Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4])[OH:2].[C:9](O)(=[O:11])[CH3:10].B(F)(F)F>CCOCC>[CH3:10][C:9]([C:5]1[CH:6]=[CH:7][CH:8]=[C:1]([OH:2])[C:3]=1[OH:4])=[O:11]
Reactant: CC(=O)O
Reactant: Oc1ccccc1O
Agent: FB(F)F
Solvent: CCOCC
Product: CC(=O)c1cccc(O)c1O

Procedure:
6-Amino-2,3-dimethoxyacetophenone (2) was also prepared according to published methods. The starting catechol (28) was acetylated, in microwave oven set at 300 Watt power, by reacting with mixture of acetic acid (29) and BF3. Et2O to yield 2,3-dihydroxyacetophenone (30) which was further reacted with diiodomethane in DMF, in the presence of K2CO3, to afford 2,3-methylenedioxyacetophenone (31). Subsequent nitration of compound 31 with 70% HNO3 afforded 2,3-methylenedioxy-6-nitroacetophenone (32). Without purification, compounds 32 was hydrogenated, and purified with column chromatography to provide 6-amino-2,3-methylenedioxyacetophenone (2).10 Another published method was followed in preparation of 6-amino-3-methoxy-4-benzyloxyacetophenone (3). First, the benzylation of the starting acetovanillone (33) with benzylbromide (34) gave 4-benzyloxy-3-methoxyacetophenone (35) which was nitrated to yield 4-benzyloxy-3-methoxy-6-nitroacetophenone (36).11 The so-obtained compound 36 was reduced with SnCl2 to afford compound 3.
Reaction SMILES: Cl[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([Cl:9])=[C:4]([Cl:10])[N:3]=1.CN1CCCC1.[CH:17](Cl)([Cl:19])[Cl:18].[OH-].[Na+]>>[Cl:8][C:7]1[C:2]([CH:17]([Cl:19])[Cl:18])=[N:3][C:4]([Cl:10])=[C:5]([Cl:9])[CH:6]=1
Reactant: ClC(Cl)Cl
Reactant: Clc1cc(Cl)c(Cl)nc1Cl
Agent: CN1CCCC1
Agent: [Na+]
Agent: [OH-]
Product: Clc1cc(Cl)c(C(Cl)Cl)nc1Cl

Procedure:
2,3,5,6-Tetrachloropyridine (1.1 g, 0.005 mole) was combined with 5 ml of N-methylpyrrolidine and 5 ml (about 0.062 mole) of chloroform in a reaction vessel and to the resulting solution 6 g of 50 percent aqueous sodium hydroxide (0.075 mole) was added with stirring. After 30 minutes the title compound was shown to be present in the reaction mixture by gas chromatography at approximately 15 percent conversion.
Reaction SMILES: C1C(=O)N([I:8])C(=O)C1.[CH3:9][O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:17]([OH:21])=[N:16][CH:15]=[CH:14]2>CC#N>[I:8][C:14]1[C:13]2[C:18](=[CH:19][CH:20]=[C:11]([O:10][CH3:9])[CH:12]=2)[C:17]([OH:21])=[N:16][CH:15]=1
Reactant: O=C1CCC(=O)N1I
Reactant: COc1ccc2c(O)nccc2c1
Solvent: CC#N
Product: COc1ccc2c(O)ncc(I)c2c1
Yield: 87.3 %

Procedure:
To a solution of NIS (3.31 g, 14.73 mmol) in CH3CN (25 mL) was added 6-methoxyisoquinolin-1-ol (2.58 g, 14.73 mmol). The resulting suspension was slowly warmed to reflux and maintained refluxing for 2 h. After concentration, the residue was taken into water. The solid was collected through filter paper washing with hot water to give a crude product 4-iodo-6-methoxyisoquinolin-1-ol (3.87 g, 87% yield) which was used in the next step with out further purification. MS: MS m/z 302(M++1). 1H NMR (400 MHz, CHLOROFORM-d) δ 16.12 (br. s., 1H), 12.86 (d, J=9.0 Hz, 1H), 12.34 (d, J=5.8 Hz, 1H), 11.89 (dd, J=8.8, 2.5 Hz, 1H), 11.76 (d, J=2.3 Hz, 1H), 8.70-8.62 (m, 3H).
Reaction SMILES: CC1C=CC(S(O[CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[O:28][CH3:29])[C:15]=3[O:14]2)(=O)=O)=CC=1.[CH3:30][NH2:31]>>[CH3:30][NH:31][CH2:12][CH:13]1[CH2:17][C:16]2[CH:18]=[CH:19][CH:20]=[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])[C:15]=2[O:14]1
Reactant: CN
Reactant: COc1ccccc1-c1cccc2c1OC(COS(=O)(=O)c1ccc(C)cc1)C2
Product: CNCC1Cc2cccc(-c3ccccc3OC)c2O1

Procedure:
The title compound was prepared (0.250 g, 76%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-[7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.501 g, 1.22 mmol) and methylamine (4.56 g, 150.0 mmol). mp 157-159° C.
Reaction SMILES: [CH2:1]([O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=2)=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH2:4][CH3:5].C([Li])CCC.C([O:28][B:29](OC(C)C)[O:30]C(C)C)(C)C.Cl>O1CCCC1>[CH2:1]([O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([B:29]([OH:30])[OH:28])=[CH:15][CH:14]=2)=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CCCCCOc1ccc(-c2ccc(Br)cc2)cc1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCCCCOc1ccc(-c2ccc(B(O)O)cc2)cc1
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 84.3 %

Procedure:
To a stirred suspension of 4-(4-n-pentoxyphenyl)bromo-benzene (1.0 g, 3.13 mmol) in anhydrous tetrahydrofuran (20 ml) at -78° C. under a nitrogen atmosphere was added n-butyllithium in hexanes (2.5M, 1.32 ml, 3.30 mmol). After a period of 15 min, triisopropyl-borate (760 μl, 3.30 mmol) was added. Stirring at -78° C. was continued for 15 min and then at 25° C. for 40 min. The mixture was acidified with 0.5N HCl (20 mL) and then partitioned between ether (50 ml) and water (40 ml). The organic phase was washed with water (3×) and brine and dried with magnesium sulfate. The solvent was removed in vacuo to give 4-(4-n-pentoxyphenyl)phenylboronic acid (750 mg) as a solid: 1H NMR (400MHz, DMSO-d6) δ0.89 (t, 3H, J=7.2 Hz), 1.38 (m, 4H), 1.72 (m, 2H), 3.99 (t, 2H, J=6.5 Hz), 6.99 (d, 2H, J=8.8 Hz), 7.57 (d, 2H, J=8.2 Hz), 7.60 (d, 2H, J=8.8 Hz), 7.83 (d, 2H, J=8.2 Hz).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.[C:13]1([C:19]2[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=2)[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]=1>CCOCC>[C:13]1([C:19]2[CH:20]=[CH:21][C:22]([C:23](=[O:24])[C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=3)=[CH:26][CH:27]=2)[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]=1
Reactant: O=C(O)c1ccc(C2=CCCCC2)cc1
Reactant: Brc1ccccn1
Agent: [Li]CCCC
Solvent: CCOCC
Product: O=C(c1ccc(C2=CCCCC2)cc1)c1ccccn1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
40 g of 2-bromopyridine in 50 ml of absolute ether are added dropwise slowly at -60° C with stirring and in a nitrogen atmosphere to 175 ml of a 1.5 N solution of butyl-lithium in ether, followed, 15 minutes after the completion of the addition, by a solution of 15 g of p-(1-cyclohexenyl)-benzoic acid in 250 ml of absolute ether. The cooling bath is then removed, the reaction mixture is allowed to warm up to room temperature and it is stirred for 2 hours at room temperature. Working up is carried out by pouring the reaction solution onto a mixture of ice and ammonium chloride and partitioning it between ether and water. The ether phase is separated off and washed successively with water, 0.1 N sodium hydroxide solution and water, dried over sodium sulphate and evaporated under reduced pressure. Distillation under reduced pressure of the evaporation residue yields, in the fraction boiling at 200° C (0.9 mm Hg), crude 2-{[p-(1-cyclohexenyl)-phenyl]-oxomethyl}-pyridine of the formula ##STR3## of melting point 58°-60° C.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]2[N:16]=[CH:15][N:14]=[C:13]3[C:9]=2[N:10]=[CH:11][N:12]3C2CCCCO2)=[CH:6][N:5]=[CH:4][N:3]=1.[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31]2[C:40]3[CH:39]=[CH:38][C:37]([CH3:41])=[C:36]([NH2:42])[C:35]=3[CH:34]=[CH:33][N:32]=2)=[CH:26][CH:25]=1>CN(C=O)C>[N:16]1[C:8]([C:7]2[C:2]([NH:42][C:36]3[C:35]4[CH:34]=[CH:33][N:32]=[C:31]([NH:30][C:27]5[CH:28]=[CH:29][C:24]([Cl:23])=[CH:25][CH:26]=5)[C:40]=4[CH:39]=[CH:38][C:37]=3[CH3:41])=[N:3][CH:4]=[N:5][CH:6]=2)=[C:9]2[C:13]([NH:12][CH:11]=[N:10]2)=[N:14][CH:15]=1
Reactant: Cc1ccc2c(Nc3ccc(Cl)cc3)nccc2c1N
Reactant: Clc1ncncc1-c1ncnc2c1ncn2C1CCCCO1
Solvent: CN(C)C=O
Product: Cc1ccc2c(Nc3ccc(Cl)cc3)nccc2c1Nc1ncncc1-c1ncnc2[nH]cnc12
Temperature: 70 °C

Procedure:
In a 2 mL microwave reaction tube were added 6-(4-chloropyrimidin-5-yl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (31 mg, 98 mop and N1-(4-chlorophenyl)-6-methylisoquinoline-1,5-diamine (28 mg, 98 μmol) in DMF (0.6 mL). The mixture was thoroughly mixed and flushed with argon then sealed. It was stirred at 70° C. The temperature was raised to 90° C. after 2 hrs and allowed over night. The reaction mixture was partitioned in EtOAc and NaHCO3. The organic layer was washed with brine and dried over Na2SO4. The residue was treated with MeOH (3 mL) and conc HCl (0.2 mL). The mixture was stirred for 2 hrs, then partitioned between NaHCO3 and EtOAc (10 mL each). The organic layer was collected and purified by prep HPLC (MeCN/H2O=5-95% with 0.1% TFA). Desired fractions were combined and neutralized with NaHCO3 (sat., aq.) and extracted with DCM. The DCM layer was washed with brine then dried over Na2SO4, then dried over a stream of N2 to give a yellow solid N5-(5-(9H-purin-6-yl)pyrimidin-4-yl)-N1-(4-chlorophenyl)-6-methylisoquinoline-1,5-diamine. MS Found: (ESI pos. ion) m/z 480 (M+H+).
Reaction SMILES: [Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.[I:12][C:13]1[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=1[CH2:15][OH:16]>ClCCl.CCOCC>[I:12][C:13]1[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=1[CH:15]=[O:16]
Reactant: OCc1ccccc1I
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: CCOCC
Product: O=Cc1ccccc1I
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 95.9 %

Procedure:
A suspension of pyridinium chlorochromate (8.28 g, 38.4 mmol) and dry celite (5.00 g) in dry dichloromethane was stirred at room temperature for 15 min. 2-Iodobenzyl alcohol (3.03 g, 12.9 mmol) in dry dichloromethane (50 ml) was added. The suspension was shielded from light and stirred at room temperature for 2 h after which it was diluted with ether, and filtered through celite. The cloudy brown filtrate was concentrated to a red-brown gummy solid which was dissolved in dichloromethane and passed through a short silica column, eluting with dichloromethane. The solution was concentrated to give 2-iodobenzaldehyde (19) as a pale yellow oil (2.87 g, 95%).
Reaction SMILES: [CH:1]([NH:4][CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2].Br[CH2:9][CH2:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13]>C(O)C>[CH:1]([N:4]([CH:5]([CH3:7])[CH3:6])[CH2:9][CH2:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])([CH3:3])[CH3:2]
Reactant: CC(C)NC(C)C
Reactant: CCOC(=O)CCCBr
Solvent: CCO
Product: CCOC(=O)CCCN(C(C)C)C(C)C
Yield: 21.4 %

Procedure:
Ethyl 4-diisopropylaminobutyrate may be obtained in the following manner: diisopropylamine (40.4 g) is added dropwise to a solution of ethyl 4-bromobutyrate (39 g) in ethanol (80 cc). The solution obtained is heated to reflux for 6 hours. After the insoluble material formed has been filtered off, the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The residue is taken up with distilled water (15 cc) and 4 N aqueous hydrochloric acid solution (100 cc). The aqueous phase is washed with ethyl ether (3×75 cc) and then alkalinized with 10 N aqueous sodium hydroxide solution. The oil formed is extracted with ethyl ether (3×75 cc). The organic phase obtained is concentrated to dryness under reduced pressure (2.7 kPa). Ethyl 4-diisopropylaminobutyrate (9.2 g) is thereby obtained in the form of an oil, which is employed in the crude state in the subsequent syntheses.
Reaction SMILES: Cl[C:2]1[CH:11]=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:12])[CH:8]=2)[N:3]=1.[OH:13][C:14]1[CH:32]=[CH:31][C:17]([O:18][CH:19]([CH3:30])[C:20]([O:22][CH2:23][CH2:24][NH:25][C:26](=[O:29])[O:27][CH3:28])=[O:21])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:12][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([O:13][C:14]1[CH:15]=[CH:16][C:17]([O:18][CH:19]([CH3:30])[C:20]([O:22][CH2:23][CH2:24][NH:25][C:26](=[O:29])[O:27][CH3:28])=[O:21])=[CH:31][CH:32]=1)[CH:11]=[N:10]2
Reactant: Clc1ccc2nc(Cl)cnc2c1
Reactant: COC(=O)NCCOC(=O)C(C)Oc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)NCCOC(=O)C(C)Oc1ccc(Oc2cnc3cc(Cl)ccc3n2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 1.99 g of 2,6-dichloroquinoxaline, 2.83 g of methyl 2-[[2-(4-hydroxyphenoxy)propionyl]oxy]ethylcarbamate, 1.4 g of potassium carbonate and 20 ml of N,N-dimethylformamide is stirred at room temperature overnight. For the working-up, the mixture is poured on to ice-water and extracted with ethyl acetate. The extracts are washed with water and sodium chloride solution, dried over sodium sulphate and evaporated. By chromatography on silica gel with hexane/ethyl acetate (2:1) there is obtained pure methyl 2-[[2-[p-[(6-chloro-2-quinoxalinyl)oxy]phenoxy]propionyl]oxy]ethylcarbamate; m.p. 103°-104.5° C.
Reaction SMILES: CC1C=CC(S(O[CH2:12][C@@H:13]([C:15]2[C:24]([CH3:25])=[CH:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]=2[Cl:26])[OH:14])(=O)=O)=CC=1.CC(C)([O-])C.[K+]>C1COCC1>[Cl:26][C:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:23]=[C:24]([CH3:25])[C:15]=1[C@@H:13]1[CH2:12][O:14]1
Reactant: Cc1ccc(S(=O)(=O)OC[C@H](O)c2c(C)cc3ccccc3c2Cl)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: Cc1cc2ccccc2c(Cl)c1[C@@H]1CO1
Reaction time: 1 h

Procedure:
To a solution of (R)-2-(1-chloro-3-methylnaphthalen-2-yl)-2-hydroxyethyl 4-methylbenzenesulfonate (1.38 g, 3.54 mmol) in THF (39 mL) at 0° C. was added potassium tert-butoxide (3.90 mL of 1.0 M solution in THF, 3.90 mmol). After stirring for 1 h, the reaction mixture was quenched with saturated aqueous NH4Cl, and then diluted with EtOAc. The organic phase was washed with water and brine, dried over Na2SO4, filtered and concentrated and purified by flash column chromatography (silica gel, 0 to 20% ethyl acetate/hexanes) to give (R)-2-(1-chloro-3-methylnaphthalen-2-yl)oxirane. 1H-NMR: 400 MHz, (CDCl3) δ 8.26 (d, J=8.4 Hz, 1H), 7.74 (d, J=7.6 Hz, 1H), 7.57-7.48 (m, 3H), 4.13 (t, J=3.6 Hz, 1H), 3.34 (t, J=5.6 Hz, 1H), 2.97 (dd, J=5.2, 2.8 Hz, 1H), 2.64 (s, 3H).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([F:20])=[C:8]([C:10]2[CH:15]=[C:14]([CH3:16])[N:13]=[C:12]([CH:17]=O)[C:11]=2[CH3:19])[CH:9]=1)[CH3:2].[NH2:21][CH:22]1[CH2:26][CH2:25][N:24]([CH3:27])[C:23]1=[O:28].S([O-])([O-])(=O)=O.[Mg+2]>C(Cl)Cl>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([F:20])=[C:8]([C:10]2[CH:15]=[C:14]([CH3:16])[N:13]=[C:12](/[CH:17]=[N:21]/[CH:22]3[CH2:26][CH2:25][N:24]([CH3:27])[C:23]3=[O:28])[C:11]=2[CH3:19])[CH:9]=1)[CH3:2]
Reactant: CCOc1ccc(F)c(-c2cc(C)nc(C=O)c2C)c1
Reactant: CN1CCC(N)C1=O
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Solvent: ClCCl
Product: CCOc1ccc(F)c(-c2cc(C)nc(/C=N/C3CCN(C)C3=O)c2C)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 241.4 %

Procedure:
To a stirred mixture of 4-(5-ethoxy-2-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carbaldehyde (which may be prepared as described in Description 141) (2980 mg, 10.904 mmol) and 3-amino-1-methyl-pyrrolidin-2-one (508.12 mg, 4.4514 mmol) in anhydrous DCM (10 mL) at room temperature, was added magnesium sulfate (3937.5 mg, 32.711 mmol). The resulting mixture was left to stir at room temperature for 3 h. The reaction mixture was filtered through a plug of cotton wool and the filtrate was washed with brine. The organic layer was collected by means of a PhaseSep cartridge. Evaporation of solvent under reduced pressure gave yellow oil, 3-[(E)-[4-(5-ethoxy-2-fluoro-phenyl)-3,6-dimethyl-2-pyridyl]methyleneamino]-1-methyl-pyrrolidin-2-one (3.97 g, 10.746 mmol, 98.6% yield). To a portion of this material (3920 mg, 10.611 mmol) in anhydrous THF (35 mL) under nitrogen at room temperature, was added phenyl vinyl sulfone (2141.9 mg, 12.733 mmol) and silver acetate (1771.1 mg, 10.611 mmol). The resulting mixture was left to stir in the dark for 10 min. DBU (0.7932 mL, 5.3055 mmol) was added. The resulting mixture was left to stir in the dark for 2 h. The dark filtrate was evaporated and further dried under house vac. It was purified by silica gel chromatography (100 g SiO2) eluting with ethyl acetate in iso-hexane (30-100%) followed by methanol in ethyl acetate (0-15%). Evaporation of desired fractions gave 3-(benzenesulfonyl)-2-[4-(5-ethoxy-2-fluoro-phenyl)-3,6-dimethyl-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one (3880 mg, 7.2166 mmol, 68.0% yield) as brown solid. To a stirred solution of this material in anhydrous THF (30 mL) under nitrogen at 0° C., was added potassium tert-butoxide (4048.9 mg, 36.083 mmol). The resulting mixture was left to stir for 2 h and acetic acid (2.07 mL, 36.08 mmol) was added. Stirring was continued for 15 min at room temperature. Evaporation of solvent under reduced pressure gave a dark oily residue. It was purified by silica gel chromatography (50 g SiO2) eluting with ethyl acetate in iso-hexane (30-100%). Evaporation of desired fractions gave brown oil, 2-[4-(5-ethoxy-2-fluoro-phenyl)-3,6-dimethyl-2-pyridyl-7-methyl-1,7-diazaspiro[4.4]non-1-en-6-one (D142) (543 mg, 1.373 mmol, 19.0% yield);
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:36])[CH2:5][CH:6]([C:30]1[CH:31]=[N:32][CH:33]=[N:34][CH:35]=1)[CH:7]=[CH:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([N:19]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[CH3:20])[N:14]=1)[CH3:2].[H][H]>CCO.[Pd]>[CH2:1]([O:3][C:4](=[O:36])[CH2:5][CH:6]([C:30]1[CH:31]=[N:32][CH:33]=[N:34][CH:35]=1)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([N:19]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[CH3:20])[N:14]=1)[CH3:2]
Reactant: [H][H]
Reactant: CCOC(=O)CC(C=CCCCCc1cccc(N(C)Cc2ccc(OC)cc2)n1)c1cncnc1
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)CC(CCCCCCc1cccc(N(C)Cc2ccc(OC)cc2)n1)c1cncnc1
Yield: 73.1 %

Procedure:
A mixture of 6-11 (1.23 g, 2.51 mmol) and 10% Pd/C (0.200 g) in EtOH (25 mL) was stirred under a balloon of hydrogen for 2 days. Filtration through celite and evaporative removal of the solvent followed by purification on silica gel (70:25:5 CHCl3:EtOAc:MeOH) afforded 0.900 g of 6-12.
Reaction SMILES: [OH:1][CH:2]([CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH2:3][C:4]#[N:5].[O:11]1[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12]1>CCOCC>[NH2:5][CH2:4][CH2:3][CH:2]([O:1][CH:12]1[CH2:13][CH2:14][CH2:15][CH2:16][O:11]1)[CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: C1=COCCC1
Reactant: CCCCCC(O)CC#N
Solvent: CCOCC
Product: CCCCCC(CCN)OC1CCCCO1
Temperature: 25 °C
Reaction time: 16 h
Yield: 93.6 %

Procedure:
A mixture of 3-hydroxycaprylonitrile (5.2 g., 36.8 millimole), dihydropyran (3.8 g., 45 millimole), and p-toluenesulfonic acid·hydrate (catalytic amount) is stirred at 25° C. for 16 hours, then diluted with ether (100 ml.). The resulting solution is washed with 5% aqueous sodium hydroxide (25 ml.) and water (2×25 ml.), dried over magnesium sulfate, and filtered. Evaporation of the filtrate in vacuo affords the title compound as a pale yellow oil (7.9 g., 95%), pmr (CDCl3) δ 0.93 (3H, t), 2.54 (2H, q) and 4.68 (H, m).
Reaction SMILES: [CH3:1][Si:2]([C:5]1[CH2:9][CH:8]=[CH:7][CH:6]=1)([CH3:4])[CH3:3].C([Li])CCC.Cl[Si:16]([CH3:19])([CH3:18])[CH3:17]>>[CH3:1][Si:2]([CH3:4])([CH3:3])[C:5]1[CH2:9][CH:8]=[C:7]([Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:6]=1
Reactant: C[Si](C)(C)C1=CC=CC1
Reactant: C[Si](C)(C)Cl
Agent: [Li]CCCC
Product: C[Si](C)(C)C1=CCC([Si](C)(C)C)=C1
Temperature: 40 °C

Procedure:
Freshly distilled trimethylsilylcyclopentadiene (1.6 g, 11.5 mmole) is dissolved in 10 ml of absolute ligroin. To this solution is added a solution of butyllithium (1.9N, 6.35 ml, 12.0 mmole) in ligroin dropwise with stirring. The mixture is stirred for one hour at room temperature. Chlorotrimethylsilane (2.6 g, 24 mmole) is added to the mixture under an argon sweep, and the resulting mixture heated for 3 hours at 40° C. The ligroin solution is filtered, the solvent evaporated, and the residue distilled under a vacuum to give 1,3-bis(trimethylsilyl)cyclopentadiene, b.p. 45° C./3 mm Hg.
Reaction SMILES: [K].[OH:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]=[CH:10][C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1.I[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][OH:27].C1OCCOCCOCCOCCOCCOC1>C1(C)C=CC=CC=1>[OH:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]=[CH:10][C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1
Reactant: O=[N+]([O-])c1ccc(C=Cc2ccc(O)cc2)cc1
Reactant: OCCCCCCI
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [K]
Solvent: Cc1ccccc1
Product: O=[N+]([O-])c1ccc(C=Cc2ccc(OCCCCCCO)cc2)cc1

Procedure:
To 500 ml of toluene in a one liter round bottom flask, fitted with a condenser and magnetic stirrer, is added 14 g (0.05 M) of 4-hydroxy-4'-nitrostilbene potassium salt, 14 g of 6-iodo-1-hexanol, and 0.5 g of 18-crown-6 ether. The mixture is refluxed for about 20 hours, and then the reaction medium is filtered hot, and the product crystallizes from the toluene on cooling, m.p. 154°-157° C.
Reaction SMILES: [CH3:1][S:2][C:3]1[C:4]2[CH:11]=[CH:10][S:9][C:5]=2[N:6]=[CH:7][N:8]=1.[Li+].CC([N-]C(C)C)C.CN([CH:23]=[O:24])C>C1COCC1.O>[CH3:1][S:2][C:3]1[C:4]2[CH:11]=[C:10]([CH:23]=[O:24])[S:9][C:5]=2[N:6]=[CH:7][N:8]=1
Reactant: CSc1ncnc2sccc12
Reactant: CN(C)C=O
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CSc1ncnc2sc(C=O)cc12
Temperature: -78 °C
Reaction time: 1 h
Yield: 51 %

Procedure:
4-(Methylthio)thieno[2,3-d]pyrimidine (J. Heterocycl. Chem. 1975, 12, 921-924) (1 g) in THF (5 mL) was added to a preformed solution of LDA [BuLi (1.6M in hexanes, 3.8 mL) and di-isopropylamine (0.85 mL)] in THF (20 mL) at −78° C. The reaction mixture was allowed to stir for 1 hour at −78° C. and then DMF (1.1 mL) was added. The reaction mixture was stirred at −78° C. for 30 minutes then allowed to warm to ambient temperature and stirred for a further 3 hours. The reaction mixture was diluted with water and the product was extracted with EtOAc (4×30 mL). The combined organic extracts were washed with brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo. Purification by flash chromatography on silica eluting with DCM afforded the title compound as a white solid (1.17 g, 51%);
Reaction SMILES: C(OO[CH:6]1[CH2:10][CH:9]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])[CH:8]=[CH:7]1)(=O)C.[K].[Cl:20][C:21]1[C:22]2[C:23]3[C:24](=[C:32]([CH3:35])[O:33][N:34]=3)[C:25](=[O:31])[NH:26][C:27]=2[CH:28]=[CH:29][CH:30]=1>CN(C=O)C.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Si:12]([O:11][CH:9]1[CH2:10][CH:6]([N:26]2[C:27]3[CH:28]=[CH:29][CH:30]=[C:21]([Cl:20])[C:22]=3[C:23]3=[N:34][O:33][C:32]([CH3:35])=[C:24]3[C:25]2=[O:31])[CH:7]=[CH:8]1)([C:15]([CH3:16])([CH3:17])[CH3:18])([CH3:13])[CH3:14]
Reactant: CC(=O)OOC1C=CC(O[Si](C)(C)C(C)(C)C)C1
Reactant: Cc1onc2c1c(=O)[nH]c1cccc(Cl)c12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [K]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1onc2c1c(=O)n(C1C=CC(O[Si](C)(C)C(C)(C)C)C1)c1cccc(Cl)c21
Temperature: 55 °C
Reaction time: 6 h
Yield: 99.4 %

Procedure:
To a stirred solution of 4-(t-butyldimethylsilanyloxy)cyclopent-2-enyloxy acetate (3.4 g, 13.3 mmol) in DMF (140 mL) was added tetrakis(triphenylphosphine)palladium (1.54 g, 1.3 mmol) and 9-chloro-3-methyl-5H-isoxazolo[4,3-c]quinolin-4-one potassium salt (4.4 g, 16.2 mmol). The reaction mixture was stirred at 55° C. for 6 hours. It was diluted with ethyl acetate, washed (brine), dried (Na2SO4), filtered and concentrated. Column chromatography (silica gel, hexanes/ethyl acetate, gradient) gave desired product (5.7 g, 67%). 1H NMR (CDCl3, 400 MHz) δ; 7.83 (m, 1H); 7.22 (m, 2H); 6.50 (t, 1H); 5.84 (m, 2H); 4.85 (t, 1H); 2.82 (s, 3H); 2.78 (m, 1H); 2.02 (m, 1H); 0.81 (s, 9H); 0.02 (s, 3H); 0.00 (s, 3H).