Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:3]2[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[CH:11]1([SH:17])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.CC(C)([O-])C.[K+].Cl>C1COCC1>[CH:11]1([S:17][C:2]2[C:3]3[CH:10]=[CH:9][NH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1
Reactant: SC1CCCCC1
Reactant: Clc1ncnc2[nH]ccc12
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: C1CCOC1
Product: c1nc(SC2CCCCC2)c2cc[nH]c2n1
Temperature: 25 °C
Yield: 22.4 %

Procedure:
To a solution of 100 mg (0.651 mmol) of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine dissolved in 3.0 mL of THF was added 0.10 mL (0.818 mmol) of cyclohexylmercaptan and 100 mg (0.847 mmol) of 95% potassium tert-butoxide and the resulting mixture heated at reflux for 3.5 hr. After cooling to room temperature, the reaction mixture was acidified to pH 1 with 2 N HCl and concentrated in vacuo. The residue was then partitioned between ethylacetate and 1 N HCl. The aqueous layer was extracted with ethyl acetate, the ethyl acetate layers were combined, washed with brine, dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified by silica-gel chromatography (1:3 ethylacetate/hexanes) providing 34 mg (22%) of the title compound as a white solid. Mp 162-163° C. 1H NMR (400 MHz) d: 1.22-1.36 (m, 1H), 1.45-1.64 (m, 5H), 1.75-1.79 (m, 2H), 2.12-2.14 (m, 2H), 4.18-4.20 (m, 1H), 6.50 (d, 1H, J=3.7 Hz), 7.19 (d, 1H, J=3.5 Hz), 8.61 (s, 1H), 10.0 (br s, 1H). LRMS: 234 (M+1).
Reaction SMILES: C(O)(C(F)(F)F)=O.[C:8]([C:11]1([C:14]2[CH:51]=[CH:50][CH:49]=[CH:48][C:15]=2[CH2:16][CH2:17][C:18]2[C:23]([C:24]([F:27])([F:26])[F:25])=[CH:22][N:21]=[C:20]([NH:28][C:29]3[CH:34]=[CH:33][C:32]([CH:35]4[CH2:40][CH2:39][N:38](C(OC(C)(C)C)=O)[CH2:37][CH2:36]4)=[CH:31][CH:30]=3)[N:19]=2)[CH2:13][CH2:12]1)(=[O:10])[NH2:9]>C(Cl)Cl>[NH:38]1[CH2:39][CH2:40][CH:35]([C:32]2[CH:31]=[CH:30][C:29]([NH:28][C:20]3[N:19]=[C:18]([CH2:17][CH2:16][C:15]4[CH:48]=[CH:49][CH:50]=[CH:51][C:14]=4[C:11]4([C:8]([NH2:9])=[O:10])[CH2:12][CH2:13]4)[C:23]([C:24]([F:27])([F:26])[F:25])=[CH:22][N:21]=3)=[CH:34][CH:33]=2)[CH2:36][CH2:37]1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(Nc3ncc(C(F)(F)F)c(CCc4ccccc4C4(C(N)=O)CC4)n3)cc2)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: NC(=O)C1(c2ccccc2CCc2nc(Nc3ccc(C4CCNCC4)cc3)ncc2C(F)(F)F)CC1
Yield: 93.5 %

Procedure:
A solution of TFA (0.65 mL, 8.5 mmol) and tert-butyl 4-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A6) (0.13 mg, 0.21 mmol) in DCM (20 mL) was stirred for 24 hours at room temperature under nitrogen. The volatiles were removed in vacuo and the residue was taken up in MeOH and loaded onto an SCX cartridge (10 g). The column was eluted with 5 column volumes of MeOH and then 5 column volumes of 5% v/v aqueous ammonia in MeOH to elute the amine product. The ammoniacal filtrate was evaporated under reduced pressure and the resulting solid was dried under high vacuum to give the title compound 2 as a white solid (100 mg, 93%); 1H NMR (400 MHz, d6-DMSO) δ 10.14 (s, 1H), 8.67 (s, 1H), 7.66 (d, J=8.6 Hz, 2H), 7.37-7.27 (m, 3H), 7.25-7.14 (m, 3H), 6.99 (s, 1H), 6.00 (s, 1H), 3.22-3.13 (m, 2H), 3.13-3.06 (m, 2H), 3.01 (d, J=11.9 Hz, 2H), 2.62-2.52 (m, peaks obscured by solvent), 1.67 (d, J=10.7 Hz, 2H), 1.57-1.40 (m, 4H), 0.97 (s, 2H). LCMS-A: rt 4.963 min; m/z 510 [M+H]+.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([C:10]2[CH:11]=[C:12]3[C:17](=[N:18][CH:19]=2)[N:16]([C:20]([NH2:22])=[O:21])[CH2:15][CH2:14][CH2:13]3)[CH:7]=[N:8][CH:9]=1)(=[O:3])[CH3:2].[BH4-].[Na+]>CO>[OH:3][CH:1]([C:4]1[CH:5]=[C:6]([C:10]2[CH:11]=[C:12]3[C:17](=[N:18][CH:19]=2)[N:16]([C:20]([NH2:22])=[O:21])[CH2:15][CH2:14][CH2:13]3)[CH:7]=[N:8][CH:9]=1)[CH3:2]
Reactant: CC(=O)c1cncc(-c2cnc3c(c2)CCCN3C(N)=O)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(O)c1cncc(-c2cnc3c(c2)CCCN3C(N)=O)c1
Reaction time: 0.5 h
Yield: 75 %

Procedure:
6-(5-Acetyl-pyridin-3-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide (20 mg, 0.067 mmol) is dissolved in 2.0 mL of MeOH and NaBH4 (7.7 mg, 0.20 mmol) is added. The mixture is stirred for 30 min and then MeOH is removed at room temperature and saturated aqueous NH4Cl (2 mL) is added along with water (2 mL) and EtOAc (5 mL). The mixture is stirred for 5 min and the aqueous layer is separated and extracted with EtOAc (2×3 ml). The organic layers are combined and concentrated to give the crude product. Purification by reversed phase chromatography affords 15 mg of the titled product.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9]C(=O)C(F)(F)F)=[CH:5][C:4]=1[C:16]([F:19])([F:18])[F:17].Cl.Cl.[CH3:22][N:23]1[CH:28]2[CH2:29][CH2:30][CH2:31][CH:24]1[CH2:25][NH:26][CH2:27]2.C(N(C(C)C)C(C)C)C>CC#N>[CH3:22][N:23]1[CH:28]2[CH2:29][CH2:30][CH2:31][CH:24]1[CH2:25][N:26]([CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][C:4]=1[C:16]([F:17])([F:18])[F:19])[CH2:27]2
Reactant: O=C(Nc1ccc(CBr)c(C(F)(F)F)c1)C(F)(F)F
Reactant: CN1C2CCCC1CNC2
Agent: Cl
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CN1C2CCCC1CN(Cc1ccc(N)cc1C(F)(F)F)C2
Temperature: 50 °C
Reaction time: 1.5 h

Procedure:
A solution of 296 mg (0.85 mMol) N-(4-bromomethyl-3-trifluoromethyl-phenyl)-2,2,2-trifluoro-acetamide (WO 2005/051366; Step 14.2) in 5 ml of CH3CN is added at 5° C. within 30 min to a solution of 213 mg (1.00 mMol) 9-methyl-3,9-diaza-bicyclo[3.3.1]nonane dihydrochloride (synthesized according to Barnes, Roderick A. et al.: J. Am. Chem. Soc. 1953, 75, 975) and 0.7 ml (4 mMol) ethyldiisopropylamine in 10 ml CH3CN. After 1.5 h at 5-10° C., the solvent is evaporated off under reduced pressure. The residue is dissolved in EtOAc and washed with NaHCO3. The aq. phase is re-extracted with EtOAc and the combined organics are washed with water, brine and dried over Na2SO4. The solvent is evaporated off under reduced pressure and the residue is dissolved in a mixture of 10 ml MeOH and 2 ml of a 2 M NaOH solution and stirred at 50° C. for 3 h. The MeOH is evaporated off under reduced pressure, the mixture is diluted with water and extracted 3 times with EtOAc. The combined organics are washed with water and brine and dried (Na2SO4). The solvent is evaporated off under reduced pressure to give the crude product which is purified by column chromatography (SiO2; CH2Cl2/EtOH/NH3 95:4.5:0.5) to afford the title compound as a crystalline solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]([O:13]C)=O)=[CH:4][CH:3]=1.[NH4+:15].[OH-]>CO>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]([NH2:15])=[O:13])=[CH:4][CH:3]=1
Reactant: [NH4+]
Reactant: COC(=O)CCCc1ccc(N)cc1
Agent: [OH-]
Solvent: CO
Product: NC(=O)CCCc1ccc(N)cc1
Yield: 70 %

Procedure:
To a solution of compound 27 (300 mg, 1.55 mmol) in CH3OH (5 mL) was added NH4OH (32) at room temperature with stirring. The reaction mixture was stirred at room temperature for 6 h and concentrated in vacuo. The residue was diluted with water and extracted with DCM/CH3OH (10:1). The combined organic layers were dried over Na2SO4 and concentrated to dryness to give compound 33 (194 mg, 70%) as a white solid. The crude product was used directly for the next step without purification.
Reaction SMILES: [CH3:1][CH2:2][C@@:3]1([OH:27])[C:8](=[O:9])[O:7][CH2:6][C:5]2[C:10]([N:12]3[C:24](=[CH:25][C:4]1=2)[C:23]1[N:22]=[C:21]2[C:16]([CH:17]=[C:18]([OH:26])[CH:19]=[CH:20]2)=[CH:15][C:14]=1[CH2:13]3)=[O:11].[CH:28](=O)[CH2:29]C.S(=O)(=O)(O)O.FC(F)(F)C(O)=O.S(OOS([O-])(=O)=O)([O-])(=O)=O.[K+].[K+]>O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Fe+2]>[CH3:28][CH2:29][C:15]1[C:14]2[CH2:13][N:12]3[C:10](=[O:11])[C:5]4[CH2:6][O:7][C:8]([C@:3]([OH:27])([CH2:2][CH3:1])[C:4]=4[CH:25]=[C:24]3[C:23]=2[N:22]=[C:21]2[C:16]=1[CH:17]=[C:18]([OH:26])[CH:19]=[CH:20]2)=[O:9]
Reactant: CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2cc3cc(O)ccc3nc2-1
Reactant: CCC=O
Agent: [Fe+2]
Agent: O=S(=O)(O)O
Agent: O=S(=O)([O-])OOS(=O)(=O)[O-]
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: CCc1c2c(nc3ccc(O)cc13)-c1cc3c(c(=O)n1C2)COC(=O)[C@]3(O)CC
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
The 10-hydroxy camptothecin (800 mg; 2.2 mmol) is suspended in water (24 ml). Iron (II) sulfate heptahydrate (250 mg, 0.85 millimoles) is added to the suspension and then followed by the addition of propionaldehyde (3 ml). The reaction mixture is then cooled in an ice bath and concentrated sulfuric acid (1 ml) and trifluoroacetic acid (24 ml) are added. After stirring the homogeneous solution for 15 minutes, potassium persulfate (3.5 g; 6 mol equivalent) is added, and the mixture is slowly warmed to room temperature. After approximately 15 hours, the reaction mixture is diluted with water and the product is extracted using excess chloroform. The crude product is washed thrice with 5% methanol in ether and dried to obtain 806 mg of the desired compound. 1H NMR (300 MHz; DMSO-d6): 0.87 δ (3H, t, J=7 Hz); 1.62 δ (3H, t, J=7 Hz); 1.85 δ (2H, 1q, J=5 Hz); 3.18 δ (2H, q, J=5 Hz); 5.19 δ (2H, m); 5.40 δ (2H, s); 6.51 δ (1H, bs); 7.23 δ (2H, m); 7.39 δ (1H, d, J=10 Hz); 8.01 δ (1H, d, J=9Hz) 13C NMR: δ7.3, 13.6, 22.4, 29.8, 72.0, 95.8, 102.7, 117.9, 120.4, 124.8, 144.6, 145.3, 156.5, 158.3, 200.1 FAB MS: 403 (M+1)+
Reaction SMILES: C1([C@@H:4](C2C=CC(B3OC(C)(C)C(C)(C)O3)=CC=2)[N:5]2[CH2:10][CH2:9][C@:8]([CH2:17][C:18]([OH:21])(C)C)(C3C=CC=CC=3)OC2=O)CC1.Br[C:39]1[CH:44]=[CH:43][C:42]([C@H:45]([CH:64]2[CH2:66][CH2:65]2)[N:46]2[CH2:51][CH2:50][C@:49]([CH2:58][C:59]([OH:62])([CH3:61])[CH3:60])([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)[O:48][C:47]2=[O:63])=[CH:41][CH:40]=1.BrC1C=CN(C)C(=O)C=1>>[CH:64]1([C@@H:45]([C:42]2[CH:43]=[CH:44][C:39]([C:8]3[CH:9]=[CH:10][N:5]([CH3:4])[C:18](=[O:21])[CH:17]=3)=[CH:40][CH:41]=2)[N:46]2[CH2:51][CH2:50][C@:49]([CH2:58][C:59]([OH:62])([CH3:61])[CH3:60])([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)[O:48][C:47]2=[O:63])[CH2:66][CH2:65]1
Reactant: CC(C)(O)C[C@]1(c2ccccc2)CCN([C@H](c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)C2CC2)C(=O)O1
Reactant: CC(C)(O)C[C@]1(c2ccccc2)CCN([C@H](c2ccc(Br)cc2)C2CC2)C(=O)O1
Agent: Cn1ccc(Br)cc1=O
Product: Cn1ccc(-c2ccc([C@H](C3CC3)N3CC[C@](CC(C)(C)O)(c4ccccc4)OC3=O)cc2)cc1=O

Procedure:
The title compound was prepared from 3-{(S)-cyclopropyl-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]methyl}-(S)-6-(2-hydroxy-2-methyl-propyl)-6-phenyl-[1,3]oxazinan-2-one {prepared in analogy to the intermediate in Example 3 from 3-[(S)-(4-bromo-phenyl)-cyclopropyl-methyl]-(S)-6-(2-hydroxy-2-methyl-propyl)-6-phenyl-[1,3]oxazinan-2-one} and 4-bromo-1-methyl-1H-pyridin-2-one following a procedure analogous to that described in Example 3. LC-MS (Method 1): tR=3.34 min; Mass spectrum (ESI+): m/z=487 [M+H]+.
Reaction SMILES: [F:1][CH:2]([F:29])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:28])[CH3:27])=[O:4].Br[C:31]1[CH:32]=[CH:33][C:34]([CH:37]([NH:39][C:40](=[O:49])[O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH3:38])=[N:35][CH:36]=1.C(=O)([O-])[O-].[Na+].[Na+].ClCCl>O1CCOCC1.O>[F:29][CH:2]([F:1])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:31]3[CH:32]=[CH:33][C:34]([CH:37]([NH:39][C:40](=[O:49])[O:41][CH2:42][C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)[CH3:38])=[N:35][CH:36]=3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:28])[CH3:27])=[O:4]
Reactant: CC1(C)O[C@H](c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)[C@@H](CF)N1C(=O)C(F)F
Reactant: CC(NC(=O)OCc1ccccc1)c1ccc(Br)cn1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Solvent: ClCCl
Product: CC(NC(=O)OCc1ccccc1)c1ccc(-c2ccc([C@H]3OC(C)(C)N(C(=O)C(F)F)[C@@H]3CF)cc2)cn1
Temperature: 80 °C

Procedure:
A mixture of the product of Example 22, Step 3, benzyl (1-(5-bromopyridin-2-yl)ethyl)carbamate, 2.0M sodium carbonate in water (3.1 mL, 6.2 mmol) in dioxane is degassed with nitrogen. 1,1′-bis(diphenylphosphino)ferrocene dichloropalladium(ii) complex with dichloromethane (169 mg, 0.21 mmol) is added and the mixture heated to 80° C. overnight. After cooling to room temperature the reaction mixture is diluted with water (25 mL) and extracted with ethylacetate. The organic phase is separated, dried over MgSO4, and concentrated under reduced pressure. The crude material is purified using silica chromatography eluting from 25% ethylacetate/heptane to 35% ethylacetate/heptane to give the title product (1.00 g): m/z: 541.22.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[CH2:9][C:10]([O:12][CH3:13])=[O:11].COC1C=CC=CC=1OC>CO>[CH3:13][O:12][C:10]([CH2:9][O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:11]
Reactant: Oc1ccccc1
Reactant: COC(=O)CCl
Solvent: CO
Solvent: COc1ccccc1OC
Product: COC(=O)COc1ccccc1

Procedure:
Illustrative Embodiment 1 is repeated with a mixture of 32 g of phenol, 56 g of methyl chloroacetate, 13 g of methanol and 8 g of dimethoxy benzene (as a gas chromatograph standard). Methyl phenoxy acetate is formed.
Reaction SMILES: [NH2:1][CH:2]1[C:19](=[O:20])[N:4]2[C:5]([C:16]([OH:18])=[O:17])=[C:6]([CH2:9][S:10][C:11]3[NH:15][N:14]=[N:13][CH:12]=3)[CH2:7][S:8][C@H:3]12.C[Si](CC(N)=O)(C)C.[S:29]1[CH:34]=[C:33]([C:35](=[N:39][O:40][CH3:41])[C:36](O)=[O:37])[S:32][CH2:31][CH2:30]1.P(Cl)(Cl)(Cl)=O>C(OCC)(=O)C.CN(C)C=O>[S:29]1[CH:34]=[C:33]([C:35](=[N:39][O:40][CH3:41])[C:36]([NH:1][CH:2]2[C:19](=[O:20])[N:4]3[C:5]([C:16]([OH:18])=[O:17])=[C:6]([CH2:9][S:10][C:11]4[NH:15][N:14]=[N:13][CH:12]=4)[CH2:7][S:8][C@H:3]23)=[O:37])[S:32][CH2:31][CH2:30]1
Reactant: CON=C(C(=O)O)C1=CSCCS1
Reactant: NC1C(=O)N2C(C(=O)O)=C(CSc3cnn[nH]3)CS[C@H]12
Agent: C[Si](C)(C)CC(N)=O
Solvent: CN(C)C=O
Solvent: O=P(Cl)(Cl)Cl
Solvent: CCOC(C)=O
Product: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=C(CSc3cnn[nH]3)CS[C@H]12)C1=CSCCS1
Yield: 71.7 %

Procedure:
A solution of 7-amino-3-(1H-1,2,3-triazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (1.57 g.) and trimethylsilylacetamide (4.6 g.) in ethyl acetate (20 ml.) and a mixture of 2-(2,3-dihydro-1,4-dithiin-5-yl)-2-methoxyiminoacetic acid (syn isomer, 1.1 g.), N,N-dimethylformamide (0.44 g.) and phosphoryl chloride (0.92 g.) were treated in a similar manner to that of Example 21 to give 7-[2-(2,3-dihydro-1,4-dithiin-5-yl)-2-methoxyiminoacetamido]-3-(1H-1,2,3-triazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 1.85 g.).
Reaction SMILES: [Cl:1][C:2]1[N:3]([C:11]2[C:12]([F:22])=[CH:13][C:14]3[O:19][CH2:18][C:17](=[O:20])[NH:16][C:15]=3[CH:21]=2)[N:4]=[C:5]2[C:10]=1[CH2:9][CH2:8][CH2:7][CH2:6]2.[H-].[Na+].[CH2:25](I)[CH3:26].O>CN(C)C=O>[Cl:1][C:2]1[N:3]([C:11]2[C:12]([F:22])=[CH:13][C:14]3[O:19][CH2:18][C:17](=[O:20])[N:16]([CH2:25][CH3:26])[C:15]=3[CH:21]=2)[N:4]=[C:5]2[C:10]=1[CH2:9][CH2:8][CH2:7][CH2:6]2
Reactant: CCI
Reactant: O=C1COc2cc(F)c(-n3nc4c(c3Cl)CCCC4)cc2N1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCN1C(=O)COc2cc(F)c(-n3nc4c(c3Cl)CCCC4)cc21
Reaction time: 3 h

Procedure:
To a solution of 3-chloro-2-[7-fluoro-2H-1,4- benzoxazin-3(4H)-on-6-yl]-4,5,6,7-tetrahydro-2H-indazole (1.0 g) in N,N-dimethylformamide (10 ml), sodium hydride (0.3 g) and ethyl iodide (0.5 g) were successively added, and the resultant mixture was heated at 50° to 60° C., followed by stirring for 3 hours. The reaction mixture was poured into water, and the precipitated crystals were collected by filtration and purified by silica gel column chromatography using a mixture of ethyl acetate and hexane as an eluent to give Compound No. 1 (0.9 g). m.p., 101.5°-102.5° C.
Reaction SMILES: [Si]([O:8][C@H:9]([CH3:35])[C@@H:10]([NH:24][C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[C:27]([Cl:33])[C:26]=1[CH3:34])[C:11]1[O:12][C:13]([C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([Cl:23])[CH:17]=2)=[N:14][N:15]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:33][C:27]1[C:26]([CH3:34])=[C:25]([NH:24][C@@H:10]([C:11]2[O:12][C:13]([C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([Cl:23])[CH:17]=3)=[N:14][N:15]=2)[C@H:9]([OH:8])[CH3:35])[CH:32]=[CH:31][C:28]=1[C:29]#[N:30]
Reactant: Cc1c(N[C@@H](c2nnc(-c3ccc(O)c(Cl)c3)o2)[C@@H](C)O[Si](C)(C)C(C)(C)C)ccc(C#N)c1Cl
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: Cc1c(N[C@@H](c2nnc(-c3ccc(O)c(Cl)c3)o2)[C@@H](C)O)ccc(C#N)c1Cl
Temperature: -78 °C
Reaction time: 3 h
Yield: 63.3 %

Procedure:
To a 100 mL round bottom flask was added 4-((1R,2R)-2-(tert-butyldimethylsilyloxy)-1-(5-(3-chloro-4-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methyl benzonitrile (586 mg, 0.9 mmol, 1.0 equiv.) and 60 mL of anhydrous THF. The solution was cooled to −78° C. and TBAF (1 mL, 0.99 mmol, 1.1 equiv., 1M in THF) was added dropwise via a syringe. The solution was stirred for 3 h while the temperature was kept below −30° C. The reaction was quenched with 25 mL of saturated ammonium chloride and diluted with 25 mL of EtOAc. The layers were separated and the organic layer was washed with distilled water (1×25 mL) and brine (1×25 mL). The organic layer was dried over Na2SO4 and was concentrated in vacuo to yield an off-white solid. The product was purified via automated flash chromatography (0→50% EtOAc/hexanes→100% EtOAc, 24 g of silica gel; TLC Rf=0.43, 100% EtOAc, vanillin stain) to provide the desired product as a white solid (239 mg, 63% yield). Other data: 1H NMR (400 MHz, acetone-d6, δ in ppm) 7.92 (d, J=2.15 Hz, 1H), 7.80 (dd, J=2.15, 8.6 Hz, 1H), 7.49 (d, J=8.6 Hz, 1H), 7.17 (d, J=8.6 Hz, 1H), 6.89 (d, J=8.79 Hz, 1H), 5.87 (d, J=8.79 Hz, 1H), 5.02 (dd, J=5.66, 8.79 Hz, 1H), 4.51 (m, 1H), 2.36 (s, 3H), 1.41 (d, J=6.45 Hz, 3H); LRMS (ESI+) exact mass calcd for C19H16Cl2N4O3 [M]+ 419.26. found 419.2.
Reaction SMILES: [C:1]1(=[O:21])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][N:2]1[CH2:10][CH2:11][O:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][OH:18])=[CH:15][CH:14]=1>[O-2].[Mn+4].[O-2].ClCCl>[C:1]1(=[O:21])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][N:2]1[CH2:10][CH2:11][O:12][C:13]1[CH:14]=[CH:15][C:16]([CH:17]=[O:18])=[CH:19][CH:20]=1
Reactant: O=C1c2ccccc2CN1CCOc1ccc(CO)cc1
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Product: O=Cc1ccc(OCCN2Cc3ccccc3C2=O)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A mixture of 4-[2-(2,3-dihydro-1H-isoindol-1-on-2-yl)-ethoxy]benzyl alcohol (2.97 g), manganese(IV) oxide (9.12 g) and dichloromethane (180 ml) was stirred for 3 hours at room temperature. The mixture was filtered through a Soxhlet thimble and the residue extracted with refluxing dichloromethane for 3 hours. The solvent was then evaporated to afford the title compound, mp 134°-135° C.
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7]O)=[CH:5][CH:4]=1.C(Br)(Br)(Br)[Br:12].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[CH3:1][S:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][Br:12])=[CH:5][CH:4]=1
Reactant: CSc1ccc(CO)cc1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CSc1ccc(CBr)cc1
Temperature: 25 °C
Yield: 71 %

Procedure:
To a mixture of 4-(methylthio)benzyl alcohol (2.00 g) and carbon tetrabromide (6.45 g) in dichloromethane (40 mL) was added triphenylphosphine (4.08 g), and the mixture was stirred for an hour at ambient temperature. After evaporation of the solvent, the residue was purified by a silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (20:1) to give 4-(methylthio)benzyl bromide (2.00 g) as a colorless oil.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH:4]1[CH:10]=[CH:9][N:8]([S:11]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=2)(=[O:13])=[O:12])[C:7]2[CH:21]=[CH:22][CH:23]=[CH:24][C:6]=2[S:5]1.[Cl:25][C:26]1[CH:27]=[C:28]([CH:32]=[CH:33][C:34]=1[Cl:35])[C:29](Cl)=[O:30].C1(C2C=CC=CC=2C(Cl)=O)C=CC=CC=1>>[OH:1][CH2:2][CH2:3][CH:4]1[CH:10]=[CH:9][N:8]([S:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:29](=[O:30])[C:28]3[CH:32]=[CH:33][C:34]([Cl:35])=[C:26]([Cl:25])[CH:27]=3)=[CH:16][CH:15]=2)(=[O:13])=[O:12])[C:7]2[CH:21]=[CH:22][CH:23]=[CH:24][C:6]=2[S:5]1
Reactant: O=C(Cl)c1ccc(Cl)c(Cl)c1
Reactant: Nc1ccc(S(=O)(=O)N2C=CC(CCO)Sc3ccccc32)cc1
Agent: O=C(Cl)c1ccccc1-c1ccccc1
Product: O=C(Nc1ccc(S(=O)(=O)N2C=CC(CCO)Sc3ccccc32)cc1)c1ccc(Cl)c(Cl)c1

Procedure:
Compound 4 as prepared in Example 25 was treated as described in Example 26 with 3,4-dichlorobenzoyl chloride (0.085 g, 0.41 mM) substituted for 2-phenylbenzoyl chloride to give the product. m/z (MH+)537
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[CH2:16][S:15][C@H:6]1[O:7][C:8]1[C:9](Br)=[N:10][CH:11]=[CH:12][CH:13]=1)(=[O:3])[CH3:2].[CH3:27][C:28]1[O:32][C:31](B(O)O)=[CH:30][CH:29]=1>>[C:1]([O:4][C@@H:5]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[CH2:16][S:15][C@H:6]1[O:7][C:8]1[C:9]([C:31]2[O:32][C:28]([CH3:27])=[CH:29][CH:30]=2)=[N:10][CH:11]=[CH:12][CH:13]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cccnc1Br
Reactant: Cc1ccc(B(O)O)o1
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cccnc1-c1ccc(C)o1

Procedure:
By carrying out the operation analogously to example 1, starting from 2-bromo-3-pyridinyl 2,3,4-tri-O-acetyl-5-thio-β-D-xylopyranoside, obtained according to preparation III, and 5-methyl-2-furanboronic acid, the desired product is obtained in the form of a white solid (yield=45%).
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:13]([OH:23])[C@@H:12]([CH2:24][O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:11][C@H:10]1[N:33]=[N+]=[N-])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(S)CCS.C(N(CC)CC)C>CO>[CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:13]([OH:23])[C@@H:12]([CH2:24][O:25][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[O:11][C@H:10]1[NH2:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [N-]=[N+]=N[C@@H]1O[C@H](COCc2ccccc2)[C@H](O)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Agent: SCCCS
Solvent: CCN(CC)CC
Solvent: CO
Product: N[C@@H]1O[C@H](COCc2ccccc2)[C@H](O)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Temperature: 25 °C
Reaction time: 10 h
Yield: 93.8 %

Procedure:
A mixture of 2,3,6-tri-O-benzyl-β-D-galactopyranosyl azide (3.00 g, 6.31 mmol), propane-1,3-dithiol (3.40 g, 31.50 mmol), and triethylamine (3.50 g, 31.5 mmol) in MeOH (31 ml) was stirred under nitrogen at room temperature for 10 hours. The reaction mixture was evaporated and purified by chromatography using CHCl3/EtOH 10:0.3 v/v to give 2,3,6-tri-O-benzyl-β-D-galactopyranosyl amine (2.66 g, 94%);
Reaction SMILES: [OH:1][NH2:2].C([O:5][C:6](=O)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][N:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1)C>CN(C=O)C.CO>[OH:1][NH:2][C:6](=[O:5])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][N:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1
Reactant: NO
Reactant: CCOC(=O)CCCCCCN(c1ccccn1)c1ccc(OC)cn1
Solvent: CO
Solvent: CN(C)C=O
Product: COc1ccc(N(CCCCCCC(=O)NO)c2ccccn2)nc1
Reaction time: 28 h
Yield: 60 %

Procedure:
HONH2 (50% aqueous, 2 mL) was added to III (11.65 mg, 0.033 mmol) in DMF (0.5 mL) and MeOH (2 mL) at rt. The reaction mixture was stirred for 28 h, after which the solvents were evaporated under reduced pressure. The resulting residue was dissolved and co-evaporated with toluene (2×10 mL) then was purified by silica gel column chromatography eluting with CH2Cl2/MeOH (100:4 then 100:6) to furnish IV as a colourless oil (6.76 mg, 60%).