Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)=[CH:9][CH2:10][CH2:11][CH2:12][C:13]([O:15]C)=[O:14])=[CH:4][CH:3]=1.[CH3:23][C:24]1[CH:29]=[CH:28][C:27]([S:30](Cl)(=[O:32])=[O:31])=[CH:26][CH:25]=1.C(N(CC)CC)C>C(Cl)Cl>[CH3:23][C:24]1[CH:29]=[CH:28][C:27]([S:30]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[CH:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[CH:4][CH:3]=2)(=[O:32])=[O:31])=[CH:26][CH:25]=1
Reactant: COC(=O)CCCC=C(c1ccc(N)cc1)c1cccnc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)Nc2ccc(C(=CCCCC(=O)O)c3cccnc3)cc2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of 3 g of methyl 6-(4-aminophenyl)-6-(3-pyridyl)-hex-5-enoate, 1.9 g of 4-methylbenzene-sulphonic acid chloride and 5 ml of triethylamine in 100 ml of methylene chloride is stirred for one hour at ambient temperature. The organic phase is washed with water, evaporated down and the residue is purified pyer a silica gel column with ethyl acetate. The product fraction is evaporated down and heated in a mixture of 50 ml of ethanol and 3 ml of 10N sodium hydroxide solution to 50° C. for one hour. The reaction mixture is diluted with water and neutralised by the addition of citric acid. The agueous phase is extracted with ethyl acetate, dried and evaporated down. The residue is recrystallised from ethyl acetate/diisopropylether.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][NH2:10])=[CH:5][CH:4]=1.N1C=CC=CC=1.[C:17](Cl)(=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19]>O>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]([C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])[NH2:10])=[CH:5][CH:4]=1
Reactant: CC(C)(C)C(=O)Cl
Reactant: NNc1ccc(Cl)cc1
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: CC(C)(C)C(=O)N(N)c1ccc(Cl)cc1
Temperature: 0 °C
Reaction time: 64 h

Procedure:
A quantity (25.0 g.; 0.14 mole) of (4-chlorophenyl)-hydrazine hydrochloride was suspended in 150 ml. of pyridine. The suspension was cooled to 0° C. and 16.9 g. (0.14 mole) of pivaloyl chloride was added with stirring. The reaction mixture was set aside at about 25° C. for 64 hrs. when 300 ml. of water was added. The precipitate that formed was collected on a filter and washed repeatedly with water, 1 N hydrochloric acid, and finally with water. The filter cake was dried under reduced pressure and 60° C. to remove water. After two recrystallizations from benzene and technical hexane there was thus obtained 24.1 g. of pivalic acid (4-chlorophenyl)hydrazide having a melting point of 137° to 138° C.
Reaction SMILES: C([BH3-])#N.[CH3:4][C:5]1([N:11]2[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]2)[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.[NH2:18][C:19]1[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][C:20]=1[OH:29].C(O)(=O)C>C(Cl)Cl>[CH3:4][C:5]1([N:11]2[CH2:16][CH2:15][CH:14]([NH:18][C:19]3[CH:24]=[C:23]([C:25]([F:26])([F:27])[F:28])[CH:22]=[CH:21][C:20]=3[OH:29])[CH2:13][CH2:12]2)[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1
Reactant: CC1(N2CCC(=O)CC2)CCOCC1
Reactant: Nc1cc(C(F)(F)F)ccc1O
Agent: [BH3-]C#N
Solvent: ClCCl
Solvent: CC(=O)O
Product: CC1(N2CCC(Nc3cc(C(F)(F)F)ccc3O)CC2)CCOCC1
Temperature: 100 °C
Yield: 59.1 %

Procedure:
Polymer supported cyanoborohydride (191 mg, 0.82 mmol) was added to a solution of 1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinone (D12, 87 mg, 0.44 mmol), 2-amino-4-(trifluoromethyl)phenol (D7, 74 mg, 0.42 mmol, 4.3 mmol/g) and acetic acid (0.12 mL, 2.09 mmol) in DCM (2.5 mL). The mixture was heated by microwave at 100° C. for 10 min before being filtered and concentrated by rotary evaporation to give a yellow oil, which was purified via flash column chromatography (silica, DCM to 0.5% NH3/9.5% MeOH/90% DCM) to give 2-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]amino}-4-(trifluoromethyl)phenol (D14, 89 mg, 60%) as an off-white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[C:3]=1[OH:15].[C:16](N1C=CN=C1)(N1C=CN=C1)=[O:17]>O1CCCC1>[O:10]1[CH2:11][CH2:12][CH2:13][CH2:14][CH:9]1[O:8][C:4]1[C:3]2[O:15][C:16](=[O:17])[NH:1][C:2]=2[CH:7]=[CH:6][CH:5]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: Nc1cccc(OC2CCCCO2)c1O
Solvent: C1CCOC1
Product: O=c1[nH]c2cccc(OC3CCCCO3)c2o1
Yield: 87.2 %

Procedure:
To a solution of 2-amino-6-(tetrahydropyran-2-yloxy)phenol (2.0 g) in anhydrous tetrahydrofuran (30 ml) was added 1,1′-carbonyldiimidazole (2.03 g), and the mixture was refluxed for 2 hours under nitrogen atmosphere. After cooling, the reaction mixture was concentrated in vacuo. The residue was purified by flash chromatography (chloroform:methanol=40:1, v/v) and crystallized with diisopropyl ether to give 7-(tetrahydropyran-2-yloxy)-2(3H)-benzoxazolone (1.96 g).
Reaction SMILES: C1([NH2+]C2CCCCC2)CCCCC1.[C:14]([NH:24][C@H:25]([C:35]([O-:37])=[O:36])[CH2:26][CH:27]([C:31]([CH3:34])([CH3:33])[CH3:32])[C:28]([O-:30])=[O:29])([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15].C1([NH2+]C2CCCCC2)CCCCC1.C(Cl)(Cl)Cl.[CH3:55][N:56]([CH2:58][CH2:59]Cl)[CH3:57]>O1CCOCC1>[CH3:55][N:56]([CH3:57])[CH:58]([O:36][C:35](=[O:37])[C@H:25]([CH2:26][CH:27]([C:31]([CH3:32])([CH3:33])[CH3:34])[C:28]([OH:30])=[O:29])[NH:24][C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[CH3:59]
Reactant: CC(C)(C)C(C[C@H](NC(=O)OCc1ccccc1)C(=O)[O-])C(=O)[O-]
Reactant: CN(C)CCCl
Agent: C1CCC([NH2+]C2CCCCC2)CC1
Solvent: C1COCCO1
Solvent: ClC(Cl)Cl
Product: CC(OC(=O)[C@H](CC(C(=O)O)C(C)(C)C)NC(=O)OCc1ccccc1)N(C)C
Temperature: 70 °C
Yield: 88.4 %

Procedure:
To 1.10 g N-carbobenzyloxy-γ-tert.butyl-L-glutamic acid-dicyclohexyl ammonium salt, 1.8 ml chloroform and 1.9 ml solution of dimethylaminoethylchloride in the amount of 0.46 g, which stoichiometrically corresponds to two times molar volume, in dioxane were added to be subjected to reflux in oil bath at 70° C. for 30 hrs. After cooling down to a room temperature, said reaction mixture was similarly treated as in Step Example 1 to obtain N-carbobenzyloxy-γ-tert.butyl-L-glutamic acid-α-dimethylaminoethyl ester in the amount of 766 mg (yield; 88.4%).
Reaction SMILES: C(O[CH:4]=[C:5]([C:11](=[O:22])[C:12]1[CH:17]=[C:16]([F:18])[C:15]([F:19])=[C:14]([Cl:20])[C:13]=1F)[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.ClC1C(F)=C(C=C(F)C=1F)C(CC(OCC)=O)=O.[NH2:41][C:42]1[C:47]([F:48])=[CH:46][C:45]([Cl:49])=[C:44]([NH:50][CH2:51][C:52]2[CH:57]=[CH:56][C:55]([O:58][CH3:59])=[CH:54][CH:53]=2)[N:43]=1>C(Cl)(Cl)Cl>[Cl:20][C:14]1[C:15]([F:19])=[C:16]([F:18])[CH:17]=[C:12]2[C:13]=1[N:41]([C:42]1[C:47]([F:48])=[CH:46][C:45]([Cl:49])=[C:44]([NH:50][CH2:51][C:52]3[CH:57]=[CH:56][C:55]([O:58][CH3:59])=[CH:54][CH:53]=3)[N:43]=1)[CH:4]=[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[C:11]2=[O:22]
Reactant: CCOC=C(C(=O)OCC)C(=O)c1cc(F)c(F)c(Cl)c1F
Reactant: COc1ccc(CNc2nc(N)c(F)cc2Cl)cc1
Agent: CCOC(=O)CC(=O)c1cc(F)c(F)c(Cl)c1F
Solvent: ClC(Cl)Cl
Product: CCOC(=O)c1cn(-c2nc(NCc3ccc(OC)cc3)c(Cl)cc2F)c2c(Cl)c(F)c(F)cc2c1=O
Temperature: 90 °C
Reaction time: 0.33 h

Procedure:
To 2 ml chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 0.56 g of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added 0.66 g of 2-amino-5-chloro-3-fluoro-6-(p-methoxybenzylamino)pyridine. The solution was concentrated under reduced pressure. To the residue were added 0.5 g of anhydrous potassium carbonate and 1.5 ml of N,N-dimethylformamide, and the mixture was stirred at 90° C. for 20 minutes and allowed to cool. The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water, and the chloroform layer was washed with 300 ml of distilled water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The solution was allowed to stand after adding 4 ml of ethanol. The precipitate was collected by filtration, washed with ethanol and diisopropylether successively to obtain 0.56 g of the title compound as a pale yellow powder.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[O:11]=[CH:12][C:13]1[CH:21]=[CH:20][CH:19]=[C:16]([O:17][CH3:18])[C:14]=1[OH:15].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:18][O:17][C:16]1[C:14]([O:15][C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)=[C:13]([CH:21]=[CH:20][CH:19]=1)[CH:12]=[O:11]
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: COc1cccc(C=O)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1cccc(C=O)c1Oc1ccc([N+](=O)[O-])cc1
Temperature: 100 °C
Yield: 71 %

Procedure:
A mixture of 14.10 g (0.10 mole) of 4-fluoronitrobenzene, 16.40 g (0.10 mole) of o-vanillin, 30 g of powdered potassium carbonate, and 40 mL of DMF is heated with stirring to the boiling point. After 10 minutes the mixture is cooled to 100° C. and 300 mL of ice water is added. Petroleum ether (200 mL) is added and the entire mixture is filtered and the cake is washed with 200 mL of water and then 200 mL of petroleum ether. The damp cake is slurried in 100 mL of methanol and filtered; wt 19.50 g (71% yield); mp 130°-131° C.; mass spectrum (DEI), 273 (M+).
Reaction SMILES: B(F)(F)F.CCOCC.[C:10]([NH:20][CH:21]([C:23]([OH:25])=[O:24])[CH3:22])([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11].CO[CH:28](OC)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C(OCC)C>[CH3:22][CH:21]1[C:23](=[O:25])[O:24][CH:28]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:20]1[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11]
Reactant: CC(NC(=O)OCc1ccccc1)C(=O)O
Reactant: COC(OC)c1ccccc1
Agent: FB(F)F
Solvent: CCOCC
Product: CC1C(=O)OC(c2ccccc2)N1C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 96 h

Procedure:
Boron trifluoride diethyl etherate (12.56 mL, 100 mmol) was added to a −78° C. solution of N-carbobenzoxy-dl-alanine (4.47 g, 20 mmol) and benzaldehyde dimethyl acetal (2.97 mL, 19.8 mmol) in diethyl ether (100 mL). After stirring at ambient temperature for 4 days, the reaction mixture was recooled to 0° C., quenched with saturated aqueous sodium bicarbonate and extracted with diethyl ether. The combined organic extracts were dried (sodium sulfate) and concentrated in vacuo. Chromatography over silica eluting with 5-45% ethyl acetate/hexane afforded benzyl 4-methyl-5-oxo-2-phenyl-1,3-oxazolidine-3-carboxylate.
Reaction SMILES: O[C@@H:2]1[C:19]2[C@:14]([CH3:21])([CH2:15][CH2:16][C:17](=[O:20])[CH:18]=2)[C@@H:13]2[C@H:4]([C@H:5]3[C@@:9]([CH2:11][CH2:12]2)([CH3:10])[C:8](=[O:22])[CH2:7][CH2:6]3)[C@@H:3]1O.CS(Cl)(=O)=O.CS(O[C@@H]1C2[C@](C)(CCC(=O)C=2)[C@@H]2[C@H]([C@H]3[C@@](CC2)(C)C(=O)CC3)[C@@H]1OS(C)(=O)=O)(=O)=O.[N-:60]=[N+:61]=[N-:62].[Na+]>N1C=CC=CC=1.CN(C)C=O>[N:60]([C:2]1[C:19]2[C@:14]([CH3:21])([CH2:15][CH2:16][C:17](=[O:20])[CH:18]=2)[C@@H:13]2[C@H:4]([C@H:5]3[C@@:9]([CH2:11][CH2:12]2)([CH3:10])[C:8](=[O:22])[CH2:7][CH2:6]3)[CH:3]=1)=[N+:61]=[N-:62]
Reactant: [N-]=[N+]=[N-]
Reactant: C[C@]12CCC(=O)C=C1[C@@H](O)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Agent: CS(=O)(=O)Cl
Agent: C[C@]12CCC(=O)C=C1[C@@H](OS(C)(=O)=O)[C@@H](OS(C)(=O)=O)[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Agent: [Na+]
Solvent: c1ccncc1
Solvent: CN(C)C=O
Product: C[C@]12CCC(=O)C=C1C(N=[N+]=[N-])=C[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12

Procedure:
Conversion of 6α,7α-dihydroxy-4-androstene-3,17-dione to the corresponding 6α,7α-dimethanesulfonate ester by treatment with methanesulfonyl chloride in pyridine in a manner similar to that described in Example 22B followed by treatment of the resulting 6α,7α-dimethanesulfonyloxy-4-androstene-3,17-dione with sodium azide in dimethylformamide in a manner similar to that described in above Example 22C does not yield an identifiable amount of 6-azido-4,6-androstadiene-3,17-dione. Similarly, treatment of 6α,7α-dimethanesulfonyloxy-4-androstene-3,17-dione with sodium azide in aqueous methanol in the presence of acetic acid in a manner similar to that described in Example 6, does not yield an identifiable quantity of 6-azido-4,6-androstadiene-3,17-dione.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[N:9]=[C:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:7]=[CH:6][CH:5]=1.[CH3:18]I>CN(C)C=O.O>[Br:3][C:4]1[N:9]=[C:8]([N:10]([CH3:18])[C:11](=[O:17])[O:12][C:13]([CH3:14])([CH3:16])[CH3:15])[CH:7]=[CH:6][CH:5]=1
Reactant: CI
Reactant: CC(C)(C)OC(=O)Nc1cccc(Br)n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CN(C(=O)OC(C)(C)C)c1cccc(Br)n1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
6.9 g (17.2 mmol) of 60% sodium hydride in oil are added portionwise to a solution of 39 g (14.3 mmol) of tert-butyl (6-bromopyrid-2-yl)carbamate in 400 ml of dimethylformamide. After stirring for 20 minutes at room temperature, 17.8 ml (28.6 mmol) of methyl iodide are added dropwise. The reaction medium is stirred at room temperature for 18 hours, taken up in water and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, filtered and evaporated.
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[C:19]([C:20]([F:23])([F:22])[F:21])=[N:18][N:17]=[N:16]2)=[CH:11][CH:10]=1)C1C=CC=CC=1>C(O)C.O1CCCC1.[C].[Pd]>[F:23][C:20]([F:21])([F:22])[C:19]1[N:15]([C:12]2[CH:11]=[CH:10][C:9]([OH:8])=[CH:14][CH:13]=2)[N:16]=[N:17][N:18]=1
Reactant: FC(F)(F)c1nnnn1-c1ccc(OCc2ccccc2)cc1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: Oc1ccc(-n2nnnc2C(F)(F)F)cc1
Reaction time: 2 h
Yield: 99.8 %

Procedure:
A solution of 1-(4-benzyloxy-phenyl)-5-trifluoromethyl-1H-tetrazole (45.3 mmol) in ethanol (100 ml) and tetrahydrofuran (100 ml) was hydrogenated at room temperature and atmospheric pressure over 10% palladium-carbon catalyst (6 g). After 2 h, the mixture was filtered and the filtrate was evaporated to give the title compound (10.4 g) as a cream solid.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[OH:6][CH2:7][CH2:8][C@@H:9]1[C@@H:13]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[C@H:12]([O:22][CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[CH2:11][C@@H:10]1[OH:29].CCN(CC)CC.C([O-])(O)=O.[Na+]>ClCCl>[CH3:1][S:2]([O:6][CH2:7][CH2:8][C@H:9]1[C@@H:10]([O:29][S:2]([CH3:1])(=[O:4])=[O:3])[CH2:11][C@@H:12]([O:22][CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[C@@H:13]1[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])(=[O:4])=[O:3]
Reactant: CCCCCCCC[C@@H]1[C@@H](CCO)[C@@H](O)C[C@H]1OC1CCCCO1
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCCC[C@@H]1[C@@H](CCOS(C)(=O)=O)[C@@H](OS(C)(=O)=O)C[C@H]1OC1CCCCO1
Temperature: 25 °C
Yield: 49.9 %

Procedure:
MsCl (0.60 mL, 7.72 mmol) was added to an ice cold solution of 6-1 (447 mg, 1.31 mmol) and Et3N (1.3 mL, 9.33 mmol) in dichloromethane (5 mL). The reaction was allowed to warm to room temperature and after 3 h, saturated NaHCO3 solution was added. The resulting mixture was extracted with dichloromethane (3×) and the combined dichloromethane solution was dried (Na2SO4), filtered and evaporated. Purification of the residue by flash chromatography on silica gel (Combiflash unit by Isco) gave the title compound (326 mg, 50%).
Reaction SMILES: Br[C:2]1[C:3]2[N:4]([N:8]=[C:9]([NH2:11])[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[CH:12]([S:15]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)(=[O:17])=[O:16])([CH3:14])[CH3:13]>>[CH3:14][CH:12]([S:15]([C:18]1[CH:23]=[CH:22][C:21]([C:2]2[C:3]3[N:4]([N:8]=[C:9]([NH2:11])[N:10]=3)[CH:5]=[CH:6][CH:7]=2)=[CH:20][CH:19]=1)(=[O:16])=[O:17])[CH3:13]
Reactant: CC(C)S(=O)(=O)c1ccc(B(O)O)cc1
Reactant: Nc1nc2c(Br)cccn2n1
Product: CC(C)S(=O)(=O)c1ccc(-c2cccn3nc(N)nc23)cc1

Procedure:
8-[4-(Propane-2-sulfonyl)-phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine was prepared from 8-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (500.0 mg, 2.347 mmol) and 4-isopropylsulfonylbenzeneboronic acid (650.0 mg, 2.850 mmol) in a manner analogous to Step 2c. The reaction product was isolated as an off-white solid (0.317 g, 42%). MP=175-177° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.64 (d, J=6.6 Hz, 1H), 8.39 (d, J=7.4 Hz, 2H), 7.96 (d, J=7.5 Hz, 2H), 7.85 (d, J=7.4 Hz, 1H), 7.06-7.00 (m, 1H), 6.21 (br s, 2H), 3.54-3.42 (m, 1H), 1.19 (d, J=6.5 Hz, 6H). MS=317 (MH)+.
Reaction SMILES: [C:1]([Si:5]([CH3:11])([CH3:10])[O:6][CH2:7][C:8]#[CH:9])([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.[O:17]=[C:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1>C1COCC1>[Si:5]([O:6][CH2:7][C:8]#[C:9][C:18]1([OH:17])[CH2:19][CH2:20][N:21]([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:22][CH2:23]1)([C:1]([CH3:3])([CH3:4])[CH3:2])([CH3:10])[CH3:11]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: C#CCO[Si](C)(C)C(C)(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(O)(C#CCO[Si](C)(C)C(C)(C)C)CC1
Temperature: -78 °C
Reaction time: 1 h
Yield: 121 %

Procedure:
To a solution of tert-butyldimethyl(prop-2-yn-1-yloxy)silane (0.5 mL, 2.46 mmol) in 30 mL of anhydrous THF was added dropwise n-BuLi (1.2 mL, 2.95 mmol) at −78° C. under N2. After stirring for 1 h at −78° C., tert-butyl 4-oxopiperidine-1-carboxylate (588.4 mg, 2.95 mmol) in THF (2 mL) was added dropwise to the above solution at −78° C. under N2. The resulting mixture was stirred at −78° C. under N2 for 2 h, then allowed to warm to r.t. and stirred for another 1.5 h. The reaction mixture was cooled to −78° C. and quenched by sat. NH4Cl aq., and the resulting mixture was extracted with EtOAc (50 mL, 30 mL). The combined organic phase was washed with brine, dried over anhy. Na2SO4 and concentrated in vacuo to afford 1.10 g of title compound. LC-MS: m/z 370.7 (M+H)+. 1H NMR (CHLOROFORM-d) δ: 4.37 (s, 2H), 3.74 (d, J=6.2 Hz, 2H), 3.35-3.24 (m, 2H), 2.46 (t, J=6.2 Hz, 1H), 1.92-1.84 (m, 2H), 1.71 (ddd, J=12.9, 9.1, 3.8 Hz, 2H), 1.47 (s, 9H), 0.92 (s, 9H), 0.13 (s, 6H).
Reaction SMILES: Cl.[CH2:2]([NH:18][C:19]1[CH:27]=[CH:26][C:22]([C:23](Cl)=[O:24])=[CH:21][CH:20]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17].[NH2:28][C:29]([NH2:31])=[O:30].[Na].CC(C)=O>C(Cl)Cl>[CH2:2]([NH:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([NH:28][C:29]([NH2:31])=[O:30])=[O:24])=[CH:21][CH:20]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: NC(N)=O
Reactant: CCCCCCCCCCCCCCCCNc1ccc(C(=O)Cl)cc1
Agent: Cl
Agent: [Na]
Solvent: CC(C)=O
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCCNc1ccc(C(=O)NC(N)=O)cc1

Procedure:
The 12.6 g. of 4-(hexadecylamino)benzoyl chloride hydrochloride in methylene chloride is added to 5 g. of sodium urea in 30 ml. of acetone and the mixture is stirred at 20° C. for 18 hours. Dilute alkali is added and the solid washed with alkaline aqueous acetone. Recrystallization from ethanol gives pure white crystals of product.
Reaction SMILES: [CH:1]1([Mg]Br)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:9](OCC)(=[O:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11]>CCOCC.C1COCC1>[CH:1]1([C:9](=[O:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Br[Mg]C1CCCCC1
Reactant: CCOC(=O)C(=O)OCC
Solvent: C1CCOC1
Solvent: CCOCC
Product: CCOC(=O)C(=O)C1CCCCC1
Temperature: 0 °C
Yield: 86 %

Procedure:
Cyclohexyl magnesium bromide (Aldrich) in ether (2 M, 150 mL) was pumped under vacuum to remove ethyl ether, at rt, the residue obtained was then dissolved in anhydrous THF (100 mL) while cooled with an ice water bath. The solution was then added to a solution of diethyl oxalate (60 g) in THF (150 mL) at -30--40° C. in 10 min. The reaction mixture was warmed to 0° C. for 5 min, and quenched with 10% HCl (100 mL), extracted with ethyl acetate (200 mL), the extract was washed with water (30 mL), brine (50 mL) and dried with sodium sulfate, then filtered. The filtrate was concentrated to give an oil. It was distilled 40-50° C. at 1 mm Hg to remove the starting material and the left over is the product (total of 46 g, 86% yield, purity>90%, it can be distilled at 1 mm Hg, 75-80° C.): 1H NMR δ 1.20-1.40 (m, 8H), 1.62-1.94 (m, 5H), 3.02 (broad s, 1H), 4.30 (q, J=8 Hz, 2H). 13C-NMR δ 13.91, 25.11, 25.58, 27.36, 46.13, 62.07, 161.84, 197.51.
Reaction SMILES: [P:1]([O:5][C@H:6]1[O:14][C@H:13]([CH2:15][OH:16])[C@@H:11]([OH:12])[C@H:9]([OH:10])[C@H:7]1[OH:8])([O-:4])([O-:3])=[O:2].[Na+].[Na+].O>C(O)C>[P:1]([O:5][C@H:6]1[O:14][C@H:13]([CH2:15][OH:16])[C@@H:11]([OH:12])[C@H:9]([OH:10])[C@H:7]1[OH:8])([OH:4])([OH:3])=[O:2]
Reactant: O=P([O-])([O-])O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: O=P(O)(O)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Temperature: 25 °C
Reaction time: 2160 h

Procedure:
A 3.76-gram portion of disodium α-D-glucose-1-phosphate was dissolved in 33.3 ml of a 0.3 M solution of cis-[Pt(NH3)2 -(H2O)2 ](NO3)2. The resulting solution had an initial pH of 5.2. The solution was stoppered with a porous plug and then stirred for 90 days at room temperature, turning deep blue in color. During that period, water was periodically added to maintain the solution volume at 40 ml. At the end of the three month period, 60 ml of ethanol were added to the solution and a dark blue material was precipitated by placing the mixture in a freezer overnight. The supernatant was decanted, and the precipitate was washed with 70% ethanol, and then it was redissolved in 40 ml of water. The solution was filtered; and the blue material was reprecipitated by the addition of 50 ml ethanol to the solution. After overnight storage in a freezer, additional decanting, washing, and drying by the procedures described in Example 1, there were obtained 2.548 grams of the above-identified complex as a dark blue solid.
Reaction SMILES: [Cl:1][CH2:2][C:3]([NH:5][C:6]([O:8][CH:9]1[CH2:14][CH2:13][C:12]([CH2:16][S:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)([OH:15])[CH:11]([C:24]2([CH3:32])[O:31][CH:25]2[CH2:26][CH:27]=[C:28]([CH3:30])[CH3:29])[CH:10]1[O:33][CH3:34])=[O:7])=[O:4].ClC1C=CC=C(C(OO)=[O:43])C=1>ClCCl.C(OCC)(=O)C>[Cl:1][CH2:2][C:3]([NH:5][C:6]([O:8][CH:9]1[CH2:14][CH2:13][C:12]([CH2:16][S:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:43])([OH:15])[CH:11]([C:24]2([CH3:32])[O:31][CH:25]2[CH2:26][CH:27]=[C:28]([CH3:29])[CH3:30])[CH:10]1[O:33][CH3:34])=[O:7])=[O:4]
Reactant: COC1C(OC(=O)NC(=O)CCl)CCC(O)(CSc2ccccc2)C1C1(C)OC1CC=C(C)C
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: COC1C(OC(=O)NC(=O)CCl)CCC(O)(CS(=O)c2ccccc2)C1C1(C)OC1CC=C(C)C
Yield: 84.8 %

Procedure:
In dichloromethane (2 ml) was dissolved 4-O-(chloroacetylcarbamoyl)-2-(1,2-epoxy-1,5-dimethyl-4-h-exenyl)-3-methoxy-1-phenylthiomethyl-1,4-cyclohexanediol (200 mg). To the solution was added, under ice-cooling, m-chloroperbenzoic acid (80.9 mg), and the mixture was stirred for 30 minutes. The reaction mixture was diluted with ethyl acetate (70 ml), which was washed with a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous saline solution, followed by drying over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was then purified by means of a silica gel column chromatography (carrier 10 g, developing solvent: ethyl acetate - hexane=1:2) to afford 4-O-(chloroacetylcarbamoyl)-2-(1,2-epoxy-1,5-dimethyl-4-hexenyl)-3-methoxy-1-phenylsulfinylmethyl-1,4-cyclohexanediol (175 mg: yield 85%) as colorless powder.