Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:9](=[N:22][OH:23])[CH2:10][N:11]2[C:15](=[O:16])[C:14]3=[CH:17][CH:18]=[CH:19][CH:20]=[C:13]3[C:12]2=[O:21])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].I[CH2:31][CH2:32][CH3:33].O>CN(C)C=O>[Cl:1][C:2]1[C:3]([C:9](=[N:22][O:23][CH2:31][CH2:32][CH3:33])[CH2:10][N:11]2[C:12](=[O:21])[C:13]3=[CH:20][CH:19]=[CH:18][CH:17]=[C:14]3[C:15]2=[O:16])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: CCCI
Reactant: O=C1c2ccccc2C(=O)N1CC(=NO)c1ncc(Cl)cc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCON=C(CN1C(=O)c2ccccc2C1=O)c1ncc(Cl)cc1Cl
Temperature: 25 °C
Reaction time: 18 h
Yield: 79.2 %

Procedure:
To 265 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-(hydroxyimino)ethyl]phthalimide in 2 ml of N,N-dimethylformamide, 310 mg of potassium carbonate and 387 mg of 1-iodopropane were added, and the mixture was stirred at room temperature for 18 hours. After completion of the reaction, the reaction mixture was mixed with 30 ml of water and extracted with ethyl acetate (50 ml×1), the resulting organic layer was washed with water (50 ml×1) and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 15:85 to 25:75) as the eluent to obtain 235 mg of the desired product as a yellow resinous substance.
Reaction SMILES: S(=O)(=O)(O)O.[OH:6][C@:7]12[CH2:24][CH2:23][C@@:21]3([CH3:22])[C@@H:17]([CH2:18][CH2:19][C:20]3=[O:25])[C@@H:16]1[CH2:15][CH2:14][C:13]1[C@:8]2([CH3:27])[CH2:9][CH2:10][C:11](=[O:26])[CH:12]=1.[C-:28]#[N:29].[K+].O>CO>[CH3:22][C@@:21]12[C:20]([OH:25])([C:28]#[N:29])[CH2:19][CH2:18][C@H:17]1[C@@H:16]1[CH2:15][CH2:14][C:13]3[C@@:8]([CH3:27])([C:7]1([OH:6])[CH2:24][CH2:23]2)[CH2:9][CH2:10][C:11](=[O:26])[CH:12]=3
Reactant: C[C@]12CCC(=O)C=C1CC[C@H]1[C@@H]3CCC(=O)[C@@]3(C)CC[C@@]12O
Reactant: [C-]#N
Agent: O=S(=O)(O)O
Agent: [K+]
Solvent: O
Solvent: CO
Product: C[C@]12CCC(=O)C=C1CC[C@H]1[C@@H]3CCC(O)(C#N)[C@@]3(C)CCC12O
Reaction time: 2.5 h

Procedure:
Sulfuric acid (2.07 ml) is added to 9α-hydroxyandrost-4-ene-3,17-dione (I, 21.14 g) and potassium cyanide (6.70 g) slurried in methanol (71.5 ml) and water (6.8 ml) at <5°. The mixture is allowed to warm to 15° over 0.5 hr, then warmed to 30° over 1 hr. The mixture is stirred at 30° for 2.5 hr, then cooled to 2° and sulfuric acid (0.32 ml) is added. The mixture is then stirred at 30° for 2 hr and water (13 ml) is added. Next, water (52 ml) is added over 12 hr, maintaining the mixture at 30°. The mixture is stirred 5 hr at 30°, then cooled to 0° and quenched with sulfuric acid (1 ml). Methanol (89 ml) is added and the mixture is heated to 55°. The solvent is then removed by reduced pressure until the boiling point begins to rise rapidly. The mixture is then cooled to 32° and water (105 ml) is added over 12 min. The mixture is further cooled to 0° and the the solids are collected by vacuum filtration and washed with water to give the title compound, mp 230°-233° (with decomposition). ##STR1##
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:18]2[O:17][CH2:16][CH2:15][O:14][C:13]=2[C:12]([CH2:19]O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:23])=O>C(Cl)(Cl)Cl>[CH2:1]([O:8][C:9]1[C:18]2[O:17][CH2:16][CH2:15][O:14][C:13]=2[C:12]([CH2:19][Cl:23])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCc1ccc(OCc2ccccc2)c2c1OCCO2
Reactant: O=S(Cl)Cl
Solvent: ClC(Cl)Cl
Product: ClCc1ccc(OCc2ccccc2)c2c1OCCO2
Reaction time: 0.25 h
Yield: 96.7 %

Procedure:
To a solution, cooled to -10° C., of 10 g (0.037 mole) of 5-benzyloxy-8-hydroxymethyl-1,4-benzodioxane (XIp), code number 760 701, in 100 ml of chloroform were slowly added 4.6 g (0.039 mole) of thionyl chloride. They were left in contact for 15 minutes, then the solvents were evaporated, the residue was taken up in chloroform, washed with a solution of sodium bicarbonate, dried and the solvent was evaporated. 10.4 g of unstable product were obtained which, after checking by chromatography on a thin silica layer, was used in the synthesis of the compound of formula (XIm), code number 770 119.
Reaction SMILES: [S:1]1[CH:5]=[C:4]([C:6]([OH:8])=O)[N:3]=[CH:2]1.[CH3:9][NH:10][O:11][CH3:12].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.O>[CH3:12][O:11][N:10]([CH3:9])[C:6]([C:4]1[N:3]=[CH:2][S:1][CH:5]=1)=[O:8]
Reactant: O=C(O)c1cscn1
Reactant: CNOC
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: O
Solvent: ClCCl
Product: CON(C)C(=O)c1cscn1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture of thiazole-4-carboxylic acid (1 g, 7.74 mmol), N,O-dimethylhydroxylamine (1.51 g, 15.5 mmol), and HATU (3.83 g, 10.07 mmol) in CH2Cl2 (25 mL) was added TEA (4.84 mL, 34.85 mmol). The reaction was stirred at room temperature overnight. The reaction was diluted with CH2Cl2 and water. The organics were concentrated and purified by chromatography (60-70% EtOAc/hexanes) to yield N-methoxy-N-methylthiazole-4-carboxamide as a clear oil. 1H NMR (CDCl3) δ: 8.83 (s, 1H), 8.10 (s, 1H), 3.79 (s, 3H), 3.46 (s, 3H)
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])/[C:5]/2=[CH:14]\[NH:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[CH:18][CH:17]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:42][O:43][CH2:44][C:45](=O)[CH3:46].C(O)(=O)C.C(=O)(O)[O-].[Na+]>CN1CCCC1=O.C(Cl)Cl>[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])/[C:5]/2=[CH:14]\[NH:15][C:16]1[CH:17]=[CH:18][C:19]([N:22]2[CH2:23][CH2:24][N:25]([CH:45]([CH3:46])[CH2:44][O:43][CH3:42])[CH2:26][CH2:27]2)=[CH:20][CH:21]=1
Reactant: O=C1NC(=O)c2ccc(I)cc2/C1=C/Nc1ccc(N2CCNCC2)cc1
Reactant: COCC(C)=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Solvent: CN1CCCC1=O
Product: COCC(C)N1CCN(c2ccc(N/C=C3\C(=O)NC(=O)c4ccc(I)cc43)cc2)CC1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 71.4 %

Procedure:
(4Z)-6-Iodo-4-{[(4-piperazin-1-ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione (47.4 mg, 0.1 mmol) is dissolved in N-methylpyrrolidinone (1 mL) and methylene chloride (0.3 mL), followed by addition of sodium triacetoxyborohydride (244 mg, 1.15 mmol), 1-methoxy-propan-2-one (0.232 mL, 2.58 mmol) and acetic acid (0.15 mL, 2.6 mmol). After stirring at room temperature for 40 min, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 39 mg (71%) of the title compound as a yellow solid. MS (ESI) m/z 547.4 (M+H)+1.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]([OH:17])([C:13]([F:16])([F:15])[F:14])[C:9]([F:12])([F:11])[F:10])[CH:5]=[N:6][CH:7]=1.C([Mg]Cl)(C)C.CN([CH:26]=[O:27])C>C1COCC1>[F:10][C:9]([F:12])([F:11])[C:8]([C:4]1[CH:5]=[N:6][CH:7]=[C:2]([CH:3]=1)[CH:26]=[O:27])([OH:17])[C:13]([F:16])([F:15])[F:14]
Reactant: CN(C)C=O
Reactant: OC(c1cncc(Br)c1)(C(F)(F)F)C(F)(F)F
Agent: CC(C)[Mg]Cl
Solvent: C1CCOC1
Product: O=Cc1cncc(C(O)(C(F)(F)F)C(F)(F)F)c1
Reaction time: 0.17 h

Procedure:
To a stirred solution of 258 (0.347 g, 1.07 mmol) in dry THF, cooled to 0° C., was added isopropyl magnesium chloride (1.2 mL, 2.4 mmol) drop wise and stirred for 10 min followed by the addition of DMF (0.015 ml, 1.94 mmol) to the reaction and stirred for additional 2 h. After completion of the reaction, it was quenched with saturated ammonium chloride solution. The organic layer was separated and aqueous phase was extracted again with diethyl ether, the combined organic layer was dried over sodium sulphate and concentrated to get the crude compound 5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)nicotinaldehyde 259 used directly to proceed for the next step.
Reaction SMILES: [CH3:1][NH:2][S:3]([C:6]([F:18])([F:17])[C:7]([F:16])([F:15])[C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10])(=[O:5])=[O:4].[CH2:19]([C:21]1[O:22][CH2:23][CH2:24][N:25]=1)[CH3:20].C(=O)([O-])[O-].[Na+].[Na+]>>[C:6]([S:3]([N:2]([CH2:19][CH2:21][NH2:25])[CH3:1])(=[O:5])=[O:4])([C:7]([C:8]([C:9]([F:10])([F:11])[F:12])([F:13])[F:14])([F:15])[F:16])([F:18])[F:17].[CH3:1][N:2]([CH2:23][CH2:24][NH:25][C:21](=[O:22])[CH2:19][CH3:20])[S:3]([C:6]([F:18])([F:17])[C:7]([F:15])([F:16])[C:8]([F:13])([F:14])[C:9]([F:10])([F:11])[F:12])(=[O:5])=[O:4]
Reactant: CNS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Reactant: CCC1=NCCO1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: CCC(=O)NCCN(C)S(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Product: CN(CCN)S(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Temperature: 140 °C

Procedure:
C4F9SO2—N(CH3)CH2CH2—NH2 was prepared by the following procedure: N-Methylnonafluorobutanesulfonamide (626 g, 2 moles, 3M Company, St. Paul, Minn.), 2-ethyl-2-oxazoline (198 g, 2 moles, Alfa Aesar, Ward Hill, Mass.), and sodium carbonate (17 g, 0.16 mole, EMD Chemicals, Gibbstown, N.J.) were combined and heated for 16 hours at 140° C. to form N-(2-(N-methylnonafluorobutanesulfonamido)ethyl)propionamide. This amide was twice extracted with 250 mL deionized water, heated for 18 hours at 100° C. with a mixture of 250 mL concentrated hydrochloric acid and 100 mL deionized water, extracted with 925 mL of 24 weight percent aqueous sodium hydroxide solution, extracted with 250 mL 10 weight percent aqueous sodium hydroxide solution, and distilled to provide N-(2-aminoethyl)-N-methylnonafluorobutanesulfonamide (538 g; 75 percent recovery; 94 percent pure by gas chromatography (GC); distilled at 104-109° C. under 2 mm Hg pressure).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:11]=[CH:10][C:9]([CH:12]([CH3:15])[CH2:13][NH2:14])=[CH:8][CH:7]=2)=[CH:2]1.[CH2:16]([N:18]([CH2:22][CH3:23])[C:19](Cl)=[O:20])[CH3:17]>>[CH2:16]([N:18]([CH2:22][CH3:23])[C:19]([NH:14][CH2:13][CH:12]([C:9]1[CH:10]=[CH:11][C:6]([C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)=[CH:7][CH:8]=1)[CH3:15])=[O:20])[CH3:17]
Reactant: CC(CN)c1ccc(-c2ccsc2)cc1
Reactant: CCN(CC)C(=O)Cl
Product: CCN(CC)C(=O)NCC(C)c1ccc(-c2ccsc2)cc1

Procedure:
The title compound was prepared from 2-(4-(3-thienyl)phenyl)propylamine (see example 14) and N,N-diethylcarbamoyl chloride in a manner analogous to the procedure described in example 14. The NMR spectrum was consistent with the proposed title structure.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]([C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=3)[N:13]=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)([O-:3])=O.[F:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29]C#N)=[CH:25][CH:24]=1>>[F:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[O:3][N:1]=[C:4]3[CH:5]=[CH:6][C:7]([C:10]4[N:14]([C:15]5[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=5)[N:13]=[CH:12][CH:11]=4)=[CH:8][C:9]=23)=[CH:25][CH:24]=1
Reactant: Cc1ccc(-n2nccc2-c2ccc([N+](=O)[O-])cc2)cc1
Reactant: N#CCc1ccc(F)cc1
Product: Cc1ccc(-n2nccc2-c2ccc3noc(-c4ccc(F)cc4)c3c2)cc1

Procedure:
The title compound, light grey solid (50 mg, 38%), MS (ISP) m/z=370.2 [(M+H)+], mp 173° C., was prepared in accordance with the general method of example 1 from 5-(4-nitro-phenyl)-1 p-tolyl-1H-pyrazole (intermediate E) (100 mg, 353 μmol) and commercially available 2-(4-fluoro-phenyl)-acetonitrile.
Reaction SMILES: COC1C=CC(C[N:8]2[C:12]3[N:13]=[CH:14][C:15]4[CH2:16][NH:17][CH2:18][CH2:19][C:20]=4[C:11]=3[CH:10]=[N:9]2)=CC=1.C1(C)C=CC=CC=1.[F:30][C:31]([F:36])([F:35])[C:32]([OH:34])=[O:33]>>[F:30][C:31]([F:36])([F:35])[C:32]([O-:34])=[O:33].[CH:10]1[C:11]2[C:20]3[CH2:19][CH2:18][NH2+:17][CH2:16][C:15]=3[CH:14]=[N:13][C:12]=2[NH:8][N:9]=1
Reactant: COc1ccc(Cn2ncc3c4c(cnc32)CNCC4)cc1
Reactant: O=C(O)C(F)(F)F
Solvent: Cc1ccccc1
Product: O=C([O-])C(F)(F)F
Product: c1nc2[nH]ncc2c2c1C[NH2+]CC2

Procedure:
A solution of 3-(4-methoxy-benzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine (1.90 g, 6.46 mmol) in trifluoroacetic acid (20 mL) was heated at 65° C. for 16 hours. On completion of the reaction, toluene (10 mL) was added and the reaction mixture evaporated to dryness under reduced pressure to give the desired product as a dark brown gel. The crude product was triturated with 1,4-dioxane. The resulting solid was filtered to give the desired product, 6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-7-ium 2,2,2-trifluoroacetate as a tan powder (2.52 g, 97%)
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:7]2[S:8][C:9](=[O:11])[S:10][C:6]=2[C:5](=O)[C:4](=O)[O:3]1.[C:15]1([NH2:22])[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[NH2:21].O.[O-2].[O-2].[O-2].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.[Al+3].[Al+3]>>[CH3:1][C:2]1([CH3:14])[O:3][C:4]2[C:5](=[N:21][C:16]3[C:15]([N:22]=2)=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:6]2[S:10][C:9](=[O:11])[S:8][C:7]1=2
Reactant: CC1(C)OC(=O)C(=O)c2sc(=O)sc21
Reactant: Nc1ccccc1N
Agent: O=[Si]=O
Agent: [Al+3]
Agent: [O-2]
Solvent: O
Product: CC1(C)Oc2nc3ccccc3nc2-c2sc(=O)sc21

Procedure:
4,4-Dimethyl-4H-[1,3]dithiolo[4,5-c]pyran-2,6,7-trione (5) (150 mg, 0.65 mmol), o-phenylenediamine (75 mg, 0.65 mmol) and montmorillonite KSF (100 mg) were mixed in a mortar until a homogeneous solid was obtained then the solid mixture was transferred into a test tube and irradiated with microwaves for 4 min. The resulting mixture was purified by chromatography (silica gel, CH2Cl2) to give pure 4,4-Dimethyl-4H-5-oxa-1,3-dithia-6,1,1-diaza-cyclopenta[a]anthracen-2-one (7). Yield: 90 mg (45%).
Reaction SMILES: [S:1]1[C:5]2[S:6][CH:7]=[CH:8][C:4]=2[CH:3]=[CH:2]1.Cl[C:10]([C:12]1[CH:13]=[C:14]([CH:18]([CH3:21])[C:19]#[N:20])[CH:15]=[CH:16][CH:17]=1)=[O:11].[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl>[S:1]1[C:5]2[S:6][CH:7]=[CH:8][C:4]=2[CH:3]=[C:2]1[C:10]([C:12]1[CH:13]=[C:14]([CH:18]([CH3:21])[C:19]#[N:20])[CH:15]=[CH:16][CH:17]=1)=[O:11]
Reactant: c1cc2ccsc2s1
Reactant: CC(C#N)c1cccc(C(=O)Cl)c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CC(C#N)c1cccc(C(=O)c2cc3ccsc3s2)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 37.2 %

Procedure:
A mixture of thieno[2,3-b]thiophene (23.8 g) and 2-(3-chloroformyl-phenyl)propionitrile (29.6 g) is added dropwise to a suspension of anhydrous aluminium chloride (50 g) in methylene chloride (425 cc). After 16 hours at 25° C., the reaction mixture is heated under reflux for 40 minutes and then, after cooling, distilled water (600 cc) and 12N hydrochloric acid (50 cc) are added. The organic phase is decanted and the aqueous phase is extracted twice with methylene chloride (total 200 cc). The combined methylene chloride solutions are washed three times with distilled water (total 1500 cc), and then stirred with 5N aqueous sodium hydroxide solution (50 cc) for 2 hours at 25° C. The organic phase is decanted, washed four times with distilled water (total 2000 cc) and dried over anhydrous sodium sulphate, decolourizing charcoal (5 g) is added, and the organic phase is filtered and evaporated. The residue obtained (43.6 g) is chromatographed on a column (4.8 cm diameter, 47 cm height) containing silica gel (410 g). Elution is carried out with methylene chloride (total 1500 cc). The first fraction (500 cc) is discarded, whilst the two following fractions are combined and concentrated to dryness. 2-{3-(Thieno[2,3-b]thien-2-yl)carbonylphenyl}propionitrile (16.9 g) is obtained in the form of an oil. Rf = 0.60 (silica gel chromatographic plate; solvent: methylene chloride).
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][C:19]2[C:20](=[O:28])[NH:21][NH:22][C:23]=2[C:24]([F:27])([F:26])[F:25])=[CH:14][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:29][C:30]([O:32][CH2:33][C@H:34]1[O:39][C@H:38](Br)[C@H:37]([O:41][C:42]([CH3:44])=[O:43])[C@@H:36]([O:45][C:46]([CH3:48])=[O:47])[C@@H:35]1[O:49][C:50]([CH3:52])=[O:51])=[O:31].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][C:19]2[C:20]([O:28][C@@H:38]3[O:39][C@H:34]([CH2:33][O:32][C:30](=[O:31])[CH3:29])[C@@H:35]([O:49][C:50](=[O:51])[CH3:52])[C@H:36]([O:45][C:46](=[O:47])[CH3:48])[C@H:37]3[O:41][C:42](=[O:43])[CH3:44])=[N:21][NH:22][C:23]=2[C:24]([F:27])([F:26])[F:25])=[CH:14][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=c1[nH][nH]c(C(F)(F)F)c1Cc1ccc(CCCOCc2ccccc2)cc1
Reactant: CC(=O)OC[C@H]1O[C@H](Br)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CC(=O)OC[C@H]1O[C@@H](Oc2n[nH]c(C(F)(F)F)c2Cc2ccc(CCCOCc3ccccc3)cc2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 60 °C
Reaction time: 20 h
Yield: 41.8 %

Procedure:
To a solution of 4-({4-[3-(benzyloxy)propyl]phenyl}methyl)-5-trifluoromethyl-1,2-dihydro-3H-pyrazole-3-one (0.83 g) and acetobromo-α-D-glucose (1.5 g) in acetonitrile (12 mL) was added potassium carbonate (0.55 g), and the mixture was stirred at 60° C. for 20 hours. Insoluble materials were removed by filtration, and the solvent of the filtrate was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/1-1/2) to give 4-({4-[3-(benzyloxy)propyl]phenyl}methyl)-5-trifluoromethyl-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-1H-pyrazole (0.64 g).
Reaction SMILES: C([O:5][C:6]([NH:8][CH2:9][C:10]1[O:14][N:13]=[C:12]([C@@H:15]2[CH2:19][C:18](=[N:20][O:21][CH3:22])[CH2:17][N:16]2[C:23]([C:25]2[CH:30]=[CH:29][C:28]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[CH:27][CH:26]=2)=[O:24])[N:11]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+].[CH3:53][N:54]([CH3:60])[CH2:55][CH2:56]C(O)=O.C(Cl)CCl>CN(C1C=CN=CC=1)C>[C:28]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:29]=[CH:30][C:25]([C:23]([N:16]2[CH2:17][C:18](=[N:20][O:21][CH3:22])[CH2:19][C@H:15]2[C:12]2[N:11]=[C:10]([CH2:9][NH:8][C:6](=[O:5])[CH2:56][CH2:55][N:54]([CH3:60])[CH3:53])[O:14][N:13]=2)=[O:24])=[CH:26][CH:27]=1
Reactant: CON=C1C[C@@H](c2noc(CNC(=O)OC(C)(C)C)n2)N(C(=O)c2ccc(-c3ccccc3)cc2)C1
Reactant: CN(C)CCC(=O)O
Agent: CN(C)c1ccncc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCCl
Product: CON=C1C[C@@H](c2noc(CNC(=O)CCN(C)C)n2)N(C(=O)c2ccc(-c3ccccc3)cc2)C1
Temperature: 0 °C
Reaction time: 1 h
Yield: 52 %

Procedure:
4-{[(2S,4EZ)-2-(5-{[(tert-butoxycarbonyl)amino]methyl}-1,2,4-oxadiazol-3-yl)-4-(methoxyimino)pyrrolidinyl]carbonyl}-1,1′-biphenyl (Example 50) was treated with a 25% TFA/DCM solution at 0° C. The reaction was monitored by LC/MS and stopped after completion. The reaction was then made basic with sodium carbonate solution (10%) and extracted with DCM. The combined organic phases were dried over magnesium sulfate. Solvent removal afforded a crude product, which was used without purification in the next step. The residue was dissolved in DCM at room temperature, DMAP (1.1 equivalent) and N,N-dimethyl-β-alanine (1 equivalent) were added. The reaction mixture was then cooled down to 0° C. and EDC (1.1 equivalent) was added portion-wise. After stirring for 1 hour at 0° C., the reaction mixture was allowed to warm to room temperature. The reaction was monitored by TLC and LC/MS. Usually after 12 hours stirring at RT, the reaction mixture was hydrolyzed, washed with sodium carbonate solution (10%), dried over MgSO4, and evaporated in vacuo to give a crude product. Flash chromatography on silica gel, eluting with 60% EtOAc in hexane, gave the title compound as a mixture of E- and Z-isomers in 52% yield (82% purity by HPLC).
Reaction SMILES: [N+:1]([C:4]1[CH:18]=[CH:17][C:7]([CH2:8]P(=O)(OCC)OCC)=[CH:6][CH:5]=1)([O-:3])=[O:2].[Cl:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH:23]=O>>[Cl:19][C:20]1[CH:27]=[CH:26][CH:25]=[C:22](/[CH:23]=[CH:8]/[C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:18][CH:17]=2)[CH:21]=1
Reactant: CCOP(=O)(Cc1ccc([N+](=O)[O-])cc1)OCC
Reactant: O=Cc1cccc(Cl)c1
Product: O=[N+]([O-])c1ccc(/C=C/c2cccc(Cl)c2)cc1

Procedure:
In an analogous manner to that described in Example 36 a), the reaction of diethyl (4-nitrobenzyl)phosphonate with 3-chlorobenzaldehyde yields the (E)-1-chloro-3-[2-(4-nitrophenyl)ethenyl]-benzene as an orange crystalline solid; MS: m/e=259 (M)+.
Reaction SMILES: C[O:2][C:3]([C:5]1[C:10]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[CH:9][CH:8]=[CH:7][N:6]=1)=O.[BH4-].[Na+].CO>C1COCC1.CCOC(C)=O>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][CH:11]([C:10]2[C:5]([CH2:3][OH:2])=[N:6][CH:7]=[CH:8][CH:9]=2)[CH2:12][CH2:13]1)=[O:18])([CH3:23])([CH3:21])[CH3:22]
Reactant: COC(=O)c1ncccc1C1CCN(C(=O)OC(C)(C)C)CC1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC(c2cccnc2CO)CC1
Temperature: 0 °C
Yield: 49.9 %

Procedure:
A solution of 3′,4′,5′,6′-tetrahydro-2′H-[3,4]bipyridinyl-2,1′-dicarboxylic acid 1′-t-butyl ester 2-methyl ester (1.9 g, 5.9 mmol, 1.0 eq.) in THF (50 mL) was maintained under nitrogen. To the mixture was added NaBH4 (1.1 g, 29.5 mmol, 5.0 eq.), followed by the dropwise addition of MeOH (15 mL), while stirring at 0° C. The resulting solution was stirred for 30 minutes at room temperature. The resulting solution was diluted with EtOAc (150 mL). The resulting mixture was washed with a saturated solution of NH4Cl (1×100 mL), then with saturated aqueous NaCl (2×100 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with EtOAc/PE (1:1) to yield the title compound (860 mg) as a white solid. MS m/z: [M+H]+ calcd for C16H25N2O3, 293. found 293.
Reaction SMILES: [NH2:1][CH2:2][C:3]([N:5]([CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[F:12])=[O:4].[CH3:21][C:22]1[CH:23]=[C:24]([N:28]=[C:29]=[O:30])[CH:25]=[CH:26][CH:27]=1>>[F:12][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[N:5]([CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:3](=[O:4])[CH2:2][NH:1][C:29]([NH:28][C:24]1[CH:25]=[CH:26][CH:27]=[C:22]([CH3:21])[CH:23]=1)=[O:30]
Reactant: Cc1cccc(N=C=O)c1
Reactant: CC(C)(C)OC(=O)CN(C(=O)CN)c1ccccc1F
Product: Cc1cccc(NC(=O)NCC(=O)N(CC(=O)OC(C)(C)C)c2ccccc2F)c1
Yield: 47.6 %

Procedure:
Using a procedure similar to that described in Example 1, but starting with tert-butyl 2-[2-amino-N-(2-fluorophenyl)acetamido]acetate (2.5 g) and 3-methylphenyl isocyanate (1.2 g), and after recrystallisation in diisopropyl ether, tert-butyl 2-{N-(2-fluorophenyl)-2-[3-(3-methylphenyl)ureido]-acetamido}acetate (1.75 g), m.p. 148° C., is obtained.