Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([C:4]2[C:13]([CH:14]=[O:15])=[C:12]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH2:3][CH2:2]1.[C:23](#[N:25])[CH3:24]>>[CH:1]1([C:4]2[C:13]([CH:14]=[CH:24][C:23]#[N:25])=[C:12]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH2:3][CH2:2]1.[CH:1]1([C:4]2[C:13]([CH:14]([OH:15])[CH2:24][C:23]#[N:25])=[C:12]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH2:2][CH2:3]1
Reactant: O=Cc1c(C2CC2)nc2ccccc2c1-c1ccc(F)cc1
Reactant: CC#N
Product: N#CC=Cc1c(C2CC2)nc2ccccc2c1-c1ccc(F)cc1
Product: N#CCC(O)c1c(C2CC2)nc2ccccc2c1-c1ccc(F)cc1

Procedure:
3-[2-Cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enenitrile is prepared by reacting 2-cyclopropyl-4-(4-fluorophenyl)quinoline-3-carbaldehyde with acetonitrile in the presence of a base and then adding a dehydrating to the reaction mixture to conduct dehydration. Under ordinary conditions, novel 3-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3-hydroxypropionitrile is formed as an intermediate in the above reaction. Incidentally, when the above reaction is conducted in an organic solvent, 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-prop-2-enenitrile is directly formed.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[S:23][C:22]3[C:21]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[N:20][C:19](Cl)=[N:18][C:17]=3[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:31][S-:32].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[S:23][C:22]3[C:21]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[N:20][C:19]([S:32][CH3:31])=[N:18][C:17]=3[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C[S-]
Reactant: CC(C)(C)OC(=O)N1CCN(Cc2cc3nc(Cl)nc(N4CCOCC4)c3s2)CC1
Agent: [Na+]
Solvent: CN(C)C=O
Product: CSc1nc(N2CCOCC2)c2sc(CN3CCN(C(=O)OC(C)(C)C)CC3)cc2n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 97.6 %

Procedure:
A solution of 4-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (100 mg, 0.22 mmol) and sodium thiomethoxide (30 mg, 0.44 mmol) in DMF was heated at 100° C. in a sealed tube under nitrogen for 1 h. More sodium thiomethoxide (15 mg, 0.22 mmol) was added, and the heating pursued for 1 h. The mixture was left to cool to RT and was then partitioned between a sat. sodium carbonate solution and EtOAc. The organic layer was isolated, dried (MgSO4) and evaporated to dryness to afford 4-(2-methylsulfanyl-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester as a yellow solid (100 mg, 98%).
Reaction SMILES: [OH-].[K+].[CH3:3][CH:4]([OH:6])[CH3:5].[OH:7][C:8]1[C:21]2[C:20](=[O:22])[C:19]3[C:14](=[C:15]([OH:23])[CH:16]=[CH:17][CH:18]=3)[O:13][C:12]=2[CH:11]=[C:10]([OH:24])[CH:9]=1.[CH2:25]([CH:27]1[O:29][CH2:28]1)Cl>O.CO>[O:6]1[CH2:5][CH:4]1[CH2:3][O:24][C:10]1[CH:9]=[C:8]([OH:7])[C:21]2[C:20](=[O:22])[C:19]3[C:14]([O:13][C:12]=2[CH:11]=1)=[C:15]([O:23][CH2:25][CH:27]1[O:29][CH2:28]1)[CH:16]=[CH:17][CH:18]=3
Reactant: ClCC1CO1
Reactant: CC(C)O
Reactant: O=c1c2cccc(O)c2oc2cc(O)cc(O)c12
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=c1c2cccc(OCC3CO3)c2oc2cc(OCC3CO3)cc(O)c12

Procedure:
To a solution of 0.28 g (5.0 mmol) of potassium hydroxide in 3 ml of water was added 25 ml of 2-propanol and the 1.3 g (5.33 mmol) of 1,3,5-trihydroxyxanthone. To the above mixture was the added 7.5 ml (93.47 mmol) of epichlorohydrin, and the mixture was treated as example 4 to yield a pale yellow powder (MeOH) (21), 0.45 g (1.26 mmol, 35%)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:13]=[C:14]=[S:15])[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N:23]1[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][CH2:31][OH:32])[CH2:25][CH2:24]1>C1(C)C=CC=CC=1>[ClH:16].[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N:23]1[CH2:24][CH2:25][N:26]([CH2:29][CH2:30][CH2:31][O:32][C:14](=[S:15])[NH:13][C:5]2[CH:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][CH3:10])=[C:7]([O:11][CH3:12])[CH:6]=2)[CH2:27][CH2:28]1
Reactant: COc1cc(N=C=S)cc(OC)c1OC
Reactant: OCCCN1CCN(c2ccccc2Cl)CC1
Solvent: Cc1ccccc1
Product: COc1cc(NC(=S)OCCCN2CCN(c3ccccc3Cl)CC2)cc(OC)c1OC
Product: Cl
Yield: 42.6 %

Procedure:
A mixture of 3,4,5-trimethoxyphenylisothiocyanate (2.0 mmol) (produced as in Example 22) and 3-[4-(2-chlorophenyl) -1-piperazinyl]propanol (510 mg; 2.0 mmol) in toluene (40 ml) was refluxed for 16 h. The solvent was evaporated and the residue resuspended in ethyl acetate filtered and evaporated to dryness. The residue was submitted to flash chromatography on silica gel 60 eluting with toluene/ethyl acetate (1:1). The product was taken up in ethanol, which was treated with hydrogen chloride in ether to give 220 mg of the title compound. M.p. 182°-183° C. MS (70 eV): m/z 479 (M+, 0.5%), 254 (47), 225 (82), 209 (100), 182 (29).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[O:19][C@@H:20]3[O:46][C@H:45]([CH2:47][O:48]C(=O)C(C)(C)C)[C@@H:37]([O:38]C(=O)C(C)(C)C)[C@H:29]([O:30]C(=O)C(C)(C)C)[C@H:21]3[O:22]C(=O)C(C)(C)C)[CH:12]=[CH:11]2)=[CH:4][CH:3]=1.O.O.[OH-].[Li+]>CO>[C@@H:20]1([O:19][C:17]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:18]=2[N:10]([CH2:9][CH2:8][C:5]2[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=2)[CH:11]=[CH:12]3)[O:46][C@H:45]([CH2:47][OH:48])[C@@H:37]([OH:38])[C@H:29]([OH:30])[C@H:21]1[OH:22]
Reactant: CC(C)(C)C(=O)OC[C@H]1O[C@@H](Oc2cccc3ccn(CCc4ccc(O)cc4)c23)[C@H](OC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@@H]1OC(=O)C(C)(C)C
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: OC[C@H]1O[C@@H](Oc2cccc3ccn(CCc4ccc(O)cc4)c23)[C@H](O)[C@@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 8 h
Yield: 72.4 %

Procedure:
To a solution of 1-[2-(4-hydroxyphenyl)ethyl]-7-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-indole (50 mg) in methanol (1 mL) were added water (0.1 mL) and lithium hydroxide monohydrate (11 mg), and the mixture was stirred at room temperature overnight. The reaction mixture was purified by column chromatography on silica gel (eluent: methylene chloride/methanol=8/1-5/1) to give the title compound (20 mg).
Reaction SMILES: [C:1]([NH2:5])(=[O:4])[CH:2]=[CH2:3].C(N)CC.[CH2:10]([P:12](OC)(=[O:15])[O:13][CH3:14])[CH3:11]>>[CH3:14][O:13][P:12]([CH2:10][CH3:11])([CH2:3][CH2:2][C:1]([NH2:5])=[O:4])=[O:15]
Reactant: C=CC(N)=O
Reactant: CCP(=O)(OC)OC
Solvent: CCCN
Product: CCP(=O)(CCC(N)=O)OC
Temperature: 50 °C
Reaction time: 5 h
Yield: 92.3 %

Procedure:
71 g of acrylamide and 120 g of n-propylamine are mixed at room temperature under nitrogen and the mixture is heated to 50° C. 122 g of dimethyl ethanephosphonate are added dropwise to the reaction solution in the course of 30 minutes. The reaction mixture is then stirred for 5 hours at reflux temperature and the solvent (low-boiling solvent such as excess propylamine+N-methyl-N-propylamine) is removed by vacuum distillation. The crude product is obtained in a yield of 175 g with a 94.4% purity, which corresponds to a theoretical yield of 92.3%.
Reaction SMILES: Cl.[NH2:2][C@@:3]([C:7]([OH:9])=[O:8])([CH3:6])[CH2:4][CH3:5].[Cl-].[Na+].S(Cl)([Cl:14])=O.[CH3:16][OH:17]>>[CH3:5][CH:4]([CH3:16])[C@@:3]([NH2:2])([CH3:6])[C:7]([OH:9])=[O:8].[ClH:14].[CH3:16][O:17][C:7](=[O:8])[C@:3]([CH3:6])([CH2:4][CH3:5])[NH2:2]
Reactant: CC[C@](C)(N)C(=O)O
Reactant: O=S(Cl)Cl
Reactant: CO
Agent: Cl
Agent: [Cl-]
Agent: [Na+]
Product: CC(C)[C@](C)(N)C(=O)O
Product: CC[C@](C)(N)C(=O)OC
Temperature: 25 °C

Procedure:
To a well-stirred suspension of the previous mixture of (S)-isovaline hydrochloride and sodium chloride in methanol (3 L) was slowly added thionyl chloride (373 g, 3.13 mole). After the addition was complete the reaction mixture was refluxed for 3 hours. The resulting mixture was cooled to room temperature and filtered. The resulting white filter cake was washed several times with methanol. The combined methanol filtrate and washings were concentrated using a rotary evaporator. Toluene was added to the resulting crude residue and then removed using the rotary evaporator yielding 187 g of the expected (S)-isovaline methyl ester hydrochloride.
Reaction SMILES: C(=[N:14][CH:15]([CH:18]([C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:23]=[CH:22][CH:21]=1)[CH3:19])[C:16]#[N:17])(C1C=CC=CC=1)C1C=CC=CC=1.Cl>O1CCOCC1>[NH2:14][CH:15]([CH:18]([C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:23]=[CH:22][CH:21]=1)[CH3:19])[C:16]#[N:17]
Reactant: CC(c1ccnc2ccccc12)C(C#N)N=C(c1ccccc1)c1ccccc1
Agent: Cl
Solvent: C1COCCO1
Product: CC(c1ccnc2ccccc12)C(N)C#N
Temperature: 25 °C
Reaction time: 8 h
Yield: 102.5 %

Procedure:
To 2-(Benzhydrylideneamino)-3-quinolin-4-yl-butyronitrile (3.0 g, 7.3 mmol) in 30 ml dioxane, 1N HCl (30 ml, 29.99 mmol) was added and the reaction mixture stirred at room temperature overnight. The solution was then concentrated under reduced pressure, partitioned between water (10 ml) and EtOAc (10 ml). The organic layer was dried over sodium sulfate, filtered and concentrated to give 1.58 g (88%) of the product which was used as such for the subsequent step.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[C:7]([O:12]CC3C(Cl)=CC=C([N+]([O-])=O)C=3Cl)[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:25])[CH:3]=1.[CH3:26][N:27](C)[CH:28]=O>>[OH:12][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[N:5]=[C:4]([CH3:25])[CH:3]=[C:2]2[N:27]([CH3:28])[CH3:26]
Reactant: CN(C)C=O
Reactant: Cc1cc(Cl)c2cccc(OCc3c(Cl)ccc([N+](=O)[O-])c3Cl)c2n1
Product: Cc1cc(N(C)C)c2cccc(O)c2n1

Procedure:
A mixture of 4-chloro-8-(2,6-dichloro-3-nitrobenzyloxy)-2-methylquinoline (200 mg) and N,N-dimethylformamide (3 ml) was heated under reflux for 18 hours. The reaction mixture was partitioned into ethyl acetate and saturated aqueous solution of sodium bicarbonate. The organic layer was washed with water, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by preparative thin-layer chromatography (dichloromethane-methanol) to give 8-hydroxy-2-methyl-4-dimethylaminoquinoline (26 mg) as a brownish powder.
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:16]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@H:15]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C@@H:14]([CH2:33][O:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][NH:40]C(=O)C(F)(F)F)[O:13][C@H:10]1[O:11][CH3:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>C(O)C>[NH2:40][CH2:39][CH2:38][CH2:37][CH2:36][CH2:35][O:34][CH2:33][C@H:14]1[O:13][C@@H:10]([O:11][CH3:12])[C@H:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C@@H:16]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C@@H:15]1[O:25][CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: CO[C@@H]1O[C@H](COCCCCCNC(=O)C(F)(F)F)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Agent: Cl
Solvent: CCO
Product: CO[C@@H]1O[C@H](COCCCCCN)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1

Procedure:
To a stirred solution of methyl 2,3,4-tri-O-benzyl-6-O-(N-trifluoroacetyl-5-aminopentyl)-β-D-glucopyranoside (799 mg, theoretically 1.71 mmol, structure (13) from Example 4) in 10 mL of ethanol at room temperature was added a solution of 5M (3 mL, 15 mmol). The solution was heated to reflux for 2 hours. The solvents were removed under reduced pressure. The reaction mixture was diluted with dichloromethane (70 mL) and washed with aqueous HCl (25 mL, 15 mmol). The water layer was re-extracted with dichloromethane (3×50 mL), and the combined organic layers were washed with saturated aqueous NaCl (1×75 mL) and dried over magnesium sulfate. Concentration and crystallization from ethyl acetate/petroleum ether provided pure analog having structure (9), methyl 6-O-(5-aminopentyl)-2,3,4-tri-O-benzyl-β-D-glucopyranoside, (675 mg, 72% from methyl 2,3,4-tri-O-benzyl-6-O-trifluoromethylsulfonyl-β-D-glucopyranoside) as a white solid: m.p. 95-95.5° C.; RF 0.19 (6% methanol in dichloromethane); 1H NMR (500 MHz, CDCl3) δ 7.35-7.24 (m, 15H), 4.92 (d, J=7.5 Hz 1H), 4.90 (d, J=7.6 Hz, 1H), 4.85 (d,J=11.0 Hz, 1H), 4.78 (d, J=11.0 Hz, 1H), 4.70 (d, J=11.0 Hz, 1H), 4.60 (d, J=11.0 Hz, 1H), 4.32 (7.8, 1H), 3.66-3.59 (m, 3H), 3.56 (s, 3H), 3.48-3.36 (m, 3H), 2.94 (dd, J=12.5, 2.1 Hz, 1H), 2.68 (dd, J=12.0, 6.8 Hz, 1H), 2.64-2.53 (m, 2H), 1.71 (s, 2H), 1.59-1.53 (m, 2H), 1.51-1.45 (m, 2H), 1.42-1.36 (m, 2H), 13C NMR (500 MHz, CDCl3) δ 138.55, 138.47, 138.17, 128.39, 128.33, 128.03, 127.95, 127.85, 127.77, 127.60, 127.57, 104.72, 84.56, 82.45, 79.74, 75.66, 75.02, 74.74, 74.16, 62.62, 57.20, 50.69, 49.72, 32.49, 29.65, 23.37; IR (thin film) 3280(m), 3095(w), 3065(w), 3035(w), 2935(s), 2915(s), 2860(s), 1496(w), 1454(m), 1404(w), 1393(w), 1358(m), 1214(m), 1115(s), 1072(s), 1037(m), 1027(m), 1009(m), 911(w), 826(s), 747(s), 696(s) cm−1; HRMS m/e calc'd for C33H43O6N (M+H): 550.3168, found 550.3179; [α]D20+9.3° (c=0.15, acetonitrile).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=C([CH:7]=[CH:8][C:9]=1[N:10]1[CH2:15][CH2:14][CH2:13][NH:12][C:11]1=[O:16])C#N.[OH-:17].[Na+].[CH2:19]([OH:21])[CH3:20]>>[Cl:1][C:2]1[CH:3]=[C:20]([CH:7]=[CH:8][C:9]=1[N:10]1[CH2:15][CH2:14][CH2:13][NH:12][C:11]1=[O:16])[C:19]([OH:17])=[O:21]
Reactant: CCO
Reactant: [OH-]
Reactant: N#Cc1ccc(N2CCCNC2=O)c(Cl)c1
Agent: [Na+]
Product: O=C(O)c1ccc(N2CCCNC2=O)c(Cl)c1
Temperature: 100 °C
Reaction time: 1 h

Procedure:
350 mg (1.49 mmol) 3-chloro-4-(tetrahydro-pyrimidin-2-on-1-yl)-benzonitrile are suspended in 5 ml of ethanol and combined with 2.0 ml of 10-molar aqueous sodium hydroxide solution. The mixture is stirred for one hour at 100° C. and then evaporated down i. vac. The aqueous residue is combined with ice, acidified with acetic acid and extracted with ethyl acetate. The combined organic phases are washed with water and sat. sodium chloride solution, dried over magnesium sulphate and evaporated down i. vac. The aqueous phase is acidified with 6-molar hydrochloric acid, extracted 5 times with ethyl acetate, the combined organic phases are washed with sat. sodium chloride solution, dried over magnesium sulphate and evaporated down i. vac.
Reaction SMILES: [CH2:1](S(C1N(C2C=CC=CC=2)N=NN=1)(=O)=O)[CH2:2][CH2:3][CH3:4].[K].C[Si](C)(C)N[Si](C)(C)C.[CH:29]([C@@H:31]1[CH2:36][CH2:35][C@H:34]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH2:33][CH2:32]1)=O.O>COCCOC>[CH:29](/[C@@H:31]1[CH2:36][CH2:35][C@H:34]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH2:33][CH2:32]1)=[CH:1]\[CH2:2][CH2:3][CH3:4]
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@@H](C=O)CC1
Reactant: CCCCS(=O)(=O)c1nnnn1-c1ccccc1
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: [K]
Solvent: COCCOC
Solvent: O
Product: CCC/C=C/[C@H]1CC[C@@H](NC(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 67 %

Procedure:
To a mixture of 5-butylsulfonyl-1-phenyl-1H-tetrazole (3.54 g) and anhydrous ethylene glycol dimethyl ether (60 ml) at −60° C. was added 0.5 M hexamethyldisilazane potassium solution (in toluene, 26.6 ml), and the mixture was stirred for 20 minutes. Under the same condition, a solution of t-butyl cis-4-formylcyclohexylcarbamate (3.02 g) in anhydrous ethylene glycol dimethyl ether (15 ml) was added to the mixture. And the reaction mixture was gradually warmed to 25° C. and stirred overnight. To the reaction mixture was added water, and the mixture was stirred for 1 hour, then extracted with diethyl ether, and the organic layer was washed with brine, dried over sodium sulfate, and then the solvent was removed in vacuo. The residue was purified by a silica gel chromatography (eluent: gradient from 100% hexane/0% ethyl acetate to 0% hexane/100% ethyl acetate) to give 2.38 g of t-butyl cis-{4-[(E)-1-pentenyl]cyclohexyl}carbamate.
Reaction SMILES: [O:1]=[CH:2][C:3]1[CH:11]=[CH:10][C:8]([OH:9])=[C:5]([O:6][CH3:7])[CH:4]=1.[C:12](O)(=[O:34])/[CH:13]=[CH:14]\[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=[CH:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33].C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C1C=CN=CC=1.ClCCl.O>[CH3:7][O:6][C:5]1[CH:4]=[C:3]([CH:11]=[CH:10][C:8]=1[O:9][C:12](=[O:34])[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=[CH:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[CH:2]=[O:1]
Reactant: COc1cc(C=O)ccc1O
Reactant: CCCCCCCCCC=CC=CC=CC=CC=C/C=C\C(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: O
Solvent: ClCCl
Product: CCCCCCCCCC=CC=CC=CC=CC=CC=CC(=O)Oc1ccc(C=O)cc1OC
Temperature: 25 °C
Reaction time: 16 h
Yield: 79.7 %

Procedure:
To a solution of vanillin (330 mg, 2.17 mmol), cis-docosahexaenoic acid (870 mg, 2.65 mmol) and catalytic amount of 4-(dimethylamino)pyridine in dichloromethane (15 mL) was added a solution of N,N′-dicyclohexylcarbodiimide (720 mg, 3.50 mmol) in DCM (5 mL) for 5 min at ice cold temperature. The mixture was stirred at rt for 16 h and diluted with water. DCM layer was separated and the aqueous layer was extracted with DCM (3×100 mL). The combined DCM layer was washed with water, brine and dried over sodium sulfate. The solution was filtered and the residue was chromatographed over silica gel column using hexane-ethyl acetate (95:5) mixture as an eluent to give the product as an oil (800 mg, 80%). 1H NMR (400 MHz, CDCl3) δ 9.94 (1H, s, —CHO), 7.49 (1H, d, J=1.6 Hz, H-2), 7.47 (1H, dd, J=8.0, 1.6 Hz, H-6), 7.20 (1H, d, J=8.0 Hz, H-5), 5.30-5.48 (12H, m, H-4′, 5′, 7′, 8′, 10′, 11′, 13′, 14′, 16′, 17′, 19′, 20′, 3.89 (3H, s, —OCH3), 2.80-2.88 (10H, m, H-6′, 9′, 12′, 15′, 18′), 2.58-2.67 (2H, m, H-2′), 2.22-2.25 (2H, m, H-21′), 2.05-2.11 (2H, m, H-3′), 0.97 (3H, t, J=7.4 Hz, H-22′).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[S:18][C:13]2=[N:14][CH:15]=[CH:16][CH:17]=[C:12]2[C:11]=1[C:19]([O:21]CC)=O.[NH3:24].C(Cl)Cl>C(O)C>[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[S:18][C:13]2=[N:14][CH:15]=[CH:16][CH:17]=[C:12]2[C:11]=1[C:19]([NH2:24])=[O:21]
Reactant: N
Reactant: CCOC(=O)c1c(Nc2ccc(I)cc2F)sc2ncccc12
Solvent: ClCCl
Solvent: CCO
Product: NC(=O)c1c(Nc2ccc(I)cc2F)sc2ncccc12
Temperature: 95 °C

Procedure:
A solution of Example 1 (250 mg, 0.56 mmol) in ethanol (5 mL) was added to liquid ammonia (15 mL) and the mixture heated in a Parr apparatus to 95° C. at 800 psi for 18 hours. The volatiles were removed in vacuo to give an oily brown residue. Repeated trituration with ethanol and DCM afforded the title compound as a white solid (18 mg). δH (DMSO-d6) 11.20 (1H, bs), 8.34 (1H, d, J=3.4 Hz), 8.20 (1H, dd, J 8.2, 1.3 Hz), 7.76 (1H, dd, J 10.4, 1.8 Hz), 7.62 (1H, d, J=8.2 Hz), 7.57 (2H, br s), 7.49-7.39 (2H, m). LCMS (ES+) RT 3.11 minutes, 412 (M+H)+.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:17]([NH:25][C:26]1[CH:38]=[C:37](Br)[CH:36]=[CH:35][C:27]=1[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C)C(=O)C>[C:17]([NH:25][C:26]1[CH:38]=[C:37]([C:5]2[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=2)[CH:36]=[CH:35][C:27]=1[C:28]([O:30][C:31]([CH3:33])([CH3:34])[CH3:32])=[O:29])(=[O:24])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: OB(O)c1ccc(O)cc1
Reactant: CC(C)(C)OC(=O)c1ccc(Br)cc1NC(=O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: CC(C)(C)OC(=O)c1ccc(-c2ccc(O)cc2)cc1NC(=O)c1ccccc1
Temperature: 110 °C
Reaction time: 20 h

Procedure:
39 mg of 4-hydroxyphenylboronic acid, 49 mg of sodium carbonate and 6 mg of polymer supported bis(acetato)triphenylphosphine palladium(II) were added to 2.5 mL of N,N-dimethylacetamide solution containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate, and stirred at 110° C. for 20 hours. After the reaction mixture was cooled to room temperature, 6 mg of polymer supported bis(acetato)triphenylphosphine palladium(II) was added and stirred at 110° C. for 22 hours. After the reaction mixture was cooled to room temperature, insoluble were removed by filtration and ethyl acetate and 10% citric acid, aqueous solution were added. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with 10% citric acid aqueous solution and a saturated sodium chloride aqueous solution sequentially, and the solvent was evaporated under reduced pressure. The obtained residue was purified with silica gel column chromatography [Flash Tube 2008 manufactured by Trikonex company, eluent; hexane: ethyl acetate=2:1] to obtain tert-butyl 2-(benzamido)-4-(4-hydroxyphenyl)benzoate.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:13][CH:12]([C:14]([OH:16])=[O:15])[O:11][C:10]2=[O:17])=[CH:5][CH:4]=1)#[N:2].[Cl-:18].[OH:19][NH3+:20].C(=O)([O-])[O-].[Na+].[Na+]>CO.O>[ClH:18].[ClH:18].[NH2:2][C:1](=[N:20][OH:19])[C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:13][CH:12]([C:14]([OH:16])=[O:15])[O:11][C:10]2=[O:17])=[CH:7][CH:8]=1
Reactant: [Cl-]
Reactant: [NH3+]O
Reactant: N#Cc1ccc(N2CC(C(=O)O)OC2=O)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: Cl
Product: NC(=NO)c1ccc(N2CC(C(=O)O)OC2=O)cc1

Procedure:
27.9 g of 3-(4-cyanophenyl)-2-oxo-5-oxazolidine carboxylic acid [obtainable according to Example 1] and 26.4 g of hydroxylammonium chloride are boiled for 5 h in a mixture of 750 ml of methanol and 30 ml of water in the presence of 53.4 g of sodium carbonate. The precipitate formed is filtered off with suction, washed with methanol and dried. Treatment with hydrochloric acid gives 3-[4-(amino(hydroxylimino)methyl)phenyl]-2-oxo-5-oxazolidinecarboxylic acid, hydrochloride, m.p. 205°-208°.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](O)=[O:6].[C:11](N1C=CN=C1)([N:13]1C=CN=C1)=O.CN.C1COCC1.[Cl-].[NH4+]>CN(C=O)C>[I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([NH:13][CH3:11])=[O:6]
Reactant: O=C(O)c1cccc(I)c1
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: CN
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CNC(=O)c1cccc(I)c1
Temperature: 50 °C
Reaction time: 0.25 h

Procedure:
To a solution of 3-iodobenzoic acid (1.5 g, 6 mmol) in anhydrous DMF (10 mL) was added 1,1′-carbonyldiimidazole (1.2 g, 7.2 mmol). The reaction mixture was heated to 50° C. under an atmosphere of nitrogen for 1 h. Upon cooling to room temperature, a solution of methylamine in THF (2 M, 6 mL, 10 mmol) was added. The reaction was stirred at r.t. for 15 min and then transferred into a solution of cold, saturated ammonium chloride (200 mL). The resulting precipitate was collected by filtration and dried to afford the title compound as a white solid, mp 94-97° C.