Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[Cl:2][C:3]1[N:8]=[CH:7][C:6]([CH2:9][N:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]2=[NH:16])=[CH:5][CH:4]=1.C(N(CC)CC)C.[Cl:24][C:25]([Cl:30])([Cl:29])[C:26](Cl)=[O:27].O>ClCCl>[Cl:24][C:25]([Cl:30])([Cl:29])[C:26]([N:16]=[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][N:10]1[CH2:9][C:6]1[CH:7]=[N:8][C:3]([Cl:2])=[CH:4][CH:5]=1)=[O:27]
Reactant: N=c1ccccn1Cc1ccc(Cl)nc1
Reactant: O=C(Cl)C(Cl)(Cl)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: O=C(N=c1ccccn1Cc1ccc(Cl)nc1)C(Cl)(Cl)Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 62 %

Procedure:
70 mg (0.27 mmol) of the 1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-imine hydrochloride obtained by the method described in another method of Synthetic Example P1 was dissolved in 4 ml of anhydrous dichloromethane, 94 μl (0.68 mmol, 68 mg) of triethylamine and 33 g (0.27 mmol, 49 mg) of trichloroacetyl chloride were added thereto in sequence, and the resulting mixture was stirred at room temperature for 1 hour. After the reaction was completed, water was added thereto to stop the reaction and liquid separation was performed with dichloromethane and water. The organic layer was washed once with water and twice with 1% hydrochloric acid, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Diethyl ether was added thereto to precipitate a solid, and thus the solid was collected and dried to obtain the subject material. Amount obtained 61 mg (yield 62%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([C:8](=[N:21][S:22]([C:24]([CH3:27])([CH3:26])[CH3:25])=[O:23])[C:9]([F:20])([F:19])[CH2:10][O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])[CH:7]=1.[CH3:29][Mg+].[Br-]>C(OCC)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([C:8]([NH:21][S:22]([C:24]([CH3:27])([CH3:26])[CH3:25])=[O:23])([C:9]([F:20])([F:19])[CH2:10][O:11][Si:12]([C:15]([CH3:18])([CH3:16])[CH3:17])([CH3:14])[CH3:13])[CH3:29])[CH:7]=1
Reactant: C[Mg+]
Reactant: CC(C)(C)S(=O)N=C(c1cc(Br)ccc1F)C(F)(F)CO[Si](C)(C)C(C)(C)C
Agent: [Br-]
Solvent: CCOCC
Product: CC(C)(C)S(=O)NC(C)(c1cc(Br)ccc1F)C(F)(F)CO[Si](C)(C)C(C)(C)C
Temperature: -35 °C

Procedure:
To a solution of N-(1-(5-bromo-2-fluorophenyl)-3-(tert-butyldimethylsilyloxy)-2,2-difluoropropylidene)-2-methylpropane-2-sulfinamide (12 g, 24.04 mmol) in diethyl ether (120 mL) was added CH3MgBr (3M in Diethyl ether) (41 mL, 120 mmol) at −25° C. The reaction mixture was brought to 0° C. and maintained for 30 min. Reaction mixture was again cooled to −35° C. and quenched by drop wise addition of saturated ammonium chloride solution. Organic layer was separated and washed with brine and dried over anhydrous sodium sulphate. Crude compound was purified by column chromatography on silica gel with 8% ethyl acetate in Hexane to furnish title compound as a colorless liquid. Yield=8.8 g (71%). TLC (20% ethyl acetate in Hexane): Rf=0.33),
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[CH:9][C:8]([NH:11][NH2:12])=[CH:7][CH:6]=1)[CH3:2].[CH3:14][CH:15]([CH3:21])[C:16](=O)[CH2:17][C:18]#[N:19]>>[NH2:19][C:18]1[N:11]([C:8]2[CH:9]=[CH:10][C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:13])=[CH:6][CH:7]=2)[N:12]=[C:16]([CH:15]([CH3:21])[CH3:14])[CH:17]=1
Reactant: CC(C)C(=O)CC#N
Reactant: CCOC(=O)c1ccc(NN)cc1
Product: CCOC(=O)c1ccc(-n2nc(C(C)C)cc2N)cc1
Yield: 88.2 %

Procedure:
Using the same method as Example A83, 4-hydrazinobenzoic acid ethyl ester (from Example A82, 3 g, 16.6 mmol) and 4-methyl-3-oxopentanenitrile (from Example A83, 2.7 g, 27.9 mmol) were combined to afford ethyl 4-(5-amino-3-isopropyl-1H-pyrazol-1-yl)benzoate (4 g, 88% yield), which was used to the next reaction without further purification.
Reaction SMILES: C(OC(=O)COC1C=CC(Cl)=CC=1[C:16]#[C:17][Si:18]([CH3:21])([CH3:20])[CH3:19])(C)(C)C.Br[C:24]1[CH:29]=[C:28]([S:30]([CH2:33][CH2:34][CH3:35])(=[O:32])=[O:31])[CH:27]=[CH:26][C:25]=1[F:36]>>[F:36][C:25]1[CH:26]=[CH:27][C:28]([S:30]([CH2:33][CH2:34][CH3:35])(=[O:32])=[O:31])=[CH:29][C:24]=1[C:16]#[C:17][Si:18]([CH3:21])([CH3:20])[CH3:19]
Reactant: CC(C)(C)OC(=O)COc1ccc(Cl)cc1C#C[Si](C)(C)C
Reactant: CCCS(=O)(=O)c1ccc(F)c(Br)c1
Product: CCCS(=O)(=O)c1ccc(F)c(C#C[Si](C)(C)C)c1
Yield: 97 %

Procedure:
Following the general method as outlined in Intermediate 2, starting from 2-bromo-1-fluoro-4-(propylsulfonyl)benzene (Intermediate 106) and trimethylsilylacetilene, the title compound was obtained as a brown liquid in 97% yield.
Reaction SMILES: Cl.Cl[CH2:3][C:4]1[CH:5]=[C:6]([C:16]([CH3:20])([CH3:19])[C:17]#[N:18])[CH:7]=[C:8]([CH2:10][N:11]2[CH:15]=[N:14][CH:13]=[N:12]2)[CH:9]=1.S([O-])([O-])(=O)=O.[CH3:26][S:27]C(N)=[NH2+].CSC(N)=[NH2+].[OH-].[Na+].CN(C)C=O>O>[CH3:19][C:16]([C:6]1[CH:7]=[C:8]([CH2:10][N:11]2[CH:15]=[N:14][CH:13]=[N:12]2)[CH:9]=[C:4]([CH2:3][S:27][CH3:26])[CH:5]=1)([CH3:20])[C:17]#[N:18]
Reactant: CC(C)(C#N)c1cc(CCl)cc(Cn2cncn2)c1
Reactant: CSC(N)=[NH2+]
Agent: Cl
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CSCc1cc(Cn2cncn2)cc(C(C)(C)C#N)c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of the product from Example 28 (0.6 g), S-methylthiouronium sulphate (0.56 g), 10N aqueous sodium hydroxide (1 ml) and dimethylformamide (5 ml) was stirred at room temperature for 18 h, diluted with water (20 ml) and extracted twice with dichloromethane. The extracts were combined, dried and evaporated to dryness under reduced pressure, and the residue was purified by flash column chromatography, eluting with methanol:ethyl acetate (1:49 by volume) to give 2-methyl-2-[3-methylthiomethyl-5-(1H-1,2,4-triazol-1-ylmethyl)phenyl]-propiononitrile. Nmr in deuteriochloroform: δ 8.12(1H,s), 8.0(1H,s), 7.4(1H,m), 7.27(1H,m), 7.15(1H,m), 5.38(2H,s), 3.66(2H,s), 2.0(3H,s), 1.72(6H,s).
Reaction SMILES: [C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].C(OC([N:15]1[CH2:18][CH:17]([NH:19][C:20](=[O:36])[CH2:21][NH:22][C:23](=[O:35])[C:24]2[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=2[Cl:34])[CH2:16]1)=O)(C)(C)C>>[OH:7][C:1]([C:3]([F:6])([F:5])[F:4])=[O:2].[NH:15]1[CH2:18][CH:17]([NH:19][C:20]([CH2:21][NH:22][C:23](=[O:35])[C:24]2[CH:29]=[C:28]([C:30]([F:33])([F:31])[F:32])[CH:27]=[CH:26][C:25]=2[Cl:34])=[O:36])[CH2:16]1
Reactant: CC(C)(C)OC(=O)N1CC(NC(=O)CNC(=O)c2cc(C(F)(F)F)ccc2Cl)C1
Solvent: O=C(O)C(F)(F)F
Product: O=C(CNC(=O)c1cc(C(F)(F)F)ccc1Cl)NC1CNC1

Procedure:
The title compound was prepared as colorless oil from TFA de-protection of 3-[2-(2-chloro-5-trifluoromethyl-benzoylamino)-acetylamino]-azetidine-1-carboxylic acid tert-butylester using the procedure described in Step D of Example 1.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH:6]=[O:7].[N+:8]([C:11]1[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=1[CH2:13]Br)([O-:10])=[O:9]>>[N+:8]([C:11]1[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=1[CH2:13][N:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH:6]=[O:7])([O-:10])=[O:9]
Reactant: O=Cc1ncc[nH]1
Reactant: O=[N+]([O-])c1ccccc1CBr
Product: O=Cc1nccn1Cc1ccccc1[N+](=O)[O-]
Yield: 94.4 %

Procedure:
With stirring and external cooling, 4.80 g of 2-imidazolecarboxaldehyde is added and the cooling bath removed. Slight external heating results in a yellow solution. The reaction mixture is chilled in ice and 10.8 g of 2-nitrobenzyl bromide is added. The reaction mixture is stirred at 0° C. for 18 hours. The volatiles are removed in vacuo to a residue which is stirred with ice water, filtered and the cake washed well with water and suction dried to give 10.9 g of the desired product as a solid, m.p. 141-144° C. MH+ 232.
Reaction SMILES: [C:1](OC)(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.[CH3:16][N:17]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:18][C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:20].Cl>CCCCCC.C(O)(=O)C.O1CCCC1>[OH:4][C:3]1[CH2:5][C:19]([CH2:18][N:17]([CH3:16])[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:20][C:1](=[O:6])[CH:2]=1
Reactant: CN(CC(=O)c1ccccc1)c1ccccc1
Reactant: COC(=O)CC(C)=O
Agent: Cl
Agent: [H-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: CCCCCC
Product: CN(CC1(c2ccccc2)CC(O)=CC(=O)O1)c1ccccc1

Procedure:
The title compound was prepared as described in General Method 1 using 6.7 mmol of methyl acetoacetate, 7.3 mmol of NaH 60% dispersion in oil, 7.0 mmol of 1.6 M n-butyl lithium in hexane, 6.7 mmol of 2-(methylphenylamino)-1-phenylethanone and 40 mL of tetrahydrofuran. The reaction mixture was acidified to pH 7 with conc. HCl and then taken to pH 3 with acetic acid. The product was flash chromatographed using CH2Cl2 /MeOH (99/1) to give a solid (m.p. 152-153° C.). 1H NMR (CDCl3) δ 2.9 (d, 1 H), 3.05 (s, 3 H), 3.1 (d, 1 H), 3.2 (d, 1 H), 3.3 (d, 1 H), 3.7 (ABq, 2 H), 6.7-6.8 (m, 3 H), 7.2-7.3 (m, 2 H), 7.3-7.5 (m, 5 H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[N:9]([CH2:23][CH:24]([CH3:26])[CH3:25])[S:10]([C:13]1[CH:14]=[C:15]([CH:20]=[CH:21][CH:22]=1)[C:16](OC)=[O:17])(=[O:12])=[O:11].[BH4-].[Li+]>O1CCCC1>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[N:9]([CH2:23][CH:24]([CH3:26])[CH3:25])[S:10]([C:13]1[CH:22]=[CH:21][CH:20]=[C:15]([CH2:16][OH:17])[CH:14]=1)(=[O:11])=[O:12]
Reactant: COC(=O)c1cccc(S(=O)(=O)N(CC(C)C)c2ccc(C)cc2C)c1
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: Cc1ccc(N(CC(C)C)S(=O)(=O)c2cccc(CO)c2)c(C)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Methyl 3-(N-(2,4-dimethylphenyl)-N-isobutylsulfamoyl)benzoate (400 mg, 1.065 mmol) was dissolved in tetrahydrofuran (THF) (10 mL). To this solution was added lithium borohydride (2M in THF) (0.932 mL, 1.864 mmol). The reaction was left to stir overnight, at room temperature, overnight. The reaction was quenched by the addition of 5% citric acid (10 mL), and the reaction allowed to stir, under nitrogen for 1 hour. The reaction mixture was then diluted with ethyl acetate (25 mL), and the product extracted to the organic phase. The organic phase was dried by passing it through a hydrophobic frit, and then concentrated in vacuo to give the desired product, N-(2,4-dimethylphenyl)-3-(hydroxymethyl)-N-isobutylbenzenesulfonamide, 378.7 mg.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([NH:11][C:12](=[O:26])[C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[CH:15][C:14]=2[CH3:25])[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].Br[C:28]1[CH:36]=[CH:35][C:31]([C:32]([OH:34])=[O:33])=[CH:30][CH:29]=1.C(C1C=C(NC(C2C=CC(N3CCN(C4C=CC(C(O)=O)=CC=4)CC3)=C(F)C=2)=O)C=CC=1)(C)(C)C>>[C:1]([C:5]1[CH:6]=[C:7]([NH:11][C:12]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][N:22]([C:28]4[CH:36]=[CH:35][C:31]([C:32]([OH:34])=[O:33])=[CH:30][CH:29]=4)[CH2:21][CH2:20]3)=[CH:15][C:14]=2[CH3:25])=[O:26])[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: O=C(O)c1ccc(Br)cc1
Reactant: Cc1cc(N2CCNCC2)ccc1C(=O)Nc1cccc(C(C)(C)C)c1
Agent: CC(C)(C)c1cccc(NC(=O)c2ccc(N3CCN(c4ccc(C(=O)O)cc4)CC3)c(F)c2)c1
Product: Cc1cc(N2CCN(c3ccc(C(=O)O)cc3)CC2)ccc1C(=O)Nc1cccc(C(C)(C)C)c1

Procedure:
4-{4-[4-(3-tert-Butyl-phenylcarbamoyl)-3-methyl-phenyl]-piperazin-1-yl}-benzoic acid was synthesized by the coupling of N-(3-tert-butyl-phenyl)-2-methyl-4-piperazin-1-yl-benzamide and 4-bromo benzoic acid in a manner similar to the one described in the synthesis of 4-{4-[4-(3-tert-butyl-phenylcarbamoyl)-2-fluoro-phenyl]-piperazin-1-yl}-benzoic acid above. LCMS calcd for C29H33N3O3 (m/e) 471, obsd 472 (M+H).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([CH3:12])[C:5]([C:8]([O:10]C)=[O:9])=[N:6][CH:7]=1.[OH-].[Na+].Cl>O1CCOCC1>[Cl:1][C:2]1[N:3]=[C:4]([CH3:12])[C:5]([C:8]([OH:10])=[O:9])=[N:6][CH:7]=1
Reactant: COC(=O)c1ncc(Cl)nc1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: Cc1nc(Cl)cnc1C(=O)O
Yield: 84.1 %

Procedure:
A solution of methyl 5-chloro-3-methylpyrazine-2-carboxylate (0.117 g, 0.627 mmol) (Step 3 of Intermediate 24) and sodium hydroxide 5N (0.150 ml, 0.752 mmol) in dioxane (5 mL) was stirred at room temperature for 30 minutes. The reaction mixture was acidified with 2N HCl to pH 4 and extracted with EtOAc (2×). The combined organic extracts were dried over Na2SO4 and the filtrate was concentrated to afford the title compound (91.0 mg, 84%). MS m/z=172.9 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][CH:6]([N:11]([CH2:15][CH2:16][CH3:17])[CH2:12][CH2:13][CH3:14])[CH2:5]2.[F:18][C:19]([F:24])([F:23])C([O-])=O.[Na+]>CN1C=CC=CC1=O.C(OCC)(=O)C.[Cu]I>[F:18][C:19]([F:24])([F:23])[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][CH:6]([N:11]([CH2:15][CH2:16][CH3:17])[CH2:12][CH2:13][CH3:14])[CH2:5]2
Reactant: CCCN(CCC)C1Cc2ccc(Br)cc2C1
Reactant: O=C([O-])C(F)(F)F
Agent: [Cu]I
Agent: Cn1ccccc1=O
Agent: [Na+]
Solvent: CCOC(C)=O
Product: CCCN(CCC)C1Cc2ccc(C(F)(F)F)cc2C1
Temperature: 25 °C

Procedure:
A solution of 5-bromo-2-(di-n-propylamino)indan (Example 11), sodium trifluoroacetate, and copper (I) iodide in N-methylpyridone is heated at 160° C. for 4 h under nitrogen (Chem Lett 1981, 1719). The reaction mixture is cooled to room temperature and diluted with ethyl acetate. The mixture is filtered through a layer of Celite pad and the filtrate is washed with water, brine, dried (MgSO4), filtered, and concentrated. The oil is purified by liquid chromatography to give the title compound as a yellow oil.
Reaction SMILES: C([O:4][CH:5]1[O:22][C@H:21]([C:23]([O:25][CH3:26])=[O:24])[C@@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:6]1[O:7][C:8](=[O:10])[CH3:9])(=O)C.C(N)C1C=CC=CC=1>CN(C=O)C>[C:8]([O:7][C@@H:6]1[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@@H:21]([C:23]([O:25][CH3:26])=[O:24])[O:22][CH:5]1[OH:4])(=[O:10])[CH3:9]
Reactant: COC(=O)[C@H]1OC(OC(C)=O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Solvent: CN(C)C=O
Solvent: NCc1ccccc1
Product: COC(=O)[C@H]1OC(O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 16 h
Yield: 84 %

Procedure:
Methyl 1,2,3,4-tetra-O-acetyl-D-glucopyranuronate F13-2 (1.2 g, 3.2 mmol) was dissolved in dry DMF (10 mL) under N2. To the solution, benzylamine (0.42 mL, 3.8 mmol) was added. The mixture was stirred at r.t. for 16 hours. The solvent was removed under reduced pressure and the residue was purified by flash chromatography (Hexane:EtOAc=1:2, by volume) to afford a white solid F13c in 84% yield. 1H NMR (600 MHz, CDCl3) δ 5.50-5.55 (m, 1H), 5.11-5.27 (m, 1H), 4.85-4.91 (m, 1H), 5.39-4.56 (m, 2H), 3.70-3.72 (m, 3H), 1.99-2.05 (m, 9H). 13C NMR (150 MHz, CDCl3) δ 170.68, 170.45, 170.34, 170.30, 169.94, 169.81, 168.77, 167.83, 95.59, 90.36, 72.98, 72.66, 71.81, 70.97, 69.73, 69.61, 69.34, 68.12, 53.21, 53.11, 20.85, 20.84, 20.77, 20.70, 20.66, 20.65.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].[CH3:15][N:16]([CH3:22])[C@@H:17]1[CH2:21][CH2:20][NH:19][CH2:18]1.C([O-])(O)=O.[Na+]>C1COCC1>[N+:12]([C:3]1[CH:4]=[C:5]([C:8]([F:11])([F:10])[F:9])[CH:6]=[CH:7][C:2]=1[N:19]1[CH2:20][CH2:21][C@@H:17]([N:16]([CH3:22])[CH3:15])[CH2:18]1)([O-:14])=[O:13]
Reactant: CN(C)[C@@H]1CCNC1
Reactant: O=[N+]([O-])c1cc(C(F)(F)F)ccc1F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: CN(C)[C@@H]1CCN(c2ccc(C(F)(F)F)cc2[N+](=O)[O-])C1
Temperature: 25 °C

Procedure:
To a solution of 1-fluoro-2-nitro-4-(trifluoromethyl)benzene (0.67 mL, 4.78 mmol) in THF (25 mL) was added (R)-N,N-dimethylpyrrolidin-3-amine (0.66 g, 5.74 mmol) and NaHCO3 (1.1 g, 13.15 mmol). The reaction was stirred at RT and monitored by LCMS for disappearance of starting material and formation of product. The mixture was concentrated, diluted with CH2Cl2, washed with H2O and then brine. Drying with MgSO4 was followed by filtration and concentration to afford the product as an orange oil.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7](=O)[CH2:8][C:9]#[CH:10])[CH:2]=1.Cl.[NH2:13][OH:14]>>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7](=[N:13][OH:14])[CH2:8][C:9]#[CH:10])[CH:2]=1
Reactant: NO
Reactant: C#CCC(=O)c1cccnc1
Agent: Cl
Product: C#CCC(=NO)c1cccnc1

Procedure:
Employing the general method of Example 5 above, 2.95 g (18.5 mmol) of 1-(3-pyridinyl)-3-butyne-1-one was converted to 2.1 g (66%) of the corresponding oxime by reaction with hydroxylamine hydrochloride.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][NH:4][C:5]1[C:6](=[O:22])[N:7]([C:18]([CH3:21])([CH3:20])[CH3:19])[S:8](=[O:17])(=[O:16])[C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.Cl[C:24]1[C:29]([Cl:30])=[CH:28][C:27]([C:31]([F:34])([F:33])[F:32])=[CH:26][N:25]=1>CN(C=O)C>[C:18]([N:7]1[C:6](=[O:22])[C:5]([NH:4][CH2:3][CH2:2][NH:1][C:24]2[C:29]([Cl:30])=[CH:28][C:27]([C:31]([F:34])([F:32])[F:33])=[CH:26][N:25]=2)=[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[S:8]1(=[O:17])=[O:16])([CH3:19])([CH3:21])[CH3:20]
Reactant: CC(C)(C)N1C(=O)C(NCCN)=C(c2ccccc2)S1(=O)=O
Reactant: FC(F)(F)c1cnc(Cl)c(Cl)c1
Solvent: CN(C)C=O
Product: CC(C)(C)N1C(=O)C(NCCNc2ncc(C(F)(F)F)cc2Cl)=C(c2ccccc2)S1(=O)=O
Temperature: 120 °C
Yield: 38.3 %

Procedure:
4-[(2-Aminoethyl)amino]-2-tert-butyl-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.088 g, 0.27 mmol), 2,3-dichloro-5-(trifluoromethyl)pyridine (0.065 g, 0.30 mmol) and TEA (0.055 g, 0.54 mmol) was dissolved in dry DMF (3 ml) and heated in a microwave reactor at 120° C. for 25 mins. The reaction mixture was extracted with EtOAc (75 ml) and the organic phases were washed with water (3×50 ml), dried over MgSO4, filtered and evaporated. The residue was purified by silica gel column chromatography using petroleum ether and EtOAc (85:15) as eluant, to give the title compound (0.052 g, 38%). 1H NMR (500 MHz, CDCl3): δ 8.3-8.25 (m, 1H), 7.67-7.62 (m, 2H), 7.49-7.43 (m, 2H), 7.43-7.35 (m, 3H), 6.47-6.41 (m, 1H), 5.47-5.41 (m, 1H), 3.52 (q, 2H), 3.09 (q, 2H), 1.7 (s, 9H); 13C NMR (125 MHz, CDCl3): δ 159.4, 155.7, 143.7, 143.6, 135.5, 133.2, 133.1, 131.5, 129.4, 128.5, 125, 124.6, 122.4, 116.8, 116.6, 115, 107.1, 61.4, 45.4, 40.9, 27.5; Mass Spectrum: M−H+ 503.
Reaction SMILES: [C:1]1([C:6]([CH:8]([CH3:12])[C:9](O)=[S:10])=[O:7])[S:5][CH:4]=[CH:3][CH:2]=1.[NH2:13][CH2:14][C:15]([OH:17])=[O:16].C1(N=C=NC2CCCCC2)CCCCC1>CS(C)=O>[C:1]1([C:6]([CH:8]([CH3:12])[C:9]([NH:13][CH2:14][C:15]([OH:17])=[O:16])=[S:10])=[O:7])[S:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(C(=O)c1cccs1)C(O)=S
Reactant: NCC(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CS(C)=O
Product: CC(C(=O)c1cccs1)C(=S)NCC(=O)O
Yield: 55.2 %

Procedure:
To a solution of 21.6 g (0.1 mole) of 2-(2-thenoyl) thiopropionic acid and 7.5 g (0.1 mole) of glycine in 100 ml of dimethylsulfoxide, 20.6 g of N,N'-dicyclohexyl-carbodiimide are added, under stirring, between 15° to 20° C. Stirring is continued for half an hour more, most of the solvent is evaporated under vacuum, 200 ml of water are added and the solution is taken to pH 9 with NaOH. Dicyclohexylurea is eliminated by filtration, then it is acidified with HCl. 14.2 g (yield 52%) of N-[2-(2-thenoyl)thiopropionyl]-glycine are obtained. The product is unitary in TLC.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(OC)(O[CH3:18])(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH3:18][O:5][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][C:9]([N+:11]([O-:13])=[O:12])=[CH:10][C:2]=1[OH:1]
Reactant: COS(=O)(=O)OC
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)c1ccc([N+](=O)[O-])cc1O
Reaction time: 24 h
Yield: 98.9 %

Procedure:
To a solution of 2-hydroxy-4-nitrobenzoic acid (8.0 g, 0.0424 mol) in acetone (240 mL) and dimethyl sulfate (4.48 mL, 0.047 mol) was added potassium carbonate (5.85 g, 0.044 mol), stirred for 24 hrs. and evaporated. To the residue was added ethyl acetate and 2 N HCl (pH 3). The ethyl acetate extract was washed, dried (MgSO4) and evaporated to give 2-hydroxy-4-nitro-benzoic acid methyl ester (8.27 g) as a yellow solid; 1H-NMR (DMSO-d6) δ 11.62 (s, 1H), 9.74 (s, 1H), 8.76 (d, 2H), 8.70-2 (d, 2H), 8.29 (s, 1H), 8.11 (s, 1H), 7.71-7 (m, 2H), 7.55 (m, 2H), 8.33-5 (d, 1H), 7.15-9 (t, 1H), 4.27 (s, 2H), 2.80 (s, 3H); LC/MS (ESI+): 228 (M+2Na)
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20]>O1CCCC1.O>[CH2:22]([O:21][C:19]([NH:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=[O:6])=[O:20])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: Nc1cc(C(=O)O)ccc1F
Reactant: O=C(Cl)OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: C1CCOC1
Product: O=C(Nc1cc(C(=O)O)ccc1F)OCc1ccccc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 3-amino-4-fluorobenzoic acid (30 g, 193 mmol) in a mixture of tetrahydrofuran (300 mL) and water (300 mL) was added cesium carbonate (157 g, 483 mmol) and benzyl chloroformate (30.4 mL, 213 mmol). This mixture was stirred at ambient temperature for 16 hours, and was concentrated to about 200 mL. The residue was acidified with 2N HCl to a pH 3, and was partitioned between ethyl acetate and brine. The precipitated solid was collected by filtration, washed with ethyl acetate and water, and dried to provide the title compound. MS (DCI/NH3) m/z 290 (M+H)+.
Reaction SMILES: [C:1]([OH:14])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]([OH:12])=[O:11].[CH2:15](O)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C(C)=CC=CC=1>C1(C)C=CC(S(O)(=O)=O)=CC=1.O>[C:1]1(=[O:14])[O:13][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][O:12][C:10](=[O:11])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(O)CCCCCCCCC(=O)O
Reactant: OCCCCCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1C
Solvent: O
Product: O=C1CCCCCCCCC(=O)OCCCCCCO1
Temperature: 165 °C

Procedure:
Crystalline poly (hexamethylene sebacate) was prepared using a kettle equipped with a stirrer, nitrogen gas inlet tube, thermometer and condenser by reacting sebacic acid with 1,6hexamethylene glycol in the presence of a p-toluenesulfonic acid catalyst as follows: sebacic acid and hexamethylene glycol were added to the reaction kettle in a respective 1.0 to 1.1 molar ratio along with 0.5 wt % p-toluenesulfonic acid. The 10 mole % excess of glycol was used to ensure the predominant presence of hydroxyl end groups in the reaction product. The mixture was heated to 165°C while stirring. At 165°C, an amount of xylene was added to assist refluxing and this temperature was maintained until water evolution ceased (4 hrs.). Afterwards, the condensers were removed and the excess glycol and catalyst were removed by sparging with nitrogen for 0.5 hours at 165°C. On cooling to room temperature, the poly (hexamethylene sebacate) crystallized into an off-white solid. Next, the poly (HMS) from above was purified by precipitation from a benzene solution into methanol using techniques well known in the art. The precipitated poly (HMS) was collected by filtration and dried in vacuo. Analytical data on this purified material indicate an acid number of 1.06, an hydroxyl number of 34.4, an Mn of 3165 g/mole, an MWD (Mw /Mn) of 1.41 by GPC in chloroform, a glass transition temperature of about -62°C and a crystalline melting point of about 65°C.