Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC[C:6]1[CH2:13][S:12][CH:11]2[N:8]([C:9](=[O:30])[CH:10]2[NH:14][C:15](=[O:29])[CH2:16][C:17]2[N:18]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[OH:28])[S:20][CH:21]=2)[C:7]=1[C:31]([OH:33])=[O:32])(=O)C.[SiH](CC)(CC)CC.FC(F)(F)C(O)=O.C(Cl)C[Cl:50]>>[Cl:50][C:6]1[CH2:13][S:12][CH:11]2[N:8]([C:9](=[O:30])[CH:10]2[NH:14][C:15](=[O:29])[CH2:16][C:17]2[N:18]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[OH:28])[S:20][CH:21]=2)[C:7]=1[C:31]([OH:33])=[O:32]
Reactant: ClCCCl
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)C(NC(=O)Cc3csc(-c4ccccc4O)n3)C2SC1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: O=C(Cc1csc(-c2ccccc2O)n1)NC1C(=O)N2C(C(=O)O)=C(Cl)CSC12
Yield: 35 %

Procedure:
The procedure used for the preparation of 9a was repeated with 8b (390 mg, crude from previous reaction), Et3SiH (0.80 mL, 5.0 mmol), and trifluoroacetic acid (1.50 mL, 19.5 mmol ) in dry ClCH2CH2Cl (8 mL ) at 0° C. under nitrogen to give 9b (50.0 mg, 35% for two steps) as a white solid after chromatographic separation on RP C-18 (gradient CH3CN/H2O: 25-30%, containing 1% HOAc). mp 155° C. (dec); IR (KBr) 3600-2800 (br), 3280, 1780, 1661 cm-1 ; 1H NMR (DMSO-d6) δ3.63 (1H, d, J=18.0 Hz), 3.74 (2H, s, CH2), 3.93 (1H, d, J=18.0 Hz), 5.15 (1H, d, J=4.7 Hz), 5.70 (1H, dd, J=8.0 and 4.7 Hz), 6.88 (1H, t, J=7.7 Hz), 6.96 (1H, d, J=7.7 Hz), 7.25 (1H, t, J=7.7 Hz), 7.40 (1H, s), 7.94 (1H, d, J=7.7 Hz), 9.16 (1H, d, J=8.0 Hz, NH), 11.30 (1H, s, OH), 13.80 (1H, br s, CO2H); FDMS m/z 451 (M+, 35Cl), 452 (M+ +1, 35Cl), 453 (M+, 37Cl), 454 (M+ +1, 37Cl); Anal. Calcd for C18H14ClN3O5S2 : C, 47.84; H, 3.12; N, 9.30. Found: C, 48.12; H, 3.16; N, 9.36
Reaction SMILES: [CH:1]1([S:4](Cl)(=[O:6])=[O:5])[CH2:3][CH2:2]1.[CH2:8]([OH:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.N1C=CC=CC=1>C(Cl)Cl>[CH:1]1([S:4]([O:15][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1
Reactant: O=S(=O)(Cl)C1CC1
Reactant: OCc1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=S(=O)(OCc1ccccc1)C1CC1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Cyclopropyl sulfonyl chloride (2 g, 14.2 mmol) was added drop-wise at 0° C. to a solution of Benzyl alcohol (2.1 g, 28.4 mmol) and Pyridine (2.35 g, 29.8 mmol) in DCM (20 mL) and continued stirring at 25° C. for 16 h. The reaction mixture was diluted with DCM (100 mL), washed with 1N aq.HCl solution followed by water and brine; Organic layer collected was dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the Benzyl cyclopropanesulfonate. 1H NMR (300 MHz, CD3OD) δ ppm 4.3-4.1 (2H, t), 2.7-2.6 (1H, m), 1.8-1.6 (2H, m), 1.6-1.4 (2H, m), 1.2-1.1 (4H, m), 1.0-0.9 (3H, t).
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]1([OH:24])[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[N:19]=3)[N:14]=[CH:13][C:12]=2[F:23])[CH2:5]1.[O:25]=[C:26]1[NH:31][C:30]2[N:32]=[C:33]([CH:36]=O)[CH:34]=[CH:35][C:29]=2[S:28][CH2:27]1.CCN(CC)CC.[BH4-].[Na+]>C(Cl)Cl.CCO>[F:23][C:12]1[CH:13]=[N:14][C:15]2[C:20]([C:11]=1[CH2:10][CH2:9][N:6]1[CH2:7][CH2:8][C:4]([CH2:3][NH:2][CH2:36][C:33]3[CH:34]=[CH:35][C:29]4[S:28][CH2:27][C:26](=[O:25])[NH:31][C:30]=4[N:32]=3)([OH:24])[CH2:5]1)=[N:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2
Reactant: O=Cc1ccc2c(n1)NC(=O)CS2
Reactant: COc1ccc2ncc(F)c(CCN3CCC(O)(CN)C3)c2n1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc2ncc(F)c(CCN3CCC(O)(CNCc4ccc5c(n4)NC(=O)CS5)C3)c2n1
Reaction time: 2 h
Yield: 71.6 %

Procedure:
To a stirred solution of 3-(aminomethyl)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinol hydrochloride salt (0.21 mmole) in dry CH2Cl2 (25 mL) and dry EtOH (20 mL) at RT was added 3-oxo-3,4-dihydro-2H-pyrido[1,4]thiazine-6-carboxaldehyde (0.04 g, 0.21 mmole) and Et3N (0.06 mL, 0.42 mmole). After 24 h at RT was added NaBH4 (0.01 g, 0.23 mmole). After 2 h, silica gel (5 g) was added to the reaction solution and the suspension was concentrated under vacuum to a dry solid. Purification on silica (CHCl3/MeOH, 9:1 containing 5% NH4OH) afforded the title compound (0.075 g, 72%) as light yellow solid: 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 8.08 (d, J=9.0 Hz, 1H), 7.54 (d, J=7.8 Hz, 1H), 7.00 (d, J=9.0 Hz, 1H), 6.88 (d, J=7.8 Hz, 1H), 4.38 (s, 2H), 4.03 (s, 3H), 3.81 (m, 2H), 3.37 (m, 4H), 3.12 (m, 4H), 2.72 (m, 2H), 2.54 (m, 2H), 1.92 (m, 2H). LC-MS (ES) m/e 499 (M+H)+.
Reaction SMILES: C.F[C:3]1([C:9](=[O:12])[CH2:10]F)[CH2:8][CH2:7][O:6][C:4]1=[O:5]>>[C:9]([CH:3]1[CH2:8][CH2:7][O:6][C:4]1=[O:5])(=[O:12])[CH3:10]
Reactant: O=C(CF)C1(F)CCOC1=O
Agent: C
Product: CC(=O)C1CCOC1=O

Procedure:
The fluorination of 2-Acetyl butyrolactone (3.2 gm, 0.025 m) was carried out in a manner similar to that described in Example 6. Work up gave 2-fluoro-2-acetyl butyrolactone(nc) [NMR (CDCl3); 1H, δH =4.5 ppm (m), 2H; 2.87 ppm (m), 1H; 2.55 ppm (m)1H; 2.47 ppm (d), JHF =5.0 Hz, 3H; 19F, δF =-163.4 ppm (ddqd), J=11.8, 11.8, 4.9, and 1.5 Hz]. Accurate mass measurement:--Found (CI, methane), 147.0442; C6H8O3F requires 147.0457]. A small multiplet at -173.8 ppm and triplet of doublets at -237.9 ppm (Jtriplet =46.3 Hz, Jdoublet =6.8 Hz) in the reaction product were attributed to 2-fluoro-2-(fluoroacetyl)butyrolactone. The conversion was ca. 70% and the yield was ca. 85%.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([O:11]C)=O.C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>CN(C=O)C>[NH:1]1[C:2]2[C:3](=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:8][C:9]1=[O:11]
Reactant: COC(=O)Cc1ccccc1N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C1Cc2ccccc2N1
Yield: 103.2 %

Procedure:
Stir the mixture of methyl 2-(2-aminophenyl)acetate (4.8 g, 29.1 mmol) and potassium carbonate (8.0 g, 58.2 mmol) in DMF (15 mL) at room temperature overnight. TLC (PE:EtOAc=2:1) shows the reaction is complete. Concentrate the reaction mixture under reduced pressure to give the crude product. Purify by chromatography (silica gel, EtOAc:PE=1:2) to afford the title compound (4.0 g, 95%). MS: (M+1): 134.2.
Reaction SMILES: C(O[CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[CH:16]([NH2:17])[C:15](=[O:18])[N:10]2[C:11]=1[C:12]([OH:14])=[O:13])(=O)C.[NH2:19][N:20]1[C:25]([NH2:26])=[CH:24][C:23]([NH2:27])=[N:22][C:21]1=[S:28].CO.N>C(#N)C>[NH2:17][CH:16]1[C:15](=[O:18])[N:10]2[C:11]([C:12]([O-:14])=[O:13])=[C:6]([CH2:5][S:28][C:21]3[N:22]=[C:23]([NH2:27])[CH:24]=[C:25]([NH2:26])[N+:20]=3[NH2:19])[CH2:7][S:8][C@H:9]12
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)C(N)[C@H]2SC1
Reactant: Nc1cc(N)n(N)c(=S)n1
Agent: N
Solvent: CO
Solvent: CC#N
Product: Nc1cc(N)[n+](N)c(SCC2=C(C(=O)[O-])N3C(=O)C(N)[C@H]3SC2)n1
Temperature: 0 °C
Reaction time: 2 h
Yield: 72.3 %

Procedure:
Under an anhydrous condition, a solution containing 2.72 g of 3-acetoxymethyl-7-amino-3-cephem-4-carboxylic acid and 1.50 g of 1,4,6-triamino-2(1H)-pyrimidinethione suspended in 20 ml of dry acetonitrile was cooled to 0° C.; and 4.8 ml of boron trifluoride diethylether was added. The temperature of the reaction solution was increased to 50° C; the solution was stirred for two hours; and then 10 ml of methyl alcohol was added. The resultant solution was stirred for 10 minutes and was added with 30 ml of ice water. The pH of the solution was adjusted to 7.1 by adding aqueous ammonia solution. After concentration under a reduced pressure, e.g., about 20 mmHg, the solution was adjusted to pH 3.7 with 2N-aqueous hydrochloric acid; and allowed to stand at a room temperature for 24 hrs. The precipitates resulted from the reaction solution were filtered, washed with 10 ml of distilled water and with 10 ml of methyl alcohol, and dried to give 2.55 g of the title compound as a solid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[NH:7][C@@H:8]1[CH2:12][CH2:11][N:10]([C:13](=O)[C@H:14]([OH:16])[CH3:15])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].B.CO>C1COCC1>[C:1]([O:5][C:6](=[O:18])[NH:7][C@@H:8]1[CH2:12][CH2:11][N:10]([CH2:13][C@H:14]([OH:16])[CH3:15])[CH2:9]1)([CH3:3])([CH3:2])[CH3:4]
Reactant: C[C@@H](O)C(=O)N1CC[C@@H](NC(=O)OC(C)(C)C)C1
Agent: B
Solvent: CO
Solvent: C1CCOC1
Product: C[C@@H](O)CN1CC[C@@H](NC(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 51.6 %

Procedure:
[(R)-1-((R)-2-Hydroxy-propyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester (244 mg) was prepared from [(R)-1-((R)-2-hydroxy-propionyl)-pyrrolidin-3-yl]carbamic acid tert-butyl ester (500 mg) and 1 M borane in THF (6 mL). The reaction was stirred at room temperature for 30 min and then stirred at 50° C. for 8 h. The reaction was added to methanol (20 mL). The solvent was evaporated and crude compound was purified by flash chromatography using DCM:methanol gradient.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1.P(Cl)(Cl)(Cl)=O.[C:15]([O-])(=[O:17])C.[Na+]>CN(C)C=O.O>[CH:8]1[CH:9]=[C:4]2[CH:3]=[C:2]([CH:15]=[O:17])[O:1][C:5]2=[CH:6][CH:7]=1
Reactant: CC(=O)[O-]
Reactant: c1ccc2occc2c1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: O=P(Cl)(Cl)Cl
Product: O=Cc1cc2ccccc2o1
Reaction time: 8 h

Procedure:
A solution of benzofuran (163 g, 1.39 mole) in dimethylformamide (264 g, dried over magnesium sulfate overnight) in a 2-1, 3-necked flask was stirred and treated dropwise with phosphorus oxychloride (233 g, 136 ml). The solution was heated and stirred on a steam bath for 8 hrs. Another 88 g of dry dimethylformamide, followed by 70 g (42 ml) of phosphorus oxychloride, was added and the heating and stirring were continued overnight. After cooling, the solution was slowly poured into a stirred solution of 260 g of sodium acetate in 1500 ml of water. The solution was extracted four times with 500 ml of ether. The ether extracts were washed with dilute aqueous sodium hydroxide solution and then with water. The solution was then dried over magnesium sulfate and filtered.
Reaction SMILES: [ClH:1].[C:2]([C:4]1[CH:5]=[C:6]([CH:34]=[CH:35][CH:36]=1)[C:7]([NH:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([C:16]([N:18]([CH3:20])[CH3:19])=[O:17])[CH2:12][C@H:11]1[NH:21][C:22]([C:24]1[S:25][C:26]2[CH2:27][N:28]([CH3:33])[CH2:29][CH2:30][C:31]=2[N:32]=1)=[O:23])=[O:8])#[N:3].Cl.[CH3:38][O:39][NH2:40].C(=O)([O-])O.[Na+]>C(O)C.CO.C(Cl)Cl.C(N(CC)CC)C>[ClH:1].[NH2:3][C:2](=[N:40][O:39][CH3:38])[C:4]1[CH:5]=[C:6]([CH:34]=[CH:35][CH:36]=1)[C:7]([NH:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([C:16]([N:18]([CH3:19])[CH3:20])=[O:17])[CH2:12][C@H:11]1[NH:21][C:22]([C:24]1[S:25][C:26]2[CH2:27][N:28]([CH3:33])[CH2:29][CH2:30][C:31]=2[N:32]=1)=[O:23])=[O:8]
Reactant: CON
Reactant: CN1CCc2nc(C(=O)N[C@@H]3C[C@@H](C(=O)N(C)C)CC[C@@H]3NC(=O)c3cccc(C#N)c3)sc2C1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Solvent: CCO
Product: CON=C(N)c1cccc(C(=O)N[C@H]2CC[C@H](C(=O)N(C)C)C[C@H]2NC(=O)c2nc3c(s2)CN(C)CC3)c1
Reaction time: 48 h

Procedure:
Saturated HCl in ethanol (30 mL) was added to the compound obtained in Example 367 (300 mg) at room temperature. The mixture was stirred for 2 days and then concentrated under reduced pressure, thereby yielding a pale yellow solid. The solid was dissolved in methanol (10 mL). O-Methylhydroxylamine hydrochloride (1.01 g) and triethylamine (1.69 mL) were added to the solution at room temperature. The mixture was stirred for 2 hours, and methylene chloride and saturated aqueous sodium hydrogencarbonate were added to the reaction mixture to partition the mixture, followed by extracting the aqueous layer with methylene chloride. The extract was combined with the organic layer and then dried over sodium sulfate anhydrate, and the solvent was removed under reduced pressure. The residue was purified sequentially through silica gel medium-pressure chromatography (methylene chloride:methanol=20:1→7:1) and fractional reversed phase high performance liquid chromatography (acetonitrile-water-formic acid), and the product was treated with 1N HCl, to thereby yield the title compound (51.8 mg) as a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:14]=[CH:13][C:12]2[C:11]3[C:6](=[CH:7][C:8]([Br:15])=[CH:9][CH:10]=3)[CH2:5][C:4]=2[CH:3]=1.[OH-].[Na+].Br[CH2:19][CH2:20][CH2:21][CH2:22][C:23]1[CH:30]=[CH:29][C:28]2[CH2:27][CH2:26][C:25]=2[CH:24]=1>CS(C)=O>[C:25]12[CH2:26][CH2:27][C:28]=1[CH:29]=[CH:30][C:23]([CH2:22][CH2:21][CH2:20][CH2:19][C:5]1([CH2:19][CH2:20][CH2:21][CH2:22][C:23]3[CH:24]=[C:25]4[C:28](=[CH:29][CH:30]=3)[CH2:27][CH2:26]4)[C:4]3[CH:3]=[C:2]([Br:1])[CH:14]=[CH:13][C:12]=3[C:11]3[C:6]1=[CH:7][C:8]([Br:15])=[CH:9][CH:10]=3)=[CH:24]2
Reactant: BrCCCCc1ccc2c(c1)CC2
Reactant: Brc1ccc2c(c1)Cc1cc(Br)ccc1-2
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Product: Brc1ccc2c(c1)C(CCCCc1ccc3c(c1)CC3)(CCCCc1ccc3c(c1)CC3)c1cc(Br)ccc1-2
Temperature: 80 °C
Reaction time: 4 h

Procedure:
To an oven-dried three-neck round-bottom flask under nitrogen, were added 25.97 g of 2,7-dibromofluorene, 32.06 g sodium hydroxide, 1.33 g KI, and 300 mL anhydrous DMSO. The 46 g 3-(4-bromobutyl)bicyclo[4.2.0]octa-1(6),2,4-triene 300 mL anhydrous DMSO was added via cannula. The reaction was heated to 80° C. After 4 hours, the reaction was quenched by the addition of DI water (10 mL). The excess salt was removed by filtration. 500 mL Ethyl acetate was added, and extracted with DI water (3×300 mL) and brine (3×300 mL). The combined organic layer was dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the solvent was removed by rotary evaporation. The product (43 g) was purified by flash chromatography using hexane. The structure was confirmed by NMR.
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=2[F:17])[C:5]([NH2:18])=[CH:4][CH:3]=1.[CH:19]1([S:22](Cl)(=[O:24])=[O:23])[CH2:21][CH2:20]1>>[F:8][C:7]1[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=2[F:17])=[C:5]([NH:18][S:22]([CH:19]2[CH2:21][CH2:20]2)(=[O:24])=[O:23])[CH:4]=[CH:3][C:2]=1[F:1]
Reactant: O=S(=O)(Cl)C1CC1
Reactant: Nc1ccc(F)c(F)c1Nc1ccc(I)cc1F
Product: O=S(=O)(Nc1ccc(F)c(F)c1Nc1ccc(I)cc1F)C1CC1

Procedure:
According to the general procedure A, 5,6-difluoro-N1-(2-fluoro-4-iodophenyl)benzene-1,2-diamine was reacted with cyclopropanesulfonyl chloride to obtain the desired product. 1H NMR: (500 MHz, CDCl3): δ=7.38-7.37 (d, 1H), 7.35-7.34 (m, 1H), 121-1 Id (m, 1H), 7.20-7.0 (q, 1H), 6.68 (s, 1H, br), 6.15-6.12 (q, 1H), 5.65 (s, 1H, br), 3.25-3.20 (m, 1H), 2.4-2.3 (m, 2H), 2.0-1.8 (m, 2H); m/z=467 [M−1]−.
Reaction SMILES: [CH:1]1([C:4]2[C:12]([C:13]3[NH:17][C:16]([O:18][CH3:19])=[N:15][N:14]=3)=[CH:11][C:7]([C:8]([OH:10])=O)=[C:6]([CH3:20])[CH:5]=2)[CH2:3][CH2:2]1.Cl.[F:22][C:23]1([C:27]2[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][CH:28]=2)[CH2:26][NH:25][CH2:24]1.CC1NC(C2C=C(C=CC=2C)C(O)=O)=C(C)N=1.Cl.N1CC(C2C=CC(C#N)=CC=2)C1>>[CH:1]1([C:4]2[C:12]([C:13]3[NH:17][C:16]([O:18][CH3:19])=[N:15][N:14]=3)=[CH:11][C:7]([C:8]([N:25]3[CH2:24][C:23]([C:27]4[CH:28]=[CH:29][C:30]([C:31]#[N:32])=[CH:33][CH:34]=4)([F:22])[CH2:26]3)=[O:10])=[C:6]([CH3:20])[CH:5]=2)[CH2:2][CH2:3]1
Reactant: N#Cc1ccc(C2(F)CNC2)cc1
Reactant: COc1nnc(-c2cc(C(=O)O)c(C)cc2C2CC2)[nH]1
Agent: Cc1nc(C)c(-c2cc(C(=O)O)ccc2C)[nH]1
Agent: Cl
Agent: N#Cc1ccc(C2CNC2)cc1
Product: COc1nnc(-c2cc(C(=O)N3CC(F)(c4ccc(C#N)cc4)C3)c(C)cc2C2CC2)[nH]1

Procedure:
The title compound was prepared using standard chemical manipulations and procedures similar to those used for the preparation of compound 5, except 4-cyclopropyl-5-(5-methoxy-4H-1,2,4-triazol-3-yl)-2-methylbenzoic acid (compound 91.6) and 4-(3-fluoroazetidin-3-yl)benzonitrile (compound 43.4) were used in place of 3-(2,4-dimethyl-1H-imidazol-5-yl)-4-methylbenzoic acid (compound 5.7) and 4-(azetidin-3-yl)benzonitrile hydrochloride (compound 5.2), respectively. m/z (ES+) 432 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 13.66-13.01 (br, 1H), 7.96 (d, J=8.0 Hz, 2H), 7.76 (d, J=8.0 Hz, 2H), 7.61 (s, 1H), 6.86 (s, 1H), 4.60-4.38 (m, 4H), 3.91 (s, 3H), 2.82 (m, 1H), 2.34 (s, 3H), 0.94 (m, 2H), 0.71 (m, 2H).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:18]=[CH:17][C:12]([O:13][CH2:14][C:15]#[N:16])=[CH:11][C:10]=1[N+:19]([O-])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.O.[Sn](Cl)Cl.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[NH2:19][C:10]1[CH:11]=[C:12]([CH:17]=[CH:18][C:9]=1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[O:13][CH2:14][C:15]#[N:16]
Reactant: N#CCOc1ccc(OCc2ccccc2)c([N+](=O)[O-])c1
Agent: Cl[Sn]Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Product: N#CCOc1ccc(OCc2ccccc2)c(N)c1
Yield: 97.2 %

Procedure:
A solution of 6.9 g (4-benzyloxy-3-nitro-phenoxy)-acetonitrile, 200 ml of ethyl acetate, and 27.4 g of tin (II) chloride dihydrate was stirred at room temperature for 17 hours, poured into ethyl acetate, added saturated sodium bicarbonate solution, extracted twice with ethyl acetate, dried (MgSO4), evaporated, and obtained 6.0 g of (3-amino-4-benzyloxy-phenoxy)-acetonitrile as a light brown oil.
Reaction SMILES: COC1C=CC([C:9]2[N:14]([CH3:15])[C:13](=[O:16])[N:12]([CH3:17])[C:11](=[N:18][C:19]3[C:24]([CH3:25])=[CH:23][C:22]([CH3:26])=[CH:21][C:20]=3[CH3:27])[CH:10]=2)=CC=1SC.ClC1C=CC=C(C(OO)=O)C=1.O>CN(C)C=O>[CH3:15][N:14]1[CH:9]=[CH:10][C:11](=[N:18][C:19]2[C:20]([CH3:27])=[CH:21][C:22]([CH3:26])=[CH:23][C:24]=2[CH3:25])[N:12]([CH3:17])[C:13]1=[O:16]
Reactant: COc1ccc(-c2cc(=Nc3c(C)cc(C)cc3C)n(C)c(=O)n2C)cc1SC
Agent: O=C(OO)c1cccc(Cl)c1
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cc(C)c(N=c2ccn(C)c(=O)n2C)c(C)c1
Reaction time: 0.5 h
Yield: 82.8 %

Procedure:
To a solution of 3,4-dihydro-6-(4-methoxy-3-methylthiophenyl)-1,3-dimethyl-4-(2,4,6-trimethylphenylimino)-2(1H)-pyrimidinone (1.5 g) in N,N-dimethylformamide (15 ml) was added m-chloroperbenzoic acid (1.58 g), and stirred at 5°-10° C. for 30 minutes, and at ambient temperature for 5 hours. To the reaction mixture was added water (50 ml), and extracted with ethyl acetate. The organic layer was washed with aqueous sodium bicarbonate solution, dried over sodium sulfate, and evaporated. The residue was chromatographed on silica gel, eluting with chloroform. The fractions containing a sulfonyl compound were collected, dissolved in 1-N-hydrochloric acid and neutralized by aqueous sodium bicarbonate solution to give powdery 3,4-dihydro-6-(4- ro methoxy-3-methylsulfonylphenyl)-1,3-dimethyl-4-(2,4,6-trimethylphenylimino)-2(1H)-pyrimidinone (0.78 g).
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH:10]([N:14]([CH2:18][CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[CH2:15][CH2:16][CH3:17])[CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].N1C=CC=CC=1.[CH3:31][S:32](Cl)(=[O:34])=[O:33]>C(Cl)Cl>[CH3:31][S:32]([N:22]1[CH2:21][CH2:20][CH:19]([CH2:18][N:14]([CH:10]2[CH2:9][CH2:8][C:7]3[C:12](=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=3)[CH2:11]2)[CH2:15][CH2:16][CH3:17])[CH2:24][CH2:23]1)(=[O:34])=[O:33]
Reactant: CCCN(CC1CCNCC1)C1CCc2ccc([N+](=O)[O-])cc2C1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCCN(CC1CCN(S(C)(=O)=O)CC1)C1CCc2ccc([N+](=O)[O-])cc2C1
Temperature: 25 °C
Reaction time: 24 h
Yield: 85.3 %

Procedure:
To an ice-cold solution of (7-nitro-1,2,3,4-tetrahydro-naphthalen-2-yl)-piperidin-4-ylmethyl-propyl-amine (420 mg, 1.3 mmol) and pyridine (154 μl, 1.5 mmol, 1.2 eq.) in methylene chloride (30 mL) under an inert atmosphere methanesulfonyl chloride (154 μl, 1.9 mmol, 1.5 eq) was added dropwise. The reaction was allowed to warm to room temperature and stir for 24 h. The reaction was quenched with water and the methylene chloride layer separated, dried (MgSO4), and concentrated to afford (1-methanesulfonyl-piperidin-4-ylmethyl)-(7-nitro-1,2,3,4-tetrahydro-naphthalen-2-yl)-propyl-amine as a beige solid (454 mg).
Reaction SMILES: [C:1]([O:4][C:5]1[CH:13]=[C:12]([CH3:14])[C:11]([CH2:15][CH3:16])=[CH:10][C:6]=1[C:7](Cl)=[O:8])(=[O:3])[CH3:2].[Na].[C:18](CC(OCC)=O)#[N:19].[H-].[Na+].[OH-].[Na+]>CCOCC.O>[C:18]([C:2]1[C:1](=[O:3])[O:4][C:5]2[C:6]([C:7]=1[OH:8])=[CH:10][C:11]([CH2:15][CH3:16])=[C:12]([CH3:14])[CH:13]=2)#[N:19]
Reactant: CCc1cc(C(=O)Cl)c(OC(C)=O)cc1C
Reactant: CCOC(=O)CC#N
Agent: [H-]
Agent: [Na+]
Agent: [Na]
Solvent: O
Solvent: CCOCC
Product: CCc1cc2c(O)c(C#N)c(=O)oc2cc1C
Reaction time: 18 h

Procedure:
2-Acetoxy-5-ethyl-4-methylbenzoyl chloride (11.5 g) in dry ether (75 ml) was added slowly to a stirred, refluxing suspension of the sodium salt of ethyl cyanoacetate [prepared from ethyl cyanoacetate (14.97 g) and a 60% suspension of sodium hydride in mineral oil (5.00 g)] in dry ether (275 ml). Refluxing was continued for 18 hours, the mixture cooled and poured into water (500 ml) containing 2.5N sodium hydroxide (30 ml). The alkaline phase was separated, washed with ether (× 3), acidified with 12N hydrochloric acid and filtered. Recrystallisation from ethanol-dilute hydrochloric acid gave 3-cyano-6-ethyl-4-hydroxy-7-methyl coumarin, m.p. 224°-226° C. (Found; C, 68.22; H, 5.01; N, 5.64; C13H11NO3 requires; C, 68.11; H, 4.84; N, 6.11.)
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:7][C:8]1[CH:9]=[C:10]([C:15]2([C:31]([F:34])([F:33])[F:32])[O:19][N:18]=[C:17]([C:20]3[CH:29]=[CH:28][C:23]([C:24]([NH:26][OH:27])=[NH:25])=[C:22]([CH3:30])[CH:21]=3)[CH2:16]2)[CH:11]=[C:12]([Cl:14])[CH:13]=1.[CH2:35](Br)[C:36]#[CH:37]>CN(C)C=O.O>[Cl:7][C:8]1[CH:9]=[C:10]([C:15]2([C:31]([F:32])([F:34])[F:33])[O:19][N:18]=[C:17]([C:20]3[CH:29]=[CH:28][C:23]([C:24]([NH:26][O:27][CH2:37][C:36]#[CH:35])=[NH:25])=[C:22]([CH3:30])[CH:21]=3)[CH2:16]2)[CH:11]=[C:12]([Cl:14])[CH:13]=1
Reactant: Cc1cc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)ccc1C(=N)NO
Reactant: C#CCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: C#CCONC(=N)c1ccc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)cc1C
Temperature: 25 °C
Reaction time: 20 h

Procedure:
Caesium carbonate (0.122 g) was added to a solution of 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-N-hydroxy-2-methyl-benzamidine (0.1 g) (Example P1) in N,N-dimethylformamide (8 ml). Propargyl bromide (80% w/v in toluene) (0.028 ml) was added. The reaction mixture was stirred at ambient temperature for 20 hours. The reaction mixture was diluted with water and the mixture extracted twice with ethyl acetate. The combined organic phases were washed with water, dried over sodium sulfate, and concentrated. The residue was purified by preparative HPLC to give Compound No. A2 of Table A (0.054 g) as a yellow oil.
Reaction SMILES: Br[C:2]1[CH:18]=[CH:17][C:5]2[N:6]=[C:7]([C:9]3[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=3)[S:8][C:4]=2[CH:3]=1.BrC1SC2C=C(OC)C=CC=2[N:24]=1.FC1C=CC(B(O)O)=CN=1>>[CH3:16][O:15][C:12]1[N:11]=[CH:10][C:9]([C:7]2[S:8][C:4]3[CH:3]=[C:2]([NH2:24])[CH:18]=[CH:17][C:5]=3[N:6]=2)=[CH:14][CH:13]=1
Reactant: COc1ccc(-c2nc3ccc(Br)cc3s2)cn1
Reactant: COc1ccc2nc(Br)sc2c1
Agent: OB(O)c1ccc(F)nc1
Product: COc1ccc(-c2nc3ccc(N)cc3s2)cn1

Procedure:
The title compound was prepared according the method described for the preparation of 6-bromo-2-(6-methoxypyridin-3-yl)-1,3-benzothiazole, by reacting 2-bromo-6-methoxy-benzothiazole (1.09 g, 4.46 mmol) with 2-fluoropyridine-5-boronic acid (0.692 g, 4.9 mmol). The crude product was purified by flash column chromatography (0 to 2% methanol in DCM), to give the title compound (0.57 g). 1H NMR δ 8.88 (d, 1H) 8.58 (td, 1H) 7.98 (d, 1H) 7.76 (d, 1H) 7.38 (dd, 1H) 7.16 (dd, 1H) 3.86 (s, 3H); MS m/z (M+H) 261.
Reaction SMILES: [Si:1]([OH:5])([OH:4])([OH:3])[OH:2].[NH2:6][C:7]([NH2:9])=[O:8].[CH:10](=[O:12])C>>[Si:1]([OH:5])([OH:4])([OH:3])[OH:2].[NH2:6][C:7]([NH2:9])=[O:8].[CH2:10]=[O:12]
Reactant: CC=O
Agent: NC(N)=O
Agent: O[Si](O)(O)O
Product: C=O

Procedure:
One mol by weight of metasilicic acid and one mol by weight of urea are mixed, heated to 95° to 150° C. for 20 to 60 minutes, until the reaction is substantially complete, thereby producing white granules of urea silicate. The said urea silicate is mixed into about one mol of acetoaldehyde in an aqueous solution and the urea silicate goes into solution. The unreacted metasilicic acid is filtered out. About 15% to 25% of said metasilicic acid is filtered out. The urea silicate formaldehyde solution is heated to 70° to 110° C. for 20 to 60 minutes, until the desired viscosity is obtained, thereby producing poly (formaldehyde urea silicate) resin. The resin may be produced as a thick clear resin or a solid, depending on the length of time the resin is heated.