Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]2[N:8]=[CH:9][S:10][C:6]=2[CH:5]=1)([O-:3])=[O:2].C[Mg+].[Br-].[CH:16](Cl)(Cl)Cl>C1COCC1>[CH3:16][C:5]1[C:6]2[S:10][CH:9]=[N:8][C:7]=2[CH:11]=[CH:12][C:4]=1[N+:1]([O-:3])=[O:2]
Reactant: ClC(Cl)Cl
Reactant: O=[N+]([O-])c1ccc2ncsc2c1
Agent: C[Mg+]
Agent: [Br-]
Solvent: C1CCOC1
Product: Cc1c([N+](=O)[O-])ccc2ncsc12
Reaction time: 2 h
Yield: 46 %

Procedure:
To a solution of 6-nitrobenzothiazole (1.4 g, 7.7 mmol) in 50 mL of THF was added 5.1 mL of MeMgBr (15.3 mmol) dropwise in 0.5 h period at 0° C. The reaction mixture was then stirred for additional 2 h. It was quenched by adding THF solution of 2,3-dichloro-5,6-dicyanobenzoquinone until the color of the solution turns to dark green. The reaction mixture was concentrated in vacuo to yield a dark solid which was subjected to column chromatography (CHCl3, neat) to provide 0.68 g (3.5 mmol, 46%) of the desired product.
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[C:9]([O:17][CH3:18])=[N:10][N:11]2[C:15](Br)=[CH:14][S:13][C:12]=12)([CH3:4])([CH3:3])[CH3:2].[Si]([O:27][C:28]1[CH:33]=[C:32]([O:34][CH3:35])[C:31](B(O)O)=[C:30]([O:39][CH3:40])[CH:29]=1)(C(C)(C)C)(C)C.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.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>[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[C:9]([O:17][CH3:18])=[N:10][N:11]2[C:15]([C:31]3[C:30]([O:39][CH3:40])=[CH:29][C:28]([OH:27])=[CH:33][C:32]=3[O:34][CH3:35])=[CH:14][S:13][C:12]=12)([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1nn2c(Br)csc2c1NC(=O)OC(C)(C)C
Reactant: COc1cc(O[Si](C)(C)C(C)(C)C)cc(OC)c1B(O)O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: COc1cc(O)cc(OC)c1-c1csc2c(NC(=O)OC(C)(C)C)c(OC)nn12
Temperature: 110 °C
Yield: 53.1 %

Procedure:
To a solution of tert-butyl(3-bromo-6-methoxypyrazolo[5,1-b][1,3]thiazol-7-yl)carbamate (375 mg, 1.08 mmol) in 1,4-dioxane (25 ml) and water (12.5 ml) were added (4-{[tert-butyl(dimethyl)silyl]oxy}-2,6-dimethoxyphenyl)boronic acid (505 mg, 1.61 mmol), tetrakis(triphenylphosphine)palladium(0) (125 mg, 0.108 mmol) and potassium carbonate (298 mg, 2.15 mmol), and the mixture was heated to reflux at 110° C. for two hours and 35 minutes. The reaction mixture was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by medium pressure silica gel column chromatography (n-heptane/ethyl acetate=10% then 70%) to obtain the title compound (242 mg, 0.574 mmol).
Reaction SMILES: C=CC.C[CH:5]1C(C)=[CH:11][CH:10]2[CH:6]1[CH:7]1[CH:15]=[CH:14][CH:9]2[CH2:8]1.[CH3:16][C:17]1[CH:22]2[CH2:23][CH:19](CC2)[C:18]=1C>>[CH3:11][C:10]1[CH:9]2[CH2:8][CH:7]([CH2:15][CH2:14]2)[C:6]=1[CH3:5].[CH3:16][C:17]1[CH2:22][CH:23]=[CH:19][CH:18]=1
Reactant: CC1=CC2C3C=CC(C3)C2C1C
Agent: CC1=C(C)C2CCC1C2
Solvent: C=CC
Product: CC1=CC=CC1

Procedure:
At 170° C., 156 g of propylene were reacted with 243 g of dimethyldicyclopentadiene for 20 hours, and by vacuum distillation 93 g of dimethylnorbornene were obtained. Then, 91 g of the thus prepared dimethylnorbornene were reacted with 135 g of dimethyldicyclopentadiene at 165° C. for 20 hours, and for the resultant reaction liquid, vacuum distillation was carried out to obtain 73 g of a 1:1 adduct of dimethylnorbornene and methylcyclopentadiene, i.e., a 2:1 adduct of methylcyclopentadiene and propylene at a boiling point of 97° C./2 mmHg.
Reaction SMILES: [CH3:1][N:2]1[C:11](=[O:12])[C:10]2[C:5](=[N:6][CH:7]=[CH:8][N:9]=2)[NH:4][C:3]1=[S:13].[OH-].[Na+].[Cl:16][C:17]1[CH:32]=[CH:31][C:20]([C:21]([C:23]2[CH:30]=[CH:29][C:26]([CH2:27]Br)=[CH:25][CH:24]=2)=[O:22])=[CH:19][CH:18]=1>C(O)C.O>[Cl:16][C:17]1[CH:18]=[CH:19][C:20]([C:21]([C:23]2[CH:30]=[CH:29][C:26]([CH2:27][S:13][C:3]3[N:2]([CH3:1])[C:11](=[O:12])[C:10]4[C:5](=[N:6][CH:7]=[CH:8][N:9]=4)[N:4]=3)=[CH:25][CH:24]=2)=[O:22])=[CH:31][CH:32]=1
Reactant: O=C(c1ccc(Cl)cc1)c1ccc(CBr)cc1
Reactant: Cn1c(=S)[nH]c2nccnc2c1=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Cn1c(SCc2ccc(C(=O)c3ccc(Cl)cc3)cc2)nc2nccnc2c1=O
Temperature: 25 °C
Reaction time: 24 h
Yield: 27.9 %

Procedure:
To a solution of 3-methylpteridin-4-one-2-thione, (194 mg) in ethanol (5 ml) were added 1N-aqueous sodium hydroxide solution (1.2 ml) and 4-(4-chlorobenzoyl) benzyl bromide (310 mg) and the mixture was stirred at room temperature for 24 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed with saturated aqueous NaCl solution and dried over anhydrous sodium sulfate. The solvent was then distilled off and the residue was purified by silica gel column chromatography (ethyl acetate) to provide the title compound as white powder (118 mg, 28%).
Reaction SMILES: [NH2:1][C:2]([CH3:53])([CH3:52])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH3:16])[N:11]=[C:10]2[C:17]1[N:22]=[C:21]2[C:23]([C:45]([NH:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])=[CH:24][N:25](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:20]2=[N:19][CH:18]=1.[F:54][C:55]([F:60])([F:59])[C:56]([OH:58])=[O:57]>ClCCl>[F:54][C:55]([F:60])([F:59])[C:56]([OH:58])=[O:57].[NH2:1][C:2]([CH3:53])([CH3:52])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH3:16])[N:11]=[C:10]2[C:17]1[N:22]=[C:21]2[C:23]([C:45]([NH:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])=[CH:24][NH:25][C:20]2=[N:19][CH:18]=1
Reactant: Cn1nc(-c2cnc3c(n2)c(C(=O)NC(C)(C)C)cn3C(c2ccccc2)(c2ccccc2)c2ccccc2)c2cc(OCCCC(C)(C)N)ccc21
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cn1nc(-c2cnc3[nH]cc(C(=O)NC(C)(C)C)c3n2)c2cc(OCCCC(C)(C)N)ccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 13 %

Procedure:
To a solution of 2-(5-(4-amino-4-methylpentyloxy)-1-methyl-1H-indazol-3-yl)-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (88 mg, 0.12 mmol) in 3 mL of dichloromethane was added trifluoroacetic acid (3 mL). The reaction mixture was stirred overnight at 25° C. After solvent evaporation, the residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 40% acetonitrile/60% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min) to afford 2-(5-(4-amino-4-methylpentyloxy)-1-methyl-1H-indazol-3-yl)-N-tert-butyl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide 2,2,2-trifluoroacetate as yellow solid (9 mg, 13%). LCMS: (M+H)+=464; 1H NMR (300 MHz, CD3OD): δ 9.01 (s, 1H), 8.26 (s, 1H), 7.85 (s, 1H), 7.56 (d, 1H, J=9.0 Hz), 7.24 (dd, 1H, J1=9.0 Hz, J2=2.4 Hz), 4.15-4.12 (m, 5H), 1.87-1.84 (m, 4H), 1.59 (s, 9H), 1.27 (s, 6H).
Reaction SMILES: [C:1]([C:4]([CH:7]1[CH2:16][C:15](=[O:17])[C:14]2[C:9](=[CH:10][C:11]([O:20]C)=[CH:12][C:13]=2[O:18]C)[O:8]1)([CH3:6])[CH3:5])(=[O:3])[NH2:2].Br.C(O)(=O)C>>[C:1]([C:4]([CH:7]1[CH2:16][C:15](=[O:17])[C:14]2[C:9](=[CH:10][C:11]([OH:20])=[CH:12][C:13]=2[OH:18])[O:8]1)([CH3:6])[CH3:5])(=[O:3])[NH2:2]
Reactant: COc1cc(OC)c2c(c1)OC(C(C)(C)C(N)=O)CC2=O
Agent: Br
Solvent: CC(=O)O
Product: CC(C)(C(N)=O)C1CC(=O)c2c(O)cc(O)cc2O1

Procedure:
5,5-Dimethyl-8-hydroxy-6-oxatetracycline is obtained analogously from 5,5-dimethyl-8-benzyloxy-10-0-benzyl-6-oxatetracycline [obtainable by reaction of 2-(1-carbamoyl-1-methylethyl)-5,7-dimethoxy-4-chromanone with HBr/acetic acid to give 2-(1-carbamoyl-1-methylethyl)-5,7-dihydroxy-4-chromanone, benzylation, conversion into the nitrile, reaction with Raney nickel to give 2-(1-formyl-1-methylethyl)-5,7-dibenzyloxy-4-chromanone, condensation with 2-phenyl-2-thiazolin-5-one to give 2-phenyl-4-[2-methyl-2-(5,7-dibenzyloxy-chroman-4-on-2-yl)-propylidene]-2-thiazolin-5-one, condensation with acetonedicarboxylic acid monomethyl ester-monoamide and subsequent epimerization with pyridine to give 4-de-dimethylamino-4-thiobenzamido-5,5-dimethyl-8-benzyloxy-10-0-benzyl-12a-dehydroxy-6-oxatetracycline and 12a-hydroxylation, splitting off the thiobenzoyl group and methylation].
Reaction SMILES: [NH:1]1[C:5]([C:6]2[CH:14]=[CH:13][C:9]([C:10]([O-])=[O:11])=[CH:8][CH:7]=2)=[N:4][N:3]=[N:2]1.O.[NH2:16][NH2:17]>C(O)C>[NH:1]1[C:5]([C:6]2[CH:14]=[CH:13][C:9]([C:10]([NH:16][NH2:17])=[O:11])=[CH:8][CH:7]=2)=[N:4][N:3]=[N:2]1
Reactant: NN
Reactant: O=C([O-])c1ccc(-c2nnn[nH]2)cc1
Solvent: O
Solvent: CCO
Product: NNC(=O)c1ccc(-c2nnn[nH]2)cc1
Temperature: 25 °C
Yield: 47.5 %

Procedure:
0.20 g (0.99 mmol) of the 4-(1H-tetrazol-5-yl)benzoate was heated with ethanol (3.2 ml) and 0.84 g (16.8 mmol) of hydrazine monohydrate under reflux for 8.5 hours, and then the reaction solution was cooled to room temperature, and the precipitated pale yellow solid was collected by filtration through a Kiriyama funnel, washed with methanol and dried under reduced pressure to obtain the desired product (0.096 g, yield 47%, purity 99%).
Reaction SMILES: [O:1]=[C:2]1[NH:7][C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][CH2:15][CH3:16])=[N:5][CH:4]=[C:3]1[C:17]([O:19]CC)=[O:18].[OH-].[Na+].Cl>>[O:1]=[C:2]1[NH:7][C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][CH2:15][CH3:16])=[N:5][CH:4]=[C:3]1[C:17]([OH:19])=[O:18]
Reactant: CCOC(=O)c1cnc(-c2ccccc2OCC)[nH]c1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: CCOc1ccccc1-c1ncc(C(=O)O)c(=O)[nH]1
Yield: 100.2 %

Procedure:
A solution of ethyl 1,6-dihydro-6-oxo-2-(2-ethoxyphenyl)pyrimidine-5-carboxylate (2 g., 6.9 mmole) in 1N NaOH (20 ml., 20 mmole) was heated at reflux for 10 minutes. The solution was cooled and acidified with 6N HCl to yield the title product (1.8 g., m.p. 168°-184°). Recrystallization from acetonitrile gave 1.2 g. of colorless crystals, m.p. 186°-188°.
Reaction SMILES: [S:1]1(=[O:13])(=[O:12])[C@@H:5]2[CH2:6][C:7](=[O:8])[N:4]2[CH:3]([C:9]([O-:11])=[O:10])[CH2:2]1.C(=O)(O)[O-].[K+].[H][H]>CO.[Pd]>[S:1]1(=[O:13])(=[O:12])[C@@H:5]2[CH2:6][C:7](=[O:8])[N:4]2[CH:3]([C:9]([OH:11])=[O:10])[CH2:2]1
Reactant: O=C([O-])C1CS(=O)(=O)[C@@H]2CC(=O)N12
Reactant: [H][H]
Agent: [Pd]
Agent: O=C([O-])O
Agent: [K+]
Solvent: CO
Product: O=C(O)C1CS(=O)(=O)[C@@H]2CC(=O)N12

Procedure:
To a solution of 350 mg of benzyl (3S, 5R and 3R, 5S)penam-3-carboxylate 1,1-dioxide in 12 ml of methanol was added 75 mg of potassium bicarbonate followed by 350 mg of 10% palladium on carbon. The mixture was shaken under an atmosphere of hydrogen at atmospheric pressure until hydrogen absorption ceased. The catalyst was removed by filtration and then the solvent was removed by evaporation in vacuo. The residue was partitioned between water and ethyl acetate at pH 8. The aqueous layer was removed, and the pH was lowered to 1.5. The acidic aqueous phase was extracted liberally with ethyl acetate. The ethyl acetate extracts were combined, dried (Na2SO4) and concentrated in vacuo. The residue was recrystallized from ethyl acetate-methanol, to give 41 mg of the title compound, mp 164°-167° C. The NMR spectrum (100 MHz; DMSO-d6) showed absorptions at 4.97 (m, 1H), 4.86 (q, 1H), 3.90 (m, 2H) and 3.65 (m, 2H) ppm. The IR spectrum (film) showed absorptions at 1770 and 1725 cm-1. The product had no optical activity.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9](=O)[CH3:10]>CO.[Pd]>[CH2:9]([C:3]1[CH:4]=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=1[OH:1])[CH3:10]
Reactant: CC(=O)c1ccc(C)cc1O
Agent: [Pd]
Solvent: CO
Product: CCc1ccc(C)cc1O
Reaction time: 24 h

Procedure:
A mixture of 1-(2-hydroxy-4-methyl-phenyl)-ethanone (5 g, 33.3 mmol) and 10 wt % Pd/C (2 g, Degussa type) in MeOH (50 mL) was stirred under a balloon of H2 for 24 hours. The reaction mixture was filtered through a pad of celite washing with EtOAc. The filtrate was concentrated to a clear oil (4.5 g, 99%). 1H NMR (400 MHz, CDCl3): δ 1.23 (t, J=7.6 Hz, 3H), 2.27 (s, 3H), 2.59 (q, J=7.6 Hz, 2H), 4.68 (s, 1H), 6.59 (s, 1H), 6.71 (d, J=7.7 Hz, 1H), 7.01 (d, J=7.7 Hz, 1H).
Reaction SMILES: C([O:3][C:4](=[O:30])[C:5]1[CH:10]=[CH:9][C:8]([NH:11][CH2:12][CH2:13][CH2:14][Si:15]([CH3:29])([CH3:28])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[CH:7][CH:6]=1)C.COCCO.[OH-].[K+].C(O)(=O)C>O.C1(C)C=CC=CC=1>[CH3:29][Si:15]([CH3:28])([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH2:14][CH2:13][CH2:12][NH:11][C:8]1[CH:7]=[CH:6][C:5]([C:4]([OH:30])=[O:3])=[CH:10][CH:9]=1
Reactant: CCCCCCCCCCCC[Si](C)(C)CCCNc1ccc(C(=O)OCC)cc1
Agent: [K+]
Agent: [OH-]
Solvent: COCCO
Solvent: O
Solvent: CC(=O)O
Product: CCCCCCCCCCCC[Si](C)(C)CCCNc1ccc(C(=O)O)cc1
Reaction time: 0.75 h

Procedure:
To 11.50 g (26.5 mmol) of ethyl-4-(4,4-dimethyl-4-sila-n-hexadecylamino)-benzoate in 150 ml of freshly distilled 2-methoxy-ethanol (peroxide free) refluxing under nitrogen, is gradually added a solution of 10.0 g (approx. 161 mmol) of potassium hydroxide in 17 ml of water. After the addition, refluxing is continued for 45 mins. Then 15 ml (250 mmol) of acetic acid (100%) is added and the reaction mixture cooled. Toluene is then added and the mixture agitated. The organic phase is recovered, washed with 4 portions of water, dried over anh. sodium sulfate, filtered and the filtrate evaporated to yield crude title product as a semi-solid residue, which upon recrystallization from heptane-hexane (50/50) gives refined title product, m.p. (88)--89°-90°.
Reaction SMILES: N1C=C([C:6]2[C:7]3[CH:14]=[CH:13][N:12](COCC[Si](C)(C)C)[C:8]=3[N:9]=[CH:10][N:11]=2)C=N1.[O-:23]CC.[Na+].C(O)C.C(OC(=O)C(C#N)CC(OCC)OCC)C>>[N:9]1[C:8]2[NH:12][CH:13]=[CH:14][C:7]=2[C:6]([OH:23])=[N:11][CH:10]=1
Reactant: C[Si](C)(C)CCOCn1ccc2c(-c3cn[nH]c3)ncnc21
Reactant: CC[O-]
Agent: CCOC(=O)C(C#N)CC(OCC)OCC
Agent: [Na+]
Solvent: CCO
Product: Oc1ncnc2[nH]ccc12
Temperature: 45 °C
Reaction time: 1 h
Yield: 68.3 %

Procedure:
Formamidine acetate (5, 1.04 Kg, 10 mol, 1.25 equiv) was added to 7.52 L of (21% wt) sodium ethoxide (EtONa) in ethanol (EtOH, 62.5 equiv) and the resulting solution was stirred for 60 minutes. 2-cyano-4,4-diethoxy-butyric acid ethyl ester (4, 1.8 Kg, 8.0 mol) was then added and the resulting reaction mixture was refluxed for seven hours. The stirring was turned off after the solution was cooled and the solids were allowed to settle. The supernatant ethanol solution was removed, leaving the solids in the bottom of the reaction flask. The ethanol was evaporated and the residue was added back to the solids remaining in the reaction flask with water and ice at a ratio of 600 mL/mol. A solution of 6 N aqueous HCl was added to the resulting solution at a ratio of 500 mL/mol at 15° C. The resulting solution was then heated at 45° C. for 45 minutes. The solution was again cooled to 15° C. and the pH was adjusted to 8.0 with the addition of aqueous ammonium hydroxide. The precipitated solids were collected by filtration, washed with water (2×225 mL/mol) and pulled dry. The solids were further washed with 1:1 ethyl acetate/heptane (500 mL/mol), then heptane (2×250 mL/mol) and dried in vacuum to afford 7H-pyrrolo[2,3-d]pyrimidin-4-ol (7, 738.6 g, 1081 g theoretical, 68.3%) as yellow to brown to yellow crystalline material. For 7: 1H NMR (DMSO-d6, 300 MHz) δ ppm 11.88 (bs, 1H), 11.80 (bs, 1H), 7.81 (s, 1H), 7.02 (dd, 1H, J=3.2, 2.3 Hz), 6.42 (dd, 1H, J=3.5, 2.3 Hz); C6H5N3O (MW, 135.12), LCMS (EI) m/e 136 (M++H) and (M++Na) m/e 158.
Reaction SMILES: [H-].[Na+].C1OCCOCCOCCOCCOCCOC1.Cl[CH:22](Cl)[C:23]([OH:25])=[O:24].[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([OH:34])=[C:30]([C:35]([CH:43]2[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]2)([CH:37]2[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]2)[OH:36])[CH:29]=1>O1CCOCC1>[Cl:27][C:28]1[CH:33]=[CH:32][C:31]2[O:34][CH:22]([C:23]([OH:25])=[O:24])[O:36][C:35]([CH:37]3[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]3)([CH:43]3[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]3)[C:30]=2[CH:29]=1
Reactant: O=C(O)C(Cl)Cl
Reactant: Oc1ccc(Cl)cc1C(O)(C1CCCCC1)C1CCCCC1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Product: O=C(O)C1Oc2ccc(Cl)cc2C(C2CCCCC2)(C2CCCCC2)O1
Temperature: 60 °C
Reaction time: 6 h

Procedure:
To a suspension of 1.6 g of NaH (60% dispersion in mineral oil) and 131 mg of 18-crown-6 ether in 60 ml of anhydrous dioxane, a solution of 16.4 ml of a solution of dichloroacetic acid (1 M) in anhydrous dioxane was slowly added at room temperature. The reaction mixture was heated to 60° C. and a solution of 3.2 g of 4-Chloro-2-(dicyclohexyl-hydroxy-methyl)-phenol in 42 ml anhydrous dioxane was added and stirred at 90° C. for 6 h. After cooling to 0° C., the reaction mixture was quenched with 8 ml of isopropanol and poured on ice. The aqueous phase was extracted with ether, then acidified with HCl (2 M, to pH 1), and extracted with ethyl acetate. The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was recrystallized from n-heptane to yield a bright yellow product. Yield: 2.5 g.
Reaction SMILES: [C-]#N.[Na+].Br[C:5]1[CH:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:6]=1[CH3:12].[CH3:13][NH:14]CCNC.[OH-].[NH4+]>[Cu]I.O.C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH3:12][C:6]1[CH:7]=[CH:8][C:9]([CH3:11])=[CH:10][C:5]=1[C:13]#[N:14]
Reactant: Cc1ccc(C)c(Br)c1
Reactant: CNCCNC
Agent: [Cu]I
Agent: [C-]#N
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Solvent: O
Product: Cc1ccc(C)c(C#N)c1
Temperature: 110 °C
Reaction time: 24 h

Procedure:
An oven dried screw cap test tube was charged with NaCN (93 mg, 1.898 mmol), dried KI (52 mg, 0.313 mmol, 20 mol %) and CuI (30 mg, 0.158 mmol, 10 mol %), evacuated and backfilled with argon three times. 2-Bromo-1,4-dimethylbenzene (215 μL, 1.557 mmol), N,N′-dimethylethylenediamine (165 μL, 1.549 mmol) and anhydrous toluene (1 mL) were added under argon. The tube was sealed and the reaction mixture was stirred magnetically at 110° C. for 24 h. The resulting yellow suspension was cooled to room temperature, 2 mL of ethyl acetate, 1 mL of ammonium hydroxide (30%) and 1 mL of water were added. The mixture was stirred at 25° C. for 10 min, then the organic layer was washed with 1 mL of water and dried over MgSO4. The GC analysis showed consumption of the majority of the starting material, and formation of the title compound (as confirmed by GC-MS).
Reaction SMILES: [C:1]([O:4][CH2:5][C@H:6]1[O:11][CH:10]=[CH:9][C@@H:8]([OH:12])[C@@H:7]1[OH:13])(=[O:3])[CH3:2].[CH3:14][O:15][CH2:16][C:17](OC=C)=[O:18]>C(COC)OC>[CH3:14][O:15][CH2:16][C:17]([O:12][C@H:8]1[C@H:7]([OH:13])[C@@H:6]([CH2:5][O:4][C:1](=[O:3])[CH3:2])[O:11][CH:10]=[CH:9]1)=[O:18]
Reactant: C=COC(=O)COC
Reactant: CC(=O)OC[C@H]1OC=C[C@@H](O)[C@@H]1O
Solvent: COCCOC
Product: COCC(=O)O[C@@H]1C=CO[C@H](COC(C)=O)[C@H]1O
Reaction time: 2 h
Yield: 93.8 %

Procedure:
325 mg (1.73 mmol) of 6-O-acetylglucal are dissolved in 1 ml of dimethoxyethane, 1 ml of vinyl methoxyacetate and 325 mg of lipase Fp (Pseudomonas fluorescens, Amano) are added, and the mixture is stirred at room tempera-tufa for 51/2hours. Filtering off the enzyme and flash chromatography on silica gel (ethyl acetate/hexane 1:2) result in 422 mg (1.62 mmol, 93.8% yield) of the desired 3-O-methoxyacetyl-6-O-acetylglucal.
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:5]=2[N:6]=1.[Br:12]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:12][CH2:11][C:8]1[CH:9]=[CH:10][C:4]2[S:3][C:2]([CH3:1])=[N:6][C:5]=2[CH:7]=1
Reactant: Cc1ccc2sc(C)nc2c1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: Cc1nc2cc(CBr)ccc2s1

Procedure:
8.16 g of 2,5-dimethylbenzothiazole was dissolved in 50 ml of carbon tetrachloride. To the solution were added 8.9 g of N-bromosuccinimide and 82 mg of benzoyl peroxide. The mixture was refluxed for 3 hours. The resulting insolubles were removed by filtration. The solvent of the filtrate was removed by distillation under reduced pressure to obtain 5-bromomethyl-2-methylbenzothiazole. It was suspended in 100 ml of 50% acetic acid. To the suspension was added 14.00 g of hexamethylenetetramine, and the mixture was refluxed for 1 hour. The reaction mixture was mixed with 200 ml of water. The resulting mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium hydrogencarbonate solution, water and a saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by a column chromatography (eluant: n-hexane/ethyl acetate=3/1) to obtain 3.54 g of colorless crystals of 2-methyl-5-formylbenzothiazole having a melting point of 92°-94° C.
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[O:5]1[C:9]2[CH:10]=[CH:11][C:12]([C:14]([CH3:19])([CH3:18])[CH:15]=[N:16][OH:17])=[CH:13][C:8]=2[O:7]C1>C(Cl)Cl>[OH:7][C:8]1[CH:13]=[C:12]([C:14]([CH3:19])([CH3:18])[CH:15]=[N:16][OH:17])[CH:11]=[CH:10][C:9]=1[OH:5]
Reactant: CC(C)(C=NO)c1ccc2c(c1)OCO2
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CC(C)(C=NO)c1ccc(O)c(O)c1
Temperature: 0 °C
Reaction time: 3 h

Procedure:
To a suspension of anhydrous AlCl3 (193 mg, 1.45 mmol) in dry CH2Cl2 (1 mL), a solution of Compound J (60 mg, 0.29 mmol) in dry CH2Cl2 (1 mL) was added drop-wise at room temperature under N2 atmosphere and stirred at the same temperature for 3 hours. The reaction mixture was cooled to 0° C., 20 mL of cold distilled water was added, the reaction mixture was allowed to attain room temperature and stirred for 12 hours at the same temperature under N2 atmosphere. The reaction mixture was evaporated to dryness and triturated several times with 2:1 ethyl acetate-CH2Cl2 and followed by 10:1 ethyl acetate-methanol. The organic solutions were combined and evaporated to dryness. The crude material was purified by preparative thin-layer chromatography using 2:1 petroleum ether-ethyl acetate to obtain the desired Compound No. 9 (30 mg, 53%) as a white foam.
Reaction SMILES: [CH2:1]([S:4][CH2:5][C@@H:6]([C:8]([OH:10])=O)[NH2:7])[CH:2]=[CH2:3].[OH-].[Na+].[C:13]1([N:19]=[C:20]=[S:21])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[C:13]1([N:19]2[C:8](=[O:10])[CH:6]([CH2:5][S:4][CH2:1][CH:2]=[CH2:3])[NH:7][C:20]2=[S:21])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: S=C=Nc1ccccc1
Reactant: C=CCSC[C@H](N)C(=O)O
Agent: [Na+]
Agent: [OH-]
Product: C=CCSCC1NC(=S)N(c2ccccc2)C1=O

Procedure:
When 5 g of S-allylcysteine (0.031 mole), 1.24 g of sodium hydroxide (0.31 mole) and 4.19 g of phenylisothiocyanate (0.031 mole) were reacted according to the procedure for the preparation of the compound of Example 2, 8.59 g of crude product was obtained which did not require purification by chromatography. Crystallization of the crude product from isopropyl alcohol gave pure title compound: RF on silica gel=0.44 [ethyl acetate-hexane (2:3)].
Reaction SMILES: [Br:1][C:2]1[CH:9]=[C:6]([CH:7]=[O:8])[C:5]([OH:10])=[CH:4][CH:3]=1.[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][C@H:20](OS(C)(=O)=O)[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C([O-])([O-])=O.[K+].[K+]>CN(C)C=O>[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH:20]([O:10][C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:9][C:6]=2[CH:7]=[O:8])[CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]
Reactant: O=Cc1cc(Br)ccc1O
Reactant: CC(C)(C)OC(=O)N1CC[C@H](OS(C)(=O)=O)C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC(Oc2ccc(Br)cc2C=O)C1
Yield: 54 %

Procedure:
In a manner similar to the method described in example 4a, 5-bromosalicylaldehyde (3.6 g, 18 mmol) (Aldrich) reacted with (S)-3-methanesulfonyloxy-pyrrolidine-1-carboxylic acid tert-butyl ester (5.3 g, 20 mmol) and K2CO3 in N,N-dimethylformamide to give (R/S)-3-(4-bromo-2-formyl-phenoxy)-pyrrolidine-1-carboxylic acid tert-butyl ester as an orange oil (Yield 3.6 g, 54%).