Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[CH3:11])[CH:6]=O.[C:12]([CH:16]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:14][CH3:15])=[O:13]>C1(C)C=CC=CC=1>[CH3:15][O:14][C:12](=[O:13])[CH:16]=[CH:6][C:5]1[CH:8]=[CH:9][C:10]([CH3:11])=[C:3]([O:2][CH3:1])[CH:4]=1
Reactant: COc1cc(C=O)ccc1C
Reactant: COC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Product: COC(=O)C=Cc1ccc(C)c(OC)c1
Yield: 97.7 %

Procedure:
A mixture of 3-methoxy-4-methylbenzaldehyde (19.3 g, 0.129 mol), carbomethoxy methylene triphenylphosphorane (51 g) in toluene (250 ml) was refluxed for 24 h. The mixture was quenched with aqueous ammonium chloride and extracted with ethyl acetate and concentrated in vacuo to give a residue. The residue was purified by flash chromatography using ethyl acetate-heptane (1:1) to give 3-(3-methoxy4-methyl-phenyl)acrylic acid methyl ester (27 g, 0.126 mol). A mixture of 3-(3-methoxy4-methyl-phenyl)acrylic acid methyl ester (27 g), sodium hydroxide (14 g), water (70 ml), methanol (140 ml) and tetrahydrofuran (70 ml) was refluxed at 50° C. for 1 h. The mixture was concentrated in vacuo and then water added. The mixture was filtered and 5 M HCl was added until precipitation occurred. The mixture was filtered and the solid precipitate washed with water and dried in-vacuo to give 3-(3-methoxy-4-methylphenyl)acrylic acid (23.5 g, 0.122 mol).
Reaction SMILES: [N:1]1[C:8](Cl)=[N:7][C:5](Cl)=[N:4][C:2]=1[Cl:3].[Cl-].[Al+3].[Cl-].[Cl-].Cl.[C:15]1([CH3:21])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>ClC1C=CC=CC=1Cl>[Cl:3][C:2]1[N:4]=[C:5]([C:18]2[CH:19]=[CH:20][C:15]([CH3:21])=[CH:16][CH:17]=2)[N:7]=[C:8]([C:18]2[CH:19]=[CH:20][C:15]([CH3:21])=[CH:16][CH:17]=2)[N:1]=1
Reactant: Clc1nc(Cl)nc(Cl)n1
Reactant: Cc1ccccc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: Clc1ccccc1Cl
Product: Cc1ccc(-c2nc(Cl)nc(-c3ccc(C)cc3)n2)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a stirring mixture of 1 eq of cyanuric chloride and 3 eq of aluminum chloride in o-dichlorobenzene at ice bath temperature was added concentrated HCl (13 wt % based on cyanuric chloride). After 10 minutes, 1.9 eq of toluene was added and the reaction mixture was stirred at ice bath temperature for 30 minutes. The cooling bath was removed, the reaction mixture was allowed to warm to room temperature, and stirred for 21 h. HPLC analysis indicated about 95% cyanuric chloride conversion to 2-chloro-4,6-bis(4-methylphenyl)-1,3,5-triazine and the isomer 2-chloro-4-(4-methylphenyl)-6-(2-methylphenyl)-1,3,5-triazine.
Reaction SMILES: [SH:1][C:2]1[CH:9]=[C:8]([C:10]2[C:11]([C:15]([F:18])([F:17])[F:16])=[N:12][NH:13][CH:14]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[CH:19]1([CH2:23]Br)[CH2:22][CH2:21][CH2:20]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH:19]1([CH2:23][S:1][C:2]2[CH:9]=[C:8]([C:10]3[C:11]([C:15]([F:16])([F:18])[F:17])=[N:12][NH:13][CH:14]=3)[CH:7]=[CH:6][C:3]=2[C:4]#[N:5])[CH2:22][CH2:21][CH2:20]1
Reactant: N#Cc1ccc(-c2c[nH]nc2C(F)(F)F)cc1S
Reactant: BrCC1CCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: N#Cc1ccc(-c2c[nH]nc2C(F)(F)F)cc1SCC1CCC1
Yield: 21.6 %

Procedure:
0.9 g (3.3 mmol) of 2-mercapto-4-(3-trifluoromethylpyrazolyl)benzonitrile, 0.5 g (3.3 mmol) of cyclobutylmethyl bromide and 0.55 g (4.0 mmol) of potassium carbonate were stirred in 5 ml of N,N-dimethylformamide at room temperature overnight. The resulting reaction mixture was poured into 50 ml of water and the organic matters were extracted with 20 ml of ethyl acetate twice. The ethyl acetate layers were combined, then washed with 30 ml of water twice and dried over anhydrous magnesium sulfate, and the ethyl acetate was distilled off under reduced pressure. Purification of the residue by silica gel column chromatography afforded 0.24 g of 2-cyclobutylmethylthio-4-(3-trifluoromethylpyrazolyl)benzonitrile (yield 21.2%) as a pale yellow powder (m.p. 102-103° C.).
Reaction SMILES: O[CH2:2][C@H:3]1[CH2:8][CH2:7][CH2:6][CH2:5][N:4]1[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1.C(N(CC)CC)C.CS([Cl:30])(=O)=O.C(=O)([O-])O.[Na+]>ClCCl>[Cl:30][C@@H:6]1[CH2:7][CH2:8][CH2:2][CH2:3][N:4]([CH2:9][CH2:10][C:11]2[CH:12]=[CH:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=2)[CH2:5]1
Reactant: CS(=O)(=O)Cl
Reactant: COc1ccc(CCN2CCCC[C@@H]2CO)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc(CCN2CCCC[C@@H](Cl)C2)cc1
Reaction time: 4 h

Procedure:
(R)-2-Hydroxymethyl-1-(4-methoxyphenethyl)piperidine (617 mg) was dissolved in 10 ml of dichloromethane. Triethylamine (0.30 g, 2.7 mmol) and methanesulfonyl chloride (0.30 g, 2.6 mmol) were added to the obtained solution under stirring under cooling on ice. They were stirred under cooling on ice for 1 hour and then at room temperature for 4 hours. The reaction liquid was distributed in dichloromethane and saturated aqueous sodium hydrogencarbonate solution. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain (R)-3-chloro-1-(4-methoxy-phenethyl)homopiperidine in the form of a light yellow oil (632 mg, 97%).
Reaction SMILES: [Cl:1][C:2]1[C:3](I)=[CH:4][C:5]([O:23][CH3:24])=[C:6]([CH:22]=1)[C:7]([N:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1)=[O:8].[C:26]1(B(O)O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:18]([O:17][C:15]([N:12]1[CH2:13][CH2:14][N:9]([C:7]([C:6]2[C:5]([O:23][CH3:24])=[CH:4][C:3]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[C:2]([Cl:1])[CH:22]=2)=[O:8])[CH2:10][CH2:11]1)=[O:16])([CH3:21])([CH3:20])[CH3:19]
Reactant: OB(O)c1ccccc1
Reactant: COc1cc(I)c(Cl)cc1C(=O)N1CCN(C(=O)OC(C)(C)C)CC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: COc1cc(-c2ccccc2)c(Cl)cc1C(=O)N1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Yield: 90.8 %

Procedure:
A mixture of tert-butyl 4-(5-chloro-4-iodo-2-methoxybenzoyl)piperazine-1-carboxylate (300 mg, 0.56 mmol), phenylboronic acid (82 mg, 0.67 mmol), Pd(PPh3)4 (129 mg, 0.1 mmol), Na2CO3 (180 mg, 1.68 mmol) in 1,4-dioxane (10 mL) and water (2 mL) was stirred at reflux under argon for 16 h. The mixture was allowed to cool to room temperature and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=30:1) to afford the desired product (219 mg, 80% yield).
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9](O)=[O:10])=[CH:7][CH:6]=1)([CH3:3])[CH3:2].[N+:14](=C)=[N-:15].O.NN>C1COCC1>[CH:1]([O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH:14][NH2:15])=[O:10])=[CH:7][CH:6]=1)([CH3:3])[CH3:2]
Reactant: C=[N+]=[N-]
Reactant: CC(C)Oc1ccc(C(=O)O)cc1
Agent: NN
Solvent: O
Solvent: C1CCOC1
Product: CC(C)Oc1ccc(C(=O)NN)cc1
Reaction time: 0.25 h
Yield: 98.5 %

Procedure:
A solution of 4-isopropoxy-benzoic acid (2.5 g, 13.8 mmol) in THF (5 ml) was treated with fresh ethereal diazomethane (ca. 20 mg/ml) (0.79 ml, 18.9 mmol, 1.4 eq.) at r.t. and stirred for 15 min. The crude product was then evaporated to dryness, dissolved in ethanol (10 ml) and heated under reflux with hydrazine monohydrate (3.5 ml, 71 mmol, 5 eq.) for 48 hrs. The volatiles were then completely evaporated and the product was dried overnight under high vacuum at 40° C. to afford the title compound (2.64 g, 99% yield) as a light brown solid. MS: m/e=194 (M+).
Reaction SMILES: [OH:1][CH2:2][C@@H:3]1[O:8][C:6](=[O:7])[CH2:5][CH2:4]1.[Si:9](Cl)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10]>C(Cl)Cl.N1C=CN=C1>[Si:9]([O:1][CH2:2][C@@H:3]1[O:8][C:6](=[O:7])[CH2:5][CH2:4]1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: O=C1CC[C@H](CO)O1
Agent: c1c[nH]cn1
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OC[C@H]1CCC(=O)O1

Procedure:
The methodology of Taniguchi et al. (Tetrahedron, 30, 3532, 1974) and Farina et al. (Tetrahedron Lett., 29, 1239, 1988) for the syntheses of D-ribose derivatives provided a model for our synthetic approach to the syntheses of the corresponding L-ribose derivatives. Nitrous acid deamination of D-glutamic acid (1) gave lactone 2, which was then converted to the corresponding ester 3 by treatment of compound 2, with ethanol and catalytic amount of p-toluenesulfonic acid (See Scheme 1). Reduction of compound 3 with NaBH4 in ethanol gave (R)-4-(hydroxymethyl)-4-butyrolactone (4). Protection of the hydroxy group of compound 4 with tert-butyldimethylsilyl chloride in methylene chloride using imidazole as catalyst produced (R)-4-([(tert-butyldimethylsilyl)oxy]methyl)-4-butyrolactone (5), which was then converted to the corresponding lactol 6 by reduction with diisobutyaluminum hydride (DIBAL) in toluene at -78° C. Acetylation of 6 with acetic anhydride and triethylamine afforded the key sugar intermediate, 1-O-acetyl-5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose (7) as a mixture of alpha and beta anomers: MS, m/e 231 (M+ --CH3CO), 215 M+ --CH3COO); NMR(CDCl3)) delta 0.10 (s, 6H, SiMe2), 0.95 (s, 9H, tert-butyl), 1.85-2.15 (m, 7H, CH2CH2 and COCH3), 3.50-3.65 (M, 2H, 5-H), 4.10-4.30 (m, 1H, 4-H), 6.20-6.30 (m, 1H, 1-H).
Reaction SMILES: C([O:4][CH2:5][C:6]1[C:7]2[S:15][CH:14]=[C:13]([Br:16])[C:8]=2[C:9](Cl)=[N:10][CH:11]=1)(=O)C.[NH4+:17].[OH-]>O1CCOCC1>[NH2:17][C:9]1[C:8]2[C:13]([Br:16])=[CH:14][S:15][C:7]=2[C:6]([CH2:5][OH:4])=[CH:11][N:10]=1
Reactant: [NH4+]
Reactant: CC(=O)OCc1cnc(Cl)c2c(Br)csc12
Agent: [OH-]
Solvent: C1COCCO1
Product: Nc1ncc(CO)c2scc(Br)c12
Yield: 84 %

Procedure:
A mixture of Example 277D (3.1 g, 9.7 mmol), concentrated NH4OH (62 mL), and dioxane (62 mL) was heated to 150° C. in a sealed tube for 36 hours, filtered, and concentrated to provide a soid which was triturated with water (20 mL), collected and dried to give 2.1 g (84% yield) of the desired product. MS (ESI(+)) m/e 258.9, 260.8 (M+H)+.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][C:5]1[CH:14]=[CH:13][C:8]2[NH:9][C:10](=[O:12])[O:11][C:7]=2[CH:6]=1.Cl.[F:16][C:17]1[CH:29]=[CH:28][C:20]([CH2:21][CH:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[CH:19][CH:18]=1.C(N(CC)CC)C>C(O)C>[F:16][C:17]1[CH:18]=[CH:19][C:20]([CH2:21][CH:22]2[CH2:23][CH2:24][N:25]([CH2:2][CH2:3][CH2:4][C:5]3[CH:14]=[CH:13][C:8]4[NH:9][C:10](=[O:12])[O:11][C:7]=4[CH:6]=3)[CH2:26][CH2:27]2)=[CH:28][CH:29]=1
Reactant: O=c1[nH]c2ccc(CCCCl)cc2o1
Reactant: Fc1ccc(CC2CCNCC2)cc1
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: O=c1[nH]c2ccc(CCCN3CCC(Cc4ccc(F)cc4)CC3)cc2o1
Yield: 93 %

Procedure:
A suspension of 5.5 g of 6-(3-chloropropyl)-3H-benzoxazol-2-one in 50 ml of ethanol is admixed with 5.7 g of 4-(4-fluorobenzyl)piperidine hydrochloride and 7.2 ml of triethylamine. The mixture is stirred under reflux for one hour and subjected to customary workup to give 8.5 g of 6-{3-[4-(4-fluorobenzyl)piperid-1-yl]propyl}-3H-benzoxazol-2-one, m.p. 105-107°.
Reaction SMILES: [C:1]1([S:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:15]1([CH3:23])[CH:20]=[C:19]([CH3:21])[CH:18]=[C:17]([CH3:22])[CH:16]=1.[Br-:24].[Al+3].[Br-].[Br-].Br>>[Br-:24].[C:9]1([S+:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:16]2[C:17]([CH3:22])=[CH:18][C:19]([CH3:21])=[CH:20][C:15]=2[CH3:23])[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: Cc1cc(C)cc(C)c1
Reactant: O=S(c1ccccc1)c1ccccc1
Agent: Br
Agent: [Al+3]
Agent: [Br-]
Product: Cc1cc(C)c([S+](c2ccccc2)c2ccccc2)c(C)c1
Temperature: 0 °C
Yield: 80 %

Procedure:
To 38 g of diphenyl sulfoxide were added 500 ml of mesitylene and 340 g of aluminum bromide, followed by allowing a reaction to take place at 90° C. for 12 hours. After the reaction solution was cooled, a mixture of 100 ml of concentrated hydrobromic acid solution and 500 ml of ice water were poured. An aqueous layer was extracted with benzene and the organic layer was washed with water and dried over anhydrous MgSO4, followed by filtration and removal of the solvent, whereby 58 g (Yield: 80%) of diphenyl-2,4,6-trimethylphenylsulfonium bromide was obtained as white crystal.
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH2:21][C:22]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])([CH3:24])[CH3:23])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].[CH2:32](I)[CH3:33]>CN(C=O)C>[C:1]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH2:21][C:22]([N:25]([CH2:32][CH3:33])[S:26]([CH3:29])(=[O:28])=[O:27])([CH3:23])[CH3:24])[CH2:12][CH2:13]1)([O:3][C:4]([CH3:7])([CH3:5])[CH3:6])=[O:2]
Reactant: CC(C)(COc1ccccc1N1CCN(C(=O)OC(C)(C)C)CC1)NS(C)(=O)=O
Reactant: CCI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCN(C(C)(C)COc1ccccc1N1CCN(C(=O)OC(C)(C)C)CC1)S(C)(=O)=O
Reaction time: 0.5 h

Procedure:
To a solution of N-boc-4-[2-(2-methanesulfonylamino-2-methyl-propoxy)-phenyl]-piperazine (197 mg, 0.46 mmol) in 4 mL of DMF was added NaH (55 mg of a 60% dispersion in oil, 1.38 mmol). After stirring for about 30 minutes, EtI (550 uL, 6.88 mmol) was added. After stirring at 45° C. for about an hour, the mixture was quenched with saturated aqueous sodium bicarbonate. The mixture was diluted with EtOAc, washed with water and brine, and then dried (Na2SO4), filtered and concentrated. The material was combined with 0.36 mmol of crude material from a previous reaction and purified by silica gel chromatography (35 g SiO2, 10 to 30% EtOAc/hexanes, over 30 minutes at 35 mL/min.) to afford about 323 mg (0.71 mmol, 86% combined yield) of the final compound. LRMS (electrospray): 456.2 [M+1]
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8]3=[C:9]([CH2:11][CH2:12][N:7]3[C@H:6]3[CH2:13][CH2:14][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][C@@H:5]23)[CH:10]=1.[CH3:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1B(O)O>>[CH3:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:2]1[CH:3]=[C:4]2[C:8]3=[C:9]([CH2:11][CH2:12][N:7]3[C@H:6]3[CH2:13][CH2:14][N:15]([C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[CH2:16][C@@H:5]23)[CH:10]=1
Reactant: CC(C)(C)OC(=O)N1CC[C@H]2[C@@H](C1)c1cc(Br)cc3c1N2CC3
Reactant: Cc1ccccc1B(O)O
Product: Cc1ccccc1-c1cc2c3c(c1)[C@@H]1CN(C(=O)OC(C)(C)C)CC[C@@H]1N3CC2

Procedure:
The title compound was prepared by the method of Example 89 step C from tert-butyl(6aS,10aR)-2-bromo-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)carboxylate (189 mg, 0.5 mmol) and 2-methylphenylboronic acid (136 mg, 1.0 mmol) to afford after chromatographic purification the title compound (90 mg, 46%). 1H NMR (CDCl3, 300 MHz) δ 7.11–7.18 (m,4H), 6.82 (s, 1H), 6.77 (s, 1H), 3.86–4.30 (m, 2H), 3.58–3.64 (m, 1H), 2.76–3.42 (m, 7H), 2.20 (s, 3H), 1.70–1.85 (m, 2H), 1.40 (s, 9H) ppm. MS-ApCI: 391 [M+H+].
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([NH:8]/[C:9](=[C:16]2\[C:17](=[O:25])[NH:18][C:19]3[C:24]\2=[CH:23][CH:22]=[CH:21][CH:20]=3)/[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:6][CH:7]=1.[C:26](OC(=O)C)(=[O:28])[CH3:27]>C(O)(=O)C>[C:26]([NH:1][C:2]1[CH:3]=[C:4]([NH:8]/[C:9](=[C:16]2\[C:17](=[O:25])[NH:18][C:19]3[C:24]\2=[CH:23][CH:22]=[CH:21][CH:20]=3)/[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:6][CH:7]=1)(=[O:28])[CH3:27]
Reactant: CC(=O)OC(C)=O
Reactant: Nc1cccc(N/C(=C2\C(=O)Nc3ccccc32)c2ccccc2)c1
Solvent: CC(=O)O
Product: CC(=O)Nc1cccc(N/C(=C2\C(=O)Nc3ccccc32)c2ccccc2)c1

Procedure:
Prepared analogously to Example 31 from (Z)-3-[1-(3-aminophenylamino)-1-phenyl-methylidene]-2-indolinone and acetic anhydride in glacial acetic acid.
Reaction SMILES: O=[CH:2][C:3](=[CH2:5])[CH3:4].N.[N:7]1C=C(C)[CH:10]=[C:9](C)[C:8]=1[CH3:15]>C(C(C)=O)C>[CH2:9]([C:8]1[CH:15]=[CH:5][C:3]([CH3:4])=[CH:2][N:7]=1)[CH3:10]
Reactant: Cc1cnc(C)c(C)c1
Reactant: C=C(C)C=O
Agent: N
Solvent: CCC(C)=O
Product: CCc1ccc(C)cn1

Procedure:
When the process of the present invention is performed in the form of a fixed bed, the catalyst of the present invention is packed in a reactor and heated to a reaction temperature. Then, the mixture of methacrolein, methyl ethyl ketone, ammonia and optionally an inert gas is supplied in the reactor to proceed the gas phase catalytic reaction while maintaining the suitable reaction temperature. Thus, a reaction product gas containing 2,3,5-collidine and 2-ethyl-5-methylpyridine is obtained.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:16](=[O:17])[CH:15]3[CH:10]([CH:11]4[O:18][CH:14]3[CH2:13][CH2:12]4)[C:9]2=[O:19])=[C:4]([CH2:20][CH3:21])[CH:3]=1.[F:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.[F-].[Cs+].ClCCl>COCCOC>[CH2:20]([C:4]1[C:5]([CH:8]2[C:16](=[O:17])[CH:15]3[CH:10]([CH:11]4[O:18][CH:14]3[CH2:13][CH2:12]4)[C:9]2=[O:19])=[CH:6][CH:7]=[C:2]([C:26]2[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=2)[CH:3]=1)[CH3:21]
Reactant: OB(O)c1ccc(F)cc1
Reactant: CCc1cc(Br)ccc1C1C(=O)C2C3CCC(O3)C2C1=O
Agent: [Cs+]
Agent: [F-]
Solvent: ClCCl
Solvent: COCCOC
Product: CCc1cc(-c2ccc(F)cc2)ccc1C1C(=O)C2C3CCC(O3)C2C1=O
Temperature: 80 °C

Procedure:
A mixture of (1RS,2SR,6RS,7SR)-4-(4-bromo-2-ethylphenyl)-10-oxatricyclo-[5.2.1.02,6]decane-3,5-dione (200 mg, 0.57 mmol), 4-fluorophenylboronic acid (112 mg, 0.80 mmol) and cesium fluoride (260 mg, 1.71 mmol) are stirred together in degassed 1,2-dimethoxyethane (5 ml) at room temperature under an atmosphere of nitrogen for 40 minutes at room temperature. [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (74 mg, 0.09 mmol) is added, and the reaction mixture is heated to 80° C. for 20 hours. The mixture is cooled to room temperature, filtered through a plug of diatomaceous earth, washing with 2M aqueous hydrochloric acid and dichloromethane. The organic phase is collected, and the aqueous phase is extracted with dichloromethane. The organic solutions are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure. The residue is purified by column choramtography on silica gel to give (1RS,2SR,6RS,7SR)-4-(3-ethyl-4′-fluorobiphen-4-yl)-10-oxatricyclo[5.2.1.02,6]decane-3,5-dione.
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])(=[O:13])[CH3:12].[OH:19][C:20]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:21]=1[C:22](OC)=[O:23]>O1CCCC1>[OH:19][C:20]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:21]=1[C:22](=[O:23])[CH2:12][C:11]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]
Reactant: COC(=O)c1cc(OC)ccc1O
Reactant: CC(=O)OC(C)(C)C
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1ccc(O)c(C(=O)CC(=O)OC(C)(C)C)c1
Temperature: -78 °C
Reaction time: 0.92 h
Yield: 82.1 %

Procedure:
A solution of lithium bis(trimethylsilyl)amide (1.0 M in tetrahydrofuran, 61.5 mL, 61.5 mmol) was stirred at −78° C. and treated over a 5 min period with a solution of tert-butyl acetate (5.2 mL, 38.4 mmol) in tetrahydrofuran (13 mL). The resulting mixture was stirred at −78° C. for 55 min, and then treated dropwise with a solution of methyl 2-hydroxy-5-methoxybenzoate (1.63 mL, 10.98 mmol) in tetrahydrofuran (13 mL) over a 5 min period. The resulting solution was warmed slowly to rt where it stirred for 3 days. At the conclusion of this period, the solution was treated with ice-cold saturated aqueous ammonium chloride, and then extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated under vacuum to provide an oil. The oil was purified by column chromatography (silica gel, 20-30% ethyl acetate-hexane), and the effluent was concentrated to yield a residue. The residue was recrystallized from hexane to provide tert-butyl 3-(2-hydroxy-5-methoxyphenyl)-3-oxopropanoate as yellow crystals (2.40 g, 82%). 1H NMR (400 MHz, CDCl3) δ ppm 1.46 (s, 9 H) 3.79 (s, 3 H) 3.89 (s, 2 H) 6.95 (d, J=9.2 Hz, 1 H) 7.11 (d, J=3.1 Hz, 1 H) 7.14 (dd, J=8.6, 2.5 Hz, 1 H) 11.54 (s, 1 H). Mass spectrum m/z 289.19 (M+Na)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[CH3:11].[H-].[Na+].[CH3:14][Si:15]([CH3:22])([CH3:21])[CH2:16][CH2:17][O:18][CH2:19]Cl.C(OCC)(=O)C>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:19][O:18][CH2:17][CH2:16][Si:15]([CH3:22])([CH3:21])[CH3:14])[N:6]=[C:5]2[CH3:11]
Reactant: C[Si](C)(C)CCOCCl
Reactant: Cc1n[nH]c2ccc(Br)cc12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1nn(COCC[Si](C)(C)C)c2ccc(Br)cc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.2 %

Procedure:
To a solution of 5-bromo-3-methylindazole 104 (2 g, 9.48 mmol) in anhydrous DMF (20 mL), cooled in ice bath, was added-sodium hydride (60% w/w, 0.57 g, 14.25 mmol) and (2-trimethylsilylethoxy)methyl chloride (2.5 mL, 14.16 mmol) in a dropwise manner. The reaction mixture was allowed to warm to room temperature and was stirred for 1 hour. Ethyl acetate (200 mL) was added. The organic layer was washed with saturated ammonium chloride solution, water and brine. The organic layer was dried over sodium sulfate. The organic solvent was evaporated under reduced pressure. The crude product was purified by flash column chromatography to yield the desired 5-bromo-3-methyl-N-(2-trimethylsilanylethoxymethyl)indazole 116 (2.95 g, 8.65 mmol) as a mixture of the 1H- and 2H-indazole regioisomers.
Reaction SMILES: [CH:1]1([N:7]=[C:8]=[N:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[O:16]1CCOCC1>>[C:8]([NH:7][CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)([NH:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:16]
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: C1COCCO1
Product: O=C(NC1CCCCC1)NC1CCCCC1
Reaction time: 0.5 h

Procedure:
0.05 mole of 1,4-dihydroxy-2-naphthoic acid was dissolved in 70 ml of DMF, and 10 ml of a 40% aqueous solution of sodium hydroxide was added dropwise to the solution while introducing nitrogen gas. Then, 0.05 mole of α-bromo-propionylethylamide dissolved in 15 ml of DMF was added dropwise and the reaction was conducted at 50° C. for 3 to 4 hours under agitation. After completion of the reaction, the reaction mixture was poured into ice-hydrochloric acid and crystals were recovered by filtration and recrystallized from acetonitrile to obtain a compound having a melting point of 192° C. Then, 0.01 mole of 1-hydroxy-4-[1-(ethylaminocarbonyl)ethoxy]-2-naphthoic acid so obtained was dissolved in 60 ml of dry dioxane, and 0.01 mole of dicyclohexylcarbodiimide was added to the solution. The reaction was conducted at 50° to 60° C. for 30 minutes under agitation. After completion of the reaction, the reaction mixture was filtered and dicyclohexylurea formed as a by-product was removed. The filtrate was concentrated under reduced pressure and n-hexane was added. Precipitated crystals were recovered by filtration and recrystallized from n-hexane to obtain a compound having a melting point of 95° C. (the yield being 65%). From the results of the elementary analysis, it was confirmed that the compound was the compound (2) illustrated above.