Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][CH:7]([OH:9])[CH3:8].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>ClCCl>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7](=[O:9])[CH3:8]
Reactant: CC(O)Cc1ccco1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CC(=O)Cc1ccco1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a solution of 1-(2-furyl)-propan-2-ol (3.25 g) in dichloromethane (200 ml) was added in one portion pyridinium chlorochromate (13.0 g). The resulting mixture was stirred at room temperature for 5 h and then filtered through a small bed of silica. The organics were evaporated to give the crude product which was used without further purification (3.53 g).
Reaction SMILES: Cl[C:2]1[C:3]2[S:18][C:17]([NH2:19])=[N:16][C:4]=2[N:5]=[C:6]([S:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:7]=1.[NH2:20][C@H:21]([CH3:24])[CH2:22][OH:23]>>[NH2:19][C:17]1[S:18][C:3]2[C:2]([NH:20][C@H:21]([CH3:24])[CH2:22][OH:23])=[N:7][C:6]([S:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)=[N:5][C:4]=2[N:16]=1
Reactant: C[C@@H](N)CO
Reactant: Nc1nc2nc(SCc3ccccc3)nc(Cl)c2s1
Product: C[C@H](CO)Nc1nc(SCc2ccccc2)nc2nc(N)sc12

Procedure:
Prepared by the method of example 2 step a), using the product of example 1 step c) and (R)-(−)-2-amino-1-propanol.
Reaction SMILES: [C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].[CH2:9]([C@@H:11]1[CH2:16][NH:15][CH2:14][CH2:13][N:12]1[C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH:28]([F:30])[F:29])=[CH:23][CH:22]=1)=[O:18])C.FC(F)OC1C=CC(CO)=CC=1>>[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].[CH3:9][C@@H:11]1[CH2:16][NH:15][CH2:14][CH2:13][N:12]1[C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH:28]([F:30])[F:29])=[CH:23][CH:22]=1)=[O:18]
Reactant: CC[C@@H]1CNCCN1C(=O)OCc1ccc(OC(F)F)cc1
Agent: O=C(O)/C=C/C(=O)O
Agent: OCc1ccc(OC(F)F)cc1
Product: C[C@@H]1CNCCN1C(=O)OCc1ccc(OC(F)F)cc1

Procedure:
(R)-4-Difluoromethoxybenzyl 2-methylpiperazine-1-carboxylate fumarate was prepared from (R) 1-chlorocarbonyl-2-methyl-4-tert-butoxycarbonylpiperazine and 4-difluoromethoxybenzyl alcohol according to the methods described for Examples 48 and 54 to give the product as a white solid (24.0%); melting point 123.9–124.5° C.; NMR δH (400 MHz, DMSO-d6) 1.174(3H, d, J 7.0 Hz), 2.622(1H, m), 3.003(2H, m), 3.766(1H, dd, J 2.5, 13 Hz), 4.187(1H, m), 5.067(2H, m), 6.542 (2H, s), 7.178(2H, d, J 9.0 Hz), 7.244(1H, t, J 74.0) and 7.424(2H, d, J 8.5 Hz).
Reaction SMILES: Br[CH2:2][CH2:3][CH:4]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[NH2:17][CH2:18][CH2:19][CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:5]1([CH:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:3][CH2:2][NH:17][CH2:18][CH2:19][CH:20]2[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH2:25]2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: BrCCC(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)OC(=O)N1CCC(CCN)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CC(C)(C)OC(=O)N1CCC(CCNCCC(c2ccccc2)c2ccccc2)CC1
Temperature: 65 °C
Reaction time: 8 h

Procedure:
3-bromo-1,1-diphenylpropane (2.6 g, 9 mmol) and tert-butyl 4-(2-aminoethyl)piperidine-1-carboxylate (4.7 g, 21 mmol) were mixed together in acetonitrile (100 ml) and potassium carbonate (1.3 g, 9 mmol) was added. The resulting mixture was heated to 65° C. with stirring under N2 overnight. After that time the mixture was cooled and concentrated under reduced pressure. The residue was partitioned between DCM and water. The DCM layer was washed with water, dried over MgSO4 and concentrated under reduced pressure to give the crude product as a clear oil. The crude product was purified by combiflash (0-10% MeOH/DCM) to give tert-butyl 4-(2-(3,3-diphenylpropylamino)ethyl)piperidine-1-carboxylate 48
Reaction SMILES: [CH:1]([C:4]1[C:5](=[O:16])[NH:6][C:7]2[C:12]([CH:13]=1)=[C:11]([OH:14])[CH:10]=[CH:9][C:8]=2[CH3:15])([CH3:3])[CH3:2].[CH2:17](Br)[CH:18]=[CH:19][CH3:20].C(=O)([O-])[O-].[K+].[K+].C(Cl)(Cl)Cl.O>CN(C)C=O>[CH2:17]([O:14][C:11]1[CH:10]=[CH:9][C:8]([CH3:15])=[C:7]2[C:12]=1[CH:13]=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:16])[NH:6]2)[CH:18]=[CH:19][CH3:20]
Reactant: CC=CCBr
Reactant: Cc1ccc(O)c2cc(C(C)C)c(=O)[nH]c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: ClC(Cl)Cl
Solvent: O
Product: CC=CCOc1ccc(C)c2[nH]c(=O)c(C(C)C)cc12
Temperature: 70 °C
Reaction time: 2.5 h
Yield: 68.4 %

Procedure:
3-Isopropyl-5-hydroxy-8-methyl-1,2-dihydrocarbostyril (2.2 g, 10.13 mmol) was dissolved in dimethylformamide (25 ml). Crotylbromide (1.22ml, 12.11 mmol) and potassium carbonate (2.8 g, 20.26 mmol) were added to the solution, and the mixture was stirred at 70° C. for 2.5 hours. After the mixture was cooled, chloroform-water was added for phase separation. The organic phase was washed with water, and saturated aqueous sodium chloride solution in this order, and dried. The solvent was distilled off under reduced pressure, and the residue was recrystallized from chloroform-n-hexane. As a result, 1.88 g of the title compound was obtained as colorless needles (68%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:12]([OH:14])=[O:13])[C:5]2[O:10][CH2:9][CH2:8][NH:7][C:6]=2[CH:11]=1.C(N(CC)CC)C.[C:22](Cl)(=[O:24])[CH3:23].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl>[C:22]([N:7]1[C:6]2[CH:11]=[C:2]([Cl:1])[CH:3]=[C:4]([C:12]([OH:14])=[O:13])[C:5]=2[O:10][CH2:9][CH2:8]1)(=[O:24])[CH3:23]
Reactant: O=C(O)c1cc(Cl)cc2c1OCCN2
Reactant: CC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CC(=O)N1CCOc2c(C(=O)O)cc(Cl)cc21
Yield: 65.2 %

Procedure:
A solution of 10 g of 6-chloro-3,4-dihydro-2H-1,4-benzoxazine-8-carboxylic acid and 6.5 ml of triethylamine in 100 ml of chloroform was cooled, and 4.4 g of acetyl chloride was added thereto with stirring. The resulting mixture was stirred at room temperature for 2 hours. To the liquid reaction mixture were added an aqueous solution of sodium hydrogen carbonate and chloroform, and the resulting organic layer was separated, washed with water, and then dried with magnesium sulfate. The solvent was distilled off under reduced pressure, thereby obtaining 7.8 g of 4-acetyl-6-chloro-3,4-dihydro-2H-1,4-benzoxazine-8-carboxylic acid. Melting point: 76°-77° C.
Reaction SMILES: [Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[C:4]([CH:19]([OH:22])[CH:20]=[CH2:21])[C:3]=1[CH3:23].C(N(CC)CC)C.[Si:31](OS(C(F)(F)F)(=O)=O)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]>C(Cl)Cl>[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[C:4]([CH:19]([O:22][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH:20]=[CH2:21])[C:3]=1[CH3:23]
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: C=CC(O)c1c(C)c(Br)c2ccccc2c1-c1ccc(Cl)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=CC(O[Si](C)(C)C(C)(C)C)c1c(C)c(Br)c2ccccc2c1-c1ccc(Cl)cc1
Reaction time: 0.75 h
Yield: 84.1 %

Procedure:
To a stirring 23° C. DCM solution (32 mL) of 1-(4-bromo-1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)prop-2-en-1-ol (1.47 g, 3.79 mmol) and triethylamine (2.3 mL, 16.5 mmol) was added TBDMS-OTf (2.0 mL, 11.65 mmol) and the reaction was stirred and monitored by TLC. After 45 minutes, an additional 2 mL of TBDMSOTf was added and the mixture allowed to stir overnight. The dark mixture was then quenched 10% NaHCO3 and the color dissipated. The mixture was washed with brine, dried with sodium sulfate and concentrated in vacuo. Column chromatography using silica gel with EtOAc in hexanes gave desired silylated product (1.60 g, 84% yield). 1H-NMR: (400 MHz, CDCl3): δ 8.39 (d, J=8.4 Hz, 1H); 7.55-745 (m, 3H); 7.34-7.30 m, 1H); 7.26-7.24 (m, 1H); 7.24-7.18 (d, J=8.0 Hz, 1H); 7.16-7.14 (m, 1H); 6.09-6.01 (m, 1H); 5.32-5.30 (m, 1H); 5.13-5.03 (m, 2H); 2.77 (s, 3H); 0.87 (s, 6H); 0.83 (s, 9H).
Reaction SMILES: [CH3:1][CH:2]([CH3:11])[CH2:3][CH2:4][CH2:5][CH2:6][C:7]#[C:8]C=O.[CH3:12][O:13][CH:14](OC)[O:15][CH3:16]>>[CH3:12][O:13][CH:14]([O:15][CH3:16])[C:8]#[C:7][CH2:6][CH2:5][CH2:4][CH2:3][CH:2]([CH3:11])[CH3:1]
Reactant: CC(C)CCCCC#CC=O
Reactant: COC(OC)OC
Product: COC(C#CCCCCC(C)C)OC

Procedure:
One gm. (0.007 mole) of 8-methylnon-2-yn-1-al, 10 gm. (0.1 mole) of trimethylorthoformate and 0.2 g of para-toluene-sulfuric acid were distilled. Methyl formate and methyl alcohol were collected. The solution was diluted with 15 ml of water and extracted with ether. The ether solution was washed with 5% sodium bicarbonate, and then water. The ether extract was dried over sodium sulfate, concentrate and distilled under vacuum to give 1,1-dimethoxy-8-methyl-non-2-yne.
Reaction SMILES: [F:1][C:2]([F:53])([F:52])[C:3]1[CH:4]=[C:5]([CH:45]=[C:46]([C:48]([F:51])([F:50])[F:49])[CH:47]=1)[CH2:6][N:7]([CH2:18][C:19]1[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][C:20]=1[N:29]([CH2:32][C@H:33]1[CH2:38][CH2:37][C@H:36]([CH2:39][C:40]([O:42]CC)=[O:41])[CH2:35][CH2:34]1)[CH2:30][CH3:31])[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][OH:17])=[CH:10][N:9]=1.[OH-].[Na+].Cl.C(OCC)(=O)C>C(O)C>[F:53][C:2]([F:1])([F:52])[C:3]1[CH:4]=[C:5]([CH:45]=[C:46]([C:48]([F:49])([F:50])[F:51])[CH:47]=1)[CH2:6][N:7]([CH2:18][C:19]1[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][C:20]=1[N:29]([CH2:32][C@H:33]1[CH2:34][CH2:35][C@H:36]([CH2:39][C:40]([OH:42])=[O:41])[CH2:37][CH2:38]1)[CH2:30][CH3:31])[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][OH:17])=[CH:12][N:13]=1
Reactant: CCOC(=O)C[C@H]1CC[C@H](CN(CC)c2ccc(C(F)(F)F)cc2CN(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2ncc(OCCO)cn2)CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: CCOC(C)=O
Product: CCN(C[C@H]1CC[C@H](CC(=O)O)CC1)c1ccc(C(F)(F)F)cc1CN(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1ncc(OCCO)cn1
Temperature: 60 °C
Reaction time: 2 h

Procedure:
Ethyl trans-[4-({[2-({(3,5-bis-trifluoromethyl-benzyl)-[5-(2-hydroxy-ethoxy)-pyrimidin-2-yl]-amino}-methyl)-4-trifluoromethyl-phenyl]-ethyl-amino}-methyl)-cyclohexyl]-acetate (122 mg) is dissolved in ethanol (4 ml), and thereto is added 1N-aqueous sodium hydroxide solution (1 ml) and the mixture is stirred at 60° C. for 2 hours. The reaction solution is cooled to room temperature, and thereto are added 1N-hydrochloric acid and ethyl acetate, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=7:3→3:7) to give trans-[4-({[2-({(3,5-bis-trifluoromethyl-benzyl)-[5-(2-hydroxy-ethoxy)-pyrimidin-2-yl]-amino}-methyl)-4-trifluoromethyl-phenyl]-ethylamino}-methyl)-cyclohexyl]-acetic acid (50 mg). MS (m/z): 737 [M+H]+
Reaction SMILES: [OH:1][C:2]1[N:6]([C:7]2[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=2)[N:5]=[CH:4][CH:3]=1.[CH2:15]([C:17]1[CH:22]=[CH:21][C:20]([CH2:23]O)=[C:19]([F:25])[CH:18]=1)[CH3:16]>>[CH2:15]([C:17]1[CH:22]=[CH:21][C:20]([CH2:23][O:1][C:2]2[N:6]([C:7]3[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=3)[N:5]=[CH:4][CH:3]=2)=[C:19]([F:25])[CH:18]=1)[CH3:16]
Reactant: CCc1ccc(CO)c(F)c1
Reactant: N#Cc1ccnc(-n2nccc2O)c1
Product: CCc1ccc(COc2ccnn2-c2cc(C#N)ccn2)c(F)c1

Procedure:
The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and (4-ethyl-2-fluorophenyl)methanol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 1.23 (3H, t, J=7.6 Hz), 2.66 (2H, q, J=7.6 Hz), 5.26 (2H, s), 5.81 (1H, d, J=2.0 Hz), 6.95 (1H, d, J=11.2 Hz), 7.00 (1H, d, J=7.6 Hz), 7.35 (1H, d, J=8.0 Hz), 7.38 (1H, dd, J=1.6 Hz, 5.2 Hz), 7.57 (1H, d, J=1.6 Hz), 8.00-8.01 (1H, m), 8.69 (1H, d, J=0.8 Hz, 5.2 Hz). [M+H] Calc'd for C18H15FN4O, 323; Found, 323.
Reaction SMILES: [N+:1]([C:4]1[CH:20]=[CH:19][C:7]([CH2:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:6][CH:5]=1)([O-])=O>C(O)C.C(OCC)(=O)C.[Pd]>[CH3:18][C:15]1[CH:14]=[CH:13][C:12]([S:9]([CH2:8][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:20][CH:19]=2)(=[O:11])=[O:10])=[CH:17][CH:16]=1
Reactant: Cc1ccc(S(=O)(=O)Cc2ccc([N+](=O)[O-])cc2)cc1
Agent: [Pd]
Solvent: CCO
Solvent: CCOC(C)=O
Product: Cc1ccc(S(=O)(=O)Cc2ccc(N)cc2)cc1
Yield: 89.2 %

Procedure:
In ethanol (10 ml) and ethyl acetate (60 ml) was dissolved 4-methylphenyl 4-nitrobenzyl sulfone (0.5 g; G. Bram et al., Synthesis, 1987, 56-59). To the mixture was added 10% palladium on carbon (0.05 g) and catalytic hydrogenation was carried out at room temperature over night. The catalyst was filtered off, and the solvent was evaporated to give 4-aminobenzyl 4-methylphenyl sulfone (0.4 g) as colorless crystals.
Reaction SMILES: [N:1]([C:4]([CH3:17])([CH3:16])[CH:5]=[C:6]1[CH2:11][C:10]([CH3:13])([CH3:12])[CH2:9][C:8]([CH3:15])([CH3:14])[CH2:7]1)=[N+]=[N-].[ClH:18].CC1(C)CC(C)(C)CC(=CC(N)C)C1>>[ClH:18].[CH3:17][C:4]([NH2:1])([CH3:16])[CH:5]=[C:6]1[CH2:7][C:8]([CH3:15])([CH3:14])[CH2:9][C:10]([CH3:13])([CH3:12])[CH2:11]1
Reactant: CC1(C)CC(=CC(C)(C)N=[N+]=[N-])CC(C)(C)C1
Agent: CC(N)C=C1CC(C)(C)CC(C)(C)C1
Agent: Cl
Product: CC(C)(N)C=C1CC(C)(C)CC(C)(C)C1
Yield: 69 %

Procedure:
Prepared from azide 30 by the same procedure as for amine 24 (Example 4). Amine hydrochloride 31 obtained as a colorless solid in 69% yield. 1H-NMR (CDCl3, TMS): 0.91 and 0.98 (total 12H, both s, c-Hex-3,5-CH3); 1.26 (2H, s, c-Hex-4-CH2); 1.68 (6H, s, —C(CH3)2N); 1.84 and 2.10 (both 2H, both s, c-Hex-2,6-CH2); 5.15 (1H, s, ═CH—) and 8.5 ppm (3H, br s, NH3+).
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[CH2:12][CH:11]=[CH:10]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:16]([C:20]1[CH:21]=[C:22](Br)[CH:23]=[C:24]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:25]=1)([CH3:19])([CH3:18])[CH3:17].C([O-])(=O)C.[Na+].Cl>[Cl-].C1([P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(#N)C.C(#N)C.Cl[Pd]Cl.CN1CCCC1=O>[C:16]([C:20]1[CH:21]=[C:22]([C:11]2[CH2:12][C:13]3[C:9]([CH:10]=2)=[CH:8][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[CH:15][CH:14]=3)[CH:23]=[C:24]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:25]=1)([CH3:19])([CH3:18])[CH3:17]
Reactant: C1=Cc2cc(-c3ccccc3)ccc2C1
Reactant: CC(C)(C)c1cc(Br)cc(C(C)(C)C)c1
Agent: Cl[Pd]Cl
Agent: CC(=O)[O-]
Agent: Cl
Solvent: CN1CCCC1=O
Solvent: CC#N
Product: CC(C)(C)c1cc(C2=Cc3cc(-c4ccccc4)ccc3C2)cc(C(C)(C)C)c1
Temperature: 60 °C
Yield: 28 %

Procedure:
A 100 mL three-neck round bottom flask equipped with a condenser, magnetic stir bar, thermometer, and a nitrogen inlet was dried, purged with nitrogen, then charged with 5-phenylindene (5.8 g, 0.03 mol), 3,5-di-tert-butylbromobenzene (8.1 g, 0.03 mol), sodium acetate (4.9 g, 0.06 mol), dichloropalladium (II) bis(acetonitrile) (0.026 g, 0.10 mmol), tetraphenylphosphonium chloride (0.225 g, 0.60 mmol), and anhydrous 1-methyl-2-pyrrolidinone (45 mL). The reaction mixture was heated to 60° C. for 24 hours without any conversion of starting materials. The temperature was then raised to 140° C. for 16 hours after which GC analysis showed >95% conversion of 5-phenylindene. The reaction mixture was cooled, mixed with chilled 5% aqueous HCl (250 mL) and extracted with diethyl ether (3×100 mL). The combined diethyl ether extracts were water washed and then dried over anhydrous magnesium sulfate. Rotary evaporation gave crude product (12.5 g) as a viscous red-brown oil. Crystals of 2-(3,5-di-tert-butylphenyl)-5-phenylindene (6.4 g) precipitated from a concentrated solution (˜50%) of the crude product in acetone-methanol (70:30). Three consecutive recrystallizations from acetone-methanol yielded 2-(3,5-di-tert-butylphenyl)-5-phenylindene (3.2 g, 99.9% purity by GC) as pale tan crystals (mp 122-3° C.). 1HNMR (CD2Cl2, 500MHz) 40:60 mixture of isomeric alkenes; δ7.65-7.25 (mults, 12H); 3.82, 3.80 (s, 2H); 1.30 (s, 18H).
Reaction SMILES: P(=O)(O)(O)O.[NH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([NH2:13])[N:8]=1.[CH3:14][CH2:15][C:16](=O)[CH2:17][C:18](=O)[CH2:19][CH3:20]>>[NH2:6][C:7]1[CH:12]=[CH:11][C:10]2[C:9](=[N:13][C:16]([CH2:15][CH3:14])=[CH:17][C:18]=2[CH2:19][CH3:20])[N:8]=1
Reactant: Nc1cccc(N)n1
Reactant: CCC(=O)CC(=O)CC
Agent: O=P(O)(O)O
Product: CCc1cc(CC)c2ccc(N)nc2n1

Procedure:
To 50 ml. of 85% phosphoric acid is added with stirring 2,6-diaminopyrdine (6.55 g., 0.06 mole) followed by 3,5-heptanedione (7.7 g., 0.06 mole). The mixture is heated on the steam bath under nitrogen atmosphere for 16 hours. The reaction mixture is poured into crushed ice and neutralized with concentrated ammonium hydroxide and extracted with methylene chloride (3 × 250 ml.). The combined extracts are dried, filtered and concentrated in vacuo. Crystallization of the residue from ethyl acetate affords 2-amino-5,7-diethyl-1,8-naphthyridine melting at 187°-189° C.
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[C:11]([NH:13][C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][CH:6]1[O:8][CH2:7]1.[CH:19]([NH2:22])([CH3:21])[CH3:20]>C(O)C>[Cl:1][C:2]1[CH:12]=[C:11]([NH:13][C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][CH:6]([OH:8])[CH2:7][NH:22][CH:19]([CH3:21])[CH3:20]
Reactant: CN(C)C(=O)Nc1ccc(OCC2CO2)c(Cl)c1
Reactant: CC(C)N
Solvent: CCO
Product: CC(C)NCC(O)COc1ccc(NC(=O)N(C)C)cc1Cl
Reaction time: 4 h

Procedure:
A solution of 40 g of 1-[o-chloro-p-(N',N'-dimethyl-ureido)-phenoxy]-2,3-epoxy-propane and 40 g of isopropylamine in 40 ml of ethanol is heated to boiling for 4 hours. Thereafter the mixture is concentrated by evaporation in vacuo and the residue is dissolved in 2 N hydrochloric acid. After extraction with ether, the hydrochloric acid layer is separated off and rendered alkaline by adding concentrated sodium hydroxide solution. The base which has separated out is extracted by shaking with methylene chloride. After evaporation of the solvent and after recrystallisation of the residue from ethyl acetate, the 1-[o-chloro-p-(N',N'-dimethylureido)-phenyoxy]-2-hydroxy-3-isopropylamino-propane of formula ##STR18## is obtained in crystals of melting point 130° C.
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[C:9]([C:11]([F:14])([F:13])[CH3:12])[N:10]=[C:6]2[N:5]=[C:4]([CH3:15])[CH:3]=1.[F:16][C:17]1[CH:18]=[C:19]([CH:21]=[CH:22][C:23]=1[C:24]([F:27])([F:26])[F:25])[NH2:20]>C(O)C>[F:13][C:11]([C:9]1[N:10]=[C:6]2[N:5]=[C:4]([CH3:15])[CH:3]=[C:2]([NH:20][C:19]3[CH:21]=[CH:22][C:23]([C:24]([F:25])([F:26])[F:27])=[C:17]([F:16])[CH:18]=3)[N:7]2[N:8]=1)([F:14])[CH3:12]
Reactant: Nc1ccc(C(F)(F)F)c(F)c1
Reactant: Cc1cc(Cl)n2nc(C(C)(F)F)nc2n1
Solvent: CCO
Product: Cc1cc(Nc2ccc(C(F)(F)F)c(F)c2)n2nc(C(C)(F)F)nc2n1
Temperature: 50 °C

Procedure:
A suspension of Intermediate 3 (0.1 g, 0.43 mmol) and 3-fluoro-4-(trifluoromethyl)aniline (ALFAAESAR, 0.077 g, 0.43 mmol) in ethanol (5 mL) was heated at 50° C. for 1 h. The reaction mixture was concentrated under vacuum, redissolved in DCM (20 mL) and washed with aq. Na2CO3 (2×15 mL). The organic layer was dried over anhydrous Na2SO4 filtered and concentrated under vacuum to afford a white solid.
Reaction SMILES: [H][H].CNC.ClCl.ClC1C=C(C=C2C(=O)COC2=O)C=CC=1Cl.C[O:25][C:26]1[CH:31]=[C:30](OC)[CH:29]=[CH:28][C:27]=1[CH:34]=[C:35]1[C:39](=[O:40])[CH2:38][O:37][C:36]1=[O:41]>>[O:25]1[CH:29]=[CH:30][CH:31]=[C:26]1[C:27](=[CH2:28])[CH:34]=[C:35]1[C:39](=[O:40])[CH2:38][O:37][C:36]1=[O:41]
Reactant: COc1ccc(C=C2C(=O)COC2=O)c(OC)c1
Reactant: [H][H]
Agent: CNC
Agent: ClCl
Agent: O=C1COC(=O)C1=Cc1ccc(Cl)c(Cl)c1
Product: C=C(C=C1C(=O)COC1=O)c1ccco1

Procedure:
The other subclass of the furandiones used in accordance with the present invention are the 3-(arylalkylene)2,4(3H,5H) furandiones, including, for example, those represented by the following general formula: ##STR3## where R represents hydrogen, N,N-dimethyl amine and chlorine. For example, the 3-(arylalkylene)2,4(3H,5H) furandiones include 3[(3,4-dichlorophenyl)methylene]2,4(3H,5H)-furandione; 3[(2,4-dimethoxyphenyl)methylene]2,4(3H,5H)-furandione and 3[(4-N,N-dimethylamino)methylene]2,4(3H,5H) furandione, the structural formulae of which are as follows: ##STR4##
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]=[CH:10][C:11]([OH:13])=O.Cl.[CH3:15][NH:16][O:17][CH3:18].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C(N(C(C)C)CC)(C)C>ClCCl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]=[CH:10][C:11]([N:16]([O:17][CH3:18])[CH3:15])=[O:13]
Reactant: O=C(O)C=Cc1ccc(F)cc1F
Reactant: CNOC
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CON(C)C(=O)C=Cc1ccc(F)cc1F
Temperature: 25 °C
Reaction time: 24 h
Yield: 86.5 %

Procedure:
3-(2,4-Difluoro-phenyl)-acrylic acid (9.5 g, 51.4 mmol) prepared in Step 1, N,O-dimethylhydroxylamine hydrochloride (6.5 g, 66.8 mmol), HOBT (7.6 g, 56.5 mmol), EDAC (10.8 g, 56.5 mmol) and diisopropylethylamine (9.8 mL, 56.5 mmol) were added to dichloromethane (250.0 mL). The reaction mixture stirred at room temperature for 24 hours, quenched with a saturated solution of ammonium chloride, and then extracted with dichloromethane. The extract was washed with brine, dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure to give a yellow liquid residue. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/3) to give 10.1 g of the titled compound as a yellow liquid.
Reaction SMILES: [CH3:1][C:2]1([CH:7]=[CH:8][O:9][C:10](=[O:12])[CH3:11])[NH:5][C:4](=[O:6])[CH2:3]1.[H][H]>C(OCC)(=O)C.[Pd]>[CH3:1][C:2]1([CH2:7][CH2:8][O:9][C:10](=[O:12])[CH3:11])[NH:5][C:4](=[O:6])[CH2:3]1
Reactant: [H][H]
Reactant: CC(=O)OC=CC1(C)CC(=O)N1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CC(=O)OCCC1(C)CC(=O)N1

Procedure:
A solution of 4-methyl-4-(2-acetoxyvinyl)-2-azetidinone (10.0 g, 0.065 mole) in 200 ml ethyl acetate containing 100 mg of 10% Pd/C is hydrogenated on a Parr shaker at 25° C. under 40 psi hydrogen for 15 minutes. The mixture is filtered through a bed of Supercel and washed with additional ethyl acetate. The combined filtrate is evaporated in vacuo to give 4-methyl-4-(2-acetoxyethyl)-2-azetidinone.
Reaction SMILES: Br[C:2]1[CH:24]=[C:23]([F:25])[C:22]([F:26])=[CH:21][C:3]=1[O:4][CH2:5][C:6]([N:8]([CH:18]([CH3:20])[CH3:19])[NH:9][C:10](=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7].C([O-])([O-])=O.[Na+].[Na+].[CH2:33]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1B(O)O)[CH3:34]>COCCOC>[CH2:33]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[C:2]1[CH:24]=[C:23]([F:25])[C:22]([F:26])=[CH:21][C:3]=1[O:4][CH2:5][C:6]([N:8]([CH:18]([CH3:20])[CH3:19])[NH:9][C:10](=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])[CH3:34]
Reactant: CCc1ccccc1B(O)O
Reactant: CC(C)N(NC(=O)c1ccccc1)C(=O)COc1cc(F)c(F)cc1Br
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: CCc1ccccc1-c1cc(F)c(F)cc1OCC(=O)N(NC(=O)c1ccccc1)C(C)C
Yield: 72.7 %

Procedure:
A solution of benzoic acid N′-[2-(2-bromo-4,5-difluoro-phenoxy)-acetyl]-N′-isopropyl-hydrazide (100 mg, 0.234 mmol) in DME (3 ml)/2M Na2CO3 (0.435 ml, 0.864 mmol) was treated with 2-ethylphenylboronic acid (70 mg, 0.468 mmol) and Pd[PPh3]4 (27 mg, 0.0234 mmol) in a microwave oven at 150° C. for 10 min. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude was absorbed on silica and purified on a silica gel column with a 20-40% ethyl acetate in hexanes gradient to afford the product as a white solid (77 mg, 73%). MS m/e 453.30 (M+H+)