Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[S:9]([NH2:12])(=[O:11])=[O:10].[Cl:13][C:14]1[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][C:15]=1[S:21](Cl)(=[O:23])=[O:22]>N1C=CC=CC=1>[Cl:13][C:14]1[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][C:15]=1[S:21]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[S:9]([NH2:12])(=[O:10])=[O:11])(=[O:23])=[O:22]
Reactant: Cc1ccc(N)c(S(N)(=O)=O)c1
Reactant: O=S(=O)(Cl)c1cccc(Cl)c1Cl
Solvent: c1ccncc1
Product: Cc1ccc(NS(=O)(=O)c2cccc(Cl)c2Cl)c(S(N)(=O)=O)c1
Temperature: 25 °C
Reaction time: 17 h
Yield: 607.2 %

Procedure:
To a solution of 2-amino-5-methyl-benzenesulfonamide (1.86 g, 1 mmol) in pyridine (20 mL), 2,3-dichlorobenzenesulphonyl chloride (3.0 g, 1.25 mmol) was added at 0° C. The reaction was stirred at RT for 17 h. The pyridine was removed in vacuo and the residue was dissolved in ethyl acetate. The organic phase was washed with aqueous 1N HCl, water and brine, dried over sodium sulfate, and concentrated under reduced pressure. The crude product was purified by flash column chromatography using ethyl acetate/hexane (1:1) as eluent to give the title compound (2.4 g, 60%).
Reaction SMILES: [OH-].[Li+].[CH2:3]([O:7][C:8]1[CH:9]=[C:10]([CH2:28][CH2:29][C:30]([O:32]C)=[O:31])[CH:11]=[CH:12][C:13]=1[CH2:14][CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH3:25])=[C:19]([O:26][CH3:27])[CH:18]=1)[CH2:4][CH2:5][CH3:6]>O1CCCC1>[CH2:3]([O:7][C:8]1[CH:9]=[C:10]([CH2:28][CH2:29][C:30]([OH:32])=[O:31])[CH:11]=[CH:12][C:13]=1[CH2:14][CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH3:25])=[C:19]([O:26][CH3:27])[CH:18]=1)[CH2:4][CH2:5][CH3:6]
Reactant: CCCCOc1cc(CCC(=O)OC)ccc1CCCc1ccc(OCC)c(OC)c1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CCCCOc1cc(CCC(=O)O)ccc1CCCc1ccc(OCC)c(OC)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 79.3 %

Procedure:
ml (1.1 mmol) of aqueous 1N lithium hydroxide solution are added to a solution of 240 mg (0.56 mmol) of methyl 3-{3-butoxy-4-[3-(4-ethoxy-3-methoxyphenyl)propyl]phenyl}propanoate in 3 ml of tetrahydrofuran. The reaction mixture is stirred at room temperature for 12 hours. The reaction medium is concentrated and then taken up in water and acidified by addition of aqueous hydrochloric acid solution and then extracted with ethyl acetate. The organic phases are combined, washed with saturated aqueous sodium chloride solution and then dried over magnesium sulfate and filtered. The solvents are evaporated off. After recrystallization of the residue obtained from 6 ml of cyclohexane, 184 mg (79%) of 3-{3-butoxy-4-[3-(4-ethoxy-3-methoxyphenyl)propyl]phenyl}propanoic acid are obtained in the form of a white solid with a melting point of 66° C.
Reaction SMILES: O.O.O.C([O-])(=O)C.[Pb+2].C([O-])(=O)C.[N+:13]([C:16]1[CH:23]=[CH:22][C:19]([CH2:20][SH:21])=[CH:18][CH:17]=1)([O-:15])=[O:14].Br[N:25]1[C:29](=[O:30])[CH2:28][CH2:27][C:26]1=[O:31]>CO>[N+:13]([C:16]1[CH:23]=[CH:22][C:19]([CH2:20][S:21][N:25]2[C:29](=[O:30])[CH2:28][CH2:27][C:26]2=[O:31])=[CH:18][CH:17]=1)([O-:15])=[O:14]
Reactant: O=[N+]([O-])c1ccc(CS)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: CC(=O)[O-]
Agent: [Pb+2]
Solvent: O
Solvent: CO
Product: O=C1CCC(=O)N1SCc1ccc([N+](=O)[O-])cc1
Temperature: 50 °C
Reaction time: 1 h
Yield: 64.9 %

Procedure:
Lead (II) acetate trihydrate (0.759 g, 2.0 mmol) and 4-nitrobenzyl mercaptan (0.745 g, 4.4 mmol) were stirred together in methanol (24 cm3) solution at room temperature. After 1 h, the products were filtered and the residue was washed with a small volume of cold methanol. The residue was dried in vacuo over calcium chloride and then suspended in dry acetonitrile (20 cm3). Following the evaporation of the solvent under reduced pressure, the residue was suspended in dry benzene (20 cm3) and the solvent was again evaporated under reduced pressure. Finally, the residue was re-suspended in dry benzene (64 cm3) and N-bromosuccinimide (0.783 g, 4.4 mmol) was added in three portions over a period of 45 min to the stirred suspension at room temperature. The reactants were then heated at 50° C., under an atmosphere of argon, for 14 h. The cooled products were filtered and the filtrate was evaporated under reduced pressure to give a solid. The latter material was crystallized from ethyl acetate--hexane to give N-(4-nitrobenzylmercapto)succinimide 18 (0.76 g, 65%) (Found: C, 49.85; H, 3.8; N, 10.4. C11H10N2O4S requires: C, 49.6; H, 3.8; N, 10.5%), m.p. 146°-148° C.; δH [CDCl3 ] 2.73 (4 H, s), 4.18 (2 H, s), 7.50 (2 H, m), 8.17 (2 H, m); δC [CDCl3 ] 28.4, 40.5, 123.8, 130.3, 141.9, 147.5, 176.2.
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:29])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7](/[CH:11]=[C:12]2/[CH:13]=[C:14]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=3)[CH:15]([CH2:18][N:19]([CH3:21])[CH3:20])[CH2:16][CH2:17]/2)[CH:6]=1.C[Si](C)(C)[Cl:32].O>CC(C)=O>[ClH:32].[CH3:2][O:3][C:4](=[O:29])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7](/[CH:11]=[C:12]2\[CH:13]=[C:14]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=3)[CH:15]([CH2:18][N:19]([CH3:21])[CH3:20])[CH2:16][CH2:17]\2)[CH:6]=1
Reactant: C[Si](C)(C)Cl
Reactant: COC(=O)c1cccc(/C=C2/C=C(c3cccc(O)c3)C(CN(C)C)CC2)c1
Agent: Cl
Solvent: O
Solvent: CC(C)=O
Product: COC(=O)c1cccc(/C=C2\C=C(c3cccc(O)c3)C(CN(C)C)CC2)c1
Yield: 27.6 %

Procedure:
8.1 g potassium tert-butylate and 35.4 g 3-(benzoic acid methyl ester)-methyltriphenylphosphonium chloride were suspended in 800 ml analytical grade toluene under a nitrogen atmosphere at room temperature and the suspension was then stirred at 70° C. for one hour. 7 g 3-(3-(tert-butyl-diphenyl-silanyloxy)-cyclohex-2-enone in 100 ml analytical grade toluene were added at this temperature and the mixture was stirred at 70° C. for 3 days. The mixture was quenched with 500 ml water. The phases were separated and the aqueous phase was washed 3 times with 200 ml ethyl acetate each time. The combined organic phases were dried over magnesium sulfate and then freed from solvent in vacuo. The residue obtained in this way was taken up in a mixture of 150 ml ethyl acetate and 150 ml diiso-ether. The solid which had precipitated out was filtered off and washed with diiso-ether. The combined organic phases were freed from the solvent in vacuo. The residue (16.7 g) was dissolved in 70 ml tetrahydrofuran, and 16.7 ml tetrabutylammonium fluoride were added. After a reaction time of 10 minutes the reaction solution was quenched with 50 ml water and extracted three times with 50 ml ethyl acetate each time. The combined organic phases were dried over magnesium sulfate and then freed from the solvent in vacuo. The residue was purified by column chromatography on silica gel with ethyl acetate/methanol=9/1. 2.5 g E-3-[4-dimethylaminomethyl-3-(3-hydroxy-phenyl)-cyclohex-2-enylidenemethyl]-benzoic acid methyl ester base were obtained as the first product fraction. To liberate the hydrochloride, the base was dissolved in 50 ml acetone, and an equimolar amount of trimethylchlorosilane and water was added. 2 g (36.8% of theory) E-3-[4-dimethylaminomethyl-3-(3-hydroxy-phenyl)-cyclohex-2-enylidenemethyl]-benzoic acid methyl ester hydrochloride (37) were obtained in this way. 1.8 g (27.6% of theory) Z-3 [4-Dimethylaminomethyl-3-(3-hydroxy-phenyl)-cyclohex-2-enylidenemethyl]-benzoic acid methyl ester were obtained as the second product fraction. To liberate the hydrochloride, the base was dissolved in 50 ml acetone, and an equimolar amount of trimethylchlorosilane and water was added. 1.5 g (27.6% of theory) Z-3-[4-dimethylaminomethyl-3-(3-hydroxy-phenyl)-cyclohex-2-enylidenemethyl]-benzoic acid methyl ester hydrochloride (38) were obtained in this way.
Reaction SMILES: [ClH:1].[N:2]1([CH2:9][CH2:10][NH:11][C:12]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22]C=3)[CH2:16][CH2:15]2)=[O:13])[CH2:8][CH2:7]CC[CH2:4][CH2:3]1.[N:26]1C=CC=CC=1N1CCNCC1.O1CCCC1>Cl>[ClH:1].[CH2:8]([N:2]([CH2:3][CH3:4])[CH2:9][CH2:10][NH:11][C:12]([N:14]1[CH2:15][CH2:16][N:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:26]=2)[CH2:18][CH2:19]1)=[O:13])[CH3:7]
Reactant: O=C(NCCN1CCCCCC1)N1CCN(c2ccccc2)CC1
Reactant: c1ccc(N2CCNCC2)nc1
Agent: Cl
Solvent: C1CCOC1
Product: CCN(CC)CCNC(=O)N1CCN(c2ccccn2)CC1

Procedure:
This compound was prepared according to the procedure used to synthesize the compound of Example 9. A mixture of 5.0 g (0.03 mole) of 1',1'-carbonyldiimidazole, 3.6 g (0.03 mole) of unsym-diethylethylenediamine, and 5.0 g (0.03 mole) of 1-(2-pyridinyl)piperazine in a total of 200 ml of tetrahydrofuran gave an oil as residue. The hydrochloride was formed in ethereal hydrogen chloride and the collected solid was recrystallized from methanol-ethyl ether to yield 7.3 g (63%) of title compound as a white solid, m.p. 183°-185° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[C:10]([NH2:15])=[CH:11][CH:12]=[CH:13][CH:14]=1.[S:16](N)(N)(=[O:18])=[O:17]>COCCOCCOC.CCOCC>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[NH:15][S:16]1(=[O:18])=[O:17]
Reactant: NS(N)(=O)=O
Reactant: Nc1ccccc1Nc1ccccc1F
Solvent: COCCOCCOC
Solvent: CCOCC
Product: O=S1(=O)Nc2ccccc2N1c1ccccc1F
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 23.3 %

Procedure:
Dry diglyme (10 mL) was added to a flask equipped with a dropping funnel under a nitrogen atmosphere and brought to a vigorous reflux N-(2-fluorophenyl)benzene-1,2-diamine (1.2 g, 6.0 mmol) and sulfamide (0.69 g, 7.2 mmol) were dissolved in 5 mL of diglyme and placed in the dropping funnel. The mixture was added dropwise to the flask over 15 minutes and then refluxing was continued for an additional 15 minutes. The mixture was cooled to ambient temperature and diluted with ether, washed with water, 2N HCl, water, brine, dried over anhydrous magnesium sulfate, and concentrated. The crude product was purified via Isco chromatography (Redisep, silica, gradient 5-50% (ethyl acetate containing 2% formic acid) in hexane) to afford 1-(2-fluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (0.37 g).
Reaction SMILES: [C:1]([NH:14][C@H:15]([C:24]([OH:26])=[O:25])[CH2:16][CH2:17][CH2:18][CH2:19][NH:20][N:21]=[C:22]=[S:23])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[OH-].[Na+:28]>O>[C:1]([NH:14][C@H:15]([C:24]([O-:26])=[O:25])[CH2:16][CH2:17][CH2:18][CH2:19][NH:20][N:21]=[C:22]=[S:23])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[Na+:28]
Reactant: CCCCCCCCCCCC(=O)N[C@@H](CCCCNN=C=S)C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCCCCCCCCCC(=O)N[C@@H](CCCCNN=C=S)C(=O)[O-]

Procedure:
0.147 g of Nα-lauroyl-Nε-isothiocyanato-L-Lysine was combined and stirred with 2 g of RO water and 0.39 mL of 1.00 M NaOH in a 50 mL single neck round bottom flask and filtered into a 250 mL single neck round bottom flask to yield a clear pale amber solution. The flask was then immersed while rotating into a dry ice/acetone bath to yield a solid coating on the walls of the flask, whereupon the flask was evacuated (0.10 mm Hg) and removed from the ice bath. Evacuation for one hour yielded a dry white solid powder of the water soluble surfactant Sodium Nα-lauroyl-Nε-isothiocyanato-L-Lysinate. [mp 47-55° C. to small droplets of clear colorless viscous liquid; IR (mineral oil mull, cm−1), 3300m amide N—H str; 2188s, 2107s N═C str; 1627s, amide C═O str; 1593s carboxylate C═O str].
Reaction SMILES: Br[C:2]1[C:14](=[O:15])[N:13]([CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:5]2[N:6]=[C:7]([NH:11][CH3:12])[N:8]=[C:9]([CH3:10])[C:4]=2[CH:3]=1.[OH:21][CH2:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1.CO.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.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>[CH:16]1([N:13]2[C:5]3[N:6]=[C:7]([NH:11][CH3:12])[N:8]=[C:9]([CH3:10])[C:4]=3[CH:3]=[C:2]([C:27]3[CH:26]=[CH:25][CH:24]=[C:23]([CH2:22][OH:21])[CH:28]=3)[C:14]2=[O:15])[CH2:20][CH2:19][CH2:18][CH2:17]1
Reactant: CNc1nc(C)c2cc(Br)c(=O)n(C3CCCC3)c2n1
Reactant: OCc1cccc(B(O)O)c1
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: [Na+]
Solvent: Cc1ccccc1
Solvent: CO
Product: CNc1nc(C)c2cc(-c3cccc(CO)c3)c(=O)n(C3CCCC3)c2n1
Yield: 81.2 %

Procedure:
6-Bromo-8-cyclopentyl-4-methyl-2-methylamino-8H-pyrido[2,3-d]pyrimidin-7-one (5.00 g, 14.83 mmol), 3-(hydroxymethyl)phenylboronic acid (3.38 g, 22.24 mmol) and Pd(PPh3)4 (0.685 g, 0.593 mmol) were suspended in Toluene (20 mL), MeOH (10 mL) and sat. NaHCO3 (10 mL) and then heated to 100° C. overnight. The reaction was deemed complete by MS and TLC. The organic layer was injected directly onto a column, eluting with CH2Cl2 then 4% MeOH in CH2Cl2. The fractions containing the desired material, as deemed by MS, were combined and evaporated in vacuo to give a greenish beige solid. This was triturated with MeCN and filtered to give crop one, 4.7 g. A second crop was obtained of 0.25 g. A third crop was obtained of 0.10 g. The three crops were deemed to be of sufficient purity based on NMR's and were combined and washed again with MeCN to give a solid (4.39 g, 81.24%).
Reaction SMILES: Cl[CH2:2][CH2:3][S:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH2:11]([N:13]([CH2:17][CH3:18])[CH2:14][CH2:15][NH2:16])[CH3:12].C(=O)([O-])[O-].[Na+].[Na+].[C:25]([OH:32])(=[O:31])/[CH:26]=[CH:27]\[C:28]([OH:30])=[O:29]>C(#N)C.CO.C(OCC)C>[C:25]([OH:32])(=[O:31])/[CH:26]=[CH:27]\[C:28]([OH:30])=[O:29].[CH2:11]([N:13]([CH2:17][CH3:18])[CH2:14][CH2:15][NH:16][CH2:2][CH2:3][S:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH3:12]
Reactant: CCN(CC)CCN
Reactant: ClCCSc1ccccc1
Agent: O=C(O)/C=C\C(=O)O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Solvent: CO
Solvent: CCOCC
Product: CCN(CC)CCNCCSc1ccccc1
Yield: 43.2 %

Procedure:
A mixture of 60.24 g (0.350 mole) of [(2-chloroethyl)thio]benzene, 84 g (0.72 mole) of N,N-diethylethylenediamine, and 80.0 g (0.75 mole) of sodium carbonate in 1.5 liters of acetonitrile was refluxed for 16 hr. The solvent was removed in vacuo, and the residue was partitioned between methylene chloride and dilute sodium hydroxide. The methylene chloride solution was dried over sodium sulfate, and the solvent was removed in vacuo to give an oil. This was dissolved in 800 ml of methanol. A solution of approximately 2 equivalents of maleic acid in methanol was added followed by the addition of anhydrous diethyl ether until the solution became slightly cloudy. A white solid precipitated at -5° C. to give 73.15 g (43.2%) of title compound, a white crystalline solid, mp 131°-133° C.
Reaction SMILES: C([O:5][C:6](=[O:31])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([N:13]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[S:14]([C:17]2[CH:21]=[CH:20][N:19]([CH3:22])[N:18]=2)(=[O:16])=[O:15])[CH:8]=1)(C)(C)C>FC(F)(F)C(O)=O.ClCCl>[Cl:30][C:27]1[CH:26]=[CH:25][C:24]([CH2:23][N:13]([S:14]([C:17]2[CH:21]=[CH:20][N:19]([CH3:22])[N:18]=2)(=[O:15])=[O:16])[C:9]2[CH:8]=[C:7]([CH:12]=[CH:11][CH:10]=2)[C:6]([OH:31])=[O:5])=[CH:29][CH:28]=1
Reactant: Cn1ccc(S(=O)(=O)N(Cc2ccc(Cl)cc2)c2cccc(C(=O)OC(C)(C)C)c2)n1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cn1ccc(S(=O)(=O)N(Cc2ccc(Cl)cc2)c2cccc(C(=O)O)c2)n1
Reaction time: 3 h
Yield: 16.9 %

Procedure:
A solution of 3-[(4-chloro-benzyl)-(1-methyl-1H-pyrazole-3-sulfonyl)-amino]-benzoic acid tert-butyl ester (1.33 g, 0.02 mol) in a mixture of trifluoroacetic acid/dichloromethane (20 ml, 1:1 v/v) was stirred for 3 hrs. The reaction mixture was concentrated to dryness in vacuo to afford the title compound as a white solid (1.37 g). HPLC retention time 2.75 Mass spectrum (ES+) m/z 405.9 (M+).
Reaction SMILES: [CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:62])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([O:50][Si](C(C)(C)C)(C)C)[CH:46]([O:58][CH2:59][CH:60]=[CH2:61])[CH2:45]2)[CH:7]([CH3:63])[CH2:6][CH2:5][C:4]1=[O:64])[CH3:2]>C(#N)C.C(OCC)(=O)C>[CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:62])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([OH:50])[CH:46]([O:58][CH2:59][CH:60]=[CH2:61])[CH2:45]2)[CH:7]([CH3:63])[CH2:6][CH2:5][C:4]1=[O:64])[CH3:2]
Reactant: C=CCOC1CC(C=C(C)C2OC(=O)C3CCCCN3C(=O)C(=O)C3(O)OC(C(OC)CC(C)CC(C)=CC(CC)C(=O)CCC2C)C(OC)CC3C)CCC1O[Si](C)(C)C(C)(C)C
Solvent: CC#N
Solvent: CCOC(C)=O
Product: C=CCOC1CC(C=C(C)C2OC(=O)C3CCCCN3C(=O)C(=O)C3(O)OC(C(OC)CC(C)CC(C)=CC(CC)C(=O)CCC2C)C(OC)CC3C)CCC1O
Temperature: 25 °C
Reaction time: 4 h
Yield: 41.7 %

Procedure:
To a solution of 17-ethyl-1-hydroxy-12-[2'-(4"-(tert-butyldimethylsiloxy)-3"-allyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (115 mg) (STEP 31A) in acetonitrile (2.5 ml) was added a solution of 2% HF in aqueous acetonitrile (40 μl), and the mixture was stirred at room temperature. After 4 hours, the solution was diluted with ethyl acetate and quenched with saturated sodium bicarbonate. The layers were separated, and the organic layer was washed with brine and dried over magnesium sulfate. Purification of the concentrate by flash chromatography on silica gel (ethyl acetate:hexane (1:2)) gave the title compound (42 mg). 1H NMR consistent with the desired structure.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]3[N:19]=[C:18]([CH3:20])[NH:17][C:16](=[O:21])[C:15]=3[N+:22]([O-:24])=[O:23])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.FC(F)(F)S(O[CH2:31][C:32]([F:35])([F:34])[F:33])(=O)=O.[Na].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:9][CH2:10][N:11]([C:14]3[C:15]([N+:22]([O-:24])=[O:23])=[C:16]([O:21][CH2:31][C:32]([F:35])([F:34])[F:33])[N:17]=[C:18]([CH3:20])[N:19]=3)[CH2:12][CH2:13]2)=[CH:4][CH:3]=1
Reactant: Cc1nc(N2CCC(c3ccc(F)cc3)CC2)c([N+](=O)[O-])c(=O)[nH]1
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na]
Solvent: CC(C)=O
Product: Cc1nc(OCC(F)(F)F)c([N+](=O)[O-])c(N2CCC(c3ccc(F)cc3)CC2)n1

Procedure:
In analogy to the procedure described in example 9, the 6-[4-(4-fluoro-phenyl)-piperidin-1-yl]-2-methyl-5-nitro-3H-pyrimidin-4-one (example 7) was treated with 2,2,2-trifluoro-ethyl trifluoromethanesulfonate, sodium and potassium carbonate in acetone at room temperature to yield the 4-[4-(4-fluoro-phenyl)-piperidin-1-yl]-2-methyl-5-nitro-6-(2,2,2-trifluoro-ethoxy)-pyrimidine as a yellow oil; MS: [M+H]+=415; and the 6-[4-(4-fluoro-phenyl)-piperidin-1-yl]-2-methyl-5-nitro-3-(2,2,2-trifluoro-ethyl)-3H-pyrimidin-4-one as yellow solid; m.p. 61-64° C.; MS: [M+H]+=415.
Reaction SMILES: [C:1]([NH:9][C:10](SC)=[N:11][C:12](=[O:20])[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([NH2:30])=[O:29])=[CH:26][CH:25]=1>C(O)(C)C>[NH2:30][C:28]([C:27]1[CH:31]=[CH:32][C:24]([NH:23][C:10]([NH:9][C:1](=[O:8])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[N:11][C:12](=[O:20])[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=2)=[CH:25][CH:26]=1)=[O:29]
Reactant: NC(=O)c1ccc(N)cc1
Reactant: CSC(=NC(=O)c1cccc(Br)c1)NC(=O)c1ccccc1
Solvent: CC(C)O
Product: NC(=O)c1ccc(NC(=NC(=O)c2cccc(Br)c2)NC(=O)c2ccccc2)cc1
Yield: 68.2 %

Procedure:
A mixture of 7.55 g (0.02 mole) of N-benzoyl-N-'-(3-bromobenzoyl)carbamimidothioic acid, methyl ester, 2.72 g (0.02 mole) of 4-aminobenzamide and 250 ml of isopropyl alcohol was heated at reflux for 48 hours resulting in precipitation of a solid. The solid was collected by filtration and washed with two 50 ml portions of hot isopropyl alcohol to give 6.35 g of the desired product as a white solid, mp 282°-283° C.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@@H:11]1[C:15](=[CH2:16])[C@H:14]([CH2:17][OH:18])[C@@H:13]([OH:19])[C@@H:12]1[F:20].[C:21]([CH:24]([CH:26]([C:28]([O-:30])=O)[OH:27])[OH:25])([O-])=[O:22].[Na+].[K+]>C(Cl)Cl.C(O)(C)C.C(Cl)(Cl)Cl>[C@@H:11]1([N:6]2[C:7]3[N:8]=[CH:9][N:10]=[C:2]([NH2:1])[C:3]=3[N:4]=[CH:5]2)[O:27][C@H:26]([CH2:28][OH:30])[C@@H:24]([OH:25])[C@H:21]1[OH:22].[NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@@H:11]1[C:15](=[CH2:16])[C@H:14]([CH2:17][OH:18])[C@@H:13]([OH:19])[C@@H:12]1[F:20]
Reactant: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: C=C1[C@@H](n2cnc3c(N)ncnc32)[C@@H](F)[C@H](O)[C@H]1CO
Agent: [K+]
Agent: [Na+]
Solvent: CC(C)O
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
(+)-(1R,2R,3R,5R)-3-(6-amino-9H-9-purinyl)-2-fluoro-5-(hydroxymethyl)-4-methylenecyclopentan-1-ol (15) Diisobutylaluminum hydride (DIBAL-H, 1.6 mL, 1.0 M in toluene) was added slowly into the solution of compound 14 (160.0 mg, 0.33 mmol) in anhydrous CH2Cl2 at −78° C. After 30 min at the same temperature, the reaction was diluted with isopropyl alcohol/chloroform (4:1) co-solvent (30 mL) and saturated potassium sodium tartrate solution (10 mL) was added. The mixture was stirred at room temperature for 2 h and the organic layer was collected. The aqueous layer was extracted with isopropyl alcohol/chloroform (4:1) co-solvent (3×10 mL) and organic layer were combined, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on a silica gel (MeOH:CH2Cl2=1:20 to1:10) to give adenosine analogue 15 (70.0 mg, 76%) as a white solid. mp: 215-218° C. (dec.) [α]25D +151.80° (c 0.23, CHCl3) UV (H2O) λmax 259.0 nm (ε 13998, pH 2), 260.0 nm (ε 15590, pH 7), 260.0 nm (ε 15579, pH 11); 1H NMR (400 MHz, CDCl3) δ 8.22 (s, 1H), 8.06 (d, J=2.4 Hz, 1H), 5.86 (dd, J=2.4 and 25.6 Hz, 1H), 5.42 (t, J=2.4 Hz, 1H), 4.93 (td, J=3.2 and 52.4 Hz, 1H), 4.92 (s, 1H, partially buried inside the H2O peak), 4.40 (td, J=3.2 and 10.8 Hz, 1H), 3.88-3.76 (m, 2H), 2.78 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 156.0, 152.5, 149.9, 146.1 (d, J=1.0 Hz), 141.1 (d, J=5.2 Hz), 117.9, 111.8, 95.9 (d, J=186.0 Hz), 72.9 (d, J=22.9 Hz), 61.8 (d, J=3.4 Hz), 57.6 (d, J 17.2 Hz), 51.1. Anal. Calcd. for C12H14FN5O2: C, 51.61; H, 5.05; N, 25.08. Found: C, 51.74; H, 5.09; N, 24.92.
Reaction SMILES: [CH2:1]([O:3][C:4]([C@@H:6]([NH:20][C@@H:21]1[C:27](=[O:28])[N:26]([CH2:29][C:30]([O:32]C(C)(C)C)=[O:31])[C:25]2[CH:37]=[CH:38][CH:39]=[CH:40][C:24]=2[S:23][CH2:22]1)[CH2:7][CH2:8][N:9]1[C:13](=[O:14])[C:12]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:11]2[C:10]1=[O:19])=[O:5])[CH3:2].C(OCC)(=O)C.[ClH:47]>>[ClH:47].[CH2:1]([O:3][C:4]([C@@H:6]([NH:20][C@@H:21]1[C:27](=[O:28])[N:26]([CH2:29][C:30]([OH:32])=[O:31])[C:25]2[CH:37]=[CH:38][CH:39]=[CH:40][C:24]=2[S:23][CH2:22]1)[CH2:7][CH2:8][N:9]1[C:10](=[O:19])[C:11]2=[CH:18][CH:17]=[CH:16][CH:15]=[C:12]2[C:13]1=[O:14])=[O:5])[CH3:2]
Reactant: CCOC(=O)[C@H](CCN1C(=O)c2ccccc2C1=O)N[C@H]1CSc2ccccc2N(CC(=O)OC(C)(C)C)C1=O
Agent: Cl
Solvent: CCOC(C)=O
Product: CCOC(=O)[C@H](CCN1C(=O)c2ccccc2C1=O)N[C@H]1CSc2ccccc2N(CC(=O)O)C1=O
Reaction time: 4 h

Procedure:
In hydrogen chloride-ethyl acetate solution (5N, 5 ml) is dissolved 0.2 g of tert-butyl 3(R)-[1(S)-ethoxycarbonyl-3-phthalimidopropyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate, and the solution is allowed to stand at room temperature for 4 hours. Petroleum ether (100 ml) is added to the reaction solution, and the deposited precipitate is collected by filtration to give 0.18 g of 3(R)-[1(S)-ethoxycarbonyl-3-phthalimidopropyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid.hydrochloride as a colorless powder.