Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH2:10][C:9]2=[O:13])=[CH:4][CH:3]=1.[C:14](Cl)([N:16]=[C:17]=[O:18])=[O:15]>C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[C:9]3[O:13][C:17](=[O:18])[NH:16][C:14](=[O:15])[C:10]=3[CH2:11][CH2:12]2)=[CH:6][CH:7]=1
Reactant: O=C=NC(=O)Cl
Reactant: O=C1CCCC1c1ccc(F)cc1
Solvent: CCOC(C)=O
Product: O=c1[nH]c(=O)c2c(o1)C(c1ccc(F)cc1)CC2
Temperature: 130 °C
Yield: 52.6 %

Procedure:
A mixture of 2-(4-fluorophenyl)cyclopentanone (18.557 g, 104 mmol) and carbonisocyanatidic chloride (19.77 g, 187 mmol) was heated at 58° C. for 1 h and at 130° C. for 2 h. Upon cooling to room temperature, the tarrified reaction mixture was dissolved in ethyl acetate and washed with saturated aqueous solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 7-(4-fluorophenyl)-6,7-dihydrocyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (13.527 g, 54.7 mmol, 52.5% yield) as brown solid. LC-MS (M+H)+=248.1. 1H NMR (500 MHz, CDCl3) δ ppm 11.80 (1H, br s), 7.31-7.39 (2H, m), 7.16-7.22 (2H, m), 4.30-4.38 (1H, m), 2.63-2.73 (1H, m), 2.53-2.63 (2H, m), 1.84-1.95 (1H, m).
Reaction SMILES: [N+:1]([C:4]1[C:9](Cl)=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])([O-:3])=[O:2].[C:17]1([S-:23])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[Na+]>CN(C)C=O>[N+:1]([C:4]1[C:9]([S:23][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])([O-:3])=[O:2]
Reactant: CCOC(=O)Cc1cccc(Cl)c1[N+](=O)[O-]
Reactant: [S-]c1ccccc1
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)Cc1cccc(Sc2ccccc2)c1[N+](=O)[O-]

Procedure:
A mixture of ethyl 2-(2-nitro-3-chlorophenyl)acetate (8.4 g.), sodium benzenethiolate (4.6 g.), and dimethylformamide (50 ml.) was treated in a similar manner to the above to give yellow needles of the captioned compound (7.25 g.). mp 65° to 67° C.
Reaction SMILES: [C:1](Cl)([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.[NH:21]1[CH:25]=[CH:24][N:23]=[CH:22]1.C(N(CC)CC)C>C(Cl)Cl>[C:1]([N:21]1[CH:25]=[CH:24][N:23]=[CH:22]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: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: c1c[nH]cn1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: c1ccc(C(c2ccccc2)(c2ccccc2)n2ccnc2)cc1
Temperature: 25 °C
Yield: 90.2 %

Procedure:
To a solution of trityl chloride (5.58 g, 20.0 mmol.) in dry methylene chloride (100 ml) cooled down to 0° C. and stirred under Ar, was added dropwise over 1.5 hours a solution of imidazole (1.36 g, 20.0 mmol.) and triethylamine (2.7 mml, 20 mmol.) in 50 ml dry methylene chloride. At the end of the addition, the reaction mixture was allowed to warm up to room temperature and stirred under Ar at that temperature overnight. The reaction mixture was then washed with 20 ml of a 10% solution of ammonium chloride, then with 20 ml of distilled water. The organic phase was dried over magnesium sulfate and evaporated in vacuo to yield quantitatively a white solid. Recrystallization from methylene chloride/hexanes yielded 5.60 g of (5) (yield=90% after recrystallization). m.p. 214° C.; 1H NMR (200 MHz, CDCl3) δ 7.43 (m, 1H, NCHN), 7.3-7.4 (m, 9H, 3×C6H5), 7.1-7.2 (m, 6H, 3×C6H5), 7.0 (m, 1H, Ph3CNCH═CH), 6.81 (m, 1H, Ph3CNCH═CH); 13C NMR (50 MHz, CDCl3) δ 142.3, 139.0, 129.6, 128.2, 128.3, 121.6.
Reaction SMILES: [CH3:1][S:2]([N:5]1[C:13]2[CH2:12][CH:11]([C:14]3[S:15][CH:16]=[CH:17][CH:18]=3)[CH2:10][C:9](=O)[C:8]=2[C:7]([CH3:20])=[CH:6]1)(=[O:4])=[O:3].[C:21]([NH:24][NH2:25])([NH2:23])=[NH:22].[ClH:26].Cl.O>C(O)C>[ClH:26].[NH:24]([N:25]=[C:9]1[CH2:10][CH:11]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)[CH2:12][C:13]2[N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH:6]=[C:7]([CH3:20])[C:8]1=2)[C:21]([NH2:23])=[NH:22]
Reactant: Cc1cn(S(C)(=O)=O)c2c1C(=O)CC(c1cccs1)C2
Reactant: N=C(N)NN
Agent: Cl
Solvent: CCO
Solvent: O
Product: Cc1cn(S(C)(=O)=O)c2c1C(=NNC(=N)N)CC(c1cccs1)C2
Yield: 100.1 %

Procedure:
A mixture of 1-methanesulfonyl-3-methyl-6-(2-thienyl)-4,5,6,7-tetrahydroindol-4-one (0.20 g), aminoguanidine hydrochloride (0.075 g), concentrated hydrochloric acid (0.032 ml), water (0.032 ml) and ethanol (30 ml) was refluxed for 1 hour. Under reduced pressure, the solvent was evaporated, and the residue was recrystallized from ethanol to give 4-guanidinoimino-1-methanesulfonyl-3-methyl-6-(2-thienyl)-4,5,6,7-tetrahydroindole hydrochloride (Compound 18) (0.26 g) as colorless crystals.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:17])[C:5]1[CH:13]=[C:12]([N+:14]([O-:16])=[O:15])[CH:11]=[C:7]([C:8](O)=[O:9])[CH:6]=1)[CH3:2].C(Cl)(=O)C([Cl:21])=O.CN(C=O)C>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:17])[C:5]1[CH:13]=[C:12]([N+:14]([O-:16])=[O:15])[CH:11]=[C:7]([C:8]([Cl:21])=[O:9])[CH:6]=1)[CH3:2]
Reactant: CCOC(=O)c1cc(C(=O)O)cc([N+](=O)[O-])c1
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CCOC(=O)c1cc(C(=O)Cl)cc([N+](=O)[O-])c1
Reaction time: 2 h

Procedure:
To a solution of 5-nitroisophtalic acid monoethyl ester (80 g) in DCM (700 ml) at 25° C. was added 2M oxalyl chloride solution in DCM (63 ml), and DMF (5 ml). The reaction was stirred for 2 h and then concentrated in vacuum. The residue was triturated with toluene and again concentrated in vacuum leaving the title compound (60 g). Rt=1.40 min for derivatised methylester (method D).
Reaction SMILES: [H-].[Na+].C1COCC1.C(OP([CH2:16][C:17]#[N:18])(=O)OCC)C.[C:19]1([CH:25]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[N:26]2[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>O.C(OC(=O)C)C>[C:19]1([CH:25]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[N:26]2[CH2:31][CH2:30][C:29](=[CH:16][C:17]#[N:18])[CH2:28][CH2:27]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: CCOP(=O)(CC#N)OCC
Reactant: O=C1CCN(C(c2ccccc2)c2ccccc2)CC1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: N#CC=C1CCN(C(c2ccccc2)c2ccccc2)CC1
Reaction time: 0.5 h

Procedure:
2.9 g (97 mmol) 80% sodium hydride are suspended in abs. THF and a solution of 21.5 g (121 mmol) diethyl-(cyanomethyl)-phosphonate in 150 ml abs. THF is added dropwise under light cooling. The mixture is subsequently stirred 30 minutes at RT and then a solution of 26.5 g (100 mmol) N-(diphenylmethyl)4-piperidone in 80 ml abs. THF is added dropwise. The suspension is left to stand overnight and subsequently added to 200 ml acetic acid ethyl ester and 100 ml water. The organic phase is separated and washed with 100 ml water, dried over sodium sulfate and the solvent is removed under vacuum. The residue is chromatographically purified over silica gel with dichloromethane. Yield: 22.7 g (78%).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]2[N:9]=[C:10]([S:12][CH2:13][CH2:14][OH:15])[N:11]=[C:4]2[N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[C:36]1[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O.O1CCCC1>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]2[N:9]=[C:10]([S:12][CH2:13][CH2:14][O:15][C:36]3[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=3)[N:11]=[C:4]2[N:3]=1
Reactant: Oc1ccncc1
Reactant: Cc1cc(C)n2nc(SCCO)nc2n1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Product: Cc1cc(C)n2nc(SCCOc3ccncc3)nc2n1
Reaction time: 0.25 h

Procedure:
A mixture of 2-({5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}sulfanyl)ethan-1-ol (100 mg, 0.446 mmol), triphenylphosphine (175 mg, 0.670 mmol), 4-hydroxypyridine (55 mg, 0.58 mmol), and tetrahydrofuran (0.5 mL) was added to a 20 mL scintillation vial. The mixture was placed in a sonicating bath, and diisopropyl azodicarboxylate (0.133 mL, 0.67 mmol) was added dropwise. Sonication was allowed to continue for 15 min, and progress of the reaction was monitored by HPLC with UV detection at 215 nm. Water (5 mL) was added to the mixture, stirred, and decanted. The oily residue was dissolved in 50 mL of ethyl acetate and extracted with 3 mL of 1 M aqueous HCl. The acidic layer was separated, and the pH was adjusted to basic with saturated aqueous sodium bicarbonate. The basic layer was extracted with 4 mL of ethyl acetate which was dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude material was purified by silical gel chromatography using a gradient elution of 0-10% methanol in dichloromethane. The title compound was obtained as a white powder (0.025 g, 19% yield). EM (calc.): 301.1; MS (ESI) m/e: 302.1 (M+H)+. 1H NMR (DMSO-d6, 400 MHz) δ ppm: 8.38 (dd, 2H), 7.13 (s, 1H), 7.04 (dd, 2H), 4.43 (t, 2H), 3.62 (t, 2H), 2.67 (s, 3H), 2.55 (s, 3H).
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si](O[C:27]1[C:32](/[CH:33]=[CH:34]\[C:35]2[CH:40]=[C:39]([O:41][CH3:42])[C:38]([O:43][CH3:44])=[C:37]([O:45][CH3:46])[CH:36]=2)=[CH:31][CH:30]=[C:29]([O:47][Si](C(C)(C)C)(C)C)[C:28]=1[O:55][Si](C(C)(C)C)(C)C)(C(C)(C)C)(C)C.C(O)(=[O:65])C.O>C1COCC1>[OH:65][C:30]1[C:29]([OH:47])=[C:28]([OH:55])[CH:27]=[C:32](/[CH:33]=[CH:34]\[C:35]2[CH:40]=[C:39]([O:41][CH3:42])[C:38]([O:43][CH3:44])=[C:37]([O:45][CH3:46])[CH:36]=2)[CH:31]=1
Reactant: COc1cc(/C=C\c2ccc(O[Si](C)(C)C(C)(C)C)c(O[Si](C)(C)C(C)(C)C)c2O[Si](C)(C)C(C)(C)C)cc(OC)c1OC
Reactant: CC(=O)O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: COc1cc(/C=C\c2cc(O)c(O)c(O)c2)cc(OC)c1OC
Temperature: 25 °C
Yield: 122.9 %

Procedure:
Tetrabutylammonium fluoride (1.37 mL, 1.37 mmol, 1M in THF) was added to a solution of 32 (0.45 g, 0.69 mmol) and glacial acetic acid (78 μL, 1.37 mmol) in THF (6 mL) at 0° C. The reaction mixture was allowed to warm to room temperature overnight, then cooled to 0° C. and water was added. The reaction mixture was extracted with TBME (3×) and the organic phase was dried (Na2SO4) and concentrated in vacuo. The residue was partitioned between CH3CN and cyclohexane and the CH3CN layer was separated and concentrated in vacuo to give the crude product (0.27 g). Purification by column chromatography (SiO2 1:1 EtOAc:cyclohexane) gave ZSB-79 (0.127 g, 58%) as a 86:14 mixture of Z:E isomers:
Reaction SMILES: [CH2:1]([CH:3]([CH2:24][CH2:25][CH2:26][CH3:27])[CH2:4][N:5]1[C:17]2[C:16]3[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=3[C:14]([CH:22]=[O:23])=[CH:13][C:12]=2[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH3:2].[Al+3].[Cl-].[Cl-].[Cl-].[F:32][C:33]1[CH:41]=[CH:40][CH:39]=[CH:38][C:34]=1[C:35](Cl)=[O:36]>C(Cl)Cl>[CH2:1]([CH:3]([CH2:24][CH2:25][CH2:26][CH3:27])[CH2:4][N:5]1[C:17]2[C:16]3[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=3[C:14]([CH:22]=[O:23])=[CH:13][C:12]=2[C:11]2[C:6]1=[CH:7][CH:8]=[C:9]([C:35](=[O:36])[C:34]1[CH:38]=[CH:39][CH:40]=[CH:41][C:33]=1[F:32])[CH:10]=2)[CH3:2]
Reactant: CCCCC(CC)Cn1c2ccccc2c2cc(C=O)c3ccccc3c21
Reactant: O=C(Cl)c1ccccc1F
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CCCCC(CC)Cn1c2ccc(C(=O)c3ccccc3F)cc2c2cc(C=O)c3ccccc3c21
Temperature: 25 °C
Reaction time: 17 h
Yield: 93.9 %

Procedure:
To 11-(2-ethylhexyl)-11H-benzo[a]carbazole-5-carbaldehyde (1.40 g, 3.91 mmol) in CH2Cl2 (20 ml) are added AlCl3 (1.21 g, 9.07 mmol) and 2-fluorobenzoyl chloride (0.70 g, 4.41 mmol) at 0° C. After stirring at room temperature for 17 hours, the reaction mixture is poured into ice-water. The crude product is extracted with CH2Cl2 and washed with water and brine. After drying over MgSO4 and concentration, the crude product is purified by column chromatography on silica gel eluting with CH2Cl2 to obtain an off-white solid (1.76 g, 93%). The structure is confirmed by 1H-NMR spectrum (CDCl3). δ [ppm]: 0.82-0.91 (m), 1.17-1.43 (m), 2.24 (m), 4.69 (m), 7.25 (t), 7.33 (t), 7.57-7.77 (m), 8.12 (d), 8.57 (d), 8.60 (s), 8.64 (s), 9.63 (d), 10.38 (s); 19F-NMR spectrum (CDCl3). δ [ppm]−111.97.
Reaction SMILES: O=[C:2]1[NH:7][C:6]2[CH:8]=[CH:9][CH:10]=[C:11]([C:12](O)=[O:13])[C:5]=2[O:4][CH2:3]1.S(C)C.[NH4+].[Cl-]>C1COCC1>[O:4]1[C:5]2[C:11]([CH2:12][OH:13])=[CH:10][CH:9]=[CH:8][C:6]=2[NH:7][CH2:2][CH2:3]1
Reactant: O=C1COc2c(cccc2C(=O)O)N1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CSC
Solvent: C1CCOC1
Product: OCc1cccc2c1OCCN2

Procedure:
To a suspension of 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazine-8-carboxylic acid (1.51 g, 7.8 mmol) in anhydrous THF (10 mL) was added BH3.Me2S (2 M in THF, 10 mL, 20 mmol) dropwise under nitrogen at 0° C. The resulted mixture was allowed to rise to r.t., and the reaction was continued to be carried out at this temperature overnight. Then, saturated aqueous NH4Cl (30 mL) was added in, and the resulted mixture was extracted with EtOAc (200 mL×2). The combined organic layers were washed with saturated aqueous NaHCO3 solution (30 mL), brine (30 mL), dried (Na2SO4) and filtered before it was concentrated under reduced pressure. The resulted crude product (3,4-dihydro-2H-benzo[1,4]oxazin-8-yl)-methanol, which was utilized in the following step without further purification. MS m/z: 166.2 (M+H)+.
Reaction SMILES: [CH:1]1([CH2:4][S:5]([C:8]([CH3:13])([CH3:12])[C:9]([OH:11])=O)(=[O:7])=[O:6])[CH2:3][CH2:2]1.S(Cl)(Cl)=O.C(N(CC)C(C)C)(C)C.[CH2:27]([N:29]1[C:33]([C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)=[N:32][C:31]([NH2:42])=[N:30]1)[CH3:28]>C(Cl)Cl>[CH:1]1([CH2:4][S:5]([C:8]([CH3:13])([CH3:12])[C:9]([NH:42][C:31]2[N:32]=[C:33]([C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)[N:29]([CH2:27][CH3:28])[N:30]=2)=[O:11])(=[O:6])=[O:7])[CH2:2][CH2:3]1
Reactant: CCn1nc(N)nc1-c1ccc(OC)cc1
Reactant: CC(C)(C(=O)O)S(=O)(=O)CC1CC1
Solvent: CCN(C(C)C)C(C)C
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Product: CCn1nc(NC(=O)C(C)(C)S(=O)(=O)CC2CC2)nc1-c1ccc(OC)cc1
Temperature: 25 °C
Yield: 92.7 %

Procedure:
Activation of 0.43 g (2.09 mmol) of 2-cyclopropylmethanesulfonyl-2-methyl-propionic acid as the corresponding acid chloride is achieved by treatment with thionyl chloride (3 mL) at 50° C. for 3 h. The reaction is cooled to room temperature and excess thionyl chloride is removed under reduced pressure. The crude acid chloride is dissolved in THF (5 mL) and N,N-diisopropylethylamine (0.39 mL, 2.25 mmol) solution is added followed by 0.30 g (1.38 mmol) of 1-ethyl-5-(4-methoxy-phenyl)-1H-[1,2,4]triazol-3-ylamine. After complete addition the reaction is heated to 70° C. for 18 h. The reaction is cooled to room temperature and the reaction mixture is diluted with DCM (20 mL) and washed with saturated aqueous NaHCO3 solution (20 mL). The combined organic layers are dried over Na2SO4, filtered and the filtrate is concentrated under reduced pressure. The residue is slurried in DCM/ether (1/1, 10 mL) to yield 0.52 g of 2-cyclopropylmethanesulfonyl-N-[1-ethyl-5-(4-methoxy-phenyl)-1H-[1,2,4]triazol-3-yl]-2-methyl-propionamide. Yield: 92%; ES-MS: m/z 407 [M+H].
Reaction SMILES: C(OC([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[C:19]([O:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH:18]=2)[CH2:12]1)=O)C1C=CC=CC=1.[C:31]([OH:40])(=[O:39])[C@H:32]([C@@H:34]([C:36]([OH:38])=[O:37])[OH:35])[OH:33]>[Pd].C(O)C>[C:31]([OH:40])(=[O:39])[C@H:32]([C@@H:34]([C:36]([OH:38])=[O:37])[OH:35])[OH:33].[CH2:29]([O:28][C:26](=[O:27])[CH2:25][O:24][C:19]1[CH:18]=[C:17]([CH:13]2[CH2:14][CH2:15][CH2:16][NH:11][CH2:12]2)[CH:22]=[CH:21][C:20]=1[CH3:23])[CH3:30]
Reactant: CCOC(=O)COc1cc(C2CCCN(C(=O)OCc3ccccc3)C2)ccc1C
Agent: [Pd]
Agent: O=C(O)[C@@H](O)[C@H](O)C(=O)O
Solvent: CCO
Product: CCOC(=O)COc1cc(C2CCCNC2)ccc1C
Temperature: 25 °C
Reaction time: 2 h
Yield: 54.8 %

Procedure:
A 250 mL Parr bottle was charged with 0.18 g of 10% palladium on carbon (50% water) and covered with 20 mL ethanol. 3-(3-ethoxycarbonylmethoxy-4-methyl-phenyl)-piperidine-1-carboxylic acid benzyl ester (1.78 g, 4.33 mmol) was dissolved in 50 mL ethanol and added to the catalyst suspension. The reaction was hydrogenated at 50 psi for 2 h. The catalyst was filtered through a celite plug. The filter cake was washed with 150 mL ethanol and the filtrated concentrated under reduced pressure. The resultant oil was taken up in 20 mL hot ethanol to which was added D-tartaric acid (650 mg, 4.33 mmol) in 10 mL hot ethanol. The solution was allowed to stir 24 h at ambient temperature. The white crystalline precipitate was collected by filtration to yield 1.014 g (55%) of (2-methyl-5-piperidin-3-yl-phenoxy)-acetic acid ethyl ester D-tartaric acid salt as a white crystalline solid.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[C:5]([O:8][C@H:9]1[C@H:22]([OH:23])[C@@H:21]([CH2:24][OH:25])[O:20][C@@H:11]([O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])[C@@H:10]1[N:26]=[N+:27]=[N-:28])(=[O:7])[CH3:6].O.CCOC(C)=O>N1C(C)=CC(C)=CC=1C>[C:5]([O:8][C@H:9]1[C@H:22]([OH:23])[C@@H:21]([CH2:24][O:25][C:1](=[O:3])[CH3:2])[O:20][C@@H:11]([O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:14])[CH3:15])[C@@H:10]1[N:26]=[N+:27]=[N-:28])(=[O:7])[CH3:6]
Reactant: CC(=O)Cl
Reactant: CC(=O)O[C@H]1[C@H](O)[C@@H](CO)O[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H]1N=[N+]=[N-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: Cc1cc(C)nc(C)c1
Product: CC(=O)OC[C@H]1O[C@@H](O[Si](C)(C)C(C)(C)C)[C@H](N=[N+]=[N-])[C@@H](OC(C)=O)[C@@H]1O
Temperature: -40 °C
Reaction time: 8 h
Yield: 94 %

Procedure:
Acetyl chloride (1.5 mL, 21.1 mmol) was added slowly to a solution of tert-butyldimethylsilyl 3-O-acetyl-2-azido-2-deoxy-β-D-glucopyranoside (7.25 g, 20 mmol) in 2,4,6-collidine (47 mL) under nitrogen at −40° C. After stirring at −40° C. overnight, water was added. The mixture was poured into EtOAc and extracted with 1 N HCl, brine and saturated NaHCO3. The organic phase was dried over Na2SO4, filtered and the solvents were removed in vacuo. Flash chromatography on silica gel (Hexanes:EtOAc 5:1→4:1) afforded 7 (7.59 g, 18.8 mmol, 94%) as a colorless solid. [α]24D: −31.6 (c 1.00, CH2Cl2); IR (thin film on NaCl) 3459, 2112, 1747, 1233, 1042, 841 cm−1; 1H-NMR (300 MHz, CDCl3) δ 4.81-4.74 (m, 1H), 4.62 (d, J=7.6 Hz, 1H), 4.37-4.31 (m, 2H), 3.75-3.46 (m, 2H), 3.53 (dd, J=7.7, 10.3 Hz, 1H), 3.13-3.09 (m, 1H), 2.18 (s, 3H), 2.10 (s, 3H), 0.94 (s, 9H), 0.17 (s, 6H); 13C-NMR (75 MHz, CDCl3) δ 171.8, 171.5, 97.2, 75.5, 74.3, 69.8, 66.0, 63.4, 25.8, 21.2, 21.1, 18.2, −4.2, −5.0; FAB MS (C16H29N3O7Si) m/z (M+) calcd 403.1775, obsd 403.1779.
Reaction SMILES: CC(C)(OC([NH:7][O:8][CH2:9][C:10]([NH:12][NH:13][C:14](=[O:27])[C:15]1[CH:20]=[C:19]([S:21]([OH:24])(=[O:23])=[O:22])[CH:18]=[C:17]([OH:25])[C:16]=1[OH:26])=[O:11])=O)C.FC(F)(F)C(O)=O>ClCCl.CCOCC>[NH2:7][O:8][CH2:9][C:10]([NH:12][NH:13][C:14](=[O:27])[C:15]1[CH:20]=[C:19]([S:21]([OH:24])(=[O:22])=[O:23])[CH:18]=[C:17]([OH:25])[C:16]=1[OH:26])=[O:11]
Reactant: CC(C)(C)OC(=O)NOCC(=O)NNC(=O)c1cc(S(=O)(=O)O)cc(O)c1O
Solvent: ClCCl
Solvent: CCOCC
Solvent: O=C(O)C(F)(F)F
Product: NOCC(=O)NNC(=O)c1cc(S(=O)(=O)O)cc(O)c1O
Temperature: 25 °C
Reaction time: 2 h
Yield: 124.5 %

Procedure:
A suspension of 2,3-dihydroxy-5-sulfobenzoic acid, 2-[[[(1,1-dimethylethoxy)carbonyl] aminooxy]acetyl]hydrazide (1.3 g, 3.0 mmole) in 10 ml of dichloromethane at -10° C. was treated dropwise with 10 ml of trifluoroacetic acid. The mixture was allowed to warm to room temperature and was stirred for 2 hours. The mixture was diluted with 30 ml of ether and filtered to give 1.2 g of a white solid.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH2:11][C:12]#[N:13])[CH:7]=[CH:8][C:9]=1[Cl:10].Cl[CH2:15][CH2:16][O:17][CH2:18][CH2:19]Cl.O>CS(C)=O>[Cl:3][C:4]1[CH:5]=[C:6]([C:11]2([C:12]#[N:13])[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[CH:7]=[CH:8][C:9]=1[Cl:10]
Reactant: N#CCc1ccc(Cl)c(Cl)c1
Reactant: ClCCOCCCl
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: N#CC1(c2ccc(Cl)c(Cl)c2)CCOCC1
Reaction time: 1 h
Yield: 35.1 %

Procedure:
NaH (420 mg, 10.5 mmol, 60%, w/w) was added to a solution of 2-(3,4-dichlorophenyl)acetonitrile (930 mg, 5 mmol) in DMSO (20 ml) at room temperature. After stirring for 40 minutes at room temperature (15° C.), 1-chloro-2-(2-chloroethoxy)ethane (786.5 mg, 5.5 mmol) was added. The mixture was stirred for another 1 hour, then poured into water (5.0 mL), and the mixture was extracted with EtOAc-toluene (2:1, 3×30 mL). The combined organic extracts were washed with 2N aq. HCl (30 mL), water (30 mL) and brine (30 mL), dried over MgSO4, filtered, and concentrated to 5 mL. The precipitated solids were collected by filtration and washed with cold diethylether (10 mL) to afford the title compound (450 mg, yield 35%). 1H NMR (400 MHz, CDCl3): 7.58 (d, J=2.0 Hz, 1H), 7.52 (d, J=1.6 Hz, 1H), 7.34 (dd, J=2.0 Hz, J=8.8 Hz, 1H), 4.08-4.12 (m, 2H), 3.85-3.92 (m, 2H), 2.2.02-2.13 (m, 4H). LC-MS (M+H): m/z 229.1 (M-CN).
Reaction SMILES: C(N)C1C=CC=CC=1.[CH:9]1([CH2:12][NH2:13])[CH2:11][CH2:10]1.[F:14][C:15]1[CH:37]=[CH:36][C:18]([CH2:19][N:20]2[CH2:24][CH2:23][N:22]([C:25]3[CH:26]=[C:27]([CH:32]=[CH:33][N:34]=3)[C:28](OC)=[O:29])[C:21]2=[O:35])=[CH:17][CH:16]=1>>[CH:9]1([CH2:12][NH:13][C:28](=[O:29])[C:27]2[CH:32]=[CH:33][N:34]=[C:25]([N:22]3[CH2:23][CH2:24][N:20]([CH2:19][C:18]4[CH:17]=[CH:16][C:15]([F:14])=[CH:37][CH:36]=4)[C:21]3=[O:35])[CH:26]=2)[CH2:11][CH2:10]1
Reactant: NCC1CC1
Reactant: COC(=O)c1ccnc(N2CCN(Cc3ccc(F)cc3)C2=O)c1
Solvent: NCc1ccccc1
Product: O=C(NCC1CC1)c1ccnc(N2CCN(Cc3ccc(F)cc3)C2=O)c1
Yield: 54 %

Procedure:
Following the procedure as described in Example 15, making variations as required to replace benzylamine with cyclopropylmethanamine to react with methyl 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinate, N-(cyclopropylmethyl)-2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinamide was obtained as a colorless solid in 54% yield: mp 135-137° C.; 1H NMR (300 MHz, CDCl3) δ 8.57 (s, 1H), 8.35 (d, J=5.1 Hz, 1H), 7.38 (d, J=5.1 Hz, 1H), 7.29-7.24 (m, 2H), 7.05-6.99 (m, 2H), 6.50 (br s, 1H), 4.45 (s, 2H), 4.07-4.02 (m, 2H), 3.46-3.26 (m, 4H), 1.08-0.97 (m, 1H), 0.56-0.50 (m, 2H), 0.28-0.23 (m, 2H); MS (ES+) m/z 369.2 (M+1).
Reaction SMILES: [Na].C(O[CH2:6][C:7]1[CH2:14][S:13][CH:12]2[N:9]([C:10](=[O:25])[CH:11]2[NH:15][C:16](=[O:24])[CH2:17][C:18]2[O:19][CH2:20][CH2:21][S:22][CH:23]=2)[C:8]=1[C:26]([OH:28])=[O:27])(=O)C.C(=O)(O)[O-].[Na+].[CH3:34][C:35]1[S:36][C:37](=[S:40])[NH:38][N:39]=1>O>[C:26]([C:8]1[N:9]2[CH:12]([S:13][CH2:14][C:7]=1[CH2:6][S:40][C:37]1[S:36][C:35]([CH3:34])=[N:39][N:38]=1)[CH:11]([NH:15][C:16](=[O:24])[CH2:17][C:18]1[O:19][CH2:20][CH2:21][S:22][CH:23]=1)[C:10]2=[O:25])([OH:28])=[O:27]
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)C(NC(=O)CC3=CSCCO3)C2SC1
Reactant: Cc1n[nH]c(=S)s1
Agent: O=C([O-])O
Agent: [Na+]
Agent: [Na]
Solvent: O
Product: Cc1nnc(SCC2=C(C(=O)O)N3C(=O)C(NC(=O)CC4=CSCCO4)C3SC2)s1
Temperature: 60 °C
Reaction time: 6 h
Yield: 45.6 %

Procedure:
The sodium salt of 3-acetoxymethyl-2-carboxy-7-[(5,6-dihydro-1,4-oxathiin-2-yl )acetamido]-8-oxo-5-thia-1-aza-bicyclo[4,2,0]oct-2-ene (14 g.) is dissolved in distilled water (350 cc.). Sodium bicarbonate (2.69 g.) followed by 2-methyl-5-thioxo-1,3,4-thiadiazoline (4.65 g.) are added to the solution and the reaction mixture is heated with stirring at 60° C. for 6 hours. After cooling, the reaction mixture is washed with ethyl acetate (2 × 150 cc.) and then acidified to pH 2 by addition of 4N hydrochloric acid in the presence of ethyl acetate (350 cc.). After decanting the organic phase, the aqueous phase is extracted twice with ethyl acetate (total 150 cc.). The organic extracts are combined, washed six times with water (total 600 cc.), dried over sodium sulphate, treated with decolourizing charcoal, filtered and then concentrated under reduced pressure (20 mm.Hg) to a final volume of 80 cc. After 30 minutes at 2° C., the solid compound which has formed is filtered off and then washed twice with ethyl acetate (10 cc.) and finally with diisopropyl ether (100 cc.). After drying under reduced pressure (0.5 mm.Hg), 2-carboxy-7-[(5,6-dihydro-1,4-oxathiin-2-yl )acetamido]-3-[(5-methyl-1,3,4-thiadiazol-2-yl )thiomethyl]-8-oxo-5-thia-1-aza-bicyclo[4,2,0]oct-2-ene (7.5 g.) is obtained.