Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH2:14][CH:13]([CH3:15])[N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11][C:10]=2[C:23](OCC)=[O:24])[CH:5]=[CH:6][C:7]=1[Cl:8].ClC1C=C(C2CCN(C(OC(C)(C)C)=O)C(C)C=2C(OCC)=O)C=CC=1Cl.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1(C)C=CC=CC=1.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH2:14][CH:13]([CH3:15])[N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11][C:10]=2[CH2:23][OH:24])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CCOC(=O)C1=C(c2ccc(Cl)c(Cl)c2)CC(C)N(C(=O)OC(C)(C)C)C1
Agent: CCOC(=O)C1=C(c2ccc(Cl)c(Cl)c2)CCN(C(=O)OC(C)(C)C)C1C
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CC1CC(c2ccc(Cl)c(Cl)c2)=C(CO)CN1C(=O)OC(C)(C)C
Temperature: -20 °C
Reaction time: 2 h

Procedure:
A mixture of regioisomers 1-(1,1-dimethylethyl) 3-ethyl 4-(3,4-dichlorophenyl)-6-methyl-5,6-dihydro-1,3(2H)-pyridinedicarboxylate and 1-(1,1-dimethylethyl) 3-ethyl 4-(3,4-dichlorophenyl)-2-methyl-5,6-dihydro-1,3(2H)-pyridinedicarboxylate (P21, 0.45 g) was dissolved in toluene (15 mL) and cooled to −20° C. Lithium aluminium hydride 1.0M in THF (0.869 mL) was added dropwise at −20° C. and the mixture was stirred at this temperature for 2 h. The reaction was then quenched with a saturated solution of NH4Cl (10 mL) and diluted with ethyl acetate (20 mL); the organic layer was separated, washed with water (20 mL), dried and concentrated in vacuo. Purification by chromatography on silica gel eluting with a gradient 100% cyclohexane-50% cyclohexane/ethyl acetate afforded 240 mg of title compound as colourless oil. The structure of the major regioisomer was confirmed by nOe NMR experiments.
Reaction SMILES: [OH-].[Li+].[C:3]([C:7]1[N:11]([CH2:12][CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:10]2[CH:19]=[CH:20][C:21]([S:23]([N:26]3[CH:30]=[CH:29][C:28]([C:31]([O:33]C)=[O:32])=[CH:27]3)(=[O:25])=[O:24])=[CH:22][C:9]=2[N:8]=1)([CH3:6])([CH3:5])[CH3:4]>C1COCC1.O>[C:3]([C:7]1[N:11]([CH2:12][CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:10]2[CH:19]=[CH:20][C:21]([S:23]([N:26]3[CH:30]=[CH:29][C:28]([C:31]([OH:33])=[O:32])=[CH:27]3)(=[O:25])=[O:24])=[CH:22][C:9]=2[N:8]=1)([CH3:6])([CH3:4])[CH3:5]
Reactant: COC(=O)c1ccn(S(=O)(=O)c2ccc3c(c2)nc(C(C)(C)C)n3CC2CCOCC2)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)c1nc2cc(S(=O)(=O)n3ccc(C(=O)O)c3)ccc2n1CC1CCOCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Lithium hydroxide (25 mg, 1.0 mmol) was added to mixture of methyl 1-{[2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}-1H-pyrrole-3-carboxylate (90 mg, 0.2 mmol) in 10 mL of THF-H2O (7:3) at 0° C. The reaction mixture was stirred overnight at room temperature and acidified to pH=1. Upon evaporation and dried in vacuo, the residue was dissolved in DMF (10 mL) and then used directly for step A. Purity:>80% (checked by LCMS). MS (ESI) (M+H)+=445.99.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([CH:20]2[CH2:22][CH2:21]2)=[C:6]([CH:8]2[C:13](=[O:14])[C:12]([CH3:16])([CH3:15])[O:11][C:10]([CH3:18])([CH3:17])[C:9]2=[O:19])[CH:7]=1.[Cl:23][C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=1[OH:31].C(=O)([O-])[O-].[Cs+].[Cs+]>FC(F)(F)S([O-])(=O)=O.[Cu+2].FC(F)(F)S([O-])(=O)=O.C1(C)C=CC=CC=1>[CH:20]1([C:5]2[CH:4]=[CH:3][C:2]([O:31][C:25]3[CH:26]=[CH:27][C:28]([Cl:30])=[CH:29][C:24]=3[Cl:23])=[CH:7][C:6]=2[CH:8]2[C:13](=[O:14])[C:12]([CH3:16])([CH3:15])[O:11][C:10]([CH3:17])([CH3:18])[C:9]2=[O:19])[CH2:21][CH2:22]1
Reactant: Oc1ccc(Cl)cc1Cl
Reactant: CC1(C)OC(C)(C)C(=O)C(c2cc(Br)ccc2C2CC2)C1=O
Agent: [Cu+2]
Agent: O=C([O-])[O-]
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: Cc1ccccc1
Product: CC1(C)OC(C)(C)C(=O)C(c2cc(Oc3ccc(Cl)cc3Cl)ccc2C2CC2)C1=O
Temperature: 160 °C

Procedure:
To a mixture of 4-(5-bromo-2-cyclopropylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione (0.208 g, 0.57 mmol), 2,4-dichlorophenol (473 mg, 2.85 mmol), cesium carbonate (0.400 g, 1.13 mmol), copper (II) trifluoromethanesulfonate (10 mg, 0.03 mmol) and activated (powdered) 5 Å molecular sieves (0.330 g) is added anhydrous toluene (3.5 ml). The mixture is purged with nitrogen then heated at 160° C. for 1 hour under microwave irradiation. After cooling to room temperature the reaction mixture is diluted with dichloromethane and 2M hydrochloric acid, then filtered and the organic phase separated. After concentration in vacuo the residue is purified by preparative reverse phase HPLC to afford 4-[2-cyclopropyl-5-(2,4-dichlorophenoxy)-phenyl]-2,2,6,6-tetramethylpyran-3,5-dione.
Reaction SMILES: [C:1]1([C:7]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([CH2:11][CH2:12][CH2:13][N:14]([CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=2)[CH3:15])[C:8]([NH2:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C(O)=O.CO.[Pd]>[C:26]1([C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)([CH2:11][CH2:12][CH2:13][N:14]([CH2:16][CH2:17][C:18]2[CH:19]=[CH:20][C:21]([CH2:24][NH2:25])=[CH:22][CH:23]=2)[CH3:15])[C:8]([NH2:10])=[O:9])[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: CN(CCCC(C(N)=O)(c1ccccc1)c1ccccc1)CCc1ccc(C#N)cc1
Agent: [Pd]
Solvent: CO
Solvent: O=CO
Product: CN(CCCC(C(N)=O)(c1ccccc1)c1ccccc1)CCc1ccc(CN)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
10% Palladium-on-carbon (0.3 g) was added to a solution of 2,2-diphenyl-5-[N-(4-cyanophenethyl)-N-methylamino]pentanamide (0.3 g-see Example 13) in 5% formic acid in methanol (21 ml). The mixture was stirred at room temperature under nitrogen for 1 hour, then filtered and the filtrate concentrated in vacuo to give a gum which was purified by column chromatography on silica eluting with dichloromethane containing methanol (2% up to 10%). The product-containing fractions were combined and concentrated in vacuo to give an oil which crystallised on standing. The solid was triturated with ether to give the title compound as buff crystals, yield 0.1 g, m.p. 139°-142°.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:18])[C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:17])[CH:5]=[CH:4][N:3]=1.Cl[C:20]1[N:25]=[C:24]([CH3:26])[CH:23]=[C:22]([CH3:27])[N:21]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:16][C:15]1[CH:14]=[CH:13][CH:12]=[C:11]([Cl:17])[C:10]=1[C:9]([NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:20]2[N:25]=[C:24]([CH3:26])[CH:23]=[C:22]([CH3:27])[N:21]=2)[CH:7]=1)=[O:18]
Reactant: Cc1cc(C)nc(Cl)n1
Reactant: Nc1cc(NC(=O)c2c(Cl)cccc2Cl)ccn1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: Cc1cc(C)nc(Nc2cc(NC(=O)c3c(Cl)cccc3Cl)ccn2)n1
Temperature: 25 °C
Yield: 6.4 %

Procedure:
To a microwave tube was added N-(2-aminopyridin-4-yl)-2,6-dichlorobenzamide (0.25 g, 0.89 mmol), 2-chloro-4,6-dimethylpyrimidine (0.19 g, 1.34 mmol), Pd2(dba)3 (0.81 g, 0.089 mmol), XantPhos (0.104 g, 0.179 mmol), Cs2CO3 (0.85 g, 2.6 mmol) and dioxane (4 mL). The mixture was degassed with N2 for 10 min. The resulting mixture was irradiated in a microwave reactor at 140° C. for 3 hours and then cooled to room temperature. The mixture was filtered through Celite and concentrated under reduced pressure. The residue was purified by column chromatography to afford the desired product as a white solid (22 mg, yield: 8%). 1H NMR (500 MHz, MeOH-d4): δ 8.96 (d, J=1.5 Hz, 1H), 8.17 (d, J=5.5 Hz, 1H), 7.41-7.54 (m, 4H), 6.77 (s, 1H), 2.44 (s, 6H). LCMS (ESI) m/z: 388.0 [M+H+].
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([NH2:19])[C:11]([NH:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:12][CH:13]=2)=[CH:4][N:3]=1.[CH3:20][O:21][C:22]1[CH:23]=[CH:24][C:25]([C:30]2[S:31][C:32]([CH3:35])=[CH:33][N:34]=2)=[C:26]([CH:29]=1)[CH:27]=O.OOS([O-])=O.[K+].S([O-])([O-])(=O)=S.[Na+].[Na+]>CN(C=O)C.O>[C:15]([N:14]1[C:11]2[CH:12]=[CH:13][C:8]([C:5]3[CH:4]=[N:3][C:2]([NH2:1])=[N:7][CH:6]=3)=[CH:9][C:10]=2[N:19]=[C:27]1[C:26]1[CH:29]=[C:22]([O:21][CH3:20])[CH:23]=[CH:24][C:25]=1[C:30]1[S:31][C:32]([CH3:35])=[CH:33][N:34]=1)([CH3:16])([CH3:18])[CH3:17]
Reactant: COc1ccc(-c2ncc(C)s2)c(C=O)c1
Reactant: CC(C)(C)Nc1ccc(-c2cnc(N)nc2)cc1N
Agent: O=S([O-])([O-])=S
Agent: O=S([O-])OO
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc(-c2ncc(C)s2)c(-c2nc3cc(-c4cnc(N)nc4)ccc3n2C(C)(C)C)c1
Reaction time: 1 h
Yield: 56.1 %

Procedure:
To a solution of 4(2-amino-pyrimidin-5-yl)-N1-tert-butyl-benzene-1,2-diamine (100 mg, 0.39 mmol) in DMF (10 mL) is added 5-methoxy-2-(5-methyl-thiazol-2-yl)-benzaldehyde (99 mg, 0.43 mmol) at room temperature. Oxone (239 mg, 0.39 mmol) in H2O (2 mL) is added and the solution is stirred for 1 hour. Saturated sodium thiosulfate solution (5 mL) is added and the mixture is extracted with EtOAc (3×10 mL) and H2O (10 mL). The combined organic layer is dried with MgSO4 and filtered. The filtrate is concentrated and the residue is purified by silica gel flash column chromatography eluting with 10% MeOH in CH2Cl2 to afford the title compound (103 mg, 56%) as a white solid. LCMS (ESMS): m/z 471.20 (M++1)
Reaction SMILES: [OH:1][C:2]1([CH2:8][CH2:9][N:10]2[C:14](=[O:15])[CH2:13][S:12][CH:11]2[CH2:16][CH2:17][CH2:18][C:19]2[CH:28]=[CH:27][C:22]([C:23](OC)=[O:24])=[CH:21][CH:20]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.O.[NH2:30][NH2:31].ClCCl>CO>[OH:1][C:2]1([CH2:8][CH2:9][N:10]2[C:14](=[O:15])[CH2:13][S:12][CH:11]2[CH2:16][CH2:17][CH2:18][C:19]2[CH:28]=[CH:27][C:22]([C:23]([NH:30][NH2:31])=[O:24])=[CH:21][CH:20]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1
Reactant: COC(=O)c1ccc(CCCC2SCC(=O)N2CCC2(O)CCCCC2)cc1
Reactant: NN
Solvent: ClCCl
Solvent: CO
Solvent: O
Product: NNC(=O)c1ccc(CCCC2SCC(=O)N2CCC2(O)CCCCC2)cc1

Procedure:
A solution of methyl 4-{3-[3-[2-(1-hydroxycyclohexyl)ethyl]-4-oxo-2-thiazolidinyl]propyl}benzoate (4.1 g., 0.01 mole) and hydrazine hydrate (2.5 g., 0.05 mole) in methanol (25 ml.) is stored at 25° C. for 48 hours. The solvent is then removed by distillation at reduced pressure. The residue is treated with water and enough 2 N hydrochloric acid to give a neutral mixture. The title compound is isolated by extraction into dichloromethane and subsequent drying and evaporation of the extract.
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]=1B(O)O.C[CH:15]([CH:19]1[C:23]2=[C:24](Br)[C:25]3[C:26]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:27][C:28]([F:31])=[CH:29][C:30]=3[N:22]2[CH2:21][CH2:20]1)[C:16]([O-:18])=[O:17]>>[F:31][C:28]1[CH:27]=[C:26]([S:32]([CH3:35])(=[O:34])=[O:33])[C:25]2[C:24]([C:2]3[CH:3]=[CH:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[CH:1]=3)=[C:23]3[CH:19]([CH2:15][C:16]([OH:18])=[O:17])[CH2:20][CH2:21][N:22]3[C:30]=2[CH:29]=1
Reactant: CC(C(=O)[O-])C1CCn2c1c(Br)c1c(S(C)(=O)=O)cc(F)cc12
Reactant: OB(O)c1ccc2ccccc2c1
Product: CS(=O)(=O)c1cc(F)cc2c1c(-c1ccc3ccccc3c1)c1n2CCC1CC(=O)O

Procedure:
Starting from 2-naphthylboronic acid and (+/−)-methyl[9-bromo-6-fluoro-8-(methylsulfonyl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl]acetate (Example 126, Step 1), the title compound was synthesized following the procedures described in Step 2 of Example 126 and Step 10 of Example 7.
Reaction SMILES: [C@H:1]12[CH2:6][C@H:5]1[CH2:4][NH:3][C@@H:2]2[CH2:7][NH:8][C:9]([C:11]1[N:18]2[C:14]([S:15][CH:16]=[CH:17]2)=[N:13][C:12]=1[CH3:19])=[O:10].[N:20]1([C:25]2[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=2[C:27](O)=[O:28])[CH:24]=[CH:23][CH:22]=[N:21]1>>[N:20]1([C:25]2[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=2[C:27]([N:3]2[CH2:4][C@H:5]3[C@H:1]([CH2:6]3)[C@H:2]2[CH2:7][NH:8][C:9]([C:11]2[N:18]3[C:14]([S:15][CH:16]=[CH:17]3)=[N:13][C:12]=2[CH3:19])=[O:10])=[O:28])[CH:24]=[CH:23][CH:22]=[N:21]1
Reactant: Cc1nc2sccn2c1C(=O)NC[C@H]1NC[C@@H]2C[C@@H]21
Reactant: O=C(O)c1ccccc1-n1cccn1
Product: Cc1nc2sccn2c1C(=O)NC[C@@H]1[C@H]2C[C@H]2CN1C(=O)c1ccccc1-n1cccn1

Procedure:
prepared by reaction of 6-Methyl-imidazo[2,1-b]thiazole-5-carboxylic acid [(1S,2S,5R)-1-(3-aza-bicyclo[3.1.0]hex-2-yl)methyl]-amide with 2-Pyrazol-1-yl-benzoic acid. LC-MS (basic): tR=1.20 min; [M+H]+=447.1.
Reaction SMILES: [C:1](=[O:22])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]1.CCN(C(C)C)C(C)C.[CH3:32][O:33][C:34]1[CH:39]=[CH:38][C:37]([N:40]2[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)=[CH:36][CH:35]=1>CN(C=O)C>[CH3:32][O:33][C:34]1[CH:35]=[CH:36][C:37]([N:40]2[CH2:45][CH2:44][N:43]([C:1]([O:2][CH2:3][CH2:4][N:5]3[CH2:6][CH2:7][N:8]([CH3:11])[CH2:9][CH2:10]3)=[O:22])[CH2:42][CH2:41]2)=[CH:38][CH:39]=1
Reactant: CN1CCN(CCOC(=O)Oc2ccc([N+](=O)[O-])cc2)CC1
Reactant: COc1ccc(N2CCNCC2)cc1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(N2CCN(C(=O)OCCN3CCN(C)CC3)CC2)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 17.2 %

Procedure:
2-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate (Intermediate 4; 680 mg, 2.2 mmol) was dissolved in DMF (20 mL). DIPEA (0.76 mL, 4.4 mmol) and 4-(4-methoxyphenyl)piperazine (422 mg, 2.2 mmol) were added and the reaction mixture was stirred at room temperature for 24 hours, and the reaction mixture was then concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 500:8:1 mixture of DCM:EtOH:NH3, followed by a 50:8:1 mixture of DCM:EtOH:NH3). The residue was recrystallised from EtOAc to give 2-(4-methyl-piperazin-1-yl)ethyl 4-(4-methoxyphenyl)piperazine-1-carboxylate (137 mg, 17%) as a white solid.
Reaction SMILES: FC(F)(F)C(O)=O.[CH:8]([N:11]1[C:15]([C:16]2[N:25]=[C:24]3[N:18]([CH2:19][CH2:20][O:21][C:22]4[CH:29]=[C:28]([CH:30]5[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]5)[CH:27]=[CH:26][C:23]=43)[CH:17]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9].C(=O)([O-])[O-].[K+].[K+].Br[CH2:43][CH2:44][O:45][CH3:46]>CN(C=O)C.C(Cl)Cl>[CH:8]([N:11]1[C:15]([C:16]2[N:25]=[C:24]3[C:23]4[CH:26]=[CH:27][C:28]([CH:30]5[CH2:35][CH2:34][N:33]([CH2:43][CH2:44][O:45][CH3:46])[CH2:32][CH2:31]5)=[CH:29][C:22]=4[O:21][CH2:20][CH2:19][N:18]3[CH:17]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9]
Reactant: CC(C)n1ncnc1-c1cn2c(n1)-c1ccc(C3CCNCC3)cc1OCC2
Reactant: COCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COCCN1CCC(c2ccc3c(c2)OCCn2cc(-c4ncnn4C(C)C)nc2-3)CC1
Temperature: 60 °C
Reaction time: 4 h
Yield: 47.5 %

Procedure:
To a solution of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetic acid salt (300 mg, 0.61 mmol) in DMF (3.5 mL) were added potassium carbonate (290 mg, 2.10 mmol) and 1-bromo-2-methoxy-ethane (93 mg, 0.67 mmol). The resultant reaction mixture was stirred at 60° C. for 4 hours before being cooled to RT and diluted with DCM. The mixture was washed sequentially with sodium hydrogen carbonate solution (sat. aq.), water and brine then dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by flash column chromatography (SiO2, gradient 0-8% MeOH in DCM) and triturated with petroleum ether to afford 286 as a white solid (127 mg, 0.29 mmol, 48%). LCMS: RT=3.02 min, [M+H]+=437. 1H NMR δ (ppm) (DMSO-d6): 8.28 (1H, d, J=8.28 Hz), 7.86 (1H, d, J=0.62 Hz), 7.85 (1H, s), 7.01 (1H, dd, J=8.36, 1.77 Hz), 6.85 (1H, d, J=1.72 Hz), 5.90-5.80 (1H, m), 4.45 (4H, m), 3.40 (2H, t, J=5.89 Hz), 3.20 (3H, s), 2.93 (2H, d, J=11.11 Hz), 2.01 (2H, dd, J=12.41, 10.21 Hz), 1.70 (2H, d, J=12.52 Hz), 1.58 (2H, ddd, J=24.42, 12.21, 3.61 Hz), 1.44 (6H, d, J=6.60 Hz). 3H obscured by solvent.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([NH:8][NH2:9])=[O:7])=[CH:4][CH:3]=1.[C:12](OCC)(OCC)(OCC)[CH3:13]>>[Br:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]2[O:7][C:12]([CH3:13])=[N:9][N:8]=2)=[CH:4][CH:3]=1
Reactant: CCOC(C)(OCC)OCC
Reactant: NNC(=O)c1ccc(Br)cc1
Product: Cc1nnc(-c2ccc(Br)cc2)o1
Yield: 87 %

Procedure:
A stirred suspension of 4-bromobenzoic hydrazide (4.0 g, 18.6 mmol) in triethyl orthoacetate (15 ml) was heated under reflux for 24 h. The reaction mixture was cooled and the precipitate filtered, washed with 60-80° C. petroleum ether (20 ml) and dried to give the title compound as a yellow solid (3.86 g, 87%).
Reaction SMILES: [CH:1]([C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[CH:5][CH:4]=1)=[CH2:2].C(N(CC)CC)C.[CH3:17][S:18](Cl)(=[O:20])=[O:19]>C(OCC)C>[CH:1]([C:3]1[CH:9]=[CH:8][C:6]([NH:7][S:18]([CH3:17])(=[O:20])=[O:19])=[CH:5][CH:4]=1)=[CH2:2]
Reactant: C=Cc1ccc(N)cc1
Reactant: CS(=O)(=O)Cl
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: C=Cc1ccc(NS(C)(=O)=O)cc1
Reaction time: 2 h
Yield: 70 %

Procedure:
To a solution of 500 g (4.2 moles) of 4-vinylaniline and 460 g (4.2 moles) of triethylamine in 1000 cc of anhydrous diethyl ether under a nitrogen atmosphere was added dropwise 478 g (4.2 moles) of methanesulfonyl chloride. The temperature of the reaction vessel was kept below 5° C. by an ice bath during the course of the reaction. When addition was complete (40 min.), the mixture was stirred for an additional 2 hours and the contents of the flask then brought to room temperature. The mixture was filtered and extracted with 500 cc of 1.0 M HCl solution. The etheral portion was separated, dried and the ether removed on a rotary evaporator. The resulting oily solid was extracted with 500 cc of ethanol and recrystallized from ethane/water and then from toluene. 70-75% yield after recrystallization. M.P. = 97° C.
Reaction SMILES: [C:1]1([C:7]2[CH2:8][CH2:9][C:10]3[C:15]([C:16]=2[C:17](=[O:26])[C:18]2[CH:23]=[CH:22][C:21]([O:24]C)=[CH:20][CH:19]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[S-]CC.[Na+].[Cl-].[NH4+]>CN(C=O)C>[C:1]1([C:7]2[CH2:8][CH2:9][C:10]3[C:15]([C:16]=2[C:17](=[O:26])[C:18]2[CH:19]=[CH:20][C:21]([OH:24])=[CH:22][CH:23]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COc1ccc(C(=O)C2=C(c3ccccc3)CCc3ccccc32)cc1
Agent: CC[S-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: O=C(C1=C(c2ccccc2)CCc2ccccc21)c1ccc(O)cc1
Temperature: 80 °C
Yield: 86.3 %

Procedure:
To 2.0 grams (0.006 mole) of the above dihydronaphthalene dissolved in 10 ml. of N,N-dimethyl formamide were added 7.5 mmoles of sodium thioethoxide in 15 ml. of DMF. The addition was carried out under a nitrogen atmosphere and at 80° C. The mixture was maintained at 80° C. for fifteen hours. The mixture then was cooled and poured into an iced aqueous ammonium chloride solution. The resulting mixture was extracted with ethyl acetate, and the ethyl acetate extract was washed four times with aqueous sodium chloride solution. The ethyl acetate then was dried over magnesium sulfate and evaporated to give an oil which was chromatographed rapidly over a 2"×2" silica column using benzene to elute impurities. The product then was eluted with ethyl acetate to give, upon evaporation of the ethyl acetate, 1.69 grams (88%) of 3-phenyl-4-(4-hydroxybenzoyl)-1,2-dihydronaphthalene as a clear pale yellow oil.
Reaction SMILES: C[O:2][C:3](=[O:25])[C:4]1[CH:9]=[C:8]([N:10]2[C:15](=[O:16])[N:14]([CH2:17][CH:18]([OH:22])[CH2:19][O:20][CH3:21])[C:13](=[O:23])[CH:12]=[N:11]2)[CH:7]=[CH:6][C:5]=1[Cl:24].C(N(CC)CC)C.[Si:33](Cl)([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34].[OH-].[Na+]>C1COCC1>[C:36]([Si:33]([CH3:35])([CH3:34])[O:22][CH:18]([CH2:19][O:20][CH3:21])[CH2:17][N:14]1[C:13](=[O:23])[CH:12]=[N:11][N:10]([C:8]2[CH:7]=[CH:6][C:5]([Cl:24])=[C:4]([CH:9]=2)[C:3]([OH:2])=[O:25])[C:15]1=[O:16])([CH3:39])([CH3:38])[CH3:37]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: COCC(O)Cn1c(=O)cnn(-c2ccc(Cl)c(C(=O)OC)c2)c1=O
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COCC(Cn1c(=O)cnn(-c2ccc(Cl)c(C(=O)O)c2)c1=O)O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To Intermediate 2 (14.8 g, 40 mmol) in THF (200 ml) and triethylamine (44 mmol, 4.45) at 0° C., is added t-butyldimethylsilylchloride (TBDMS-Cl) (44 mmol, 6.63 g). The reaction is allowed to warm to room temperature and stirred overnight. 1 N NaOH solution (100 ml) is added, and the reaction is stirred at 40° C. for 4 h. THF is evaporated under reduced pressure, and the resulting mixture is acidified with 1 N HCl to pH<2. The mixture is extracted with ethyl acetate (2×100 ml). The organic phase is washed with brine solution, dried over MgSO4, and concentrated in vacuo to give 5-{4-[2-(tert-Butyl-dimethyl-silanyloxy)-3-methoxy-propyl]-3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl}-2-chloro-benzoic acid.
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:3]=1[C:4]([O:6]CC)=O.[C:14](#[N:16])[CH3:15].[H-].[Na+].CCOCC>O1CCCC1>[Cl:1][C:2]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:3]=1[C:4]([CH2:15][C:14]#[N:16])=[O:6]
Reactant: CC#N
Reactant: CCOC(=O)c1ccc(Cl)cc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: N#CCC(=O)c1ccc(Cl)cc1Cl
Temperature: 25 °C
Yield: 28.1 %

Procedure:
A mixture of 43.8 g of ethyl 2,4-dichloro-benzoate and 8.2 g of anhydrous acetonitrile is added dropwise to a suspension of 6.1 g of 80% strength sodium hydride in 100 ml of anhydrous tetrahydrofuran in the course of about 1 hour under reflux. The mixture is heated at the boiling point under reflux for a further hour and cooled to room temperature and 150 ml of ether are added. The precipitate is filtered off with suction and dissolved in 50 ml of ice-water and the solution is acidified to pH=6 with 10% strength hydrochloric acid. The precipitate is filtered off cold with suction, rinsed with ice-water and dried in vacuo at 40° C. 12 g of 2,4-dichlorobenzoylacetonitrile of melting point 96°-98° C. are obtained.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].I[CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:36]=[CH:35][C:15]([O:16][CH2:17][C:18]2[N:19]=[C:20](/[CH:23]=[CH:24]/[C:25]3[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=3)[O:21][CH:22]=2)=[CH:14][CH:13]=1.[NH:37]1[CH:41]=[C:40]([C:42]([O:44][CH2:45][CH3:46])=[O:43])[N:39]=[N:38]1.O>CN(C)C=O>[F:32][C:31]([F:34])([F:33])[C:28]1[CH:29]=[CH:30][C:25](/[CH:24]=[CH:23]/[C:20]2[O:21][CH:22]=[C:18]([CH2:17][O:16][C:15]3[CH:35]=[CH:36][C:12]([CH2:11][CH2:10][CH2:9][CH2:8][N:37]4[CH:41]=[C:40]([C:42]([O:44][CH2:45][CH3:46])=[O:43])[N:39]=[N:38]4)=[CH:13][CH:14]=3)[N:19]=2)=[CH:26][CH:27]=1
Reactant: CCOC(=O)c1c[nH]nn1
Reactant: FC(F)(F)c1ccc(/C=C/c2nc(COc3ccc(CCCCI)cc3)co2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1cn(CCCCc2ccc(OCc3coc(/C=C/c4ccc(C(F)(F)F)cc4)n3)cc2)nn1
Temperature: 70 °C
Reaction time: 5 h
Yield: 24.1 %

Procedure:
Potassium carbonate (2.4 g) was added to a solution of 4-[[4-(4-iodobutyl)phenoxy]methyl]-2-{(E)-2-[4-(trifluoromethyl)phenyl]ethenyl}-1,3-oxazole (7.5 g) and ethyl 1H-1,2,3-triazole-4-carboxylate (2.1 g) in dimethylformamide (100 ml), and the mixture was stirred at 70° C. for 5 hr. After the reaction was completed, the reaction mixture was combined with water and extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; ethyl acetate:hexane=3:1), and recrystallized from ethyl acetate-hexane to give the titled compound (1.85 g) as a colorless crystal powder.