Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][CH:8]2[CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[C:26]4[C:21](=[CH:22][C:23]([Cl:27])=[CH:24][CH:25]=4)[CH:20]=[CH:19]3)[CH2:14][CH2:13]2)=[CH:4][CH:3]=1.[CH3:28][N:29]=[C:30]=[O:31]>ClCCl>[Cl:27][C:23]1[CH:22]=[C:21]2[C:26](=[CH:25][CH:24]=1)[N:18]([CH:15]1[CH2:14][CH2:13][N:12]([CH2:11][CH:8]3[C:9]4[C:5](=[CH:4][CH:3]=[C:2]([NH:1][C:30]([NH:29][CH3:28])=[O:31])[CH:10]=4)[CH2:6][CH2:7]3)[CH2:17][CH2:16]1)[CH:19]=[CH:20]2
Reactant: Nc1ccc2c(c1)C(CN1CCC(n3ccc4cc(Cl)ccc43)CC1)CC2
Reactant: CN=C=O
Solvent: ClCCl
Product: CNC(=O)Nc1ccc2c(c1)C(CN1CCC(n3ccc4cc(Cl)ccc43)CC1)CC2
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 1-[1-(6-aminoindan-1-ylmethyl)piperidin-4-yl]-5-chloro-1H-indole, 10h (0.9 g) in dichloromethane (10 mL) was added methylisocyanate (0.2 mL). The mixture was stirred at room temperature for 16 hours. Dichloromethane was evaporated. Upon addition of ethyl acetate the title compound 19a crystallized. The crystalline product was filtered off and dried overnight at 80° C. in vacua. Yield 0.6 g. mp: 193-195° C. 1H NMR (DMSO-d6): δ 1.70-1.85 (m, 1H); 1.90-2.35 (m, 7H); 2.35-2.85 (m, 4H); 2.65 (d, 3H); 3.05-3.15 (m, 2H); 3.25 (quin, 1H); 4.35-4.45 (m, 1H); 5.95 (dt, 1H); 6.45 (d, 1H); 7.00-7.20 (m, 3H); 7.50-7.65 (m, 4H); 8.35 (s, 1H).
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:5]=1F)=O.[NH2:13][NH2:14]>C(O)CO>[CH3:11][O:10][C:7]1[CH:6]=[C:5]2[C:4]([C:2]([CH3:1])=[N:13][NH:14]2)=[CH:9][CH:8]=1
Reactant: COc1ccc(C(C)=O)c(F)c1
Reactant: NN
Solvent: OCCO
Product: COc1ccc2c(C)n[nH]c2c1
Temperature: 150 °C

Procedure:
100 g of 2-fluoro-4-methoxy-acetophenone in 400 mL of ethylene glycol was stirred at room temperature with hydrazine (0.624 mol, 20 g) for 4 h after which the reaction mixture was heated to 150° C. for 48 h. TLC analysis indicated complete reaction. Partitioned the reaction mixture into dichloromethane and brine. Dried organic phase over sodium sulphate and evaporated to a solid. Re-crystallized from hexane/dicholomethane gave 6-methoxy-3-methyl-1H-indazole.
Reaction SMILES: [CH3:1][CH:2]([NH:5][S:6]([C:9]1[CH:20]=[C:13]2[C:14]([O:16]C(=O)[NH:18][C:12]2=[CH:11][CH:10]=1)=O)(=[O:8])=[O:7])[CH2:3][CH3:4].[CH3:21][N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1>C(O)C.C(OCC)C>[CH3:21][N:22]1[CH2:27][CH2:26][N:25]([C:14](=[O:16])[C:13]2[C:12](=[CH:11][CH:10]=[C:9]([S:6](=[O:7])(=[O:8])[NH:5][CH:2]([CH2:3][CH3:4])[CH3:1])[CH:20]=2)[NH2:18])[CH2:24][CH2:23]1
Reactant: CN1CCNCC1
Reactant: CCC(C)NS(=O)(=O)c1ccc2[nH]c(=O)oc(=O)c2c1
Solvent: CCO
Solvent: CCOCC
Product: CCC(C)NS(=O)(=O)c1ccc(N)c(C(=O)N2CCN(C)CC2)c1

Procedure:
In a manner analogous to that described in Example 1, the reaction of 5-[N-(2-butyl)-sulfamoyl]-isatoic anhydride with 1-methylpiperazine yields 5-[N-(2-butyl)-sulfamoyl]-anthranilic acid (4-methyl)-piperazide with a melting point of 130°-132° (from an ethanol/diethyl ether mixture). The hydrochloride melts at 246°-248°.
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:11])[C@@H:5]1[CH2:9][C@@H:8]([OH:10])[CH2:7][NH:6]1.C(N(CC)CC)C.[CH:19](OC)=[O:20]>>[CH3:2][O:3][C:4](=[O:11])[C@@H:5]1[CH2:9][C@@H:8]([OH:10])[CH2:7][N:6]1[CH:19]=[O:20]
Reactant: COC(=O)[C@@H]1C[C@@H](O)CN1
Reactant: COC=O
Agent: Cl
Solvent: CCN(CC)CC
Product: COC(=O)[C@@H]1C[C@@H](O)CN1C=O
Yield: 77.4 %

Procedure:
To a suspension of (2S,4R)-4-hydroxyproline methyl ester hydrochloride (9.08 g, 50.0 mmol) in methyl formate (90.0 ml) was added triethylamine (11.85 ml, 85.0 mmol). The mixture was refluxed for 5 h. The precipitate was filtered off, and the filtrate was concentrated in vacuo. The residue was subjected to silica gel column chromatography (Wakogel™ C-300, heptane-ethyl acetate=4:1→3:2) to give (2S,4R)-N-formyl-4-hydroxyproline methyl ester (6.70 g, yield: 77.4%).
Reaction SMILES: [C:1]([C:5]1[C:10](=[O:11])[C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:8][C:7](=O)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:17]([O:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23])[CH3:18].B(F)(F)F.CCOCC>O1CCCC1>[C:1]([C:5]1[C:10](=[O:11])[C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:8][C:7](=[N:23][C:22]2[CH:24]=[CH:25][CH:26]=[C:20]([O:19][CH2:17][CH3:18])[CH:21]=2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CCOc1cccc(N)c1
Reactant: CC(C)(C)C1=CC(=O)C=C(C(C)(C)C)C1=O
Agent: FB(F)F
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCOc1cccc(N=C2C=C(C(C)(C)C)C(=O)C(C(C)(C)C)=C2)c1
Yield: 2.7 %

Procedure:
A mixture of 22.0 g (0.10 mole) of 3,5-di-tertiary-butyl-p-benzoquinone, 15.1 g (0.11 mole) of m-ethoxyaniline, 125 ml of tetrahydrofuran and 1 ml of boron trifluoride etherate was heated at reflux for about 40 hours. The reaction mixture was evaporated to give an oil which was partitioned between hexane and 10% hydrochloric acid. The hexane phase was dried by filtering through Whatman IPS phase separation filter paper, then evaporated to give a solid. This solid was triturated with hexane, collected, rinsed with hexane, air dried and then recrystallized from ethanol to give a red solid. 1.0 g of this red solid was recrystallized from ethanol to give 0.9 g of red-orange crystalline 2,6-di-tertiary-butyl-4-(3'-ethoxyphenylimino)-2,5-cyclohexadiene-1-one, m.p. 105°-107° C. Calculated for C22H29NO2 : % C, 77.8; % H, 8.6; % N, 4.1; Found: % C, 77.4; % H, 8.5; % H, 3.9.
Reaction SMILES: [Li]CCCC.[S:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[CH:8]=[CH:7]1.C(OC([N:22]1[CH2:27][CH2:26][C:25]2([CH2:32][CH2:31][C:30](=O)[CH2:29][CH2:28]2)[CH2:24][CH2:23]1)=O)(C)(C)C>C(OCC)C>[S:6]1[C:7]([C:30]2[CH2:31][CH2:32][C:25]3([CH2:26][CH2:27][NH:22][CH2:23][CH2:24]3)[CH2:28][CH:29]=2)=[CH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]1=2
Reactant: CC(C)(C)OC(=O)N1CCC2(CCC(=O)CC2)CC1
Reactant: c1ccc2sccc2c1
Agent: [Li]CCCC
Solvent: CCOCC
Product: C1=C(c2cc3ccccc3s2)CCC2(C1)CCNCC2
Temperature: -78 °C
Reaction time: 2 h

Procedure:
Was prepared according to method A with the following variation: n-BuLi (1.6 M in hexanes (4 mL, 6.4 mmol)) was added drop-wise to a solution of benzothiophene (778 mg, 5.80 mL) in diethyl ether (10 mL). The reaction was warmed to reflux for 1 h and then cooled to −78° C. 9-Oxo-3-aza-spiro[5.5]undecane-3-carboxylic acid tert-butyl ester (500 mg, 1.87 mmol) in diethyl ether was added drop-wise and the mixture was stirred at −78° C. for 2 h. Mp. 107.3-110.2° C.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[C:7]([CH2:12][OH:13])[CH:6]=1)=[O:4].[CH3:14][N:15]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:16]1C=C[CH:19]=[C:18]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:17]=1>CC(=O)CC>[OH:11][C:8]1[CH:9]=[CH:10][C:5]([C:3](=[O:4])[CH2:2][N:22]([CH:18]([CH3:19])[CH2:17][CH2:16][N:15]([CH3:14])[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:6][C:7]=1[CH2:12][OH:13]
Reactant: O=C(CBr)c1ccc(O)c(CO)c1
Reactant: CN(c1ccccc1)c1cccc(NCc2ccccc2)c1
Solvent: CCC(C)=O
Product: CC(CCN(C)c1ccccc1)N(CC(=O)c1ccc(O)c(CO)c1)Cc1ccccc1
Yield: 66.6 %

Procedure:
A solution of 2-bromo-1-[4-hydroxy-3-(hydroxymethyl)phenyl]ethanone (9.1 g) and N-methyl-N-phenyl-N'-(phenylmethyl)-1,3-benzenediamine (16.6 g) in butanone (200 ml) was heated under reflux for 4 hours. The mixture was cooled at 0° and the amine hydrobromide was filtered off. The filtrate was evaporated and a solution of the residue in 2 N hydrochloric acid (200 ml) was extracted with ethyl acetate. The acidic solution was basified with solid sodium bicarbonate and then extracted with ethyl acetate. The solvents were evaporated to give a brown gum (10.7 g). The crude product in ethyl acetate was filtered through a column of silica (100 g) to yield a light brown gum (7.9 g).
Reaction SMILES: [CH:1]([C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=1[O:16][CH3:17])[C:10]([OH:12])=[O:11])=[CH:2][CH2:3][CH2:4][CH2:5][CH3:6].[H][H]>[C].[Pd].C(O)C>[CH2:1]([C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=1[O:16][CH3:17])[C:10]([OH:12])=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: [H][H]
Reactant: CCCCC=Cc1cc(C(=O)O)ccc1OC
Agent: [Pd]
Solvent: CCO
Product: CCCCCCc1cc(C(=O)O)ccc1OC
Yield: 71.9 %

Procedure:
3-(1-Hexenyl)-4-methoxybenzoic acid (160 mg, 0.683 mmol) and ethanol (7 ml) were mixed, and to this solution was added 10% palladium-carbon catalyst (30 mg). The mixture was stirred at room temperature for 3 hours in a steam of hydrogen. The palladium-carbon catalyst was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by washing with hexane to give 3-hexyl-4-methoxybenzoic acid (116 mg, 72%) as colorless crystals.
Reaction SMILES: [CH3:1][C:2]([CH2:6][CH2:7][CH:8]=[C:9]([CH3:47])[CH2:10][CH2:11][CH:12]=[C:13]([CH3:46])[CH2:14][CH2:15][CH:16]=[C:17]([CH3:45])[CH2:18][CH2:19][CH:20]=[C:21]([CH3:44])[CH2:22][CH2:23][C:24](=[O:43])[CH:25]([CH3:42])[CH2:26][CH2:27][CH:28]=[C:29]([CH3:41])[CH2:30][CH2:31][CH:32]=[C:33]([CH3:40])[CH2:34][CH2:35][CH:36]=[C:37]([CH3:39])[CH3:38])=[CH:3][CH2:4][OH:5].[CH3:48][C:49](OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=[O:50].CCOCC>N1C=CC=CC=1>[C:49]([O:5][CH2:4][CH:3]=[C:2]([CH3:1])[CH2:6][CH2:7][CH:8]=[C:9]([CH3:47])[CH2:10][CH2:11][CH:12]=[C:13]([CH3:46])[CH2:14][CH2:15][CH:16]=[C:17]([CH3:45])[CH2:18][CH2:19][CH:20]=[C:21]([CH3:44])[CH2:22][CH2:23][C:24](=[O:43])[CH:25]([CH3:42])[CH2:26][CH2:27][CH:28]=[C:29]([CH3:41])[CH2:30][CH2:31][CH:32]=[C:33]([CH3:40])[CH2:34][CH2:35][CH:36]=[C:37]([CH3:39])[CH3:38])(=[O:50])[CH3:48]
Reactant: CC(=O)OCc1c2ccccc2c(COC(C)=O)c2ccccc12
Reactant: CC(C)=CCCC(C)=CCCC(C)=CCCC(C)C(=O)CCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCO
Solvent: c1ccncc1
Solvent: CCOCC
Product: CC(=O)OCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC(=O)C(C)CCC=C(C)CCC=C(C)CCC=C(C)C
Temperature: 0 °C
Reaction time: 5 h

Procedure:
To a solution of 3,7,11,15,19,23,27,31,35-nonamethyl-2,6,10,14,18,26,30,34-hexatriacontaoctaen-22-on-1-ol 6.5 g) in pyridine (1 g), acetic anhdyride (3.0 g) is added, and the resulting mixture is allowed to stand at room temperature for 5 hours. The reaction mixture is poured into ice water and shaken with ether. The ether layer is washed with water, dried and evaporated. The residual material (6.5 g) is chromatographed on silica gel (70 g) using benzene to give 1-acetoxy-3,7,11,15,19,23,27,31,35-nonamethyl-2,6,10,14,18,26,30,34-hexatriacontaoctaen-22-one (6.1 g). A solution of this compound in ethanol (6 ml) is dropwise added to a solution of sodium borohydride (0.1 g) in ethanol (10 ml) while cooling with ice, and stirring is continued for 3 hours. The reaction mixture is poured into an aqueous saturated solution of ammonium chloride and extracted with ether. The ether extract is washed with water, dried and concentrated. The residual material (4.8 g) is treated as in Example 1 (5) a) to give 1-acetoxy-3,7,11,15,19,23,27,31, 35-nonamethyl-2,6,10,14,18,26,30,34-hexatriacontaoctaen- 22-ol (2.1 g) as a fraction (1) and 3,7,11,15,19,23,27,31,35-nonamethyl-2,6,10,14,18,26,30,34-hexatriacontaoctaene-1,22-diol (0.9 g) as a fraction (2). The latter is treated with acetic anhydride as above to give 1-acetoxy-3,7,11,15,19,23,27,31,35-nonamethyl-2,6,10,14,18,26,30,34-hexatriacontaoctaen-22-ol (0.82 g).
Reaction SMILES: C(ON=O)(C)(C)C.Br[CH2:9][C:10](=[CH2:14])[C:11]([OH:13])=[O:12].[N+:15]([C:18]1[CH:19]=[C:20]([CH:22]=[C:23]([N+:25]([O-:27])=[O:26])[CH:24]=1)N)([O-:17])=[O:16].NC1C=CC=CC=1>CC#N>[N+:15]([C:18]1[CH:19]=[C:20]([CH:22]=[C:23]([N+:25]([O-:27])=[O:26])[CH:24]=1)[CH2:9][C:10](=[CH2:14])[C:11]([OH:13])=[O:12])([O-:17])=[O:16]
Reactant: C=C(CBr)C(=O)O
Reactant: Nc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Agent: CC(C)(C)ON=O
Solvent: CC#N
Solvent: Nc1ccccc1
Product: C=C(Cc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1)C(=O)O
Temperature: 17.5 °C
Reaction time: 1 h
Yield: 59.5 %

Procedure:
To a solution of t-butylnitrite (535 μl, 4.5 mmol) and 2-(bromomethyl)acrylic acid (7.42 g, 45.0 mmol) in CH3CN (10 ml), 3,5-dinitroaniline (549 mg, 3.0 mmol) was added during 20 minutes, while maintaining the temperature of the reaction mixture at 15-20° C. At the end of the addition of the aniline extra t-butylnitrite (180 μl, 1.5 mmol) was added to the reaction mixture. After heating to 35° C. for 5 minutes, the mixture was stirred at room temperature for one hour. The volatile material in the reaction mixture was then removed at reduced pressure. The remaining crystalline residue was washed with heptane (5×50 ml) to remove unreacted 2-(bromomethyl)acrylic acid. Column chromatography (heptane-ethyl acetate-methanol-acetic acid 5:4:1:0.04) of the remaining crude product followed by crystallization from toluene gave 450 mg (60%) of 2-(3,5-dinitrobenzyl)acrylic acid as yellow needles. 1H NMR (CDCl3, 300 MHz) δ 8.93, (t, 1H, J=2.1 Hz), 8.43, (d, 2H, J=2.1 Hz), 6.56, (s, 1H), 5.93, (m, 1H), 3.85, (s, 2H).
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([N+:12]([O-:14])=[O:13])[CH:8]=2)[N:3]=1.[CH3:15][O:16][C:17]1[C:22]2[CH:23]([NH2:26])[CH2:24][O:25][C:21]=2[CH:20]=[CH:19][CH:18]=1.C(N(C(C)C)C(C)C)C>CN1CCCC1=O>[CH3:15][O:16][C:17]1[C:22]2[CH:23]([NH:26][C:2]3[CH:11]=[CH:10][C:9]4[C:4](=[CH:5][CH:6]=[C:7]([N+:12]([O-:14])=[O:13])[CH:8]=4)[N:3]=3)[CH2:24][O:25][C:21]=2[CH:20]=[CH:19][CH:18]=1
Reactant: O=[N+]([O-])c1ccc2nc(Cl)ccc2c1
Reactant: COc1cccc2c1C(N)CO2
Solvent: CN1CCCC1=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1cccc2c1C(Nc1ccc3cc([N+](=O)[O-])ccc3n1)CO2
Temperature: 140 °C
Reaction time: 2 h
Yield: 65.2 %

Procedure:
A mixture of 2-chloro-6-nitro-quinoline (3.8 g, 18.2 mmol) in 1-methyl-2-pyrrolidone (5 mL) with the above described rac-4-methoxy-2,3-dihydro-benzofuran-3-ylamine (3.61 g, 21.9 mmol) and N-ethyldiisopropylamine (4.68 mL, 27.3 mmol) was stirred at 140° C. for 2 h. Cooled to 23° C., poured onto water and extracted twice with ethyl acetate, dried over Na2SO4 and evaporated totally to give a crude product which was purified by silica gel column chromatography with heptane/dichloromethane followed by trituration with diethyl ether to give the title compound as a yellow solid (4.0 g, 65%); MS: m/e=336.3 (M+H+).
Reaction SMILES: [Mg].Br[CH2:3][CH2:4][CH2:5][C:6]([F:9])([F:8])[F:7].[CH3:10][CH2:11][C:12](=[O:15])[CH2:13][CH3:14]>O1CCCC1>[F:7][C:6]([F:9])([F:8])[CH2:5][CH2:4][CH2:3][C:12]([CH2:13][CH3:14])([OH:15])[CH2:11][CH3:10]
Reactant: CCC(=O)CC
Reactant: FC(F)(F)CCCBr
Agent: [Mg]
Solvent: C1CCOC1
Product: CCC(O)(CC)CCCC(F)(F)F
Reaction time: 1 h
Yield: 76.1 %

Procedure:
1.3 g of magnesium, 10.0 g of 1-bromo-4,4,4-trifluorobutane and 20 g of tetrahydrofuran were added to a four-necked flask equipped with a nitrogen feeding pipe, a reflux condenser, a dropping funnel and a thermometer, and a Grignard reagent was prepared by a conventional method. Then, a mixture containing 5.0 g of 3-pentanone and 4 g of tetrahydrofuran was dropwise added to the obtained Grignard reagent at a temperature of 25 to 35° C. over 30 minutes, followed by stirring at the same temperature for 1 hour. The reaction mixture was treated by a conventional method, and the resulting organic phase was washed with water, followed by drying with anhydrous magnesium sulfate. Thereafter, the resultant was concentrated under reduced pressure, thereby obtaining 7.9 g of 7,7,7-trifluoro-3-ethyl-3-heptanol in the form of a pale yellow oily matter.
Reaction SMILES: [C:1](OCC(CC)CCCC)(=[O:15])/[CH:2]=[CH:3]\[C:4]([O:6][CH2:7][CH:8]([CH2:13][CH3:14])[CH2:9][CH2:10][CH2:11][CH3:12])=[O:5].[H][H]>C(C(CCCC)CO)C>[CH2:1]([OH:15])[CH2:2][CH2:3][CH2:4][OH:5].[CH2:13]([CH:8]([CH2:9][CH2:10][CH2:11][CH3:12])[CH2:7][OH:6])[CH3:14]
Reactant: [H][H]
Reactant: CCCCC(CC)COC(=O)/C=C\C(=O)OCC(CC)CCCC
Solvent: CCCCC(CC)CO
Product: OCCCCO

Procedure:
The resulting solution of di-(2-ethylhexyl) maleate in 2-ethylhexan-1-ol is treated with hydrogen, in a trickle procedure, over a Cu/Mg silicate catalyst, at 190° C. and under a pressure of 200 bar, and the ester is cleaved to give butane-1,4-diol and 2-ethylhexanol. The mean space-time yield in a 3,300 hour experiment is 40 g of butanediol per liter per hour.
Reaction SMILES: Cl([O-])(=O)(=O)=O.[OH:6][C:7]1[CH:29]=[CH:28][C:10]([CH:11]=[CH:12][CH2+:13]2[C:18]3[CH:19]=[C:20]([O:25][CH3:26])[C:21]([O:23][CH3:24])=[CH:22][C:17]=3[CH:16]=[C:15]([CH3:27])O2)=[CH:9][CH:8]=1.O.[NH2:31][NH2:32]>C(O)C>[OH:6][C:7]1[CH:29]=[CH:28][C:10]([CH:11]=[CH:12][C:13]2[C:18]3[CH:19]=[C:20]([O:25][CH3:26])[C:21]([O:23][CH3:24])=[CH:22][C:17]=3[CH2:16][C:15]([CH3:27])=[N:32][N:31]=2)=[CH:9][CH:8]=1
Reactant: NN
Reactant: COc1cc2c(cc1OC)[CH2+](C=Cc1ccc(O)cc1)OC(C)=C2
Agent: [O-][Cl+3]([O-])([O-])[O-]
Solvent: CCO
Solvent: O
Product: COc1cc2c(cc1OC)C(C=Cc1ccc(O)cc1)=NN=C(C)C2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
4.5 g (10.6 mM) of 1-(4-hydroxystyryl)-3-methyl-6,7-dimethoxy-2-benzopyrylium perchlorate (m.p. 298° to 300° C. d.) are suspended in 90 ml of 99.5% ethanol, 1.6 ml (31.8 mM) of 100% hydrazine hydrate are added, and the solution is stirred for 2 hours at room temperature. After evaporation at reduced pressure the residue is suspended in 100 ml of water, filtered, washed with 3×5 ml of water, the crude product is resuspended in hot water, filtered, washed with 3×5 ml of water and dried at 80° to 100° C. Yield 2.65g, m.p. 205° to 207° C. (decomp.). This crude product is purified by refluxing in 12 ml of ethanol and subsequent drying. Yield 2.37 g (66.4%), m.p. 209° to 211° C. (decomp.).
Reaction SMILES: [CH2:1]=[CH:2][C:3](=[O:9])[CH2:4][CH2:5][CH2:6][CH:7]=[CH2:8].[CH3:10][CH:11]1[C:16](=[O:17])[CH2:15][CH2:14][CH2:13][C:12]1=[O:18].C(N(CC)CC)C>C(OCC)(=O)C>[CH3:10][C:11]1([CH2:1][CH2:2][C:3](=[O:9])[CH2:4][CH2:5][CH2:6][CH:7]=[CH2:8])[C:16](=[O:17])[CH2:15][CH2:14][CH2:13][C:12]1=[O:18]
Reactant: C=CCCCC(=O)C=C
Reactant: CC1C(=O)CCCC1=O
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: C=CCCCC(=O)CCC1(C)C(=O)CCCC1=O
Temperature: 25 °C
Reaction time: 24 h

Procedure:
1,7-Octadien-3-one(0.24 g), 2-methyl-1,3-cyclohexanedione(0.5 g) and triethylamine (1 ml) are added to ethyl acetate (10 ml), and the mixture is stirred at room temperature for 24 hours. The triethylamine and acetic acid are evaporated off and the residue is purified by silica gel column chromatography(methylene chloride) to recover 0.39 g of the above-indicated compound. [IR 1700-1730 cm-1, 920 cm-1 ; NMR 1.10 ppm(3H, singlet, --CH3), 4.6-6.0 ppm(3H, multiplet, vinyl)].
Reaction SMILES: C[O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=2[CH2:23][N:24]2[CH2:28][CH2:27][O:26][C:25]2=[O:29])[CH:8]=[CH:9][C:10]=1[O:11][CH3:12].[OH-].[Li+].Cl>O1CCOCC1.O>[CH3:12][O:11][C:10]1[CH:9]=[CH:8][C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:20])[F:22])=[CH:15][C:14]=2[CH2:23][N:24]2[CH2:28][CH2:27][O:26][C:25]2=[O:29])=[CH:6][C:5]=1[CH2:4][C:3]([OH:30])=[O:2]
Reactant: COC(=O)Cc1cc(-c2ccc(C(F)(F)F)cc2CN2CCOC2=O)ccc1OC
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: COc1ccc(-c2ccc(C(F)(F)F)cc2CN2CCOC2=O)cc1CC(=O)O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To [4-methoxy-2′-(2-oxo-oxazolidin-3-ylmethyl)-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid methyl ester (0.060 g, 1.42 mmol) in 1,4-dioxane:H2O (2:1; 2 mL) was added lithium hydroxide (14 mmol), and the reaction was stirred overnight at room temperature. The pH was adjusted to pH6 with 10% aqueous HCl, and the mixture was extracted with EtOAc. The crude material was purified by silica gel chromatography (0-100% EtOAc in hexanes) to give the title compound. M+H is 410.
Reaction SMILES: [NH2:1][CH2:2][CH:3]([C:9]1([CH3:14])[O:13][CH2:12][CH2:11][O:10]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5].[N+:15]([C:18]1[CH:28]=[CH:27][CH:26]=[C:20]2[C:21]([O:23][C:24](=O)[C:19]=12)=[O:22])([O-:17])=[O:16]>>[N+:15]([C:18]1[CH:28]=[CH:27][CH:26]=[C:20]2[C:19]=1[C:24](=[O:23])[N:1]([CH2:2][CH:3]([C:9]1([CH3:14])[O:10][CH2:11][CH2:12][O:13]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:21]2=[O:22])([O-:17])=[O:16]
Reactant: CCOC(=O)C(CN)C1(C)OCCO1
Reactant: O=C1OC(=O)c2c1cccc2[N+](=O)[O-]
Product: CCOC(=O)C(CN1C(=O)c2cccc([N+](=O)[O-])c2C1=O)C1(C)OCCO1

Procedure:
Ethyl 3-(4-nitro-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(2-methyl-[1,3]dioxolan-2-yl)propionate was prepared (0.64 g, 51%) in the same manner as described in the above example 5 (20) from ethyl 3-amino-2-(2-methyl-[1,3]dioxolan-2-yl)propionate (0.68 g, 3.34 mmol) and 3-nitrophthalic anhydride (0.84 g, 4.33 mmol), and the obtained product was identified with the following NMR data.
Reaction SMILES: [C:1]([OH:5])(=[O:4])[CH:2]=O.O.[CH3:7][O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[CH2:14][CH2:13][CH2:12]2.S(=O)(=O)(O)O>COCCOCCOC>[CH3:7][O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[C:14](=[CH:2][C:1]([OH:5])=[O:4])[CH2:13][CH2:12]2
Reactant: COc1ccc2c(c1)CCCC2=O
Reactant: O=CC(=O)O
Agent: O=S(=O)(O)O
Solvent: O
Solvent: COCCOCCOC
Product: COc1ccc2c(c1)CCC(=CC(=O)O)C2=O
Temperature: 85 °C
Yield: 85.5 %

Procedure:
Glyoxalic acid (30 mL, 303 mmol) and water (14 mL) were added to a stirred solution of 6-methoxy tetralone (25 g, 141 mmol) in diglyme (50 mL) followed by sulphuric acid (6.5 mL, 35 mmol). The reaction mixture was heated to 85° C. overnight. The reaction mixture was cooled to 0° C., and resulting solids were filtered off and washed with water (3×25 mL), dried under reduced pressure to afford title compound (28 g, 85%) as solid. 1H NMR (300 MHz, DMSO-d6): δ 12.9 (bs, 1H), 7.9 (d, J=8.4 Hz, 1H), 7.0 (m, 2H), 6.6 (s, 1H), 3.8 (s, 3H), 3.3 (m, 2H), 3.0 (m, 2H). ESI-MS m/z: 233 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:22]=[C:21]([CH3:23])[C:5]([O:6][C:7]2[C:12]([CH3:13])=[C:11]([NH:14][CH:15]([CH2:18][CH3:19])[CH2:16][CH3:17])[CH:10]=[C:9]([CH3:20])[N:8]=2)=[C:4]([CH3:24])[CH:3]=1.C([Li])CCC.[CH3:30][C:31]([CH3:33])=[O:32]>C1COCC1>[CH2:16]([CH:15]([NH:14][C:11]1[CH:10]=[C:9]([CH3:20])[N:8]=[C:7]([O:6][C:5]2[C:21]([CH3:23])=[CH:22][C:2]([CH2:30][CH:31]([OH:32])[CH3:33])=[CH:3][C:4]=2[CH3:24])[C:12]=1[CH3:13])[CH2:18][CH3:19])[CH3:17]
Reactant: CCC(CC)Nc1cc(C)nc(Oc2c(C)cc(Br)cc2C)c1C
Reactant: CC(C)=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCC(CC)Nc1cc(C)nc(Oc2c(C)cc(CC(C)O)cc2C)c1C
Temperature: -78 °C
Reaction time: 0.17 h

Procedure:
To a solution of [2-(4-bromo-2,6-dimethyl-phenoxy)-3,6-dimethyl-pyridin-4-yl]-(1-ethyl-propyl)-amine in dry THF was added n-butyllithium at −78° C. After stirring at −78° C. for 10 min, acetone was added and the resulting mixture was stirred at −78° C. for 30 min, the dry-ice bath was removed. After stirring for 5 min, the mixture was quenched with brine and extracted with ethyl acetate. The organic layer was separated, dried, and concentrated to dryness. The residue was purified through silica gel chromatography to give the title compound. 1H NMR(CDCl3) d 7.17(s,2H), 6.08(s,1H), 3.73(d,1H), 3.33(m,1H), 2.19(s,3H), 2.15(s,3H), 2.12(s,6H), 1.4–1.7(m,4H), 1.26(s,6H), 0.96(t,6H) ppm.