Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O[C:2]1[CH:17]=[C:16]([OH:18])[CH:15]=[CH:14][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][C:7]=1[OH:13])=O.C([O-])(=O)C.[Na+].Cl.[Br:25][C:26]1[CH:27]=[C:28]([NH:32][NH2:33])[CH:29]=[CH:30][CH:31]=1>>[Br:25][C:26]1[CH:27]=[C:28]([N:32]2[C:2]3[C:3](=[CH:14][CH:15]=[C:16]([OH:18])[CH:17]=3)[C:4]([C:6]3[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][C:7]=3[OH:13])=[N:33]2)[CH:29]=[CH:30][CH:31]=1
Reactant: O=C(c1ccc(O)cc1O)c1ccc(O)cc1O
Reactant: NNc1cccc(Br)c1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Product: Oc1ccc(-c2nn(-c3cccc(Br)c3)c3cc(O)ccc23)c(O)c1
Yield: 8.1 %

Procedure:
Prepared according to Method B from 2,2′,4,4′-tetrahydroxybenzophenone (0.123 g, 0.5 mmol), sodium acetate (0.041 g, 0.5 mmol) and 3-bromophenylhydrazine hydrochloride (0.112 g, 0.5 mmol) to give 0.016 g of product as a tan solid.
Reaction SMILES: OCC[C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10](NC)=[C:9](C(=O)C)[CH:8]=[CH:7]2.C(#N)CC#N>N1C=CC=CC=1>[CH:10]1[C:11]2[C:6](=[CH:5][CH:4]=[CH:13][CH:12]=2)[CH:7]=[CH:8][CH:9]=1
Reactant: CNc1c(C(C)=O)ccc2cc(CCO)ccc12
Solvent: N#CCC#N
Solvent: c1ccncc1
Product: c1ccc2ccccc2c1
Temperature: 95 °C

Procedure:
To a solution of 201 mg (0.83 mmol) of 1-(6-2-hydroxyethyl-methylamino-2-naphthyl)-1-ethanone in pyridine (6 mL), malononitrile (236 mg, 3.6 mmol) was added and the mixture was heated at 95° C. for 24 hours. The solvent was removed in vacuo, and the residue was chromatographed by radial chromatography (4 mm SiO2 1% MeOH/CH2Cl2) to give 150 mg (73%) of 2-(1,1-dicyanopropen-2-yl)-6-2-hydroxyethyl)-methyl-amino)-naphthalene.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH3:14])[CH:11]=[C:10]([N:15]3[CH:19]=[C:18](I)[N:17]=[CH:16]3)[N:9]=2)=[CH:4][CH:3]=1.[C:21]([NH:25][S:26]([C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)(=[O:28])=[O:27])([CH3:24])([CH3:23])[CH3:22]>>[C:21]([NH:25][S:26]([C:29]1[CH:30]=[CH:31][CH:32]=[C:33]([C:18]2[N:17]=[CH:16][N:15]([C:10]3[CH:11]=[C:12]([CH3:14])[CH:13]=[C:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)[N:9]=3)[CH:19]=2)[CH:34]=1)(=[O:28])=[O:27])([CH3:24])([CH3:22])[CH3:23]
Reactant: CC(C)(C)NS(=O)(=O)c1cccc(B(O)O)c1
Reactant: Cc1cc(-c2ccc(Cl)cc2)nc(-n2cnc(I)c2)c1
Product: Cc1cc(-c2ccc(Cl)cc2)nc(-n2cnc(-c3cccc(S(=O)(=O)NC(C)(C)C)c3)c2)c1

Procedure:
The title compound was prepared from 2-(4-chloro-phenyl)-6-(4-iodo-imidazol-1-yl)-4-methyl-pyridine (example E.95) (0.198 g, 0.5 mmol) and commercially available 3-(tert-butylsulfamoyl)-benzeneboronic acid (0.141 g, 0.55 mmol) according to the general procedure VI. Obtained as a white solid (0.028 g, 12%). MS (ISP) 482.4 [(M+H)+].
Reaction SMILES: [NH2:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([C:6]([NH:8][CH2:9][CH2:10][N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])=[O:7])=[C:4]([OH:19])[CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:39][O:40][CH:41]([CH3:45])[CH2:42][CH2:43]O.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[NH2:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([C:6]([NH:8][CH2:9][CH2:10][N:11]([CH2:12][CH3:13])[CH2:14][CH3:15])=[O:7])=[C:4]([O:19][CH2:43][CH2:42][CH:41]([O:40][CH3:39])[CH3:45])[CH:3]=1
Reactant: CCN(CC)CCNC(=O)c1cc(Cl)c(N)cc1O
Reactant: COC(C)CCO
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCN(CC)CCNC(=O)c1cc(Cl)c(N)cc1OCCC(C)OC
Reaction time: 8 h
Yield: 52.4 %

Procedure:
A stirred solution of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-hydroxybenzamide (1.715 g, 6 mmoles; prepared according to Preparation 1B), triphenylphosphine (1.58 g, 6 mmoles), 3-methoxy-1-butanol (0.62 g, 6 mmoles) in dry tetrahydrofuran (50 ml) was treated dropwise with diethyl azodicarboxylate (1.1 g of 95% purity material, 6 mmoles). The solution was left to stir overnight. After evaporation of the solvent the residue was dissolved in methylene chloride. The solution was washed with 0.4N NaOH, water, dried and the solvent evaporated. The residue was chromatographed over deactivated silica using methylene chloride (100), methanol (2.5), ammonium hydroxide (0.5) solvent system. The appropriate fractions were combined and the solvent evaporated. The residue (1.7 g) was crystallized from toluene to yield 1.17 g (52%) of the title compound, m.p. 76°-78° C.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](Cl)=[O:7].[NH2:9][C:10]1[CH:11]=[C:12]([CH:25]=[CH:26][CH:27]=1)[C:13]([C:15]1[CH:23]=[C:22]2[C:18]([CH2:19][C:20](=[O:24])[NH:21]2)=[CH:17][CH:16]=1)=[O:14]>C1COCC1>[O:24]=[C:20]1[CH2:19][C:18]2[C:22](=[CH:23][C:15]([C:13]([C:12]3[CH:11]=[C:10]([NH:9][C:6]([C:2]4[S:1][CH:5]=[CH:4][CH:3]=4)=[O:7])[CH:27]=[CH:26][CH:25]=3)=[O:14])=[CH:16][CH:17]=2)[NH:21]1
Reactant: O=C(Cl)c1cccs1
Reactant: Nc1cccc(C(=O)c2ccc3c(c2)NC(=O)C3)c1
Solvent: C1CCOC1
Product: O=C1Cc2ccc(C(=O)c3cccc(NC(=O)c4cccs4)c3)cc2N1
Temperature: 25 °C
Yield: 84 %

Procedure:
A dry 250 mL flask was charged with Thiophene-2-carbonyl chloride (1.14 g, 7.77 mmol) and THF (60 mL). 6-(3-Amino-benzoyl)-1,3-dihydro-indol-2-one (as prepared in Example 40, 1.508 g, 5.978 mmol) was added to the THF solution of the acid chloride, and the mixture was allowed to reflux for 3 h. The reaction mixture was then allowed to cool to room temperature. The room temperature reaction mixture was concentrated in vacuo. The solid residue was suspended in boiling EtOAc. The suspension was allowed to cool to room temperature before filtering to afford the Thiophene-2-carboxylic acid [3-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide as a tan solid (1.82 g, 5.02 mmol, 84%).
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][C:6]([CH3:26])([CH3:25])[C:7]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][CH2:18][N:19]2[CH2:23][CH2:22][CH2:21][C@H:20]2[CH3:24])=[CH:11][CH:10]=1)=O)C.O.[NH2:29][NH2:30]>C(#N)C>[CH3:25][C:6]1([CH3:26])[C:7]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][CH2:18][N:19]3[CH2:23][CH2:22][CH2:21][C@H:20]3[CH3:24])=[CH:11][CH:10]=2)=[N:30][NH:29][C:4](=[O:3])[CH2:5]1
Reactant: NN
Reactant: CCOC(=O)CC(C)(C)C(=O)c1ccc(OCCCN2CCC[C@H]2C)cc1
Solvent: CC#N
Solvent: O
Product: C[C@@H]1CCCN1CCCOc1ccc(C2=NNC(=O)CC2(C)C)cc1

Procedure:
The product from step 4 (0.75 g, 2.1 mmol) and hydrazine hydrate (2.0 mL) in acetonitrile (25 mL) were heated to reflux for 24 h. The reaction was cooled, concentrated and the product recrystallized using Et2O-hexanes to give 600 mg (71%); Mp 118-121; MS m/z 344 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:28]=[C:27]([N+:29]([O-:31])=[O:30])[CH:26]=[C:25]([Cl:32])[C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([O:23]C)=[C:9]([CH:22]=1)[C:10]([NH:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])=[O:11].B(Br)(Br)Br>C(Cl)Cl>[Cl:1][C:2]1[CH:28]=[C:27]([N+:29]([O-:31])=[O:30])[CH:26]=[C:25]([Cl:32])[C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([OH:23])=[C:9]([CH:22]=1)[C:10]([NH:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])=[O:11]
Reactant: CCCCCCCCCNC(=O)c1cc(Oc2c(Cl)cc([N+](=O)[O-])cc2Cl)ccc1OC
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CCCCCCCCCNC(=O)c1cc(Oc2c(Cl)cc([N+](=O)[O-])cc2Cl)ccc1O
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 99.4 %

Procedure:
To a solution of 5-(2,6-dichloro-4-nitro-phenoxy)-2-methoxy-N-nonyl-benzamide (173 mg, 0.36 mmol) in CH2Cl2 (3 ml) was added a solution of BBr3 (0.72 ml of a 1 M solution in CH2Cl2). The resulting mixture was stirred at RT for 1.5 h then quenched by addition of MeOH (1 ml) and water (10 ml). The resulting mixture was stirred at RT for 30 min then further diluted with 1 M HCl (10 ml) and extracted with CH2Cl2 (3×5 ml). The combined CH2Cl2 extracts were washed with brine, dried over Na2SO4, filtered and concentrated to give the title compound of Step D (168 mg) as a viscous oil. The title product of Step D was used in the next step without further purification. MS (APCl−) Calc.: 468.1, Found: 467.2 (M−1).
Reaction SMILES: Cl.[NH2:2][C@@H:3]([CH2:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([O:18][CH3:19])=[O:17])[CH:11]=1)[C:4]([NH2:6])=[O:5].[CH3:20][C:21]1[CH:22]=[C:23]([CH:45]=[CH:46][CH:47]=1)[CH2:24][C@@H:25]([C:42](O)=[O:43])[NH:26][C:27](=[O:41])[CH:28]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.CN(C)CCCN=C=NCC.Cl>C(Cl)Cl>[CH3:19][O:18][C:16]([C:12]1[CH:11]=[C:10]([CH2:9][CH2:8][CH2:7][C@H:3]([NH:2][C:42](=[O:43])[C@H:25]([CH2:24][C:23]2[CH:45]=[CH:46][CH:47]=[C:21]([CH3:20])[CH:22]=2)[NH:26][C:27](=[O:41])[CH:28]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:4]([NH2:6])=[O:5])[CH:15]=[CH:14][CH:13]=1)=[O:17]
Reactant: COC(=O)c1cccc(CCC[C@H](N)C(N)=O)c1
Reactant: Cc1cccc(C[C@H](NC(=O)C(c2ccccc2)c2ccccc2)C(=O)O)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN1CCOCC1
Solvent: O
Solvent: ClCCl
Product: COC(=O)c1cccc(CCC[C@H](NC(=O)[C@H](Cc2cccc(C)c2)NC(=O)C(c2ccccc2)c2ccccc2)C(N)=O)c1

Procedure:
To a solution of (S)-2-amino-5-(3-carbomethoxyphenyl)-pentanamide HCl (0.30 g, 0.80 mmol), of 3-methyl-N-(2,2-diphenylacetyl)-L-phenylalanine (0.23 g, 0.80 mmol), 1-hydroxybenzotriazole hydrate (0.135 g, 0.89 mmol) and N-methylmorpholine (0.35 ml, 3.2 mmol) in CH2Cl2 (25 mL) is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.HCl (0.23 g, 1.2 mmol) in one portion, and the mixture is stirred at room temperature for 16 hours. The solution is then washed with 1 N HCl (100 mL), saturated aqueous NaHCO3 (1×50 mL), water (1×50 mL) and brine (1×50 mL), dried over MgSO4, and evaporated. The residual solid is triturated with ether to yield N-[4-(3-methoxycarbonyl-phenyl)-1(S)-(aminocarbonyl)-butyl]-3-methyl-Nα-(2,2-diphenylacetyl)-L-phenylalaninamide as a light yellow solid.
Reaction SMILES: [C:1]([C:3]1[CH:29]=[CH:28][C:6]([CH2:7][NH:8][C:9](=[O:27])[CH:10]([O:24][CH2:25][CH3:26])[N:11]2[CH:15]=[C:14]([CH3:16])[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[OH:23])=[N:12]2)=[CH:5][CH:4]=1)#[N:2].C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:37][C:38]([NH2:40])=[O:39]>CN(C=O)C.CCOC(C)=O.O>[C:38]([CH2:37][O:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[C:13]1[C:14]([CH3:16])=[CH:15][N:11]([CH:10]([O:24][CH2:25][CH3:26])[C:9]([NH:8][CH2:7][C:6]2[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:29][CH:28]=2)=[O:27])[N:12]=1)(=[O:39])[NH2:40]
Reactant: CCOC(C(=O)NCc1ccc(C#N)cc1)n1cc(C)c(-c2ccccc2O)n1
Reactant: NC(=O)CI
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(C(=O)NCc1ccc(C#N)cc1)n1cc(C)c(-c2ccccc2OCC(N)=O)n1
Reaction time: 2 h
Yield: 66.7 %

Procedure:
To a stirred solution of (RS)-N-(4-cyano-benzyl)-2-ethoxy-2-[3-(2-hydroxy-phenyl)-4-methyl-pyrazol-1-yl]-acetamide (200 mg) at r.t. in DMF (4 ml) under an argon atmosphere were added cesium carbonate (200 mg) followed by iodoacetamide (114 mg). The mixture was then stirred for 2 h. The mixture was diluted with EtOAc and water. The aqueous phase was extracted with EtOAc. The combined organics were washed with water. A solid started to precipitate out of the organic phase in the separating funnel. This solid was collected by filtration and washed with cyclohexane to give (RS)-2-[3-(2-carbamoylmethoxy-phenyl)-4-methyl-pyrazol-1-yl]-N-(4-cyano-benzyl)-2-ethoxy-acetamide (153 mg) as white powder. The organic layer of the filtrate was separated and washed with brine, dried (MgSO4), filtered and concentrated to leave a yellow solid. This was taken in Et2O (5 ml) and 5 drops of methanol were added. The suspension was stirred for 30 min at r.t. and this second crop of product was collected by filtration, washed with Et2O and dried to give more (RS)-2-[3-(2-carbamoylmethoxy-phenyl)-4-methyl-pyrazol-1-yl]-N-(4-cyano-benzyl)-2-ethoxy-acetamide (31 mg) of an off-white powder. MS 448.5 ([M+H]+)
Reaction SMILES: [C:1]1([CH2:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C=CC=CC=1.[NH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>O>[C:1]1([CH2:7][C:8]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(Cl)Cc1ccccc1
Reactant: Nc1ccccc1
Solvent: O
Solvent: c1ccccc1
Product: O=C(Cc1ccccc1)Nc1ccccc1
Temperature: 0 °C
Yield: 65.6 %

Procedure:
A mixture of 5.84 g (37.81 mmol) phenylacetyl chloride and 50 mL benzene was stirred at 0° C. A solution of 3.52 g (2.0 equivs.) aniline and 50 mL benzene was added dropwise. After addition was complete, the mixture was allowed to warm to room temperature and stirred for 3 hrs. The mixture was poured into 100 mL water and was extracted with 3×100 mL ethyl acetate. The organic layers were combined and washed sequentially with 100 mL portions of 5% aqueous hydrochloric acid, water, saturated sodium carbonate and water. The organic layer was dried, filtered and solvent was removed from the filtrate to provide 5.24 g (24.80 mmol, 65%) phenylacetanilide as a tan solid, mp=114°-116° C. NMR (CDCl3 /TMS): 3.73 (s, 2H), 7.08 (t, 1H), 7.18 (bs, 1H), 7.25-7.43 (m, 9H). Mass spectrum
Reaction SMILES: [OH:1][C:2]1[C:6]([O:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:5][S:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:20][N:21]([CH3:25])[C:22](Cl)=[O:23]>C(#N)C.O>[CH3:20][N:21]([CH3:25])[C:22](=[O:23])[O:1][C:2]1[C:6]([O:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:5][S:4][N:3]=1
Reactant: CN(C)C(=O)Cl
Reactant: Oc1nsnc1Oc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: CN(C)C(=O)Oc1nsnc1Oc1ccccc1
Yield: 95.7 %

Procedure:
In acetonitrile were suspended 0.80 g of 3-hydroxy-4-phenoxy-1,2,5-thiadiazole and 0.46 g of potassium carbonate and after adding 0.36 g of dimethylcarbamoyl chloride to the suspension, the mixture was refluxed for 12 hours. After allowing to cool, the reaction mixture was poured in water and extracted with ether. The ether layer was washed twice each time with a diluted aqueous solution of sodium hydroxide, water, and then a saturated aqueous sodium chloride solution. The ether layer thus washed was dried with anhydrous magnesium sulfate, concentrated, and thereafter purified by silica gel column chromatography to provide 0.85 g of 3-phenoxy-1,2,5-thiadiazol-4-yl N,N-dimethylcarbamate.
Reaction SMILES: [CH3:1][N:2]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:9][C:8](=[O:17])[C:4]([C:5]([OH:7])=[O:6])=[C:3]1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[OH-].[Na+].[Br:26]Br>CO.O>[Br:26][C:9]1[C:8](=[O:17])[C:4]([C:5]([OH:7])=[O:6])=[C:3]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:2]([CH3:1])[C:10]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: BrBr
Reactant: Cn1c(-c2ccccc2)cc(=O)c(C(=O)O)c1-c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: Cn1c(-c2ccccc2)c(Br)c(=O)c(C(=O)O)c1-c1ccccc1
Yield: 63.6 %

Procedure:
3.75 gms of 1-methyl-2,6-diphenyl-4-oxonicotinic acid was dissolved in 40 mls of methanol. The pH was adjusted to 12 with the addition of aqueous NaOH. A methanolic solution of bromine (2.95 gms Br2 in 50 mls methanol) was added. Additional NaOH was added as required to maintain a basic medium. Removal of the solvent yielded a semisolid that was taken up in 100 mls of water. Water insoluble material was removed by filtration. Acidification of the aqueous solution provided 3.0 gms of 5-bromo-1-methyl-2,6-diphenyl-4-oxonicotinic acid (mp 242°-243°, with decomposition) as a white solid.
Reaction SMILES: C(=O)(O)[O-].[Na+].[CH2:6]([O:17][P:18]([OH:21])([OH:20])=[O:19])[CH:7]([OH:16])[CH:8]([OH:15])[CH:9]([OH:14])[CH:10]([OH:13])[CH:11]=[O:12].[Ba].C1N=C(N)C2N=CN([C@@H]3O[C@H](COP(OP(OC[C@H]4O[C@@H](N5C=C(C(N)=O)CC=C5)[C@H](O)[C@@H]4O)(O)=O)(O)=O)[C@@H](O)[C@H]3O)C=2N=1.II>CN(C=O)C>[CH2:6]([O:17][P:18]([OH:21])([OH:20])=[O:19])[C@H:7]1[O:16][C@@H:11]([OH:12])[C@H:10]([OH:13])[C@@H:9]([OH:14])[C@@H:8]1[OH:15]
Reactant: O=CC(O)C(O)C(O)C(O)COP(=O)(O)O
Agent: II
Agent: NC(=O)C1=CN([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n4cnc5c(N)ncnc54)[C@H](O)[C@@H]3O)[C@@H](O)[C@H]2O)C=CC1
Agent: O=C([O-])O
Solvent: CN(C)C=O
Product: O=P(O)(O)OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O
Reaction time: 4 h

Procedure:
Following the procedure described above, 10mg of the T4 methyl ester diglycolate in 0.52ml dry DMF was reacted with 1.3mg NHS and 2.3mg ECDI. To 8.7mg G-6-PDH (0.08μ mole) in 1.65ml 1mg/ml sodium bicarbonate was added 5mg G-6-P and 12.5mg NADH, followed by 0.335ml DMF, followed by 9.5μmole ester prepared above in 0.215ml DMF. In 4 hours, a 47% loss in activity was observed. The hapten number was found to be 12 by UV and 13.2 by iodine analysis.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([O:15][P:16]([CH:19]([O:23][CH2:24][CH3:25])[O:20][CH2:21][CH3:22])([CH3:18])=[O:17])[CH3:14].[CH3:26][O:27][C:28]1[CH:38]=[CH:37][C:31]([CH:32]=[CH:33][N+:34]([O-:36])=[O:35])=[CH:30][CH:29]=1.[Cl-].[NH4+]>O1CCCC1.CCCCCC>[CH3:26][O:27][C:28]1[CH:29]=[CH:30][C:31]([CH:32]([CH2:33][N+:34]([O-:36])=[O:35])[CH2:18][P:16]([CH:19]([O:23][CH2:24][CH3:25])[O:20][CH2:21][CH3:22])(=[O:17])[O:15][CH2:13][CH3:14])=[CH:37][CH:38]=1
Reactant: COc1ccc(C=C[N+](=O)[O-])cc1
Reactant: CCOC(OCC)P(C)(=O)OCC
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: CCOC(OCC)P(=O)(CC(C[N+](=O)[O-])c1ccc(OC)cc1)OCC
Reaction time: 0.17 h

Procedure:
To a solution of 8.7 g of diisopropylamine in 40 ml of tetrahydrofuran at -78° C. under an atmosphere of nitrogen are added 53.6 ml of a 1.6M solution of n-butyllithium in hexane. This solution is then stirred for a period of 10 minutes at this temperature, after which time a solution of 15.0 g of ethyl(diethoxymethyl)methylphosphinate in 20 ml of tetrahydrofuran is added. This mixture is then stirred for a period of 1 hour at -78° C. after which time a solution of 12.8 g of 4-methoxy-β-nitrostyrene in 20 ml of tetrahydrofuran is introduced. This mixture is then allowed to warm to room temperature when 40 ml of a saturated ammonium chloride solution is added. The aqueous layer is then extracted with 2×25 ml of diethyl ether and the organic extracts are combined and dried over magnesium sulphate. The solvent is then evaporated under reduced pressure and the crude product chromatographed on silica gel using ethyl acetate as an eluent to give ethyl 2-(4-methoxyphenyl)-3-nitropropyl(diethoxymethyl)phosphinate as a viscous oil, 31P=+42.4 and +42.1 ppm (CDCl3).
Reaction SMILES: CS(C1C=CC(N)=CC=1)(=O)=O.[CH3:12][S:13]([C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:25])[C:19]2=[O:26])(=[O:15])=[O:14].[CH:27]1[C:32]([NH:33][NH2:34])=[CH:31][CH:30]=[C:29]([S:35]([NH2:38])(=[O:37])=[O:36])[CH:28]=1.Cl>O>[CH3:12][S:13]([C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:25])[C:19]2=[O:26])(=[O:15])=[O:14].[CH3:12][S:13]([C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:25])[C:19]2=[N:34][NH:33][C:32]1[CH:31]=[CH:30][C:29]([S:35]([NH2:38])(=[O:36])=[O:37])=[CH:28][CH:27]=1)(=[O:15])=[O:14]
Reactant: NNc1ccc(S(N)(=O)=O)cc1
Agent: CS(=O)(=O)c1ccc(N)cc1
Agent: CS(=O)(=O)c1ccc2c(c1)C(=O)C(=O)N2
Agent: Cl
Solvent: O
Product: CS(=O)(=O)c1ccc2c(c1)C(=NNc1ccc(S(N)(=O)=O)cc1)C(=O)N2

Procedure:
5-Methylsulfonyl-1H-indole-2,3-dione was prepared from 4-methylsulfonylaniline according to Procedure A: 1H NMR (DMSO-d6): δ 3.21 (s, 3H), 7.07(d, J=8.3 Hz, 1H), 7.92 (d, J=1.7 Hz, 1H), 8.05 (dd, J=8.2, 2.0 Hz, 1H), 11.46 (s,1H); APCI−MS m/z 225 (M)−. The title compound was prepared from 5-methylsulfonyl-1H-indole-2,3-dione and 4-sulfonamidophenylhydrazine hydrochloride according to Procedure G: mp>250° C.; 1H NMR (DMSO-d6): δ 3.20 (s, 3H), 7.11 (d, J=8.3 Hz, 1H), 7.26 (s, 2H), 7.65 (d, J=8.9 Hz, 2H), 7.78 (d, J=8.7 Hz, 2H), 7.79 (dd, J=8.2, 1.9 Hz, 1H), 8.06 (d, J=1.6 Hz, 1H), 11.54 (s, 1H), 12.75 (s, 1H); APCI−MS m/z 394 (M)−. Anal. Calcd for C15H14N4O5S2.0.9 H2O: C, 43.87; H, 3.88; N, 13.64; S, 15.62. Found: C, 43.96; H, 3.80; N, 13.58; S, 15.67.
Reaction SMILES: CS(O)(=O)=O.C[O:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][CH2:16][CH2:17][N:18]2[CH:22]=[CH:21][N:20]=[N:19]2)=[CH:10][CH:9]=1.Br.[OH-].[Na+]>>[N:18]1([CH2:17][CH2:16][CH2:15][CH2:14][C:11]2[CH:10]=[CH:9][C:8]([OH:7])=[CH:13][CH:12]=2)[CH:22]=[CH:21][N:20]=[N:19]1
Reactant: COc1ccc(CCCCn2ccnn2)cc1
Agent: Br
Agent: CS(=O)(=O)O
Agent: [Na+]
Product: Oc1ccc(CCCCn2ccnn2)cc1
Temperature: 85 °C
Reaction time: 0.17 h
Yield: 84.7 %

Procedure:
1-[4-(4-Methoxyphenyl)butan-1-yl]-1H-1,2,3-triazole methanesulfonate (4.0 g, 12.22 mmol) was added into 48% hydrobromic acid (8 ml) and the mixture was heated at 80-90° C. for 6 hours. The reaction mixture was ice-cooled and 4N-sodium hydroxide (32 ml) was added dropwise. The mixture was washed with toluene. 6N Hydrochloric acid was added to the aqueous layer to adjust pH to 6.3. The mixture was extracted with ethyl acetate (30 ml) and tetrahydrofuran (15 ml) and then washed with water. Activated carbon (200 mg) was added and the mixture was stirred at room temperature for 10 min. The mixture was filtrated and concentrated under reduced pressure. To the residue was added ethyl acetate (10 ml), and the mixture was refluxed. After allowing to cool and stirring for 30 min, hexane (10 ml) was added and the mixture was stirred at room temperature for 30 min. The precipitated crystals were collected by filtration and dried under reduced pressure to give 4-[4-(1H-1,2,3-triazol-1-yl)butyl]phenol (2.25 g, yield 85%).
Reaction SMILES: [CH2:1]([N:3]1[C:7]([CH3:8])=[CH:6][C:5]([C:9]([CH2:11][C@H:12]2[N:15]([C:16](=P(CCCC)(CCCC)CCCC)[C:17]([O:19][CH2:20][CH:21]=[CH2:22])=[O:18])[C:14](=[O:36])[C@@H:13]2[C@H:37]([OH:39])[CH3:38])=O)=[N:4]1)[CH3:2].C1(C=CC(O)=CC=1)O.C(OCC)(=O)C.CCCCCC.C(OCC)(=O)C>C1(C)C=CC=CC=1>[OH:39][C@@H:37]([C@H:13]1[C:14](=[O:36])[N:15]2[C:16]([C:17]([O:19][CH2:20][CH:21]=[CH2:22])=[O:18])=[C:9]([C:5]3[CH:6]=[C:7]([CH3:8])[N:3]([CH2:1][CH3:2])[N:4]=3)[CH2:11][C@H:12]12)[CH3:38]
Reactant: C=CCOC(=O)C(N1C(=O)[C@H]([C@@H](C)O)[C@H]1CC(=O)c1cc(C)n(CC)n1)=P(CCCC)(CCCC)CCCC
Agent: Oc1ccc(O)cc1
Solvent: Cc1ccccc1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: C=CCOC(=O)C1=C(c2cc(C)n(CC)n2)C[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12
Reaction time: 64 h

Procedure:
Allyl 2-{(3S,4R)-4-[(1-ethyl-5-methylpyrazol-3-yl)carbonylmethyl]-3-[(R)-1-hydroxyethyl]-2-oxoazetidinyl}-2-(tri-n-butylphosphoranylidene)acetate (2.6), in toluene (120 ml) containing hydroquinone (20 mg) was heated under reflux in an argon atmosphere for 4 h, allowed to stand for 64 h, and then heated under reflux for a further 2 h. The mixture was cooled and then loaded onto a column (4.5×12 cm) of silica gel (particle size 0.040-0.063 mm), elutin with ethyl acetate/hexane mixtures; 1:1; 6:4; 7:3; 8:2; 9:1 (250 ml of each), followed by ethyl acetate. This Dave the carbapenem (436 mg); υmax(CH2Cl2) 3604, 2976, 1774, 1716, 1600, 1546, 1311, 1189 cm−1; λmax(EtOH)/nm 321.5 (ε/dm3 mol−1 cm−1 14,856), δ(CDCl3) 1.36 (d, J 6.3 Hz), 1.39 (t, J7.3 Hz) (together 5H), 1.80 (1H, d, J 5.0 Hz), 2.28 (3H,s), 3.19 (1H, dd J 2.7 & 6.7 Hz), 3.28 (1H, dd, J 9.0 & 18.6 Hz), 3.60 (1H, dd, J 9.9 & 18.5 Hz), 4.08 (2H, q, J 7.3 Hz), 4.16-4.30 (2H, m), 4.68-4.90 (2H, m), 5.27 (1H, m, approx d, J ca. 12 Hz), 5.46 (m, approx d, J ca. 17 Hz), 5.93-6.08 (1H, m), 7.00 (1H, s) ppm; [Found m/z 345.1693. C18H23N3O4 requires m/z 345.1689].