Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH:3][C:4](=[O:36])[NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][C@@H:29]3[CH3:34])[C:15]3[CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][C:16]=3[N:17]=2)=[CH:8][C:7]=1[F:35])[CH3:2].[ClH:37].CO>O1CCOCC1>[ClH:37].[CH2:1]([NH:3][C:4]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][C@@H:29]3[CH3:34])[C:15]3[CH2:20][NH:19][CH2:18][C:16]=3[N:17]=2)=[CH:8][C:7]=1[F:35])=[O:36])[CH3:2]
Reactant: CCNC(=O)Nc1ccc(-c2nc3c(c(N4CCOC[C@@H]4C)n2)CN(C(=O)OC(C)(C)C)C3)cc1F
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: CCNC(=O)Nc1ccc(-c2nc3c(c(N4CCOC[C@@H]4C)n2)CNC3)cc1F
Yield: 100 %

Procedure:
(S)-tert-butyl 2-(4-(3-ethylureido)-3-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (510 mg, 1.02 mmol) was stirred in a solution of 4M HCl in Dioxane (10 ml), and methanol (3 ml) until analysis by LCMS indicated reaction was complete. Solvent was removed in vacuo to afford a light brown solid (450 mg, 1.02 mmol, 100%).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][CH:8]=[CH:9][C:10]=1[C:11]([OH:13])=[O:12])=[O:4].[ClH:14]>CO>[ClH:14].[CH3:1][O:2][C:3]([C@H:5]1[C@@H:10]([C:11]([OH:13])=[O:12])[CH2:9][CH2:8][NH:7][CH2:6]1)=[O:4]
Reactant: COC(=O)c1cnccc1C(=O)O
Agent: Cl
Solvent: CO
Product: COC(=O)[C@@H]1CNCC[C@@H]1C(=O)O
Yield: 100 %

Procedure:
Pyridine-3,4-dicarboxylic acid 3-methyl ester (5.00 g, 27.6 mmol), prepared by the method of J. C. S. Perkin I, 1981, 3012, in methanol (50 ml) was treated with excess ethereal hydrogen chloride and the solution evaporated to dryness. The resulting salt in methanol (100 ml) was hydrogenated over platinum oxide (500 mg) at 50 p.s.i. and ambient temperature until uptake ceased (24 h). The catalyst was removed by filtration through Hyflo and the filtrate evaporated to give the title compound (6.17 g, 100%), m.p. 180°-184° (dec) δ(360 MHz, D2O ) 2.10-2.20 (2H, m, 5-CH2); 3.19-3.25 (2H, m, 3-CH, 4-CH); 3.27-3.32 (1H, m, 6-CH ax); 3.34-3.39 (1H, m, 6-CH eq); 3.51 (1H,dd, J13 Hz and 4 Hz, 2-CH eq); 3.60 91H, dd, J 7.5 Hz and 13 Hz, 2-CH ax).
Reaction SMILES: CO[C:3]([C:5]1[C:14]2[O:13][CH2:12][CH2:11][O:10][C:9]=2[CH:8]=[C:7](S(=O)(=O)NC)[CH:6]=1)=[O:4].[CH3:20][N:21]1[CH2:25][CH2:24][CH2:23][CH:22]1[CH2:26][NH2:27]>C(O)(=O)C.O>[CH3:20][N:21]1[CH2:25][CH2:24][CH2:23][CH:22]1[CH2:26][NH:27][C:3]([C:5]1[C:14]2[O:13][CH2:12][CH2:11][O:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4]
Reactant: CNS(=O)(=O)c1cc2c(c(C(=O)OC)c1)OCCO2
Reactant: CN1CCCC1CN
Solvent: O
Solvent: CC(=O)O
Product: CN1CCCC1CNC(=O)c1cccc2c1OCCO2
Yield: 112 %

Procedure:
169 g of methyl-7-methylsulfamoyl-1,4-benzodioxane-5-carboxylate, 53 ml of water and 81 g of 1-methyl-2-aminomethylpyrrolidine were introduced into a balloon flask provided with a reflux condenser. The mixture was heated on a water bath until a test sample was totally soluble in dilute acids. The resulting crystals were dissolved in a solution of 50 ml of acetic acid in 1,250 ml of water and then the solution was filtered over carbon black and the base was reprecipitated by the addition of 100 ml of 20% ammonia. The crystals were dried off, washed with water and dried. 182 g of N-(1-methyl-2-pyrrolidylmethyl)-1,4-benzodioxane-5-carboxamide was produced (M.P.: 189°-190° C.; yield: 83.6%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10]([CH3:25])=[N:11][N:12]([CH3:24])[C:13]=1[CH:14]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[F:23])[OH:15].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10]([CH3:25])=[N:11][N:12]([CH3:24])[C:13]=1[C:14]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[F:23])=[O:15]
Reactant: Cc1nn(C)c(C(O)c2ccc(F)cc2F)c1-c1ccc(F)cc1Cl
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: Cc1nn(C)c(C(=O)c2ccc(F)cc2F)c1-c1ccc(F)cc1Cl
Temperature: 25 °C
Reaction time: 16 h

Procedure:
4-(2-Chloro-4-fluorophenyl)-α-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol (i.e. the product of Synthesis Example 6) (90 mg, 0.25 mmol) was dissolved in dichloromethane (8 mL), and pyridinium dichromate (113 mg, 0.3 mmol) was added in one portion. The reaction mixture was stirred at ambient temperature for 16 h, and then the reaction mixture was partitioned between water (5 mL) and dichloromethane (5 mL). The organic phase was washed with additional water (5 mL) and with brine (5 mL), dried over Na2SO4 and concentrated under reduced pressure to give a viscous residue. This residue was purified by column chromatography through silica gel eluted with a gradient of ethyl acetate in hexane (25% to 30%) to give the title product, a compound of the present invention, as a pale yellow viscous oil (29 mg).
Reaction SMILES: [CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([CH:14]3[CH2:17][N:16]([C:18]([O:20]C4C=CC([N+]([O-])=O)=CC=4)=O)[CH2:15]3)=[O:13])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[CH2:30]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:33][CH2:32][NH:31]1.CCN(C(C)C)C(C)C.C(O)(C)C>ClCCCl.ClCCl>[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([CH:14]3[CH2:15][N:16]([C:18]([N:31]4[CH2:32][CH2:33][C:34]5[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=5)[CH2:30]4)=[O:20])[CH2:17]3)=[O:13])[CH2:7][CH2:6]2)[CH2:2][CH2:3][CH2:4]1
Reactant: O=C(Oc1ccc([N+](=O)[O-])cc1)N1CC(C(=O)N2CCCN(C3CCC3)CC2)C1
Reactant: c1ccc2c(c1)CCNC2
Solvent: ClCCl
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(C1CN(C(=O)N2CCc3ccccc3C2)C1)N1CCCN(C2CCC2)CC1
Temperature: 25 °C
Yield: 18.9 %

Procedure:
4-Nitrophenyl 3-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]azetidine-1-carboxylate (50 mg, 0.12 mmol), 1,2,3,4-tetrahydroisoquinoline (25 μl, 0.19 mmol) and DIPEA (42 μl, 0.24 mmol) were stirred in 1,2-dichloroethane (2 ml) and isopropanol (1 ml) at 120° C. in a sealed tube for 16 hrs. The mixture was then cooled to RT, diluted with dichloromethane (30 ml) and washed with 1M aq. K2CO3 (2×15 ml), dried (MgSO4), filtered and concentrated at reduced pressure. The residue was purified by silica FCC (eluting with 99:1:1 to 92:8:1 gradient of DCM/MeOH/2M NH3 in MeOH) to give the title compound (9 mg, 19% yield) as colourless oil.
Reaction SMILES: [CH2:1]([C:7]1[N:8]([CH2:20][CH2:21][CH2:22][CH2:23][NH2:24])[C:9]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N:12]=[CH:11][C:10]=2[N:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[C:25]1([S:31](Cl)(=[O:33])=[O:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[CH2:1]([C:7]1[N:8]([CH2:20][CH2:21][CH2:22][CH2:23][NH:24][S:31]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)(=[O:33])=[O:32])[C:9]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N:12]=[CH:11][C:10]=2[N:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCCc1nc2cnc3ccccc3c2n1CCCCN
Reactant: O=S(=O)(Cl)c1ccccc1
Product: CCCCCCc1nc2cnc3ccccc3c2n1CCCCNS(=O)(=O)c1ccccc1
Yield: 43.6 %

Procedure:
Using the general method of Example 233 Part B except that the reaction was run at ambient temperature, 4-(2-hexyl-1H-imidazo[4,5-c]quinolin-1-yl)butan-1-amine (1.20 g, 3.7 mmol) was reacted with benzenesulfonyl chloride (429 μL, 3.7 mmol) to provide 0.75 g of N-[4-(2-hexyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzenesulfonamide as a light yellow solid, m.p. 137.0-138.1° C.
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][O:9][C:10]1[C:11]2[N:18]=[C:17]([NH:19][C:20]([N:22]3[CH2:26][CH2:25][CH:24]([NH2:27])[CH2:23]3)=[O:21])[S:16][C:12]=2[N:13]=[CH:14][N:15]=1.C(N(CC)C(C)C)(C)C.[F:37][C:38]1[CH:45]=[CH:44][C:41]([CH:42]=O)=[CH:40][C:39]=1[C:46]([F:49])([F:48])[F:47].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.O.C1(C)C=CC=CC=1>[CH3:8][O:9][C:10]1[C:11]2[N:18]=[C:17]([NH:19][C:20]([N:22]3[CH2:26][CH2:25][C@@H:24]([NH:27][CH2:42][C:41]4[CH:44]=[CH:45][C:38]([F:37])=[C:39]([C:46]([F:49])([F:47])[F:48])[CH:40]=4)[CH2:23]3)=[O:21])[S:16][C:12]=2[N:13]=[CH:14][N:15]=1
Reactant: COc1ncnc2sc(NC(=O)N3CCC(N)C3)nc12
Reactant: O=Cc1ccc(F)c(C(F)(F)F)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: CO
Product: COc1ncnc2sc(NC(=O)N3CC[C@@H](NCc4ccc(F)c(C(F)(F)F)c4)C3)nc12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 52.8 %

Procedure:
A suspension of the trifluoroacetic acid salt of 3-amino-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (2.35 g, 5.8 mmol) in methanol (50 mL) was treated with N,N-diisopropylethylamine (1.5 mL, 8.6 mmol). The resulting mixture was stirred at 25° C. for 30 min. At this time, the reaction was treated with 4-fluoro-3-(trifluoromethyl)benzaldehyde (1.34 g, 6.96 mmol) followed by toluene (50 mL). The resulting mixture was stirred at 60° C. for 1 h and then concentrated in vacuo. Additional toluene (200 mL) was then added. The reaction mixture was stirred for 15 min and then concentrated in vacuo. This procedure was repeated a few times until the reaction mixture became homogenous when dissolved in toluene. After the final concentration to remove toluene, the reaction mixture was diluted with dichloroethane (100 mL) and then treated with acetic acid (351 mg, 5.8 mmol) and sodium triacetoxyborohydride (3.7 g, 17.4 mmol). The resulting reaction mixture was allowed to stir at 25° C. overnight. The reaction mixture was poured into water and extracted with ethyl acetate. The combined organics were washed with water, a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, gradient elution 1:1 ethyl acetate/hexanes to 100% ethyl acetate) afforded (R)-3-(4-fluoro-3-trifluoromethyl-benzylamino)-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (1.44 g, 52.8%) as a foamy solid; ES-HRMS m/e calcd for C19H18F4N6O2S (M+H)+ 471.1221, found 471.1221.
Reaction SMILES: C1(C([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:36])[C@@H:24]([NH:25][C:26](=[O:35])[C@@H:27]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[OH:28])[C@H:21]3[S:20][CH2:19][C:18]=2[S:37][CH:38](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[S:39][C:40]2[N:41]=[N:42][NH:43][CH:44]=2)=[O:16])C2C=CC=CC=2)C=CC=CC=1.FC(F)(F)C(O)=O>C1(OC)C=CC=CC=1.ClCCl.CO>[C:26]([NH:25][C@@H:24]1[C:23](=[O:36])[N:22]2[C:17]([C:15]([OH:16])=[O:14])=[C:18]([S:37][CH2:38][S:39][C:40]3[N:41]=[N:42][NH:43][CH:44]=3)[CH2:19][S:20][C@H:21]12)(=[O:35])[C@@H:27]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[OH:28]
Reactant: O=C(OC(c1ccccc1)c1ccccc1)C1=C(SC(Sc2c[nH]nn2)C(c2ccccc2)(c2ccccc2)c2ccccc2)CS[C@@H]2[C@H](NC(=O)[C@H](O)c3ccccc3)C(=O)N12
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(O)C1=C(SCSc2c[nH]nn2)CS[C@@H]2[C@H](NC(=O)[C@H](O)c3ccccc3)C(=O)N12
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 24.6 %

Procedure:
To a solution of 7β-D-mandelamido-3-(trityl-1,2,3-triazol-4-ylthiomethylthio)-3-cephem-4-carboxylic acid diphenylmethyl ester (445 mg: 0.502 mMol.) in a mixture of anisole (0.8 ml) and dichloromethane (2 ml) under ice cooling is added trifluoroacetic acid (2 ml), and the mixture is stirred under ice cooling for 30 minutes and at room temperature for 20 minutes. The reaction mixture is diluted with methanol (10 ml) and concentrated. The residue is dissolved in dilute aqueous sodium hydrogen carbonate water, washed with ethyl acetate, acidified with 10% hydrochloric acid, and extracted with ethyl acetate. The extract is dried over sodium sulfate and concentrated. The residue is pulverized with ether to give 7β-D-mandelamido-3-(1,2,3-triazol-4-ylthiomethylthio)-3-cephem-4-carboxylic acid (59.2 mg) as yellowish white powder. Yield: 25%.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:11][C:12](=[O:14])[CH3:13].C(=O)([O-])[O-].[K+].[K+].[Cl:21][CH2:22][CH2:23][CH2:24]Cl>CN(C)C=O>[Cl:21][CH2:22][CH2:23][CH2:24][O:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:11][C:12](=[O:14])[CH3:13]
Reactant: CC(=O)Nc1ccc([N+](=O)[O-])cc1O
Reactant: ClCCCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(=O)Nc1ccc([N+](=O)[O-])cc1OCCCCl
Temperature: 50 °C
Reaction time: 1 h

Procedure:
A mixture of 98.1 g (0.5 mol) of N-[2-hydroxy-4-nitrophenyl)acetamide and 69.2 g (0.5 mol) of potassium carbonate in 500ml of dimethylformamide was heated to 50° C. with stirring, 113.0 g (1 mol) of 1,3-dichloropropane were then added and heating was continued at 50° C. for one hour.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH3:13])=[N:10][C:9]=2[C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH:17]2[CH2:22][C:23]2[O:24][CH:25]=[C:26]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[N:27]=2)=[O:15])=[CH:4][CH:3]=1.[Br:34]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Br:34][C:25]1[O:24][C:23]([CH2:22][CH:17]2[CH2:18][O:19][CH2:20][CH2:21][N:16]2[C:14]([C:9]2[N:10]=[C:11]([CH3:13])[S:12][C:8]=2[C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[O:15])=[N:27][C:26]=1[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1nc(C(=O)N2CCOCC2Cc2nc(-c3ccccc3)co2)c(-c2ccc(F)cc2)s1
Solvent: ClC(Cl)(Cl)Cl
Product: Cc1nc(C(=O)N2CCOCC2Cc2nc(-c3ccccc3)c(Br)o2)c(-c2ccc(F)cc2)s1
Temperature: 25 °C
Reaction time: 24 h
Yield: 66.2 %

Procedure:
The compound of example 67 (0.152 g) was dissolved in carbon tetrachloride (10 ml) and was then treated with N-bromosuccinimide (0.058 g) and stirred under argon at room temperature for 24 h. A further quantity of N-bromosuccinimide (0.006 g) was added and the mixture stirred for a further 1 h. The mixture was filtered through a cotton wool plug and the filtrate was evaporated to dryness under reduced pressure. The residue was column chromatographed (silica gel, 0→40% ethyl acetate-pentane) to give the title compound (0.117 g).
Reaction SMILES: C(O)C.Br[C:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=1[CH:11]=[O:12].[N+:13]([C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1)([O-:15])=[O:14].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.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>[N+:13]([C:16]1[CH:21]=[C:20]([C:5]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[CH:11]=[O:12])[CH:19]=[CH:18][CH:17]=1)([O-:15])=[O:14]
Reactant: O=CC1=C(Br)CCCC1
Reactant: O=[N+]([O-])c1cccc(B(O)O)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: O=CC1=C(c2cccc([N+](=O)[O-])c2)CCCC1
Temperature: 25 °C
Yield: 73.7 %

Procedure:
Ethanol (11.1 mL) was added to a solution of 2-bromocyclohex-1-enecarbaldehyde (2.22 g) in toluene (22.2 mL). 3-Nitrophenylboronic acid (2.34 g), tetrakis(triphenylphosphine)palladium (270 mg) and a 1 N sodium carbonate solution (14.0 mL) were added to the mixture. The atmosphere of the reaction system was replaced with nitrogen. Then, the reaction solution was stirred with heating under reflux for three hours. The reaction solution was cooled to room temperature, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a residue. The residue was purified by silica gel column chromatography to obtain the title compound (2.00 g).
Reaction SMILES: [CH2:1]([S:7]([OH:10])(=[O:9])=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[CH3:11][C:12]([N:14]([OH:49])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:21]([CH2:23][CH2:24][C:25]([N:27]([OH:48])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][NH:33][C:34]([CH2:36][CH2:37][C:38]([N:40]([OH:47])[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][NH2:46])=[O:39])=[O:35])=[O:26])=[O:22])=[O:13]>>[CH2:1]([S:7]([O-:10])(=[O:9])=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[CH3:11][C:12]([N:14]([OH:49])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:21]([CH2:23][CH2:24][C:25]([N:27]([OH:48])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][NH:33][C:34]([CH2:36][CH2:37][C:38]([N:40]([OH:47])[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][NH2:46])=[O:39])=[O:35])=[O:26])=[O:22])=[O:13]
Reactant: CCCCCCS(=O)(=O)O
Agent: CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN
Product: CCCCCCS(=O)(=O)[O-]

Procedure:
Following a procedure analogous to that of Example 1, hexane-1-sulphonic acid and desferrioxamine-B are reacted to give the hexane-1-sulphonate salt of desferrioxamine-B. Mp 138° C. C31H62O11 N6S Calcd C: 51.22%, H:8.60%, N:11.56%, S:4.41%; Found C: 51.04%, H: 8.50%, N:11.40%, S:4.19%.
Reaction SMILES: [Br:1][C:2]1[C:3]([O:8][CH:9]2[CH2:14][CH2:13]S(=O)(=O)[CH2:11][CH2:10]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[O:17]1CCC(O)CC1>>[Br:1][C:2]1[C:3]([O:8][CH:9]2[CH2:14][CH2:13][O:17][CH2:11][CH2:10]2)=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: OC1CCOCC1
Reactant: O=S1(=O)CCC(Oc2ncccc2Br)CC1
Product: Brc1cccnc1OC1CCOCC1

Procedure:
The title compound was prepared in a manner similar to that described in Step A for the synthesis of 4-((3-bromopyridin-2-yl)oxy)tetrahydro-2H-thiopyran 1,1-dioxide using tetrahydro-2H-pyran-4-ol. 1H NMR (400 MHz, DMSO-d6) δ 8.11 (dd, J=4.8, 1.7, 1H), 7.99 (dd, J=7.7, 1.7, 1H), 6.90 (dd, J=7.7, 4.8, 1H), 5.22 (m, 1H), 3.86-3.77 (m, 2H), 3.49 (m, 2H), 1.95 (m, 2H), 1.61 (m, 2H).
Reaction SMILES: [NH2:1][C@H:2]([C:4]([N:6]1[CH:14]2[CH:9]([CH2:10][CH2:11][CH2:12][CH2:13]2)[CH2:8][C@H:7]1[C:15]([OH:17])=[O:16])=[O:5])[CH3:3].[NH:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]([CH2:27][CH2:28][C:29](=O)[C:30]([OH:32])=[O:31])=[CH:19]1.C([BH3-])#N.[Na+]>>[C:30]([CH:29]([NH:1][C@H:2]([C:4]([N:6]1[CH:14]2[CH:9]([CH2:10][CH2:11][CH2:12][CH2:13]2)[CH2:8][C@H:7]1[C:15]([OH:17])=[O:16])=[O:5])[CH3:3])[CH2:28][CH2:27][C:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[NH:18][CH:19]=1)([OH:32])=[O:31]
Reactant: O=C(O)C(=O)CCc1c[nH]c2ccccc12
Reactant: C[C@H](N)C(=O)N1C2CCCCC2C[C@H]1C(=O)O
Agent: [BH3-]C#N
Agent: [Na+]
Product: C[C@H](NC(CCc1c[nH]c2ccccc12)C(=O)O)C(=O)N1C2CCCCC2C[C@H]1C(=O)O

Procedure:
Condense 1-[(S)-alanyl]octahydroindole-2(S)-carboxylic acid (preparable as described in Example 1) and 4-(3-indolyl)-2-oxobutyric acid with sodium cyanoborohydride, using the procedure described in Example 5 to yield the title compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[NH:7][CH2:8][CH2:9][C:10](=[C:12]1C(=O)OC(C)(C)[O:14][C:13]1=O)[OH:11])([CH3:4])([CH3:3])[CH3:2]>O1CCOCC1>[C:1]([O:5][C:6]([N:7]1[CH2:8][CH2:9][C:10](=[O:11])[CH2:12][C:13]1=[O:14])=[O:22])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)NCCC(O)=C1C(=O)OC(C)(C)OC1=O
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)N1CCC(=O)CC1=O
Yield: 102.8 %

Procedure:
A stirred solution of [3-(2,2-dimethyl-4,6-dioxo-[1,3]dioxin-5-ylidene)-3-hydroxy-propyl]-carbamic acid tert-butyl ester (9.2 g, 29.2 mmol) obtained from Example 41 in 180 ml of dioxane was heated to reflux for 2 hours. The mixture was evaporated under reduced pressure to give the crude product 2,4-dioxo-piperidine-1-carboxylic acid tert-butyl ester (6.4 g) as a yellow oil which was used as such.
Reaction SMILES: [C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:58]/[O:59][C:60]([C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])([CH3:62])[CH3:61])/[C:27]([NH:29][CH:30]2[C:56](=[O:57])[N:32]3[C:33]([C:40]([O:42][CH:43]([C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)[C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)=[O:41])=[C:34]([CH2:38]I)[CH2:35][S:36](=[O:37])[C@H:31]23)=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br.[OH:71][C:72]1[CH:73]=[C:74]2[C:79](=[CH:80][C:81]=1[OH:82])[CH:78]=[N:77][N:76]=[CH:75]2.C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O>[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:58]/[O:59][C:60]([C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])([CH3:62])[CH3:61])/[C:27]([NH:29][CH:30]2[C:56](=[O:57])[N:32]3[C:33]([C:40]([O:42][CH:43]([C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)[C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)=[O:41])=[C:34]([CH2:38][N:76]4[N:77]=[CH:78][C:79]5[C:74]([CH:73]=[C:72]([OH:71])[C:81](=[O:82])[CH:80]=5)=[CH:75]4)[CH2:35][S:36](=[O:37])[C@H:31]23)=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)C(C)(C)O/N=C(\C(=O)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CI)CS(=O)[C@H]12)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Reactant: Oc1cc2cnncc2cc1O
Agent: Br
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)C(C)(C)O/N=C(\C(=O)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(Cn3cc4cc(O)c(=O)cc-4cn3)CS(=O)[C@H]12)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Temperature: 25 °C
Reaction time: 3 h
Yield: 95.8 %

Procedure:
A mixture of diphenylmethyl 7-[(Z)-2-(2-tritylaminothiazol-4-yl)-2-(1-t-butoxycarbonyl-1-methylethoxyimino)acetamido]-3-iodomethyl-3-cephem-4-carboxylate 1-oxide (IIa, 538 mg, 0.5 mmol), 6,7-dihydroxyphthalazine hydrobromide (158 mg, 0.65 mmol) and triethylamine (0.1 ml, 0.7 mmol) in DMF (1.5 ml) was stirred at room temperature for 3 hr. The reaction mixture was diluted with EtOAc (100 ml), washed with aqueous sodium thiosulfate, water, and aqueous sodium chloride, dried over magnesium sulfate and concentrated to yield 547 mg of a crude product, which was chromatographed on a silica gel column (7 g, 5% methanol in chloroform). The desired fractions were combined and concentrated to yield 532 mg (Yield 97%) of the title compound.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:17]2[CH:16]=[CH:15][N:14]=[C:13]([O:18][CH3:19])[C:12]=2[C:11]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]#[N:28])=[CH:22][CH:21]=2)=[N:10]1.C1C(=O)N([Br:36])C(=O)C1.O>CN(C=O)C>[Br:36][C:16]1[C:17]2[N:9]([C:3]3[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=3[F:1])[N:10]=[C:11]([C:20]3[CH:25]=[CH:24][C:23]([CH2:26][C:27]#[N:28])=[CH:22][CH:21]=3)[C:12]=2[C:13]([O:18][CH3:19])=[N:14][CH:15]=1
Reactant: COc1nccc2c1c(-c1ccc(CC#N)cc1)nn2-c1c(F)cccc1F
Reactant: O=C1CCC(=O)N1Br
Solvent: O
Solvent: CN(C)C=O
Product: COc1ncc(Br)c2c1c(-c1ccc(CC#N)cc1)nn2-c1c(F)cccc1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 89.9 %

Procedure:
To a solution of (4-(1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl)phenyl)acetonitrile (148.1 mg) obtained in Step A of Example 39 in DMF (5 mL) was added NBS (77 mg) at 0° C., and the mixture was allowed to be warmed to room temperature, and stirred overnight. The reaction mixture was poured into water, and the mixture was extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (161 mg).