Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([O:4][C:5]([C:7]1[CH:8]([CH3:28])[CH2:9][N:10]2[C:14](=[CH:15][C:16]([O:18]C3C=CC([N+]([O-])=O)=CC=3)=O)[CH2:13][S:12][C:11]=12)=[O:6])([CH3:3])[CH3:2].[CH3:29][NH:30][CH3:31]>O>[CH3:29][N:30]([CH3:31])[C:16](=[O:18])[CH:15]=[C:14]1[CH2:13][S:12][C:11]2=[C:7]([C:5]([O:4][CH:1]([CH3:2])[CH3:3])=[O:6])[CH:8]([CH3:28])[CH2:9][N:10]12
Reactant: CC(C)OC(=O)C1=C2SCC(=CC(=O)Oc3ccc([N+](=O)[O-])cc3)N2CC1C
Reactant: CNC
Solvent: O
Product: CC(C)OC(=O)C1=C2SCC(=CC(=O)N(C)C)N2CC1C
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To 1.50 g of 4-nitrophenyl (7-isopropoxycarbonyl-6-methyl-2,3,5,6-tetrahydropyrrolo[2,1-b]thiazol-3-ylidene)acetate, was added 40 ml of a 25% aqueous solution of dimethylamine and the mixture was stirred at room temperature for 3 days. 40 ml of water was added thereto and the precipitate thus formed was collected by filtration, washed with water and dissolved in chloroform. After drying and distilling off the solvent, the crude crystals thus obtained were recrystallized from a solvent mixture of ether and n-hexane. Thus 0.6 g of the title compound was obtained.
Reaction SMILES: [H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Br[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:23]([C:28]#[N:29])=[CH:24][CH:25]=[CH:26][CH:27]=2)=[CH:18][CH:17]=1>O1CCCC1>[C:28]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[C:19]1[CH:18]=[CH:17][C:16]([CH2:15][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10])=[CH:21][CH:20]=1)#[N:29]
Reactant: N#Cc1ccccc1-c1ccc(CBr)cc1
Reactant: CCOC(=O)CC(=O)OCC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)C(Cc1ccc(-c2ccccc2C#N)cc1)C(=O)OCC
Yield: 95 %

Procedure:
To a mixture of sodium hydride (2.86 g) and tetrahydrofuran (250 mL) were added a solution of diethyl malonate (16.7 mL) in tetrahydrofuran (100 mL) and then 4′-(bromomethyl)biphenyl-2-carbonitrile (15 g), and the mixture was stirred at room temperature for 16 hr. The reaction mixture was concentrated under reduced pressure, and the obtained residue was extracted with 5% aqueous potassium hydrogen sulfate solution and ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a colorless oil (18.3 g, 95%).
Reaction SMILES: [Cl:1][S:2]([OH:5])(=O)=[O:3].[F:6][C:7]([F:21])([F:20])[C:8]([N:10]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:12][CH:11]1[CH3:19])=[O:9]>>[F:21][C:7]([F:6])([F:20])[C:8]([N:10]1[C:18]2[C:13](=[CH:14][C:15]([S:2]([Cl:1])(=[O:5])=[O:3])=[CH:16][CH:17]=2)[CH2:12][CH:11]1[CH3:19])=[O:9]
Reactant: O=S(=O)(O)Cl
Reactant: CC1Cc2ccccc2N1C(=O)C(F)(F)F
Product: CC1Cc2cc(S(=O)(=O)Cl)ccc2N1C(=O)C(F)(F)F
Temperature: 60 °C
Reaction time: 1 h
Yield: 7587.5 %

Procedure:
Chlorosulfonic acid (25 ml, 0.37 mmol) was cooled down to 0° C. in a three necked flask equipped with a thermometer. N-trifluoroacetyl-2-methyl-indoline (17 g, 74.23 mmol) was added thereto in several portions. After the resulting mixture was stirred at 60° C. for 1 hour, the reaction mixture was slowly poured into 200 ml of ice water. The precipitate thus formed was collected by filtration and dried to afford 9.2 g of the title compound.
Reaction SMILES: [CH2:1]([O:3]/[C:4](=[CH:10]\[C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([N:23]([CH3:36])[C:24]([O:26]C3C=CC([N+]([O-])=O)=CC=3)=O)[CH:18]=2)=[CH:13][CH:12]=1)/[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:2].[CH:37]1([NH2:43])[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1>>[CH:37]1([NH:43][C:24](=[O:26])[N:23]([C:19]2[CH:18]=[C:17]([C:14]3[CH:13]=[CH:12][C:11](/[CH:10]=[C:4](\[O:3][CH2:1][CH3:2])/[C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:16][CH:15]=3)[CH:22]=[CH:21][CH:20]=2)[CH3:36])[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1
Reactant: CCOC(=O)/C(=C/c1ccc(-c2cccc(N(C)C(=O)Oc3ccc([N+](=O)[O-])cc3)c2)cc1)OCC
Reactant: NC1CCCCC1
Product: CCOC(=O)/C(=C/c1ccc(-c2cccc(N(C)C(=O)NC3CCCCC3)c2)cc1)OCC
Yield: 51.8 %

Procedure:
In a manner similar to that of Example 43d, starting with 1.75 g (3 mmol) of ethyl (Z)-2-ethoxy-3-{3′-[methyl(4-nitrophenoxycarbonyl)amino]biphenyl-4-yl}acrylate (prepared according to Example 43c) and 0.42 mL (3.7 mmol) of cyclohexylamine, 0.7 g (50%) of ethyl (Z)-3-[3′-(3-cyclohexyl-1-methylureido)biphenyl-4-yl]-2-ethoxyacrylate is obtained.
Reaction SMILES: [S:1]1[C:5]2[CH2:6][CH:7]3[CH:12]([C:4]=2[CH:3]=[CH:2]1)[CH2:11][NH:10][CH2:9][CH2:8]3.C(N(CC)CC)C.Cl[C:21]([O:23][CH2:24][CH3:25])=[O:22]>C(Cl)Cl>[CH2:24]([O:23][C:21]([N:10]1[CH2:11][CH:12]2[CH:7]([CH2:6][C:5]3[S:1][CH:2]=[CH:3][C:4]=32)[CH2:8][CH2:9]1)=[O:22])[CH3:25]
Reactant: c1cc2c(s1)CC1CCNCC21
Reactant: CCOC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)N1CCC2Cc3sccc3C2C1
Temperature: 22 °C
Yield: 73 %

Procedure:
A 0° C. solution of product from Example 29, step h) (885 mg, 4.1 mmol) in CH2Cl2 (20 ml) was treated with triethylamine (1.71 ml, 12.3 mmol) and ethyl chloroformate (472 μl, 4.92 mmol) and the reaction was warmed to 22° C. Next, the reaction mixture was diluted with CH2Cl2 (20 ml) and washed with brine (25 ml). The organic layer was dried (MgSO4) and the solvent evaporated in vacuo to give the crude product that was purified by silica-gel chromatography (hexanes:EtOAc-50:50) to give 748 mg (73%) of the subtitle compound. MS calculated for C13H17NO2S+H 252, observed 252.
Reaction SMILES: [C:1]1([CH2:17][CH2:18][CH2:19][C:20]([N:22]2[CH2:36][CH2:35][CH2:34][N:33](S(C3C=CC=CC=3[N+]([O-])=O)(=O)=O)[CH2:32][C:31]3[N:49]=[C:27]([CH:28]=[CH:29][CH:30]=3)[CH2:26][N:25](S(C3C=CC=CC=3[N+]([O-])=O)(=O)=O)[CH2:24][CH2:23]2)=[O:21])[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1.C1(S)C=CC=CC=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:1]1([CH2:17][CH2:18][CH2:19][C:20]([N:22]2[CH2:36][CH2:35][CH2:34][NH:33][CH2:32][C:31]3[N:49]=[C:27]([CH:28]=[CH:29][CH:30]=3)[CH2:26][NH:25][CH2:24][CH2:23]2)=[O:21])[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1
Reactant: O=C(CCCc1ccc2ccc3cccc4ccc1c2c34)N1CCCN(S(=O)(=O)c2ccccc2[N+](=O)[O-])Cc2cccc(n2)CN(S(=O)(=O)c2ccccc2[N+](=O)[O-])CC1
Agent: O=C([O-])[O-]
Agent: Sc1ccccc1
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C(CCCc1ccc2ccc3cccc4ccc1c2c34)N1CCCNCc2cccc(n2)CNCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 87.8 %

Procedure:
A mixture of 6-(1-Pyrenebutyryl)-3,10-bis(2-nitrobenzenesulfonyl)-3,6,10,16-tetraazabicyclo[10.3.1]-hexadeca-1(16),12,14-triene (2.26 g, 2.6 mmol), thiphenol (0.87 g, 7.8 mmol) and K2CO3 (3.22 g, 23.4 mmol) in 20 mL of DMF was stirred at rt overnight. The solvent was evaporated and the residue was dissolved in CHCl3—H2O. The organic phase was separated and the aqueous phase was extracted with CHCl3. The combined organic phase was dried (Na2SO4) and concentrated. The residue was purified by flash chromatography on a silica gel column using CH2Cl2 and then 3:1 CH2Cl2—MeOH as eluents to give 1.12 g (65%) of the title compound as a white foam.
Reaction SMILES: [CH2:1]1[CH2:6][C@@H:5]([NH2:7])[C@H:4]([NH2:8])[CH2:3][CH2:2]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O=[C:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]1.C(=O)(O)[O-].[Na+]>ClCCl>[NH2:7][C@@H:5]1[CH2:6][CH2:1][CH2:2][CH2:3][C@H:4]1[NH:8][CH:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: N[C@@H]1CCCC[C@H]1N
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(N[C@@H]2CCCC[C@H]2N)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 65.8 %

Procedure:
A mixture of (1R,2R)-cyclohexane diamine (20 g, 175 mmol) and sodium triacetoxyborohydride (25 g, 120 mmol) in dichloromethane (550 mL) was added with a solution of tert-butyl 4-oxopiperidine-1-carboxylate (18.4 g, 92 mmol) in dichloromethane (800 mL) dropwise over a period of 45 minutes and stirred at room temperature overnight. An aqueous solution of sodium bicarbonate (5%, 200 mL) was added to the reaction mixture, layers were separated, and the aqueous layer was extracted with dichloromethane (2×150 mL). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to afford the crude product which was purified by dry column vacuum chromatography to give the title compound as a pale yellow oil (18.0 g, 66%). 1H NMR (300 MHz, METHANOL-D4): δ ppm 3.99 (td, J=13.3, 3.3 Hz, 2H), 2.95-2.70 (m, 3H), 2.40-2.15 (m, 2H), 2.05 (m, 1H), 1.95-1.85 (m, 2H), 1.85-1.65 (m, 3H), 1.44 (s, 9H), 1.95-1.35 (m, 6H)
Reaction SMILES: [CH3:1][O:2][C:3](=[O:22])[CH2:4][CH:5]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)=[CH:11][CH:10]=1)[C:6]#[C:7][CH3:8].N1C2C(=CC=CC=2)C=CC=1.[H][H]>C(OCC)(=O)C.S([O-])([O-])(=O)=O.[Ba+2].[Pd+2].S([O-])([O-])(=O)=O>[CH3:1][O:2][C:3](=[O:22])[CH2:4][CH:5]([C:9]1[CH:10]=[CH:11][C:12]([O:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)=[CH:13][CH:14]=1)/[CH:6]=[CH:7]\[CH3:8]
Reactant: CC#CC(CC(=O)OC)c1ccc(OC2CCCCO2)cc1
Reactant: [H][H]
Agent: [Pd+2]
Agent: O=S(=O)([O-])[O-]
Agent: [Ba+2]
Solvent: c1ccc2ncccc2c1
Solvent: CCOC(C)=O
Product: C/C=C\C(CC(=O)OC)c1ccc(OC2CCCCO2)cc1
Yield: 93.5 %

Procedure:
To a solution of 3-[4-(tetrahydropyran-2-yloxy)-phenyl]-hex-4-ynoic acid methyl ester (4.07 g) obtained in Step 1 in ethyl acetate (70 mL) were added successively quinoline (1.52 mL) and 5% palladium-barium sulfate (0.4 g), followed by stirring the reaction mixture under normal pressure in an atmosphere of hydrogen at room temperature for 15.5 hours. Then, after the reaction mixture was filtered through Celite, water and 1N aqueous hydrochloric acid solution were added to the filtrate, followed by extraction with ethyl acetate. The organic layer was washed successively with 1N aqueous hydrochloric acid solution and saturated brine, dried and concentrated to give (Z)-3-[4-(tetrahydropyran-2-yloxy)-phenyl]-hex-4-enoic acid methyl ester (3.83 g).
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]1[S:10][CH:11]=[C:12]([Sn](C)(C)C)[N:13]=1)([CH3:4])([CH3:3])[CH3:2].[Cl:19][C:20]1[CH:25]=[CH:24][N:23]2[C:26](I)=[CH:27][N:28]=[C:22]2[CH:21]=1.[Li+].[Cl-]>O1CCOCC1.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:18])[NH:7][CH2:8][C:9]1[S:10][CH:11]=[C:12]([C:26]2[N:23]3[CH:24]=[CH:25][C:20]([Cl:19])=[CH:21][C:22]3=[N:28][CH:27]=2)[N:13]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Clc1ccn2c(I)cnc2c1
Reactant: CC(C)(C)OC(=O)NCc1nc([Sn](C)(C)C)cs1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Agent: [Li+]
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)NCc1nc(-c2cnc3cc(Cl)ccn23)cs1
Temperature: 90 °C
Yield: 38.8 %

Procedure:
To a solution of (4-trimethylstannyl-thiazol-2-ylmethyl)-carbamic acid tert-butyl ester (0.480 g, 1.27 mmol, 1.0 eq.) [prepared as in the PCT application WO2004046101, Jun. 3, 2004, filed Nov. 10, 2003] in anhydrous dioxane (4 mL), add 7-chloro-3-iodo-imidazo[1,2-a]pyridine (0.354 g, 1.27 mmol, 1.0 eq.) and LiCl (0.162 g, 3.0 eq.). Add Pd(PPh3)4 (0.102 g, 0.07 eq.). Deoxygenate the reaction mixture and fill with nitrogen. Stir at 90° C. over night, cool, then dilute with 5% MeOH/DCM (100 mL), wash with saturated aqueous saturated sodium chloride (2×20 mL), water (2×20 mL), dry, filter, and concentrate. Chromatograph on silica gel first with a 50%-100% EtOAc/DCM gradient then a 5% MeOH/DCM gradient to afford 0.180 g of the title compound, which is used in the next step without further purification: MS(ES), m/z 365 (M+1).
Reaction SMILES: [CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[C:13]([O:16][CH:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[CH:14]=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([N:30]=[C:31]=[O:32])=[CH:26][CH:25]=1>>[F:23][C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31]([N:20]2[CH2:21][CH2:22][CH:17]([O:16][C:13]3[CH:14]=[CH:15][C:8]4[CH2:7][CH2:6][N:5]([CH:1]5[CH2:2][CH2:3][CH2:4]5)[CH2:11][CH2:10][C:9]=4[CH:12]=3)[CH2:18][CH2:19]2)=[O:32])=[CH:26][CH:25]=1
Reactant: O=C=Nc1ccc(F)cc1
Reactant: c1cc2c(cc1OC1CCNCC1)CCN(C1CCC1)CC2
Product: O=C(Nc1ccc(F)cc1)N1CCC(Oc2ccc3c(c2)CCN(C2CCC2)CC3)CC1

Procedure:
Example 67 was prepared from 3-cyclobutyl-7-(piperidin-4-yloxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (E6) and 4-fluorophenyl-isocyanate using the method described for Example 66 (E66); MS (ES+) m/e 438 [M+H]+.
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH:13]=[CH:12]2)=[C:4]([NH2:17])[N:3]=1.[O-:18][CH2:19][CH3:20].[Na+].Cl>C(O)C>[CH:11]1([N:8]2[CH:7]=[N:6][C:5]3[C:9]2=[N:10][C:2]([O:18][CH2:19][CH3:20])=[N:3][C:4]=3[NH2:17])[CH2:16][CH2:15][CH2:14][CH:13]=[CH:12]1
Reactant: CC[O-]
Reactant: Nc1nc(Cl)nc2c1ncn2C1C=CCCC1
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CCOc1nc(N)c2ncn(C3C=CCCC3)c2n1
Temperature: 0 °C
Yield: 92 %

Procedure:
A mixture of 2-chloro-9-(2-cyclohexenyl)-9H-adenine (310 mg., 1.24 mmole) and a solution of sodium ethoxide in ethanol (0.25-1 N, ~10 ml.) was refluxed overnight under an atmosphere of nitrogen. The reaction mixture was poured into ice-water, neutralized with 1 N HCl and extracted with ethyl acetate (20 ml.). The extracts were washed with water, dried over Na2SO4 and filtered. The filtrate was evaporated and the residue then subjected to silica gel chromatography (silica gel 7 g., eluted with 1% CH3OH-CHCl3) to give the title product in 92% yield; m.p. 67°-72° C. IR(KBr): 3320, 2940, 1640, 1595, 1465, 1410, 1385, 1340 cm-1. UV: λmaxEtOH 254 nm (ε 8400), 269 nm (ε 12600). NMR(CDCl3): 1.44 (3H, t, J=7 Hz), 2.00(6H, m), 4.45(2H, q, J= 7 Hz), 5.20(1H, m), 5.95(2H, m), 6.16(2H, s), 7.62(1H, s).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[O:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[C:7]=2[CH:6]=[CH:5][CH:4]=1.O.[NH2:17]N>CO.[Ni]>[NH2:17][C:6]1[C:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[O:9][C:8]=2[C:3]([O:2][CH3:1])=[CH:4][CH:5]=1
Reactant: NN
Reactant: COc1cccc2c1oc1ccccc12
Agent: [Ni]
Solvent: O
Solvent: CO
Product: COc1ccc(N)c2c1oc1ccccc12
Reaction time: 2 h

Procedure:
Intermediate 38 (550 mg, 2.26 mmol) was taken in methanol (10 ml) and raney nickel catalyst (100 mg, 18% w/w) was added. The reaction mixture was refluxed and to this was added hydrazine hydrate (99%) solution (2 ml) slowly over a period of 10 min. The refluxing continued for 2 h. The catalyst was filtered and the filterate was concentrated and diluted with water (100 ml) and further extracted with ethyl acetate (3×25 ml). The organic layer was washed with water and concentrated to give the product as brown solid (500 mg);mp: 167-169° C.
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@H:8]([C:19]2[CH:24]=[CH:23][C:22]([CH:25]3[CH2:27][CH2:26]3)=[C:21]([CH2:28][C:29]3[CH:38]=[CH:37][C:32]4[O:33][CH2:34][CH2:35][O:36][C:31]=4[CH:30]=3)[CH:20]=2)[O:7][CH:6]1OC(=O)C)(=[O:3])[CH3:2].N[C:44](N)=[S:45].FC(F)(F)S(O[Si](C)(C)C)(=O)=O.CI.C(N(C(C)C)CC)(C)C>O1CCOCC1.C(OCC)(=O)C>[C:12]([O:11][C@@H:10]1[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@H:8]([C:19]2[CH:24]=[CH:23][C:22]([CH:25]3[CH2:27][CH2:26]3)=[C:21]([CH2:28][C:29]3[CH:38]=[CH:37][C:32]4[O:33][CH2:34][CH2:35][O:36][C:31]=4[CH:30]=3)[CH:20]=2)[O:7][CH:6]([S:45][CH3:44])[C@H:5]1[O:4][C:1](=[O:3])[CH3:2])(=[O:14])[CH3:13]
Reactant: NC(N)=S
Reactant: CC(=O)OC1O[C@@H](c2ccc(C3CC3)c(Cc3ccc4c(c3)OCCO4)c2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: CCOC(C)=O
Solvent: CI
Solvent: CCN(C(C)C)C(C)C
Product: CSC1O[C@@H](c2ccc(C3CC3)c(Cc3ccc4c(c3)OCCO4)c2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 80 °C
Reaction time: 3 h

Procedure:
Step-X: To a stirred solution of acetic acid (3S,4R,5S,6S)-3,4,5-triacetoxy-6-[4-cyclopropyl-3-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-phenyl]-tetrahydro-pyran-2-yl ester (1.9 g, 3.3 mmol) in dioxane (8 ml) was added thiourea followed by trimethylsilyl trifluoromethane sulfonate (0.88 ml, 4.8 mmol). The reaction mixture was heated to 80° C. for 3 h. Reaction mixture was cooled to room temperature and added methyl iodide (0.52 ml, 8.1 mmol) followed by diisopropylethyl amine (2.79 ml, 16.2 mmol) and stirred for additional 3 h. Reaction mixture was diluted with ethyl acetate (40 ml) and washed with water (40 ml). The organic layer was concentrated. The resulting residue was taken in methanol (10 ml) and heated to 60° C. for 2 h, then cooled to 0° C. and stirred for additional 1 h. The resulting solid was filtered and washed with methanol to give 750 mg of acetic acid (3S,4R,5S,6S)-4,5-diacetoxy-6-[4-cyclopropyl-3-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-phenyl]-2-methylsulfanyl-tetrahydro-pyran-3-yl ester. 1H NMR (400 MHz, DMSO-d6): δ 0.55-0.59 (m, 2H), 0.85 (d, J=8.8 Hz, 2H), 1.70 (s, 3H), 1.82-1.89 (m, 1H), 1.93 (s, 3H), 2.03 (s, 3H), 2.08 (s, 3H), 3.95 (d, J=15.2 Hz, 1H), 4.02 (d, J=16.8 Hz, 1H), 4.00 (s, 4H), 4.65 (d, J=10.0 Hz, 1H), 4.87 (d, J=10.0 Hz, 1H), 5.03-5.12 (m, 2H), 5.34 (t, J=10.0 Hz, 1H), 6.58-6.60 (m, 2H), 6.73 (d, J=7.6 Hz, 1H), 6.91 (d, J=8.0 Hz, 1H), 7.04 (d, J=8.0 Hz, 1H), 7.15 (d, J=8.0 Hz, 1H). MS (ES) m/z 588.3 (M+18).
Reaction SMILES: [C:1]1([N:7]2[C:11](=[O:12])[C:10]3[CH:13]=[CH:14][CH:15]=[CH:16][C:9]=3[Se:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:17][C@H:18]([C:21]([OH:23])=[O:22])[CH2:19][SH:20]>CO>[C:1]1([NH:7][C:11]([C:10]2[CH:13]=[CH:14][CH:15]=[CH:16][C:9]=2[Se:8][S:20][CH2:19][C@@H:18]([C:21]([OH:23])=[O:22])[NH2:17])=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=c1c2ccccc2[se]n1-c1ccccc1
Reactant: N[C@@H](CS)C(=O)O
Solvent: CO
Product: N[C@@H](CS[Se]c1ccccc1C(=O)Nc1ccccc1)C(=O)O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
2,74 g (10 mmol) 2-phenyl-1,2-benzoisoselenazole-3(2H)-one and 1,21 g (10 mmol) L-cysteine are dissolved in 25 ml trifluororacetic acid. This solution is stirred for 18 hours at room temperature. Then, 150 ml of an ice-water mixture are added to this solution. The deposited precipitate after some stirring becomes solid. It is sucked off and finally dissolved in methanol. After evaporation of the solvent, a residue remains which is washed with ether.
Reaction SMILES: [C:1]([O:5][C:6](=[O:15])[NH:7][CH2:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].[C:16](Cl)(=[O:27])[O:17][CH2:18][C:19]1[CH:24]=[C:23]([Cl:25])[CH:22]=[C:21]([Cl:26])[CH:20]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:1]([O:5][C:6]([NH:7][CH2:8][CH:9]1[CH2:10][CH2:11][N:12]([C:16]([O:17][CH2:18][C:19]2[CH:20]=[C:21]([Cl:26])[CH:22]=[C:23]([Cl:25])[CH:24]=2)=[O:27])[CH2:13][CH2:14]1)=[O:15])([CH3:4])([CH3:2])[CH3:3]
Reactant: O=C(Cl)OCc1cc(Cl)cc(Cl)c1
Reactant: CC(C)(C)OC(=O)NCC1CCNCC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCC1CCN(C(=O)OCc2cc(Cl)cc(Cl)c2)CC1

Procedure:
A reaction mixture comprising tert-butyl(piperidin-4-ylmethyl)carbamate (1 g, 4.67 mmol), 3,5-dichlorobenzyl carbonochloridate, (1.117 g, 4.67 mmol) and sodium bicarbonate (15 mL, 4.67 mmol) in DCM (15.55 mL) was stirred at room temperature for 18 hours. The reaction mixture was separated and the organic portion was dried over MgSO4, filtered and solvent concentrated under reduced pressure to give the title compound as a yellow oil;
Reaction SMILES: [C:1]([O:5][C:6](=[O:36])[NH:7][C@@H:8]1[C@@H:13]([OH:14])[C@H:12]([CH2:15][C:16]2[CH:21]=[C:20]([O:22][CH:23]([C:28]([F:31])([F:30])[F:29])[C:24]([F:27])([F:26])[F:25])[C:19]([N+:32]([O-:34])=[O:33])=[C:18]([F:35])[CH:17]=2)[CH2:11]S[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].O[O:38][S:39]([O-:41])=O.[K+].CC([O-])=O.[Na+].S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+].C([O-])([O-])=O.[K+].[K+]>C1COCC1.O>[C:1]([O:5][C:6](=[O:36])[NH:7][C@@H:8]1[C@@H:13]([OH:14])[C@H:12]([CH2:15][C:16]2[CH:21]=[C:20]([O:22][CH:23]([C:24]([F:25])([F:27])[F:26])[C:28]([F:29])([F:31])[F:30])[C:19]([N+:32]([O-:34])=[O:33])=[C:18]([F:35])[CH:17]=2)[CH2:11][S:39](=[O:41])(=[O:38])[CH2:9]1)([CH3:3])([CH3:4])[CH3:2]
Reactant: CC(C)(C)OC(=O)N[C@H]1CSC[C@@H](Cc2cc(F)c([N+](=O)[O-])c(OC(C(F)(F)F)C(F)(F)F)c2)[C@@H]1O
Reactant: O=S([O-])OO
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Agent: O=S([O-])S(=O)(=O)[O-]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@H]1CS(=O)(=O)C[C@@H](Cc2cc(F)c([N+](=O)[O-])c(OC(C(F)(F)F)C(F)(F)F)c2)[C@@H]1O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of {(3R,4S,5S)-5-[3-fluoro-4-nitro-5-(2,2,2-trifluoro-1-trifluoromethyl-ethoxy)-benzyl]-4-hydroxy-tetrahydro-thiopyran-3-yl}-carbamic acid tert-butyl ester (3.31 g, 6.0 mmol) in THF-H2O 1:1 (150 mL) was added oxone (7.6 g, 12.0 mmol). After stirring the reaction mixture for 2 h at 25° C., 2.5 g NaOAc and 3 g sodium metabisulfite were added. The reaction mixture was stirred for 0.5 h, basified with saturated aq. K2CO3-solution and the product was extracted with EtOAc. Combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated to provide the title compound after chromatographic purification (Combi-Flash, 40 g silicagel, hexane-EtOAc 95:5 to EtOAc) as a colorless amorphous solid: TLC (toluene-THF 1:1) Rf=0.45; HPLC RtA=2.21 min; ESIMS [M+NH4]+=602; 1H NMR (400 MHz, CDCl3): δ 6.92 (d, 1H), 6.85 (s, 1H), 5.05 (m, 1H), 4.92 (d, 1H), 4.02 (m, 1H), 3.45 (m, 1H), 3.34 (m, 2H), 3.22 (dd, 1H), 3.18 (m, 1H), 2.94 (m, 1H), 2.82 (dd, 1H), 2.74 (dd, 1H), 2.52 (m, 1H), 1.43 (s, 9H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[C:12](Cl)=[C:11]1[C:6]([CH:7]=[CH:8][C:9]([O:17][CH3:18])=[CH:10]1)=[N:5]2.[CH3:19][O:20][CH2:21][CH2:22][CH2:23][CH2:24][NH2:25]>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[C:12]([NH:25][CH2:24][CH2:23][CH2:22][CH2:21][O:20][CH3:19])=[C:11]1[C:6]([CH:7]=[CH:8][C:9]([O:17][CH3:18])=[CH:10]1)=[N:5]2
Reactant: COc1ccc2nc3cc(Cl)ccc3c(Cl)c2c1
Reactant: COCCCCN
Product: COCCCCNc1c2ccc(Cl)cc2nc2ccc(OC)cc12

Procedure:
Following the general procedure of Example 1 and making non-critical variations, but using 6,9-dichloro-2-methoxyacridine and commercially available 4-methoxybutan-1-amine, the title compound was obtained; MS (Found M+1=345).
Reaction SMILES: [N:1]([CH:4]1[C:10](=[O:11])[N:9]2[CH:5]1[CH2:6][C:7](OS(C1C(C)=CC=CC=1)(=O)=O)=[C:8]2[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])=[N+:2]=[N-:3].C(N(CC)CC)C.[CH2:40]([NH:43][CH2:44][CH2:45][CH3:46])[CH2:41][CH3:42]>CN(C)C=O.C(OC(=O)C)C>[N:1]([CH:4]1[C:10](=[O:11])[N:9]2[CH:5]1[CH2:6][C:7]([N:43]([CH2:44][CH2:45][CH3:46])[CH2:40][CH2:41][CH3:42])=[C:8]2[C:12]([O:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:13])=[N+:2]=[N-:3]
Reactant: Cc1ccccc1S(=O)(=O)OC1=C(C(=O)OCc2ccccc2)N2C(=O)C(N=[N+]=[N-])C2C1
Reactant: CCCNCCC
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CCCN(CCC)C1=C(C(=O)OCc2ccccc2)N2C(=O)C(N=[N+]=[N-])C2C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of benzyl 6-azido-3-toluenesulfonyloxy-1-azabicyclo[3.2.0]hept-2-en-7-one-2-carboxylate (0.1 mmol) in anhydrous dimethylformamide (1 ml) is cooled in an ice-bath and stirred while triethylamine (0.2 mmol) and dipropylamine (0.12 mmol) are added. The resulting solution is allowed to warm to room temperature and kept there overnight. The solution is diluted with ethylacetate, washed with water, pH 3 phosphate buffer, 5% sodium bicarbonate solution, and brine, dried with magnesium sulfate, filtered, and evaporated under vacuum to afford benzyl 6-azido-3-dipropylamino-1-azabicyclo[3.2.0]hept-2-en-7-one-2-carboxylate.