Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[C:10](=[O:11])[C:9]2[NH:8][CH:7]=[N:6][C:5]=2[N:4]=[C:2]1[NH2:3].C[Si](C)(C)N[Si](C)(C)C.S([O-])([O-])(=O)=O.[NH4+].[NH4+].[SiH3]NC1NC(=O)C2NC=NC=2N=1.[O:40]1[C:42]2[CH2:43][CH2:44][CH2:45][C:41]1=2>C1(C)C(C)=CC=CC=1.O1CCCC1.[Pd].CO>[OH:40][CH:41]1[CH2:45][CH:44]([N:6]2[CH:7]=[N:8][C:9]3[C:10](=[O:11])[NH:1][C:2]([NH2:3])=[N:4][C:5]2=3)[CH:43]=[CH:42]1
Reactant: C1CC2=C(C1)O2
Reactant: Nc1nc2nc[nH]c2c(=O)[nH]1
Agent: [Pd]
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: O=S(=O)([O-])[O-]
Solvent: Cc1ccccc1C
Solvent: CO
Solvent: C1CCOC1
Product: Nc1nc2c(ncn2C2C=CC(O)C2)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
105.8 g (0.7 mol) of guanine are reacted in 600 ml of dry xylene with 500 ml of hexamethyldisilazane and 4 g of ammonium sulfate for 2 days to give the pertrimethylsilyl compound. The oily silylguanine compound is dissolved in 400 ml of dry tetrahydrofuran and the solution is added dropwise to a solution of the palladium(0) catalyst (5 mol %) prepared in situ as described above in 450 ml of tetrahydrofuran at 0° C. A solution of the equivalent amount of epoxycyclopentene in 200 ml of tetrahydrofuran is then added dropwise over a period of 2-3 hours. The resulting solution is stirred at room temperature for 3 days. 400 ml of methanol are added and the mixture is heated under reflux for 1 hour. During this operation, a very voluminous precipitate is formed, and can be converted into a homogeneous suspension after further stirring. The suspension thus obtained is filtered. 4.7 g of a mixture of the compounds 1.12.1. and 1.12.2. crystallize out of the filtrate. The residue on the filter is stirred with 1.2 l of water and filtered off with suction again. This residue on the filter is washed with ethanol and then boiled up in several portions with 1 l of ethanol. On cooling, this ethanolic solution gives 4.75 g of 9-[(1RS,4SR)-4-hydroxy-cyclopent-2-en-1-yl]guanine as beige crystals of melting point 265°-273° C. (decomposition) (compound of Example 1.12.1.). 1H NMR (270 MHz, de-DMSO), δ[ppm]: 10.56 (s, 1H), 7.60 (s, 1H), 6.42 (s, 2H), 6.15 (m, 1H), 5.95 (m, 1H), 5.24 (d, 1H), 5.20 (m, 1H), 4.70 (m, 1H), 2.82 (m, 1H), 1.60 (m, 1H). If the residue on the filter is boiled up again with 1.5 l of water, 5.0 g of 7-[(1RS,4SR)-4-hydroxy-cyclopent-2-en-1-yl]guanine of melting point >310° C. crystallize out of the aqueous filtrate (compound of Example 1.12.2.). 1H NMR (270 MHz, d6 -DMSO), δ[ppm]: 10.80 (s, 1H), 7.84 (s, 1H), 6.15 (m, 1H), 6.13 (s, 2H), 6.01 (m, 1H), 5.61 (m, 1H), 5.18 (d, 1H), 4.68 (m, 1H), 2.88 (m, 1H), 1.60 (m, 1H). The residue which remains on the filter of 82.7 g consists of a mixture of the compounds of Example 1.12.1. and 1.12.2.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C:4](=[CH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=1)[CH2:5][C:6]([OH:8])=[O:7]>CO.[Pd]>[CH3:1][O:2][C:3](=[O:18])[CH:4]([CH2:9][C:10]1[CH:11]=[CH:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=1)[CH2:5][C:6]([OH:8])=[O:7]
Reactant: COC(=O)C(=Cc1ccc(OC)cc1)CC(=O)O
Agent: [Pd]
Solvent: CO
Product: COC(=O)C(CC(=O)O)Cc1ccc(OC)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 99.2 %

Procedure:
To a solution of 2-(4-methoxybenzylidene)succinic acid 1-methyl ester (3 g) in methanol (100 ml) was added 10% palladium on carbon (0.6 g) and the solution was stirred for 16 hours under hydrogen atomosphere at room temperature. The catalyst was filtered off and the filtrate was concentrated under reduced pressure to give the titled compound (3 g) as a colorless oily substance.
Reaction SMILES: [C:1]([C:4](=[CH:10][CH2:11][CH3:12])[C:5]([O:7][CH2:8][CH3:9])=[O:6])(=[O:3])[CH3:2].[Br:13]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[C:1]([C:4](=[CH:10][CH:11]([Br:13])[CH3:12])[C:5]([O:7][CH2:8][CH3:9])=[O:6])(=[O:3])[CH3:2]
Reactant: CCC=C(C(C)=O)C(=O)OCC
Reactant: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)(Cl)Cl
Product: CCOC(=O)C(=CC(C)Br)C(C)=O
Temperature: 25 °C
Yield: 98.2 %

Procedure:
A mixture of 8.06 g (0.047 mole) ethyl 2-acetyl-2-pentenoate and 8.43 g (0.047 mole) N-bromosuccinimide in 50 ml of carbon tetrachloride was heated at reflux for 15 minutes. The mixture was quickly cooled to room temperature, and the succinimide removed by filtration. Concentration of the solution in vacuo afforded 11.5 g (98%) of ethyl 2-acetyl-4-bromo-2-pentenoate.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([CH2:6][CH2:7][CH:8](C(O)=O)[C:9]([OH:11])=[O:10])=[CH:2]1.[OH-].[NH4+]>COCCOCCOC>[S:1]1[CH:5]=[CH:4][C:3]([CH2:6][CH2:7][CH2:8][C:9]([OH:11])=[O:10])=[CH:2]1
Reactant: O=C(O)C(CCc1ccsc1)C(=O)O
Agent: [NH4+]
Agent: [OH-]
Solvent: COCCOCCOC
Product: O=C(O)CCCc1ccsc1
Yield: 96.1 %

Procedure:
The product from Step C (2.4 g, 11.0 mmol) was dissolved in 2-methoxyethyl ether (20 mL) and refluxed for 24 hours. The reaction was cooled to room temperature and basified to pH 9 with concentrated ammonium hydroxide. The mixture was extracted once with diethyl ether and set aside. The aqueous layer was acidified with concentrated hydrochloride acid and extracted four times with diethyl ether. The extract were combined and dried over sodium sulfate, filtered and concentrated to give 4-thiophen-3-yl-butyric acid (1.8 g, 95%) as an oil.
Reaction SMILES: O[CH2:2][C:3]1[C:4]2[N:5]([CH:9]=[CH:10][N:11]=2)[CH:6]=[CH:7][CH:8]=1.[SH:12][C:13]1[NH:14][C:15]2[C:21]([CH3:22])=[CH:20][CH:19]=[CH:18][C:16]=2[N:17]=1>>[N:11]1[CH:10]=[CH:9][N:5]2[CH:6]=[CH:7][CH:8]=[C:3]([CH2:2][S:12][C:13]3[NH:17][C:16]4[CH:18]=[CH:19][CH:20]=[C:21]([CH3:22])[C:15]=4[N:14]=3)[C:4]=12
Reactant: OCc1cccn2ccnc12
Reactant: Cc1cccc2nc(S)[nH]c12
Product: Cc1cccc2[nH]c(SCc3cccn4ccnc34)nc12

Procedure:
A solution of 20 g (0.13 mole) of 2-methyl-6-nitroaniline in 22.9 ml of concentrated aqueous hydrochloric acid, 200 ml of tetrahydrofuran, and 350 ml of methanol was hydrogenated at room temperature using 25 p.s.i. of hydrogen gas over 2.0 g of 5% palladium on carbon. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was dissolved in 150 ml of ethanol and neutralized with 17.2 g (0.26 mole) of potassium hydroxide dissolved in 30 ml of water. Potassium ethylxanthate (23 g, 0.155 mole) was added and the mixture was heated at reflux for 18 hours. Upon cooling, a solid was collected, washed with water, and air dried to yield 6.2 g of 2-mercapto-4-methylbenzimidazole, as confirmed by the nmr and infrared spectra. The title compound (987 mg) was prepared by the method of Example 6 using 8-hydroxymethylimidazo[1,2-a]pyridine as the hydrochloride salt (700 mg, 3.8 mmole) and using 655 mg (4.0 mmole) of 2-mercapto-4-methylbenzimidazole instead of 2-mercapto-5-methoxybenzimidazole. Structure assignment was supported by the nmr and infrared spectra.
Reaction SMILES: [N:1]1([S:7]([C:10]2[CH:11]=[C:12]([CH:17]=[CH:18][CH:19]=2)[C:13]([NH:15][NH2:16])=[O:14])(=[O:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:20][C:21]1[CH:22]=[CH:23][C:24]([OH:30])=[C:25]([C:27](=O)[CH3:28])[CH:26]=1>CO.C(O)(=O)C>[Cl:20][C:21]1[CH:22]=[CH:23][C:24]([OH:30])=[C:25](/[C:27](=[N:16]/[NH:15][C:13](=[O:14])[C:12]2[CH:17]=[CH:18][CH:19]=[C:10]([S:7]([N:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)(=[O:8])=[O:9])[CH:11]=2)/[CH3:28])[CH:26]=1
Reactant: NNC(=O)c1cccc(S(=O)(=O)N2CCCCC2)c1
Reactant: CC(=O)c1cc(Cl)ccc1O
Solvent: CC(=O)O
Solvent: CO
Product: C/C(=N\NC(=O)c1cccc(S(=O)(=O)N2CCCCC2)c1)c1cc(Cl)ccc1O
Temperature: 120 °C
Yield: 54.1 %

Procedure:
3-(piperidin-1-ylsulfonyl)benzohydrazide (65 mg, 0.229 mmol) and 1-(5-chloro-2-hydroxyphenyl)ethanone (39.1 mg, 0.229 mmol) was dissolved in methanol (Volume: 4 ml) in the presence of acetic acid as a catalyst and then the reaction mixture was heated via microwave irradiation to 120° C. for 30 min. Reaction was monitored by TLC. After completion of the reaction, following cooling, the solvent was removed by vacuum and the resulting crude material was purified by flash column chromatography (2% CH3OH/CH2Cl2) afforded the product (E)-N′-(1-(5-chloro-2-hydroxyphenyl)ethylidene)-3-(piperidin-1-ylsulfonyl)benzohydrazide (55 mg, 0.124 mmol, 53.9% yield) as a solid. 1H NMR (CDCl3, 400 MHz): δ 8.09 (m, 2H), 7.85 (d, 1H, J=8.0 Hz), 7.62 (t, 1H, J=8.0 Hz), 7.41 (d, 1H, J=2.4 Hz), 7.22 (d, 1H, J=8.0 Hz), 6.93 (d, 1H, J=8.8 Hz), 2.97 (m, 4H), 2.41 (s, 3H), 1.61 (m, 4H), 1.40 (m, 2H). Mass [M+H]+:436.9
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13](=[O:14])[C:12]3[S:15][CH2:16][CH2:17][S:18][C:11]=3[C:10]2=[O:19])=[CH:5][CH:4]=1.[BH4-].[Na+]>CO.O1CCCC1>[OH:14][CH:13]1[C:12]2[S:15][CH2:16][CH2:17][S:18][C:11]=2[C:10](=[O:19])[N:9]1[C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=1
Reactant: COc1ccc(N2C(=O)C3=C(SCCS3)C2=O)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: COc1ccc(N2C(=O)C3=C(SCCS3)C2O)cc1
Temperature: 0 °C
Yield: 98.1 %

Procedure:
2,3,6,7-Tetrahydro-6-(4-methoxyphenyl)-5H-1,4-dithiino[2,3-C]pyrrole-5,7-dione (8.50 g) was suspended in methanol-tetrahydrofuran (1:1, 80 ml) and, under ice-cooling and stirring, sodium borohydride (0.88 g) was added. The mixture was stirred for about 3 hours and then poured into ice water. After extraction with ethyl acetate, the extract was washed with water, dried (over Na2SO4) and evaporated to give 2,3,6,7-tetrahydro-7-hydroxy-6-(4-methoxyphenyl)-5H-1,4-dithiino[2,3-C]pyrrol-5-one (8.40 g) as crystals.
Reaction SMILES: [CH:1]1([C:7]([OH:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:10]1[CH2:15]CCC[CH2:11]1.CC1C=CC(S(O)(=O)=O)=CC=1>C(O)(C)C>[CH:10]([O:8][C:7]([CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)=[O:9])([CH3:15])[CH3:11]
Reactant: O=C(O)C1CCCCC1
Reactant: C1CCCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC(C)O
Product: CC(C)OC(=O)C1CCCCC1
Temperature: 71.5 °C
Reaction time: 6 h
Yield: 4752.1 %

Procedure:
To a solution of cyclohexanecarboxylic acid (22.0 g, 172 mmol) in isopropanol (66 mL) and cyclohexane (44 mL) p-TsOH (653 mg, 3.43 mmol) was added. The mixture was heated with stirring to 70-73° C. and solvent was slowly distilled off whereas the volume was kept relatively constant by addition of fresh solvent mixture. After 6 h, a second portion of p-TsOH (653 mg, 3.43 mmol) was added and the reaction mixture was stirred at 71° C. overnight (without distilling off solvent). After a total of 24 h, the cooled reaction mixture was concentrated to ¼ volume. Ice and saturated aq. NaHCO3 were added and the mixture was extracted twice with TBME. The organic phases were washed to neutral with diluted aq. NaCl solution, combined, dried over sodium sulfate and concentrated. The crude product (28.5 g) was distilled at 40° C. (0.2-0.16 mbar) to afford 27.75 g (93%) cyclohexanecarboxylic acid isopropyl ester as a colorless liquid, GC purity 98% (area). 1H-NMR (CDCl3, 400 MHz): ppm 1.21 (d, 6H), 1.17-1.34 (m, 3H), 1.35-1.49 (m, 2H), 1.55-1.80 (m, 3H), 1.82-1.92 (m, 2H), 2.20-2.29 (m, 1H), 4.94-5.04 (m, 1H).
Reaction SMILES: N(O[CH2:4][CH2:5][CH:6](C)C)=O.[C:9]([OH:18])(=O)[C:10]1[C:11](=[CH:13][CH:14]=[CH:15][CH:16]=1)N.[OH-].[Na+]>C(COC)OC>[CH:15]1[CH:16]=[C:10]2[C:11]([CH:6]3[O:18][CH:9]2[CH:4]=[CH:5]3)=[CH:13][CH:14]=1
Reactant: CC(C)CCON=O
Reactant: Nc1ccccc1C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: COCCOC
Product: C1=CC2OC1c1ccccc12
Yield: 51 %

Procedure:
Solutions of 20 ml of isoamyl nitrite in glyme (20 ml) and of 13.7 g of anthranilic acid in glyme (45 ml) were added simultaneously by drops to a refluxing mixture of glyme (50 ml) and furna (50 ml). Refluxing was continued for ten minutes and the brown solution was cooled, made basic with aqueous sodium hydroxide (1N), and extracted with petroleum ether. The extract was washed thoroughly with water, clarified with Norit®, dried, and evaporated to give an oil. The oil solidified on cooling to give 7 g (51% yield) of light yellow solid. Recrystalization of the yellow solid from petroleum ether gave colorless crystalline solid of 1,4-dihydronaphthalene1,4-endo-oxide (IIIa), m.p. 53°-54° C. (lit. m. p. 56° C.).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([O:14][CH2:15][CH:16]3[CH2:18][CH2:17]3)=[CH:12][CH:11]=[CH:10][N+:9]=2[O-])=[CH:4][CH:3]=1.[CH2:20]([N:22](CC)CC)C.CN(C)C(Cl)=O.C[Si](C#N)(C)C>C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:20]#[N:22])[CH:11]=[CH:12][C:13]=2[O:14][CH2:15][CH:16]2[CH2:18][CH2:17]2)=[CH:4][CH:3]=1
Reactant: CCN(CC)CC
Reactant: [O-][n+]1cccc(OCC2CC2)c1-c1ccc(Cl)cc1
Agent: CN(C)C(=O)Cl
Agent: C[Si](C)(C)C#N
Solvent: CC#N
Product: N#Cc1ccc(OCC2CC2)c(-c2ccc(Cl)cc2)n1
Temperature: 90 °C
Reaction time: 0.08 h
Yield: 59.3 %

Procedure:
To a solution of 25 g 2-(4-chloro-phenyl)-3-cyclopropylmethoxy-pyridine 1-oxide in 500 mL acetonitrile, 9.23 g triethylamine and 10.73 g dimethylcarbamoylchlorid were added. After 5 minutes at room temperature, 27.88 g trimethylsilylcyanid was added. The reaction mixture was stirred at 90° C. over 15 h. The reaction mixture was partitioned between water and ethyl acetate; then extracted. The organic phase was washed with brine; then dried over MgSO4 and purified by chromatography on silica gel with a gradient of heptane to heptane:ethyl acetate 2:1 to yield 15.30 g (59.26%) of the title compound as light yellow solid, MS 285.1 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[C:7](/[CH:8]=[CH:9]/[C:10](OCC)=[O:11])=[CH:6][N:5]=[C:4]([O:15][CH3:16])[N:3]=1.C[O-].[Na+].CO>CO>[CH3:16][O:15][C:4]1[N:5]=[CH:6][C:7]2[CH:8]=[CH:9][C:10](=[O:11])[NH:1][C:2]=2[N:3]=1
Reactant: CCOC(=O)/C=C/c1cnc(OC)nc1N
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1ncc2ccc(=O)[nH]c2n1
Temperature: 25 °C
Reaction time: 4 h
Yield: 79.7 %

Procedure:
To a solution of 0.87 g of ethyl (2E)-3-(4-amino-2-methoxypyrimidin-5-yl)acrylate in 50 mL of methanol, 2.31 g of a 28% sodium methoxide/methanol solution was added at room temperature, and the mixture was heated under reflux while stirring for 4 hours. The reaction mixture was cooled to room temperature, and the solvent was then distilled off under reduced pressure. To the resultant residue, a saturated aqueous ammonium chloride solution and chloroform were added, the organic layer was separated, and the aqueous layer was extracted with chloroform. The organic layer and the extract were combined, the resultant solution was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The solid thus obtained was washed with diethyl ether to obtain 0.55 g of 2-methoxypyrido(2,3-d)pyrimidin-7(8H)-one as a yellow solid.
Reaction SMILES: [Li+].[CH3:2][CH:3]([N-]C(C)C)C.[C:9]1([CH:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:16]#[N:17])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(Br)C.P([O-])([O-])([O-])=O>C1COCC1>[C:18]1([C:15]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)([CH2:2][CH3:3])[C:16]#[N:17])[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: CC(C)[N-]C(C)C
Reactant: N#CC(c1ccccc1)c1ccccc1
Agent: O=P([O-])([O-])[O-]
Agent: [Li+]
Solvent: CCBr
Solvent: C1CCOC1
Product: CCC(C#N)(c1ccccc1)c1ccccc1
Temperature: -30 °C
Reaction time: 1 h
Yield: 67 %

Procedure:
173 ml (0.259 mol) of a 1.5 M solution of LDA in THF were added dropwise to a solution of 50.0 g (0.259 mol) of diphenylacetonitrile in 500 ml of THF (abs.) at −78° C. under argon, and the mixture was then stirred at −30° C. for one hour. Then, at −78° C., 28.23 g (0.259 mol) of ethyl bromide were added. The mixture was allowed to reach room temperature and was stirred for 16 hours. Subsequently, 80 ml of phosphate buffer (pH 7) were added and the mixture was evaporated. The residue was taken up in water and extracted three times with ethyl acetate. The combined organic phases were dried over MgSO4, and the solvent was stripped off under reduced pressure. The crude product was chromatographed on silica gel with n-heptane/acetic acid (20:1). 38.2 g (67%) of 2,2-diphenylbutyronitrile were obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH2:15]Cl)=[N:13][N:14]=[C:10]3[CH2:9][N:8]=[C:7]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:6]=2[CH:23]=1.[NH2:24][OH:25].[H-].[Na+]>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH2:15][NH:24][OH:25])=[N:13][N:14]=[C:10]3[CH2:9][N:8]=[C:7]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:6]=2[CH:23]=1
Reactant: ClCc1nnc2n1-c1ccc(Cl)cc1C(c1ccccc1)=NC2
Reactant: NO
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: ONCc1nnc2n1-c1ccc(Cl)cc1C(c1ccccc1)=NC2

Procedure:
In the manner given in Example 15, 8-chloro-1-(chloromethyl)-6-phenyl-4H-s-triazolo[4,3-a][1,4]-benzodiazepine is treated with a cold mixture of hydroxylamine and sodium hydride in dimethylformamide to give 8-chloro-1-[(hydroxyamino)methyl]-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]([C:12]1[CH:16]=[CH:15][S:14][CH:13]=1)O)=[O:7])([CH3:4])([CH3:3])[CH3:2].P(Cl)(Cl)(Cl)(Cl)[Cl:18].[OH-].[Na+]>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]([Cl:18])[C:12]1[CH:16]=[CH:15][S:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: CC(C)(C)OC(=O)NCC(O)c1ccsc1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCC(Cl)c1ccsc1
Reaction time: 0.17 h
Yield: 55.8 %

Procedure:
To a solution of 12.2 g of 2-t-butoxycarbonylamino-1-(3-thienyl)ethanol [prepared as described in step (a) above] in 100 ml of absolute methylene chloride was added a solution of 10.4 g of phosphorus pentachloride in 200 ml of absolute methylene chloride at 0° to -5° C. After the addition, the reaction mixture was stirred for 10 minutes. To the reaction mixture was added a 4N aqueous solution of sodium hydroxide, and the mixture was stirred for 5 minutes. The methylene chloride layer was separated, washed with large amount of water and dried over anhydrous magnesium sulfate, and the solvent was evaporated off. The residue was subjected to silica gel column chromatography using a 1:4 by volume mixture of ethyl acetate and cyclohexane as eluent, to yield 7.3 g of the title compound melting at 63°-65° C.
Reaction SMILES: Cl.[Br:2][C:3]1[CH:8]=[C:7]([C:9]2[C:18]3[C:19]4[CH:25]=[CH:24][CH:23]=[CH:22][C:20]=4[S:21][C:17]=3[C:16]([Br:26])=[C:15]3[C:10]=2[CH:11]=[CH:12][CH:13]=[CH:14]3)[CH:6]=[C:5]([Br:27])[C:4]=1[O:28][P:29](=[O:40])([O:35]C(C)(C)C)[O:30]C(C)(C)C>O1CCOCC1>[Br:2][C:3]1[CH:8]=[C:7]([C:9]2[C:18]3[C:19]4[CH:25]=[CH:24][CH:23]=[CH:22][C:20]=4[S:21][C:17]=3[C:16]([Br:26])=[C:15]3[C:10]=2[CH:11]=[CH:12][CH:13]=[CH:14]3)[CH:6]=[C:5]([Br:27])[C:4]=1[O:28][P:29](=[O:30])([OH:35])[OH:40]
Reactant: CC(C)(C)OP(=O)(Oc1c(Br)cc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1Br)OC(C)(C)C
Agent: Cl
Solvent: C1COCCO1
Product: O=P(O)(O)Oc1c(Br)cc(-c2c3ccccc3c(Br)c3sc4ccccc4c23)cc1Br
Reaction time: 4.5 h
Yield: 86 %

Procedure:
HCl (4 N in dioxane, 1.5 mL, 6 mmol) was added to a room temp[erature, stirred solution of phosphoric acid di-tert-butyl ester 2,6-dibromo-4-(6-bromo-benzo [b]naphtho[2,3-d]thiophen-11-yl)-phenyl ester (0.290 g, 0.384 mmol) in dioxane (6 mL). After 4.5 h, the solvent was removed and the solid was triturated with ether, petroleum ether and dried in vacuo to provide the title compound as a white solid (0.220, 86%): NMR (DMSO-d6); δ8.29 (d, J=8 Hz, 1 H), 8.08 (d, J=8 Hz, 1 H), 7.83 (s, 2 H), 7.80 (ddd, J=8, 7, 1 Hz, 1 H), 7.64 (ddd, J=8, 7, 1 Hz, 1 H), 7.56-7.51 (m, 2 H), 7.26 (ddd, J=8, 7, 1 Hz, 1 H), 6.71 (d, J=8 Hz, 1 H); MS (+FAB): [M+], 3 bromine isotope pattern, 640, 642, 644, 646; Anal. Calc. for C22H12Br3O4PS: C, 41.09, H, 1.88, N, 0.00. Found: C, 41.71, H, 2.22, N, 0.07.
Reaction SMILES: CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[C:23]([C:27]1[CH:28]=[C:29]([C:33]2[CH:38]=[C:37]([CH2:39][CH2:40][CH2:41][OH:42])[N:36]=[C:35]([C:43]#[N:44])[N:34]=2)[CH:30]=[CH:31][CH:32]=1)([CH3:26])([CH3:25])[CH3:24]>C(Cl)Cl.CCOC(C)=O>[C:23]([C:27]1[CH:28]=[C:29]([C:33]2[CH:38]=[C:37]([CH2:39][CH2:40][CH:41]=[O:42])[N:36]=[C:35]([C:43]#[N:44])[N:34]=2)[CH:30]=[CH:31][CH:32]=1)([CH3:26])([CH3:24])[CH3:25]
Reactant: CC(C)(C)c1cccc(-c2cc(CCCO)nc(C#N)n2)c1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(C)(C)c1cccc(-c2cc(CCC=O)nc(C#N)n2)c1
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
Dess-Martin periodinane (679 mg) was added to a solution of 4-(3-tert-butyl-phenyl)-6-(3-hydroxy-propyl)-pyrimidine carbonitrile (394 mg) in DCM (5 ml) and the resulting suspension was stirred at room temperature for 45 mins. Reaction mixture was diluted with EtOAc (100 ml) then washed with water (2×100 ml). Organic layer was dried over MgSO4 and concentrated in vacuo. The residue was columned on silica gel using petrol and ethyl acetate (1:1) as eluent to generate 4-(3-tert-butyl-phenyl)-6-(3-oxo-propyl)-pyrimidine-2-carbonitrile as a pale yellow solid (266 mg).
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH:17]([OH:20])[CH2:18][OH:19])[CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>C(Cl)Cl>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH:17]([O:20][S:29]([CH3:28])(=[O:31])=[O:30])[CH2:18][O:19][S:29]([CH3:28])(=[O:31])=[O:30])[CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CS(=O)(=O)Cl
Reactant: OCC(O)c1ccc2cnn(Cc3ccccc3)c2c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCC(OS(C)(=O)=O)c1ccc2cnn(Cc3ccccc3)c2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 70.7 %

Procedure:
A solution of 1-(1-Benzyl-1H-indazol-6-yl)-ethane-1,2-diol (0.27 g, 1.0 mmol) and Et3N (0.35 mL, 2.5 mmol) in dry CH2Cl2 (5 mL) was cooled in an ice bath before dropwise addition of MsCl (0.155 mL, 2.0 mmol) over 5 min. The resulting mixture was left to stir for 2 h, warming slowly to RT. After dilution with further CH2Cl2, the solution was washed quickly with 1.0 M aq. HCl (20 mL), sat. aq. NaHCO3 (40 mL) and brine (20 mL), dried over Na2SO4, filtered and concentrated at 25° C. to afford the crude product. The crude product was part-purified by rapid column chromatography on silica using 1:1 Et2O/CH2Cl2 as eluent, again concentrating at 25° C., giving the title compound (0.30 g, 71%) as an off-white, gummy foam. 1H NMR: (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.81 (d, J=8.3 Hz, 1H), 7.42 (s, 1H), 7.34-7.23 (m, 3H), 7.17 (dd, J=18.1, 7.6 Hz, 3H), 5.89 (dd, J=8.5, 3.2 Hz, 1H), 5.66 (d, J=15.8 Hz, 1H), 5.60 (d, J=15.8 Hz, 1H), 4.52 (dd, J=11.8, 8.6 Hz, 1H), 4.40 (dd, J=11.8, 3.2 Hz, 1H), 3.04 (s, 3H), 2.75 (s, 3H). MS (ES+): 425 ([M+H]+), calcd for [C18H20N2O6S2+H]+ 425.1.
Reaction SMILES: C([Li])CCC.Br[C:7]1[CH:12]=[C:11]([Br:13])[CH:10]=[C:9]([Br:14])[CH:8]=1.[C:15]1([CH3:34])[CH:20]=[C:19]([CH3:21])[CH:18]=[C:17]([CH3:22])[C:16]=1[B:23]([C:25]1[C:30]([CH3:31])=[CH:29][C:28]([CH3:32])=[CH:27][C:26]=1[CH3:33])F>CCCCCC.C(OCC)C>[Br:13][C:11]1[CH:12]=[C:7]([B:23]([C:25]2[C:26]([CH3:33])=[CH:27][C:28]([CH3:32])=[CH:29][C:30]=2[CH3:31])[C:16]2[C:17]([CH3:22])=[CH:18][C:19]([CH3:21])=[CH:20][C:15]=2[CH3:34])[CH:8]=[C:9]([Br:14])[CH:10]=1
Reactant: Cc1cc(C)c(B(F)c2c(C)cc(C)cc2C)c(C)c1
Reactant: Brc1cc(Br)cc(Br)c1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CCOCC
Product: Cc1cc(C)c(B(c2cc(Br)cc(Br)c2)c2c(C)cc(C)cc2C)c(C)c1
Temperature: -78 °C
Reaction time: 2 h

Procedure:
6.25 ml (0.01 mol) of 1.6 M butyllithium in hexane are added over 5 minutes at -78° C. to a suspension of 3.14 g (0.01 mol) of 1,3,5-tribromobenzene in 50 ml of diethyl ether. The reaction mixture is stirred at -78° C. for 2 hours, during which a yellow-orange suspension is produced. 2.68 g (0.01 mol) of solid dimesitylfluoroborane are added, and the reaction mixture is warmed to room temperature over about one hour. The mixture is then diluted with 50 ml of hexane and cooled to 0° C. The solid produced is filtered, washed several times with cold hexane and then washed with water and, finally, with methanol, until the solid is colourless. Drying gives 3.54 g (0.0073 mol; i.e. 73% of theory) of a white solid (1,3-dibromo-5-dimesitylborylbenzene). Following purification by chromatography (hexane; SiO2) a melting point of 190-191° C. is obtained. Elemental analysis for C24H25BBr2 gives: C calc.: 59.55%; found: 59.52% H calc.: 5.21%; found: 5,12%