Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[CH:2]=[C:3]2[C:8]3=[C:9]([C:11]([NH:13][C:14](=[O:15])[C:7]3=[CH:6][CH:5]=[CH:4]2)=[O:12])[CH:10]=1.[CH2:16]=[O:17]>CN(C)C=O>[OH:17][CH2:16][N:13]1[C:14](=[O:15])[C:7]2[CH:6]=[CH:5][CH:4]=[C:3]3[C:8]=2[C:9](=[CH:10][CH:1]=[CH:2]3)[C:11]1=[O:12]
Reactant: O=C1NC(=O)c2cccc3cccc1c23
Reactant: C=O
Solvent: CN(C)C=O
Product: O=C1c2cccc3cccc(c23)C(=O)N1CO
Reaction time: 8 h

Procedure:
30 g. (0.15 mole) of 1,8-naphthalimide and 12.5 ml. of 37% aqueous formaldehyde (0.17 mole) are combined in 100 ml. of dimethylformamide and heated on a hot plate (90°-110°) until all the materials dissolve. The solution is then allowed to stand overnight at 25°. The resulting precipitate is filtered off, washed with water and recrystallized from dioxane. This material is dried overnight at 25° (0.1 mm.) to yield 26.4 g. of the titled compound which has an indistinct melting point.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.Br[CH2:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:13]=1>>[N:1]1([CH2:11][C:12]2[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:13]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: COC(=O)c1ccc(CBr)cc1
Reactant: c1ccc2[nH]ccc2c1
Product: COC(=O)c1ccc(Cn2ccc3ccccc32)cc1

Procedure:
Following a procedure and using relative proportions of starting materials similar to those described in Example 65, but using indole and methyl 4-(bromomethyl)benzoate as starting material, the title compound was obtained as a solid.
Reaction SMILES: [F:1][C:2]1[C:3]([NH2:11])=[C:4]([NH2:10])[CH:5]=[C:6]([F:9])[C:7]=1[F:8].[CH:12]([N:15]=[C:16]=S)([CH3:14])[CH3:13].CC1C=CC(S([O-])(=O)=O)=CC=1.C[N+]1(CCN=C=NC2CCCCC2)CCOCC1>N1C=CC=CC=1>[F:1][C:2]1[C:3]2[N:11]=[C:16]([NH:15][CH:12]([CH3:14])[CH3:13])[NH:10][C:4]=2[CH:5]=[C:6]([F:9])[C:7]=1[F:8]
Reactant: CC(C)N=C=S
Reactant: Nc1cc(F)c(F)c(F)c1N
Agent: C[N+]1(CCN=C=NC2CCCCC2)CCOCC1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Solvent: c1ccncc1
Product: CC(C)Nc1nc2c(F)c(F)c(F)cc2[nH]1
Yield: 56.9 %

Procedure:
3,4,5-Trifluoro-1,2-phenylenediamine (6.0 g, 31.2 mmol), isopropyl isothiocyanate (3.6 g, 35.6 mmol), 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate (17.0 g, 40.1 mmol) and pyridine (225 mL) were used according to general procedure I. The title compound was recrystallized from 1,4-dioxane to provide a white solid (4.07 g, 57%); m.p. 182-184° C.; 1H NMR (DMSO-d6) δ: 10.97 (br s, 1H, NH), 7.01 (m, 1H, Ar—H), 6.80 (br s, 1H, NH), 3.91 (m, 1H, CH), 1.20 (d, J=6.4 Hz, 6H, overlapping CH3).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C:11]([NH2:13])=[O:12])=[CH:5][CH:4]=1)#[N:2].Cl>[Pd].C(OCC)C>[NH2:13][C:11]([CH2:10][CH2:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:1][NH2:2])=[CH:4][CH:5]=1)=[O:12]
Reactant: N#Cc1ccc(CCC(N)=O)cc1
Agent: [Pd]
Agent: Cl
Solvent: CCOCC
Product: NCc1ccc(CCC(N)=O)cc1
Yield: 88 %

Procedure:
Prepared analogously to Example 43b) from 4-cyanobenzenepropanamide by catalytic hydrogenation using palladium/activated charcoal and in the presence of 1 equivalent of 2N hydrochloric acid in a yield of 88% of theory. Colourless crystals (diethylether).
Reaction SMILES: [C:1](#[N:4])[CH:2]=[CH2:3].[CH2:5](S)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]>>[CH3:5][C:6]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[CH2:1].[C:1](#[N:4])[CH:2]=[CH2:3]
Reactant: CCCCCCCCS
Solvent: C=CC#N
Product: C=C(C)c1ccccc1
Reaction time: 4 h

Procedure:
A one-gallon, glass-lined latex reactor was charged with 1691 g of deionized water, 107 g of polystyrene seed latex (400 Angstrom number average particle size) (30% active), 0.2 g of disodium ethylene diaminetetraacetic acid, 1.0 g of sodium bicarbonate, and 20 g of 43% aqueous sodium n-dodecylbenzene sulfonate. The mixture was purged with nitrogen, and the reactor was then evacuated with a water aspirator three times at room temperature. After the final evacuation, the reactor was pressurized with 10 psi (69 KPa) of nitrogen. The reactor was heated to 85° C. and stirred at 150 rpm. An aqueous feed consisting of 154 g of water, 27.7 g of 43% aqueous sodium n-dodecylbenzene sulfonate, and 2.7 g of sodium persulfate and a monomer feed consisting of 750 g of α-methylstyrene, 187.5 g of acrylonitrile, (providing a ratio α-methylstyrene/acrylonitrile of 80/20) and 0.68 g of n-octyl mercaptan (first monomer feed stream) were started simultaneously and added at rates of 37.4 and 234.6 g per hour to the reaction, respectively. After four hours, addition of first monomer feed stream was halted and the second monomer feed stream consisting of 41.4 g of acrylonitrile and 0.53 g of n-octyl mercaptan was started at a rate of 20.7 g per hour. The aqueous feed rate was changed to 15.5 g per hour. The additions of aqueous feed and second monomer stream were continued for three additional hours. Total monomer feed resulted in a ratio, α-methylstyrene/acrylonitrile, of 77/23. The second monomer feed was then halted, the aqueous feed continued for an additional 15 minutes, and the mixture was retained at 85° C. for 15 minutes. An antifoaming agent (antifoam H-10, 15% active, available from Dow Corning Corporation) was added and volatile components were steam distilled from the mixture. The reaction went to 92% conversion.
Reaction SMILES: C([O:8][CH2:9][C:10]1[N:11]([C:27]2[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=2)[CH:12]=[C:13]([C:15]2[C:16]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N:17][O:18][C:19]=2[CH3:20])[N:14]=1)C1C=CC=CC=1.FC(F)(F)C(O)=O.FC(F)(F)S(O)(=O)=O.C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH3:20][C:19]1[O:18][N:17]=[C:16]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:15]=1[C:13]1[N:14]=[C:10]([CH2:9][OH:8])[N:11]([C:27]2[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=2)[CH:12]=1
Reactant: Cc1onc(-c2ccccc2)c1-c1cn(-c2ccc([N+](=O)[O-])cc2)c(COCc2ccccc2)n1
Agent: O=C([O-])O
Agent: O=S(=O)(O)C(F)(F)F
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1onc(-c2ccccc2)c1-c1cn(-c2ccc([N+](=O)[O-])cc2)c(CO)n1
Reaction time: 3 h
Yield: 56.2 %

Procedure:
To a solution of 4-[2-benzyloxymethyl-1-(4-nitro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazole (200 mg, 0.43 mmol) in DCM (10 mL) at 0° C. was added trifluoroacetic acid (0.98 mL) and trifluoromethanesulfonic acid (0.06 mL) and the resulting mixture stirred vigorously for 3 h. The mixture was then poured onto a saturated solution of sodium hydrogen carbonate and stirred for 30 min. The resulting precipitate was then filtered off, washed with water and then dried to afford the title compound (91 mg, 56%) which was obtained as a white solid. MS: m/e=377.4 [M+H]+.
Reaction SMILES: C(O[C:6]([NH:8][C@@H:9]([CH2:21][O:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]#[N:30])[CH:24]=1)[CH2:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:7])(C)(C)C.[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][CH:41]([O:44][C:45]2[CH:53]=[CH:52][C:48](C(O)=O)=[CH:47][CH:46]=2)[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>Cl.O1CCOCC1.O1CCOCC1.O>[C:29]([C:25]1[CH:24]=[C:23]([CH:28]=[CH:27][CH:26]=1)[O:22][CH2:21][C@H:9]([NH:8][C:6](=[O:7])[C:48]1[CH:47]=[CH:46][C:45]([O:44][CH:41]2[CH2:40][CH2:39][N:38]([C:36]([O:35][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:37])[CH2:43][CH2:42]2)=[CH:53][CH:52]=1)[CH2:10][C:11]([O:13][CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:12])#[N:30]
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2ccc(C(=O)O)cc2)CC1
Reactant: CC(C)(C)OC(=O)N[C@@H](COc1cccc(C#N)c1)CC(=O)OCc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCC(Oc2ccc(C(=O)N[C@@H](COc3cccc(C#N)c3)CC(=O)OCc3ccccc3)cc2)CC1
Reaction time: 16 h

Procedure:
1.46 g (3.56 mmol) of benzyl (3R)-3-(t-butoxycarbonyl)amino-4-(3-cyanophenoxy)butyrate was dissolved in 10 ml of 4 N dioxane hydrochloride and 5 ml of dioxane, and the solution was stirred for 15 hours. The solvent was evaporated, and the residue was dissolved in 20 ml of dichloromethane. 1.14 g (3.56 mmol) of 4-(1-t-butoxycarbonyl-4-piperidyloxy)benzoic acid, 2.48 ml (17.8 mmol) of triethylamine, 748 mg (3.92 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 529 mg (3.92 mmol) of 1-hydroxybenzotriazole were added to the solution, and they were stirred for 16 hours. The reaction liquid was diluted with water. After the extraction with ethyl acetate, the organic layer was successively washed with water, 1 N sodium hydroxide and saturated aqueous NaCl solution, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was treated by the silica gel column chromatography to obtain the title compound.
Reaction SMILES: N#N.[Br:3][C:4]1[C:11]([F:12])=[CH:10][C:7]([CH2:8][OH:9])=[CH:6][C:5]=1[F:13].CCN(CC)CC.[S:21](Cl)([CH3:24])(=[O:23])=[O:22]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:24][S:21]([O:9][CH2:8][C:7]1[CH:10]=[C:11]([F:12])[C:4]([Br:3])=[C:5]([F:13])[CH:6]=1)(=[O:23])=[O:22]
Reactant: OCc1cc(F)c(Br)c(F)c1
Reactant: CS(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Agent: N#N
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCc1cc(F)c(Br)c(F)c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 4-bromo-3,5-difluorobenzyl alcohol (100 mg, 0.45 mmol) in dry CH2Cl2 (3 mL) was treated at 0° C. with Et3N (0.081 mL, 0.58 mmol) followed by DMAP (5 mg, 0.045 mmol) and Ms-Cl (0.037 mL, 0.47 mmol). After stirring at 0° C. for 0.5 h and at rt for 0.5 h, the reaction was quenched with water (2 mL). The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give crude (4-bromo-3,5-difluorophenyl)methyl methanesulfonate as a yellow oil. This material was dissolved in dry DMF (3 mL) and treated with NaN3 (29 mg, 0.45 mmol) at 80° C. until completion of the reaction. The reaction mixture was then cooled down to rt and partitioned between EA and water. The layers were separated and the org. layer dried over MgSO4, filtered and concentrated under reduced pressure to give crude 1-(azidomethyl)-4-bromo-3,5-difluorobenzene as a yellow oil. LC-MS-conditions 07: tR=0.90 min.
Reaction SMILES: CN(C)C=O.P(Cl)(Cl)(Cl)=O.C(C1N=C([C@@H:19]2[CH2:23][C@@H:22]([O:24][S:25]([CH3:28])(=[O:27])=[O:26])[CH2:21][N:20]2[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=2)=[O:30])SC=1)(O)=O.O.N>O1CCCC1>[CH3:28][S:25]([O:24][CH:22]1[CH2:21][N:20]([C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=2)=[O:30])[CH2:19][CH2:23]1)(=[O:26])=[O:27]
Reactant: CS(=O)(=O)O[C@@H]1C[C@@H](c2nc(C(=O)O)cs2)N(C(=O)OCc2ccc([N+](=O)[O-])cc2)C1
Agent: N
Solvent: C1CCOC1
Solvent: CN(C)C=O
Solvent: O=P(Cl)(Cl)Cl
Product: CS(=O)(=O)OC1CCN(C(=O)OCc2ccc([N+](=O)[O-])cc2)C1
Reaction time: 0.5 h
Yield: 124.5 %

Procedure:
To a mixture of dimethylformamide (0.45 ml) and tetrahydrofuran (10 ml) was dropwise added phosphorus oxychloride (0.46 ml) at -5°∫5° C., and the mixture was stirred at the same temperature for 30 minutes. To the mixture was added a solution of (2S,4R)-2-(4-carboxythiazol-2-yl) -4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl) pyrrolidine (1.54 g) in tetrahydrofuran (20 ml) at -5°∫5° C., followed by stirring at the same temperature for 30 minutes. The mixture was dropwise added to concentrated ammonia water (15 ml) at 0°-10° C. with stirring. The mixture was stirred at the same condition for 2 hours. Tetrahydrofuran was removed under reduced pressure to give a residue, which was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to give (2S, 4R)-2-(4-carbamoylthiazol)-2-yl) -4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.4 g).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[CH3:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([N:16]=[C:17]=[O:18])=[CH:12][CH:11]=1>C1(C)C=CC=CC=1>[CH3:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]([NH:1][C:2]2[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=2)=[O:18])=[CH:12][CH:11]=1
Reactant: Nc1ccncc1
Reactant: COc1ccc(N=C=O)cc1
Solvent: Cc1ccccc1
Product: COc1ccc(NC(=O)Nc2ccncc2)cc1
Temperature: 110 °C
Reaction time: 4 h

Procedure:
4-Aminopyridine (100 mg, 1.06 mmol) and 4-methoxyphenyl isocyanate (158.5 mg, 1.06 mmol) were dissolved in toluene, and the mixture was then stirred at 110° C. for 4 hr.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH3:27])[C:5]2[N:10]=[C:9]([C:11]3[N:15]([C:16]4[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][N:17]=4)[N:14]=[C:13]([S:23][CH3:24])[CH:12]=3)[O:8][C:7](=[O:25])[C:6]=2[CH:26]=1.ClCCl.[Mg].[OH2:32]>>[Cl:1][C:2]1[CH:3]=[C:4]([CH3:27])[C:5]2[N:10]=[C:9]([C:11]3[N:15]([C:16]4[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][N:17]=4)[N:14]=[C:13]([S:23]([CH3:24])=[O:32])[CH:12]=3)[O:8][C:7](=[O:25])[C:6]=2[CH:26]=1
Reactant: O
Reactant: CSc1cc(-c2nc3c(C)cc(Cl)cc3c(=O)o2)n(-c2ncccc2Cl)n1
Agent: [Mg]
Solvent: ClCCl
Product: Cc1cc(Cl)cc2c(=O)oc(-c3cc(S(C)=O)nn3-c3ncccc3Cl)nc12
Temperature: 25 °C
Reaction time: 22 h

Procedure:
To a mixture of 0.20 g of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-methylthio-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine-4-one, 5 ml of dichloromethane and 0.5 ml of water was added 0.18 g of magnesium bis(monoperoxophthalate) hexahydrate (MMPP), and the resulting mixture was stirred at room temperature for 22 hours. Water was added to the reaction mixture, and the mixture was extracted with methyl t-butyl ether. The organic layer was washed with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 0.20 g of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-methylsulfinyl-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine-4-one of the formula:
Reaction SMILES: O/[CH:2]=[C:3]1\[C:4](=O)[CH2:5][CH2:6][C:7]([CH3:10])([CH3:9])[CH2:8]\1.[NH2:12][NH2:13]>CO>[CH3:9][C:7]1([CH3:10])[CH2:6][CH2:5][C:4]2[NH:13][N:12]=[CH:2][C:3]=2[CH2:8]1
Reactant: NN
Reactant: CC1(C)CCC(=O)/C(=C\O)C1
Solvent: CO
Product: CC1(C)CCc2[nH]ncc2C1
Temperature: 25 °C
Reaction time: 0.83 h
Yield: 82.9 %

Procedure:
In a 100 ml round-bottomed flask, 2-[1-hydroxy-meth-(Z)-ylidene]-4,4-dimethyl-cyclohexanone (1.30 g, 8.43 mmol) was dissolved in methanol (8.5 ml). Hydrazine (0.27 ml, 8.43 mmol) was added very slowly which resulted in an exothermic reaction. The reaction mixture was stirred at room temperature for 50 min then concentrated. The residue was triturated with petroleum ether to afford 1.05 g (83%) of 5,5-dimethyl-4,5,6,7-tetrahydro-1H-indazole as a light brown solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 7.28 (s, 1H), 2.67 (t, J=6.6 Hz, 2H), 2.32 (s, 2H), 1.60 (t, J=6.6 Hz, 2H), 0.99 (s, 6H).
Reaction SMILES: [C:1]([C:5]1[CH:9]=[C:8]([C:10]([CH3:13])([CH3:12])[CH3:11])[N:7]([CH2:14][C:15]2[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=2[O:23][CH2:24][CH:25]([CH3:27])[CH3:26])[CH:18]=O)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])=[C:31]([F:42])[CH:30]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(OCC)(=O)C>[C:1]([C:5]1[CH:9]=[C:8]([C:10]([CH3:13])([CH3:12])[CH3:11])[N:7]([CH2:14][C:15]2[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=2[O:23][CH2:24][CH:25]([CH3:27])[CH3:26])[CH2:18][NH:28][C:29]2[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])=[C:31]([F:42])[CH:30]=2)[N:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)COc1ccc(C=O)cc1Cn1nc(C(C)(C)C)cc1C(C)(C)C
Reactant: CCOC(=O)CCc1ccc(N)cc1F
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: CCOC(=O)CCc1ccc(NCc2ccc(OCC(C)C)c(Cn3nc(C(C)(C)C)cc3C(C)(C)C)c2)cc1F
Temperature: 25 °C
Reaction time: 3 h
Yield: 94.5 %

Procedure:
To a solution of 3-[(3,5-di-tert-butyl-1H-pyrazol-1-yl)methyl]-4-isobutoxybenzaldehyde (0.43 g, 1.16 mmol) and ethyl 3-(4-amino-2-fluorophenyl)propanoate (0.25 g, 1.16 mmol) in 1,2-dichloroethane (8.6 mL) was added acetic acid (0.20 mL, 3.48 mmol), and the mixture was stirred at room temperature for 3 hr. Sodium triacetoxyborohydride (0.74 g, 3.48 mmol) was added, and the mixture was further stirred for 5 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogencarbonate and saturated brine, dried, and concentrated under reduced pressure to give the title compound (0.62 g, yield 100%) as a colorless oil.
Reaction SMILES: Cl.Cl.O[C:4](=[C:20]1[CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]1=O)[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[CH2:8][CH2:7]1.O.[NH2:31][NH2:32].C(N(CC)CC)C.CO.CN(C=O)C>O>[CH3:19][O:18][C:15]1[CH:14]=[CH:13][C:12]([N:9]2[CH2:8][CH2:7][N:6]([CH2:5][C:4]3[C:20]4[CH2:28][C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[C:21]=4[NH:31][N:32]=3)[CH2:11][CH2:10]2)=[CH:17][CH:16]=1
Reactant: COc1ccc(N2CCN(CC(O)=C3Cc4ccccc4C3=O)CC2)cc1
Reactant: NN
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: COc1ccc(N2CCN(Cc3n[nH]c4c3Cc3ccccc3-4)CC2)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 29 %

Procedure:
A suspension of 2-(1-hydroxy-2-(4-(4-methoxyphenyl)-piperazin-1-yl)-ethylidene)-indan-1-one dihydrochloride (0.30 g), hydrazine monohydrate (1 cm3) and triethylamine (0.30 cm3) in 1:1 methanol-DMF (10 cm3) was stirred at room temperature under argon for 24 hours. The solution was poured into water (25 cm3) and extracted with ethyl acetate (2×25 cm3). The extracts were dried (MgSO4), filtered and concentrated. Flash column chromatography on silica gel, eluting with 2% methanol-dichloromethane, gave a yellow solid, which was recrystallised from ethanol-water to give the title compound (0.07 g; 29%) as yellow crystals, m.p. 176°-178° C. (from EtOH-H2O); δH (360 MHz, d6 -DMSO) 2.55-2.58 (4H, m, 2 x NCH2 CH2N), 3.01-3.04 (4H, m, 2 x NCH2CH2N), 3.27 (2H, s, --CH2 --, partly obscured by H2O signal), 3.58 (2H, s, --CH2N), 3.67 (3H, s, OCH3), 6.79 (2H, d, JAB 9.2, 2 of ArH), 6.87 (2H, d, JAB 9.2, 2 of ArH), 7.24 (1H, dd, J 7.4 and 7.4, 1 of ArH), 7.32 (1H, dd, J 7.4 and 7.4, 1 of ArH), 7.51 (1H, d, J 7.4, 1 of ArH), 7.59 (1H, broad d, J 7.4, 1 of ArH) and 12.58 (1H, broad s, NH); m/z (CI+ ; NH3) 361 (MH+ ; 23%), 214 (30) and 193 (100).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]2[N:8]([CH3:11])[N:9]=[CH:10][C:5]2=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=2)[N:3]=1.[CH3:21][C:22]1[C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][NH:24][N:23]=1>>[CH3:20][O:19][C:15]1[CH:14]=[C:13]([NH:12][C:4]2[N:3]=[C:2]([C:26]3[C:22]([CH3:21])=[N:23][NH:24][CH:25]=3)[N:7]=[C:6]3[N:8]([CH3:11])[N:9]=[CH:10][C:5]=23)[CH:18]=[CH:17][CH:16]=1
Reactant: Cc1n[nH]cc1B1OC(C)(C)C(C)(C)O1
Reactant: COc1cccc(Nc2nc(Cl)nc3c2cnn3C)c1
Product: COc1cccc(Nc2nc(-c3c[nH]nc3C)nc3c2cnn3C)c1

Procedure:
6-Chloro-N-(3-methoxyphenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine 6 was reacted with 3-methylpyrazole-4-boronic acid pinacol ester using General Procedure A. Purification on silica yielded 120. NMR: (CDCl3): 2.80 (s, 3H, CH3), 3.87 (s, 3H, CH3), 4.06 (s, 3H, CH3), 6.86 (dd, H, ArH, J=1.7, 8.29), 7.14 (dd, H, ArH, J=1.2, 7.89), 7.25 (s, H, ArH), 7.36 (t, H, ArH, J=8.11), 7.44 (s, H, ArH), 8.32 (s, H, ArH). MS: (ESI+) MH+=336.24
Reaction SMILES: [F:1][C:2]1[CH:15]=[CH:14][C:13]2[C:4](=[C:5]([CH3:16])[N:6]=[C:7]3[C:12]=2[CH:11]=[CH:10][CH:9]=[CH:8]3)[CH:3]=1.[BH4-].[Na+].FC(F)(F)C(O)=O.C1C=CC2C3C=CC=CC=3NCC=2C=1.C(N(CC)CC)C.[CH3:47][O:48][C:49]1[CH:50]=[C:51]([S:55](Cl)(=[O:57])=[O:56])[CH:52]=[CH:53][CH:54]=1>O1CCCC1.ClCCl>[CH:2]1[CH:15]=[CH:14][C:13]2[C:12]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[NH:6][CH2:5][C:4]=2[CH:3]=1.[F:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[C:12]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[N:6]([S:55]([C:51]1[CH:52]=[CH:53][CH:54]=[C:49]([O:48][CH3:47])[CH:50]=1)(=[O:57])=[O:56])[CH:5]2[CH3:16]
Reactant: Cc1nc2ccccc2c2ccc(F)cc12
Reactant: COc1cccc(S(=O)(=O)Cl)c1
Agent: [BH4-]
Agent: [Na+]
Agent: c1ccc2c(c1)CNc1ccccc1-2
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1cccc(S(=O)(=O)N2c3ccccc3-c3ccc(F)cc3C2C)c1

Procedure:
The intermediate dihydrophenanthridine was prepared from 8-fluoro-6-methylphenanthridine, (Example 32, Method A, Step b, 2.00 g, 9.45 mmol), by treatment with sodium borohydride (1.79 g, 47.4 mmol) and trifluoroacetic acid (2.9 mL, 37.9 mmol) in tetrahydrofuran (38 mL). In a separate, second step, the dihydrophenanthridine was treated with triethylamine (2.9 mL, 21 mmol) and 3-methoxybenzenesulfonyl chloride (0.78 g, 3.8 mmol, 1.1 equivalents) in dichloromethane (5 mL) according to the procedure and in the same manner as described in Example 32, Method A, Step d. The crude product was purified by re-crystallization from a mixture of ethyl acetate-hexane to yield 8-fluoro-5-[(3-methoxyphenyl)sulfonyl]-6-methyl-5,6-dihydrophenanthridine as a homogeneous solid (1.02 g, 78% from the dihydrophenanthridine), m.p. 130-131° C.;
Reaction SMILES: CC(C)[O-].[Al+3:5].CC(C)[O-].CC(C)[O-].[O:14]=[C:15]1[C:24]2[C:19](=[N:20][CH:21]=[CH:22][CH:23]=2)[O:18][C:17]2[CH:25]=[CH:26][C:27]([CH:29]([CH3:33])[C:30]([OH:32])=[O:31])=[CH:28][C:16]1=2.O>C(O)(C)C>[O:14]=[C:15]1[C:24]2[C:19](=[N:20][CH:21]=[CH:22][CH:23]=2)[O:18][C:17]2[CH:25]=[CH:26][C:27]([CH:29]([CH3:33])[C:30]([O-:32])=[O:31])=[CH:28][C:16]1=2.[Al+3:5].[O:14]=[C:15]1[C:24]2[C:19](=[N:20][CH:21]=[CH:22][CH:23]=2)[O:18][C:17]2[CH:25]=[CH:26][C:27]([CH:29]([CH3:33])[C:30]([O-:32])=[O:31])=[CH:28][C:16]1=2.[O:14]=[C:15]1[C:24]2[C:19](=[N:20][CH:21]=[CH:22][CH:23]=2)[O:18][C:17]2[CH:25]=[CH:26][C:27]([CH:29]([CH3:33])[C:30]([O-:32])=[O:31])=[CH:28][C:16]1=2
Reactant: CC(C(=O)O)c1ccc2oc3ncccc3c(=O)c2c1
Agent: CC(C)[O-]
Agent: [Al+3]
Solvent: CC(C)O
Solvent: O
Product: CC(C(=O)[O-])c1ccc2oc3ncccc3c(=O)c2c1

Procedure:
A solution of 2 g of aluminum isopropoxide in 30 ml of isopropyl alcohol is added dropwise to a solution of 2.7 g of 2-(5-oxo-5H-[1]benzopyrano[2,3-b]pyridin-7-yl)propionic acid in 100 ml of isopropyl alcohol with stirring. The addition is accompanied by immediate formation of white crystals. The mixture is stirred under reflux for 1 hour, and 20 ml of water is added to the reaction mixture, and then the whole mixture is refluxed for an additional hour. After cooling, the crystals are filtered off, washed with isopropyl alcohol, and dried to give aluminum 2-(5-oxo-5H-[1]-benzopyrano[2,3-b]pyridin-7-yl)propionate as white crystals melting at above 250°C.
Reaction SMILES: C[O:2][C:3]([C:5]1[C:6]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[N+:20]([O-:22])=[O:21])=[CH:7][CH:8]=[C:9]([C:11](=[S:13])[NH2:12])[CH:10]=1)=[O:4].[F:23][C:24]([F:36])([F:35])[C:25]1[CH:34]=[CH:33][C:28]([C:29](=O)[CH2:30]Br)=[CH:27][CH:26]=1>>[N+:20]([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[C:6]1[C:5]([C:3]([OH:2])=[O:4])=[CH:10][C:9]([C:11]2[S:13][CH:30]=[C:29]([C:28]3[CH:33]=[CH:34][C:25]([C:24]([F:23])([F:35])[F:36])=[CH:26][CH:27]=3)[N:12]=2)=[CH:8][CH:7]=1)([O-:22])=[O:21]
Reactant: O=C(CBr)c1ccc(C(F)(F)F)cc1
Reactant: COC(=O)c1cc(C(N)=S)ccc1-c1ccccc1[N+](=O)[O-]
Product: O=C(O)c1cc(-c2nc(-c3ccc(C(F)(F)F)cc3)cs2)ccc1-c1ccccc1[N+](=O)[O-]
Yield: 40 %

Procedure:
2′-Nitro-4-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-biphenyl-2-carboxylic acid (120 mg, 40%) was prepared from 2′-nitro-4-thiocarbamoyl-biphenyl-2-carboxylic acid methyl ester (which may be prepared as described for Intermediate 4) and 4-(trifluoromethyl)phenacyl bromide (available from Oakwood Products, Inc.) using the procedure described for the preparation of Example 1. 1H NMR (300 MHz, DMSO-d6) δ 13.16 (s, 1H), 8.59 (s, 1H), 8.51 (s, 1H), 8.27-8.31 (m, 3H), 8.15 (d, J=8.1 Hz, 1H), 7.77-7.87 (m, 3H), 7.66 (t, J=8.0 Hz, 1H), 7.42-7.49 (m, 2H).