Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br.C(O)(=O)C.[Si:6]([O:23][C@@H:24]1[C@@H:28]([CH2:29][O:30][Si:31]([C:44]([CH3:47])([CH3:46])[CH3:45])([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:27][CH:26]([O:48]C)[C@H:25]1[F:50])([C:19]([CH3:22])([CH3:21])[CH3:20])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(OCC)(=O)C.O>C(Cl)Cl>[Si:6]([O:23][C@@H:24]1[C@@H:28]([CH2:29][O:30][Si:31]([C:44]([CH3:47])([CH3:46])[CH3:45])([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[O:27][CH:26]([OH:48])[C@H:25]1[F:50])([C:19]([CH3:21])([CH3:22])[CH3:20])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: COC1O[C@H](CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)[C@@H](O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)[C@@H]1F
Agent: Br
Solvent: CC(=O)O
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](OC[C@H]1OC(O)[C@@H](F)[C@@H]1O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 40 %

Procedure:
1.0 mL of 30% hydrogen bromide/acetic acid was added dropwise to a solution of 1.66 g of (3S,4R,5R)-4-((tert-butyldiphenylsilyl)oxy)-5-(((tert-butyldiphenylsilyl)oxy)methyl)-3-fluoro-2-methoxyoxolane in 10 mL of methylene chloride at room temperature, and the obtained mixture was then stirred at room temperature for 3 hours. Thereafter, ethyl acetate and water were added to the reaction mixture, and the obtained mixture was then stirred for 5 minutes. Thereafter, the organic layer was fractionated, and it was washed with a 10% sodium hydrogen carbonate aqueous solution. After that, the solvent was distilled away under reduced pressure. 10 mL of acetonitrile and 10 mL of a 10% sodium hydrogen carbonate aqueous solution were added to the obtained residue, and the obtained mixture was then stirred at room temperature for 3 hours. Subsequently, the reaction mixture was left overnight. Thereafter, ethyl acetate and water were added to the reaction mixture. The organic layer was fractionated, and the solvent was then distilled away under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/0 to 9/1), so as to obtain 0.65 g of (3S,4R,5R)-4-((tert-butyldiphenylsilyl)oxy)-5-(((tert-butyldiphenylsilyl)oxy)methyl)-3-fluorooxolan-2-ol in the form of a colorless oily product.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH:9]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][N:12]1[CH3:17])[CH3:10].[C:18](Cl)(=[O:27])[C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1>>[CH3:26][O:25][C:22]1[CH:23]=[CH:24][C:19]([C:18]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[CH2:8][CH:9]([CH3:10])[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][N:12]2[CH3:17])=[O:27])=[CH:20][CH:21]=1
Reactant: COc1ccc(C(=O)Cl)cc1
Reactant: CC(Cc1ccccc1N)C1CCCCN1C
Product: COc1ccc(C(=O)Nc2ccccc2CC(C)C2CCCCN2C)cc1

Procedure:
Reaction of 2-[2-(2-aminophenyl)-1-methylethyl]-1-methylpiperidine with anisoyl chloride, according to the procedure of Example 25, provides 4-methoxy-2'-[2-methyl-2-(1-methyl-2-piperidyl)ethyl]benzanilide as a 72:28 mixture of diastereoisomers (according to nmr), m.p. 125.5°-136.5°C. (corr.).
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][CH:12]=1)[C:6](=[N:8]O)[NH2:7].[C:15]([O:19][CH2:20][CH3:21])(=[O:18])[C:16]#[CH:17]>CO>[CH2:20]([O:19][C:15]([C:16]1[N:7]=[C:6]([C:5]2[CH:10]=[CH:11][CH:12]=[C:3]([C:2]([F:14])([F:13])[F:1])[CH:4]=2)[NH:8][CH:17]=1)=[O:18])[CH3:21]
Reactant: NC(=NO)c1cccc(C(F)(F)F)c1
Reactant: C#CC(=O)OCC
Solvent: CO
Product: CCOC(=O)c1c[nH]c(-c2cccc(C(F)(F)F)c2)n1
Temperature: 200 °C
Yield: 22.4 %

Procedure:
A mixture of 3-trifluoromethylbenzamidoxime (19.89 g, 0.0974 mol) and ethyl propiolate (9.60 g, 0.0974 mol) in 100 mL methanol was refluxed overnight. The reaction was cooled and concentrated in vacuo and trace methanol removed by azeotroping with toluene (2×100 mL). The remaining residue was heated at 200° C. for 6 h in diphenyl ether (50 mL) before cooling and diluting with cold methanol (200 mL). The solid precipitate was filtered off and sucked dry on a glass frit to give 6.2 g of the title compound as a solid.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N+:10]([O-])=[CH:9][CH:8]=[CH:7]2)([O-:3])=[O:2].[CH3:15][C:16]([O:18]C(C)=O)=[O:17]>>[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[C:9]([O:18][C:16](=[O:17])[CH3:15])[CH:8]=[CH:7]2)([O-:3])=[O:2]
Reactant: CC(=O)OC(C)=O
Reactant: O=[N+]([O-])c1ccc2c(ccc[n+]2[O-])c1
Product: CC(=O)Oc1ccc2cc([N+](=O)[O-])ccc2n1
Temperature: 25 °C
Yield: 33 %

Procedure:
A solution of compound 45A (564 mg, 2.96 mmol) in Ac2O (20 mL) was heated to 145° C. for 5 h. After cooling to rt, the reaction was concentrated and the residue purified by silica gel flash chromatography eluting with CH2Cl2 to give the title compound (227 mg, 33%) as a beige solid. LC/MS m/z 233 [M+H]+.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([NH:14][C:15]([CH3:23])([CH3:22])/[CH:16]=[CH:17]/[C:18]([O:20][CH3:21])=[O:19])[S:12][CH:13]=2)=[CH:5][CH:4]=1)#[N:2].[H][H]>C(OCC)(=O)C.[Pd]>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:10]=[C:11]([NH:14][C:15]([CH3:23])([CH3:22])[CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])[S:12][CH:13]=2)=[CH:7][CH:8]=1)#[N:2]
Reactant: [H][H]
Reactant: COC(=O)/C=C/C(C)(C)Nc1nc(-c2ccc(C#N)cc2)cs1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COC(=O)CCC(C)(C)Nc1nc(-c2ccc(C#N)cc2)cs1
Yield: 94.6 %

Procedure:
Methyl (2E)-4-{[4-(4-cyanophenyl)-1,3-thiazol-2-yl]amino}-4-methylpent-2-enoate (0.85 g, 2.6 mmol), prepared in step 1 of Example 87, was dissolved in ethyl acetate (10 mL) and 10% Pd on carbon (0.25 g, 0.20 mmol) was added. The mixture was shaken in a Parr apparatus under 40 psi of hydrogen for 16 h. The mixture was diluted with ethyl acetate, filtered through the Celite™ reagent and concentrated. Flash chromatography (10% acetone/hexane) afforded methyl 4-{[4-(4-cyanophenyl)-1,3-thiazol-2-yl]amino}-4-methylpentanoate (0.81 g, 95%) as a white solid. HRMS: calcd for C17H19N3O2S+H+, 330.12707; found (ESI, [M+H]+), 330.1292; Analytical HPLC: purity 100% at 210-370 nm, 11.2 min; 100% at 272 nm, 11.2 min; the Xterra® RP18 column, 3.5%, 150×4.6 mm column, 1.2 mL/min, 85/15-5/95 (Ammon. Form. Buff. pH=3.5/ACN+MeOH) for 10 min, hold 4 min.
Reaction SMILES: [C:1]([O:5][C:6](=[O:26])[N:7]([CH:13]1[CH:18]2[CH:14]1[CH2:15][N:16]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:17]2)[CH2:8][CH2:9][CH2:10][CH2:11]Br)(C)(C)[CH3:2].BrCCCCl.[CH2:32]([O:39][C:40]1[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][C:41]=1[CH:47]([C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[CH2:48][C:49]([OH:51])=[O:50])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.N12CCCN=C1CCCCC2>C1(C)C(C)=CC=CC=1>[CH2:19]([N:16]1[CH2:15][CH:14]2[CH:18]([CH:13]2[N:7]([C:6]([O:5][CH2:1][CH3:2])=[O:26])[CH2:8][CH2:9][CH2:10][CH2:11][O:50][C:49](=[O:51])[CH2:48][CH:47]([C:41]2[CH:42]=[C:43]([CH3:46])[CH:44]=[CH:45][C:40]=2[O:39][CH2:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[CH2:17]1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: CC(C)(C)OC(=O)N(CCCCBr)C1C2CN(Cc3ccccc3)CC21
Reactant: Cc1ccc(OCc2ccccc2)c(C(CC(=O)O)c2ccccc2)c1
Agent: ClCCCBr
Solvent: C1CCC2=NCCCN2CC1
Solvent: Cc1ccccc1C
Product: CCOC(=O)N(CCCCOC(=O)CC(c1ccccc1)c1cc(C)ccc1OCc1ccccc1)C1C2CN(Cc3ccccc3)CC21

Procedure:
The compound, 3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-(4-bromobutyl)-carbamic acid t-butyl ester, 211.5 mg, 0.5 mmole, 1 eq (prepared by reacting boc-protected 3-benzyl-3-azabicylo[3.1.0]hex-6-yl amine, which in turn, was prepared following the procedure of T. F. Braish et al., Synlett, 1996, 1100, with 1-bromo-3-chloropropane) was dissolved in xylene (15 ml). To this reaction mixture, 3-(2-benzyloxy-5-methylphenyl) 3-phenyl propionic acid (260 mg, 0.75 mmole, 1.5 eq) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.75 mmole, 1.5 eq) were added. The resulting reaction mixture was refluxed for 2 hrs. Xylene was removed under reduced pressure and the residue was purified by column chromatography by using ethyl acetate in hexane solvent system to yield the organic compound, 3-(2-benzyloxy-5-methylphenyl)-3-phenyl propionic acid 4-[(3-benzyl-3-azabicylo[3.1.0]hex-6-yl)-ethoxy carbonylamino]butyl ester.
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].[CH3:9][O:10][C:11](=[O:27])[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:15][CH:14]=1.I[CH2:29][CH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1>O1CCCC1.CN1CCCN(C)C1=O.CN1CCCN(C)C1=O>[CH3:9][O:10][C:11](=[O:27])[CH:12]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[CH:15][CH:14]=1)[CH2:29][CH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1
Reactant: ICC1CCCC1
Reactant: COC(=O)Cc1ccc(OCc2ccccc2)cc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CN1CCCN(C)C1=O
Product: COC(=O)C(CC1CCCC1)c1ccc(OCc2ccccc2)cc1
Temperature: -78 °C
Reaction time: 0.75 h
Yield: 86.6 %

Procedure:
A solution of freshly prepared lithium diisopropylamide (23 mL of a 0.31M stock solution, 7.13 mmol) was cooled to −78° C. and then treated with a solution of (4-benzyloxy-phenyl)-acetic acid methyl ester (1.66 g, 6.48 mmol) in tetrahydrofuran/1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (16.1 mL, 3:1). The resulting solution was stirred at −78° C. for 45 min. At this time, the reaction was treated with a solution of iodomethylcyclopentane (1.50 g, 7.13 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (2 mL). The reaction mixture was stirred at −78° C. for 4 h. The reaction was then warmed to 25° C. and was stirred at 25° C. for 48 h. At this time, the reaction mixture was quenched by the dropwise addition of a saturated aqueous ammonium chloride solution (10 mL). This mixture was poured into water (100 mL) and extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with a saturated aqueous lithium chloride solution (1×100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 98/2 hexanes/ethyl acetate) afforded 2-(4-benzyloxy-phenyl)-3-cyclopentyl-propionic acid methyl ester (1.90 g, 86.6%) as a white wax: mp 55-57° C.; EI-HRMS m/e calcd for C22H26O3 (M+) 338.1881 found 228.1878.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[NH:10][S:9]1(=[O:18])=[O:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:39][CH2:40][N:41]1[CH2:46][CH2:45][N:44]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[CH2:43][CH2:42]1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]([CH2:39][CH2:40][N:41]2[CH2:46][CH2:45][N:44]([C:47]([O:49][C:50]([CH3:51])([CH3:53])[CH3:52])=[O:48])[CH2:43][CH2:42]2)[S:9]1(=[O:18])=[O:17]
Reactant: CC(C)(C)OC(=O)N1CCN(CCO)CC1
Reactant: Cc1ccccc1N1c2ccccc2NS1(=O)=O
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1ccccc1N1c2ccccc2N(CCN2CCN(C(=O)OC(C)(C)C)CC2)S1(=O)=O
Yield: 68.7 %

Procedure:
In an analogous manner as general procedure II, step 1, a solution of 1-(2-methylphenyl)-1,3-dihydro-2,1,3-benzothiadiazole2,2-dioxide (0.2 g, 0.77 mmol) in tetrahydrofuran (10 mL) was cooled to 0° C., treated with triphenylphosphine (0.3 g, 1.2 mmol), tert-Butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate (0.36 g, 1.54 mmol) were added followed by diisopropylazodicarboxylate (0.23 mL, 1.2 mmol to provide tert-butyl 4-{2-[3-(2-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethyl}piperazine-1-carboxylate (0.25 g, 69%) as a white foam. HPLC purity 100.0% at 210-370 nm, 10.7 min.; Xterra RP18, 3.5 u, 150×4.6 mm column, 1.2 mL/min, 85/15-5/95 (Ammon. Form. Buff. Ph=3.5/ACN+MeOH) for 10 min, hold 4 min. HRMS: calcd for C24H32N4O4S+H+, 473.22170; found (ESI, [M+H]+Obs'd), 473.2229;
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[C:3]=1[N:14]=[N:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[CH:18][C:17]=1[NH:27][C:28](=[O:30])[CH3:29].C([O-])(=O)C.[Na+].[CH:36]([NH2:38])=O.C(OC(=O)C)(=O)C>[Cu]I.C(OCCCC)(=O)C>[C:36]([C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[C:3]=1[N:14]=[N:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[CH:18][C:17]=1[NH:27][C:28](=[O:30])[CH3:29])#[N:38]
Reactant: CCN(CC)c1ccc(N=Nc2c(Br)cc([N+](=O)[O-])cc2[N+](=O)[O-])c(NC(C)=O)c1
Reactant: NC=O
Agent: [Cu]I
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CCCCOC(C)=O
Solvent: CC(=O)OC(C)=O
Product: CCN(CC)c1ccc(N=Nc2c(C#N)cc([N+](=O)[O-])cc2[N+](=O)[O-])c(NC(C)=O)c1
Temperature: 110 °C
Reaction time: 0.25 h
Yield: 88 %

Procedure:
2-Bromo-4,6-dinitro-2'-acetylamino-4'-(N,N-diethylamino) azobenzene (479 parts), copper (I) iodide (19 parts), anhydrous sodium acetate (246 parts), formamide (180 parts), acetic anhydride (408 parts) and n-butyl acetate (2190 parts) are mixed together and heated, with stirring, to 110° C. during 15 minutes. The temperature is maintained at 110° for 30 to 50 minutes, when a solid is suddenly precipitated from the reaction mixture, indicating completion of the reaction. The mixture is allowed to cool to room temperature and the product is collected, washed with ethanol to remove residual n-butyl acetate and dried. 2-Cyano-4,6-dinitro-2'-acetylamino-4'-(N,N-diethylamino)azobenzene is obtained in 88% yield and requires no purification.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][CH:22]=3)[NH:19][N:18]=[CH:17]4)=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][C:3]=1C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[Br-].CC1[N:65]=C([Zn+])C=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:4][C:3]1[N:65]=[C:5]([C:8]2[C:13]([C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][CH:22]=3)[NH:19][N:18]=[CH:17]4)=[CH:12][CH:11]=[CH:10][N:9]=2)[CH:6]=[CH:7][CH:2]=1
Reactant: Cc1cc(-c2ncccc2-c2ccc3[nH]ncc3c2)ccc1F
Reactant: Cc1cccc([Zn+])n1
Agent: [Pd]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Product: Cc1cccc(-c2ncccc2-c2ccc3[nH]ncc3c2)n1
Temperature: 65 °C
Reaction time: 6 h
Yield: 47.4 %

Procedure:
A vial with a piercable teflon cap containing a magetic stir was charged with 5-[2-(4-fluoro-3-methylphenyl)pyridin-3-yl]-1H-indazole (0.2 g, 0.87 mmol), Pd2(dba)3(30 mg, 0.03 mmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (XPHOS, 60 mg, 0.13 mmol) under argon atmosphere. 6-Methyl-2-pyridylzinc bromide (0.5 M in THF, 4.0 mL, 2 mmol) was added to above reactants and degassed under vacuum. After three degas cycles, the reaction mixture was heated at 65° C. under argon. After 6 h, the reaction mixture was cooled to the room temperature and diluted with Rochelle salt (5 mL) and concentrated to remove the volatiles. The concentrated aqueous solution was diluted with EtOAc (30 mL) and separated the organic layer. Aqueous solution was further extracted with EtOAc (30 mL). Combined organic layers washed with aq. NaCl (10 mL), stirred over MgSO4, and filtered through a pad of Florosil/celite. The filtrate was concentrated and purified by preparative HPLC. The collected fractions were concentrated, diluted with water and neutralized with aq. NaHCO3. The resultant solid formed was collected by filtration and dried to provide 5-(2-(6-Methylpyridin-2-yl)pyridin-3-yl)-1H-indazole (118 mg, 47%) as a white solid. 1H NMR (DMSO-d6): δ 13.01 (s, 1H), 8.63 (dd, 1H, J=0.8 and 4.7 Hz), 7.99 (s, 1H), 7.89 (d, 1H, J=7.9 Hz), 7.57 (app d, 2H, J=8.5 Hz), 7.51 (dd, 1H, J=4.9 and 7.6 Hz), 7.34 (d, 1H, J=8.8 Hz), 7.26 (d, 1H, J=7.6 Hz), 7.07 (d, 1H, J=7.6 Hz), 6.97 (d, 1H, J=8.8 Hz), 2.15 (s, 3H).LCMS: rt 2.13 min (B), purity 97%, MS (m/e) 287 (MH+).
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:12]([CH2:15][C:16](=[O:18])[CH3:17])(=[O:14])[CH3:13].N1CCCCC1.C(O)(=O)C>C(O)(C)C>[N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[C:15]([C:16](=[O:18])[CH3:17])[C:12](=[O:14])[CH3:13])=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O=Cc1ccc([N+](=O)[O-])cc1
Reactant: CC(=O)CC(C)=O
Solvent: CC(C)O
Solvent: C1CCNCC1
Solvent: CC(=O)O
Product: CC(=O)C(=Cc1ccc([N+](=O)[O-])cc1)C(C)=O
Temperature: 25 °C
Reaction time: 4 h

Procedure:
30.2 g (0.2 mol) of 4-nitrobenzaldehyde and 30.0 g (0.3 mol) of acetylacetone are dissolved in 200 ml of isopropanol and treated with 1.2 ml of piperidine and 1 ml of glacial acetic acid. The mixture is warmed in a water bath until a clear solution is formed and then stirred at RT for 4 h. The product precipitates and is filtered off with suction.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3=[CH:14][C:15]4[O:19][CH2:18][O:17][C:16]=4[CH:20]=[C:12]3[O:11][CH2:10]2)[C:2]1=[O:21].CC1(C)COC2=CC3OC[C:32]4([C:42]=3[CH:43]=C12)[C:40]1[C:35](=CC=CC=1)NC4=O.BrCC1CC1C>>[CH3:35][CH:40]1[CH2:32][CH:42]1[CH2:43][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3=[CH:14][C:15]4[O:19][CH2:18][O:17][C:16]=4[CH:20]=[C:12]3[O:11][CH2:10]2)[C:2]1=[O:21]
Reactant: O=C1Nc2ccccc2C12COc1cc3c(cc12)OCO3
Reactant: CC1(C)COc2cc3c(cc21)C1(CO3)C(=O)Nc2ccccc21
Agent: CC1CC1CBr
Product: CC1CC1CN1C(=O)C2(COc3cc4c(cc32)OCO4)c2ccccc21

Procedure:
Following the procedure described in EXAMPLE 10.21, and making non-critical variations using spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)one to replace 5,5-dimethyl-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one, and 1-(bromomethyl)-2-methylcyclopropane to replace 2-(bromonmethyl)-5-(trifluoromethyl)furan, the title compound was obtained (37%) as a white solid: MS (ES+) m/z 350.3 (M+1).
Reaction SMILES: [C:1]1([C:7]2[CH:14]=[CH:13][C:10]([CH:11]=O)=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:16]=1[CH3:22]>C(OC(=O)C)(=O)C>[CH3:21][C:18]1[CH:19]=[CH:20][N:15]=[C:16](/[CH:22]=[CH:11]/[C:10]2[CH:13]=[CH:14][C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:8][CH:9]=2)[CH:17]=1
Reactant: Cc1ccnc(C)c1
Reactant: O=Cc1ccc(-c2ccccc2)cc1
Solvent: CC(=O)OC(C)=O
Product: Cc1ccnc(/C=C/c2ccc(-c3ccccc3)cc2)c1
Temperature: 150 °C
Yield: 45.3 %

Procedure:
A mixture of 4-phenylbenzaldehyde (6.45 g), 2,4-lutidine (7.59 g), and acetic anhydride (10 ml) was heated on a bath at 150° C. for 12 hours and then heated under reflux for 12 hours. The reaction mixture was concentrated to dryness under reduced pressure, and the resulting residue was purified by silica-gel column chromatography (eluent, hexane:ethyl acetate=9:1 to 5:1) to give 4.35 g of a yellow solid of (E)-4-methyl-2-(4-phenylphenyl)ethenylpyridine.
Reaction SMILES: [N+](C1C=C([N+]([O-])=O)C=[CH:6][C:5]=1[S:13]([O-:16])(=[O:15])=O)([O-])=O.[Na+].[N+](C1C=C(C=[C:28]([N+]([O-])=O)[CH:29]=1)C(O)=O)([O-])=O>>[CH:29]([S:13]([CH2:5][S:13]([CH:5]=[CH2:6])(=[O:15])=[O:16])(=[O:16])=[O:15])=[CH2:28]
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)[O-])c([N+](=O)[O-])c1
Reactant: O=C(O)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Agent: [Na+]
Product: C=CS(=O)(=O)CS(=O)(=O)C=C
Yield: 85 %

Procedure:
By the procedure used in A, except that sodium 2,4-dinitrobenzenesulfonate was substituted for 3,5-dinitrobenzoic acid, a 16.5 g (85 percent yield) sample (m.p. 59°-61° C.) of bis(vinylsulfonyl)methane was obtained. A 2 percent by weight aqueous solution was made up (no insoluble material) and let stand for more than 10 months at room temperature. Analysis of the still clear solution by high pressure liquid chromatography (HPLC) showed a 1.6 percent concentration of bis(vinylsulfonyl)methane remaining. A sample of the dry compound was also kept at room temperature for more than 10 months. A fresh 2 percent by weight solution made from this sample was found to contain 1.8 percent bis(vinylsulfonyl)methane by HPLC analysis.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[CH:7](O)[CH2:6][CH2:5]2.C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[OH-].[Na+]>O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[CH2:7][CH:6]=[CH:5]2
Reactant: OC1CCc2cc(Cl)c(Cl)cc21
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: Cc1ccccc1
Product: Clc1cc2c(cc1Cl)CC=C2
Yield: 56.5 %

Procedure:
A mixture of 17.48 g of the product of Step B, 470 ml of toluene, 0.57 g of 4-tert.-butyl-chatechol and 1.63 g of p-toluene sulfonic acid was refluxed for 2 hours and then was diluted with water. 10 ml of N sodium hydroxide solution were added and the mixture was extracted with toluene. The organic phase was evaporated to dryness under reduced pressure and the residue was taken up in hexane. The mixture was vacuum filtered and the crystalline product was dried to obtain 9 g of the desired product melting at 76° C.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[NH:8][C:9]3[C:14]([CH:15]=2)=[CH:13][C:12]([C:16]#[N:17])=[CH:11][CH:10]=3)[CH:2]=1.[C:18](#[N:20])C>>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[NH:8][C:9]3[C:14]([C:15]=2[C:18]#[N:20])=[CH:13][C:12]([C:16]#[N:17])=[CH:11][CH:10]=3)[CH:2]=1
Reactant: N#Cc1ccc2[nH]c(-c3cccnc3)cc2c1
Reactant: CC#N
Product: N#Cc1ccc2[nH]c(-c3cccnc3)c(C#N)c2c1

Procedure:
2-Pyridin-3-yl-1H-indole-5-carbonitrile (Example 8) is processed according to the method described in Example 140, using acetonitrile instead of dichloromethane, to give 2-pyridin-3-yl-1H-indole-3,5-dicarbonitrile. 1H NMR (400 MHz, MeOD) δ ppm 7.68 (dd, J=8.6 Hz, 1H), 7.72 (dd, J=8.1, 4.8 Hz, 1H), 7.75 (d, J=8.3 Hz, 1H), 8.17 (s, 1H), 8.47 (dt, J=8.1, 1.9 Hz, 1H), 8.76 (dd, J=4.8, 1.5 Hz, 1H), 9.19 (d, J=1.5 Hz, 1H). HRMS (ESI) m/z 245.0823 [(M+H) calcd for C15H9N4: 245.0827].
Reaction SMILES: C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([OH:20])=[CH:14][C:15]([CH3:19])=[N:16]2)=[CH:11][CH:10]=1)C1C=CC=CC=1>CO.[Pd]>[CH3:19][C:15]1[CH:14]=[C:13]([OH:20])[C:12]2[C:17](=[CH:18][C:9]([OH:8])=[CH:10][CH:11]=2)[N:16]=1
Reactant: Cc1cc(O)c2ccc(OCc3ccccc3)cc2n1
Agent: [Pd]
Solvent: CO
Product: Cc1cc(O)c2ccc(O)cc2n1
Reaction time: 1 h
Yield: 111.4 %

Procedure:
A solution of 3 g (10.5 mmol) of 7-benzyloxy-2-methyl-quinolin-4-ol, product of example 1 c), dissolved in 270 ml of MeOH was treated with 1 g of palladium on charcoal (10%) and then hydrogenated at RT for 1 h until HPLC analysis indicated the completion of the reaction. The catalyst was filtered off, washed with MeOH, and the solution was concentrated in vacuo. The residue was triturated with ether, collected by filtration and dried in a high vacuum to give 2.05 g (98.6%) 2-methyl-quinoline-4,7-diol as an off-white solid. ISP mass spectrum, m/e: 176.2 (M+1 calculated for C10H9NO2: 176).