Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:10]2[C:9]([CH2:11][N:12]3[C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=4[N:14]([CH2:21][CH2:22][C:23]#[N:24])[C:13]3=[O:25])=[CH:8][S:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[N:26]([Si](C)(C)C)=[N+:27]=[N-:28].C([Sn](=O)CCCC)CCC.O>CN(C=O)C>[CH3:1][C:2]1[C:10]2[C:9]([CH2:11][N:12]3[C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=4[N:14]([CH2:21][CH2:22][C:23]4[NH:28][N:27]=[N:26][N:24]=4)[C:13]3=[O:25])=[CH:8][S:7][C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: Cc1cccc2scc(Cn3c(=O)n(CCC#N)c4ccccc43)c12
Reactant: C[Si](C)(C)N=[N+]=[N-]
Agent: CCCC[Sn](=O)CCCC
Solvent: CN(C)C=O
Solvent: O
Product: Cc1cccc2scc(Cn3c(=O)n(CCc4nnn[nH]4)c4ccccc43)c12
Temperature: 150 °C
Yield: 22.6 %

Procedure:
3-[3-(4-Methyl-benzo[b]thiophen-3-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-propionitrile (58 mg, 0.17 mmol), azidotrimethylsilane (0.047 mL, 0.33 mmol) and dibutyltin oxide (4.2 mg, 0.017 mmol) are dissolved in dry DMF (2.0 mL) in microwave vial. It is then heated at 150° C. for 2 hrs in microwave reactor. Then another 0.05 mL of azidotrimethylsilane and 4.0 mg of dibutyltin oxide are added and the mixture is heated for another 2 hr at 150° C. in microwave reactor. Then water (2 mL) is added and the mixture is extracted with EtOAc (2×30 mL). The organic layers are combined and extracted with 2.0M NaOH (2×30 mL). The NaOH layers are combined and washed with EtOAc (30 mL). Then the NaOH layers are acidified with 1.0M HCl to pH=3 and it is then extracted with EtOAc (2×30 mL). All the organic layers are combined, dried (MgSO4) and concentrated to give crude product. Purification by preparative TLC using 3% MeOH in CH2Cl2 affords 15 mg (65%) of 1-(4-Methyl-benzo[b]thiophen-3-ylmethyl)-3-[2-(1H-tetrazol-5-yl)-ethyl]-1,3-dihydro-benzimidazol-2-one. LCMS (ESMS): m/z 391.07 (M+H+).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1.[C:21]1(=[O:31])[NH:25][C:24](=[O:26])[C:23]2=[CH:27][CH:28]=[CH:29][CH:30]=[C:22]12.[K].O>CN(C=O)C>[C:11]1([O:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:25]2[C:24](=[O:26])[C:23]3=[CH:27][CH:28]=[CH:29][CH:30]=[C:22]3[C:21]2=[O:31])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1
Reactant: ClCCCCCCCCOc1cccc2ccccc12
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: O
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CCCCCCCCOc1cccc2ccccc12

Procedure:
9.5 g of 1-chloro-8-(1-naphthyloxy)octane and 8.4 g of potassium phthalimide were taken up in 50 ml DMF and the resulting solution was heated at 140° for 3 hours. The reaction solution was then poured into water and extracted with dichloromethane. The extract was washed, dried and evaporated and the residue was crystallized from acetone/hexane to afford the intermediate N-[8-(1-naphthyloxy)octyl]phthalimide mp 63°-64°.
Reaction SMILES: Cl.[C:2]1([C:8]2([NH2:11])[CH2:10][CH2:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:21]([O:25][C:26]([N:28]([CH3:58])[C:29]([C:31]1[C:32]([C:51]2[CH:56]=[CH:55][C:54]([F:57])=[CH:53][CH:52]=2)=[N:33][N:34]2[C:39]([F:40])=[CH:38][C:37]([C:41]3[CH:42]=[C:43]([CH:47]=[CH:48][C:49]=3[CH3:50])[C:44](O)=[O:45])=[CH:36][C:35]=12)=[O:30])=[O:27])([CH3:24])([CH3:23])[CH3:22].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:40][C:39]1[N:34]2[N:33]=[C:32]([C:51]3[CH:56]=[CH:55][C:54]([F:57])=[CH:53][CH:52]=3)[C:31]([C:29]([N:28]([CH3:58])[C:26](=[O:27])[O:25][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:30])=[C:35]2[CH:36]=[C:37]([C:41]2[CH:42]=[C:43]([C:44](=[O:45])[NH:11][C:8]3([C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH2:10][CH2:9]3)[CH:47]=[CH:48][C:49]=2[CH3:50])[CH:38]=1
Reactant: Cc1ccc(C(=O)O)cc1-c1cc(F)n2nc(-c3ccc(F)cc3)c(C(=O)N(C)C(=O)OC(C)(C)C)c2c1
Reactant: NC1(c2ccccc2)CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Cc1ccc(C(=O)NC2(c3ccccc3)CC2)cc1-c1cc(F)n2nc(-c3ccc(F)cc3)c(C(=O)N(C)C(=O)OC(C)(C)C)c2c1
Temperature: 25 °C

Procedure:
To a solution containing 1-phenylcyclopropanamine hydrochloride (0.010 g, 0.061 mmol), diisopropylethylamine (0.086 mL, 0.49 mmol), 3-(3-(tert-butoxycarbonyl(methyl)carbamoyl)-7-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid (0.032 g, 0.061 mmol) and DMF (0.41 mL) was added HATU (0.047 g, 0.12 mmol) in one portion. The solution was maintained at room temperature for 1 h and concentrated. The resultant residue was purified on silica gel (30-100% ethyl acetate/hexanes, 45 min. gradient) to afford tert-butyl 7-fluoro-2-(4-fluorophenyl)-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carbonyl(methyl)carbamate as a residue. LCMS retention time: 2.938 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10 micron, C18, 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% CH3OH/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3OH/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 637 (MH+).
Reaction SMILES: ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH:23]1([C:26]([OH:28])=O)[CH2:25][CH2:24]1.[NH2:29][C@@H:30]([CH3:50])[C:31]([N:33]1[CH2:38][CH2:37][CH:36]([CH2:39][CH2:40][C:41]2[C:42]([NH2:49])=[N:43][C:44]([CH3:48])=[N:45][C:46]=2[Cl:47])[CH2:35][CH2:34]1)=[O:32]>C1COCC1.CCOC(C)=O>[NH2:49][C:42]1[C:41]([CH2:40][CH2:39][CH:36]2[CH2:35][CH2:34][N:33]([C:31](=[O:32])[C@@H:30]([NH:29][C:26]([CH:23]3[CH2:25][CH2:24]3)=[O:28])[CH3:50])[CH2:38][CH2:37]2)=[C:46]([Cl:47])[N:45]=[C:44]([CH3:48])[N:43]=1
Reactant: O=C(O)C1CC1
Reactant: Cc1nc(N)c(CCC2CCN(C(=O)[C@H](C)N)CC2)c(Cl)n1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cc1nc(N)c(CCC2CCN(C(=O)[C@H](C)NC(=O)C3CC3)CC2)c(Cl)n1
Yield: 78.9 %

Procedure:
Add 1-hydroxy-7-azabenzotriazole (281 mg, 2.03 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (430 mg, 2.21 mmol) to a slurry of cyclopropanecarboxylic acid (161 μL, 2.03 mmol), (2S)-2-amino-1-[4-[2-(4-amino-6-chloro-2-methyl-pyrimidin-5-yl)ethyl]-1-piperidyl]propan-1-one (600 mg, 1.84 mmol) in anhydrous THF (12 mL). Then add TEA (770 μL, 5.52 mmol) and stir the resulting mixture at RT for 12 h. Dilute the reaction mixture with EtOAc (10 mL), filter over diatomaceous earth, and concentrate the filtrate in vacuo. Purify the resulting residue by mass-guided HPLC reverse phase chromatography (Agilent® 1200 LCMS and MSD mass spectrometer, 75×30 mm Phenomenex Gemini-NX®, 5μ particle size column with a 10×20 mm guard, 12-46% ACN in 10 mM aqueous ammonium bicarbonate solution, pH 10, gradient over 9 min) to obtain the title compound as a colorless glass (572 mg, 78%). LC-ESMS m/z (35Cl/37Cl) 394.2/396.2 (M+H).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH2:7]([O:14][C:15]1[CH:20]=[CH:19][C:18](Br)=[CH:17][C:16]=1[N+:22]([O-:24])=[O:23])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.COC1C=CC(N2CCOCC2)=CC=1[N+]([O-])=O>>[CH2:7]([O:14][C:15]1[CH:20]=[CH:19][C:18]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[CH:17][C:16]=1[N+:22]([O-:24])=[O:23])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: O=[N+]([O-])c1cc(Br)ccc1OCc1ccccc1
Reactant: C1COCCN1
Agent: COc1ccc(N2CCOCC2)cc1[N+](=O)[O-]
Product: O=[N+]([O-])c1cc(N2CCOCC2)ccc1OCc1ccccc1

Procedure:
The title compound was prepared using morpholine and 1-benzyloxy-4-bromo-2-nitro-benzene (prepared from 4-bromo-2-nitro-anisol and benzyl bromide) using the general method of example “4-(4-methoxy-3-nitro-phenyl)-morpholine” as yellow solid (58%), MS: m/e=315(M+H+).
Reaction SMILES: C(N(CC)CC)C.[CH2:8]([S:10][C:11]1[CH:33]=[CH:32][CH:31]=[CH:30][C:12]=1[C:13]([NH:15][NH:16][C:17](=[O:29])[C:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[CH:20][CH:19]=1)=O)[CH3:9].[Cl-].ClC1N(C)CC[NH+]1C>C(Cl)Cl>[CH2:8]([S:10][C:11]1[CH:33]=[CH:32][CH:31]=[CH:30][C:12]=1[C:13]1[O:29][C:17]([C:18]2[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[CH:20][CH:19]=2)=[N:16][N:15]=1)[CH3:9]
Reactant: CCCCCc1ccc(C(=O)NNC(=O)c2ccccc2SCC)cc1
Agent: CN1CC[NH+](C)C1Cl
Agent: [Cl-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCc1ccc(-c2nnc(-c3ccccc3SCC)o2)cc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Triethylamine (735 μL, 5.28 mmol) was added to a stirring solution of 2-(ethylthio)-N′-(4-pentylbenzoyl)benzohydrazide (1-D) (326 mg, 0.88 mmol) and 2-chloro-1,3-dimethylimidazolinium chloride (448 mg, 2.64 mmol) in methylene chloride (10 mL). After stirring at room temperature for 18 h, the mixture was diluted with methylene chloride and washed with water, 1N HCl, 10% NaHCO3, brine, dried (MgSO4) and evaporated in vacuo. The oily residue was purified by preparative TLC (silica gel, hexane:ethyl acetate, 4:1) to provide 2-[2-(ethylthio)phenyl]-5-(4-pentylphenyl)-1,3,4-oxadiazole (1-E).
Reaction SMILES: [Mg].[F:2][C:3]([F:16])([F:15])[C:4]1[CH:5]=[C:6](Br)[CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1.Cl[C:18]1[C:27]2[C:22](=[CH:23][CH:24]=[C:25]([CH3:28])[CH:26]=2)[N:21]=[C:20]([CH3:29])[CH:19]=1.[F:30][C:31]([F:45])([F:44])[C:32]1[CH:33]=[C:34]([Mg:42][Br:43])[CH:35]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:37]=1>O.C1COCC1>[F:45][C:31]([F:30])([F:44])[C:32]1[CH:33]=[C:34]([Mg:42][Br:43])[CH:35]=[C:36]([C:38]([F:40])([F:41])[F:39])[CH:37]=1.[F:2][C:3]([F:16])([F:15])[C:4]1[CH:5]=[C:6]([C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([CH3:28])[CH:26]=3)[N:21]=[C:20]([CH3:29])[CH:19]=2)[CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1
Reactant: Cc1ccc2nc(C)cc(Cl)c2c1
Reactant: FC(F)(F)c1cc(Br)cc(C(F)(F)F)c1
Agent: FC(F)(F)c1cc([Mg]Br)cc(C(F)(F)F)c1
Agent: [Mg]
Solvent: O
Solvent: C1CCOC1
Product: Cc1ccc2nc(C)cc(-c3cc(C(F)(F)F)cc(C(F)(F)F)c3)c2c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Magnesium (1.60 g) was added to THF (60 ml) in a nitrogen atmosphere and 3,5-bis (trifluoromethyl)phenylbromide (17.58 g) was dropped. The resulting mixture was stirred for 30 minutes at room temperature and a THF solution of 3,5-bis (trifluoromethyl)phenylmagnesiumbromide was prepared. In a nitrogen atmosphere, 4-chloro-2,6-dimethylquinoline (2.88 g) and Ni(dpp)Cl2 (500 mg) were added to THF (30 ml) and dispersed. The THF solution of 3,5-bis(trifluoromethyl)phenylmagnesiumbromide prepared as above was dropped to the suspension and the resulting solution was stirred for 4 days at room temperature. Water was poured into the reaction solution, impurities were filtered, and extraction was performed using AcOEt (ethyl acetate). A drying process was applied using Na2SO4 and the solvent was removed under a reduced pressure. The residue was purified through a silica gel column (hexane/ethyl acetate=3/2) to obtain 4-(3,5-bis(trifluoromethyl)phenyl)-2,6-dimethylquinoline (4.40 g) represented by the following chemical formula (49).
Reaction SMILES: [F-:1].[K+].Cl[C:4]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:5]=1[C:6]([NH:8][CH2:9][C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])=[O:7].C1OCCOCCOCCOCCOCCOC1>CS(C)=O>[F:1][C:4]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:5]=1[C:6]([NH:8][CH2:9][C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])=[O:7]
Reactant: O=C(CNC(=O)c1cc([N+](=O)[O-])ccc1Cl)OCc1ccccc1
Reactant: [F-]
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [K+]
Solvent: CS(C)=O
Product: O=C(CNC(=O)c1cc([N+](=O)[O-])ccc1F)OCc1ccccc1
Temperature: 105 °C
Reaction time: 0.75 h
Yield: 63.6 %

Procedure:
A mixture of spray dried KF (208 mg, 3.58 mmol), intermediate 6 (250 mg, 0.71 mmol) and catalytic amount of 18-crown-6 in dry DMSO (5 mL) was stirred at 100-110° C. for 45 min. Work-up of the reaction mixture as described in example 1 gave the product as a brown color solid (150 mg, 63%), mp 56-58° C. 1H NMR (400 MHz, CDCl3): δ 9.00 (1H, dd, J=6.0, 2.8 Hz), 8.36-8.40 (1H, m), 7.31-7.38 (7H, m), 5.25 (2H, s), 4.34 (2H, d, J=4.4 Hz); LC-MS (negative ion mode): m/z 331 (M−H)−.
Reaction SMILES: Br[CH2:2][C:3]1[O:4][C:5](=[O:20])[C:6]2[C:11]([C:12]=1[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2.[N:21]1[C:29]([NH2:30])=[C:28]2[C:24]([NH:25][CH:26]=[N:27]2)=[N:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>>[NH2:30][C:29]1[N:21]=[CH:22][N:23]=[C:24]2[C:28]=1[N:27]=[CH:26][N:25]2[CH2:2][C:3]1[O:4][C:5](=[O:20])[C:6]2[C:11]([C:12]=1[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2
Reactant: Nc1ncnc2[nH]cnc12
Reactant: O=c1oc(CBr)c(-c2cccc(F)c2)c2ccccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Product: Nc1ncnc2c1ncn2Cc1oc(=O)c2ccccc2c1-c1cccc(F)c1
Yield: 62.6 %

Procedure:
The title compound was made in a similar way as that of the compound of example 1, using 3-(bromomethyl)-4-(3-fluorophenyl)-1H-isochromen-1-one (intermediate C4, 50 mg, 0.150 mmol), commercially available 9H-purin-6-amine (40.6 mg, 0.300 mmol) and K2CO3 (41.5 mg, 0.300 mmol) to give the title compound (36.4 mg, 62.6%) as a colourless solid.
Reaction SMILES: [OH:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.Br[CH2:14][C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[O:16]=[C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:14][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:11][CH:12]=1
Reactant: CCOC(=O)c1ccc(O)cc1
Reactant: O=C(CBr)OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccc(OCC(=O)OCc2ccccc2)cc1
Yield: 99 %

Procedure:
A mixture of ethyl p-hydroxybenzoate (4.98 g), benzyl bromoacetate (4.75 ml) and K2CO3 (4.14 g) was stirred for 15 hr in 30 ml of DMF. The reaction mixture was diluted with water (200 ml) and extracted with a 1:1 ether:hexane mixture. The combined organic extracts were washed (water, brine), dried (Na2SO4), filtered, and evaporated leaving 9.3 g, (99%) of the title compound as a heavy oil; TLC, Rf =0.71, Et2O: hexane (1:1).
Reaction SMILES: [C:1]([O:5][C:6](=[O:29])[NH:7][C:8]1([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH:20]=2)[CH2:13][CH2:12][C:11](=O)[C:10](=[CH:15][N:16](C)C)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].O.[NH2:31]N>C(O)C>[C:1]([O:5][C:6](=[O:29])[NH:7][C:8]1([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH:20]=2)[CH2:13][CH2:12][C:11]2[C:10](=[CH:15][NH:16][N:31]=2)[CH2:9]1)([CH3:3])([CH3:2])[CH3:4]
Reactant: NN
Reactant: CN(C)C=C1CC(NC(=O)OC(C)(C)C)(c2cccc(C(C)(C)C)c2)CCC1=O
Solvent: CCO
Solvent: O
Product: CC(C)(C)OC(=O)NC1(c2cccc(C(C)(C)C)c2)CCc2n[nH]cc2C1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To crude [1-(3-tert-Butyl-phenyl)-3-dimethylaminomethylene-4-oxo-cyclohexyl]-carbamic acid tert-butyl ester (91 mg, 0.227 mmol) was added ethanol (6 mL) and hydrazine hydrate (0.010 mL, 0.32 mmol). The reaction mixture was stirred at room temperature for 12 h then placed in a freezer overnight. The reaction mixture was concentrated under reduced pressure yielding the title compound: Rf=0.35 in 5% MeOH/CH2Cl2; retention time=1.92 min, method [7]; mass spec (ESI) 392 (25), 370 (2), 315 (24), 314 (100).
Reaction SMILES: ClCCl.[I-].[Cl:5][C:6]1[N:7](C)[CH:8]=[N+:9]2[CH:13]=[C:12]([C:14]3[CH2:15][C@@H:16]4[C@@H:33]([C@H:34]([OH:36])[CH3:35])[C:32](=[O:37])[N:17]4[C:18]=3[C:19]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=3)=[O:20])[S:11][C:10]=12>CN(C=O)C>[Cl:5][C:6]1[N:7]=[CH:8][N:9]2[CH:13]=[C:12]([C:14]3[CH2:15][C@@H:16]4[C@@H:33]([C@H:34]([OH:36])[CH3:35])[C:32](=[O:37])[N:17]4[C:18]=3[C:19]([O:21][CH2:22][C:23]3[CH:24]=[CH:25][C:26]([N+:29]([O-:31])=[O:30])=[CH:27][CH:28]=3)=[O:20])[S:11][C:10]=12
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(c3c[n+]4cn(C)c(Cl)c4s3)C[C@H]12
Agent: [I-]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(c3cn4cnc(Cl)c4s3)C[C@H]12

Procedure:
In the same manner as in Example 4-a) except that 98 mg of 4-nitrobenzyl (5R,6S)-2-(7-chloroimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate and a mixed solvent of dichloromethane and DMF (1:1), the crude 4-nitrobenzyl (5R,6S)-2-(7-chloro-6-methylimidazo[5,1-b]thiazolium-2-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate iodide was obtained as a yellowish brown oil in a yield of 99 mg.
Reaction SMILES: [C:1]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:24]=[C:23]3[C:19]([CH2:20][N:21]([C@@H:26]([CH:31]([CH3:33])[CH3:32])[C:27]([O:29][CH3:30])=[O:28])[C:22]3=[O:25])=[CH:18][CH:17]=2)=[CH:12][CH:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.NC1C=CC(C2C=C3C(CN([C@@H](C(C)C)C(OC)=O)[C:47]3=[O:50])=CC=2)=CC=1.COC1C=CC=CC=1C(Cl)=O>>[CH3:47][O:50][C:7]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:1]([NH:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH:24]=[C:23]3[C:19]([CH2:20][N:21]([C@@H:26]([CH:31]([CH3:33])[CH3:32])[C:27]([O:29][CH3:30])=[O:28])[C:22]3=[O:25])=[CH:18][CH:17]=2)=[CH:14][CH:15]=1)=[O:8]
Reactant: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(N)cc3)cc2C1=O
Reactant: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(NC(=O)c4ccccc4)cc3)cc2C1=O
Agent: COc1ccccc1C(=O)Cl
Product: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(NC(=O)c4ccccc4OC)cc3)cc2C1=O
Yield: 90 %

Procedure:
The compound of example 159 was prepared analogous to compound of example 97 by reaction of compound of example 6 with 2-methoxy benzoyl chloride.
Reaction SMILES: C(OC(=O)C)(=[O:3])C.CCN(CC)CC.[N+:15]1([O-])[C:16](=[CH:20][CH:21]=[C:22]([CH:26]=1)[C:23]([OH:25])=[O:24])C(O)=O>C(Cl)(Cl)(Cl)Cl>[OH:3][C:16]1[CH:20]=[CH:21][C:22]([C:23]([OH:25])=[O:24])=[CH:26][N:15]=1
Reactant: CC(=O)OC(C)=O
Reactant: O=C(O)c1ccc(C(=O)O)[n+]([O-])c1
Solvent: ClC(Cl)(Cl)Cl
Solvent: CCN(CC)CC
Product: O=C(O)c1ccc(O)nc1
Reaction time: 0.25 h
Yield: 79.1 %

Procedure:
20.4 g of acetic acid anhydride (0.2 mole), 20.2 g of Et3N (0.2 mole) and 50 ml of CCl4 were put up in a flask. 18.3 g of isocinchomeronic acid-N-oxide (0.1 mole) was added by portions to this solution. The temperature rose to 50° C. After completion of the reaction the solvents were distilled off. About 100 ml of 20 percent KOH was added drop by drop to the viscous residue and the acetate was saponified over a 15 minute period at 80° C. After removal of the Et3N by extraction, the aqueous solution was acidified with concentrated HCl. The precipitate was sucked off, washed with water and dried under a vacuum. 11.0 g of 6-hydroxy nicotinic acid was obtained, which was pure according to NMR. The crude yield was about 79 percent.
Reaction SMILES: [CH3:1][N:2]([CH2:6][CH2:7][CH:8]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1)[CH2:3][CH2:4][NH2:5].[C:21]([NH:23][C:24](=[N:32][CH2:33][CH2:34][S:35][CH2:36][C:37]1[N:38]=[C:39]([NH:42][C:43]([NH2:45])=[NH:44])[S:40][CH:41]=1)OC1C=CC=CC=1)#[N:22]>>[C:21]([NH:23][C:24]([NH:32][CH2:33][CH2:34][S:35][CH2:36][C:37]1[N:38]=[C:39]([NH:42][C:43]([NH2:45])=[NH:44])[S:40][CH:41]=1)=[N:5][CH2:4][CH2:3][N:2]([CH2:6][CH2:7][CH:8]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1)[CH3:1])#[N:22]
Reactant: N#CNC(=NCCSCc1csc(NC(=N)N)n1)Oc1ccccc1
Reactant: CN(CCN)CCC(c1ccccc1)c1ccccn1
Product: CN(CCN=C(NC#N)NCCSCc1csc(NC(=N)N)n1)CCC(c1ccccc1)c1ccccn1

Procedure:
Preparation is effected analogously to Example 1, using 0.8 g (3 mmol) of N-methyl-N-[3-phenyl-3-(2-pyridyl)propyl]-1,2-ethanediamine and 1.01 g (2.7 mmol) of N-cyano-N'-[2-[[(2-guanidino-4-thiazolyl)methyl]thio]ethyl]-O-phenyl-isourea as starting materials. Working up by chromatography analogously to Example 1 yields the purified title compound in the form of a viscous oil; MS (+FAB method): m/z (rel. int.[%])=551 ([M+H]+, 2), 196 (100); IR (KBr): 2164 cm-1 (C≡N). For analytical purposes a sample is converted into the maleic acid salt and recrystallised from ether/ethanol; m.p.: 115°-116° C. with decomposition.
Reaction SMILES: [S:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=[C:2]1[O:10][C:11]1[CH:12]=[CH:13][C:14]2[CH:18]=[C:17]([CH2:19]O)[S:16][C:15]=2[CH:21]=1.S(Cl)([Cl:24])=O>C(Cl)Cl>[Cl:24][CH2:19][C:17]1[S:16][C:15]2[CH:21]=[C:11]([O:10][C:2]3[S:1][C:9]4[C:4]([N:3]=3)=[N:5][CH:6]=[CH:7][CH:8]=4)[CH:12]=[CH:13][C:14]=2[CH:18]=1
Reactant: OCc1cc2ccc(Oc3nc4ncccc4s3)cc2s1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: ClCc1cc2ccc(Oc3nc4ncccc4s3)cc2s1
Temperature: 0 °C
Reaction time: 3 h
Yield: 82.6 %

Procedure:
To a cooled (0° C.) solution of [6-(thiazolo[4,5-b]pyridin-2-yloxy)-benzo[b]thiophen-2-yl]-methanol (0.13 g, 0.4 mmol) in DCM (5 mL) was added thionyl chloride (30 μL, 49 mg, 0.4 mmol) and the reaction mixture was stirred (0° C., 3 h). The reaction mixture was partitioned between DCM (20 mL) and saturated NaHCO3 (10 mL). The organic layer was separated and the aqueous layer was extracted with DCM (2×20 mL). The organic layer was dried, filtered and concentrated in vacuo to provide the title compound as a yellow solid (0.11 g, 77%). MS (ESI): mass calcd. for C15H9ClN2OS2, 332.0; m/z found, 333.0 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.57 (dd, J=4.8, 1.6, 1H), 8.07-7.91 (m, 2H), 7.77 (d, J=8.7, 1H), 7.40 (dd, J=8.7, 2.2, 1H), 7.31 (d, J=0.4, 1H), 7.25-7.14 (m, 1H), 4.86 (s, 2H).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7](=[O:9])[CH3:8].ClS([N:14]=[C:15]=O)(=O)=O.CN(C)C=O.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl>[C:7]([C:3]1[N:2]([CH3:1])[CH:6]=[C:5]([C:15]#[N:14])[CH:4]=1)(=[O:9])[CH3:8]
Reactant: CC(=O)c1cccn1C
Reactant: O=C=NS(=O)(=O)Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(=O)c1cc(C#N)cn1C
Temperature: 25 °C
Yield: 33.9 %

Procedure:
1-(1-Methyl-1H-pyrrol-2-yl)-ethanone (4.00 g, 32.48 mmol) in dry methylene chloride (30 mL) was cooled to −78° C. under nitrogen. Chlorosulfonyl isocyanate (2.8 mL, 32.5 mmol) was added dropwise, and the mixture allowed to warm to room temperature over 1 h. The reaction was cooled down to −78° C. and dimethylformamide (8 mL) was added. The reaction was allowed to warm up to room temperature (2 h) and was then poured into a 1 N sodium carbonate solution, which was extracted with methylene chloride. The organic layers were washed with water, dried (anhydrous MgSO4) and evaporated. The residue was then purified by silica gel column chromatography (ethyl acetate:hexanes 1:5 to 1:3) to afford 5-acetyl-1-methyl-1H-pyrrole-3-carbonitrile (1.63 g, 34%), which was used without further characterization.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:21])[N:5]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[Cl:20])[C:6]([CH2:12]Cl)=[N:7]2.O.[SH:23][C:24]1[N:32]=[CH:31][N:30]=[C:29]2[C:25]=1[NH:26][CH:27]=[N:28]2.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:21])[N:5]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[Cl:20])[C:6]([CH2:12][S:23][C:24]1[N:32]=[CH:31][N:30]=[C:29]3[C:25]=1[N:26]=[CH:27][NH:28]3)=[N:7]2
Reactant: Sc1ncnc2nc[nH]c12
Reactant: O=c1c2c(Cl)cccc2nc(CCl)n1-c1ccccc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=c1c2c(Cl)cccc2nc(CSc2ncnc3[nH]cnc23)n1-c1ccccc1Cl
Yield: 84.8 %

Procedure:
Prepared according to Procedure C using Intermediate 2f (300 mg, 0.883 mmol), 6-mercaptopurine monohydrate (165 mg, 0.972 mmol), K2CO3 (134 mg, 0.972 mmol), and DMF (4 mL). The crude product was recrystallized from EtOH to provide 341 mg of a pale orange crystalline solid (85%), mp 233.7-234.4° C. (decomposes). 1H NMR (DMSO-d6) δ: 13.58 (br s, 1H); 8.50 (s, 1H); 8.47 (s, 1H); 7.77-7.85 (m, 2H); 7.68 (d, J=8.1 Hz, 2H); 7.65 (d, J=7.7 Hz, 1H); 7.41-7.56 (m, 2H); 4.45 (d, J=1.2 Hz, 2H). 13C NMR (DMSO-d6) ppm:, 158.7, 156.8, 153.8, 151.5, 149.6, 149.5, 143.5, 135.4, 134.1, 133.3, 132.2, 131.6, 131.6, 130.5, 130.2, 128.8, 127.1, 117.6, 32.0. MS (ES): m/z 455.0 (M+). Anal. calcd. for C20H12Cl2N6OS.C2H6O.0.3H2: C, 52.14; H, 3.70; Cl, 13.99; N, 16.58; S, 6.33. Found: C, 52.07; H, 3.37; Cl, 13.40; N, 16.65; S, 6.42.