Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Al:1].N[CH2:3][C:4]([OH:6])=[O:5].C([N+]([O-])=O)C>>[C:4]([O-:6])(=[O:5])[CH3:3].[Al+3:1].[C:4]([O-:6])(=[O:5])[CH3:3].[C:4]([O-:6])(=[O:5])[CH3:3]
Reactant: [Al]
Reactant: NCC(=O)O
Solvent: CC[N+](=O)[O-]
Product: CC(=O)[O-]
Product: [Al+3]
Temperature: 98.88888888888889 °C

Procedure:
97.85 g of lemon-flavored hard candy stock was placed in an aluminum pan and heated at 210° F. to a mobile syrup. To this hot stock was added 2.15 g of a dry, finely-ground mixture containing 0.76 g of Al(CH3CO2)3 and 1.39 g of anhydrous glycine, C2H5NO2. The dry component was evenly distributed in the melted stock by thorough mixing and the product was poured onto a greased aluminum pan, forming a circular mass approximately 4 mm thick. As it cooled toward room temperature, it was scored with a lightly greased knife into pieces approximately 1.5 cm square. On cooling to room temperature, the squares were easily broken out of the mass. The yield was 33 pieces with an average weight of 2.4 g. The aluminum content was 1.0 mg per gram and glycine content was 13.9 mg per gram. The molar ratio of glycine to aluminum was 5 to 1. The flavor was very pleasant, without unpleasant aftertaste, and with an astringent mouth-feel.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:8][C:9]1[CH:35]=[CH:34][C:12]([C:13]([N:15]2[CH2:21][C:20]3[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=3[N:18]([CH2:26][CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)[C:17](=[O:33])[CH2:16]2)=[O:14])=[CH:11][CH:10]=1.[CH3:36][C:37]([CH3:39])=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([C:13]([N:15]2[CH2:21][C:20]3[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=3[N:18]([CH2:26][CH:27]3[CH2:28][CH2:29][N:30]([CH:37]([CH3:39])[CH3:36])[CH2:31][CH2:32]3)[C:17](=[O:33])[CH2:16]2)=[O:14])=[CH:34][CH:35]=1
Reactant: CC(C)=O
Reactant: O=C(c1ccc(Cl)cc1)N1CC(=O)N(CC2CCNCC2)c2ccccc2C1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)N1CCC(CN2C(=O)CN(C(=O)c3ccc(Cl)cc3)Cc3ccccc32)CC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
0.08 mmol of 4-(4-chlorobenzoyl)-1-(4-piperidinylmethyl)-1,3,4,5-tetrahydrobenzo[e][1,4]diazepin-2-on trifluoroacetate obtained in Example 140 and 7 mg (0.12 mmol) of acetone were dissolved in 3 ml of dichloromethane. 12 mg (0.20 mmol) of acetic acid was added to the obtained solution. After stirring at room temperature for 30 minutes. 53 mg (0.25 mmol) of sodium triacetoxyborohydride was added to the obtained mixture, and they were stirred at room temperature overnight. After the treatment with dichloromethane as the extracting solvent by an ordinary method, the obtained crude product was treated in the same manner as in step 3 in Example 1 to obtain the title compound.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[C:9](Cl)(Cl)=[S:10]>C(Cl)Cl.O>[Cl:8][C:5]1[CH:4]=[CH:3][C:2]([N:1]=[C:9]=[S:10])=[CH:7][N:6]=1
Reactant: Nc1ccc(Cl)nc1
Reactant: S=C(Cl)Cl
Solvent: ClCCl
Solvent: O
Product: S=C=Nc1ccc(Cl)nc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 101.5 %

Procedure:
A mixture of 5-amino-2-chloropyridine (5.0 g, 38.11 mmol) and thiophosgene (3.6 ml, 45.73 mmol) in DCM (75 ml) and water (35 ml) was stirred at r.t. for 18 h. The organic phase was dried (Na2SO4) and evaporated in vacuo to give the title compound as an off-white solid (6.6 g, 95%). δH (CDCl3) 8.35 (1H, dd, J 0.5, 2.2 Hz), 7.54 (1H, dd, J 2.2, 8.5 Hz), 7.40 (1H, dd, J 0.5, 8.5 Hz). LCMS (ES+) RT 3.61 minutes, 171 (M+H)+.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=1)=O.CN(C)[CH:13]=[O:14].[OH-:16].[Na+].Cl>[Pd].O>[OH:10][C:7]1[CH:8]=[CH:9][C:4]([CH:2]([CH3:1])[C:13]([OH:14])=[O:16])=[CH:5][CH:6]=1
Reactant: [OH-]
Reactant: CN(C)C=O
Reactant: CC(=O)c1ccc(O)cc1
Agent: [Pd]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CC(C(=O)O)c1ccc(O)cc1
Reaction time: 3.5 h
Yield: 85.8 %

Procedure:
A 13.6 g. portion of 4-hydroxyacetophenone was dissolved in 50 ml. of dimethylformamide, and 0.1 g. of sodium hydroxide and 2.5 g. of 5% palladium-on-carbon hydrogenation catalyst was added. The mixture was placed in a Parr hydrogenator at 45° for 3.5 hours, with shaking, and was then shaken at ambient temperature for 16.5 hours. The mixture was then filtered to remove the catalyst, and the solution was added to 5.4 g. of sodium cyanide in a Pyrex flask. The mixture was stirred at 130° for 6 hours, and was then evaporated under vacuum to obtain an oily residue. The residue was dissolved in 38 ml. of 50% aqueous sodium hydroxide and 38 ml. of water, and was stirred under reflux for 8 hours. Its pH was then adjusted to 2.0 with concentrated hydrochloric acid, 50 ml. of water was added, and the mixture was heated to reflux. It was filtered at the reflux temperature through a filter aid pad, and the filtrate was cooled and extracted twice with 125 ml. portions of ethyl acetate. The organic layers were combined and evaporated under vacuum to an oil. To it was added 50 ml. of toluene, followed by 50 ml. of hexane. The product crystallized within a few minutes, and the suspension was stirred for 1 hour before it was filtered. The solids were dried under vacuum at 40° to obtain 14.5 g. of the desired product, identical to that of Example 1. Its melting point was 127°-129°, and the yield was 85.8% of the theoretical yield.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([NH2:10])[CH:7]=[CH:6][C:5]=1[F:11].[Br:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH:17]=O>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([N:10]=[CH:17][C:16]2[CH:19]=[CH:20][CH:21]=[C:14]([Br:13])[CH:15]=2)[CH:7]=[CH:6][C:5]=1[F:11]
Reactant: COC(=O)c1cc(N)ccc1F
Reactant: O=Cc1cccc(Br)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: COC(=O)c1cc(N=Cc2cccc(Br)c2)ccc1F
Temperature: 25 °C
Yield: 100 %

Procedure:
A mixture solution of 5-amino-2-fluoro-benzoic acid methyl ester (26 g, 153.8 mmol), 3-bromo-benzaldehyde (28.5 g, 153.8 mmol) and p-toluenesulfonic acid (590 mg, 3.2 mmol) in toluene (200 mL) was heated to reflux for 12 hours. Then the reaction mixture was cooled to room temperature. The solvent was removed in vacuo and the residue was washed with ether to afford 5-[(3-bromo-benzylidene)-amino]-2-fluoro-benzoic acid methyl ester (51.7 g, quant.) as a pale-white solid: MS calcd. for C15H11BrFlNO2 337.16, obsd. (ESI+) [(M+H)+] 336.0 & 338.0.
Reaction SMILES: [CH2:1]([S:3]([N:6]([S:8]([NH:11][C:12](=[O:20])OC1C=CC=CC=1)(=[O:10])=[O:9])[CH3:7])(=[O:5])=[O:4])[CH3:2].[NH2:21][C:22]1[N:27]=[C:26]([O:28][CH2:29][CH3:30])[CH:25]=[C:24]([O:31][CH2:32][CH3:33])[N:23]=1.[C:34]1(C)C=CC=CC=1>>[CH2:1]([S:3]([N:6]([S:8]([NH:11][C:12]([NH:21][C:22]1[N:23]=[C:24]([O:31][CH2:32][CH3:33])[CH:25]=[C:26]([O:28][CH2:29][CH3:30])[N:27]=1)=[O:20])(=[O:9])=[O:10])[CH2:7][CH3:34])(=[O:4])=[O:5])[CH3:2]
Reactant: Cc1ccccc1
Reactant: CCOc1cc(OCC)nc(N)n1
Reactant: CCS(=O)(=O)N(C)S(=O)(=O)NC(=O)Oc1ccccc1
Product: CCOc1cc(OCC)nc(NC(=O)NS(=O)(=O)N(CC)S(=O)(=O)CC)n1
Temperature: 110 °C
Yield: 95.3 %

Procedure:
65.2 g of phenyl (N-ethylsulfonyl-N-methylamino)sulfonylcarbamate are dissolved in 700 ml of toluene, 36.6 g of 2-amino-4,6-diethoxypyrimidine are added at room temperature, and the mixture is heated at 110° C. for 2 hours. After cooling to room temperature, the precipitate is filtered at 0° C. and washed with 200 ml of toluene. 82.6 g of the desired product of a purity of 98.1% are obtained, which corresponds to a yield of 95.3% of theory.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([NH2:16])[N:10]=2)[C:5](F)=[N:6][CH:7]=1.[NH2:17][C:18]1[CH:19]=[C:20]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[C:21]([CH3:24])=[N:22][CH:23]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1COCC1>CN(C=O)C>[NH2:16][C:11]1[N:12]=[C:13]([CH3:15])[N:14]=[C:9]([C:4]2[C:5]([NH:17][C:18]3[CH:19]=[C:20]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[C:21]([CH3:24])=[N:22][CH:23]=3)=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[N:10]=1
Reactant: Cc1nc(N)nc(-c2cc(Cl)cnc2F)n1
Reactant: Cc1ncc(N)cc1NS(C)(=O)=O
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: Cc1nc(N)nc(-c2cc(Cl)cnc2Nc2cnc(C)c(NS(C)(=O)=O)c2)n1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 113.7 %

Procedure:
To a 15 mL round-bottom flask was added 4-(5-chloro-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.050 g, 0.209 mmol), N-(5-amino-2-methylpyridin-3-yl)methanesulfonamide (0.046 g, 0.230 mmol), and DMF (2.0 mL). The mixture was cooled to 0° C. under N2. Sodium bis(trimethylsilyl)amide, 1.0 m in THF (0.169 mL, 0.835 mmol) was then added to the solution in one portion. The now burgundy color mixture was stirred at 0° C. for 10 min then warmed up to rt and stirred for 1 h. The reaction mixture was quenched with sat. NH4Cl and partitioned between water and CHCl3. The aqueous layer was extracted with more CHCl3 (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (40 g, 3% MeOH in DCM) to afford the desired product as a yellow solid (100 mg). MS (ESI pos. ion) m/z: 421.0. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.45 (s, 6H) 3.06 (s, 3H) 7.84 (br. s., 1H) 7.97 (br. s., 1H) 8.24 (d, J=2.05 Hz, 1H) 8.38 (d, J=2.63 Hz, 1H) 8.64 (d, J=2.19 Hz, 1H) 8.75 (d, J=2.63 Hz, 1H) 9.32 (br. s., 1H) 11.98 (s, 1H).
Reaction SMILES: CC1(C)[O:6][C:5](=O)[CH:4]([CH:8]([C:13]([N:15]2[CH2:19][CH2:18][CH2:17][C@H:16]2[C:20]([NH2:22])=[O:21])=[O:14])[CH2:9][CH2:10][CH2:11][CH3:12])[O:3]1.[NH2:24][OH:25]>O1CCOCC1>[OH:25][NH:24][C:5](=[O:6])[C@@H:4]([OH:3])[C@@H:8]([CH2:9][CH2:10][CH2:11][CH3:12])[C:13]([N:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[C:20]([NH2:22])=[O:21])=[O:14]
Reactant: NO
Reactant: CCCCC(C(=O)N1CCC[C@H]1C(N)=O)C1OC(C)(C)OC1=O
Solvent: C1COCCO1
Product: CCCC[C@@H](C(=O)N1CCC[C@H]1C(N)=O)[C@H](O)C(=O)NO

Procedure:
To 1-(2,2-dimethyl-4-oxo-1,3-dioxolan-5-yl)-1-(2-(S)-aminocarbonylpyrrolidin-1-ylcarbonyl)pentane C-3 in dioxane was treated with 50% aqueous hydroxylamine for 4 h. The reaction mixture was then purified by preparative reverse-phase (C18) HPLC to afford N-hydroxy-3-(R)-n-butyl-3-[2-(S)-aminocarbonylpyrrolidin-1-ylcarbonyl)-2-(S)-hydroxypropionamide C-4.
Reaction SMILES: [NH2:1][C:2]1[CH:6]=[CH:5][N:4]([CH2:7][CH2:8][CH2:9][CH2:10][C:11]([NH2:13])=[O:12])[N:3]=1.I.[F:15][C:16]([F:24])([F:23])[CH2:17][NH:18][C:19](=[NH:22])SC.C(Cl)(Cl)Cl.CO.N>>[F:15][C:16]([F:24])([F:23])[CH2:17][N:18]=[C:19]([NH2:22])[NH:1][C:2]1[CH:6]=[CH:5][N:4]([CH2:7][CH2:8][CH2:9][CH2:10][C:11]([NH2:13])=[O:12])[N:3]=1
Reactant: CSC(=N)NCC(F)(F)F
Reactant: NC(=O)CCCCn1ccc(N)n1
Agent: I
Agent: N
Solvent: ClC(Cl)Cl
Solvent: CO
Product: NC(=O)CCCCn1ccc(NC(N)=NCC(F)(F)F)n1

Procedure:
A mixture of 5-(3-aminopyrazol-1-yl)valeramide (18.2 mg.) and (2,2,2-trifluoroethyl)-S-methylisothiourea hydroiodide (51 mg.) was heated at 100° for 20 minutes. Preparative high pressure liquid chromatography on silica gel, using CHCl3 /MeOH/ammonia (s.g. 0.880) 8:2:0.5 v/v/v as eluant gave 5-[3-(2-[2,2,2-trifluoroethyl]guanidino)pyrazol-1-yl]valeramide, m.p. 129°-130° (40%).
Reaction SMILES: COC(=O)[CH:4]([CH:11]1[CH2:13][CH:12]1[CH2:14][CH:15]1[O:19]CCO1)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[C:21]([OH:24])(=[O:23])C.O.[C:26](=O)([O-])O.[Na+]>C(OCC)C>[CH3:26][O:24][C:21](=[O:23])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH:11]1[CH2:13][CH:12]1[CH2:14][CH:15]=[O:19]
Reactant: O=C([O-])O
Reactant: CC(=O)O
Reactant: CCCCCCC(C(=O)OC)C1CC1CC1OCCO1
Agent: [Na+]
Solvent: O
Solvent: CCOCC
Product: COC(=O)CCCCCCCC1CC1CC=O
Temperature: 60 °C
Reaction time: 8 h

Procedure:
A mixture of 8-((2-((1,3-dioxolan-2-yl)methyl)cyclopropyl)octanoic acid methyl ester (0.42 g), acetic acid (16 ml) and water (4 ml) was stirred at 60° C. overnight. The reaction mixture was poured into a mixture of ice, diethyl ether and a saturated aqueous solution of sodium hydrogencarbonate. The separated organic layer was washed with water and dried over magnesium sulfate. After filtration, the filtrate was concentrated in vacuo and the obtained residue was purified by chromatography on silica gel (eluted with 5% ethyl acetate in n-hexane). The fractions including 8-(2-(formylmethyl)cyclopropyl)octanoic acid methyl ester were collected and concentrated in vacuo to give 8-(2-(formylmethyl)cyclopropyl)octanoic acid methyl ester (0.11 g) as an oil.
Reaction SMILES: [Cl:1][C:2]1[C:7](=O)[NH:6][CH:5]=[C:4]([C:9](=[O:16])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH:3]=1.P(Cl)(Cl)([Cl:19])=O>>[Cl:1][C:2]1[CH:3]=[C:4]([C:9](=[O:16])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH:5]=[N:6][C:7]=1[Cl:19]
Reactant: O=P(Cl)(Cl)Cl
Reactant: COC(=O)CCC(=O)c1c[nH]c(=O)c(Cl)c1
Product: COC(=O)CCC(=O)c1cnc(Cl)c(Cl)c1
Temperature: 75 °C

Procedure:
A suspension of 37 g (152 mmol) of methyl 4-(5-chloro-1,6-dihydro-6-oxopyridin-3-yl)-4-oxobutyrate in 230 ml of phosphorus oxychloride was heated at 75° C. for 25 hours. The phosphorus oxychloride was subsequently distilled off in vacuo. The pale red residue was taken up in 200 ml of dichloromethane, 100 ml of water was added, and the pH of the aqueous phase was brought to 8.5 using 30 percent sodium hydroxide solution. After phase separation, the aqueous phase was extracted using 100 ml of dichloromethane. The combined organic phases were treated with active charcoal and evaporated. The residue was recrystallized from 300 ml of diisopropyl ether and filtered at 2° C. The yield was 32.83 g of pale pink crystals. A further 1.76 g of product was obtained from the mother liquor in the form of crystals. The total product yield was 87 percent. The melting point of the product was 85.2° to 86° C. Other data concerning the product was:
Reaction SMILES: Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[CH2:13]([O:15][C:16](=[O:23])[CH2:17][C:18]1[NH:19][CH:20]=[CH:21][CH:22]=1)[CH3:14].[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CCN(CC)CC>C1(C)C=CC=CC=1>[CH2:13]([O:15][C:16](=[O:23])[CH2:17][C:18]1[NH:19][C:20]([C:2]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[O:4])=[CH:21][CH:22]=1)[CH3:14]
Reactant: CCOC(=O)Cc1ccc[nH]1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: C1COCCN1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CCOC(=O)Cc1ccc(C(=O)N2CCOCC2)[nH]1
Temperature: 100 °C
Yield: 43 %

Procedure:
Triphosgene (1.64 g, 5.5 mmol) was added to (1H-pyrrol-2-yl)-acetic acid ethylester (prepared following the general procedure described in; J. Org. Chem., 59(18),5230-5234, 1994) (841.0 mg, 5.5 mmol) in toluene (50 mL). The reslting mixture was heated at 100° C. for 1 hr. The reaction mixture was allowed to cool to RT and morpholine (1 mL) and Et3N (1 mL) was added. The resulting mixture was stirred at RT overnigbht and concentrated. The residue obtained was chromatographed on silica (50-100% EtOAc:Hexane) to obtain [5-(Morpholine-4-carbonyl)-1H-pyrrol-2-yl-acetic acid ethyl ester. Yield 43%. 1H-NMR (CDCl3; 400 MHz) δ 10.46 (brs, 1H), 6.43 and 6.08 (dd, J1=3.6, J2=2.68, 1H each), 4.1 (q, J=7.16, 2H), 3.85 and 3.73 (m, 4H each), 3.67 (s, 2H), 1.25 (t, J=7.16, 3H).
Reaction SMILES: [C:1]1([CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8]([OH:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:17](Br)[CH:18]=[CH2:19]>>[C:1]1([C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)([CH2:19][CH:18]=[CH2:17])[C:8]([OH:10])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C=CCBr
Reactant: O=C(O)C(c1ccccc1)c1ccccc1
Product: C=CCC(C(=O)O)(c1ccccc1)c1ccccc1

Procedure:
The compounds of the invention can be prepared by alkylation of diphenylacetic acid. For example, diphenylacetic acid was dilithiated and treated with allyl bromide to yield 2,2-diphenyl-4-pentenoic acid. This acid was cyclized to the furanone by treatment of the 2,2-diphenyl-4-pentenoic acid in formic acid with hydrogen peroxide followed by treatment with sodium hydroxide in aqueous methanol. Acidification provided the furanone which was allowed to react with trifluoromethane sulfonic anhydride in dichloromethane to afford the 5-[1-(trifluoromethanesulfonyl)methyl]-3,3-diphenyl-2- furanone. This triflate derivative was employed for alkylation of the appropriate pyrazole to produce a dihydro-3,3-diphenyl-5-(1H-pyrazol-1-ylmethyl)-2(3H)-furanone derivative or dihydro-5-[(substituted-1H-pyrazol-1-yl)methyl]-3,3-diphenyl-2(3H)-furanone derivatives.
Reaction SMILES: [Br-].[O:2]([C:10]1[CH:35]=[CH:34][C:13]([CH2:14][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:12][CH:11]=1)[Si](C(C)(C)C)(C)C.[CH2:36]([Si:41]1(C2C=CC=CC=2)[CH2:46][CH2:45][CH:44]([CH:47]2[CH2:52][CH2:51][CH:50]([CH:53]=O)[CH2:49][CH2:48]2)[CH2:43][CH2:42]1)[CH2:37][CH2:38][CH2:39][CH3:40].Br[CH2:62][C:63]([F:66])([F:65])[F:64]>>[F:64][C:63]([F:66])([F:65])[CH2:62][O:2][C:10]1[CH:11]=[CH:12][C:13]([CH2:14][CH2:53][C@H:50]2[CH2:51][CH2:52][C@H:47]([C@H:44]3[CH2:45][CH2:46][Si@H:41]([CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH2:42][CH2:43]3)[CH2:48][CH2:49]2)=[CH:34][CH:35]=1
Reactant: CCCCC[Si]1(c2ccccc2)CCC(C2CCC(C=O)CC2)CC1
Reactant: FC(F)(F)CBr
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Br-]
Product: CCCCC[Si@H]1CC[C@H]([C@H]2CC[C@H](CCc3ccc(OCC(F)(F)F)cc3)CC2)CC1

Procedure:
The general procedure of Example 38 was repeated using 4-(t-butyldimethylsiloxy)benzyltriphenylphosphonium bromide, 4-(4-n-pentyl-4-phenyl-4-silacyclohexyl)cyclohexane carbaldehyde, and 1-bromo-2,2,2-trifluoroethane, thereby obtaining the intended compound.
Reaction SMILES: [ClH:1].O1CCOCC1.[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH2:19][CH2:18][CH2:17][N:16]2C(OC(C)(C)C)=O)=[C:11]([F:27])[CH:10]=1>C(OCC)(=O)C.CO>[ClH:1].[ClH:1].[F:27][C:11]1[CH:10]=[C:9]([NH2:8])[CH:14]=[CH:13][C:12]=1[CH:15]1[CH2:19][CH2:18][CH2:17][NH:16]1
Reactant: CC(C)(C)OC(=O)N1CCCC1c1ccc(N)cc1F
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CO
Solvent: C1COCCO1
Product: Nc1ccc(C2CCCN2)c(F)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
100 ml of 4 N hydrochloric acid-dioxane solution was added to a solution of 19 g of t-butyl 2-(4-amino-2-fluoro-phenyl)-pyrrolidine-1-carboxylate obtained in Example 338 (step 2) in a mixture of 50 ml of ethyl acetate and 50 ml of methanol, with cooling with ice, and the reaction liquid was stirred overnight at room temperature. The solvent was evaporated away under educed pressure to obtain the entitled compound as a white solid.
Reaction SMILES: CCO[Si:4]([O:11][CH2:12]C)([O:8][CH2:9]C)[O:5][CH2:6]C.Cl.C[N:16]1C(=O)[CH2:19][CH2:18][CH2:17]1>>[NH2:16][CH2:17][CH2:18][CH2:19][Si:4]([O:5][CH3:6])([O:8][CH3:9])[O:11][CH3:12]
Reactant: CN1CCCC1=O
Reactant: CCO[Si](OCC)(OCC)OCC
Agent: Cl
Product: CO[Si](CCCN)(OC)OC

Procedure:
composite membranes of polyetherimide and nanodispersed silicium oxide, made by hydrolysis of TEOS in solutions of polyetherimide Ultem® in NMP by adding of 0.15 M HCl solution. After hydrolysis dense or phase inversed membranes are made from this polymer solution. Compatibility of the inorganic with the organic phase was obtained by extra addition of 3-aminopropyltrimethoxysilane (AS) (Membranes of poly(ether imide) and nanodispersed silica, S. P. Nunes, K. V. Peinemann, K, Ohlrogge, A. Alpers, M. Keller, A. T. N. Pires, J. Memb. Sci. 157 (1999) 219-226)).
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[C:9]([C:11]2[CH2:15][C:14]([C:26]([F:29])([F:28])[F:27])([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=3)[O:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[CH:4]=[N:5][OH:6].ClN1C(=O)CCC1=O.[N:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[CH2:44][NH2:45].C(N(CC)CC)C>CN(C=O)C.C1COCC1>[OH:6][NH:5][C:4](=[N:45][CH2:44][C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][N:38]=1)[C:3]1[CH:7]=[CH:8][C:9]([C:11]2[CH2:15][C:14]([C:26]([F:29])([F:27])[F:28])([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:24])([F:25])[F:23])[CH:17]=3)[O:13][N:12]=2)=[CH:10][C:2]=1[CH3:1]
Reactant: NCc1ccccn1
Reactant: Cc1cc(C2=NOC(c3cccc(C(F)(F)F)c3)(C(F)(F)F)C2)ccc1C=NO
Agent: O=C1CCC(=O)N1Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: Cc1cc(C2=NOC(c3cccc(C(F)(F)F)c3)(C(F)(F)F)C2)ccc1C(=NCc1ccccn1)NO
Temperature: 75 °C
Yield: 44 %

Procedure:
To a solution of 2-Methyl-4-[5-trifluoromethyl-5-(3-trifluoromethyl-phenyl)-4,5-dihydro-isoxazol-3-yl]-benzaldehyde oxime (250 mg) in DMF (8 mL) was added N-chloro succinimide (84 mg) and heated to 75° C. for 1 h. After cooling, the reaction mixture was poured onto ice-water and extracted with EtOAc. The combined organic layers were washed with water, dried (Na2SO4) and concentrated in vacuoto ¼ of the original volume to obtain the crude hydroxamic acid chloride. This mixture was added to a solution of 2-picolylamine (65 mg) and triethylamine (0.15 mL, 0.11 g) in THF (8 mL) and stirred at room temperature over night. After concentration in vacuo, the mixture was purified by chromatography on silica gel to obtain the title compound (138 mg, 44%).
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([NH2:12])=[N:9]2)=[N:4][CH:3]=1.ClC(Cl)(O[C:17](=[O:23])OC(Cl)(Cl)Cl)Cl.[C:25]1([CH2:31][CH2:32][NH2:33])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.O>N1C=CC=CC=1>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([NH:12][C:17]([NH:33][CH2:32][CH2:31][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:23])=[N:9]2)=[N:4][CH:3]=1
Reactant: NCCc1ccccc1
Reactant: Nc1ccc2ncc(Br)cc2n1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: O
Solvent: c1ccncc1
Product: O=C(NCCc1ccccc1)Nc1ccc2ncc(Br)cc2n1
Yield: 24 %

Procedure:
Under argon atmosphere, 201 mg (897 μmol, 1 eq) of 7-bromo-[1,5]naphthyridin-2-ylamine and 294 mg (993 μmol, 1.1 eq) of triphosgene were introduced in 10 mL of pyridine at 0° C. The mixture was stirred at reflux for 1 h. The mixture was allowed to reach rt and 238 μL (1.89 mmol, 2.1 eq) of 2-phenylethylamine were added. The mixture was stirred at reflux for 1 h. The mixture was allowed to reach rt and water was added. Aqueous layer was extracted with methylene chloride. Organic layers were dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by column chromatography using methylene chloride/ethanol: 96/4 as eluent. The solvent was evaporated to dryness to afford 80 mg of yellow powder with 24% yield.
Reaction SMILES: Cl[C:2]1[C:10]([S:11](=[O:14])(=[O:13])[NH2:12])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[NH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.Cl>O>[N+:15]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([S:11](=[O:14])(=[O:13])[NH2:12])[C:2]=1[N:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)[C:6]([OH:8])=[O:7])([O-:17])=[O:16]
Reactant: NS(=O)(=O)c1cc(C(=O)O)cc([N+](=O)[O-])c1Cl
Reactant: C1CCNCC1
Agent: Cl
Solvent: O
Product: NS(=O)(=O)c1cc(C(=O)O)cc([N+](=O)[O-])c1N1CCCCC1
Temperature: 95 °C
Reaction time: 2 h

Procedure:
A mixture of 4-chloro-3-nitro-5-sulphamyl-benzoic acid (2.8 g), piperidine (3.4 g), and water (13 ml) was stirred at 95° C for 2 hours. Then the reaction mixture was adjusted to a pH of 2.5 by the addition of 4N hydrochloric acid, and the precipitated 3-nitro-4-piperidino-5-sulphamyl-benzoic acid was collected and recrystallized from aqueous methanol. The melting point was 237°-238° C (decomp.)
Reaction SMILES: [Br:1][C:2]1[C:6]2=[N:7][C:8]([C:11]([OH:13])=[O:12])=[CH:9][CH:10]=[C:5]2[S:4][CH:3]=1.S1C2C(=NC(C(OC)=O)=CC=2)C=[CH:15]1.BrBr.CCOC(C)=O>C(Cl)(Cl)Cl.C(Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[C:6]2=[N:7][C:8]([C:11]([O:13][CH3:15])=[O:12])=[CH:9][CH:10]=[C:5]2[S:4][CH:3]=1
Reactant: COC(=O)c1ccc2sccc2n1
Reactant: O=C(O)c1ccc2scc(Br)c2n1
Agent: BrBr
Solvent: CCOC(C)=O
Solvent: ClC(Cl)Cl
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1ccc2scc(Br)c2n1
Temperature: 25 °C
Reaction time: 72 h
Yield: 21 %

Procedure:
3-Bromo-thieno[3,2-b]pyridine-5-carboxylic acid (Gronowitz, S.; Westerlund, C.; Hornfeldt, A. -B.; Acta Chem Scand. 29, 233, 1975) was esterified to the corresponding methyl ester. To a solution of the resulting methyl thieno[3,2-b]pyridine-5-carboxylate 9.7 g, 50.2 mmol) in CHCl3 at 0° C. was added a solution of bromine (16 g, 100.4 mmol) in CCl4 (150 mL) dropwise. The mixture was warmed to r.t. and stirred for 72 h. EtOAc (750 mL) was added. The mixture was washed with NaHSO3, dried (anhyd. MgSO4) and concentrated in vacuo. The residue was purified by chromatography on silica gel to give 2.84 g (21%) of the title compound and 5.5 g of starting material.