Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N+:10]([O-:12])=[O:11])([O-])=O.[F:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.O>[F:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:9]2[CH:4]=[C:5]([N+:10]([O-:12])=[O:11])[CH:6]=[CH:7][CH:8]=2)=[CH:16][CH:15]=1
Reactant: O=[N+]([O-])c1ccccc1[N+](=O)[O-]
Reactant: Oc1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CS(C)=O
Product: O=[N+]([O-])c1cccc(Oc2ccc(F)cc2)c1
Temperature: 100 °C
Reaction time: 16 h
Yield: 72 %

Procedure:
EX-634A) Dinitrobenzene (1.68 g, 10 mmol) and 4-fluorophenol (1.13 g, 10 mmol) were dissolved in anhydrous dimethylsulfoxide (25 mL), and powdered cesium carbonate (8 g, 24.8 mmol) was added. The mixture was stirred and heated to 100° C. using a reflux condenser under a nitrogen atmosphere. After 16 h, the mixture was diluted with water (120 mL), and the aqueous layer was extracted with diethyl ether (4×60 mL). The combined ether layers were washed with 3% HCl, 5% sodium hydroxide, and water, then dried over anhydrous MgSO4. The ether was removed in vacuo, and the recovered oil was purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:25) to give 1.68 g (69%) of the desired 3-(4-fluorophenoxy)nitrobenzene product as orange crystals, 97% pure by HPLC analysis. MS m/z=234 [M+H]+.
Reaction SMILES: Cl.[F:2][C:3]([F:16])([F:15])[CH2:4][O:5][C:6]1[N:11]=[CH:10][C:9]([CH:12]([NH2:14])[CH3:13])=[CH:8][CH:7]=1.[NH2:17][C:18]1[CH:19]=[C:20]([CH:24]=[C:25]([CH3:27])[N:26]=1)[C:21](O)=[O:22]>>[NH2:17][C:18]1[CH:19]=[C:20]([CH:24]=[C:25]([CH3:27])[N:26]=1)[C:21]([NH:14][CH:12]([C:9]1[CH:10]=[N:11][C:6]([O:5][CH2:4][C:3]([F:2])([F:15])[F:16])=[CH:7][CH:8]=1)[CH3:13])=[O:22]
Reactant: Cc1cc(C(=O)O)cc(N)n1
Reactant: CC(N)c1ccc(OCC(F)(F)F)nc1
Agent: Cl
Product: Cc1cc(C(=O)NC(C)c2ccc(OCC(F)(F)F)nc2)cc(N)n1
Yield: 71 %

Procedure:
The title compound is prepared in 71% yield (413 mg, a brown solid) from (−)-1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethanamine hydrochloride (422 mg, 1.6 mmol, Amine-1, single enantiomer) and 2-amino-6-methylisonicotinic acid (250 mg, 1.6 mmol) by the similar manner in Step-1 of Example 8.
Reaction SMILES: C([N:8]1[CH:14]2[CH2:15][CH2:16][CH:9]1[CH2:10][N:11]([C:17]1[CH:26]=[C:25]3[C:20]([C:21](=[O:32])[C:22]([C:29]([OH:31])=[O:30])=[CH:23][N:24]3[CH2:27][CH3:28])=[CH:19][C:18]=1[F:33])[CH2:12][CH2:13]2)C1C=CC=CC=1.Cl.[H][H].C(Cl)(Cl)Cl>CO.[Pd].CCOCC>[CH2:27]([N:24]1[C:25]2[C:20](=[CH:19][C:18]([F:33])=[C:17]([N:11]3[CH2:12][CH2:13][CH:14]4[NH:8][CH:9]([CH2:16][CH2:15]4)[CH2:10]3)[CH:26]=2)[C:21](=[O:32])[C:22]([C:29]([OH:31])=[O:30])=[CH:23]1)[CH3:28]
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCC4CCC(C3)N4Cc3ccccc3)cc21
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: CCOCC
Solvent: CO
Product: CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCC4CCC(C3)N4)cc21
Temperature: 25 °C
Yield: 19.3 %

Procedure:
7-(9-benzyl-3,9-diazabicyclo[4,2,1]non-3-yl)-6-fluoro-1-ethyl-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (963 mg, 2.15 mmoles) was dissolved in 125 ml of methanol that was previously saturated with HCl. To this solution was added 1.25 g of 10% Pd/C and the mixture was treated with an atmosphere of 45 psi hydrogen on a Parr hydrogenation apparatus at 60° C. for 4.5 hours. The mixture was then cooled to room temperature and filtered of catalyst through a celite pad. The filtrate was stripped to dryness, taken up in water (50 ml) and the pH was adjusted to 7.0 with saturated sodium bicarbonate. This aqueous layer was extracted with three times 200 ml chloroform which was dried over sodium sulfate and evaporated to give a solid residue. This residue was taken up in a small amount of chloroform and ether from which crystallized an off-white material that was filtered and dried to give 149 mg (19.3%) of the title compound, m.p. 147°-150° C.
Reaction SMILES: Br[CH2:2][C:3]1[C:8]([Cl:9])=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:10][N:11]([CH2:14][CH3:15])[CH2:12][CH3:13].[CH3:16][C:17]1[N:22]=[C:21]([SH:23])[N:20]=[C:19]([OH:24])[CH:18]=1.C(N(CC)CC)C>C(O)C>[Cl:9][C:8]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:10][N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])[C:3]=1[CH2:2][S:23][C:21]1[N:20]=[C:19]([OH:24])[CH:18]=[C:17]([CH3:16])[N:22]=1
Reactant: CCN(CC)Cc1cccc(Cl)c1CBr
Reactant: Cc1cc(O)nc(S)n1
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCN(CC)Cc1cccc(Cl)c1CSc1nc(C)cc(O)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 35.3 %

Procedure:
A mixture of {[2-(bromomethyl)-3-chlorophenyl]methyl}diethylamine (13.2 mmol), 6-methyl-2-sulfanylpyrimidin-4-ol (1.07 g, 7.5 mmol), and triethylamine (8 mL, 57.4 mmol) in absolute ethanol (50 mL) was stirred at room temperature overnight. The mixture was evaporated and then co-evaporated with EtOAc (20 mL). The solid residue was treated with water (100 mL), and the solution was extracted with dichloromethane (5×100 mL). The organic extracts were combined, dried over MgSO4, filtered, evaporated, and dried in vacuo. The crude product was purified by flash chromatography (0-15% MeOH/CH2Cl2), affording 2-[({2-chloro-6-[(diethylamino)methyl]phenyl}methyl)sulfanyl]-6-methylpyrimidin-4-ol (932 mg, 39% yield); 1H NMR (400 MHz, DMSO-d6): δ 0.96 (t, 6H, J=6.8 Hz), 2.21 (s, 3H), 2.86 (m, 4H), 4.69 (s, 2H), 6.01 (s 1H), 7.35 (m, 1H), 7.42 (m, 1H); M+ 352.
Reaction SMILES: [F:1][C:2]([F:8])([F:7])[CH2:3][CH2:4][CH:5]=O.[CH:9]([CH:11]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:10].CCOCC.CCCCCC>ClCCl>[F:1][C:2]([F:8])([F:7])[CH2:3][CH2:4]/[CH:5]=[CH:11]/[CH:9]=[O:10]
Reactant: O=CCCC(F)(F)F
Reactant: O=CC=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCCCCC
Solvent: ClCCl
Solvent: CCOCC
Product: O=C/C=C/CCC(F)(F)F

Procedure:
A solution of 12.6 g (0.1 mol) of 4,4,4-trifluorobutanal [T. Fuchikami and I. Ojima, J. Am. Chem. Soc. 104, 3527 (1982)] and 30.4 g (0.1 mol) of formylmethylenetriphenylphosphorane (see Tripett and D. M. Walker, J. Chem. Soc. 1961, 1266] in 200 ml of dichloromethane is heated under reflux for 24 hours under argon. The red solution is freed of solvent at room temperature in vacuo, and the residue is stirred thoroughly with ether/hexane (1:1). The solid portion is filtered off and subsequently washed three times with ether/hexane (1:1). The filtrate is concentrated by evaporation in vacuo and the residue is chromatographed with dichloromethane on silica gel. The product is eluted in the second fraction (Rf =0.4). 6,6,6-Trifluoro-2-trans-hexenal is obtained in the form of a light-yellow oil.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:20])[CH2:5][C:6]([C@@H:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=O)[CH3:2].[NH2:21]/[C:22](/[CH2:29][CH2:30][CH2:31][CH:32]([CH3:34])[CH3:33])=[CH:23]\[C:24]([O:26][CH2:27][CH3:28])=[O:25].[CH:35]([C:37]1[CH:45]=[CH:44][C:40]([C:41]([OH:43])=[O:42])=[CH:39][CH:38]=1)=O.N1CCCCC1>C1(C)C=CC=CC=1>[C:16]([O:15][C:13]([N:9]1[CH2:10][CH2:11][CH2:12][C@H:8]1[C:6]1[NH:21][C:22]([CH2:29][CH2:30][CH2:31][CH:32]([CH3:33])[CH3:34])=[C:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:35]([C:37]2[CH:45]=[CH:44][C:40]([C:41]([OH:43])=[O:42])=[CH:39][CH:38]=2)[C:5]=1[C:4]([O:3][CH2:1][CH3:2])=[O:20])=[O:14])([CH3:19])([CH3:18])[CH3:17]
Reactant: O=Cc1ccc(C(=O)O)cc1
Reactant: CCOC(=O)/C=C(\N)CCCC(C)C
Reactant: CCOC(=O)CC(=O)[C@@H]1CCCN1C(=O)OC(C)(C)C
Solvent: Cc1ccccc1
Solvent: C1CCNCC1
Product: CCOC(=O)C1=C(CCCC(C)C)NC([C@@H]2CCCN2C(=O)OC(C)(C)C)=C(C(=O)OCC)C1c1ccc(C(=O)O)cc1

Procedure:
To a stirred solution of tert-Butyl (2S)-2-(3-ethoxy-3-oxopropanoyl)-1-pyrrolidinecarboxylate (1.43 g, 5.02 mmol) in 30 mL of toluene, ethyl (2Z)-3-amino-7-methyl-2-octenoate (1.0 g, 5.02 mmol) was added followed by 4-formylbenzoic acid (0.904 g, 6.01 mmol) and piperidine (0.214 g, 2.51 mmol). The reaction was allowed to reflux for 3 h. The crude mixture was concentrated and carried on without purification.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[CH2:11]([O:13][CH2:14][CH2:15][NH2:16])[CH3:12].ClCCl>C(OCC)(=O)C>[CH2:11]([O:13][CH2:14][CH2:15][NH:16][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9])[CH3:12]
Reactant: O=[N+]([O-])c1ccccc1Cl
Reactant: CCOCCN
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CCOCCNc1ccccc1[N+](=O)[O-]
Reaction time: 18 h

Procedure:
According to the method of R. Iemura et al., J. Med. Chem., 29 1178-1183 (1986), combine 1-chloro-2-nitrobenzene (69.0 g, 440 mmol) and 2-aminoethyl ethyl ether (102.5 g, 1.15 mol) and heat to reflux. After 18 hours, cool and dilute the reaction mixture with ethyl acetate (400 mL). Extract with brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with dichloromethane to give N-(2-ethoxyethyl)-2-nitroaniline.
Reaction SMILES: C(O)(=O)C(O)=O.[CH2:7]([NH:11][NH2:12])[CH2:8][CH2:9][CH3:10].O=[C:14]([CH2:20][C:21](=O)[CH3:22])[C:15]([O:17][CH2:18][CH3:19])=[O:16].C(N(CC)CC)C>C(O)C>[CH2:7]([N:11]1[C:21]([CH3:22])=[CH:20][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:12]1)[CH2:8][CH2:9][CH3:10]
Reactant: CCCCNN
Reactant: CCOC(=O)C(=O)CC(C)=O
Agent: O=C(O)C(=O)O
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCCCn1nc(C(=O)OCC)cc1C
Temperature: 25 °C
Reaction time: 8 h
Yield: 61.5 %

Procedure:
Butylhydrazine oxalate (25 g, 140 mmol) was added over a period of 15 minutes to a solution of ethyl 2,4-dioxovalerate (22.2 g, 140 mmol) and triethylamine (210 mmol) in ethanol (140 mL). The resulting solution was stirred overnight at ambient temperature and concentrated under reduced pressure. Hexane was added, and an insoluble solid was removed by filtration. The hexane was removed under reduced pressure; the residue was purified by chromatography on a HORIZON HPFC system (65I cartridge, eluting with hexanes/ethyl acetate in a gradient from 80:20 to 45:55) to provide 18.1 g of ethyl 1-butyl-5-methyl-1H-pyrazole-3-carboxylate as a pale yellow oil.
Reaction SMILES: C(O[C:6]([N:8]([CH:10]1[CH2:14][CH2:13][N:12]([S:15]([C:18]2[C:19]3[C:20]([CH3:28])=[CH:21][N:22]=[CH:23][C:24]=3[CH:25]=[CH:26][CH:27]=2)(=[O:17])=[O:16])[CH2:11]1)C)=O)(C)(C)C.CC1C2C(S([Cl:43])(=O)=O)=CC=CC=2C=NC=1.C(OC(N([C@@H]1CCNC1)C)=O)(C)(C)C.BrC1C2C(S(Cl)(=O)=O)=CC=CC=2C=NC=1.C(OC(N([C@H]1CCNC1)C)=O)(C)(C)C>>[CH3:28][C:20]1[C:19]2[C:18]([S:15]([N:12]3[CH2:13][CH2:14][C@@H:10]([NH:8][CH3:6])[CH2:11]3)(=[O:17])=[O:16])=[CH:27][CH:26]=[CH:25][C:24]=2[CH:23]=[N:22][CH:21]=1.[ClH:43]
Reactant: Cc1cncc2cccc(S(=O)(=O)Cl)c12
Reactant: Cc1cncc2cccc(S(=O)(=O)N3CCC(N(C)C(=O)OC(C)(C)C)C3)c12
Agent: CN(C(=O)OC(C)(C)C)[C@@H]1CCNC1
Agent: CN(C(=O)OC(C)(C)C)[C@H]1CCNC1
Agent: O=S(=O)(Cl)c1cccc2cncc(Br)c12
Product: CN[C@@H]1CCN(S(=O)(=O)c2cccc3cncc(C)c23)C1
Product: Cl

Procedure:
3-[N-(tert-Butoxycarbonyl)-N-methylamino]-1-(4-methyl-5-isoquinolinesulfonyl)pyrrolidine (Intermediate 23b) can be prepared by using 4-methyl-5-isoquinolinesulfonyl chloride and (R)-3-[N-(tert-butoxycarbonyl)-N-methylamino]pyrrolidine in the method of Example 1-3, Step A instead of 4-bromo-5-isoquinolinesulfonyl chloride and (S)-3-[N-(tert-butoxycarbonyl)-N-methylamino]pyrrolidine, respectively, and then used in the method of Step B in a similar manner to obtain the title compound as hydrochloride.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[S:6](Cl)([C:9]1[CH:15]=[CH:14][C:12]([CH3:13])=[CH:11][CH:10]=1)(=[O:8])=[O:7].[CH3:17][C:18](C)([O-:20])C.[K+].C(OC(=O)C)(=O)C>>[S:6]([N:1]1[CH:5]=[CH:4][C:3]([C:18](=[O:20])[CH3:17])=[CH:2]1)([C:9]1[CH:15]=[CH:14][C:12]([CH3:13])=[CH:11][CH:10]=1)(=[O:8])=[O:7]
Reactant: c1cc[nH]c1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(=O)OC(C)=O
Product: CC(=O)c1ccn(S(=O)(=O)c2ccc(C)cc2)c1

Procedure:
The synthesis of 1-(N-tosyl)-3-(hydroxyethyl)pyrrole was carried out as described by Korri-Youssoufi et al., Materials Science and Engineering C15 (2001) 265-268. In a first step, 1-(N-tosyl) pyrrole was synthesized from pyrrole using tosyl chloride in the presence of a strong base, potassium tert-butoxide. Next, acylation of the 1-(N-tosyl)pyrrole with acetic anhydride made it possible to obtain 1-tosyl-3-acetylpyrrole, which was converted to methyl 2-[3-(1-N-tosylpyrrole)]acetate by oxidative transposition, using thallium nitrate in the presence of montmorillonite. Reduction under mild conditions with borane dimethyl sulfide gave the desired product, 1-(N-tosyl)-3-(hydroxyethyl)pyrrole. The overall yield of the reaction was 21.8%.
Reaction SMILES: [C:1]1([P:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([S:28]([O:31]C)(=[O:30])=[O:29])=[CH:24][CH:23]=1>>[CH3:20][O:21][C:22]1[CH:23]=[CH:24][C:25]([S:28]([O-:31])(=[O:30])=[O:29])=[CH:26][CH:27]=1.[CH3:20][P+:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: COc1ccc(S(=O)(=O)OC)cc1
Product: COc1ccc(S(=O)(=O)[O-])cc1
Product: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Yield: 181.3 %

Procedure:
A mixture of 8.89 g (44.0 mmol) of triphenylphosphine and 11.2 g (42.7 mmol) methyl 4-methoxybenzenesulfonate was allowed to react for 2 hr at 140° C. A total of 18.0 g (38.7 mmol, 90.7%) of the title compound was obtained. It was further purified by recrystallization from 90:10 toluene-acetonitrile. Analyses: mp 96.0°-98.5° C.
Reaction SMILES: [Cl:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][CH:7]2[CH2:12][CH2:11][N:10]([C:13](=[O:26])[CH2:14][NH:15][C:16]3[CH:25]=[CH:24][C:19]4[NH:20][C:21](=[O:23])[O:22][C:18]=4[CH:17]=3)[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.N[C:30]1C=CC2NC(=O)COC=2C=1>CO>[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][CH:7]2[CH2:12][CH2:11][N:10]([C:13](=[O:26])[CH2:14][NH:15][C:16]3[CH:25]=[CH:24][C:19]4[NH:20][C:21](=[O:23])[CH2:30][O:22][C:18]=4[CH:17]=3)[CH2:9][CH2:8]2)=[CH:4][CH:3]=1
Reactant: Nc1ccc2c(c1)OCC(=O)N2
Reactant: O=C(CNc1ccc2[nH]c(=O)oc2c1)N1CCC(Oc2ccc(Cl)cc2)CC1
Solvent: CO
Product: O=C1COc2cc(NCC(=O)N3CCC(Oc4ccc(Cl)cc4)CC3)ccc2N1

Procedure:
The title compound is prepared from 2-chloro-1-[4-(4-chloro-phenoxy)-piperidin-1-yl]-ethanone (Example 233) and 7-amino-4H-benzo[1,4]oxazin-3-one according to the method described in Example 206. Melting Point:207-210° C. (methanol)
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[C:8]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])[CH:7]=[C:6]([CH:18]([CH3:20])[CH3:19])[C:5]=1[NH:21][C:22]([NH:24][CH:25]([CH3:27])[CH3:26])=[S:23])([CH3:3])[CH3:2].[C:28]([Cl:31])(=[O:30])[CH3:29]>CC(C)=O>[ClH:31].[CH:1]([C:4]1[CH:9]=[C:8]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])[CH:7]=[C:6]([CH:18]([CH3:20])[CH3:19])[C:5]=1[NH:21][C:22](=[N:24][CH:25]([CH3:27])[CH3:26])[S:23][C:28](=[O:30])[CH3:29])([CH3:2])[CH3:3]
Reactant: CC(=O)Cl
Reactant: CC(C)NC(=S)Nc1c(C(C)C)cc(Oc2ccccc2F)cc1C(C)C
Solvent: CC(C)=O
Product: CC(=O)SC(=NC(C)C)Nc1c(C(C)C)cc(Oc2ccccc2F)cc1C(C)C
Product: Cl
Reaction time: 3 h

Procedure:
7.7 g of N-[2,6-diisopropyl-4-(2-fluorophenoxy)-phenyl]-N'-isopropylthiourea are dissolved in 20 ml of acetone, and 2.36 g of acetyl chloride are added dropwise with stirring at +5° to 10° C. The reaction mixture is subsequently allowed to stand for 3 hours at +10° C. The product which has crystallized out is filtered off with suction, washed with a little acetone and dried in vacuo. The title compound of the formula ##STR9## is present in the form of colourless crystals; melting point 164° C. with decomposition.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24]([O:26]C)=O)=[CH:18][CH:17]=1.[NH3:28].CO>>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24]([NH2:28])=[O:26])=[CH:18][CH:17]=1
Reactant: N
Reactant: COC(=O)CCc1ccc(OCCc2nc(-c3ccccc3)oc2C)cc1
Solvent: CO
Product: Cc1oc(-c2ccccc2)nc1CCOc1ccc(CCC(N)=O)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 80 %

Procedure:
Methyl 3-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]propionate (600 mg, 1.64 mmol) obtained in Example 16 was added to ammonia/methanol (50 ml), and the mixture was stirred for 24 hr at room temperature. The solvent was evaporated under reduced pressure. Ethyl acetate (50 ml) and 1N aqueous sodium hydroxide solution (50 ml) were added for partition. The organic layer was washed with water (50 ml) and saturated brine (50 ml), dried over magnesium sulfate, and concentrated under reduced pressure to give the title compound (464 mg, yield 80%) as a white solid.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[CH:20]=[C:19](Cl)[N:18]=[C:17]([NH:22][CH3:23])[N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.CN.[CH2:27]([N:29](CC)CC)C>C(O)C>[CH3:23][NH:22][C:17]1[N:16]=[C:15]([NH:14][S:11]([C:8]2[CH:9]=[CH:10][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][CH:7]=2)(=[O:13])=[O:12])[CH:20]=[C:19]([NH:29][CH3:27])[N:18]=1
Reactant: CCN(CC)CC
Reactant: CNc1nc(Cl)cc(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)n1
Agent: CN
Agent: Cl
Solvent: CCO
Product: CNc1cc(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(NC)n1
Temperature: 140 °C
Reaction time: 18 h
Yield: 33 %

Procedure:
0.47 g (0.0013 mol) of 4-tert-butyl-N-(6-chloro-2-methylamino-pyrimidin-4-yl)-benzenesulfonamide was dissolved in 10 ml of ethanol, treated with 1.3 g (0.019 mol) of methylamine hydrochloride and 4.7 ml (0.034 mol) of triethylamine and stirred in an autoclave at 140° C. for 18 hours. The mixture was freed completely from solvent, the residue was partitioned in ethyl acetate/water and the insoluble constituents were filtered off under suction. The filtered cake was recrystallized in methanol/diethyl ether. There was obtained 0.15 g (33%) of N-(2,6-bis-methylamino-pyrimidin-4-yl)-4-tert-butyl-benzenesulfonamide as white crystals; m.p. 316-318° C.
Reaction SMILES: Cl.[CH2:2]([O:9][C:10]1[CH:11]=[C:12]([CH:14]=[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:16]=1)[NH2:13])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:25](Cl)(=[O:29])[C:26](Cl)=[O:27]>CO>[CH2:2]([O:9][C:10]1[CH:16]=[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:14]=[C:12]2[C:11]=1[C:25](=[O:29])[C:26](=[O:27])[NH:13]2)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: Nc1cc(OCc2ccccc2)cc(OCc2ccccc2)c1
Reactant: O=C(Cl)C(=O)Cl
Agent: Cl
Solvent: CO
Product: O=C1Nc2cc(OCc3ccccc3)cc(OCc3ccccc3)c2C1=O
Temperature: 170 °C

Procedure:
A mixture of 3,5-dibenzyloxyaniline hydrochloride (J. Org. Chem., 1975, 40, 1556; 10 g) and oxalyl chloride (15 ml) was heated to 170° C. for 3 hours. The mixture was cooled to ambient temperature, methanol (45 ml) was added and the mixture was heated to reflux for 1 hour. The mixture was cooled to ambient temperature and the precipitate was isolated, washed with methanol and dried under vacuum to give 4,6-dibenzyloxy-2,3-dioxoindoline (8.8 g); NMR Spectrum: (DMSOd6) 5.22 (s, 2H), 5.28 (s, 2H), 6.12 (s, 1H), 6.42 (s, 1H), 7.3-7.55 (m, 10H), 10.97 (s, 1H).
Reaction SMILES: [NH2:1][C:2]1[C:7]([CH2:8][OH:9])=[CH:6][N:5]=[C:4]([S:10][CH3:11])[N:3]=1>C(Cl)(Cl)Cl.O=[Mn]=O>[NH2:1][C:2]1[C:7]([CH:8]=[O:9])=[CH:6][N:5]=[C:4]([S:10][CH3:11])[N:3]=1
Reactant: CSc1ncc(CO)c(N)n1
Agent: O=[Mn]=O
Solvent: ClC(Cl)Cl
Product: CSc1ncc(C=O)c(N)n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To the solution of 4-amino-5-hydroxymethyl-2-(methylthio)pyrimidine (1.0 g, 5.84 mmol) in CHCl3 (100 mL) was added MnO2 (2.5 g, 29.2 mmol, 5 equiv). The suspension was stirred at rt overnight. The mixture was filtered through celite and washed with CHCl3. The combined filtrate was concentrated to give the titled compound. 1H-NMR (500 MHz, CDCl3) δ 9.78 (s, 1H), 8.42 (s, 1H), 8.20 (broad, 1H), 5.74 (broad, 1H)), 2.55 (3, 3H).
Reaction SMILES: [CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[CH:5]=[C:4]1[C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH3:2].[C:18](Cl)(=[O:22])[C:19](Cl)=[O:20].CO.C[CH:27]([OH:29])C>C1(C)C=CC=CC=1>[CH2:16]([O:15][C:13]([C:4]1[N:3]([CH2:1][CH3:2])[C:11]2[C:6]([C:5]=1[C:18](=[O:22])[C:19]([O:29][CH3:27])=[O:20])=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)=[O:14])[CH3:17]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CC(C)O
Reactant: CCOC(=O)c1cc2cc(F)ccc2n1CC
Solvent: Cc1ccccc1
Solvent: CO
Product: CCOC(=O)c1c(C(=O)C(=O)OC)c2cc(F)ccc2n1CC
Reaction time: 1 h

Procedure:
A solution of 17 g (72 mmol) of ethyl 1-ethyl-5-fluoro-1H-indole-2-carboxylate and of 7.4 ml (84.5 mmol) of oxalyl chloride in 500 ml of toluene is heated at reflux for 6 h. An additional 5 ml (57 mmol) of oxalyl chloride are added, heating is carried out for 1 h at reflux and the mixture is allowed to return to room temperature. 200 ml of methanol are added, the mixture is stirred for 10 min and the solvents are evaporated under reduced pressure. The resulting oil is taken up in dichloromethane and the organic phase is washed with water, dried over magnesium sulphate and concentrated under reduced pressure. After recrystallizing from propan-2-ol, 14 g (43.6 mmol) of compound are obtained in the form of a white 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-1 of this invention (silica/alumina mole ratio=39.2) and the zeolite A as a comparison (silica/alumina mole ratio=32.8).
Reaction SMILES: [Cl:1][C:2]1[C:3](O)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8](OC)=[CH:7][CH:6]=2.[C:15]([O-:18])([O-])=O.[Cs+].[Cs+].BrC1C=CC(S([O:31][C@@H:32]2[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C@H:34]([C:44]([O:46][CH3:47])=[O:45])[CH2:33]2)(=O)=O)=CC=1>CN1C(=O)CCC1.O.CCOC(C)=O>[Cl:1][C:2]1[C:3]([O:31][C@H:32]2[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:38])[C@H:34]([C:44]([O:46][CH3:47])=[O:45])[CH2:33]2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[C:7]([O:18][CH3:15])[CH:6]=2
Reactant: O=C([O-])[O-]
Reactant: COc1ccc2nc(O)c(Cl)nc2c1
Reactant: COC(=O)[C@@H]1C[C@H](OS(=O)(=O)c2ccc(Br)cc2)CN1C(=O)OC(C)(C)C
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Solvent: O
Product: COC(=O)[C@@H]1C[C@@H](Oc2nc3cc(OC)ccc3nc2Cl)CN1C(=O)OC(C)(C)C
Temperature: 50 °C
Reaction time: 18 h
Yield: 35 %

Procedure:
A solution (0.35 M) of 3-chloro-6-methoxyquinoxalin-2-ol in NMP was treated with Cs2CO3 (1.5 eq) and 1-tert-butyl 2-methyl (2S,4S)-4-{[(4-bromophenyl)sulfonyl]oxy}pyrrolidine-1,2-dicarboxylate (1.1 eq). The resulting mixture was stirred at 50° C. for 18 h, then a further portion (0.1 eq) of 1-tert-butyl 2-methyl (2S,4S)-4-{[(4-bromophenyl)sulfonyl]oxy}pyrrolidine-1,2-dicarboxylate was added. After stirring for 2 h, the mixture was cooled and diluted with H2O and EtOAc. The organic phases were washed with aqueous HCl (1 N), saturated aqueous NaHCO3 and brine. The dried organic phase was concentrated to a residue that was purified by flash-chromatography (0-60% EtOAc/petroleum ether) to give the title compound (35% for two steps) as a solid. MS (ES+) m/z 438 (M+H)+