Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](B3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11]([S:27]([C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)(=[O:29])=[O:28])[CH:10]=1.Br[C:38]1[CH:39]=[C:40]([CH:44]=[O:45])[CH:41]=[N:42][CH:43]=1.C(=O)(O)[O-].[Na+]>C(#N)C.O1CCCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:38]3[CH:39]=[C:40]([CH:44]=[O:45])[CH:41]=[N:42][CH:43]=3)[CH:16]=2)[N:11]([S:27]([C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)(=[O:28])=[O:29])[CH:10]=1
Reactant: COc1ccccc1-c1cn(S(=O)(=O)c2ccc(C)cc2)c2ncc(B3OC(C)(C)C(C)(C)O3)cc12
Reactant: O=Cc1cncc(Br)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC#N
Product: COc1ccccc1-c1cn(S(=O)(=O)c2ccc(C)cc2)c2ncc(-c3cncc(C=O)c3)cc12
Temperature: 80 °C
Yield: 55.5 %

Procedure:
3-(2-Methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine (5.0 g, 9.91 mmol), commercial 5-bromo-pyridine-3-carbaldehyde 1.84 g, 9.91 mmol) and 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichloromethane adduct (405 mg, 0.495 mmol) were combined in a vial under nitrogen and dissolved in acetonitrile (25 mL) and tetrahydrofuran (25 mL). Saturated sodium bicarbonate (25 mL) was added and the system was purged with nitrogen gas. The reaction mixture was capped and heated for 15 h at 80° C. The cooled mixture was diluted with ethyl acetate and washed with brine. The combined organic layers were dried over sodium sulfate and purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes to afford 5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyridine-3-carbaldehyde (2.66 g, 55.7%). MS: m/z 484 (M+H+).
Reaction SMILES: [OH:1][C:2]1[CH2:7][C:6]([CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([OH:25])[CH:20]=2)([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([OH:16])[CH:11]=2)[O:5][C:4](=[O:26])[CH:3]=1.[C:27]([C:31]1[CH:36]=[C:35]([O:37][S:38](=[O:43])(=[O:42])[N:39]([CH3:41])[CH3:40])[C:34]([CH3:44])=[CH:33][C:32]=1[S:45]S(C1C=CC(C)=CC=1)(=O)=O)([CH3:30])([CH3:29])[CH3:28].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:27]([C:31]1[C:32]([S:45][C:3]2[C:4](=[O:26])[O:5][C:6]([CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([OH:25])[CH:20]=3)([CH2:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([OH:16])[CH:11]=3)[CH2:7][C:2]=2[OH:1])=[CH:33][C:34]([CH3:44])=[C:35]([O:37][S:38](=[O:42])(=[O:43])[N:39]([CH3:40])[CH3:41])[CH:36]=1)([CH3:30])([CH3:29])[CH3:28]
Reactant: Cc1ccc(S(=O)(=O)Sc2cc(C)c(OS(=O)(=O)N(C)C)cc2C(C)(C)C)cc1
Reactant: O=C1C=C(O)CC(CCc2cccc(O)c2)(CCc2cccc(O)c2)O1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc(SC2=C(O)CC(CCc3cccc(O)c3)(CCc3cccc(O)c3)OC2=O)c(C(C)(C)C)cc1OS(=O)(=O)N(C)C

Procedure:
The compound was synthesized following General Method 9 and using 77 mg (0.2 mmol) of 4-hydroxy-6,6-bis-[2-(3-hydroxy-phenyl)-ethyl]-5,6-dihydro-pyran-2-one (prepared in Example XX), 100 mg (0.2 mmol) of toluene-4-thiosulfonic acid S-(2-tert-butyl-4-dimethylsulfamoyloxy-5-methyl-phenyl) ester (prepared in Example UUU), 18 mg (0.8 mmol) of K2CO3 and 5 mL of DMF. The reaction was worked up as described and chromatographed on silica gel, eluting with (1:1 CH2Cl2 :EtOAc+2% MeOH), to give the title compound. 1H NMR (DMSO-d6) δ 1.45 (s, 9 H), 1.9 (s, 3 H), 2.95 (m, 4 H), 2.6 (m, 4 H), 2.95 (s, 6 H), 3.35 (m, 2 H), 6.60 (m, 6 H), 6.8 (s, 1 H), 7.05 (t, 2 H), 7.15 (s, 1 H), 9.25 (s, 2 H).
Reaction SMILES: [NH2:1][CH:2]1[C:8](=[O:9])[N:7]([CH2:10][CH3:11])[C:6]2[CH:12]=[CH:13][C:14]([N+:18]([O-:20])=[O:19])=[C:15]([O:16][CH3:17])[C:5]=2[CH2:4][CH2:3]1.Br[CH2:22][CH2:23][O:24][CH2:25][CH2:26]Br.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.C(Cl)Cl>[CH2:10]([N:7]1[C:8](=[O:9])[CH:2]([N:1]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH2:3][CH2:4][C:5]2[C:15]([O:16][CH3:17])=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=[CH:12][C:6]1=2)[CH3:11]
Reactant: CCN1C(=O)C(N)CCc2c1ccc([N+](=O)[O-])c2OC
Reactant: BrCCOCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CC#N
Product: CCN1C(=O)C(N2CCOCC2)CCc2c1ccc([N+](=O)[O-])c2OC
Yield: 33.4 %

Procedure:
Combine 3-Amino-1-ethyl-6-methoxy-7-nitro-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (0.8 g), 1-Bromo-2-(2-bromo-ethoxy)-ethane (797 mg) and Potassium carbonate (879 mg) in Acetonitrile (37 mL), heat to 85° C., After 2 days, added another eq of Potassium carbonate and 0.5 eq of 1-Bromo-2-(2-bromo-ethoxy)-ethane and continue heating. Diluted with CH2Cl2, filter, the material was concentrated onto Celite and purified by ISCO chromatography (120 g, SiO2, gradient elution 0% MeOH/DCM/to 10% MEOH/DCM) to give 1-ethyl-6-methoxy-3-morpholin-4-yl-7-nitro-1,3,4,5-tetrahydro-benzo[b]azepin-2-one as an orange solid (334 mgs). 1H-NMR (CDCl3): 7.86 (d, J=8.8 Hz, 1H), 7.09 (d, J=8.6 Hz, 1H), 4.32-4.22 (m, 1H), 3.96 (s, 3H), 3.73-3.60 (m, 5H), 3.27-3.23 (m, 1H), 2.97-2.92 (m, 1H), 2.72-2.55 (m, 4H), 2.54-2.45 (m, 1H), 2.39-2.23 (m, 2H), 1.20 (t, J=7.1 Hz, 3H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]1([C@@H:12](O)[CH3:13])[CH2:11][O:10]1.[F:15][C:16]([F:25])([F:24])[CH2:17][N:18]1[CH:22]=[N:21][NH:20][C:19]1=[O:23]>>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]1([O:10][CH2:11]1)[C@H:12]([N:20]1[C:19](=[O:23])[N:18]([CH2:17][C:16]([F:15])([F:25])[F:24])[CH:22]=[N:21]1)[CH3:13]
Reactant: C[C@H](O)[C@@]1(c2ccc(F)cc2F)CO1
Reactant: O=c1[nH]ncn1CC(F)(F)F
Product: C[C@@H](n1ncn(CC(F)(F)F)c1=O)[C@@]1(c2ccc(F)cc2F)CO1
Yield: 65.7 %

Procedure:
In the same manner as in Reference Example 5, starting from 1.36 g of (1S)-1-[(2R)-2-(2,4-difluorophenyl)-2-oxiranyl]ethanol and 0.91 g of 4-(2,2,2-trifluoroethyl)-3(2H,4H)-1,2,4-triazolone, 2-[(1R,2S)-2-(2,4-difluorophenyl)-2,3-epoxy-1-methylpropyl]-4-(2,2,2-trifluoroethyl)-3(2H,4H)-1,2,4-triazolone (1.25 g) was obtained as a colorless oil. IR ν cm-1 (film): 1716, 1704, 1652, 1616, 1558, 1508.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:12]3[CH:13]=[CH:14][C:15]([CH3:17])=[CH:16][C:11]3=[N:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.F[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[N+:25]([O-:27])=[O:26].O>CN(C)C=O>[CH3:17][C:15]1[CH:14]=[CH:13][N:12]2[C:8]([C:4]3[CH:3]=[C:2]([NH:1][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[N+:25]([O-:27])=[O:26])[CH:7]=[CH:6][CH:5]=3)=[CH:9][N:10]=[C:11]2[CH:16]=1
Reactant: Cc1ccn2c(-c3cccc(N)c3)cnc2c1
Reactant: O=[N+]([O-])c1ccccc1F
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccn2c(-c3cccc(Nc4ccccc4[N+](=O)[O-])c3)cnc2c1
Temperature: 120 °C
Yield: 10.3 %

Procedure:
3-(3-Aminophenyl)-7-methylimidazo[1,2-α]pyridine (1.0 g, 4.5 mmol) and 1-fluoro-2-nitrobenzene (0.55 ml, 5.2 mmol) were dissolved in anhydrous N,N-dimethylformamide (10 ml) and heated at 120° C. for 2 days. The cooled reaction mixture was poured into water (25 ml), extracted with ethyl acetate (2×20 ml) and the combined organic phases dried over anhydrous magnesium sulphate and concentrated in vacuo. Purification by flash chromatography eluting with 5% methanol in dichloromethane gave the title compound as an orange oil (160 mg, 10%). 1H NMR (400 MHz, d4-methanol) δH 2.61 (3H, s), 6.89-6.93 (1H, m), 7.33-7.35 (1H, m), 7.40-7.42 (1H, m), 7.47-7.52 (2H, m), 7.55-7.57 (1H, m), 7.62-7.69 (2H, m), 7.74 (1H, s), 8.06 (1H, s), 8.24 (1H, d, J 7), 8.67 (1H, d, J 8); m/z (ES+) 345 (M++H).
Reaction SMILES: [CH:1]1[C:6]([CH:7]=O)=[CH:5][C:4]2[O:9][CH2:10][O:11][C:3]=2[CH:2]=1.[CH2:12]([N:14]1[C:18](=[O:19])[CH2:17][O:16][C:15]1=[O:20])[CH3:13].C1COCC1.[H-].[Na+]>O>[CH2:12]([N:14]1[C:18](=[O:19])[C:17](=[CH:7][C:6]2[CH:1]=[CH:2][C:3]3[O:11][CH2:10][O:9][C:4]=3[CH:5]=2)[O:16][C:15]1=[O:20])[CH3:13]
Reactant: O=Cc1ccc2c(c1)OCO2
Reactant: CCN1C(=O)COC1=O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCN1C(=O)OC(=Cc2ccc3c(c2)OCO3)C1=O
Yield: 16.8 %

Procedure:
1.16 g (7.73 mmol) of piperonal and 1.00 g (7.75 mmol) of N-ethyl-2,4-oxazolidinedione are introduced into a 50 ml of eggplant-shaped flask, and a spiral condenser and a drying tube are mounted thereon. The reaction vessel is internally charged with an atmosphere of nitrogen and about 10 ml of THF dried with molecular sieve is added, followed by dissolution by stirring with a magnetic stirrer. After dissolution, 0.36 g (9.0 mmol) of NaH (60 wt. %, oily) is added little by little under stirring with magnetic stirrer. After stirring at room temperature for 2 hours, the reaction mixture is poured into water. The oily substance formed is extracted with ethyl acetate, and after drying over magnesium sulfate, the solvent is removed under reduced pressure, followed by recrystallization from methanol to give 0.34 g (1.3 mmol) of N-ethyl-5-(3,4-methylenedioxy-benzylidene)-2,4-oxazolidinedione at a yield of 17 % (m.p.=135°-137 ° C.).
Reaction SMILES: Cl.Cl.[O:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[C:11]([CH:12]3[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][C@H:20]4[CH2:25][CH2:24][C@H:23]([NH2:26])[CH2:22][CH2:21]4)[CH2:14][CH2:13]3)[C:6]=2[CH2:5][CH2:4]1.[OH:27][C:28]([CH3:33])([CH3:32])[C:29](O)=[O:30]>>[O:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[C:11]([CH:12]3[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][C@H:20]4[CH2:21][CH2:22][C@H:23]([NH:26][C:29](=[O:30])[C:28]([OH:27])([CH3:33])[CH3:32])[CH2:24][CH2:25]4)[CH2:14][CH2:13]3)[C:6]=2[CH2:5][CH2:4]1
Reactant: N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3CCO4)CC2)CC1
Reactant: CC(C)(O)C(=O)O
Agent: Cl
Product: CC(C)(O)C(=O)N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3CCO4)CC2)CC1

Procedure:
The title compound, off-white solid (85 mg, 83%), MS (ISP) m/z=415.5 [(M+H)+], mp 163° C., was prepared in accordance with the general method of example 1 from trans-4-{2-[4-(2,3-dihydro-benzofuran-4-yl)-piperidin-1-yl]-ethyl}-cyclohexylamine dihydrochloride (intermediate B) (100 mg, 0.25 mmol) and 2-hydroxy-2-methyl-propionic acid.
Reaction SMILES: Cl.[C:2]([C:4]1([NH:7][C:8]([C@@H:10]2[CH2:14][C@@H:13]([S:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])(=[O:17])=[O:16])[CH2:12][NH:11]2)=[O:9])[CH2:6][CH2:5]1)#[N:3].[CH:25](=O)[CH3:26]>>[C:2]([C:4]1([NH:7][C:8]([C@@H:10]2[CH2:14][C@@H:13]([S:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])(=[O:17])=[O:16])[CH2:12][N:11]2[CH2:25][CH3:26])=[O:9])[CH2:6][CH2:5]1)#[N:3]
Reactant: CC=O
Reactant: N#CC1(NC(=O)[C@@H]2C[C@@H](S(=O)(=O)c3ccccc3Cl)CN2)CC1
Agent: Cl
Product: CCN1C[C@H](S(=O)(=O)c2ccccc2Cl)C[C@H]1C(=O)NC1(C#N)CC1

Procedure:
(2S,4R)-4-(2-chloro-benzenesulfonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide hydrochloride from experiment K4 was reductively aminated with acetaldehyde in analogy to experiment L3 to give (2S,4R)-4-(2-chloro-benzenesulfonyl)-1-ethyl-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide as a colorless oil. MS: 382.3 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([O:14]C)=[O:13])[CH:6]=[CH:5]2.C1COCC1.O.[OH-].[Li+]>O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([OH:14])=[O:13])[CH:6]=[CH:5]2
Reactant: COC(=O)c1ccc2cc(Br)ccc2c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1ccc2cc(Br)ccc2c1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A solution of methyl 6-bromo-2-naphthoate (7.70 g, 29.0 mmol) in 2:1 THF:water (150 mL) was treated with lithium hydroxide hydrate (2.44 g, 58.1 mmol) followed by stirring at room temperature for 48 h. Concentrated under vacuum, diluted with water and cooled to 0° C. Acidified to pH3 with 4N HCl. Solids were collected by filtration, dissolved in toluene-EtOAc (ca. 2 L) and washed with brine. Dried over Na2SO4, filtered and concentrated under vacuum. Brown solid was triturated with ether, collected by filtration, and dried under vacuum to give the title compound as a nearly white solid (5.07 g, 70%).
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[CH:29]([N:30]=[C:31](Br)Br)[C:28](=[O:34])[N:10]2[C:11]=1[C:12]([O:14][CH:15]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])(=[O:3])[CH3:2].[C:35]1([NH2:42])[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[NH2:41]>C1COCC1>[C:1]([O:4][CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[CH:29]([NH:30][C:31]3[NH:41][C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=4[N:42]=3)[C:28](=[O:34])[N:10]2[C:11]=1[C:12]([O:14][CH:15]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])(=[O:3])[CH3:2]
Reactant: Nc1ccccc1N
Reactant: CC(=O)OCC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)C(N=C(Br)Br)[C@H]2SC1
Solvent: C1CCOC1
Product: CC(=O)OCC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)C(Nc3nc4ccccc4[nH]3)[C@H]2SC1
Reaction time: 4 h
Yield: 70.3 %

Procedure:
To a solution of diphenylmethyl 3-acetoxymethyl-7-dibromomethyleneaminoceph-3-em-4-carboxylate (0.608 g., 1 mmole) in THF stirred under nitrogen at ambient temperature was added orthophenylenediamine (0.216 g., 2 mmole) in THF and the reaction was allowed to continue stirring for 4 hours. The solution was then evaporated to dryness and the residue was dissolved in CH2Cl2 containing a little methanol. This solution was chromatographed on silica gel (50 g.) at -40° using CH2Cl2 /MeOH 85:15 v/v as eluant to give diphenylmethyl 3-acetoxymethyl-7-(benzimidazol-2-yl)aminoceph-3-em-4-carboxylate (0.39 g.). The product had the following n.m.r. spectrum in CDCl3 : 1.92(s,3H); 3.25(m,2H); 4.57(d,1H); 4.97(d,1H); 5.15(d,1H); 5.90(d,1H); 6.85(s,1H); 3.25(m,10H).
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([C:19]2[NH:27][C:22]3=[N:23][CH:24]=[CH:25][CH:26]=[C:21]3[CH:20]=2)[C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH:17]=[CH2:18])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:28][NH:29][CH3:30].CO>>[CH:1]1([CH2:6][CH:7]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH2:17][CH2:18][N:29]([CH3:30])[CH3:28])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[C:19]2[NH:27][C:22]3=[N:23][CH:24]=[CH:25][CH:26]=[C:21]3[CH:20]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CNC
Reactant: C=CS(=O)(=O)c1ccc(C(CC2CCCC2)c2cc3cccnc3[nH]2)cc1
Solvent: CO
Product: CN(C)CCS(=O)(=O)c1ccc(C(CC2CCCC2)c2cc3cccnc3[nH]2)cc1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 12 %

Procedure:
A mixture of 2-[2-cyclopentyl-1-(4-ethenesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridine (150 mg, 0.39 mmol) and dimethylamine solution in methanol (2 M, 3 ml, 6 mmol) was stirred at 25° C. for 20 min. Purification using a Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded (2-{4-[2-cyclopentyl-1-(1H-pyrrolo[2,3-b]pyridin-2-yl)-ethyl]-benzenesulfonyl}-ethyl)-dimethyl-amine (20 mg, 12%) as a white solid: LC/MS m/e calcd for C24H31N3O2S [M+H]+ 426.60, observed 426.1; 1H NMR (400 MHz, CD3OD) δ ppm 8.08 (d, J=4.5 Hz, 1H), 7.83-7.91 (m, 2H), 7.61 (d, J=8.1 Hz, 1H), 7.04 (dd, J=7.6, 5.1 Hz, 1H), 6.39 (s, 1H), 5.49 (s, 7H), 4.32 (t, J=7.8 Hz, 1H), 3.33-3.39 (m, 2H), 2.64-2.71 (m, 1H), 2.21-2.33 (m, 1H), 2.07-2.19 (m, 5H), 1.59-1.86 (m, 4H), 1.43-1.59 (m, 2H), 1.15-1.34 (m, 2H).
Reaction SMILES: Cl[C:2]1[C:3]([N+:12]([O-:14])=[O:13])=[C:4]([CH:8]=[C:9](Cl)[CH:10]=1)[C:5]([OH:7])=[O:6].[CH2:15]([SH:27])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26].C(=O)([O-])[O-].[K+].[K+].Cl>C(O)C.O>[CH2:15]([S:27][C:2]1[C:3]([N+:12]([O-:14])=[O:13])=[C:4]([CH:8]=[C:9]([S:27][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH:10]=1)[C:5]([OH:7])=[O:6])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]
Reactant: O=C(O)c1cc(Cl)cc(Cl)c1[N+](=O)[O-]
Reactant: CCCCCCCCCCCCS
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: O
Product: CCCCCCCCCCCCSc1cc(SCCCCCCCCCCCC)c([N+](=O)[O-])c(C(=O)O)c1
Temperature: 25 °C

Procedure:
An amount of 236 g. (1 mole) 3,5-dichloro-2-nitrobenzoic acid (Step 1) and 424 g. (2.1 moles) 1-dodecanethiol in 1.5 liter ethanol and 1 liter water was purged with nitrogen for 15-30 min. Then 430 g. (3.1 moles) anhydrous potassium carbonate were added and the reaction mixture was refluxed under an atmosphere of nitrogen for 60-72 hr. After cooling to room temperature, the solution was poured slowly into a rapidly stirred mixture of 6 liters water, 360 ml. conc. HCl and crushed ice. The precipitated solid was collected and washed well with water. The yellow material was slurried in 2.7 liters of glacial acetic acid, filtered, washed with a small amount of glacial acetic acid and dried in vacuo at 45° C. An amount of 560 g. of the product was obtained, m.p. 74°-77° C.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]([OH:11])CO)=[C:4]([C:12]2[NH:13][C:14]3[C:19]([CH:20]=2)=[C:18]([F:21])[CH:17]=[CH:16][CH:15]=3)[CH:3]=1.[O-]S([O-])=O.[Na+].[Na+].O>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[NH:13][C:14]3[C:19]([CH:20]=2)=[C:18]([F:21])[CH:17]=[CH:16][CH:15]=3)[C:5]([CH:8]=[O:11])=[CH:6][N:7]=1
Reactant: OCC(O)c1cnc(Cl)cc1-c1cc2c(F)cccc2[nH]1
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: O=Cc1cnc(Cl)cc1-c1cc2c(F)cccc2[nH]1
Temperature: 25 °C
Reaction time: 2 h
Yield: 82.1 %

Procedure:
To a solution of 1-(6-chloro-4-(4-fluoro-1H-indol-2-yl)pyridin-3-yl)ethane-1,2-diol (1.9 g, 6.21 mmol) in THF—H2O (26 mL-13 mL), NaIO4 (1.94 g, 9.31 mmol) was added, the reaction mixture was stirred at room temperature for 2 hours. Then Na2SO3 and water were added and the mixture was stirred at room temperature for 30 min. The mixture was extracted with EA. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by column chromatography (DCM:MeOH=20:1) to afford the desired product of 6-chloro-4-(4-fluoro-1H-indol-2-yl)nicotinaldehyde (1.4 g, yield: 82.4%). 1H-NMR (Methanol-d4, 400 MHz) δ 8.48 (s, 1H), 7.79 (s, 1H), 7.40 (d, J=8.4 Hz, 1H), 7.17˜7.25 (m, 1H), 6.95 (s, 1H), 6.79 (dd, J=8.0, 10.0 Hz, 1H), 6.70 (s, 1H). MS (M+H)+: 275/277.
Reaction SMILES: C(=O)([O-])[OH:2].[Na+].[CH2:6]([N:8]([CH2:47][CH3:48])[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[S:17][C:18]1[C@H:19]([CH3:46])[C@@H:20]2[C@@H:37]([C@H:38]([O:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[CH3:39])[C:36](=[O:45])[N:21]2[C:22]=1[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=1)=[O:24])=[O:10])[CH3:7].ClC1C=CC=C(C(OO)=O)C=1>C(Cl)Cl>[CH2:47]([N:8]([CH2:6][CH3:7])[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[S:17]([C:18]1[C@H:19]([CH3:46])[C@@H:20]2[C@@H:37]([C@H:38]([O:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[CH3:39])[C:36](=[O:45])[N:21]2[C:22]=1[C:23]([O:25][CH2:26][C:27]1[CH:28]=[CH:29][C:30]([N+:33]([O-:35])=[O:34])=[CH:31][CH:32]=1)=[O:24])=[O:2])=[O:10])[CH3:48]
Reactant: O=C([O-])O
Reactant: CCN(CC)C(=O)c1ccccc1SC1=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)[C@H]([C@@H](C)O[Si](C)(C)C)[C@H]2[C@H]1C
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Solvent: ClCCl
Product: CCN(CC)C(=O)c1ccccc1S(=O)C1=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)[C@H]([C@@H](C)O[Si](C)(C)C)[C@H]2[C@H]1C
Yield: 83.4 %

Procedure:
122 mg (1.45 mmol) of sodium hydrogencarbonate were added to 6 ml of a methylene chloride solution containing 304 mg (0.486 mmol) of 4-nitrobenzyl (1R,5S,6S)-2-(2-diethylcarbamoylphenylthio)-1-methyl-6-[1(R)-trimethylsilyloxyethyl]-1-carbapen-2-em-3-carboxylate (prepared as described in Example 34). The mixture was then placed in an ice bath while 105 mg (0.487 mmol) of m-chloroperbenzoic acid (80% purity) were added, with stirring. The reaction mixture was stirred for 1 hour at the same temperature, after which it was diluted with methylene chloride and washed with an ice-cooled dilute aqueous solution of sodium hydrogencarbonate. The solvent was then removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through 25 g of silica gel. Elution with a 2:1 by volume mixture of ethyl acetate and hexane afforded 260 mg (yield 83%) of the title compound as a foam-like solid.
Reaction SMILES: [CH:1]1([CH:7]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]([N:30]([CH3:38])[CH2:31][CH2:32][C:33]([O:35]CC)=[O:34])=[O:29])=[CH:24][CH:23]=2)[C:8]2[O:9][C:10]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:11]=3[C:12]=2[CH2:13][O:14][CH3:15])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.O1CCCC1.[OH-].[Na+]>C(O)C>[CH:1]1([CH:7]([NH:21][C:22]2[CH:23]=[CH:24][C:25]([C:28]([N:30]([CH3:38])[CH2:31][CH2:32][C:33]([OH:35])=[O:34])=[O:29])=[CH:26][CH:27]=2)[C:8]2[O:9][C:10]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:11]=3[C:12]=2[CH2:13][O:14][CH3:15])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CCOC(=O)CCN(C)C(=O)c1ccc(NC(c2oc3ccc(F)cc3c2COC)C2CCCCC2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: COCc1c(C(Nc2ccc(C(=O)N(C)CCC(=O)O)cc2)C2CCCCC2)oc2ccc(F)cc12
Temperature: 25 °C
Reaction time: 7 h
Yield: 86.3 %

Procedure:
To a mixture of ethyl 3-[{[4-({cyclohexyl[5-fluoro-3-(methoxymethyl)-1-benzofuran-2-yl]methyl}amino)phenyl]carbonyl}(methyl)amino]propanoate (197 mg) synthesized above, tetrahydrofuran (5 mL) and ethanol (5 mL) was added 1N aqueous sodium hydroxide solution (1.00 mL), and the mixture was stirred at room temperature for 7 hr, and concentrated under reduced pressure. The residue was dissolved in water (10 mL), and 1N hydrochloric acid (1.00 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title object compound (161 mg, 87%) as a pale-yellow solid.
Reaction SMILES: [CH3:1][CH:2]1[CH2:8][CH:7]=[CH:6][CH2:5][N:4]([S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)(=[O:11])=[O:10])[CH2:3]1.C([O-])(O)=[O:19].[Na+].C1C=C(Cl)C=C(C(OO)=O)C=1>C(Cl)Cl>[CH3:1][CH:2]1[CH2:8][CH:7]2[CH:6]([O:19]2)[CH2:5][N:4]([S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)(=[O:11])=[O:10])[CH2:3]1
Reactant: O=C([O-])O
Reactant: CC1CC=CCN(S(=O)(=O)c2ccccn2)C1
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Solvent: ClCCl
Product: CC1CC2OC2CN(S(=O)(=O)c2ccccn2)C1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To the solution of 3-methyl-1-(pyridine-2-sulfonyl)-2,3,4,7-tetrahydro-1H-azepine (1.3 g, 5.16 mmol) in CH2Cl2 (50 ml) was added NaHCO3 (1.3 g, 15.5 mmol) and then mCPBA (2.67 g, 15.5 mmol) in portions. Stirred at RT for 4 h before worked up by washing with 15% NaOH, saturated K2CO3 and brine. Dried over Na2SO4. The reaction mixture was concentrated by rotary evaporation and two insomers were seperated on column chromatography (30%-40% EtoAc/Hexane). The first elution (trans-isomer, 230 mg) was used in next steps, the second elution (cis-insomer 200 mg) was saved: MS (M+H+): 269.0; 1H-NMR (400 Hz, CDCl3): d=8.70(d, 1H), 8.0-7.75(m, 2H), 7.50 (m, 1H) 4.39(m, 1H), 3.92(m, 1H), 3.34-2.00(m, 6H), 1.40(m, 1H), 0.88(d, 3H)
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[CH3:5][O:6][C:7](=[O:17])[CH:8](Br)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[I:15]>CN(C=O)C.[Cl-].[Na+].O>[CH3:5][O:6][C:7](=[O:17])[CH:8]([N:1]=[N+:2]=[N-:3])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[I:15]
Reactant: COC(=O)C(Br)c1ccccc1I
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)C(N=[N+]=[N-])c1ccccc1I
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a suspension of NaN3 (10.6 g, 163 mmol) in DMF (100 mL) is added bromo-(2-iodophenyl)-acetic acid methyl ester (19.3 g, 54.4 mmol) and the mixture is stirred at RT for 18 h. Brine is added and the mixture is extracted with ether (10×100 mL). The combined organic layers are washed with brine and dried over sodium sulfate. The solvent is removed under reduced pressure to afford the title compound which is used directly in the next step.