Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[C:7]2[C:8]3[CH:14]=[C:13]([C:15]4[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=4)[CH:12]=[N:11][C:9]=3[NH:10][C:6]=2[CH:5]=[N:4][C:3]=1[C:21]#[N:22].[H-].[Na+].Cl[CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31]>CN(C=O)C.O>[Br:1][C:2]1[C:7]2[C:8]3[CH:14]=[C:13]([C:15]4[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=4)[CH:12]=[N:11][C:9]=3[N:10]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:6]=2[CH:5]=[N:4][C:3]=1[C:21]#[N:22]
Reactant: C[Si](C)(C)CCOCCl
Reactant: Cn1cc(-c2cnc3[nH]c4cnc(C#N)c(Br)c4c3c2)cn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Cn1cc(-c2cnc3c(c2)c2c(Br)c(C#N)ncc2n3COCC[Si](C)(C)C)cn1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 53.9 %

Procedure:
To a solution of 5-bromo-3-(1-methyl-1H-pyrazol-4-yl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (547 mg, 1.55 mmol) in DMF (25 ml) under a flow of nitrogen was added sodium hydride (93 mg, 60% dispersion in mineral oil, 2.39 mmol). After 20 min, a yellow solution had formed and (2-chloromethoxyethyl)-trimethyl-silane (358 μL, 2.02 mmol) was added. The reaction mixture was stirred at ambient temperature for 3 days, then diluted with water and sonicated. The resultant solid was collected by filtration and triturated with methanol to afford the title compound as a yellow solid (404 mg, 54%). 1H NMR (CDCl3, 300 MHz): δ 9.13 (s, 1H), 9.04 (d, J=2.2 Hz, 1H), 8.95 (d, J=2.1 Hz, 1H), 7.93-7.88 (m, 1H), 7.83-7.77 (m, 1H), 6.06 (s, 2H), 4.06 (s, 3H), 3.70-3.59 (m, 2H), 1.03-0.92 (m, 2H), -0.03 (s, 9H).
Reaction SMILES: N[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[N:5]=[CH:4][C:3]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14].N([O-])=O.[Na+].[NH2:22]C(N)=O.[S:26](=[O:28])=[O:27]>Cl.O.ClCCCl>[CH2:16]([O:15][C:13]([C:3]1[CH:4]=[N:5][N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[C:2]=1[S:26]([NH2:22])(=[O:28])=[O:27])=[O:14])[CH3:17]
Reactant: NC(N)=O
Reactant: O=S=O
Reactant: CCOC(=O)c1cnn(-c2ccccn2)c1N
Agent: Cl
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: ClCCCl
Product: CCOC(=O)c1cnn(-c2ccccn2)c1S(N)(=O)=O
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 442.5 %

Procedure:
14 g of ethyl 5-amino-1-(2-pyridyl)pyrazole-4-carboxylate was dissolved in 50 ml of conc. hydrochloric acid, and the solution obtained was cooled to -5° C., to which 5.5 g of sodium nitrite dissolved in 10 ml of water was added cropwise, and thereafter, stirred for 10 minutes, followed by addition of 0.6 g of urea. The solution thus obtained was added dropwise at 5° C. to a solution obtained by adding 2 g of sulfur dioxide and 0.6 g of cuprous chloride to 50 ml of 1,2-dichloroethane. After stirring at room temperature for 1 hour, 200 ml of ice water was added thereto, followed by extraction with chloroform. Seperation of the layer of chloroform, washing with water, drying and concentration were then carried out to obtain 13.1 g of the title compound. m.p.: 38° to 42° C.
Reaction SMILES: C(N(CC)CC)C.[CH3:8][O:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][C:19]=1[O:20][CH3:21])[C:16]1=[CH:22][C:23]([NH:27][C:28]3[C:33]([CH3:34])=[CH:32][C:31]([CH3:35])=[CH:30][C:29]=3[CH3:36])=[N:24][C:25](=[O:26])[N:15]1[CH2:14][CH2:13]2.[C:37](Cl)(=[O:39])[CH3:38]>C(Cl)(Cl)Cl>[CH3:8][O:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][C:19]=1[O:20][CH3:21])[C:16]1=[CH:22][C:23]([N:27]([C:37](=[O:39])[CH3:38])[C:28]3[C:33]([CH3:34])=[CH:32][C:31]([CH3:35])=[CH:30][C:29]=3[CH3:36])=[N:24][C:25](=[O:26])[N:15]1[CH2:14][CH2:13]2
Reactant: CC(=O)Cl
Reactant: COc1cc2c(cc1OC)-c1cc(Nc3c(C)cc(C)cc3C)nc(=O)n1CC2
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: COc1cc2c(cc1OC)-c1cc(N(C(C)=O)c3c(C)cc(C)cc3C)nc(=O)n1CC2
Temperature: 0 °C
Reaction time: 2 h

Procedure:
1.2 ml of triethylamine are added first to an ice-cold solution of 9,10-dimethoxy-2-(2,4,6-trimethyl-anilino)-6,7-dihydro-4H-pyrimido(6,1-a)isoquinolin-4-one (1.6 g) in chloroform (40.0 ml), and then a solution of acetyl chloride (0.64 ml) in chloroform (10.0 ml) is added dropwise. The mixture is stirred for 2 hours. The chloroform solution is washed successively with water, sodium carbonate solution and water, and is then dried over anhydrous sodium sulfate. The solution is filtered and the filtrate evaporated to dryness in vacuo. The residue is triturated with diethyl ether to yield the desired compound in solid form. Yield 1.6 g, m.p. 210°-212° C. (dichloromethane-petroleum ether b.p. 60°-80° C.).
Reaction SMILES: C[O:2][C:3](=[O:41])[CH:4]([F:40])[CH2:5][NH:6][C:7](=[O:39])[C:8]1[CH:13]=[CH:12][C:11]([CH:14]([NH:27][C:28]([NH:30][C:31]2[CH:36]=[C:35]([Cl:37])[CH:34]=[C:33]([Cl:38])[CH:32]=2)=[O:29])[C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH:22]=3)=[CH:17][CH:16]=2)=[CH:10][CH:9]=1>C1COCC1.CO>[C:21]1([C:18]2[CH:17]=[CH:16][C:15]([CH:14]([NH:27][C:28]([NH:30][C:31]3[CH:32]=[C:33]([Cl:38])[CH:34]=[C:35]([Cl:37])[CH:36]=3)=[O:29])[C:11]3[CH:12]=[CH:13][C:8]([C:7]([NH:6][CH2:5][CH:4]([F:40])[C:3]([OH:41])=[O:2])=[O:39])=[CH:9][CH:10]=3)=[CH:20][CH:19]=2)[CH2:26][CH2:25][CH2:24][CH2:23][CH:22]=1
Reactant: COC(=O)C(F)CNC(=O)c1ccc(C(NC(=O)Nc2cc(Cl)cc(Cl)c2)c2ccc(C3=CCCCC3)cc2)cc1
Solvent: C1CCOC1
Solvent: CO
Product: O=C(Nc1cc(Cl)cc(Cl)c1)NC(c1ccc(C(=O)NCC(F)C(=O)O)cc1)c1ccc(C2=CCCCC2)cc1

Procedure:
Hydrolysis of (RS)-3-{4-[1-(4-cyclohex-1-enylphenyl)-3-(3,5-dichlorophenyl)ureidomethyl]benzoylamino}-2-fluoropropionic acid methyl ester in a mixture of THF and methanol afforded the title compound.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]([NH:11][C:12](=[S:20])OC2C=CC=CC=2)[C:5]([O:9][CH3:10])=[N:6][C:7]=1[CH3:8].[CH3:21][O:22][C:23]1[CH:24]=[C:25]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH:26]=[C:27]([O:29][CH3:30])[CH:28]=1.C1CCN2C(=NCCC2)CC1>O1CCCC1>[CH3:1][C:2]1[N:3]=[C:4]([NH:11][C:12]([N:34]2[CH2:33][CH2:32][N:31]([C:25]3[CH:24]=[C:23]([O:22][CH3:21])[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=3)[CH2:36][CH2:35]2)=[S:20])[C:5]([O:9][CH3:10])=[N:6][C:7]=1[CH3:8]
Reactant: COc1nc(C)c(C)nc1NC(=S)Oc1ccccc1
Reactant: COc1cc(OC)cc(N2CCNCC2)c1
Solvent: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Product: COc1cc(OC)cc(N2CCN(C(=S)Nc3nc(C)c(C)nc3OC)CC2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 71.5 %

Procedure:
Phenyl N-(5,6-dimethyl-2-methoxypyrazin-3-yl)thiocarbamate (200 mg, 0.69 mmol) and 1-(3,5-dimethoxyphenyl)piperazine (154 mg, 0.69 mmol) were dissolved in anhydrous tetrahydrofuran (25 ml) and thereto DBU (105 mg, 0.69 mmol) was added. The mixture was stirred at room temperature for 2 hours, concentrated under the reduced pressure to remove the solvent and purified by column chromatography to obtain the titled compound.
Reaction SMILES: [OH-].[Li+].[CH3:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[C:14]([CH:25]=2)[C:15]([O:17]CC2C=CC=CC=2)=[O:16])[CH2:6][CH2:5]1.Cl>C1COCC1.O.C(OCC)(=O)C>[CH3:3][N:4]1[CH2:5][CH2:6][N:7]([C:10]2[CH:11]=[CH:12][C:13]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[C:14]([CH:25]=2)[C:15]([OH:17])=[O:16])[CH2:8][CH2:9]1
Reactant: CN1CCN(c2ccc(OCc3ccccc3)c(C(=O)OCc3ccccc3)c2)CC1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CN1CCN(c2ccc(OCc3ccccc3)c(C(=O)O)c2)CC1

Procedure:
Lithium hydroxide (17.25 mg, 0.72 mmol) was added to a stirred solution of phenylmethyl 5-(4-methyl-1-piperazinyl)-2-[(phenylmethyl)oxy]benzoate (may be prepared as described in Description 39; 100 mg, 0.24 mmol) in a mixture of THF:water (3:1, 10 ml). The mixture was heated to reflux for 12 h and then diluted with ethyl acetate (50 ml). 10% aqueous HCl was added to the mixture to adjust the pH to 2. The organic phase was isolated, washed with brine, dried over magnesium sulphate, and concentrated to give a white solid. The product was purified using Comflash to yield the title compound. 50 mg.
Reaction SMILES: [O:1]1[C:5]([C:6]2[CH:11]=[CH:10][C:9]([NH:12][C:13]3[N:14]=[C:15]([N:23]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:24][CH2:25][OH:26])[C:16]4[CH2:22][NH:21][CH2:20][CH2:19][C:17]=4[N:18]=3)=[CH:8][CH:7]=2)=[CH:4][N:3]=[CH:2]1.C(N(CC)CC)C.[CH3:40][N:41]([CH3:45])[C:42](Cl)=[O:43]>ClCCl.CO>[OH:26][CH2:25][CH2:24][N:23]([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[C:15]1[C:16]2[CH2:22][N:21]([C:42]([N:41]([CH3:45])[CH3:40])=[O:43])[CH2:20][CH2:19][C:17]=2[N:18]=[C:13]([NH:12][C:9]2[CH:10]=[CH:11][C:6]([C:5]3[O:1][CH:2]=[N:3][CH:4]=3)=[CH:7][CH:8]=2)[N:14]=1
Reactant: CN(C)C(=O)Cl
Reactant: OCCN(c1ccccc1)c1nc(Nc2ccc(-c3cnco3)cc2)nc2c1CNCC2
Solvent: CO
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CN(C)C(=O)N1CCc2nc(Nc3ccc(-c4cnco4)cc3)nc(N(CCO)c3ccccc3)c2C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 31.7 %

Procedure:
2-((2-(4-(Oxazol-5-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)(phenyl)amino)ethanol (50 mg, 0.12 mmol, Example 1) was dissolved in dichloromethane (5 mL) and methanol (1 mL). Triethylamine (0.016 mL, 0.12 mmol) was added followed by dimethylcarbamyl chloride (10.72 μL, 0.12 mmol). The reaction mixture was stirred at room temperature for 2 h. The solvent was evaporated under reduced pressure, the crude dissolved in few drops of dimethylformamide and acetonitrile, filtered and purified by HPLC yielding 4-((2-hydroxyethyl)(phenyl)amino)-N,N-dimethyl-2-(4-(oxazol-5-yl)phenylamino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxamide (19.0 mg, 33%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C:8](=[O:14])[C:7](=[CH:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1)[CH2:6]2.CO.C(Cl)Cl>[Pd].C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C:8](=[O:14])[CH:7]([CH2:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1)[CH2:6]2
Reactant: COc1cc2c(cc1OC)C(=O)C(=Cc1ccncc1)C2
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: ClCCl
Product: COc1cc2c(cc1OC)C(=O)C(Cc1ccncc1)C2
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 99.3 %

Procedure:
The mixture of 5,6-dimethoxy-2-(4-pyridyl)methylene-1-indanone (34 gm), methanol (325 ml), methylenedichloride (200 ml) and 5% palladium-charcoal (2 gm) is taken in a hydrogenation flask and subjected to hydrogenation under a hydrogen pressure of 2 bars for 3 hours. The catalyst is removed by filtration and the solvents are evaporated completely under vacuum to obtain a residue. Ethyl acetate (150 ml) is added to the residue and stirred for 20 minutes at 25° C. to 30° C. The contents are then cooled to 0° C., stirred for 30 minutes and filtered to give 34 gm of 5,6-dimethoxy-2-(4-pyridyl)methyl-1-indanone.
Reaction SMILES: [NH2:1][CH:2]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:15][CH:14]=1)[CH:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[CH:6]=1)[OH:4].[C:24]1([C:35](O)=[O:36])[CH:25]=[CH:26][CH:27]=[C:28]2[CH2:34][CH2:33][CH2:32][CH:31]=[CH:30][C:29]=12.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>C(#N)C.O>[C:20]([O:19][C:16]1[CH:15]=[CH:14][C:13]([CH2:12][CH:2]([NH:1][C:35]([C:24]2[CH:25]=[CH:26][CH:27]=[C:28]3[CH2:34][CH2:33][CH2:32][CH:31]=[CH:30][C:29]=23)=[O:36])[CH:3]([C:5]2[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[CH:6]=2)[OH:4])=[CH:18][CH:17]=1)([CH3:23])([CH3:22])[CH3:21]
Reactant: CC(C)(C)Oc1ccc(CC(N)C(O)c2cccc(Cl)c2)cc1
Reactant: O=C(O)c1cccc2c1C=CCCC2
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CC#N
Product: CC(C)(C)Oc1ccc(CC(NC(=O)c2cccc3c2C=CCCC3)C(O)c2cccc(Cl)c2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of (1RS,2SR)-2-amino-3-(4-tert-butoxyphenyl)-1-(3-chlorophenyl)propan-1-ol (300 mg, 0.90 mmol) in acetonitrile (20 ml) were added 6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxylic acid (169 mg, 0.90 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (258 mg, 1.35 mmol) and 1-hydroxybenzotriazole hydrate (138 mg, 0.90 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed successively with water and saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1-2:1). Recrystallization from ethyl acetate-hexane gave the objective substance (351 mg, 77%).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N:12]2[C:16]([C:17]3[C:22]([O:23]C)=[CH:21][CH:20]=[CH:19][C:18]=3[O:25]C)=[CH:15][C:14]([C:27]([NH:29][CH:30]([CH2:34][CH2:35][CH2:36][CH3:37])[C:31]([OH:33])=[O:32])=[O:28])=[N:13]2)=[CH:4][CH:3]=1.B(Br)(Br)Br.O.[OH-].[Na+]>ClCCl>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N:12]2[C:16]([C:17]3[C:18]([OH:25])=[CH:19][CH:20]=[CH:21][C:22]=3[OH:23])=[CH:15][C:14]([C:27]([NH:29][C@@H:30]([CH2:34][CH2:35][CH2:36][CH3:37])[C:31]([OH:33])=[O:32])=[O:28])=[N:13]2)=[CH:4][CH:3]=1
Reactant: CCCCC(NC(=O)c1cc(-c2c(OC)cccc2OC)n(-c2ccc(Cl)c3ccccc23)n1)C(=O)O
Agent: BrB(Br)Br
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: CCCC[C@H](NC(=O)c1cc(-c2c(O)cccc2O)n(-c2ccc(Cl)c3ccccc23)n1)C(=O)O
Temperature: -70 °C
Reaction time: 2 h

Procedure:
0.3 g of 2-{[1-(4-chloro-1-naphthyl)-5-(2,6-dimethoxyphenyl)-3-pyrazolyl]carbonylamino}hexanoic acid is dissolved in 6.7 ml of dichloromethane and the mixture is cooled to -70° C. 5.7 ml of boron tribromide, dissolved in 20 ml of dichlormethane, are added dropwise and the reaction mixture is left for 2 hours at -70° C. It is allowed to return to room temperature, and 12 ml of water are then added while cooling. Concentrated NaOH is added to pH 14. The aqueous phase is washed with ether and brought to pH 2, the product is extracted with ethyl acetate and the organic phase is dried over sodium sulphate, filtered and evaporated. The residue is crystallised from diisopropyl ether.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][O:7][C:8]([C:10](C#N)=C)=[O:9].[C:14](O)(=O)[CH:15]=CC1C=CC=CC=1.N[C@H](C(O)=O)CC1C=CC=CC=1.N[C@H](C(O)=O)CC1C=CC(O)=CC=1.S(=O)(=O)(O)O.N1C=CC=CC=1.C(OC(=O)C)(=O)C>C1(C)C=CC=CC=1>[C:8]([O:7][C:6]1[CH:1]=[CH:2][C:3]([CH:14]=[CH2:15])=[CH:4][CH:5]=1)(=[O:9])[CH3:10]
Reactant: O=C(O)C=Cc1ccccc1
Reactant: C=C(C#N)C(=O)OCCCCCC
Agent: N[C@@H](Cc1ccc(O)cc1)C(=O)O
Agent: N[C@@H](Cc1ccccc1)C(=O)O
Agent: O=S(=O)(O)O
Solvent: c1ccncc1
Solvent: CC(=O)OC(C)=O
Solvent: Cc1ccccc1
Product: C=Cc1ccc(OC(C)=O)cc1
Temperature: 30 °C
Reaction time: 2 h

Procedure:
A 1.0 L jacketed Wheaton CelStir® reactor is charged with 0.335 L of the fermentation supernatant, obtained from a PHCA fermentation, as described in Example 6. The fermentation supernatant contains PHCA, cinnamic acid (CA), phenylalanine, tyrosine (all produced by the recombinant E. coli cells), and salts at pH 6.0. The pH of the pHCA-containing fermentation supernatant is adjusted to pH 6.0 using concentrated sulfuric acid for the enzymatic decarboxylation. Cell-free extract containing PDC2 (0.30 mL, 55 Units; 2.2 mg protein), prepared as described in Example 1, is added along with 0.15 L of reagent grade toluene containing 42 mg of ProStab® 5415 (Ciba Specialty Chemicals, Tarrytown, N.Y.), as a polymerization inhibitor. The reactor is capped, placed on a magnetic stir plate, and stirred at moderate speed. The reaction temperature is set at 40° C. The reaction is allowed to proceed for 2 h before terminating. The contents of the reactor are transferred to a 500 mL separatory funnel and the layers are allowed to separate. If the organic layer contains an emulsion, it is broken by filtering through a glass-fritted Buchner funnel of medium porosity. The filtrate has two immiscible layers, a colorless organic layer and a yellow aqueous layer. The layers are separated by passing through phase-separated cellulose filter paper, which allows the organic layer to selectively pass through into the receiving flask. The organic layer is recovered and immediately transferred to a 250 mL round-bottomed flask containing a stir bar. The flask is charged with pyridine (CAS110-86-1, 0.300 mL, 3.71 mmol) and acetic anhydride (CAS108-24-7, 4.0 mL, 42.4 mmol). The progress of the acetylation reaction is monitored by TLC until all of the pHS is converted and only a single spot appears on the TLC plate. A yellow oil is recovered by rotary evaporation under vacuum (13.3 kPa) with mild heating (30° C.). The isolated oil (1.41 g) is characterized by gas chromatography. Further purification of the acetoxystyrene product could be achieved by known methods (see for example Chosnek et. al. U.S. Pat. No. 5,136,083). This prophetic Example demonstrates how the pHS extracted into the organic medium of the biphasic reaction mixture may be derivatized to give a derivatized product such as para-acetoxystyrene.
Reaction SMILES: [CH2:1]([Li])[CH2:2][CH2:3][CH3:4].Br[C:7]1[C:11](OC)([CH3:12])[CH2:10][CH2:9][C:8]=1[CH3:15].O>CCOCC>[CH2:1]([C:7]1[C:11]([CH3:12])=[CH:10][CH2:9][C:8]=1[CH3:15])[C:2]1[C:3]([CH3:4])=[CH:2][CH2:1][C:3]=1[CH3:4]
Reactant: COC1(C)CCC(C)=C1Br
Reactant: [Li]CCCC
Solvent: CCOCC
Solvent: O
Product: CC1=CCC(C)=C1CC1=C(C)CC=C1C
Reaction time: 0.17 h
Yield: 61 %

Procedure:
One equivalent of n-butyl lithium was added to a solution in which 7.038 g (34.3 mmol) of 2-bromo-3-methoxy-1,3-dimethyl-cyclopentene compound prepared in the example 3 was dissolved in 38 ml of ether at −25° C. nitrogen atmosphere. When white solid was precipitated, the temperature was elevated to 10° C. and the reaction was continued for further 10 minutes. The temperature was lowered to −25° C. and the fulvene compound prepared in the example 2 was added. Completion of reaction is determined by the development of yellow color of the reaction mixture. 50 ml of water was added to the reaction mixture and the solvent was removed using the rotatory evaporator. 50 ml of 2N HCl solution was added to the organic layer extracted with 50 ml of ethyl acetate, and the resulting mixture was vigorously shaked for 2 minutes. Water layer was removed by layer separation and the organic layer was neutralized with 50 ml of a saturated sodium bicarbonate solution. Isolated organic layer was dried over magnesium sulfate, and then the vacuum distillation was preformed to give 4.17 g of yellow 2,2′-methylenebis(1,3-dimethyl-1,3-cyclopentadiene) compound. Yield: 61%.
Reaction SMILES: [Si]([O:18][CH2:19][C@@H:20]([N:22]1[CH2:26][CH2:25][CH2:24][C:23]1=[O:27])[CH3:21])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>C1COCC1>[O:27]=[C:23]1[CH2:24][CH2:25][CH2:26][N:22]1[C@@H:20]([CH3:21])[CH2:19][OH:18]
Reactant: C[C@@H](CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)N1CCCC1=O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: C[C@@H](CO)N1CCCC1=O
Temperature: 25 °C
Yield: 199.5 %

Procedure:
A 0° C. solution of 11.20 g (29.4 mmol) of (S)-2-(2-oxopyrrolidin-1-yl)propyl tert-butyldiphenylsilyl ether (Part B) in 100 mL of THF was treated with 36.0 mL (36 mmol) of tetrabutylammonium fluoride (1 M in THF). The reaction was stirred at ambient temperature until tic analysis indicated the complete disappearance of starting material (30 min). The reaction was poured into 300 mL of H2O and the mixture extracted with CH2Cl2 (3×300 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to give 8.40 g of the corresponding (S)-2-(2-oxopyrrolidin-1-yl)propyl alcohol which was used without purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:41]=[C:40]([O:42][CH3:43])[CH:39]=[CH:38][C:4]=1[CH2:5][NH:6][C:7]1[C:8]2[CH:15]=[CH:14][N:13]([C@H:16]3[C@@H:20]4[O:21][C:22]([CH3:25])([CH3:24])[O:23][C@@H:19]4[C@@H:18]([CH2:26][N:27]([CH3:37])[CH:28]4[CH2:31][CH:30]([CH2:32][CH2:33][C:34]([OH:36])=O)[CH2:29]4)[CH2:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.C(N(CC)C(C)C)(C)C.[F:53][C:54]([F:65])([F:64])[O:55][C:56]1[CH:57]=[C:58]([NH2:63])[C:59]([NH2:62])=[CH:60][CH:61]=1>CN(C)C=O>[NH2:63][C:58]1[CH:57]=[C:56]([O:55][C:54]([F:53])([F:64])[F:65])[CH:61]=[CH:60][C:59]=1[NH:62][C:34](=[O:36])[CH2:33][CH2:32][CH:30]1[CH2:31][CH:28]([N:27]([CH2:26][C@@H:18]2[C@@H:19]3[C@@H:20]([O:21][C:22]([CH3:24])([CH3:25])[O:23]3)[C@H:16]([N:13]3[C:9]4[N:10]=[CH:11][N:12]=[C:7]([NH:6][CH2:5][C:4]5[CH:38]=[CH:39][C:40]([O:42][CH3:43])=[CH:41][C:3]=5[O:2][CH3:1])[C:8]=4[CH:15]=[CH:14]3)[CH2:17]2)[CH3:37])[CH2:29]1
Reactant: Nc1ccc(OC(F)(F)F)cc1N
Reactant: COc1ccc(CNc2ncnc3c2ccn3[C@@H]2C[C@H](CN(C)C3CC(CCC(=O)O)C3)[C@H]3OC(C)(C)O[C@H]32)c(OC)c1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COc1ccc(CNc2ncnc3c2ccn3[C@@H]2C[C@H](CN(C)C3CC(CCC(=O)Nc4ccc(OC(F)(F)F)cc4N)C3)[C@H]3OC(C)(C)O[C@H]32)c(OC)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 124 %

Procedure:
N,N,N′,N′-Tetramethyl-0-(7-azabenzotriazol-1-yl)uronium Hexafluorophosphate (1.2 g, 3.2 mmol) added to a solution 3-(3-((((3aR,4R,6R,6aS)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)propanoic acid (1.25 g, 2.10 mmol) and N,N-Diisopropylethylamine (1.2 mL, 6.9 mmol) and 4-(trifluoromethoxy)benzene-1,2-diamine (0.48 g, 2.5 mmol) in N,N-Dimethylformamide (10 mL). The mixture was stirred overnight at RT, partially concentrated to ca. 2 rats and then NaHCO3 (saturated) was added. The mixture was extracted with EtOAc (3×) and the combined organics were dried with MgSO4, filtered and concentrated. The residue was purified by flash chromatography (DCM/7N NH3 in MeOH 95:5) to give the desired compound (2 g) as an oil.
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH2:9][C:10]#[N:11])=[C:4]([CH2:12][C:13]#[N:14])[CH:3]=1.O.[CH:16]([CH:18]=O)=O.C(C=O)=O.[OH-].[K+].Cl>CO>[CH3:8][C:7]1[CH:6]=[C:5]2[C:4](=[CH:3][C:2]=1[CH3:1])[C:12]([C:13]#[N:14])=[CH:18][CH:16]=[C:9]2[C:10]#[N:11]
Reactant: Cc1cc(CC#N)c(CC#N)cc1C
Reactant: O=CC=O
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: Cc1cc2c(C#N)ccc(C#N)c2cc1C
Reaction time: 5 h
Yield: 34 %

Procedure:
17 parts of 4,5-dimethyl-1,2-bis-cyanomethyl-benzene and 7.8 parts of glyoxal hydrate (trimer) (3C2H2O2.2H2O) containing 80% of glyoxal to be liberated, are stirred in 100 parts by volume of methanol. The reaction mixture is treated at 0° to 5° C, with stirring and under nitrogen, with 10.5 parts of powdered potassium hydroxide added by small amounts. After the addition of potassium hydroxide, stirring is continued for a further 5 hours at 0° to 5° C under nitrogen. The slightly brown coloured reaction mixture is subsequently neutralised with dilute hydrochloric acid, freed from methanol in vacuo and extracted with methylene chloride. The methylene chloride extract is washed neutral with water, dried over sodium sulphate and concentrated to dryness in vacuo. Yield: 18 parts of a brown oil which is chromatographed over aluminium oxide. Elution with chlorobenzene yields 6.5 parts (34% of theory) of 6,7-dimethyl-1,4-di-cyanonaphthalene of formula ##STR46## in the form of white crystals with a melting point of 212°-220° C. Two recrystallisations from alcohol yield small white needles with a melting point of 225°-227° C.
Reaction SMILES: [CH:1]1[C:11]2[CH:10]=[CH:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[CH:6]([C:16]3[C:17]([S:37][CH3:38])=[N:18][C:19](=O)[N:20]([CH2:22][C:23]4[CH:24]=[C:25]([CH:33]=[CH:34][CH:35]=4)[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH:21]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:48])=CC=1>C1C=CC=CC=1>[CH:1]1[C:11]2[CH:10]=[CH:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[CH:6]([C:16]3[C:17]([S:37][CH3:38])=[N:18][C:19](=[S:48])[N:20]([CH2:22][C:23]4[CH:24]=[C:25]([CH:33]=[CH:34][CH:35]=4)[C:26]([O:28][C:29]([CH3:32])([CH3:30])[CH3:31])=[O:27])[CH:21]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: CSc1nc(=O)n(Cc2cccc(C(=O)OC(C)(C)C)c2)cc1C1c2ccccc2C=Cc2ccccc21
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: c1ccccc1
Product: CSc1nc(=S)n(Cc2cccc(C(=O)OC(C)(C)C)c2)cc1C1c2ccccc2C=Cc2ccccc21

Procedure:
A mixture of the product from step (v) (0.46 g) and Lawesson's reagent (0.18 g) in benzene (5 ml) was heated at reflux for 2 hours. The mixture was evaporated and purified by chromatography eluting with 10% ethyl acetate in toluene. Yield 0.5 g.