Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[N:5][O:6][C:7]=1[CH3:8].[F:9][C:10]1[CH:11]=[C:12]([C:16]2[N:31]=[C:19]3[N:20]=[C:21]([N:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)[N:22]=[C:23]([NH2:24])[N:18]3[N:17]=2)[CH:13]=[CH:14][CH:15]=1.CCN(CC)CC>CC#N>[F:9][C:10]1[CH:11]=[C:12]([C:16]2[N:31]=[C:19]3[N:20]=[C:21]([N:25]4[CH2:26][CH2:27][N:28]([CH2:2][C:3]5[CH:4]=[N:5][O:6][C:7]=5[CH3:8])[CH2:29][CH2:30]4)[N:22]=[C:23]([NH2:24])[N:18]3[N:17]=2)[CH:13]=[CH:14][CH:15]=1
Reactant: Nc1nc(N2CCNCC2)nc2nc(-c3cccc(F)c3)nn12
Reactant: Cc1oncc1CCl
Solvent: CCN(CC)CC
Solvent: CC#N
Product: Cc1oncc1CN1CCN(c2nc(N)n3nc(-c4cccc(F)c4)nc3n2)CC1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
4-Chloromethyl-5-methyl-isoxazole (1.5 eq.) was directly added to a solution of 2-(3-fluoro-phenyl)-5-piperazin-1-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine (0.14 mmol; see Example 10(a) above) and Et3N (0.3 mmol) in 3 mL of CH3CN. The resulting reaction mixture was stirred at room temp for 18 hours. It was then concentrated and purified by preparative HPLC using a mixture of aqueous CH3CN that has been buffered with 0.1% TFA.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[I:11].Br[CH2:13][CH2:14][CH:15]1[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16]1>>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:13][CH2:14][CH:15]1[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH2:16]1)[N:6]=[C:5]2[I:11]
Reactant: Fc1ccc2[nH]nc(I)c2c1
Reactant: CC(C)(C)OC(=O)N1CCCC(CCBr)C1
Product: CC(C)(C)OC(=O)N1CCCC(CCn2nc(I)c3cc(F)ccc32)C1
Yield: 56 %

Procedure:
The title compound was prepared in 56% yield from 5-fluoro-3-iodo-indazole and tert-butyl 3-(2-bromoethyl)piperidine-1-carboxylate according to the general procedure for Preparation 10A. 1H NMR (400 MHz, CDCl3): δ 1.16-1.32 (2H, m), 1.37-1.62 (11H, m), 1.78-1.87 (3H, m), 2.70-2.76 (1H, m), 2.90-2.93 (1H, m), 3.75-3.88 (2H, m), 4.42 (2H, t, J=2.0, 7.2 Hz), 7.11 (1H, d, J=8.4 Hz), 7.21 (1H, td, J=2.0, 8.8 Hz), 7.38 (1H, dd, J=4.0, 9.2 Hz).
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][C:10]([F:13])([F:12])[F:11])=[CH:5][CH:4]=1.Br[CH2:15][CH2:16][O:17]C1CCCCO1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[CH3:1][N:2]([C:3]1[CH:8]=[CH:7][C:6]([O:9][C:10]([F:11])([F:12])[F:13])=[CH:5][CH:4]=1)[CH2:15][CH2:16][OH:17]
Reactant: BrCCOC1CCCCO1
Reactant: CNc1ccc(OC(F)(F)F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CN(CCO)c1ccc(OC(F)(F)F)cc1
Temperature: 100 °C
Reaction time: 5 h
Yield: 54.4 %

Procedure:
A mixture of N-methyl-(4-trifluoromethoxyphenyl)amine (4.83 g, 24.24 mmol), 2-(2-bromoethoxy)-tetrahydropyran (6.1 g, 29.03 mmol), and potassium carbonate (3.84 g, 27.76 mmol) in DMF (20 ml) was stirred at 100° C. for 5 hours. The reaction mixture was allowed to return to room temperature, poured into water, and extracted with ethyl acetate twice. The extract was washed with water twice and brine, and dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/ethyl acetate=20/1) to afford 2-[N-methyl-(4-trifluoromethoxyphenyl)-amino]ethanol (3.1 g, yield 53%) as a pale yellow oil.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][C:5]([O:7]CC)=O.[CH3:10][CH:11]([CH2:14][CH2:15][CH2:16][CH3:17])[CH:12]=O>>[CH3:10][CH:11]([CH2:14][CH2:15][CH2:16][CH3:17])[CH:12]=[CH:2][CH2:3][CH2:4][CH2:5][OH:7]
Reactant: CCOC(=O)CCCBr
Reactant: CCCCC(C)C=O
Product: CCCCC(C)C=CCCCO
Yield: 52 %

Procedure:
6-methyl-4-decen-1-ol was prepared in the same manner according to Example 4 except that 97.5 g (0.5 mol) of ethyl 4-bromobutyrate was used in place of ethyl 5-bromovalerate and 57.1 g (0.5 mol) of 2-methyl hexanal was used in place of 2-methyl valeraldehyde.
Reaction SMILES: [CH3:1][CH:2]1[CH:10]([CH3:11])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1.C(N(CC)CC)C.[N+:19]([C:22]1[CH:30]=[CH:29][C:25]([C:26](Cl)=[O:27])=[CH:24][CH:23]=1)([O-:21])=[O:20]>ClCCl>[CH3:1][CH:2]1[CH:10]([CH3:11])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[C:26](=[O:27])[C:25]1[CH:24]=[CH:23][C:22]([N+:19]([O-:21])=[O:20])=[CH:30][CH:29]=1
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Reactant: CC1Nc2ccccc2C1C
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC1c2ccccc2N(C(=O)c2ccc([N+](=O)[O-])cc2)C1C
Temperature: 25 °C
Reaction time: 4 h
Yield: 5616.2 %

Procedure:
To a mixture of 2,3-dimethylindoline (736 mg) and triethylamine (0.836 ml) in dichloromethane (20 ml) was added p-nitrobenzoyl chloride (928 mg) and the solution was stirred at ambient temperature for 4 hours. The solution was washed successively with 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate, water and brine, and dried over magnesium sulfate. The solvent was evaporated in vacuo and the residue was solidified with n-hexane to give 2,3-dimethyl-1-(4-nitrobenzoyl)indoline (83.2 g).
Reaction SMILES: [CH3:1][C:2]([C:5]1[CH:9]=[CH:8][NH:7][N:6]=1)([CH3:4])[CH3:3].[H-].[Na+].Br[CH:13]1[CH2:17][CH2:16][N:15]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([O:25][CH3:26])[CH:19]=2)[C:14]1=[O:27].O>CN(C)C=O>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([N:15]2[CH2:16][CH2:17][CH:13]([N:7]3[CH:8]=[CH:9][C:5]([C:2]([CH3:4])([CH3:3])[CH3:1])=[N:6]3)[C:14]2=[O:27])=[CH:19][C:20]=1[O:25][CH3:26]
Reactant: COc1cc(N2CCC(Br)C2=O)ccc1Cl
Reactant: CC(C)(C)c1cc[nH]n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc(N2CCC(n3ccc(C(C)(C)C)n3)C2=O)ccc1Cl
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 3-(1,1-dimethylethyl)-1H-pyrazole (0.22 g, 1.8 mmol) in N,N-dimethylformamide (20 mL) under nitrogen at room temperature was added 60% sodium hydride in mineral oil (79 mg, 2.0 mmol). After the addition, the mixture was stirred at room temperature for ˜15 minutes, and then 3-bromo-1-(4-chloro-3-methoxyphenyl)-2-pyrrolidinone (0.5 g, 1.6 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight and then poured into water (˜100 mL). The aqueous layer was extracted twice with ethyl acetate (˜50 mL each). The organic extracts were combined, washed twice with water (˜100 mL each), dried over MgSO4 and filtered. The filtrate was concentrated. The residue was purified by medium pressure liquid chromatography (silica gel) using as eluant methylene chloride and then 10:1 (by volume) ethyl acetatemethylene chloride to give the title compound, a compound of this invention, as a solid (186 mg) melting at 128–130 ° C.
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])[CH3:2].[NH2:8][CH2:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:27])[CH2:22][CH2:21]1)[C:15](=[O:36])[N:14]([CH2:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[C:40]([O:46][CH3:47])[CH:39]=1)[C:13]2=[O:48].CCN(CC)CC>C(Cl)Cl>[C:1]([NH:8][CH2:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)=[O:27])[CH2:22][CH2:21]1)[C:15](=[O:36])[N:14]([CH2:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[C:40]([O:46][CH3:47])[CH:39]=1)[C:13]2=[O:48])(=[O:3])[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: COc1ccc(Cn2c(=O)c3cc(CN)ccc3n(C3CCN(C(=O)OCc4ccccc4)CC3)c2=O)cc1OC
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(Cn2c(=O)c3cc(CNC(C)=O)ccc3n(C3CCN(C(=O)OCc4ccccc4)CC3)c2=O)cc1OC
Reaction time: 1 h
Yield: 107.5 %

Procedure:
0.049 g of acetic anhydride is added to a solution of 0.09 g of benzyl 4-[6-(aminomethyl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carboxylate obtained in stage 5.5 and 0.09 ml of NEt3 in 3 ml of DCM and the mixture is stirred at AT for 1 h 00. DCM is added and the solution is washed with a saturated NH4Cl solution, then with a 1N HCl solution, then with a 2N NaOH solution and then with water. The organic phase is dried over Na2SO4 and filtered, and the filtrate is evaporated under reduced pressure to give 0.104 g of the expected product.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].[NH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][OH:24])=[CH:18][CH:17]=1.C([O-])([O-])=O.[Na+].[Na+]>C(O)C>[CH3:11][S:8]([C:5]1[CH:6]=[CH:7][C:2]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][OH:24])=[CH:18][CH:17]=2)=[C:3]([N+:12]([O-:14])=[O:13])[CH:4]=1)(=[O:10])=[O:9]
Reactant: CS(=O)(=O)c1ccc(Cl)c([N+](=O)[O-])c1
Reactant: Nc1ccc(CCO)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Product: CS(=O)(=O)c1ccc(Nc2ccc(CCO)cc2)c([N+](=O)[O-])c1
Temperature: 100 °C
Reaction time: 16 h
Yield: 33.6 %

Procedure:
A mixture of 2-chloro-5-methylsulfonylnitrobenzene (Kavalek, J.; et al. Collect. Czech. Chem. Commun, 1971, 36, 209., 2 g, 8.5 mmol), 4-aminophenylethyl alcohol (1.4 g, 10.2 mmol) and Na2CO3 (1.4 g, 12.7 mmol) in ethanol was stirred at 100° C. for 16 h. The insoluble matter was removed by filtration and washed with ethanol (100 mL). The filtrate was concentrated and the residue was purified by flash column chromatography on silica gel eluting with hexane/ethyl acetate (1:4) to afford 960 mg (34%) of the title compound as yellow solids: 1H-NMR (CDCl3) δ 9.84 (1H, br.s), 8.82 (1H, d, J=2.1 Hz), 7.79 (1H, dd, J=2.1 Hz, 9.1 Hz), 7.36 (2H, d, J=8.4 Hz), 7.22-7.38 (3H, m), 3.94 (2H, br.s), 3.07 (3H, s), 2.93 (2H, t, J=6.6 Hz).
Reaction SMILES: [CH3:1][CH:2]([CH2:6][CH2:7][CH:8]=[C:9]([CH3:11])[CH3:10])[CH2:3][CH:4]=[O:5]>CCCCCCC>[CH3:1][CH:2]([CH2:6][CH2:7][CH:8]=[C:9]([CH3:10])[CH3:11])[CH2:3][CH2:4][OH:5]
Reactant: CC(C)=CCCC(C)CC=O
Solvent: CCCCCCC
Product: CC(C)=CCCC(C)CCO
Temperature: 90 °C

Procedure:
3,7-dimethyloct-6-enal (154 g, 1 mol.), heptane (154 g, 100 wt. %, technical grade) and (ethylenediamine)[1,2-bis(diphenylphosphino) ethane]ruthenium(bisbenzoate) (26.5 mg, 0.033 mmol, 0.0033 mol.%) were loaded altogether in a 11 autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 30 bars hydrogen. It was then heated to 90° C. and hydrogen pressure was maintained to 30 bars during all the reaction to afford desired product with 99% selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25° C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After flash distillation, pure 3,7-trimethyloct-6-en-1-ol was obtained in 98% yield.
Reaction SMILES: [Cl:1][C:2]1[C:10]2[C:6](=[CH:7][N:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][Si](C(C)C)(C(C)C)C(C)C)=[CH:13][CH:12]=3)[N:9]=2)[CH:5]=[CH:4][C:3]=1[O:28][CH2:29][CH:30]1[CH2:32][CH2:31]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[Cl:1][C:2]1[C:10]2[C:6](=[CH:7][N:8]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=3)[N:9]=2)[CH:5]=[CH:4][C:3]=1[O:28][CH2:29][CH:30]1[CH2:31][CH2:32]1
Reactant: CC(C)[Si](Oc1ccc(-n2cc3ccc(OCC4CC4)c(Cl)c3n2)cc1)(C(C)C)C(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: Oc1ccc(-n2cc3ccc(OCC4CC4)c(Cl)c3n2)cc1
Reaction time: 1 h
Yield: 59.6 %

Procedure:
To a solution of 7-chloro-6-(cyclopropylmethoxy)-2-(4-{[tris(1-methylethyl)silyl]oxy}phenyl)-2H-indazole (112 mg) in THF (1 mL) was added a THF solution (1.0 M, 0.71 mL) of tetrabutylammonium fluoride at room temperature, and the mixture was stirred for 1 hr. The solvent was evaporated under reduced pressure, water was added to the residue, and the mixture was extracted with ethyl acetate. The separated aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound as colorless crystals (44.6 mg).
Reaction SMILES: [OH:1][C@H:2]1[C:11]2[CH:10]=[CH:9][N:8]3[CH:12]=[C:13]([CH3:15])[N:14]=[C:7]3[C:6]=2[NH:5][C@H:4]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C@H:3]1[OH:22].[C:23]1(C)C=CC(S(O)(=O)=O)=CC=1.CC(C)=O>COC(OC)(C)C>[OH:22][C@H:3]1[C@@H:2]([O:1][CH3:23])[C:11]2[CH:10]=[CH:9][N:8]3[CH:12]=[C:13]([CH3:15])[N:14]=[C:7]3[C:6]=2[NH:5][C@@H:4]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: Cc1cn2ccc3c(c2n1)N[C@H](c1ccccc1)[C@@H](O)[C@H]3O
Solvent: COC(C)(C)OC
Solvent: CC(C)=O
Product: CO[C@H]1c2ccn3cc(C)nc3c2N[C@H](c2ccccc2)[C@H]1O
Temperature: 25 °C
Reaction time: 96 h

Procedure:
To a suspension of 0.62 g (2.10 mmol) (7S,8R,9R)-7,8-dihydroxy-2-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine in dimethoxypropane is added 0.51 g (26.2 mmol) p-toluenesulphonic acid and acetone (4.0 ml). The mixture is stirred for 6 h at 60° C. and 96 h at 25° C. The reaction is quenched by adding of saturated aqueous sodium hydrogen carbonate solution. Subsequently the mixture is extracted twice with dichloromethane. The combined organic layers are washed with brine, dried over sodium sulphate and evaporated in vacuo. The crude product is purified by column chromatography (dichloromethane/methanol: 100/3) to give 0.18 g (0.52 mmol/25%) of the title compound as an amorphous solid. 1H-NMR (200 MHz,[D6] DMSO): δ=2.28 (s, 3H), 3.30 (s, 1H), 3.09-4.03 (m, 1H), 4.06 (d, 1H), 4.49 (dd, 1H), 6.67 (d, 1H), 7.22-7.44 (m, 5H), 7.54 (d, 1H), 7.69 (d, 1H).
Reaction SMILES: [N+:1]([C:4]1[CH:25]=[CH:24][C:7]([CH2:8][O:9][C:10](=[O:23])[C@H:11]([CH:20]([CH3:22])[CH3:21])[NH:12]C(OC(C)(C)C)=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].[ClH:26]>O1CCOCC1>[ClH:26].[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][O:9][C:10](=[O:23])[C@H:11]([CH:20]([CH3:21])[CH3:22])[NH2:12])=[CH:24][CH:25]=1)([O-:3])=[O:2]
Reactant: CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)OCc1ccc([N+](=O)[O-])cc1
Agent: Cl
Solvent: C1COCCO1
Product: CC(C)[C@H](N)C(=O)OCc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 88 %

Procedure:
To a solution of N-(t-butoxycarbonyl)-L-valine p-nitrobenzyl ester (3.07 g, 8.71 mmol) (obtained as described in Reference Example 46(1)) in 1,4-dioxane (31 ml) was added a solution of 4N hydrogen chloride in 1,4-dioxane (31 ml) in an ice bath, and the mixture was stirred at room temperature overnight. After checking the completion of the reaction, the reaction mixture was concentrated under reduced pressure, to the obtained residue was added ethyl acetate, and the mixture was filtered. The resulting residue was washed with ethyl acetate and dried to give L-valine p-nitrobenzyl ester hydrochloride (2.21 g, yield 88%).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[CH:5]=[O:6].CI.[C:13](=O)([O-])[O-].[Li+].[Li+]>CN(C=O)C>[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:13])[CH:5]=[O:6]
Reactant: O=Cc1ccc(O)c(O)c1
Reactant: O=C([O-])[O-]
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: CI
Product: COc1ccc(C=O)cc1O
Temperature: 90 °C
Reaction time: 1.5 h
Yield: 82.2 %

Procedure:
3,4-Dihydroxybenzaldehyde (2.76 g, 20 mmol) was dissolved in DMF (15 ml), and methyl iodide (37.4 ml, 60 mmol) and anhydrous lithium carbonate (4.4 g, 60 mmol) were successively added to this solution. After being stirred at an external temperature of 90° C. for 1.5 hours, the reaction mixture was cooled to room temperature and the inorganic salt was filtered off. A saturated aqueous solution of ammonium chloride (200 ml) was added to the filtrate to adjust the aqueous layer to a pH of from 7 to 8, and the solution was extracted with ethyl acetate (300 ml×2). The combined organic layer was washed with a saturated aqueous solution of sodium chloride (300 ml), dried over anhydrous magnesium sulfate, filtered to remove the desiccating agent, and concentrated under reduced pressure to give the title compound (2.5 g, 82.2%) (Table 1).
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2([C:14]#[N:15])[CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[OH2:16]>S(=O)(=O)(O)O>[I:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]2([C:14]([NH2:15])=[O:16])[CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:6][CH:7]=1
Reactant: O
Reactant: N#CC1(Nc2ccc(I)cc2)CCCC1
Agent: O=S(=O)(O)O
Product: NC(=O)C1(Nc2ccc(I)cc2)CCCC1
Temperature: 25 °C
Reaction time: 48 h
Yield: 94 %

Procedure:
4.2 g (13.4 mmol) of 1-(4-iodophenyl-amino)-cyclopentanecarbonitrile are dissolved in 40 ml of concentrated sulfuric acid. The reaction medium is stirred for 48 hrs at ambient temperature, then it is poured gently into water and the pH is adjusted to 7 with soda and [the mixture] extracted with ethyl acetate. The organic phases are combined and washed with water. They are dried over sodium sulfate. The solvents are evaporated and the residue is crystallized in a little dichloromethane and heptane. It is then filtered and dried. 4.2 g of 1-(4-iodophenylamino)-cyclopentanecarboxamide are obtained in the form of a pink solid. (M.Pt.=148° C., Yield=94%).
Reaction SMILES: N([C@:4]1([CH2:19][OH:20])[O:8][C@@H:7]([N:9]2[CH:16]=[CH:15][C:13](=[O:14])[NH:12][C:10]2=[O:11])[C@H:6]([OH:17])[C@@H:5]1[OH:18])=[N+]=[N-].CO[C:23](OC)([CH3:25])[CH3:24]>CC(C)=O.C(OCC)(=O)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[OH:20][CH2:19][CH:4]1[CH:5]2[O:18][C:23]([CH3:25])([CH3:24])[O:17][CH:6]2[CH:7]([N:9]2[CH:16]=[CH:15][C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:8]1
Reactant: COC(C)(C)OC
Reactant: [N-]=[N+]=N[C@]1(CO)O[C@@H](n2ccc(=O)[nH]c2=O)[C@H](O)[C@@H]1O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: CC1(C)OC2C(CO)OC(n3ccc(=O)[nH]c3=O)C2O1
Temperature: 25 °C
Reaction time: 12 h
Yield: 73.7 %

Procedure:
A mixture containing 3.0 g (10.5 mmol) of 4′-azidouridine, 0.05 g (0.26 mmol) p-toluenesulfonic acid monohydrate and 6 mL (48.8 mmol) 2,2-dimethoxypropane in 20 mL acetone was stirred at room temperature for 12 h. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate solution, dried over magnesium sulfate and evaporated to dryness under reduced pressure to give the desired product 2.20 g (64%) of as a white solid.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1)#[N:2].Br[C:13]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:14]=1[O:22][CH3:23].C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([C:3]1[CH:4]=[C:5]([C:15]2[CH:16]=[C:17]([N+:19]([O-:21])=[O:20])[CH:18]=[CH:13][C:14]=2[O:22][CH3:23])[CH:6]=[CH:7][CH:8]=1)#[N:2]
Reactant: N#Cc1cccc(B(O)O)c1
Reactant: COc1ccc([N+](=O)[O-])cc1Br
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: COCCOC
Product: COc1ccc([N+](=O)[O-])cc1-c1cccc(C#N)c1
Temperature: 90 °C
Yield: 99.9 %

Procedure:
[1,1′Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane(II) (1.43 g) was added to a stirred mixture of 3-cyanophenylboronic acid (10.0 g, 61.8 mmol) and 2-bromo-4-nitroanisole (14.35 g, 62 mmol) in 2.0N cesium carbonate (92.7 mL, 185.4 mmol) and ethylene glycol dimethylether (200 mL). The flask was purged with nitrogen and heated at 90° C. (oil bath) for 4 hours. The mixture was allowed to cool to room temperature overnight, during which time the product precipitated from solution. The solid was collected on a Buchner funnel, washed with water and dried under reduced pressure to give 2-(3-cyanophenyl)-4-nitroanisole (15.7 g).
Reaction SMILES: Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=1)=[O:3].C(NCC)C.[CH2:19]([O:21]/[C:22](=[CH:28]\[C:29]1[CH:34]=[CH:33][C:32]([C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([NH:41][CH3:42])[CH:36]=2)=[CH:31][CH:30]=1)/[C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH3:20].O>ClCCl>[CH2:19]([O:21]/[C:22](=[CH:28]\[C:29]1[CH:34]=[CH:33][C:32]([C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([N:41]([CH3:42])[C:2]([O:4][C:5]3[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=3)=[O:3])[CH:36]=2)=[CH:31][CH:30]=1)/[C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH3:20]
Reactant: CCOC(=O)/C(=C/c1ccc(-c2cccc(NC)c2)cc1)OCC
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Solvent: ClCCl
Solvent: CCNCC
Solvent: O
Product: CCOC(=O)/C(=C/c1ccc(-c2cccc(N(C)C(=O)Oc3ccc([N+](=O)[O-])cc3)c2)cc1)OCC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 126.2 %

Procedure:
0.63 g (3.1 mmol) of 4-nitrophenyl chloroformate and then 0.54 mL (3.1 mmol) of diethylamine are added to a solution of 0.68 g (2.1 mmol) of ethyl (Z)-2-ethoxy-3-(3′-methylaminobiphenyl-4-yl)acrylate in 15 mL of dichloromethane. The reaction mixture is stirred for 1 hour 30 minutes at room temperature. The reaction is worked up by addition of 10 mL of water and then extracted with dichloromethane. The organic phases are combined and then dried over magnesium sulfate. The solvents are evaporated off. 1.3 g (100%) of ethyl (Z)-2-ethoxy-3-{3′-[methyl-(4-nitrophenoxycarbonyl)amino]biphenyl-4-yl}acrylate are obtained in the form of a yellow oil.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH:7]2[CH2:17][CH2:18][C:19](O)=[O:20].[C:22](OC(=O)C)(=[O:24])C.O>C(O)=O>[CH:22]([N:9]1[C:10]2[C:2]([CH3:1])=[CH:3][CH:4]=[C:5]3[C:19](=[O:20])[CH2:18][CH2:17][CH:7]([C:6]=23)[CH:8]1[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:24]
Reactant: Cc1cccc2c1NC(c1ccccc1)C2CCC(=O)O
Reactant: CC(=O)OC(C)=O
Solvent: O=CO
Solvent: O
Product: Cc1ccc2c3c1N(C=O)C(c1ccccc1)C3CCC2=O
Temperature: 25 °C
Reaction time: 72 h
Yield: 97 %

Procedure:
7-methyl-2-phenyl-2,3-dihydroindole-3-propionic acid (13.47 g) synthesized as in Example 1, steps 1 and 2 was dissolved in formic acid (50 ml) and to the solution was added acetic anhydride (4.53 ml) under cooling with ice. The mixture was stirred for 3 days at room temperature. After adding water, the reaction mixture was extracted twice with ethyl acetate. The organic layers were combined, washed with water and saturated aqueous solution of sodium chloride successively and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was crystallized from an ether/hexane mixed solvent to yield 13.07 g (97%) of the titled compound as pale brown crystals.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]([OH:8])[CH3:7].[OH-].[Na+].Br[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]>S(=O)(=O)(O)[O-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:12]([O:8][CH:6]([C:2]1[O:1][CH:5]=[CH:4][CH:3]=1)[CH3:7])[CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CC(O)c1ccco1
Reactant: CCCCCBr
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Agent: [Na+]
Product: CCCCCOC(C)c1ccco1

Procedure:
Ten grams of the distilled 1-furylethanol (0.089 mole) is charged to a reactor with 0.61 g (2 mole percent) tetrabutylammonium bisulfate and 19.2 g of a 50 percent aqueous solution of sodium hydroxide added over a 15 minute period with stirring. This is followed by addition of 34.7 g (0.25 mole) 1-bromopentane over a period of 15 minutes and the reaction mixture allowed to stir for 3 hours. The reaction mixture is then extracted with diethyl ether which, after drying over magnesium sulfate, is evaporated. The resulting crude product is short-path distilled to obtain 2-(1-pentoxyethyl)furan in low yield (B.p. 35° C. at 0.2 mm Hg.). The structure of the 2-(1-pentoxyethyl)furan ##STR5## is confirmed by infrared and nuclear magnetic resonance spectroscopy.