Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:16]=[CH:15][C:10]([O:11][CH2:12][CH2:13][NH2:14])=[CH:9][CH:8]=2)[N:6]=1.[C:17]([NH:20][C:21]1[N:26]=[CH:25][C:24]([CH:27]([O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])[CH2:28]OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:23][CH:22]=1)(=[O:19])[CH3:18].C(N(C(C)C)CC)(C)C>CS(C)=O>[C:44]([Si:41]([CH3:43])([CH3:42])[O:40][C@H:27]([C:24]1[CH:23]=[CH:22][C:21]([NH:20][C:17](=[O:19])[CH3:18])=[N:26][CH:25]=1)[CH2:28][NH:14][CH2:13][CH2:12][O:11][C:10]1[CH:15]=[CH:16][C:7]([C:5]2[N:6]=[C:2]([CH3:1])[S:3][CH:4]=2)=[CH:8][CH:9]=1)([CH3:47])([CH3:46])[CH3:45]
Reactant: CC(=O)Nc1ccc(C(COS(=O)(=O)c2ccc(C)cc2)O[Si](C)(C)C(C)(C)C)cn1
Reactant: Cc1nc(-c2ccc(OCCN)cc2)cs1
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)Nc1ccc([C@H](CNCCOc2ccc(-c3csc(C)n3)cc2)O[Si](C)(C)C(C)(C)C)cn1
Temperature: 80 °C
Yield: 44.6 %

Procedure:
In a round-bottomed flask, 2-[4-(2-methyl-thiazol-4-yl)-phenoxy]-ethylamine (175 mg, 0.747 mmol) and toluene-4-sulfonic acid 2-(6-acetylamino-pyridin-3-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethyl ester (231 mg, 0.498 mmol) were dissolved in dimethylsulfoxide (0.50 mL), and diisopropyl ethyl amine (0.105 mL, 0.600 mmol) was added in one portion. The resulting mixture was heated to about 80° C. for about sixteen hours, and was then partitioned between diethyl ether and water. The aqueous phase was extracted with diethyl ether four times, and the combined organic extracts were then washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting white solid was purified by column chromatography (methylene chloride to 10% methanol/methylene chloride) to afford 117 mg (45%) of the desired product. LRMS ([M+1]+): 527.1.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8]/[CH:9]=[CH:10]/[CH:11]([OH:21])[CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1.[C:22](OC(=O)C)(=[O:24])[CH3:23].N1C=CC=CC=1>CCOCC>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8]/[CH:9]=[CH:10]/[CH:11]([O:21][C:22](=[O:24])[CH3:23])[CH2:12][O:13][C:14]1[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=1
Reactant: OC(/C=C/COC1CCCCO1)COc1ccc(F)cc1
Reactant: CC(=O)OC(C)=O
Solvent: CCOCC
Solvent: c1ccncc1
Product: CC(=O)OC(/C=C/COC1CCCCO1)COc1ccc(F)cc1
Reaction time: 4 h

Procedure:
A mixture of 1-(2-tetrahydropyranyloxy)-4-hydroxy-5-(4-fluorophenoxy)-trans-2-pentene (23.6 g., 0.08 mole), acetic anhydride (9.2 g., 0.09 mole), and pyridine (7.9 g., 0.1 mole) is heated at 55°-60° for 4 hours and then at 95° for an additional 4 hours. The solution is cooled, diluted with ether and washed with ice-cold saturated sodium carbonate solution, ice water (3 ×) and brine, and dried over sodium sulfate. Removal of solvent under vacuum leaves the title compound as a residual orange oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]([OH:18])=O)[CH2:11][CH2:10]2)=[O:8])=[CH:5][CH:4]=1.[CH:21]1([CH2:24][NH:25][CH2:26][C:27]2[NH:36][C:35](=[O:37])[C:34]3[CH2:33][CH2:32][CH2:31][CH2:30][C:29]=3[N:28]=2)[CH2:23][CH2:22]1>>[CH:21]1([CH2:24][N:25]([CH2:26][C:27]2[NH:36][C:35](=[O:37])[C:34]3[CH2:33][CH2:32][CH2:31][CH2:30][C:29]=3[N:28]=2)[C:16](=[O:18])[CH2:15][N:12]2[CH2:11][CH2:10][CH:9]([C:7](=[O:8])[C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)[CH2:23][CH2:22]1
Reactant: COc1ccc(C(=O)C2CCN(CC(=O)O)CC2)cc1
Reactant: O=c1[nH]c(CNCC2CC2)nc2c1CCCC2
Product: COc1ccc(C(=O)C2CCN(CC(=O)N(Cc3nc4c(c(=O)[nH]3)CCCC4)CC3CC3)CC2)cc1
Yield: 1 %

Procedure:
The title compound (26 mg, 1% yield) was prepared following the general procedure of Example 7 from 2-(4-(4-methoxybenzoyl)piperidin-1-yl)acetic acid and 2-[(cyclopropylmethyl-amino)-methyl]-5,6,7,8-tetrahydro-3H-quinazolin-4-one. 1H NMR (400 MHz, CD3OD) δ 7.75-7.83 (m, J=9.1 Hz, 2H), 6.77-6.88 (m, J=9.1 Hz, 2H), 4.48 (s, 1H), 4.26-4.44 (m, 1H), 4.04-4.26 (m, 2H), 3.67 (s, 3H), 3.37-3.59 (m, 2H), 2.93-3.19 (m, 5H), 2.39 (t, J=5.6 Hz, 2H), 2.22 (t, J=5.8 Hz, 2H), 1.91 (br. s., 3H), 1.75-1.86 (m, 1H), 1.47-1.75 (m, 4H), 0.65-0.90 (m, 1H), 0.40 (q, J=6.1 Hz, 1H), 0.16-0.32 (m, 1H), 0.06-0.16 (m, 1H), −0.13-0.06 (m, 1H). HRMS calculated for C28H36N4O4 493.2815. found (ESI, [M+H]+), 493.2826. Retention time=3.50 min.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][CH2:12][C:13]([NH2:15])=[O:14])(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[CH3:18][Si:19]([CH3:26])([CH3:25])[CH2:20][CH2:21][O:22][CH2:23]Cl.P([O-])([O-])([O-])=O>CN(C=O)C>[I:1][C:2]1[CH:3]=[C:4]([S:8]([N:11]([CH2:23][O:22][CH2:21][CH2:20][Si:19]([CH3:26])([CH3:25])[CH3:18])[CH2:12][C:13]([NH2:15])=[O:14])(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1
Reactant: C[Si](C)(C)CCOCCl
Reactant: NC(=O)CNS(=O)(=O)c1cccc(I)c1
Agent: O=P([O-])([O-])[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C[Si](C)(C)CCOCN(CC(N)=O)S(=O)(=O)c1cccc(I)c1
Reaction time: 1.5 h

Procedure:
N2-[(3-Iodophenyl)sulfonyl]glycinamide (0.14 g) was stirred with sodium hydride (60% oil dispersion, 0.02 g) in DMF (2 ml) at 21° under nitrogen for 15 min. 2-Trimethylsilylethoxymethyl chloride (0.08 ml) was added and stirring was continued for 1.5 h. The mixture was poured into pH 6.4 phosphate buffer and the product was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4), concentrated and applied to a silica Bond Elut Cartridge (5 g) in dichloromethane containing methanol. The cartridge was eluted with dichloromethane, diethyl ether and ethyl acetate to give the title compound (0.16 g), LCMS RT=3.49 min.
Reaction SMILES: C(OC(N1CCN([CH2:14][CH2:15][NH:16][C@:17]23[CH2:51][CH2:50][C@@H:49]([C:52]([CH3:54])=[CH2:53])[C@@H:18]2[C@@H:19]2[C@@:32]([CH3:35])([CH2:33][CH2:34]3)[C@@:31]3([CH3:36])[C@@H:22]([C@:23]4([CH3:48])[C@@H:28]([CH2:29][CH2:30]3)[C:27]([CH3:38])([CH3:37])[C:26]([C:39]3[CH:47]=[CH:46][C:42]([C:43]([OH:45])=[O:44])=[CH:41][CH:40]=3)=[CH:25][CH2:24]4)[CH2:21][CH2:20]2)CC1)=O)(C)(C)C.[CH2:55]([S:57]([N:60]1[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1)(=[O:59])=[O:58])[CH3:56]>>[CH2:55]([S:57]([N:60]1[CH2:61][CH2:62][N:63]([CH2:14][CH2:15][NH:16][C@:17]23[CH2:51][CH2:50][C@@H:49]([C:52]([CH3:54])=[CH2:53])[C@@H:18]2[C@@H:19]2[C@@:32]([CH3:35])([CH2:33][CH2:34]3)[C@@:31]3([CH3:36])[C@@H:22]([C@:23]4([CH3:48])[C@@H:28]([CH2:29][CH2:30]3)[C:27]([CH3:37])([CH3:38])[C:26]([C:39]3[CH:47]=[CH:46][C:42]([C:43]([OH:45])=[O:44])=[CH:41][CH:40]=3)=[CH:25][CH2:24]4)[CH2:21][CH2:20]2)[CH2:64][CH2:65]1)(=[O:59])=[O:58])[CH3:56]
Reactant: C=C(C)[C@@H]1CC[C@]2(NCCN3CCN(C(=O)OC(C)(C)C)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Reactant: CCS(=O)(=O)N1CCNCC1
Product: C=C(C)[C@@H]1CC[C@]2(NCCN3CCN(S(=O)(=O)CC)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12

Procedure:
The title compound was prepared following the method described in above for the synthesis of 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(4-(tert-butoxycarbonyl)piperazin-1-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid using 1-(ethylsulfonyl)piperazine as the alkylating reagent in Step 3. The product was isolated as a white solid (11 mg, 53%). LCMS: m/e 734.56 (M+H)+, 2.28 min (method 11). 1H NMR (400 MHz, Acetic) δ 7.99 (d, J=8.5 Hz, 2H), 7.26 (d, J=8.3 Hz, 2H), 5.34 (d, J=4.5 Hz, 1H), 4.81 (s, 1H), 4.70 (s, 1H), 3.63-3.28 (m, 7H), 3.26-3.16 (m, 1H), 3.14-2.98 (m, 6H), 2.95-2.75 (m, 1H), 2.33-1.06 (m, 22H), 1.73 (s, 3H), 1.32 (t, J=7.4 Hz, 3H), 1.23 (s, 3H), 1.10 (s, 3H), 1.06 (s, 3H), 0.98 (s, 3H), 0.97 (s, 3H).
Reaction SMILES: Cl.[C:2]([NH2:8])(=[NH:7])[CH2:3][CH2:4][CH2:5][CH3:6].C[O-].[Na+].C([O:14][CH:15]=[C:16]([C:22](OCC)=O)[C:17]([O:19][CH2:20][CH3:21])=[O:18])C>CO>[CH2:3]([C:2]1[NH:8][C:15](=[O:14])[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:22][N:7]=1)[CH2:4][CH2:5][CH3:6]
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Reactant: CCCCC(=N)N
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CCCCc1ncc(C(=O)OCC)c(=O)[nH]1
Reaction time: 2 h

Procedure:
To a solution of 2.0 g valeramidine hydrochloride and 750 mg sodium methoxide in 50 mL methanol was added 3.2 g diethyl ethoxymethylenemalonate (Aldrich) at room temperature. After 2 hours, an additional 850 mg sodium methoxide was added and the mixture was allowed to stir overnight. Solvent was removed in vacuo and the remaining material was partitioned between saturated aqueous ammonium chloride solution and ether. The organic layer was removed and the aqueous layer was extracted twice more with ether. The combined organic material was dried over MgSO4, was stripped of solvent in vacuo, and then was Still flash chromatographed in 3% MeOH in CH2Cl2 to give the title compound as a white solid. 1H NMR (250 MHz, CDCl3) δ8.73 (s, 1H), 4.37 (4 line m, 2H), 2.77 (3 line m, 2H) 1.80 (m, 2H), 1.41 (m, 2H) 1.38 (3 line m, 3H), 0.96 (3 line m, 3H).
Reaction SMILES: Br.Br[CH:3]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5][C:4]1=O.[C:11]([NH2:16])(=[S:15])[CH:12]([CH3:14])[CH3:13]>C(O)C>[CH:12]([C:11]1[S:15][C:3]2[CH2:9][CH2:8][NH:7][CH2:6][CH2:5][C:4]=2[N:16]=1)([CH3:14])[CH3:13]
Reactant: CC(C)C(N)=S
Reactant: O=C1CCNCCC1Br
Agent: Br
Solvent: CCO
Product: CC(C)c1nc2c(s1)CCNCC2

Procedure:
0.4 g (1.47 mmol) 5-Bromo-azepan-4-one hydrobromide, 0.15 g (1.47 mmol) thioisobutyramide in 3 mL ethanol were stirred under reflux for 3 h. The reaction mixture was concentrated and to the residue DCM and a small amount of methanol were added. The precipitate was removed and the filtrate was evaporated to dryness. Yield: 0.36 g (89% of theory). ESI-MS: m/z=197 (M+H)+; Rt(HPLC): 0.79 min (Method J).
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C@H:5]1[C@H:11]2[C@H:9]([O:10]2)[CH:8]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH2:6]1.CC[O:18]C(C)=O>C1COCC1.O.OS(O)(=O)=O>[OH:18][CH:9]1[C@H:11]([OH:10])[C@H:5]([O:4][CH2:3][O:2][CH3:1])[CH2:6][C:7]([C:12]([O:14][CH3:15])=[O:13])=[CH:8]1
Reactant: CCOC(C)=O
Reactant: COCO[C@@H]1CC(C(=O)OC)=C[C@H]2O[C@H]21
Agent: O=S(=O)(O)O
Solvent: C1CCOC1
Solvent: O
Product: COCO[C@@H]1CC(C(=O)OC)=CC(O)[C@@H]1O
Temperature: 25 °C
Reaction time: 2 h
Yield: 96 %

Procedure:
To a well stirred solution of compound 14 (107 mg, 0.5 mmol) in THF/H2O (3:1), concentrated H2SO4 (5 drops) was added. The reaction was stirred for 2 h at 25° C. After the completion of reaction (monitored by TLC), the reaction mixture was diluted with excess of EtOAc 20 mL The organic layer is further washed with H2O, brine, dried over anhydrous Na2SO4. Removal of solvent under reduced pressure gave crude product which on chromatographic purification with petroleum ether/ethyl acetate (2:8 v/v) gave title compound 19 as gum.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]([C@H:6]1[CH2:10][C@@H:9]([NH2:11])[CH:8]=[CH:7]1)=[O:5].[C:12]1([C:18](Cl)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>C(Cl)Cl>[C:18]([NH:11][C@@H:9]1[CH2:10][C@H:6]([C:4]([O:3][CH3:2])=[O:5])[CH:7]=[CH:8]1)([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: COC(=O)[C@@H]1C=C[C@H](N)C1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)[C@@H]1C=C[C@H](NC(c2ccccc2)(c2ccccc2)c2ccccc2)C1
Temperature: 0 °C
Reaction time: 17 h
Yield: 105.3 %

Procedure:
Methyl-(1S,4R)-4-aminocyclopent-2-ene-1-carboxylate hydrochloride (5.50 g) was suspended in methylene chloride (60 mL), to which triphenylmethyl chloride (9.06 g, 0.0325 mol) was added. The mixture was then cooled to 0° C. Triethylamine (10.8 mL, 0.0774 mol) was then added dropwise keeping the temperature less than 10° C. Upon completion of addition, the mixture was allowed to warm to 20-25° C. The mixture was left to stir at 20-25° C. for 17 hours. The mixture was then washed with water (3×50 mL). The aqueous washes were combined and extracted with DCM (50 mL). The organics were combined and washed with brine (20 mL) and the solvent was removed under reduced pressure to afford the title compound as a brown oil (12.5 g) which was used without further purification. 1H NMR (300 MHz, CDCl3, δ): 7.58 (m, 6H), 7.27 (m, 6H), 7.18 (m, 3H), 5.57 (m, 1H), 4.93 (m, 1H), 3.76 (m, 1H), 3.65 (s, 3H), 3.18 (m, 1H), 2.11 (m, 1H), 1.90 (m, 1H) and 1.53 (m, 1H).
Reaction SMILES: C([C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[C:15](C(C)(C)C)[C:14]([OH:21])=[C:13](C(C)(C)C)[CH:12]=2)[CH:8]=[C:7](C(C)(C)C)[C:6]=1[OH:30])(C)(C)C.CS(O)(=O)=O.CCCCCCCCC(C)C>C1(C)C=CC=CC=1>[C:14]1([OH:21])[CH:13]=[CH:12][C:11]([C:9]2[CH:10]=[CH:5][C:6]([OH:30])=[CH:7][CH:8]=2)=[CH:16][CH:15]=1
Reactant: CC(C)(C)c1cc(-c2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)cc(C(C)(C)C)c1O
Agent: CCCCCCCCC(C)C
Agent: CS(=O)(=O)O
Solvent: Cc1ccccc1
Product: Oc1ccc(-c2ccc(O)cc2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.2 %

Procedure:
In a three-necked flask 50 grams of 2,2′,6,6′-tetra-t-butyl-4,4′-biphenol (I) and 0.25 gm of methanesulfonic acid were mixed with a mixture of 80 ml Isopar-G (hydrocarbons C10-C11) and 20 ml of toluene. After 2 hours at 150° C., 26 grams of isobutylene is collected in a dry ice trap and the reaction cooled to room temperature and was filtered. The biphenol was dried at 130° C., giving 22.5 gram of 4,4′-biphenol (99% yield) with purity >99% were collected.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([Br:11])[CH:10]=1)[C:5]([OH:7])=O.[NH2:12][C:13]1[C:18](O)=[CH:17][CH:16]=[CH:15][N:14]=1>>[Br:11][C:9]1[CH:8]=[C:4]([C:5]2[O:7][C:18]3[C:13]([N:12]=2)=[N:14][CH:15]=[CH:16][CH:17]=3)[CH:3]=[C:2]([Br:1])[CH:10]=1
Reactant: O=C(O)c1cc(Br)cc(Br)c1
Reactant: Nc1ncccc1O
Product: Brc1cc(Br)cc(-c2nc3ncccc3o2)c1

Procedure:
3,5-Dibromo-benzoic acid and 2-amino-pyridin-3-ol were condensed to give 2-(3,5-dibromo-phenyl)-oxazolo[4,5-b]pyridine using the conditions of Clark, R. L., et al., J. Med. Chem. 21: 1158-62 (1978). This compound was converted to N-(3-bromo-5-oxazolo[4,5-b]pyridin-2-yl-phenyl)-acetamide as described in Example 82. Conversion to N-[3-(1H-Indol-4-yl)-5-oxazolo[4,5-b]pyridin-2-yl-phenyl]-acetamide was carried out as described in Example 75. 1H NMR (400 MHz, CD3OD): δ 8.39-8.43 (m, 2H), 8.28 (d, J=1.4 Hz, 1H), 8.15 (t, J=1.7 Hz, 1H), 7.95 (dt, J=4.7, 2.7 Hz, 1H), 7.38-7.41 (m, 1H), 7.30-7.34 (m, 1H), 7.25 (d, J=3.1 Hz, 1H), 7.14-7.17 (m, 2H), 6.67 (d, J=3.1 Hz, 1H), 2.13 (s, 3H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@H:17]([C:18]([O:20]C)=[O:19])[CH2:16][C:15]2[C:10](=[CH:11][C:12]([O:22][CH3:23])=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CO.O>[C:1]([O:5][C:6]([N:8]1[C@H:17]([C:18]([OH:20])=[O:19])[CH2:16][C:15]2[C:10](=[CH:11][C:12]([O:22][CH3:23])=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(=O)[C@@H]1Cc2ccc(OC)cc2CN1C(=O)OC(C)(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COc1ccc2c(c1)CN(C(=O)OC(C)(C)C)[C@H](C(=O)O)C2
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of Methyl 2-(t-butyloxycarbonyl)-7-methoxy-1,2,3,4-tetrahydroisoquinoline-3(S)-carboxylate (0.58 g, 1.81 mmol) in MeOH:H2O 1:1 (20 mL) was added 1 N NaOH (2.7 mL, 2.72 mmol) and the resulting solution was stirred at 25° C. for 18 hr. The methanol was evaporated in vacuo and the remaining aqueous portion was acidified to pH=3 with 1 N HCl and then extracted two times with EtOAc. The organic layers were washed with saturated NaCl (30 mL) and dried (MgSO4). Filtration and evaporation in vacuo gave the title compound.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH:3]([OH:6])[CH2:2]1.[Cl:7][C:8]1[S:12][C:11]([S:13](Cl)(=[O:15])=[O:14])=[CH:10][C:9]=1[N+:17]([O-:19])=[O:18].C(N(CC)CC)C>C1COCC1>[Cl:7][C:8]1[S:12][C:11]([S:13]([N:1]2[CH2:5][CH2:4][CH:3]([OH:6])[CH2:2]2)(=[O:14])=[O:15])=[CH:10][C:9]=1[N+:17]([O-:19])=[O:18]
Reactant: O=[N+]([O-])c1cc(S(=O)(=O)Cl)sc1Cl
Reactant: OC1CCNC1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=[N+]([O-])c1cc(S(=O)(=O)N2CCC(O)C2)sc1Cl
Temperature: 25 °C
Reaction time: 17 h
Yield: 36.3 %

Procedure:
To a stirred solution of (RS)-3-pyrrolidinol (0.75 g, 8.6 mmol) in THF (18 ml) was added at room temperature 5-chloro-4-nitrothiophene-2-sulfonyl chloride (1.5 g, 5.72 mmol) and triethylamine (0.88 ml, 6.3 mmol). The light yellow suspension was stirred at room temperature for 17 h, and evaporated. The crude product was further purified by column chromatography on silica gel (ethyl acetate), and subsequent crystallization from dichloromethane/MeOH/hexane to yield (RS)-1-(5-chloro-4-nitro-thiophene-2-sulfonyl)-pyrrolidin-3-ol (0.65 g, 36%) as a yellow solid. MS (EI) 312.0 [(M)+], mp 96° C.
Reaction SMILES: OCC([C@H]([C@@H]([C@@H](CO)O)O)O)=O.OCC1(O[C@H](CO)[C@@H](O)[C@@H]1O)OC.[S:26](=[O:30])(=O)([OH:28])[OH:27].CO[CH:33](OC)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>CO>[C:34]1([CH3:33])[CH:39]=[CH:38][C:37]([S:26]([OH:28])(=[O:30])=[O:27])=[CH:36][CH:35]=1
Reactant: O=S(=O)(O)O
Reactant: COC(OC)c1ccccc1
Agent: COC1(CO)O[C@H](CO)[C@@H](O)[C@@H]1O
Agent: O=C(CO)[C@@H](O)[C@H](O)[C@H](O)CO
Solvent: CO
Product: Cc1ccc(S(=O)(=O)O)cc1

Procedure:
In step one, fructose is converted to methyl fructofuranoside by reaction in methanol using sulfuric acid as the catalyst; this reaction yields an anomeric mixture of methyl α,β-fructofuranosides. In step two, the 1- and 3-hydroxyl groups of the product of step one are protected by conversion to a benzylidene derivative. For example, reaction of the described anomeric mixture of methyl α,β-fructofuransides with benzaldehyde dimethylacetal and a proton source such as p-toluenesulfonic acid, yields methyl 1,3-O-benzylidene-α-D-fructofuranoside. In step three, the 6-hydroxy group of the product of step two is protected by conversion to a trialkylsilyl ether. For example, reaction of 1,3-O-benzylidene-α-D-fructofuranoside with t-butyldimethylsilyl chloride and imidazole yields the t-butyldimethylsilyl ether derivative methyl 1,3-O-benzylidene-6-O-t-butyldimethylsilyl-α-D-fructofuranoside. In step four, the 4-hydroxy group of the product of step three is replaced with a hydrogen atom. For example, reaction of 1,3-O-benzylidene-6-O-t-butyldimethylsilyl-α-D-fructofuranoside with thiocarbonyldiimidazole affords an intermediate which is then reacted with tri-n-butyl tin hydride and azo(bis)isobutyronitrile (AIBN) to yield the deoxy derivative, methyl 1,3-O-benzylidene-6-O-t-butyl-dimethylsilyl-4-deoxy-α-D-fructofuranoside. In step five, the trialkylsilyl group is removed from the 6-O-trialkysilyl ether of the product of step four, and the resulting 6-hydroxy group is esterified. For example, reaction of methyl 1,3-O-benzylidene-6-O-t-butyl-dimethylsilyl-4-deoxy-α-D-fructofuranoside with tetrabutylammonium fluoride affords the 6-hydroxy derivative, methyl 1,3-O-benzylidene-4-deoxy-α-D-fructofuranoside which is then reacted with benzoyl chloride to give the O-ester derivative, methyl 6-O-benzoyl-1,3-O-benzylidene-4-deoxy-α-D-fructofuranoside. Compounds of Formula II, which serve as intermediates to compounds of Formula I (when A is H), are produced in step six in which the 1,3-O-benzylidene group is removed giving a derivative with 1,3-dihydroxy groups. For example, reaction of 6-O-benzoyl-1,3-O-benzylidene-4-deoxy-α-D-fructofuranoside in an acidic medium such as an alcohol containing p-toluenesulfonic acid yields the methyl 6-O-benzoyl-4-deoxy-α,β-D-fructofuranoside. The α anomer, methyl 6-O-benzoyl-4-deoxy-α-D-fructofuranoside, and β anomer, methyl 6-O-benzoyl-4-deoxy-β-D-fructofuranoside, of the anomeric mixture obtained in step six may then be separated from each other and isolated in anomerically pure form by chromatography.
Reaction SMILES: [OH:1][C:2]1[NH:7][C:6](=[O:8])[N:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:4](=[O:16])[C:3]=1[C:17]([NH:19][CH2:20][C:21]([O:23]CC)=[O:22])=[O:18].[CH3:26][O:27][C:28]1[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=1)[CH2:31]Br.C(=O)([O-])[O-].[Na+].[Na+].Cl>CN(C)C=O>[OH:1][C:2]1[N:7]([CH2:31][C:30]2[CH:33]=[CH:34][CH:35]=[C:28]([O:27][CH3:26])[CH:29]=2)[C:6](=[O:8])[N:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:4](=[O:16])[C:3]=1[C:17]([NH:19][CH2:20][C:21]([OH:23])=[O:22])=[O:18]
Reactant: CCOC(=O)CNC(=O)c1c(O)[nH]c(=O)n(Cc2ccccc2)c1=O
Reactant: COc1cccc(CBr)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cccc(Cn2c(O)c(C(=O)NCC(=O)O)c(=O)n(Cc3ccccc3)c2=O)c1
Temperature: 100 °C
Reaction time: 2.5 h
Yield: 10.7 %

Procedure:
A mixture of ethyl N-{[6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycinate (example 11a, 369 mg, 1.06 mmoles), 3-methoxybenzyl bromide (163 uL, 1.17 mmoles) and sodium carbonate (330 mg, 3.1 mmoles) in dimethylformamide (6.0 mL) was stirred under argon at 100° C. for 2.5 hours. The mixture was cooled, poured into 1 molar hydrochloric acid and extracted with ethyl acetate (×2). The ester was hydrolysed by stirring in a mixture of ethanol (3 mL) and 1 molar sodium hydroxide solution (3 mL) for 3 hours. The mixture was acidified and extracted with ethyl acetate. Purification by preparative HPLC (acetonitrile-water-0.1% TFA, 20-100%) and crystallization from ethanol-water gave the title compound (50 mg, 11%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.10 (br. s., 1 H), 10.12 (t, 1 H), 7.14-7.47 (m, 6 H), 6.69-6.97 (m, 3 H), 5.00 (s, 2 H), 5.03 (s, 2 H), 4.13 (d, J=5.56 Hz, 2 H), 3.71 (s, 3 H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:9]([CH3:13])[C:10](Cl)=[S:11])[CH:6]=[CH:7][CH:8]=1.[CH:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][C:15]=1[OH:24].C(=O)([O-])[O-].[K+].[K+].C(C(C)=O)C>O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:9]([CH3:13])[C:10](=[S:11])[O:24][C:15]2[CH:16]=[CH:17][C:18]3[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:14]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: COc1cccc(N(C)C(=S)Cl)c1
Reactant: Oc1ccc2ccccc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCC(C)=O
Product: COc1cccc(N(C)C(=S)Oc2ccc3ccccc3c2)c1
Temperature: 25 °C
Yield: 48.4 %

Procedure:
2.00 g of N-(3-methoxyphenyl)-N-methylthiocarbamoyl chloride, 1.44 g of β-naphthol and 1.66 g of anhydrous potassium carbonate were added to 50 ml of methyl ethyl ketone and heated to reflux for 15 hours. The reaction mixture was poured into water after it was cooled to room temperature and the products were extracted with benzene. The benzene solution was subsequently washed with water and aqueous saturated sodium chloride solution and then benzene was removed by distillation under reduced pressure after drying over anhydrous Magnesium sulfate. The residue was purified by the column chromatography (eluted with benzene on a silica gel) to give 1.45 g of O-2-naphthyl N-(3-methoxyphenyl)-N-methylthiocarbamate in crystalls (Yield: 45%). A part of the crystals was recrystallized from ethanol. Colorless crystalls having melting point of 93° to 94° C. were obtained.