Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[C:10]([Cl:15])[CH:9]=2)[N:5]=[C:4]([CH:16]([CH3:18])[CH3:17])[N:3]=1.[F:19][C:20]([F:34])([F:33])[C:21]1[C:22]([N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[N:23][CH:24]=[CH:25][CH:26]=1.C([O-])([O-])=O.[K+].[K+]>CC(N(C)C)=O.O>[Cl:15][C:10]1[CH:9]=[C:8]([C:6]2[CH:7]=[C:2]([N:30]3[CH2:31][CH2:32][N:27]([C:22]4[C:21]([C:20]([F:34])([F:19])[F:33])=[CH:26][CH:25]=[CH:24][N:23]=4)[CH2:28][CH2:29]3)[N:3]=[C:4]([CH:16]([CH3:18])[CH3:17])[N:5]=2)[CH:13]=[CH:12][C:11]=1[F:14]
Reactant: FC(F)(F)c1cccnc1N1CCNCC1
Reactant: CC(C)c1nc(Cl)cc(-c2ccc(F)c(Cl)c2)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: CC(C)c1nc(-c2ccc(F)c(Cl)c2)cc(N2CCN(c3ncccc3C(F)(F)F)CC2)n1

Procedure:
Dissolve 4-chloro-6-(3-chloro-4-fluorophenyl)-2-isopropyl-pyrimidine (56 mg, 0.2 mmoles) and 1-(3-(trifluoromethyl)-pyridin-2-yl)piperazine (46 mg, 0.2 mmoles) in DMA (1.5 mL) under nitrogen atmosphere. Add anhydrous powdered K2CO3 (55 mg, 0.4 mmoles) to this mixture and heat at 120° C. for 18 hours. Cool, dilute with water (5 mL), extract with EtOAc (3×2 mL) and dry over MgSO4. Filter, and concentrate under vacuum to afford crude product and purify by flash column chromatography using 7% EtOAc/hexane to afford the title product as colorless viscous oil. NMR (CDCl3) δ 1.33 (6H, d, J=1.8), 3.05 (1H, m), 3.40 (4H, m), 3.87 (4H, m), 6.68 (1H, s), 7.03 (1H, m), 7.19 (1H, t), 7.89 (2H, m), 8.07 (1H, d, J=2.3), 8.45 (1H, m). Mass spec m/z=480.22.
Reaction SMILES: [C:1]([C:4]1[C:5]([CH2:28][N:29]([CH2:32][CH3:33])[CH2:30][CH3:31])=[N:6][C:7]2[C:12]([C:13]=1[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH3:23])[CH:15]=1)=[CH:11][C:10]([O:24][CH3:25])=[C:9]([O:26][CH3:27])[CH:8]=2)(=[O:3])[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].O>O1CCCC1>[CH2:32]([N:29]([CH2:28][C:5]1[C:4]([CH:1]([OH:3])[CH3:2])=[C:13]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH3:23])[CH:15]=2)[C:12]2[C:7](=[CH:8][C:9]([O:26][CH3:27])=[C:10]([O:24][CH3:25])[CH:11]=2)[N:6]=1)[CH2:30][CH3:31])[CH3:33]
Reactant: CCN(CC)Cc1nc2cc(OC)c(OC)cc2c(-c2ccc(OC)c(OC)c2)c1C(C)=O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CCN(CC)Cc1nc2cc(OC)c(OC)cc2c(-c2ccc(OC)c(OC)c2)c1C(C)O
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 45.8 %

Procedure:
3-Acetyl-2-(N,N-diethylaminomethyl)-4-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinoline (0.5 g) was added to an ice-cooled suspension of lithium aluminum hydride (0.045 g) in tetrahydrofuran (10 ml). The mixture was stirred at room temperature for 20 minutes. Then, water (0.3 ml) was added, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure. The residue was subjected to column chromatography on silica gel. The fractions eluted with chloroform-ethanol (20:1, v/v) gave 2-(N,N-diethylaminomethyl)-4-(3,4-dimethoxyphenyl)-3-(1-hydroxyethyl)-6,7-dimethoxyquinoline (0.23 g, 45%). This compound was recrystallized from ethyl acetate-hexane to give colorless prisms, mp. 144°-145° C.
Reaction SMILES: C([NH:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:7][C:6]=1[N+:23]([O-:25])=[O:24])(=O)C.C(O)C.[OH-].[K+]>O>[CH2:11]([C:8]1[CH:9]=[CH:10][C:5]([NH2:4])=[C:6]([N+:23]([O-:25])=[O:24])[CH:7]=1)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: CCCCCCCCCCCCc1ccc(NC(C)=O)c([N+](=O)[O-])c1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CCCCCCCCCCCCc1ccc(N)c([N+](=O)[O-])c1

Procedure:
In a 1-liter flask fitted with a stirrer and reflux condenser, 61.8 grams of N-acetyl-4-n-dodecyl-2-nitroaniline (prepared in Example 2b), 320 ml of ethanol and 64 ml of 40% aqueous potassium hydroxide solution are heated for 1 hour under reflux. The reaction mixture is cooled and then poured into 1.5 liters of water. The crude product is isolated by filtration, washed repeatedly with cold water and recrystallized from methanol. The above-named product is isolated as a solid melting at 69°-71° C. in a yield of 45 grams.
Reaction SMILES: C[C:2](P(OC)(O)=O)([C:4]([O-:6])=[O:5])[CH3:3].[H-].[Na+].[Cl:14][C:15]1[CH:30]=[CH:29][C:18]2C(=O)[C:20]3[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=3[CH2:22][CH2:23][C:17]=2[CH:16]=1.O.O1CC[CH2:34][CH2:33]1>>[CH2:33]([O:6][C:4](=[O:5])[CH:2]=[C:3]1[C:18]2[CH:29]=[CH:30][C:15]([Cl:14])=[CH:16][C:17]=2[CH2:23][CH2:22][C:21]2[CH:20]=[CH:27][CH:26]=[CH:25][C:24]1=2)[CH3:34]
Reactant: O=C1c2ccccc2CCc2cc(Cl)ccc21
Reactant: C1CCOC1
Reactant: COP(=O)(O)C(C)(C)C(=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Product: CCOC(=O)C=C1c2ccccc2CCc2cc(Cl)ccc21
Reaction time: 1 h

Procedure:
Trimethylphosphonoacetate (0.53 mole) is added dropwise with stirring to a suspension of sodium hydride (0.48 mole, 50% dispersion in oil) in 250 ml of tetrahydrofuran at 30°-35° C. After the addition, the reaction is stirred for one hr at 20°-30° C. To this reaction mixture, 2-chloro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one[0.16 mole, described by S. O. Winthrop, et al., J. Org. Chem., 27, 230 (1962)] in 400 ml of tetrahydrofuran is added. After refluxing for 20 hr the red colored solution is cooled to 0° to 5° C. and water is added dropwise. The aqueous solution is evaporated to remove most of the tetrahydrofuran and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate and evaporated. The residue is subjected to chromatography on silica gel using benzene-hexane (1:1) and the eluates are evaporated to give 2-chloro-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5-ylideneacetic acid ethyl ester. The latter compound (11.0 g) is dissolved in ethanol (110 ml) and the solution is added to 10% aqueous potassium hydroxide (110 ml). The resulting solution is refluxed for 3 hr. After the removal of the ethanol by evaporation, the aqueous phase is washed with diethyl ether, adjusted to pH 2 with conc. hydrochloric acid and extracted with chloroform. The chloroform extract is washed with water, dried over magnesium sulfate and evaporated. The residue is crystallized from diethyl ether-hexane to give the title compound as crystals, mp 155°-175° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:10][CH2:11][NH2:12])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].Cl[C:14]1[N:19]=[CH:18][C:17]([CH2:20][CH3:21])=[CH:16][N:15]=1.CCN(C(C)C)C(C)C>C(O)CCC>[Br:1][C:2]1[CH:3]=[C:4]([CH2:10][CH2:11][NH:12][C:14]2[N:19]=[CH:18][C:17]([CH2:20][CH3:21])=[CH:16][N:15]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]
Reactant: COc1ccc(CCN)cc1Br
Reactant: CCc1cnc(Cl)nc1
Solvent: CCCCO
Solvent: CCN(C(C)C)C(C)C
Product: CCc1cnc(NCCc2ccc(OC)c(Br)c2)nc1
Yield: 67.5 %

Procedure:
A mixture of 2-(3-bromo-4-methoxyphenyl)ethanamine (1 g; 4.35 mmol), 2-chloro-5-ethyl-pyrimidine (0.56 g; 3.92 mmol) and DIEA (0.84 g; 6.53 mmol) in n-butanol was heated to reflux for 14 hr. Upon cooling, the reaction mixture was concentrated and partitioned between 1N HCl and ether. The aqueous phase was basified with 6N NaOH and extracted with ether. The combined organic phases were washed with a saturated solution of NaHCO3, dried over MgSO4, filtered and concentrated to provide a colorless solid, which was triturated with hexane, filtered and dried to provide the title compound as a white crystalline solid (0.89 g; 67% yield).
Reaction SMILES: [Cl-].[C:2]([C:4]1[C:16]([N+:17]([O-])=O)=[CH:15][CH:14]=[CH:13][C:5]=1[O:6][CH2:7][C@@H:8]1[CH2:12][CH2:11][CH2:10][NH2+:9]1)#[N:3].[CH3:20][N:21]=[C:22]=[O:23]>>[NH2:17][C:16]1[C:4]([C:2]#[N:3])=[C:5]([CH:13]=[CH:14][CH:15]=1)[O:6][CH2:7][C@@H:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:22]([NH:21][CH3:20])=[O:23]
Reactant: CN=C=O
Reactant: N#Cc1c(OC[C@@H]2CCC[NH2+]2)cccc1[N+](=O)[O-]
Agent: [Cl-]
Product: CNC(=O)N1CCC[C@H]1COc1cccc(N)c1C#N
Yield: 53 %

Procedure:
Prepared as in Example 209a from (S)-2-((2-cyano-3-nitrophenoxy)methyl)pyrrolidinium chloride (Example 209b) and methyl isocyanate in 53% yield as a white solid. MS 275 (MH+).
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:7][CH2:8][CH3:9])[CH2:5][NH2:6])[CH3:2].[N:10]1[CH:15]=[CH:14][C:13]([CH:16]=O)=[CH:12][CH:11]=1>>[CH2:1]([O:3][CH:4]([O:7][CH2:8][CH3:9])[CH2:5][NH:6][CH2:16][C:13]1[CH:14]=[CH:15][N:10]=[CH:11][CH:12]=1)[CH3:2]
Reactant: CCOC(CN)OCC
Reactant: O=Cc1ccncc1
Product: CCOC(CNCc1ccncc1)OCC
Yield: 43.8 %

Procedure:
According to the procedure described in the synthesis method of Compound IX-2, 2,2-diethoxyethanamine (162.8 ml, 1120 mmol) was reacted with 4-pyridinecarboxaldehyde (120 g, 1120 mmol) and the obtained residue was purified by silica gel column chromatography (eluent: ethyl acetate and ethyl acetate:ethanol=15:1) to obtain the title compound (110 g, 44%).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=1)[NH2:7])([O-:3])=[O:2].CN(C(ON1N=N[C:21]2[CH:22]=[CH:23][CH:24]=[N:25][C:20]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C[CH2:36][O:37]C(C)=O>CN(C=O)C>[CH3:20][N:25]1[CH2:24][CH2:23][CH2:22][C@H:21]1[C:36]([NH:7][C:6]1[CH:8]=[CH:9][CH:10]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1)=[O:37]
Reactant: CCOC(C)=O
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: Nc1cccc([N+](=O)[O-])c1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Product: CN1CCC[C@H]1C(=O)Nc1cccc([N+](=O)[O-])c1

Procedure:
To a solution of(S)-1-methylpyrrolidine-2-carboxylic acid (258 mg, 2 mmol) in DMF (4 mL) was added 3-nitroaniline (276 mg, 2 mmol) and HATU (760 mg). After stirring for h, it was added with EtOAc, washed with Sat. NaHCO3, brine, dried and concentrated to give (S)-1-methyl-N-(3-nitrophenyl)pyrrolidine-2-carboxamide.
Reaction SMILES: [CH3:1][S:2][C:3](=O)[NH:4][CH2:5][C:6]1[C:11]([Cl:12])=[N:10][CH:9]=[CH:8][N:7]=1.CN(C=O)C.O=P(Cl)(Cl)Cl>CC#N>[Cl:12][C:11]1[C:6]2[N:7]([C:3]([S:2][CH3:1])=[N:4][CH:5]=2)[CH:8]=[CH:9][N:10]=1
Reactant: CSC(=O)NCc1nccnc1Cl
Solvent: O=P(Cl)(Cl)Cl
Solvent: CN(C)C=O
Solvent: CC#N
Product: CSc1ncc2c(Cl)nccn12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of (3-chloro-pyrazin-2-ylmethyl)-thiocarbamic acid S-methyl ester (3.05 g, 0.0140 mol) in MeCN (70 mL) were added DMF (4.3 mL, 0.056 mol) and POCl3 (5.2 mL, 0.056 mol) at 0° C. under nitrogen. The reaction mixture was slowly warmed to rt and stirred overnight. The solvent was evaporated under reduced pressure and the residue was cooled at 0° C. and diluted with EtOAc (250 mL), then quenched with sat. aq. NaHCO3 (100 mL). The mixture was washed with brine (50 mL), and dried over anhydrous sodium sulfate. The crude material was purified by silica gel chromatography (Hex:EtOAc=80:20→70:30) to give the title compound as a light-yellow solid; LC-MS (ES, Pos.): 200/202 (3/1) [MH+]; 1H NMR (CDCl3, 400 MHz) δ 2.71 (s, 3H), 7.40 (d, J=5.1 Hz, 1H), 7.74 (dd, J=5.1, 1.0 Hz, 1H), 7.90 (s, 1H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:12][CH:11]=1)=O>>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1/[CH:1]=[CH:8]/[C:10]1[CH:11]=[CH:12][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:15]=1
Reactant: COC(=O)c1ccc(C=O)cc1
Reactant: Cc1ccccn1
Product: COC(=O)c1ccc(/C=C/c2ccccn2)cc1
Yield: 37 %

Procedure:
2-Methylpyridine (5.7 g) and methyl 4-formylbenzenecarboxylate (10 g) were processed in the same manner as in Production Example 16-1 to obtain the entitled compound (5.4 g).
Reaction SMILES: Br[CH2:2][C:3]([N:5]([CH2:8][CH3:9])[CH2:6][CH3:7])=[O:4].[NH2:10][C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1.[F:18][C:19]([F:31])([F:30])[C:20]1[CH:21]=[C:22]([S:26](Cl)(=[O:28])=[O:27])[CH:23]=[CH:24][CH:25]=1>>[CH2:6]([N:5]([CH2:8][CH3:9])[C:3](=[O:4])[CH2:2][N:10]([C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1)[S:26]([C:22]1[CH:23]=[CH:24][CH:25]=[C:20]([C:19]([F:18])([F:30])[F:31])[CH:21]=1)(=[O:28])=[O:27])[CH3:7]
Reactant: CCN(CC)C(=O)CBr
Reactant: Cc1ccc(N)cc1
Reactant: O=S(=O)(Cl)c1cccc(C(F)(F)F)c1
Product: CCN(CC)C(=O)CN(c1ccc(C)cc1)S(=O)(=O)c1cccc(C(F)(F)F)c1

Procedure:
prepared by reaction of 2-bromo-N,N-diethylacetamide with p-toluidine and 3-trifluoromethyl-benzenesulfonyl chloride
Reaction SMILES: [F:1][C:2]1[CH:36]=[CH:35][C:5]([CH2:6][C:7]2[CH:16]=[C:15]3[C:10]([C:11]([OH:34])=[C:12]([C:29](OCC)=[O:30])[C:13](=[O:28])[N:14]3[CH2:17][C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)=[N:9][CH:8]=2)=[CH:4][CH:3]=1.[NH2:37][CH2:38][C:39]1[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=1>>[F:1][C:2]1[CH:36]=[CH:35][C:5]([CH2:6][C:7]2[CH:16]=[C:15]3[C:10]([C:11]([OH:34])=[C:12]([C:29]([NH:37][CH2:38][C:39]4[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=4)=[O:30])[C:13](=[O:28])[N:14]3[CH2:17][C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:20][CH:19]=3)=[N:9][CH:8]=2)=[CH:4][CH:3]=1
Reactant: NCc1cccnc1
Reactant: CCOC(=O)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2n(Cc2ccc(S(C)(=O)=O)cc2)c1=O
Product: CS(=O)(=O)c1ccc(Cn2c(=O)c(C(=O)NCc3cccnc3)c(O)c3ncc(Cc4ccc(F)cc4)cc32)cc1

Procedure:
This compound was prepared from ethyl 7-(4-fluorobenzyl)-4-hydroxy-1-[4-(methylsulfonyl)benzyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate and 3-(aminomethyl)pyridine employing methods similar to those described in Example 5 and was obtained as a white solid; 1H NMR (CDCl3) δ 10.82 (1H, br t, J=6 Hz), 8.79 (1H, s), 8.67 (1H, d, J=5 Hz), 8.61 (1H, s), 8.44 (1H, d, J=8 Hz), 7.90 (1H, m), 7.86 (2H, d, J=8.2 Hz), 7.22 (2H, d, J=8.2 Hz), 7.07 (1H, s), 7.00 (4H, m), 5.44 (2H, br), 4.83 (2H, d, J=6 Hz), 4.05 (2H, s), 3.04 (3H, s); ES+ MS: 573 (M+H+, 100).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]2[NH2:15])=[CH:5][C:4]=1[O:16][CH3:17].[N+:18]([C:21]1[CH:22]=[C:23]([CH:27]=[CH:28][C:29]=1[N+:30]([O-:32])=[O:31])[C:24](Cl)=[O:25])([O-:20])=[O:19]>C(Cl)Cl.C(N(CC)CC)C>[CH3:17][O:16][C:4]1[CH:5]=[C:6]([C@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[NH:15][C:24](=[O:25])[C:23]2[CH:27]=[CH:28][C:29]([N+:30]([O-:32])=[O:31])=[C:21]([N+:18]([O-:20])=[O:19])[CH:22]=2)[CH:7]=[CH:8][C:3]=1[O:2][CH3:1]
Reactant: COc1ccc([C@@H]2CCCC[C@@H]2N)cc1OC
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])c([N+](=O)[O-])c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc([C@H]2CCCC[C@H]2NC(=O)c2ccc([N+](=O)[O-])c([N+](=O)[O-])c2)cc1OC
Reaction time: 8 h
Yield: 88.8 %

Procedure:
5.0 g of (−)-cis-1,2-dimethoxy-4-(2-aminocyclohexyl)benzene (compound B2) are dissolved in 40 ml of methylene chloride and 5.0 ml of triethylamine. A solution of 6.5 g of 3,4-dinitrobenzoyl chloride in 40 ml of methylene chloride is added dropwise at RT and the mixture is extracted with water, 2N hydrochloric acid, satd. sodium hydrogencarbonate solution and water again after stirring overnight. The organic phase is dried using sodium sulfate and concentrated. 8.1 g of the title compound are obtained as a solidified oil.
Reaction SMILES: [NH:1]([CH2:3][C:4]([OH:6])=[O:5])[CH3:2].[CH3:7][CH:8]([CH3:26])[CH2:9][C:10]([O:12][CH2:13][CH2:14][O:15][C:16](ON1C(=O)CCC1=O)=[O:17])=[O:11]>>[CH3:2][N:1]([C:16]([O:15][CH2:14][CH2:13][O:12][C:10](=[O:11])[CH2:9][CH:8]([CH3:7])[CH3:26])=[O:17])[CH2:3][C:4]([OH:6])=[O:5]
Reactant: CC(C)CC(=O)OCCOC(=O)ON1C(=O)CCC1=O
Reactant: CNCC(=O)O
Product: CC(C)CC(=O)OCCOC(=O)N(C)CC(=O)O
Yield: 27.6 %

Procedure:
Following the general procedure for the synthesis of acyloxyalkyl carbamates, sarcosine (0.104 g, 1.1 mmol) and (2,5-dioxoazolidinyloxycarbonyloxy)ethyl 3-methylbutanoate (0.28 g, 0.97 mmol) were reacted to provide 0.070 g (27.5% yield) of the title compound (45) as a colorless, waxy material after work-up and mass-guided preparative HPLC purification. 1H NMR (CD3OD, 400 MHz): δ=6.78 (q, 1H), 4.12 (m, 2H), 2.99 (2s, 3H), 2.23 (m, 2H), 2.12 (m, 1H), 1.52 (2d, 3H), 0.99 (t, 3H). MS (ESI) m/z 284.08 (M+Na)+, 260.13 (M−H)−.
Reaction SMILES: [ClH:1].[OH:2][CH:3]([CH2:18][O:19]C1C=CC(C(C)(C)C)=CC=1)[CH2:4][NH:5][C:6]([CH3:17])([CH3:16])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1.Cl.O[C@H](CO[C:49]1[CH:54]=[CH:53][C:52]([C:55](C)([CH3:57])[CH3:56])=[CH:51][CH:50]=1)CNC(C)(C)CC1C=CC(OC)=CC=1>>[ClH:1].[OH:2][CH:3]([CH2:18][O:19][C:50]1[CH:49]=[CH:54][CH:53]=[C:52]([CH:55]([CH3:57])[CH3:56])[CH:51]=1)[CH2:4][NH:5][C:6]([CH3:17])([CH3:16])[CH2:7][C:8]1[CH:9]=[CH:10][C:11]([O:14][CH3:15])=[CH:12][CH:13]=1
Reactant: COc1ccc(CC(C)(C)NCC(O)COc2ccc(C(C)(C)C)cc2)cc1
Reactant: COc1ccc(CC(C)(C)NC[C@H](O)COc2ccc(C(C)(C)C)cc2)cc1
Agent: Cl
Product: COc1ccc(CC(C)(C)NCC(O)COc2cccc(C(C)C)c2)cc1

Procedure:
GC/EI-MS, m/z (rel. int.) 356 (M−15, 0.1), 251 (18), 250 (100), 163 (6), 121 (21), 117 (5), 114 (10), 91 (9).
Reaction SMILES: C(O)(=O)CCC(C)=O.C(O)=O.O.[C:13]12([CH2:23]S(O)(=O)=O)[C:20]([CH3:22])([CH3:21])[CH:17]([CH2:18][CH2:19]1)[CH2:16][C:14]2=[O:15].C(O)CCCO>>[C:13]12([CH3:23])[C:20]([CH3:22])([CH3:21])[CH:17]([CH2:18][CH2:19]1)[CH2:16][C:14]2=[O:15]
Reactant: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Agent: CC(=O)CCC(=O)O
Solvent: O
Solvent: OCCCCO
Solvent: O=CO
Product: CC12CCC(CC1=O)C2(C)C

Procedure:
A crude levulinic acid composition comprising 14.9 g (0.128 mol) levulinic acid, 0.449 g (9.76×10−3 mol) formic acid, 30 g (1.66 mol) DI water, and 0.3484 g (1.50×10−3 mol) camphor sulfonic acid was esterified with 2.89 g (3.21×10−2 mol) 1,4-butanediol. The procedure for Example 6 was followed, and analysis of the reaction mixture by GC-FID showed a peak corresponding to LA-BDO-LA.
Reaction SMILES: Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[CH3:9][O:10][C:11]1[CH:12]=[C:13](B(O)O)[CH:14]=[CH:15][CH:16]=1>>[CH3:9][O:10][C:11]1[CH:16]=[C:15]([C:2]2[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=2)[CH:14]=[CH:13][CH:12]=1
Reactant: COc1cccc(B(O)O)c1
Reactant: Nc1ccc(Br)cc1
Product: COc1cccc(-c2ccc(N)cc2)c1
Yield: 16.7 %

Procedure:
The title compound (58 mg) was prepared from 4-bromoaniline (300 mg, 1.74 mmol) and 3-methoxyphenylboronic acid (344 mg, 2.26 mmol) as a yellow liquid.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[C:7]([OH:9])[C:6]([CH3:10])=[CH:5][C:3]=1[OH:4].Br[CH2:12][CH2:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][O:22][CH3:23].[OH-:24].[Na+]>ClC1C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:10][C:6]1[CH:5]=[C:3]([O:4][CH2:12][CH2:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][O:22][CH3:23])[C:2]([CH3:1])=[CH:8][C:7]=1[O:9][CH2:12][CH2:13][CH2:14][CH2:15][O:24][CH2:17][CH2:18][O:19][CH2:20][CH2:21][O:22][CH3:23]
Reactant: Cc1cc(O)c(C)cc1O
Reactant: COCCOCCOCCCCBr
Reactant: [OH-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [Na+]
Solvent: Clc1ccccc1
Product: COCCOCCOCCCCOc1cc(C)c(OCCCCOCCOCCOC)cc1C

Procedure:
10 mmol of 2,5-dimethylhydroquinone in 25 mL of chlorobenzene, 20 mmol of 1-bromo-5,8,11-trioxadodecane, 20 mmol of sodium hydroxide in the form of a 50% aqueous solution are reacted in the presence of a phase transfer catalyst, tetrabutylammonium bromide. The 1,4-dimethyl-2,5-bis(5,8,11-trioxadodecyloxy)benzene thus obtained is purified by chromatography. 1,4-bis(Bromomethyl-2,5-bis(5,8,11-trioxadodecyloxy)benzene is obtained by treatment with two equivalents of N-bromosuccinimide. Duplicative elimination by potassium tert-butoxide in THF gives the polymer.
Reaction SMILES: [CH2:1]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][CH3:18])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:19]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH:28]([CH3:30])[CH3:29])[C:23]=1[N:31]=[C:32]=[O:33])([CH3:21])[CH3:20]>>[CH2:1]([N:8]([C:9]1[CH:10]=[CH:11][C:12]([CH2:15][CH2:16][CH2:17][CH3:18])=[CH:13][CH:14]=1)[C:32]([NH:31][C:23]1[C:22]([CH:19]([CH3:20])[CH3:21])=[CH:27][CH:26]=[CH:25][C:24]=1[CH:28]([CH3:30])[CH3:29])=[O:33])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)c1cccc(C(C)C)c1N=C=O
Reactant: CCCCc1ccc(NCc2ccccc2)cc1
Product: CCCCc1ccc(N(Cc2ccccc2)C(=O)Nc2c(C(C)C)cccc2C(C)C)cc1
Yield: 27.6 %

Procedure:
By the reaction and treatment in the same manner as in Example 2 using benzyl(4-butylphenyl)amine (1.0 g) and 2,6-diisopropylphenyl isocyanate (1.7 g) as starting materials, N-benzyl-N-(4-butylphenyl)-N′-(2,6-diisopropylphenyl)urea (0.51 g) was obtained.
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][C:9](=O)[C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[O:24][C:25](=[O:27])[CH3:26])[CH2:6]1)(=[O:3])[CH3:2].Cl.[NH2:30][OH:31].O>N1C=CC=CC=1>[C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][C:9](=[N:30][OH:31])[C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[O:24][C:25](=[O:27])[CH3:26])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC(=O)[C@H]3[C@@H]4CC[C@H](OC(C)=O)[C@@]4(C)CC[C@@H]32)C1
Reactant: NO
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC(=NO)[C@H]3[C@@H]4CC[C@H](OC(C)=O)[C@@]4(C)CC[C@@H]32)C1

Procedure:
7-Oxo-5-androstene-3β,17β-diol diacetate (1 g, 2.57 mmol) and hydroxylamine hydrochloride (0.5 g) were taken in dry pyridine (8 Ml) and heated in a steam bath for 2 h. The reaction mixture was poured into water and precipitate obtained was filtered, washed with water and dried. The crude product on crystallization from methanol afforded pure oxime 7-oximino-5-androstene-3β,17β-diol diacetate (0.85 g, 86.54%), mp 236-238° C. (lit 226° C.) [Singh H., et al Indian J. Chem. 1969, 7, 1084-1087].
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)[CH2:2][CH3:3].[CH:22]([OH:24])=O.[C:25]1(C)C=CC=C[CH:26]=1>>[CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[CH:12][C:13]([CH:16]3[CH2:21][CH2:20][CH:19]([CH2:25][CH2:26][CH:22]=[O:24])[CH2:18][CH2:17]3)=[CH:14][CH:15]=2)=[CH:6][CH:5]=1)[CH2:2][CH3:3]
Reactant: CCCc1ccc(-c2ccc(C3CCCCC3)cc2)cc1
Reactant: Cc1ccccc1
Reactant: O=CO
Product: CCCc1ccc(-c2ccc(C3CCC(CCC=O)CC3)cc2)cc1

Procedure:
This cyclohexane derivative (11.8 g, 30 mmols) was dissolved in toluene (100 ml), followed by adding formic acid (5 ml), heating the mixture under reflux for 5 hours, washing the reaction mixture with water after completion of the stirring, drying over anhydrous magnesium sulfate, concentrating under reduced pressure and isolating the resulting yellow oil, to obtain 3-(4-(4-(4-propylphenyl)phenyl)cyclohexyl)propanal. This product is used in the subsequent reaction without any purification.
Reaction SMILES: [C:1]1([C:10]([OH:12])=[O:11])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]=1.[N+:13]([C:16]1[CH:23]=[CH:22][C:19]([CH2:20]Br)=[CH:18][CH:17]=1)([O-:15])=[O:14].N12CCCN=C1CCCCC2>C(O)C.C1C=CC=CC=1.[Pd]>[N+:13]([C:16]1[CH:23]=[CH:22][C:19]([CH2:20][O:11][C:10]([CH:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH2:3][CH2:2]2)=[O:12])=[CH:18][CH:17]=1)([O-:15])=[O:14]
Reactant: O=[N+]([O-])c1ccc(CBr)cc1
Reactant: O=C(O)C1=CCc2ccccc21
Agent: [Pd]
Solvent: CCO
Solvent: c1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Product: O=C(OCc1ccc([N+](=O)[O-])cc1)C1CCc2ccccc21
Reaction time: 1 h
Yield: 91.3 %

Procedure:
To a solution of 3H-Indene-1-carboxylic acid (2.0 g, 13.3 mmol) in ethanol (35 mL) was added 10% Pd/C (200 mg). The reaction mixture was stirred under an H2 atmosphere for 1 h. The mixture was filtered through Celite and concentrated in vacuo. The residue was combined with p-nitrobenzyl bromide (5.8 g, 26.8 mmoles) and 1,8-diazabicyclo[5.4.0]undec-7-ene (2.4 mL, 16.0 mmol) in 65 mL of benzene, and was stirred at 50° C. for 20 hours. After this period the heterogeneous mixture was gravity filtered and the filtrate was evaporated in vacuo. The residue was combined with CH2Cl2 and was washed with 1N HCl (2×25 mL) and sat'd NaHCO3 (2×25 mL), and the resulting CH2Cl2 solution was dried over anhydrous Na2SO4. The crude solid was purified using flash silica chromatography (0-10% EtOAc/Hexane) to yield 3.61 g (95%) of the intermediate.