CH:9]=[CH:10][CH:11]=1)(=[O:3])[CH3:2].Cl[CH:14]([CH3:18])[C:15](=O)[CH3:16].[I-].[K+]>>[C:1]([O:4][CH2:5][C:6]1[C:7]2[N:8]([C:14]([CH3:18])=[C:15]([CH3:16])[N:12]=2)[CH:9]=[CH:10][CH:11]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)C(C)Cl
Reactant: CC(=O)OCc1cccnc1N
Agent: [I-]
Agent: [K+]
Product: CC(=O)OCc1cccn2c(C)c(C)nc12
Yield: 28.2 %

Procedure:
A mixture of 2.0 g (12 mmole) of 3-(acetoxymethyl)-2-pyridinamine, 1.7 g (17 mmole) of 3-chloro-2-butanone, and one crystal of potassium iodide was heated at 100° for 4.5 hours. The mixture was allowed to cool and was partitioned between aqueous potassium carbonate and dichloromethane. The organic phase was separated, washed with water, dried over magnesium sulfate, filtered, and concentrated in vacuo. The solid was triturated with diethyl ether and collected by filtration to yield 738 mg of 8-(acetoxymethyl)-2,3-dimethylimidazo[1,2-a]pyridine, as confirmed by the nmr and infrared spectra and by elemental analysis. [Calcd. for C12H14N2O2 : C, 66.04; H, 6.47; N, 12.84. Found: C, 66.01; H, 6.38; N, 13.05.] A mixture of 700 mg (3.2 mmole) of 8-(acetoxymethyl)-2,3-dimethylimidazo[1,2-a]pyridine and 482 mg (3.2 mmole) of 2-mercaptobenzimidazole in 10 ml of 15% hydrogen bromide in acetic acid was heated on a steam bath. After being cooled to room temperature, the mixture was partitioned between 5% aqueous sodium hydroxide and dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated to an oil. Spinning disk chromatography on silica gel (using 1% by volume ethanol-dichloromethane as eluent) yielded 1.05 g of the title compound Structure assignment was supported by the nmr and infrared spectra.
Reaction SMILES: C1C=C(Cl)C=C(C(OO)=[O:9])C=1.[Br:12][C:13]1[CH:22]=[C:21]2[C:16]([C:17]3[N:25]4[CH2:26][CH2:27][CH2:28][N:29]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:24]4=[N:23][C:18]=3[CH:19]=[N:20]2)=[CH:15][CH:14]=1>C(Cl)(Cl)Cl.O>[Br:12][C:13]1[CH:22]=[C:21]2[C:16]([C:17]3[N:25]4[CH2:26][CH2:27][CH2:28][N:29]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:24]4=[N:23][C:18]=3[CH:19]=[N+:20]2[O-:9])=[CH:15][CH:14]=1
Reactant: CC(C)(C)OC(=O)N1CCCn2c1nc1cnc3cc(Br)ccc3c12
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Solvent: O
Product: CC(C)(C)OC(=O)N1CCCn2c1nc1c[n+]([O-])c3cc(Br)ccc3c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 100.6 %

Procedure:
MCPBA (800 mg of approximately 60% pure material) was added to a solution of tert-butyl 3-bromo-10,11-dihydropyrimido[1′,2′:1,2]imidazo[4,5-c]quinoline-8(9H)-carboxylate (940 mg, 2.3 mmol) in chloroform (50 mL). The reaction was stirred for one hour at room temperature, and an analysis by LC/MS indicated the presence of starting material. Additional MCPBA (540 mg) was added, and the reaction was stirred for an additional 30 minutes and then diluted with water and chloroform. The aqueous layer was separated and extracted twice with chloroform. The combined organic fractions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 0.97 g of tert-butyl 3-bromo-5-oxido-10,11-dihydropyrimido[1′,2′:1,2]imidazo[4,5-c]quinoline-8(9H)-carboxylate.
Reaction SMILES: [F:1][C:2]([F:33])([F:32])[CH2:3][NH:4][C:5]([NH:7][C:8]1[CH:9]=[C:10]([N:14]2[C:18]3[CH:19]=[CH:20][C:21]([C:23]4[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=4)[C:26](O)=[O:27])=[CH:22][C:17]=3[N:16]=[CH:15]2)[CH:11]=[CH:12][CH:13]=1)=[O:6].[CH:34]1[CH:39]=[N:38][CH:37]=[C:36]([CH2:40][NH2:41])[CH:35]=1>>[N:38]1[CH:39]=[CH:34][CH:35]=[C:36]([CH2:40][NH:41][C:26](=[O:27])[C:25]2[CH:29]=[CH:30][CH:31]=[C:23]([C:21]3[CH:20]=[CH:19][C:18]4[N:14]([C:10]5[CH:11]=[CH:12][CH:13]=[C:8]([NH:7][C:5]([NH:4][CH2:3][C:2]([F:32])([F:33])[F:1])=[O:6])[CH:9]=5)[CH:15]=[N:16][C:17]=4[CH:22]=3)[CH:24]=2)[CH:37]=1
Reactant: NCc1cccnc1
Reactant: O=C(NCC(F)(F)F)Nc1cccc(-n2cnc3cc(-c4cccc(C(=O)O)c4)ccc32)c1
Product: O=C(NCC(F)(F)F)Nc1cccc(-n2cnc3cc(-c4cccc(C(=O)NCc5cccnc5)c4)ccc32)c1

Procedure:
This compound was prepared by using procedures analogous to those described for the synthesis of Example 1 starting from 3-{1-[3-({[(2,2,2-trifluoroethyl)amino]-carbonyl}amino)phenyl]-1H-benzimidazol-5-yl}benzoic acid and picolamine (Aldrich Cat. No. A65409). LCMS (M+H)+: m/z=545.2.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]([C:14]([NH:16][CH:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:23]4[CH:24]=[CH:25][C:26]([N+:33]([O-])=O)=[C:27]([CH:32]=4)[C:28]([O:30][CH3:31])=[O:29])[CH2:18]3)=[O:15])=[C:11]([CH3:13])[N:12]=2)=[CH:4][CH:3]=1>C(O)(=O)C>[NH2:33][C:26]1[CH:25]=[CH:24][C:23]([N:19]2[CH2:20][CH2:21][CH2:22][CH:17]([NH:16][C:14]([C:10]3[S:9][C:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)=[N:12][C:11]=3[CH3:13])=[O:15])[CH2:18]2)=[CH:32][C:27]=1[C:28]([O:30][CH3:31])=[O:29]
Reactant: COC(=O)c1cc(N2CCCC(NC(=O)c3sc(-c4ccc(Cl)cc4)nc3C)C2)ccc1[N+](=O)[O-]
Solvent: CC(=O)O
Product: COC(=O)c1cc(N2CCCC(NC(=O)c3sc(-c4ccc(Cl)cc4)nc3C)C2)ccc1N
Temperature: 80 °C
Reaction time: 3 h
Yield: 92.3 %

Procedure:
Methyl 5-[3-[[2-(4-chlorophenyl)-4-methylthiazole-5-carbonyl]amino]piperidin-1-yl]-2-nitrobenzoate (14.6 g, 28.4 mmol) was suspended in acetic acid (140 mL). To this suspension, reduced iron (9.49 g, 170 mmol) was added and the mixture was stirred at 80° C. for 3 hours. The mixture was then allowed to cool and was filtered through Celite. The solvent was removed and a saturated aqueous sodium bicarbonate solution was added to the residue to make it basic. The crystallized powdery product was collected by filtration and washed with water. The resulting powder was dissolved in ethyl acetate and was filtered through Celite. The solvent was then removed to give 12.7 g (26.2 mmol, 92%) of the desired compound as a pale yellow powder.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]2[N:14]=[C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:16]=[C:4]2[N:3]=1.O.[NH2:24][NH2:25].O>O1CCOCC1>[N:8]1([C:6]2[N:5]3[N:14]=[C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH:16]=[C:4]3[N:3]=[C:2]([NH:24][NH2:25])[CH:7]=2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1
Reactant: Clc1cc(N2CCOCC2)n2nc(-c3ccccc3)cc2n1
Reactant: NN
Solvent: C1COCCO1
Solvent: O
Product: NNc1cc(N2CCOCC2)n2nc(-c3ccccc3)cc2n1
Temperature: 90 °C
Reaction time: 14 h
Yield: 90 %

Procedure:
To a solution of 5-chloro-7-morpholin-4-yl-2-phenyl-pyrazolo[1,5-a]pyrimidine (150 mg, 0.48 mM) in 1,4-dioxane (5.0 mL), there was added hydrazine monohydrate (0.23 mL, 4.8 mM) and the mixture was stirred at 90° C. for 14 hours. The reaction mixture was cooled down to room temperature, then water was added thereto and the mixture was extracted with ethyl acetate. The organic phase thus obtained was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to thus give the title compound (133 mg, yield: 90%). MS (ESI) m/z (M+H)+ 311
Reaction SMILES: [CH:1]1([C:4]2[NH:5][C:6]([C:10]3[C:11]([CH3:20])=[CH:12][C:13]([CH3:19])=[C:14]([CH:18]=3)[C:15]([OH:17])=O)=[C:7]([CH3:9])[N:8]=2)[CH2:3][CH2:2]1.CC1NC(C2C=C(C=CC=2C)C(O)=O)=C(C)N=1.Cl.[F:39][C:40]1([C:44]2[CH:51]=[CH:50][C:47]([C:48]#[N:49])=[CH:46][CH:45]=2)[CH2:43][NH:42][CH2:41]1.Cl.N1CC(C2C=CC(C#N)=CC=2)C1>>[CH:1]1([C:4]2[NH:5][C:6]([C:10]3[C:11]([CH3:20])=[CH:12][C:13]([CH3:19])=[C:14]([CH:18]=3)[C:15]([N:42]3[CH2:41][C:40]([C:44]4[CH:45]=[CH:46][C:47]([C:48]#[N:49])=[CH:50][CH:51]=4)([F:39])[CH2:43]3)=[O:17])=[C:7]([CH3:9])[N:8]=2)[CH2:2][CH2:3]1
Reactant: N#Cc1ccc(C2(F)CNC2)cc1
Reactant: Cc1cc(C)c(-c2[nH]c(C3CC3)nc2C)cc1C(=O)O
Agent: Cc1nc(C)c(-c2cc(C(=O)O)ccc2C)[nH]1
Agent: Cl
Agent: N#Cc1ccc(C2CNC2)cc1
Product: Cc1cc(C)c(-c2[nH]c(C3CC3)nc2C)cc1C(=O)N1CC(F)(c2ccc(C#N)cc2)C1

Procedure:
The title compound was prepared using standard chemical manipulations and procedures similar to those used for the preparation of compound 5, except 5-(2-cyclopropyl-4-methyl-1H-imidazol-5-yl)-2,4-dimethylbenzoic acid (compound 160.4) was used in place of 3-(2,4-dimethyl-1H-imidazol-5-yl)-4-methylbenzoic acid (compound 5.7) and 4-(3-fluoroazetidin-3-yl)benzonitrile hydrochloride (compound 43.4) was used in place of 4-(azetidin-3-yl)benzonitrile hydrochloride (compound 5.2). m/z (ES+) 429 (M+H)+. 1H NMR (400 MHz, DMSO-d6): δ 11.52 (br, 1H), 7.95 (d, J=8.4 Hz, 2H), 7.76 (dd, J=8.4 Hz, 3.2 Hz, 2H), 7.21 (d, J=6.8 Hz, 1H), 7.13 (s, 1H), 4.56-4.34 (m, 4H), 2.35 and 2.32 (2 singlets, CH3, 3H), 2.43 and 2.18 (2 singlets, CH3, 3H), 2.07 and 1.93 (2 singlets, CH3, 3H), 1.90-1.80 (m, 1H), 0.88-0.74 (m, 4H).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[S:13][N:12]=[C:11]([C:14](=[N:19][O:20][CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)[C:15]([O:17]C)=[O:16])[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CO>[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][N:12]=[C:11]([C:14](=[N:19][O:20][CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25]2)[C:15]([OH:17])=[O:16])[N:10]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)C(=NOC1CCCC1)c1nsc(NC(=O)OC(C)(C)C)n1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)OC(=O)Nc1nc(C(=NOC2CCCC2)C(=O)O)ns1
Yield: 78.9 %

Procedure:
A solution of 500 mg (1.34 mmoles) of methyl 2-(5-t-butoxycarbonylamino-1,2,4-thiadiazol-3-yl)-2-cyclopentyloxyiminoacetate and 2N NaOH solution (2 ml, 4 mmoles) in 15 ml of CH3OH was refluxed for 30 minutes. The reaction mixture was evaporated and 10 ml of ethyl acetate-H2O (1:1) was added to the solution. The water layer was separated, acidified to pH 2 with 6N HCl and extracted with ethyl acetate (10 ml×2). The organic layer was washed with brine, dried over MgSO4 and concentrated under reduced pressure to give 377 mg (78%) of the title compound. Mp. 185° C. (dec.).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:40])[CH2:4][CH2:5][CH2:6]/[CH:7]=[CH:8]\[CH2:9][C@@H:10]1[C@@H:14](/[CH:15]=[CH:16]/[C@@H:17]([O:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][O:27]2)[CH:18]([CH3:24])[CH2:19]/[CH:20]=[C:21](\[Cl:23])/[CH3:22])[C@H:13]([O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[CH2:12][C@@H]1O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:60]([Cl:64])(Cl)(Cl)Cl.N1C=CC=CC=1>CCOCC.CCCCCC.C(#N)C>[CH3:1][O:2][C:3](=[O:40])[CH2:4][CH2:5][CH2:6]/[CH:7]=[CH:8]\[CH2:9][C@@H:10]1[C@@H:14](/[CH:15]=[CH:16]/[C@@H:17]([O:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][O:27]2)[CH:18]([CH3:24])[CH2:19]/[CH:20]=[C:21](\[Cl:23])/[CH3:22])[C@H:13]([O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[CH2:12][C@H:60]1[Cl:64]
Reactant: ClC(Cl)(Cl)Cl
Reactant: COC(=O)CCC/C=C\C[C@@H]1[C@@H](/C=C/[C@@H](OC2CCCCO2)C(C)C/C=C(/C)Cl)[C@H](OC2CCCCO2)C[C@@H]1O
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCCCCC
Solvent: c1ccncc1
Solvent: CC#N
Product: COC(=O)CCC/C=C\C[C@@H]1[C@@H](/C=C/[C@@H](OC2CCCCO2)C(C)C/C=C(/C)Cl)[C@H](OC2CCCCO2)C[C@H]1Cl
Reaction time: 0.17 h

Procedure:
A solution of 1.16 g of (5Z,13E,18Z)-(8R,9S,11R,12R,15S,16RS)-9-hydroxy-19-chloro-16-methyl-11,15-bis(tetrahydropyran-2-yloxy)-5,13,18-prostatrienoic acid methyl ester, 785 mg of triphenylphosphine, and 15 ml of a solution of 0.97 ml of carbon tetrachloride, 0.79 ml of pyridine, and 48 ml of acetonitrile was stirred under argon at room temperature for 65 hours. The mixture was then diluted with 15 ml of ether and 30 ml of hexane, further stirred for 10 minutes, and filtered. The evaporation residue was extracted with a mixture of 5 ml of ether and 95 ml of hexane, filtered, and concentrated to dryness under vacuum. The residue was purified by column chromatography on silica gel with hexane/10-50% ethyl acetate as the eluent. In this way, 457 mg of the desired compound was isolated.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:17]=[C:16]3[C:12]([CH2:13][C:14](=[O:18])[NH:15]3)=[CH:11][CH:10]=2)[CH:6]=[CH:7][CH:8]=1.[CH3:19][N:20]([CH3:33])[CH2:21][CH2:22][CH2:23][C:24]1[C:25]([CH3:32])=[C:26]([CH:30]=O)[NH:27][C:28]=1[CH3:29]>>[CH3:33][N:20]([CH3:19])[CH2:21][CH2:22][CH2:23][C:24]1[C:25]([CH3:32])=[C:26]([CH:30]=[C:13]2[C:12]3[C:16](=[CH:17][C:9]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=4)=[CH:10][CH:11]=3)[NH:15][C:14]2=[O:18])[NH:27][C:28]=1[CH3:29]
Reactant: COc1cccc(-c2ccc3c(c2)NC(=O)C3)c1
Reactant: Cc1[nH]c(C=O)c(C)c1CCCN(C)C
Product: COc1cccc(-c2ccc3c(c2)NC(=O)C3=Cc2[nH]c(C)c(CCCN(C)C)c2C)c1
Yield: 77.5 %

Procedure:
6-(3-Methoxyphenyl)-1,3-dihydroindol-2-one (239 mg, 1.0 mmol) was condensed with 4-(3-dimethylaminopropyl)-3,5-dimethyl-1H-pyrrole-2-carbaldehyde (208 mg, 1.0 mmol) using method B to give 333 mg (83%) of 3-[4-(3-dimethylaminopropyl)-3,5-dimethyl-1H-pyrrol-2-ylmethylene]-6-(3-methoxyphenyl)-1,3-dihydroindol-2-one as a red solid.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:14]=[C:13]([C:15]([O:17]CC)=[O:16])[O:12][N:11]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[OH-].[Na+].Cl>C1COCC1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH:14]=[C:13]([C:15]([OH:17])=[O:16])[O:12][N:11]=2)=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: CCOC(=O)c1cc(-c2ccc([N+](=O)[O-])cc2)no1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(O)c1cc(-c2ccc([N+](=O)[O-])cc2)no1
Temperature: 25 °C
Reaction time: 0.29 h
Yield: 81.4 %

Procedure:
Ethyl 3-(4-nitrophenyl)isoxazole-5-carboxylate (11 g) was dissolved in THF (220 ml). 1 Molar aqueous NaOH (210 ml) was added and stirred at RT for 15-20 minutes. The reaction mass was acidified with 1 molar HCl. The reaction mixture was extracted with ethyl acetate, organic layer washed with brine, dried over Na2SO4 and concentrated under reduced pressure to get off white solid. Solid was crystallized from acetone/Pet ether to yield 8 g (81%) white solid. MS (ES+): m/z 235 (M+1); 1H NMR (DMSO-d6, 300 MHz) δ: 8.39 (d, 2H), 8.27 (d, 2H), 7.97 (s, 1H).
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:14]=[CH:15][C:16](=[O:19])[NH:17][N:18]=3)=[CH:9][CH:8]=2)[N:3]=1.[NH2:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=1)[CH2:24]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[NH2:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=1)[CH2:24][N:17]1[C:16](=[O:19])[CH:15]=[CH:14][C:13]([C:10]2[CH:9]=[CH:8][C:7]([C:4]3[N:3]=[C:2]([CH3:1])[O:6][N:5]=3)=[CH:12][CH:11]=2)=[N:18]1
Reactant: Nc1cccc(CO)c1
Reactant: Cc1nc(-c2ccc(-c3ccc(=O)[nH]n3)cc2)no1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1nc(-c2ccc(-c3ccc(=O)n(Cc4cccc(N)c4)n3)cc2)no1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
2.5 g (10 mmol) of 6-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-2H-pyridazin-3-one, 1.85 g (15 mmol) of 3-aminobenzyl alcohol and 3.9 g (15 mmol) of triphenylphosphine are suspended in 60 ml of THF under a nitrogen atmosphere, and the mixture is stirred at room temperature for 10 min. 2.9 g (15 mmol) of diisopropyl azodicarboxylate is then added dropwise over the course of 15 min. The reaction mixture is stirred at room temperature for 3 hours and subsequently evaporated. The residue is taken up in about 70 ml of 2-propanol, and the mixture is stirred for 15 minutes. The residue is filtered off with suction, washed well with 2-propanol, then with MTBE. The residue is dried in vacuo.
Reaction SMILES: [Br:1][C:2]1[C:3]([F:10])=[CH:4][C:5](I)=[C:6](C)[CH:7]=1.[CH2:11]([C:14]1[CH:19]=[CH:18][C:17]([C:20]#[CH:21])=[CH:16][CH:15]=1)[CH2:12][CH3:13]>C(NC(C)C)(C)C.[Cu]I>[CH2:11]([C:14]1[CH:15]=[CH:16][C:17]([C:20]#[C:21][C:5]2[CH:4]=[C:3]([F:10])[C:2]([Br:1])=[CH:7][CH:6]=2)=[CH:18][CH:19]=1)[CH2:12][CH3:13]
Reactant: C#Cc1ccc(CCC)cc1
Reactant: Cc1cc(Br)c(F)cc1I
Agent: [Cu]I
Solvent: CC(C)NC(C)C
Product: CCCc1ccc(C#Cc2ccc(Br)c(F)c2)cc1

Procedure:
20 g (63.5 mmol) of 5-bromo-4-fluoro-2-iodotoluene, 10.5 g (73 mmol) of 4-n-propylphenylacetylene, 2.5 g (3.6 mmol) of bis(triphenylphosphine)palladium-(II) chloride and 300 mg (1.8 mmol) of copper(I) iodide are initially introduced in 250 ml of diisopropylamine, the mixture is heated under reflux for 3 h and cooled, and the precipitate formed is filtered off. The filtrate is evaporated in a rotary evaporator, and the residue obtained in this way is purified by column chromatography (SiO2, heptane).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][C:3]=1[OH:11].[Cl-].[Ca+2].[Cl-].O>C(O)C>[NH2:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([OH:11])[CH:4]=1
Reactant: O=[N+]([O-])c1ccc(Cl)c(O)c1
Agent: [Ca+2]
Agent: [Cl-]
Solvent: CCO
Solvent: O
Product: Nc1ccc(Cl)c(O)c1
Temperature: 90 °C
Yield: 92.4 %

Procedure:
A suspension of 2-chloro-5-nitrophenol (25.0 g, 144 mmol), calcium chloride (40 g, 360 mmol) and reduced iron (40.2 g, 720 mmol) in ethanol (500 mL)/water (50 mL) was stirred with heating at 90° C. for 4 hr. After the reaction mixture was cooled to room temperature, the insoluble material was filtered off through a pad filled with celite, and washed with ethanol. The filtrate and the washing fluid were combined, and concentrated under reduced pressure. The obtained residue was diluted with ethyl acetate (400 mL), washed with water (250 mL×2), 5% aqueous sodium hydrogen carbonate solution (250 mL×2) and saturated brine (250 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure to give the title compound (19.1 g, 92%) as a brown powder. This was used for the next reaction without further purification.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:16]=2[CH3:22])[N:12]=[C:11]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][C:24]=2[CH3:30])[N:10]=1.[CH3:31][C:32]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[CH2:33].CC=CC1C=CC=CC=1>C(OCC)(=O)C.CC(C)[O-].[Al+3].CC(C)[O-].CC(C)[O-]>[OH:1][C:2]1[CH:7]=[C:6]([OH:8])[C:5]([C:32]([CH3:33])([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH3:31])=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][C:24]=2[CH3:30])[N:12]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:16]=2[CH3:22])[N:14]=1
Reactant: Cc1ccc(-c2nc(-c3ccc(C)cc3C)nc(-c3ccc(O)cc3O)n2)c(C)c1
Reactant: C=C(C)c1ccccc1
Agent: CC(C)[O-]
Agent: CC=Cc1ccccc1
Agent: [Al+3]
Solvent: CCOC(C)=O
Product: Cc1ccc(-c2nc(-c3ccc(C)cc3C)nc(-c3cc(C(C)(C)c4ccccc4)c(O)cc3O)n2)c(C)c1
Temperature: 175 °C
Yield: 67.7 %

Procedure:
To a 1 L three-necked, round-bottomed flask equipped with a magnetic stirrer, condenser, dropping funnel, thermometer, and a nitrogen atmosphere are charged 15.0 g (37.8 mmol) of 2-(2,4-dihydroxyphenyl)-4,6-bis-(2,4-dimethylphenyl)-s-triazine and 390 mg of aluminum isopropoxide. The mixture is heated to 175° C. and 4.47 g (37.9 mmol) of α-methylstyrene are added dropwise at a rate of one drop every two seconds. A total of six equivalents of or-methyl styrene are added in this fashion over a 4.5 hour period. After cooling to room temperature, the mixture is diluted with ethyl acetate, washed twice with water and once with brine, and is dried over anhydrous magnesium sulfate. Following filtration, the solvent is removed under reduced pressure to yield a yellow solid. The crude product is purified with medium pressure chromatography with 12% ethyl acetate/heptane to afford 13.2 g of the title compound as a yellow solid; mp 168°-170° C.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1([CH2:10][CH2:11]Br)[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4].[N-:13]=[N+:14]=[N-:15].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1([CH2:10][CH2:11][N:13]=[N+:14]=[N-:15])[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4]
Reactant: COC(=O)C1(CCBr)CCCC1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)C1(CCN=[N+]=[N-])CCCC1
Yield: 87 %

Procedure:
A solution of 1-[2-bromoethyl]cyclopentanecarboxylic acid methyl ester (49.6 g, 211 mmol) and sodium azide (54 g, 831 mmol) in DMF (200 mL) was stirred at 50° C. for 5 h under nitrogen atmosphere. Then, the solids were filtered and the filtrate was concentrated to near dryness. The residue was diluted with ethyl acetate (500 mL) and the undissolved solids were collected by filtration and the filtrate was concentrated to give the crude ethyl 1-(2-azidoethyl) cyclopentanecarboxylate which was purified by chromatography over 250 g of silica gel, eluting with 5% ethyl acetate in hexane to give 36.2 g (87% yield) of 1-[2-azidoethyl]cyclopentanecarboxylic acid methyl ester as a light brown oil. EI(+)-HRMS m/e calcd. for C9H15N3O2 (M−H)+ 196.1086, obsd. 196.1342.
Reaction SMILES: [CH3:1][C:2]1[CH2:7][CH2:6][C:5](=[O:8])[CH2:4][CH:3]=1.[BH4-].[Na+].CC[O:13][CH2:14][CH3:15]>>[CH2:14]([O:13][CH:7]1[CH2:6][CH:5]2[O:8][C:2]1([CH3:1])[CH2:3][CH2:4]2)[C:15]1[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1
Reactant: CCOCC
Reactant: CC1=CCC(=O)CC1
Agent: [BH4-]
Agent: [Na+]
Product: CC12CCC(CC1OCc1ccccc1)O2

Procedure:
By procedures similar to those described in Embodiment 3, (+)-2-exo-hydroxy-1-methyl-7-oxabicyclo[2.2.1]heptane was prepared by treatment of 4-methyl-3-cyclohexen-1-one with sodium borohydride followed by epoxidation-cyclization and ether formation to yield the desired product, b.p. 100°-101° C. (0.2 mm).
Reaction SMILES: [Cl:1][C:2]1[C:18]([Cl:19])=[CH:17][C:5]([O:6][C:7]2[CH:12]=[C:11]([O:13][CH2:14][CH2:15]O)[CH:10]=[CH:9][N:8]=2)=[C:4]([I:20])[CH:3]=1.[C:21]1(=[O:31])[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:30])[NH:22]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Cl:1][C:2]1[C:18]([Cl:19])=[CH:17][C:5]([O:6][C:7]2[CH:12]=[C:11]([O:13][CH2:14][CH2:15][N:22]3[C:23](=[O:30])[C:24]4[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=4)[C:21]3=[O:31])[CH:10]=[CH:9][N:8]=2)=[C:4]([I:20])[CH:3]=1
Reactant: O=C1NC(=O)c2ccccc21
Reactant: OCCOc1ccnc(Oc2cc(Cl)c(Cl)cc2I)c1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=C1c2ccccc2C(=O)N1CCOc1ccnc(Oc2cc(Cl)c(Cl)cc2I)c1
Temperature: 25 °C
Reaction time: 15 h
Yield: 69.7 %

Procedure:
A mixture of 2-(2-(4,5-dichloro-2-iodophenoxy)pyridin-4-yloxy)ethanol (130 mg, 0.31 mmol), isoindoline-1,3-dione (54 mg, 0.37 mmol), PPh3 (160 mg, 0.61 mmol) in THF (5 mL) at 0° C., DIAD (123 mg, 0.61 mmol) was added. The resulting mixture was allowed to warm to room temperature and stirred for 15 h. The mixture was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=20:1 to 5:1) to afford the desired product (120 mg, 71% yield). ESI-MS m/z: 555.0[M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][NH:13][C:14](=[O:31])[C:15]([C:21]2[CH:30]=[CH:29][C:28]3[CH2:27][CH2:26][CH2:25][CH2:24][C:23]=3[CH:22]=2)=[CH:16][O:17][CH2:18][C:19]#[CH:20])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(=O)([O-])[O-].[K+].[K+].C(Cl)(Cl)(Cl)[Cl:57]>O>[Cl:57][C:20]#[C:19][CH2:18][O:17][CH:16]=[C:15]([C:21]1[CH:30]=[CH:29][C:28]2[CH2:27][CH2:26][CH2:25][CH2:24][C:23]=2[CH:22]=1)[C:14]([NH:13][CH2:12][CH2:11][C:5]1[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=1)=[O:31]
Reactant: C#CCOC=C(C(=O)NCCc1ccc(OC)c(OC)c1)c1ccc2c(c1)CCCC2
Reactant: ClC(Cl)(Cl)Cl
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [F-]
Solvent: O
Product: COc1ccc(CCNC(=O)C(=COCC#CCl)c2ccc3c(c2)CCCC3)cc1OC
Temperature: 25 °C

Procedure:
Three hundred milligrams (300 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-(2-propynyloxy)-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (0.716 mmol), 20 mg (0.0766 mmol) of tetrabutylammonium fluoride, 100 mg (0.716 mmol) of potassium carbonate and 2 ml of carbon tetrachloride were mixed and stirred at room temperature. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=1:1) to give 140 mg of 3-(3-chloro-2-propynyloxy)-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1223).