Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[CH:11][C:5]([CH2:6][NH:7][CH2:8][CH2:9][CH3:10])=[CH:4][CH:3]=1.[C:13](Cl)([Cl:15])=[O:14]>C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]([CH2:8][CH2:9][CH3:10])[C:13]([Cl:15])=[O:14])=[CH:11][CH:12]=1
Reactant: CCCNCc1ccc(Cl)cc1
Reactant: O=C(Cl)Cl
Solvent: CCOC(C)=O
Product: CCCN(Cc1ccc(Cl)cc1)C(=O)Cl

Procedure:
A solution of 25.2 g. N-4-chlorobenzyl-N-propylamine in 150 ml. ethyl acetate was added to 150 ml. ethyl acetate under reflux whilst phosgene was passed through. The passage of phosgene was continued for 21/2 hours, after which the ethyl acetate was evaporated to give an oily product. Distillation gave N-4-chlorobenzyl-N-propylcarbamoyl chloride, an oil b.p. 162°-164° C./4.0 mm. Hg.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[CH:3]([CH2:7][CH2:8][CH2:9][CH3:10])[C:4](O)=[O:5].C(Cl)(=O)C([Cl:16])=O>>[F:1][C:2]([F:12])([F:11])[CH:3]([CH2:7][CH2:8][CH2:9][CH3:10])[C:4]([Cl:16])=[O:5]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CCCCC(C(=O)O)C(F)(F)F
Product: CCCCC(C(=O)Cl)C(F)(F)F
Yield: 89.7 %

Procedure:
2-Trifluoromethylhexanoic acid (2.3 g.) was added dropwise to 10 g. oxalyl chloride (10 g.) and the mixture heated to reflux for 2 hours. Distillation of the reaction mixture after this time yielded 2-trifluoromethylhexanoyl chloride (2.27 g.; 90%), b.p. 67°-70°/43 mmHg.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:3]([NH:5][C:6]1[N:10]([CH3:11])[N:9]=[C:8]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([Cl:18])[CH:13]=2)[CH:7]=1)=[O:4].CCN(C(C)C)C(C)C.Br[CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38]>CN(C=O)C>[Cl:18][C:14]1[CH:13]=[C:12]([C:8]2[CH:7]=[C:6]([NH:5][C:3](=[O:4])[C@@H:2]([NH:1][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])[CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:10]([CH3:11])[N:9]=2)[CH:17]=[CH:16][N:15]=1
Reactant: Cn1nc(-c2ccnc(Cl)c2)cc1NC(=O)[C@@H](N)Cc1ccccc1
Reactant: CCOC(=O)CBr
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)CN[C@@H](Cc1ccccc1)C(=O)Nc1cc(-c2ccnc(Cl)c2)nn1C
Temperature: 0 °C
Reaction time: 16 h

Procedure:
To a 1000 ml flask was added 8.6 g of (2S)-2-amino-N-(3-(2-chloropyridin-4-yl)-1-methyl-1H-pyrazol-5-yl)-3-phenylpropanamide 1.E, 100 ml of DMF, 6.0 ml of DIEA and the reaction was cooled to 0° C. To the reaction was then added 2.8 ml of ethyl bromoacetate and the reaction was stirred at 22° C. for 16 hours at which time the crude was partitioned between 1500 ml EtAc, 2×400 ml of saturated brine, and 2×400 ml of water (Note: no product observed in aqueous layer). The organic solvent was removed by rotary evaporation and the crude purified with a silica gel column (eluting with 30% EtAc in Hexane) to give 6.3 g of ethyl 2-((S)-1-(3-(2-chloropyridin-4-yl)-1-methyl-1H-pyrazol-5-ylamino)-1-oxo-3-phenylpropan-2-ylamino)acetate 17.7.F as a white solid.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][C:16]=1[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH3:25])=[CH:20][CH:19]=1)[CH2:12]O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:26]([N:28](CC)CC)C.CS(Cl)(=O)=O.Cl>ClCCl>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH2:12][C:26]#[N:28])[CH:14]=[CH:15][C:16]=1[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH3:25])=[CH:20][CH:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCN(CC)CC
Reactant: CCc1ccc(Cc2ccc(CO)cc2OCc2ccccc2)cc1
Agent: CS(=O)(=O)Cl
Agent: Cl
Solvent: ClCCl
Product: CCc1ccc(Cc2ccc(CC#N)cc2OCc2ccccc2)cc1
Reaction time: 2 h

Procedure:
To a solution of 3-benzyloxy-4-(4-ethylbenzyl)benzyl alcohol (0.87 g) in dichloromethane (20 mL) were added triethylamine (0.44 mL) and methanesulfonyl chloride (0.22 mL) at 0° C., and the mixture was stirred for 2 hours. To the reaction mixture was added 0.5 mol/L aqueous hydrochloric acid solution, and the mixture was extracted with diethyl ether. The organic layer was washed with water and a saturated aqueous sodium hydrogen carbonate solution, and dried over anhydrous magnesium sulfate, and the solvent was removed under reducer pressure. The residue was dissolved in dimethyl sulfoxide (10 mL). To the solution were added potassium cyanide (0.68 g) and a catalytic amount of sodium iodide, and the resulting mixture was stirred at 80° C. for 12 hours. Water was added to the reaction mixture, and the mixture was extracted with diethyl ether. The organic layer was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=5/1–3/1) to give [3-benzyloxy-4-(4-ethylbenzyl)phenyl]acetonitrile (0.41 g).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6](Br)[N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[C:3]=1[Cl:13].[F:14][C:15]1[C:23]2[O:22][C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[N:20][C:19]=2[CH:18]=[CH:17][C:16]=1B(O)O.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[CH:7]=[C:6]([C:16]2[CH:17]=[CH:18][C:19]3[N:20]=[C:21]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[O:22][C:23]=3[C:15]=2[F:14])[N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[C:3]=1[Cl:13]
Reactant: OB(O)c1ccc2nc(-c3ccccc3)oc2c1F
Reactant: COC(=O)c1nc(Br)cc(N)c1Cl
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: COC(=O)c1nc(-c2ccc3nc(-c4ccccc4)oc3c2F)cc(N)c1Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 35.6 %

Procedure:
0.024 g (0.03 mmol) of (PPh3)2PdCl2 is added to a solution of 0.3 g (1.13 mmol) of methyl 4-amino-6-bromo-3-chloropyridine-2-carboxylate in 20 ml of dioxane, and this mixture is stirred at room temperature (RT) for 30 min. In succession, 0.35 g (1.35 mmol) of (7-fluoro-2-phenyl-1,3-benzoxazol-6-yl)boronic acid, 0.47 g (3.4 mmol) of K2CO3 and 2 g (111 mmol) of H2O are then added to this mixture, which is then stirred under reflux for 6 h. The mixture is allowed to stand at RT for a further 12 h and then added to 40 ml of H2O. This mixture is extracted repeatedly with CH2Cl2, and the combined organic phase is dried over Na2SO4 and then concentrated. Purification by chromatography on silica gel using the mobile phase heptane/ethyl acetate (3/7) gives 0.16 g (36%) of product. 1H-NMR (CDCl3): δ 8.30, 8.00, 7.55 (3m, 5H, C6H5), 7.60, 7.55 (2d, 2H, benzoxazole ring), 7.30 (s, 1H, pyridine) 4.85 (bs, 2H, NH2), 4.00 (S, 3H, COOCH3).
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]([C:22]([O:24][CH2:25][CH3:26])=[O:23])N=N[C:12]=2[C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][CH3:21])=[CH:15][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:27](N1CCCC1)=[CH2:28]>C(Cl)(Cl)Cl>[C:1]1([C:7]2[N:8]=[C:9]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:28]=[CH:27][C:12]=2[C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][CH3:21])=[CH:15][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCCc1ccc(-c2nnc(C(=O)OCC)nc2-c2ccccc2)cc1
Reactant: C=CN1CCCC1
Solvent: ClC(Cl)Cl
Product: CCCc1ccc(-c2ccc(C(=O)OCC)nc2-c2ccccc2)cc1

Procedure:
Following General Procedure D, ethyl 5-phenyl-6-(4-propyl-phenyl)-1,2,4-triazine-3-carboxylate (Compound 14), (153 mg, 0.46 mmol) and crude 1-vinylpyrrolidine (Compound 38, 2 g) in CHCl3 (10 ml) were reacted to produce the title compound as a yellow oil.
Reaction SMILES: [NH2:1][C:2]([NH2:4])=[S:3].[CH2:5]([NH:7][C:8]1N=C(NCC)N=[C:10](Cl)[N:9]=1)[CH3:6].[OH-].[Na+].Cl>O1CCOCC1.O>[CH2:5]([NH:7][C:8]1[N:9]=[CH:10][N:4]=[C:2]([SH:3])[N:1]=1)[CH3:6]
Reactant: CCNc1nc(Cl)nc(NCC)n1
Reactant: NC(N)=S
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: CCNc1ncnc(S)n1
Reaction time: 2 h

Procedure:
A mixture of 1.5 g of thiourea and 4 g of 2,4-bis(ethylamino)-6-chloro-1,3,5-triazine in a mixture of 20 ml of dioxane and 20 ml of water is refluxed with stirring for 2 hours in 100 ml flask. After cooling, the mixture is mixed with 1.6 g of 50% sodium hydroxide and stirred for 10 minutes. The resulting mixture is neutralized with hydrochloric acid and extracted with ethyl acetate. The extract is concentrated under reduced pressure to give 4 g of 2,4-bis(ethylamino-6-mercapto-1,3,5-triazine. The product can be used for preparation of the objective compound without isolation.
Reaction SMILES: [C:1]1([O-:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Na+].[C:9]([O-:18])(=[O:17])C1C(=CC=CC=1)O.[Na+]>>[CH:3]1[C:4]([C:9]([OH:18])=[O:17])=[CH:5][CH:6]=[C:1]([OH:7])[CH:2]=1
Reactant: [O-]c1ccccc1
Reactant: O=C([O-])c1ccccc1O
Agent: [Na+]
Product: O=C(O)c1ccc(O)cc1

Procedure:
In contrast to published information, it has been found that the degree of conversion of sodium phenolate to sodium salicylate is practically independent of the reaction temperature. At 165° C. and at 200° C., 85-88% conversion is easily obtained, but by-product formation is reduced as the temperature is increased. For instance, reaction at 140°-150° C. gives about 9% non-salicylic acids mostly 4-HBA in the crude product mixture whereas reaction at 190°-195° C. (at 5 bar co-pressure) gives less than 0.5% non-salicylic acids in the reaction product mixture.
Reaction SMILES: [NH2:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([NH:8][CH2:9][CH2:10][N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])=[O:7])=[C:4]([O:18][CH3:19])[CH:3]=1.C(N(CC)CC)C.[CH3:27][S:28](Cl)(=[O:30])=[O:29].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH2:14]([N:11]([CH2:12][CH3:13])[CH2:10][CH2:9][NH:8][C:6](=[O:7])[C:5]1[CH:16]=[CH:17][C:2]([N:1]([S:28]([CH3:27])(=[O:30])=[O:29])[S:28]([CH3:27])(=[O:30])=[O:29])=[CH:3][C:4]=1[O:18][CH3:19])[CH3:15]
Reactant: CCN(CC)CCNC(=O)c1ccc(N)cc1OC
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCN(CC)CCNC(=O)c1ccc(N(S(C)(=O)=O)S(C)(=O)=O)cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 100.1 %

Procedure:
265 mg (1 mmol) of 4-amino-N-(2-diethylamino-ethyl)-2-methoxy-benzamide is introduced into 15 ml of methylene chloride and mixed in succession with 111 mg (1.1 mmol) of triethylamine and 126 mg (1.1 mmol) of methanesulfonic acid chloride. It is stirred for 2 hours at room temperature and then allowed to stand overnight. It is then mixed with 25 ml of saturated sodium bicarbonate solution and shaken out three times with 25 ml each of methylene chloride. The collected organic phase is dried, filtered and concentrated by evaporation. The residue is chromatographed on 10 g of basic silica gel (Isolute flash Si NH2) with a gradient from cyclohexane:ethyl acetate=100:0 to 50:50. 232 mg (52.6% of theory) of N-(2-diethylamino-ethyl)-4-(bismethanesulfonylamino)-2-methoxy-benzamide with a melting point of 144.1° C. is obtained.
Reaction SMILES: [C:1](=O)([O-])[O-:2].[K+].[K+].[CH3:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16]1[CH:24]=[CH:23][CH:22]=[CH:21][C:17]=1[C:18]([OH:20])=[O:19].C(Cl)(Cl)=O>C1(C)C=CC=CC=1.O>[CH3:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N:15]1[C:1](=[O:2])[O:20][C:18](=[O:19])[C:17]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:16]12
Reactant: O=C([O-])[O-]
Reactant: COc1ccccc1Nc1ccccc1C(=O)O
Agent: O=C(Cl)Cl
Agent: [K+]
Solvent: O
Solvent: Cc1ccccc1
Product: COc1ccccc1-n1c(=O)oc(=O)c2ccccc21
Reaction time: 8 h
Yield: 22.1 %

Procedure:
To a suspension of 24.44 g (0.177 mole) of potassium carbonate in 119 ml of toluene and 238 ml of water, stirred at 20°-40° C., was added 28.61 g (0.1176 mole) of 2-(2-methoxyphenylamino)benzoic acid, and phosgene was bubbled through the mixture for a period of 3.5 hours. The reaction was allowed to stand overnight with stirring, and the solid material was collected by filtration. The latter was dissolved in ethyl acetate and added to the toluene layer separated from the filtrate. The solution was washed twice with 200 ml 1N potassium hydroxide and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to yield 7 g of N-(2-methoxyphenyl)isatoic anhydride.
Reaction SMILES: Cl[C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([N+:14]([O-])=O)[CH:9]=1.C(=O)([O-])O.[Na+]>O1CCCC1.C(O)C.[Pd]>[N:4]1[CH:5]=[CH:6][C:7]([C:8]2[CH:9]=[C:10]([NH2:14])[CH:11]=[CH:12][CH:13]=2)=[CH:2][N:3]=1
Reactant: O=[N+]([O-])c1cccc(-c2cc(Cl)nnc2Cl)c1
Agent: [Pd]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCO
Product: Nc1cccc(-c2ccnnc2)c1
Yield: 88 %

Procedure:
A suspension of 3,6dichloro4-(3-nitro-phenyl)pyridazine (0.19 g) and sodium hydrogen carbonate (147 mg) in tetrahydrofuran (2 ml) and ethanol (5 ml) was hydrogenated over palladium on carbon (10% w/w, 50% wet, 100 mg) under hydrogen atmosphere for 3 hours. The catalyst was filtered off, and the filtrate was evaporated. The residue was diluted with ethyl acetate and an aqueous solution of sodium hydrogen carbonate. The separated organic layer was washed with brine and dried over potassium carbonate. The organic layer was evaporated under reduced pressure to give 3-(pyridazin-4-yl)phenylamine (106 mg, 88.3%).
Reaction SMILES: [C:1]([SiH2:5][O:6][C:7]([CH3:17])([CH3:16])[C@H:8]1[CH2:13][CH2:12][C@H:11]([CH2:14]O)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:37]1([N:43]2[C:47]([SH:48])=[N:46][N:45]=[N:44]2)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[C:1]([SiH2:5][O:6][C:7]([CH3:17])([CH3:16])[C@H:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][S:48][C:47]2[N:43]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[N:44]=[N:45][N:46]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[SiH2]OC(C)(C)[C@H]1CC[C@H](CO)CC1
Reactant: Sc1nnnn1-c1ccccc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)[SiH2]OC(C)(C)[C@H]1CC[C@H](CSc2nnnn2-c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of [trans-4-(tert-butyl-dimethyl-silanyloxymethyl)-cyclohexyl]-methanol (prepared as described in J. Med. Chem. (2001), 44, 531, 9.0 g, 34.8 mmol) in THF (100 mL) were added PPh3 (13.7 g, 1.5 eq.), 1-phenyl-1H-tetrazole-5-thiol (6.2 g, 1 eq.) and DIAD (10.3 mL, 1.5 eq.). The reaction mixture was stirred at rt overnight. After evaporation to dryness, the residue was chromatographed over SiO2 (Hex-EA 8-1) to afford the title sulfide (11.4 g) contaminated with some PPh3.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[CH:3]=1.[CH2:10](O)[CH2:11][CH2:12][CH3:13].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:10][CH2:11][CH2:12][CH3:13])=[C:4]([F:9])[CH:3]=1
Reactant: Oc1ccc(Br)cc1F
Reactant: CCCCO
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCCCOc1ccc(Br)cc1F
Reaction time: 8 h
Yield: 95.6 %

Procedure:
0.315 mol of each of 4-bromo-2-fluorophenol (1), 1-butanol and triphenylphosphine were dissolved in 1000 ml of tetrahydrofuran, and 0.315 mol of diisopropyl azodicarboxylate was added dropwise at about 20° C. After the mixture had been stirred overnight, the solvent was removed by distillation in a rotary evaporator, and the residue was subjected to conventional work-up, giving the compound (2) in a yield of 95.6% of theory.
Reaction SMILES: [C:1]1([C:7]2[O:8][C:9]3[C:10](=[C:12]([C:16]([OH:18])=O)[CH:13]=[CH:14][CH:15]=3)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.Cl.[NH2:21][CH:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1>>[CH3:28][N:25]1[CH2:26][CH2:27][CH:22]([NH:21][C:16]([C:12]2[CH:13]=[CH:14][CH:15]=[C:9]3[O:8][C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[N:11][C:10]=23)=[O:18])[CH2:23][CH2:24]1
Reactant: CN1CCC(N)CC1
Reactant: O=C(O)c1cccc2oc(-c3ccccc3)nc12
Agent: Cl
Product: CN1CCC(NC(=O)c2cccc3oc(-c4ccccc4)nc23)CC1
Yield: 38 %

Procedure:
N-(1-Methylpiperidin-4-yl)-2-phenylbenzoxazole-4-carboxamide was prepared from 2-phenylbenzoxazole-4-carboxylic acid and 4-amino-1-methylpiperidine dihydrochloride using the conditions described for Step C in Example 1. This compound was obtained in 38% yield as a white solid; mp 126-128° C.; 1H NMR (300 MHz, CDCl3) δ 9.26 (d, J=7.5 Hz, 1H), 8.25 (m, 2H), 8.19 (d, J=7.7 Hz, 1H), 7.70 (d, J=8.1 Hz, 1H), 7.63-7.53 (m, 3H), 7.46 (t, J=8.0 Hz, 1H), 4.20 (m, 1H), 2.86 (m, 2H), 2.37 (s, 3H), 2.33-2.13 (m, 4H), 1.85-1.73 (m, 2H); MS (APCI) m/z 336 [M+H]+.
Reaction SMILES: C(O[CH:5]=[CH2:6])(=O)C.C(N1[CH2:13][CH2:12][CH2:11][C:10]1=O)=C>>[CH3:10][CH2:11][CH2:12][CH2:13][CH2:13][CH2:12][CH2:11][CH2:10][CH2:5][CH3:6]
Reactant: C=COC(C)=O
Reactant: C=CN1CCCC1=O
Product: CCCCCCCCCC
Yield: 3957.8 %

Procedure:
A mixture of 14 g of the resin P-2 obtained in Production Example 2 of dispersion stabilizing resin, 85 g of vinyl acetate, 15 g of N-vinylpyrrolidone, 1.2 g of the macromonomer M-1 obtained in Production Example 1 of macromonomer, and 380 g of n-decane was heated to 75° C. with stirring under nitrogen gas stream. After adding thereto 1.7 g of A.I.B.N., the reaction was carried out for 4 hours and, after further adding thereto 0.5 g of A.I.B.N., the reaction was carried out for 2 hours. After cooling, the reaction mixture was passed through a 200 mesh nylon cloth to obtain a latex having a mean grain size of 0.23 μm as a white dispersion.
Reaction SMILES: [OH:1][C:2]1[C:9]([CH3:10])=[C:8]([OH:11])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH3:28])=[CH:22][CH:21]=1.O>CN(C=O)C>[CH2:27]([O:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][O:11][C:8]2[CH:7]=[CH:6][C:3]([CH:4]=[O:5])=[C:2]([OH:1])[C:9]=2[CH3:10])=[CH:21][CH:22]=1)[CH3:28]
Reactant: CCOc1ccc(CCl)cc1
Reactant: Cc1c(O)ccc(C=O)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOc1ccc(COc2ccc(C=O)c(O)c2C)cc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 17.9 %

Procedure:
To a solution of 2,4-dihydroxy-3-methylbenzaldehyde (1.00 g, 6.57 mmol) in DMF (20 mL) were added potassium carbonate (1.36 g, 9.86 mmol) and 1-(chloromethyl)-4-ethoxybenzene (1.23 g, 7.23 mmol), and the mixture was stirred at room temperature for 15 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed twice with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 3:2) to give the title compound (336 mg, yield 18%) as a white solid.
Reaction SMILES: C([C@H]1COC(=O)N1[C:14]([C@@H:16]1[CH2:20][C:19](=[O:21])[CH2:18][C@H:17]1[C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=1)=[O:15])C1C=CC=CC=1.[OH2:29].[OH-].[Li+].OO>O1CCCC1>[Cl:28][C:25]1[CH:26]=[CH:27][C:22]([C@@H:17]2[CH2:18][C:19](=[O:21])[CH2:20][C@H:16]2[C:14]([OH:15])=[O:29])=[CH:23][CH:24]=1
Reactant: O
Reactant: O=C1C[C@@H](C(=O)N2C(=O)OC[C@@H]2Cc2ccccc2)[C@H](c2ccc(Cl)cc2)C1
Agent: OO
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C1C[C@@H](C(=O)O)[C@H](c2ccc(Cl)cc2)C1
Temperature: 0 °C

Procedure:
A 100 mL round bottom flask equipped with a magnetic stir bar was charged with a solution of 1.002 g (2.52 mmol) of the product of Step C dissolved in 41 mL of tetrahydrofuran followed by the addition of 9 mL of water. The reaction mixture was stirred and cooled to 0° C. with an external ice-water bath and a fine suspension was observed. Lithium hydroxide (0.120 g, 5.02 mmol) was added followed by 1.71 mL (15.1 mmol) of 30% aqueous hydrogen peroxide. The reaction mixture was stirred for 1 h at room temperature during which time it developed a yellow color. The reaction mixture was then quenched by addition of excess saturated aqueous sodium sulfite and the tetrahydrofuran was removed in vacuo. The residue was extracted three times with methylene chloride to remove the oxazolidinone, then the aqueous layer was adjusted to pH=1-2 with 1 N hydrochloric acid. The aqueous layer was then extracted three times with ethyl acetate. The combined organic layers were dried (Na2SO4), filtered and evaporated in vacuo. The residual amorphous yellow solid (0.412 g) was used directly in the next step without further purification.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([CH3:11])[C:3]=1[NH2:12].[CH:13]1([CH2:18][C:19](Cl)=[O:20])[CH2:17][CH2:16][CH2:15][CH2:14]1.O>C(#N)C>[CH:13]1([CH2:18][C:19]([NH:12][C:3]2[C:2]([CH3:1])=[CH:7][C:6]([N+:8]([O-:10])=[O:9])=[CH:5][C:4]=2[CH3:11])=[O:20])[CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: Cc1cc([N+](=O)[O-])cc(C)c1N
Reactant: O=C(Cl)CC1CCCC1
Solvent: CC#N
Solvent: O
Product: Cc1cc([N+](=O)[O-])cc(C)c1NC(=O)CC1CCCC1
Temperature: 150 °C
Yield: 89 %

Procedure:
2,6-Dimethyl-4-nitro-phenylamine (0.98 g) and cyclopentylacetyl chloride (0.99 mL) were dissolved in acetonitrile (10 mL) and heated to 150° C. for 5 minutes in a sealed microwave process vial. Water (10 mL) was added to the reaction mixture, and the product was collected by filtration and washed with water (20 mL) and heptane (20 mL) to furnish 1.45 g (89% yield) of the title compound as a yellow solid. 1H NMR (500 MHz, DMSO-d6): 1.24 (m, 2H), 1.54 (m, 2H), 1.63 (m, 2H), 1.79 (m, 2H), 2.25 (s, 6H), 2.27 (m, 1H), 2.36 (d, 2H), 7.98 (s, 2H), 9.56 (s, 1H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5](I)=[C:6]([CH3:8])[CH:7]=1.C([Sn](CCCC)(CCCC)[C:15]1[S:16][CH:17]=[CH:18][N:19]=1)CCC>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:15]2[S:16][CH:17]=[CH:18][N:19]=2)=[C:6]([CH3:8])[CH:7]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1nccs1
Reactant: Cc1cc(Br)ccc1I
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: C1CCOC1
Product: Cc1cc(Br)ccc1-c1nccs1
Temperature: 90 °C
Yield: 40 %

Procedure:
A solution of 5-bromo-2-iodotoluene (0.15 g, 1.18 mmol) and 2-tributylstannylthiazole (0.45 g, 1.18 mmol) in THF (4 mL) in a sealed tube was degassed with a balloon of argon for 5 min. Bis(triphenylphosphine)palladium(II) chloride (1.18 mmol) was added, the reaction was capped and heated at 90° C. for 6 h. Silica gel chromatography eluting with 100% hexanes yielded 0.12 g of desired product: 1H NMR (500 MHZ, CDCl3) δ 7.95 (d, J=3.0 Hz, 1H), 7.63 (d, J=8.3 Hz, 1H), 7.50 (s, 1H), 7.44 (d, J=2.8 Hz, 2H), 2.60 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:17]([O:20][CH2:21][C:22](Cl)=[O:23])(=[O:19])[CH3:18]>CN(C)C1C=CN=CC=1.Cl>[CH:6]([C:5]1[CH:8]=[CH:9][C:2]([NH:1][C:22]([CH2:21][O:20][C:17](=[O:19])[CH3:18])=[O:23])=[CH:3][CH:4]=1)=[O:7]
Reactant: CC(=O)OCC(=O)Cl
Reactant: Nc1ccc(C=O)cc1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCN(CC)CC
Product: CC(=O)OCC(=O)Nc1ccc(C=O)cc1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 60.5 %

Procedure:
To a solution of 4-aminobenzaldehyde (1 g, 8.52 mmol) at 0° C. under nitrogen atmosphere were added triethylamine (2.3 mL, 16.5 mmol), 4-dimethylaminopyridine (0.1 g, 0.82 mmol) and acetoxyacetyl chloride (1.77 mL, 16.5 mmol). The reaction mixture was allowed to warm up to room temperature and was stirred for 2.5 h. Triethylamine (1.15 mL, 8.25 mmol) and acetoxyacetyl chloride (0.88 mL, 8.25 mmol) were added and the reaction mixture was stirred for 1 h more. The reaction mixture was poured into a 1 M hydrochloric acid solution (60 mL), then extracted with methylene chloride (20 mL×3) and the combined organic layers were washed with saturated aqueous sodium bicarbonate solution and dried over anhydrous sodium sulfate. The crude solid (3.17 g) was purified by flash column chromatography to provide pure acetic acid (4-formyl-phenylcarbamoyl)-methyl ester (1.14 g, 62% yield) as an orange solid. A mixture of 2-amino-4,6-dimethoxy-benzamide (0.15 g, 0.76 mmol), Acetic acid (4-formyl-phenylcarbamoyl)-methyl ester (0.169 g, 0.76 mmol), sodium hydrogensulfite (0.087 g, 0.84 mmol) and p-toluenesulfonic acid (15 mg, 0.076 mmol) in N,N-dimethyl acetamide (5 mL) was stirred at 150° C. for 4.5 h under nitrogen. The reaction mixture was cooled to room temperature and diluted with cold water (60 mL) to obtain a yellow solid. The yellow solid was filtered off, washed with cold water (20 mL×2), methanol and dried under vacuum to provide crude compound (230 mg, 75%).