Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Na+].Cl[CH2:3][CH:4]([OH:10])[CH2:5][S:6]([O-:9])(=[O:8])=[O:7].[CH2:11]([NH2:13])[CH3:12].[Na]>O>[CH2:11]([NH:13][CH2:3][CH:4]([OH:10])[CH2:5][S:6]([OH:9])(=[O:8])=[O:7])[CH3:12]
Reactant: CCN
Reactant: O=S(=O)([O-])CC(O)CCl
Agent: [Na+]
Agent: [Na]
Solvent: O
Product: CCNCC(O)CS(=O)(=O)O
Temperature: 4.699999809265137 °C
Reaction time: 2 h

Procedure:
A solution of 3-chloro-2-hydroxy-1-propanesulfonic acid sodium salt (10 g, 50.9 mmol) in water (total volume: 40 mL) was added over 5 hours, via a syringe pump, to a cold (4.7° C.) solution of ethyl amine in water. The mixture was stirred for an additional 2 hours at 4.7° C. then for 18 hours at room temperature. NMR: quantitative yield. The mixture was concentrated. A solid could not be obtained: the sodium salt was too hygroscopic. The solution was treated with Amberlite IR-120 Plus, acid form, ion-exchange resin to give the free acid. It was still too hygroscopic to be obtained as a solid form. Submitted as a solution: d=1.314 g/mL, 62.5% w/w of the free acid in water. The 1H and 13C NMR and MS were consistent with the structure.
Reaction SMILES: [CH2:1]([O:6][CH:7]([CH3:11])[C:8](O)=[O:9])[CH2:2][CH2:3][CH2:4][CH3:5].S(Cl)([Cl:14])=O>>[CH2:1]([O:6][CH:7]([CH3:11])[C:8]([Cl:14])=[O:9])[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CCCCCOC(C)C(=O)O
Reactant: O=S(Cl)Cl
Product: CCCCCOC(C)C(=O)Cl

Procedure:
10 ml of thionyl chloride was added to 2.0 g of α-pentyloxypropionic acid and the mixture was refluxed under heat for 2 hours. Excess of thionyl chloride was distilled off to obtain α-pentyloxypropionic acid chloride. 20 ml of dry pyridine was added thereto, and 7.0 g of 5-decyl-2-(4-hydroxyphenyl)pyrimidine dissolved in 50 ml of dry benzene was further added dropwise. After the addition, the mixture was refluxed under heat, charged into ice water and extracted with benzene. The extractwas purified with a silica gel column chromatography to obtain 5-decyl-2-(4'-α-pentyloxypropanoyloxyphenyl)pyrimidine.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[CH2:15][C:16]([O:18]C)=[O:17])=[CH:4][CH:3]=1.Cl[CH2:21][C:22]1[CH:31]=[CH:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:23]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[OH-].[K+].N1C2C(=CC=CC=2)C=CC=1>C(O)C.O.CC(=O)CC>[N:23]1[C:24]2[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:30]=[CH:31][C:22]=1[CH2:21][O:1][C:2]1[CH:3]=[CH:4][C:5]([S:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[CH2:15][C:16]([OH:18])=[O:17])=[CH:6][CH:7]=1
Reactant: ClCc1ccc2ccccc2n1
Reactant: COC(=O)Cc1ccccc1Sc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CCC(C)=O
Solvent: CCO
Product: O=C(O)Cc1ccccc1Sc1ccc(OCc2ccc3ccccc3n2)cc1
Temperature: 5 °C
Reaction time: 8 h

Procedure:
A stirred mixture of methyl 2-(4-hydroxyphenylsulfanyl)phenylacetate (5.0 g, 18.0 mmol), 2-chloromethylquinoline (3.2 g, 18.0 mmol), anhydrous potassium carbonate (6.5 g), potassium iodide (0.2 g), and butan-2-one (70 ml) was refluxed for 8 h. The hot mixture was filtered, the filtration cake was washed with boiling butan-2-one (2×15 ml) and the filtrate was again filtered with charcoal. The solution was evaporated under reduced pressure. The crystalline residue was mixed with methanol (15 ml) and left to stand overnight in a refrigerator. The crystalline methyl ester of the title acid was filtered (5.9 g, 80.8%), m.p. 100-102. 1H NMR spectrum (CDCl3): CH3(OCO) 3.64 s; CH2(COO) 3.83 s; CH2(O) 5.36 s; aromatic H of the quinoline nucleus: H(3) 7.64 d, J=8.8 Hz; H(4) 8.18 d, J=8.8 Hz; H(5) 7.82 dd, J=1.3, 8.5 Hz; H(6) 7.54 m: H(7) 7.73 m; H(8) 8.08 d, J=8.5 Hz; This ester (5.9 g, 14.2 mmol) was suspended in ethanol (75 ml), a solution of potassium hydroxide (1.5 g, 27 mmol) in water (10 ml) was added and the mixture was refluxed 30 min. Then ethanol was evaporated under reduced pressure, the mixture was diluted with water (100 ml) and the cloudy solution was filtered with charcoal. The filtrate was acidified with acetic acid to pH 4.5, the mixture was cooled to 5° C. and the formed precipitate was filtered. The crude product was purified by crystallization from ethanol (120 ml) to give the title acid (3.0 g, 52.6%), m.p. 179-181° C. For C24H19NO3S (401.5) calculated: 71.80% C, 71.80% C, 4.77% H, 3.49% N, 7.99% S; found: 71.67% C, 4.94% H, 3.41% N, 7.77% S. 1H NMR spectrum (DMSO-d6, 60° C.): CH2(COO) 3.77 s; CH2(O) 5.38 s; aromatic H of the quinoline nucleus: H(3) 7.67 d, J=8.2 Hz; H(4) 8.40 d, J=8.2 Hz; H(5) 8.03 d, J=8.5 Hz; H(6) 7.78 m; H(7) 7.61 m; H(8) 7.98 dd, J=0.9, 8.5 Hz;
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:11]1[C:12]([C:17](O)=[O:18])=[CH:13][CH:14]=[CH:15][CH:16]=1>O>[CH3:1][C:2]1[C:3]2[C:11]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:17](=[O:18])[C:4]=2[CH:5]=[C:6]([C:8]([OH:10])=[O:9])[CH:7]=1
Reactant: Cc1cc(C(=O)O)ccc1-c1ccccc1C(=O)O
Solvent: O
Product: Cc1cc(C(=O)O)cc2c1-c1ccccc1C2=O
Temperature: 180 °C
Reaction time: 3 h
Yield: 96.8 %

Procedure:
A mixture of 2′-methyl-biphenyl-2,4′-dicarboxylic acid (1.94 g) and polyphosphoric acid (50 g) was stirred at 180° C. for 3 hr. The reaction mixture was cooled to room temperature, water (100 ml) was slowly added dropwise, and the mixture was further stirred at room temperature for 10 min. This suspension was filtered, and the obtained solid was successively washed with water (50 ml) and 50 v/v % aqueous methanol solution (50 ml). The obtained solid was air-dried, and dried under reduced pressure at 80° C. to give the title compound (1.745 g, 97%).
Reaction SMILES: [OH:1][C:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][C:7]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[CH:8][CH:9]=2)[N:4]([CH3:19])[CH:3]=1.[OH-].[Na+].[CH3:22][S:23](Cl)(=[O:25])=[O:24]>O>[CH3:22][S:23]([O:1][C:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][C:7]([O:13][CH2:14][C:15]([F:18])([F:16])[F:17])=[CH:8][CH:9]=2)[N:4]([CH3:19])[CH:3]=1)(=[O:25])=[O:24]
Reactant: CS(=O)(=O)Cl
Reactant: Cn1cc(O)c(=O)c2ccc(OCC(F)(F)F)cc21
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Cn1cc(OS(C)(=O)=O)c(=O)c2ccc(OCC(F)(F)F)cc21

Procedure:
A mixture of 3-hydroxy-1-methyl-7-(2,2,2-trifluoroethoxy)-4-quinolone (0.40 g), aqueous sodium hydroxide (5M, 0.43 ml) and water (10 ml) was stirred under nitrogen at 0°. Methanesulphonyl chloride (0.25 g) was added with stirring and the pH adjusted to 9 with aqueous sodium hydroxide (5M, 0.5 ml). The resultant solid was collected by filtration, washed with water (10 ml) and crystallised from industrial methylated spirit (10 ml) to give the novel compound 1-methyl-4-oxo-7-(2,2,2-trifluoroethoxy)-1,4-dihydro-quinol-3-yl methanesulphonate, m.p. 110°-112°.
Reaction SMILES: Cl[CH2:2][CH2:3][CH:4]1[CH2:10][N:9]([CH2:11][CH3:12])[C:8](=[O:13])[C:7]2[CH:14]=[CH:15][CH:16]=[CH:17][C:6]=2[N:5]1[CH3:18].[CH3:19][NH:20][CH3:21]>C(O)C>[CH3:19][N:20]([CH3:21])[CH2:2][CH2:3][CH:4]1[CH2:10][N:9]([CH2:11][CH3:12])[C:8](=[O:13])[C:7]2[CH:14]=[CH:15][CH:16]=[CH:17][C:6]=2[N:5]1[CH3:18]
Reactant: CCN1CC(CCCl)N(C)c2ccccc2C1=O
Reactant: CNC
Solvent: CCO
Product: CCN1CC(CCN(C)C)N(C)c2ccccc2C1=O

Procedure:
A solution of 30 g (0.112 mole) of 2-(2-chloroethyl)-4-ethyl-1-methyl-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one and 10 g (0.224 mole) of dimethylamine in 300 ml of ethanol was heated at 125° C. for 8 hrs and concentrated. The residue was partitioned between chloroform and dilute sodium hydroxide. The chloroform was dried over anhydrous sodium sulfate, concentrated and distilled. Yield of product was 20.5 g (66.5%), b.p. 175°-178°/0.1 mm.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[NH:7][C:8](=O)[CH3:9].[CH3:11][N:12](C)[CH:13]=O.[H-].[Na+].Cl.CN(CCCl)C>C(O)C>[CH3:11][N:12]([CH3:13])[CH2:9][CH2:8][NH:7][C:3]1[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=1
Reactant: CC(=O)Nc1nccn1C
Reactant: CN(C)C=O
Agent: CN(C)CCCl
Agent: Cl
Agent: [H-]
Solvent: CCO
Product: CN(C)CCNc1nccn1C
Temperature: 25 °C

Procedure:
Dissolve 9.5 g. (0.0683 moles) of N-(1-methyl-2-imidazolyl)acetamide in 150 ml. of dimethylformamide under nitrogen. 3.375 g. (0.75 moles) of sodium hydride 50% suspension is added and stirred at 30°-40° C. until gas evolution ceases. The reaction mixture is cooled to room temperature and an additional 3.375 g. of sodium hydride added along with 10.8 g. (0.075 moles) of dimethylaminoethyl chloride hydrochloride. The reaction mixture is stirred at 30°-45° C. until gas evolution ceases and at 50° C. for 1/2 hour and at 90° C. for 2 hours. The mixture is cooled to room temperature, 20 ml. of ethanol added and the mixture evaporated in vacuo. The residue is taken up in 150 ml. of 6 N hydrochloric acid and refluxed for 24 hours. The aqueous acid layer is extracted with hexane and then neutralized with 50 ml. of saturated sodium carbonate. The aqueous layer is extracted with chloroform (100 ml., 10 times) the organic layer washed with saturated sodium chloride, and evaporated to dryness affording 8.8 g. of oil identified as N,N-dimethyl-N'-(1-methyl-2-imidaziolyl)-1,2-ethane-diamine, which is used as in the next step.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][CH3:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:16](Cl)(=[O:18])[CH3:17]>ClCl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]([C:16](=[O:18])[CH3:17])[CH3:15])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(=O)Cl
Reactant: CNC1CCN(C(=O)OC(C)(C)C)CC1
Agent: ClCl
Product: CC(=O)N(C)C1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 95.2 %

Procedure:
To a solution of 4-methylamino-piperidine-1-carboxylic acid tert-butyl ester (616 mg, 2.9 mmol) in CH2 Cl2 (25 ml), was added acetyl chloride (215 μl, 3.02 mmol, 1.05 eq.) dropwise. The reaction mixture was stirred at RT for 16 hrs. The crude reaction mixture was extracted with CH2 Cl2 (2×50 ml) and washed with water (10 ml) and with brine (10 ml). The solvent was removed under reduced pressure to give the expected 4-(Acetyl-methyl-amino)-piperidine-1-carboxylic acid tert-butyl ester (708 mg, 96% yield).
Reaction SMILES: [C:1]([C:5]1[CH:21]=[CH:20][C:8]([CH2:9][N:10]2[C:18]3[C:13](=[CH:14][C:15]([NH2:19])=[CH:16][CH:17]=3)[CH:12]=[CH:11]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C([O:24][C:25](=[O:35])[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([N:32]=[C:33]=[O:34])[CH:27]=1)C>>[C:1]([C:5]1[CH:21]=[CH:20][C:8]([CH2:9][N:10]2[C:18]3[C:13](=[CH:14][C:15]([NH:19][C:33]([NH:32][C:28]4[CH:27]=[C:26]([CH:31]=[CH:30][CH:29]=4)[C:25]([OH:35])=[O:24])=[O:34])=[CH:16][CH:17]=3)[CH:12]=[CH:11]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc(Cn2ccc3cc(N)ccc32)cc1
Reactant: CCOC(=O)c1cccc(N=C=O)c1
Product: CC(C)(C)c1ccc(Cn2ccc3cc(NC(=O)Nc4cccc(C(=O)O)c4)ccc32)cc1

Procedure:
The title compound was prepared from 1-(4-tert-butylbenzyl)-1H-indol-5-amine and 3-isocyanato-benzoic acid ethyl ester following the procedure of Example 5: MS (ESI) m/z 442.
Reaction SMILES: [F:1][C:2]1[C:3](=[O:9])[NH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[I-].[Na+].CN(C)C(N(C)C)=N.Br[CH2:21][C:22]1[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=1[C:24]#[N:25]>CN(C=O)C.COCCOC>[Cl:8][C:5]1[N:4]([CH2:21][C:22]2[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=2[C:24]#[N:25])[C:3](=[O:9])[C:2]([F:1])=[CH:7][N:6]=1
Reactant: O=c1[nH]c(Cl)ncc1F
Reactant: N#Cc1ccccc1CBr
Agent: CN(C)C(=N)N(C)C
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: COCCOC
Product: N#Cc1ccccc1Cn1c(Cl)ncc(F)c1=O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Example 30B was also prepared from 5-fluoro-2-chloro-3H-pyrimidin-4-one as follows. To a solution of 5-fluoro-2-chloro-3H-pyrimidin-4-one (100.00 g, 0.67 mol) in 1:1 DMF/DME (440 mL) under a nitrogen atmosphere was added sodium iodide (10 g, 67 mmol) and the resulting slurry cooled to 0° C. While maintaining the internal temperature to ≦12° C., 1,1,3,3-tetramethylguanidine (94 mL, 0.74 mol) was added dropwise over 45 minutes to form a homogeneous solution. The ice bath was removed and a solution of 2-(bromomethyl)benzonitrile (145 g, 0.74 mol) in 1:1 DMF/DME (600 mL) was added all at once and the reaction mixture heated to 70° C. for 18 h. In-process assay (by HPLC analysis) showed complete consumption of the starting material. The reaction mixture was cooled to 30° C. and then MTBE (1.14 L) and DI water (2.29 L) were added to form a slurry which was stirred at ambient temperature for 1 h. The crude product was collected by filtration and washed with MTBE (1.14 L). The phases of the filtrate were separated and the organic layer was combined with the filter-cake and concentrated to a thick slurry which was subsequently reslurried with DME (1.00 L). Insoluble impurities were removed by vacuum filtration and washed with DME (500 mL). The filtrate was concentrated to a wet residue which was reslurried with 2-propanol (365 mL) and the solid product collected by vacuum filtration. After removal of residual IPA, the product was reslurried in ethyl acetate (6 vol) at 70° C. and heptane (6 vol) was added slowly while maintaining the internal temperature at 68-70° C. At the end of the addition of heptane, insoluble materials were still visible. The mixture was stirred for an additional 10 min after which insoluble impurities were removed by hot vacuum filtration. The filtrate was slowly cooled to room temperature and then cooled further to about 0° C. by means of a salt-ice bath. The crystallized product was collected by vacuum filtration and then reslurried in ethanol (6 vol) at 50° C., cooled to 40° C., and the product collected by vacuum filtration to give 80.62 g (45%, 95.6% AUC by HPLC) of 2-(2-chloro-5-fluoro-6-oxo-6H-pyrimidin-1-ylmethyl)-benzonitrile as an off-white solid.
Reaction SMILES: CO[SiH](OC)OC.[C:8]([O:13][CH2:14][CH2:15][CH2:16][Si](OC)(OC)OC)(=[O:12])[C:9]([CH3:11])=[CH2:10]>C1(C)C=CC=CC=1.C(Cl)C=C.[Pt]>[C:8]([O:13][CH2:14][CH:15]=[CH2:16])(=[O:12])[C:9]([CH3:11])=[CH2:10]
Reactant: C=C(C)C(=O)OCCC[Si](OC)(OC)OC
Agent: [Pt]
Agent: CO[SiH](OC)OC
Solvent: C=CCCl
Solvent: Cc1ccccc1
Product: C=CCOC(=O)C(=C)C
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 86 %

Procedure:
A three-neck flask equipped with a reflux condenser, stirring rod and thermometer was charged with 50ml of toluene as a solvent, a small amount of polymerization inhibitor, 12.6 grams of allyl methacrylate ester (0.1 mole) and one cubic centimeter of Catalyst A of Example 1 as a catalyst (10-5 mole on a platinum basis). 13.4 grams of trimethoxy silane (0.11 mole) were dropwise added in one hour from a dropping funnel. The reaction temperature was maintained at about 50° C. The reaction was further carried out for 30 minutes. The gas chromatography analysis demonstrated that gamma-methacryloxypropyl trimethoxy silane was obtained in a yield of 86% on an allyl methacrylate basis.
Reaction SMILES: F[B-](F)(F)F.C(O[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH3:17])=[NH2+:10])C.[O-]CC.[Na+].[N:22]#[C:23][NH2:24]>C(O)C>[C:23]([N:24]=[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH3:17])[NH2:10])#[N:22]
Reactant: N#CN
Reactant: CCOC(=[NH2+])c1ccccc1C
Agent: CC[O-]
Agent: F[B-](F)(F)F
Agent: [Na+]
Solvent: CCO
Product: Cc1ccccc1C(N)=NC#N
Yield: 18.8 %

Procedure:
To a solution of Example 19A (2.5 g 10.00 mmol) in 10 ml of absolute ethanol was added a solution of sodium ethoxide (681 mg, 10 mmol) in 3.7 ml of absolute ethanol. The precipitate was filtered and the filtrate was treated with a solution of cyanamide (420 mg, 10 mmol) in 10 ml of absolute ethanol. The reaction mixture was refluxed for 3 days and the solvent removed under reduced pressure. The crude mixture was purified by silica gel chromatography, eluting with a gradient of 0-50% ethyl acetate in methylene chloride to provide the 0.3 g of title compound. MS (ESI+) m/z 160 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([Cl:9])=[CH:4][C:3]=1[S:10]([NH2:13])(=[O:12])=[O:11].[Cl:14][C:15]1[CH:20]=[CH:19][C:18](/[CH:21]=[CH:22]/[S:23](Cl)(=[O:25])=[O:24])=[CH:17][CH:16]=1>>[Cl:9][C:5]1[C:6]([F:8])=[CH:7][C:2]([NH:1][S:23](/[CH:22]=[CH:21]/[C:18]2[CH:19]=[CH:20][C:15]([Cl:14])=[CH:16][CH:17]=2)(=[O:24])=[O:25])=[C:3]([S:10]([NH2:13])(=[O:12])=[O:11])[CH:4]=1
Reactant: O=S(=O)(Cl)/C=C/c1ccc(Cl)cc1
Reactant: Nc1cc(F)c(Cl)cc1S(N)(=O)=O
Product: NS(=O)(=O)c1cc(Cl)c(F)cc1NS(=O)(=O)/C=C/c1ccc(Cl)cc1
Yield: 61 %

Procedure:
The title compound was synthesized as described for 226 a) in 61% yield, starting from 2-amino-5-chloro-4-fluorobenzenesulfonamide and (E)-2-(4-chlorophenyl)ethenesulfonyl chloride.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:5]([NH:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13](O)=[O:14])=[O:6].Cl.[NH2:26][OH:27]>>[OH:27][NH:26][C:13]([CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][NH:7][C:5](=[O:6])[C:4]1[CH:16]=[CH:17][C:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:2]([CH3:1])[CH:3]=1)=[O:14]
Reactant: NO
Reactant: Cc1cc(C(=O)NCCCCCC(=O)O)ccc1-c1ccccc1
Agent: Cl
Product: Cc1cc(C(=O)NCCCCCC(=O)NO)ccc1-c1ccccc1
Yield: 51.9 %

Procedure:
The procedure of the step 3 in Example 80 was repeated except that 6-(3-methyl-4-phenyl-benzamido)hexanoic acid (70 mg (0.215 mmol)) instead of 6-(3-bromo-2-methylbenzamido)hexanoic acid, and 30 mg of hydroxylamine hydrochloride (0.43 mmol) instead of 1,2-phenylenediamine were used and purified by a preparative HPLC (C18, 20% H2O/CH3CN, 20 ml/min) to obtain the title compound (38 mg, 51%).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:9]=[C:10]([CH:15]=[CH:16][C:17]=1[F:18])[NH:11][C:12](=O)[CH3:13].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>CCOCC.C1COCC1>[Cl:7][C:8]1[CH:9]=[C:10]([CH:15]=[CH:16][C:17]=1[F:18])[NH:11][CH2:12][CH3:13]
Reactant: CC(=O)Nc1ccc(F)c(Cl)c1
Agent: O=C([O-])[C@H](O)[C@@H](O)C(=O)[O-]
Agent: [Al+3]
Agent: [H-]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCNc1ccc(F)c(Cl)c1
Reaction time: 2 h
Yield: 97.5 %

Procedure:
A suspension of lithium aluminium hydride (44.1 g, 1.16 mmol) in absolute ether (700 ml) is treated dropwise with a solution of 3'-chloro-4'-fluoroacetanilide (BE Patent No. 891537; 109 g, 0.576 mol) in absolute THF (350 ml). The suspension obtained is stirred for 2 hours, then cooled to 0° and treated with a Rochelle salt solution (350 ml). The crystals obtained are filtered off and washed with ether. The organic solution is dried over magnesium sulphate and the solvent is distilled off under reduced pressure. There are obtained 97.5 g (97.5%) of 3-chloro-N-ethyl-4-fluoroaniline as an amorphous material.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[NH2:9][C:10]1[NH:14][N:13]=[C:12]([CH2:15][CH3:16])[CH:11]=1.C(N(CC)C(C)C)(C)C>C1COCC1>[CH2:15]([C:12]1[NH:13][N:14]=[C:10]([NH:9][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)[CH:11]=1)[CH3:16]
Reactant: CCc1cc(N)[nH]n1
Reactant: Clc1ccnc(Cl)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CCc1cc(Nc2ccnc(Cl)n2)n[nH]1
Temperature: 60 °C
Yield: 34.7 %

Procedure:
A mixture of 2,4-dichloropyrimidine (2.97 g, 20 mmol), 5-amino-3-ethyl-1H-pyrazole (2.44 g, 22 mmol) and N,N-diisopropylethylamine (3.8 ml, 22 mmol) in dry THF (75 ml) was heated at 60° C. for 18 hours. The volatiles were removed by evaporation, and the residue was triturated with a mixture of DCM and water. The solid product was collected by filtration, washed with water and ether, and dried to give the title compound (1.55 g, 35%) as a colourless crystalline solid.
Reaction SMILES: [C:1]1([CH3:8])[C:2]([CH3:7])=[CH:3][CH:4]=[CH:5][CH:6]=1.[C:9]1(C)C=CC=CC=1>>[CH3:8][C:1]1[CH:6]=[CH:5][C:4]([CH3:9])=[CH:3][C:2]=1[CH3:7]
Reactant: Cc1ccccc1
Reactant: Cc1ccccc1C
Product: Cc1ccc(C)c(C)c1

Procedure:
In this example, transalkylation was carried out for obtaining xylene from toluene and 1,2,4-trimethylbenzene using the zeolite C of this invention (silica/alumina mole ratio=34.1) and the zeolite A-1 as a comparison (silica/alumina mole ratio=32.8).
Reaction SMILES: C(N(CC)[C:4](=[O:15])[C:5]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[CH:6]=1)C.Br[CH2:19][C:20]([CH3:22])=[CH2:21].CC(CSC[C@H]1O[C@@H](N2C3NC=NC(=O)C=3N=C2)[C@H](O)[C@@H]1O)C>>[CH3:12][O:11][C:9]1[CH:8]=[C:7]([O:13][CH3:14])[CH:6]=[C:5]2[C:10]=1[CH:19]=[C:20]([CH3:22])[CH:21]=[C:4]2[OH:15]
Reactant: CCN(CC)C(=O)c1cc(OC)cc(OC)c1
Reactant: C=C(C)CBr
Agent: CC(C)CSC[C@H]1O[C@@H](n2cnc3c(=O)nc[nH]c32)[C@H](O)[C@@H]1O
Product: COc1cc(OC)c2cc(C)cc(O)c2c1
Yield: 50 %

Procedure:
5,7-Dimethoxy-3-methyl-1-naphthol is synthesized from N,N-diethyl-3,5-dimethoxybenzamide and 3-bromo-2-methylpropene according to the method described by Sibi et al. (J. Org. Chem. 1986, Vol. 51, pp. 271-273). The yield is approximately 50%.
Reaction SMILES: I[C:2]1[C:3](=[O:14])[CH:4]2[CH:9]([C:10]=1[O:11][CH3:12])[CH:8]1[O:13][CH:5]2[CH2:6][CH2:7]1.[Cl:15][C:16]1[N:21]=[CH:20][C:19](B(O)O)=[C:18]([CH3:25])[CH:17]=1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:15][C:16]1[N:21]=[CH:20][C:19]([C:2]2[C:3](=[O:14])[CH:4]3[CH:9]([C:10]=2[O:11][CH3:12])[CH:8]2[O:13][CH:5]3[CH2:6][CH2:7]2)=[C:18]([CH3:25])[CH:17]=1
Reactant: COC1=C(I)C(=O)C2C3CCC(O3)C12
Reactant: Cc1cc(Cl)ncc1B(O)O
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: COCCOC
Product: COC1=C(c2cnc(Cl)cc2C)C(=O)C2C3CCC(O3)C12
Temperature: 130 °C
Reaction time: 0.5 h
Yield: 64.9 %

Procedure:
A microwave vial is charged with 4-iodo-5-methoxy-10-oxa-tricyclo[5.2.1.0*2,6*]dec-4-en-3-one (184 mg, 0.6 mmol), 6-chloro-4-methylpyridine-3-boronic acid (103 mg, 0.6 mmol) and bis(triphenylphosphine)palladium dichloride (21 mg, 0.03 mmol). DME (1 ml) is added, followed by 2N aqueous sodium carbonate solution (0.6 ml, 1.2 mmol) and the reaction is heated to 130° C. by microwave irradiation, with stirring, for 30 minutes. The reaction is then diluted with 2N HCl (20 ml), extracted with ethyl acetate (20 ml), and the organic layer is removed and purified by flash chromatography on silica gel to give 4-(6-chloro-4-methyl-pyridin-3-yl)-5-methoxy-10-oxa-tricyclo[5.2.1.0*2,6*]dec-4-en-3-one (119 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([OH:11])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].[CH2:12]([NH2:15])[CH2:13][NH2:14].Cl>O>[ClH:1].[NH2:14][CH2:13][CH2:12][NH:15][C:2]1[CH:3]=[C:4]([OH:11])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9]
Reactant: NCCN
Reactant: O=[N+]([O-])c1ccc(O)cc1Cl
Agent: Cl
Solvent: O
Product: NCCNc1cc(O)ccc1[N+](=O)[O-]
Temperature: -10 °C

Procedure:
0.432 mol (75 g) of 3-chloro-4-nitrophenol is introduced into 282 ml of ethylenediamine and the reaction medium is then heated in a boiling water-bath for 13 hours. The cooled solution is then poured into 2.6 liters of iced water to which 1.09 liters of hydrochloric acid (d=1.18) has been added. After cooling at -10° C. for a few hours, the 3-β-aminoethylamino-4-nitrophenol hydrochloride crystallises. It is filtered off and washed with an ice-cold 2N solution of hydrochloric acid and then with ethanol. After recrystallisation from water, the dried product melts with decomposition at a temperature above 260° C.