Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:14])[CH3:13])=[CH:7][C:6]=1[F:15])=[O:4].[CH3:16][C:17]1[NH:21][C:20](=[O:22])[C:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([CH2:23][CH2:24][CH3:25])[N:18]=1.C(=O)([O-])[O-].[K+].CC(C)=O.[K+].C1CCCCC1.C(OCC)(=O)C>C(OCC)(=O)C>[F:15][C:6]1[CH:7]=[C:8]([NH:11][C:12](=[O:14])[CH3:13])[CH:9]=[CH:10][C:5]=1[C:3](=[O:4])[CH2:2][N:21]1[C:20](=[O:22])[C:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([CH2:23][CH2:24][CH3:25])[N:18]=[C:17]1[CH3:16]
Reactant: CCCC1(c2ccccc2)N=C(C)NC1=O
Reactant: CC(=O)Nc1ccc(C(=O)CBr)c(F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCCCC1
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: CCCC1(c2ccccc2)N=C(C)N(CC(=O)c2ccc(NC(C)=O)cc2F)C1=O
Temperature: 70 °C
Yield: 93.4 %

Procedure:
To a mixture of N-[4-(2-bromo-acetyl)-3-fluoro-phenyl]-acetamide (1.1 g, 2.8 mmol) and (+/−)-2-methyl-5-phenyl-5-propyl-3,5-dihydro-imidazol-4-one (541 mg, 2.5 mmol) in 5 mL acetone potassium carbonate (698 mg, 5 mmol) is added and the reaction mixture is heated at 70° C. for 10 min in the microwave oven (Biotage Initiator). The mixture is cooled to room temperature, filtered and the filtrate evaporated to yield the crude product which is subjected to flash chromatography. ISCO Companion CombiFlash, 40 g silica gel, cyclohexane/ethyl acetate-gradient, ethyl acetate 0-100% to give (+/−)-N-{3-fluoro-4-[2-(2-methyl-5-oxo-4-phenyl-4-propyl-4,5-dihydro-imidazol-1-yl)-acetyl]-phenyl}-acetamide (956 mg, 71%). LC/MS at 254 nm; [M+H] 410; Rt 2.850 min
Reaction SMILES: [C:1]1([N:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14]/[CH:15]=[CH:16]\[C:17]3[CH:22]=[CH:21][C:20]([C:23]4[NH:27][C:26]5[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=5[N:24]=4)=[CH:19][CH:18]=3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>[Pd].CO>[NH3:7].[C:1]1([N:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][CH2:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]4[NH:24][C:25]5[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=5[N:27]=4)=[CH:19][CH:18]=3)[CH2:9][CH2:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C(=C\c1ccc(-c2nc3ccccc3[nH]2)cc1)\CCN1CCN(c2ccccc2)CC1
Agent: [Pd]
Solvent: CO
Product: N
Product: c1ccc(N2CCN(CCCCc3ccc(-c4nc5ccccc5[nH]4)cc3)CC2)cc1
Yield: 123.4 %

Procedure:
(Z)-2-[4-[4-(4-Phenyl-1-piperazinyl)-1-butenyl]phenyl]-1H-benzimidazole (Example 21) (0.5 g) is hydrogenated with 5% palladium on carbon (0.1 g) in methanol (10 mL) and filtered. The filtrate is evaporated and the residue is purified by MPLC on silica gel eluting with 100:8:1 dichloromethane: ethanol:0.880 aqueous ammonia to give 0.31 g of the title compound as a white solid; mp 239°-243° C.
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].[C:9]([O:12][CH2:13][CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH3:18])(=[O:11])[CH3:10].[CH:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][C:20]=1[C:29](Cl)=[O:30]>C1COCC1>[CH:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][C:20]=1[C:29](=[O:30])[CH2:10][C:9]([O:12][CH2:13][CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH3:18])=[O:11]
Reactant: CC/C=C\CCOC(C)=O
Reactant: O=C(Cl)c1ccc2ccccc2c1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CC/C=C\CCOC(=O)CC(=O)c1ccc2ccccc2c1
Temperature: -20 °C
Reaction time: 0.25 h

Procedure:
Lithium diisopropylamide (133.0 mL of a 2.0M solution, 0.266 mol) is placed into a 500 mL three-necked round-bottomed flask fitted with a magnetic stirrer, internal thermometer, argon inlet, and addition funnel. The flask is cooled to -78° C. cis 3-Hexenyl acetate (17.80 g, 0.125 mol) is dissolved in THF (10 mL) and the resulting solution added to the flask over 45 min. Once addition is complete, the mixture is stirred for an additional 15 min. before being treated with a solution of 2-naphthoyl chloride (22.51 g, 0.118 mol) dissolved in THF (30 mL) over 30 min. The mixture is warmed to -20° C. and stirred at that temperature for 18 h. After warming to 0° C., the mixture is quenched with 20% HCl (70 mL). The mixture is poured into a separatory funnel containing ether (150 mL) and water (250 mL). The aqueous layer is extracted with ether (150 mL). The combined organic layers are washed with saturated NaHCO3 solution (2×100 mL), water (2×150 mL) and brine (150 mL), dried over MgSO4 and filtered. The solvent is removed by rotary evaporation to give an orange/red oil. The oil is purified by column chromatography (elution with 2% ethyl acetate/petroleum ether) to yield a colorless oil having 1H and 13C NMR spectra consistent with the desired product.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[C:9]([CH3:11])[C:8]([O:12][CH3:13])=[CH:7][C:4]=1[CH:5]=O.Cl.[NH2:15]O.C(OC(=O)C)(=O)C>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:10]=[C:9]([CH3:11])[C:8]([O:12][CH3:13])=[CH:7][C:4]=1[C:5]#[N:15]
Reactant: COc1cc(C=O)c(OC)cc1C
Reactant: NO
Agent: Cl
Solvent: c1ccncc1
Solvent: CC(=O)OC(C)=O
Product: COc1cc(C#N)c(OC)cc1C
Temperature: 105 °C
Reaction time: 2 h

Procedure:
By analogy to steps outlined in J. Med. Chem. 1976, 19(12), 1400-1404. 2,5-dimethoxy-4-methylbenzaldehyde (14.8 g, 82.2 mmol) is dissolved in pyridine (300 mL) and to it is added hydroxylamine hydrochloride (6.8 g, 98.6 mmol). The suspension is heated at 105° C. for 2 h. Acetic anhydride (15.5 mL, 164 mmol) is then added to the reaction and stirring is continued for another 2 h. The solution is evaporated to dryness and partitioned between EtOAc and saturated aqueous NaHCO3. The organic fraction is dried (Na2SO4) and evaporated to give a yellow solid which is taken up in hexanes and filtered to give 2,5-dimethoxy-4-methylbenzonitrile as a white solid. (cas # 51267-09-5) MS (ESI) m/z 178.2 (M+H).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH:12]([CH3:14])[CH3:13])[CH2:10][CH2:9][C:8]([C:15]([O:17][CH3:18])=[O:16])=[CH:7][C:6]=2[CH:19]=1.B([O-])([O-])O[C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][O:31][CH2:32][CH2:33][CH2:34][CH3:35])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].O>C1(C)C=CC=CC=1.C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:32]([O:31][CH2:30][CH2:29][O:28][C:25]1[CH:24]=[CH:23][C:22]([C:2]2[CH:3]=[CH:4][C:5]3[N:11]([CH:12]([CH3:14])[CH3:13])[CH2:10][CH2:9][C:8]([C:15]([O:17][CH3:18])=[O:16])=[CH:7][C:6]=3[CH:19]=2)=[CH:27][CH:26]=1)[CH2:33][CH2:34][CH3:35]
Reactant: CCCCOCCOc1ccc(OB([O-])[O-])cc1
Reactant: COC(=O)C1=Cc2cc(Br)ccc2N(C(C)C)CC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: O
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)OC)CCN3C(C)C)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 65.2 %

Procedure:
In toluene/ethanol/water (=10/1/1, 20.4 ml) was dissolved methyl 7-bromo-1-isopropyl-2,3-dihydro-1-benzazepine-4-carboxylate (0.50 g). To the solution were added 4-(2-butoxyethoxy)phenyl borate (0.48 g) and potassium carbonate (0.47 g), and the mixture was stirred for 30 minutes under argon atmosphere. To the mixture was added tetrakistriphenylphosphinepalladium (0.10 g), and the mixture was heated to reflux for 14 hours. After cooled to room temperature, the reaction solution was added to water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried with magnesium sulfate. The solvent was removed under reduced pressure, and the resulting residue was purified with silica gel column chromatography (hexane/ethyl acetate=20/1→8/1) to give methyl 7-[4-(2-butoxyethoxy)phenyl]-1-isopropyl-2,3-dihydro-1-benzazepine-4-carboxylate (0.44 g). Methyl 7-[4-(2-butoxyethoxy)phenyl]-1-isopropyl-2,3-dihydro-1-benzazepine-4-carboxylate (0.44 g) was dissolved in THF (8.8 ml)/methanol (8.8 ml). To the solution was added 1N sodium hydroxide (4.4 ml), and the mixture was stirred at 50° C. for 4 hours. After cooled to room temperature, pH was adjusted to approximate. 5 with 1N hydrochloric acid, and the solvent was concentrated to half under reduced pressure. The concentrated material was extracted with ethyl acetate/THF, and the extract was washed with saturated brine and dried with magnesium sulfate. The solvent was removed under reduced pressure, and the resulting residue was washed with hexane/ethyl acetate (12/1) to give 7-[4-(2-butoxyethoxy)phenyl]-1-isopropyl-2,3-dihydro-1-benzazepine-4-carboxylic acid (320 mg).
Reaction SMILES: C1C=CN=C(NS(C2C=CC(N=N[C:19]3[CH:20]=[CH:21][C:22]([OH:28])=[C:23]([C:25]([OH:27])=[O:26])[CH:24]=3)=CC=2)(=O)=O)C=1.C1C([NH2:35])=CC(C(O)=O)=C(O)C=1.C1C(N=NC2C=CC(O)=C(C(O)=O)C=2)=CC(C(O)=O)=C(O)C=1.C1C(C(NCCC(O)=O)=O)=CC=C(N=NC2C=CC(O)=C(C(O)=O)C=2)C=1>>[NH2:35][O:28][C:22]1[C:23](=[CH:24][CH:19]=[CH:20][CH:21]=1)[C:25]([OH:27])=[O:26]
Reactant: Nc1ccc(O)c(C(=O)O)c1
Reactant: O=C(O)c1cc(N=Nc2ccc(S(=O)(=O)Nc3ccccn3)cc2)ccc1O
Agent: O=C(O)CCNC(=O)c1ccc(N=Nc2ccc(O)c(C(=O)O)c2)cc1
Agent: O=C(O)c1cc(N=Nc2ccc(O)c(C(=O)O)c2)ccc1O
Product: NOc1ccccc1C(=O)O

Procedure:
sulfasalazine, mesalazine, olsalazine, balsalazide, salazosulfapyridine.
Reaction SMILES: C([NH:8][C:9]1[S:10][C:11]([Cl:20])=[CH:12][C:13]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(OC(C)(C)C)=O.FC(F)(F)C(O)=O>ClCCl.CN(C=O)C>[NH2:8][C:9]1[S:10][C:11]([Cl:20])=[CH:12][C:13]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CC(C)(C)OC(=O)Nc1sc(Cl)cc1-c1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Solvent: ClCCl
Product: Nc1sc(Cl)cc1-c1ccccc1

Procedure:
2-(N-Boc-amino)-5-chloro-3-phenyl-thiophene (66 mg, 0.21 mmol) was treated with trifluoroacetic acid (1 ml) in dichloromethane (3 ml) at ambient temperature for 1 hr. The mixture was diluted with DMF (1 ml) and the more volatile materials removed under reduced pressure. The resulting DMF solution of 2-amino-5-chloro-3-phenylthiophene was used in the subsequent coupling step without purification.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([OH:10])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[Br:11][CH2:12][CH2:13][CH2:14]Br.C(=O)([O-])[O-].[K+].[K+]>C(C(C)=O)C>[N+:1]([C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][CH:9]=1)[O:10][CH2:14][CH2:13][CH2:12][Br:11])([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1cccc(O)c1
Reactant: BrCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: O=[N+]([O-])c1cccc(OCCCBr)c1
Yield: 94.7 %

Procedure:
13.9 g of 3-nitrophenol, 101 g of 1,3-dibromopropane and 15.2 g of anhydrous potassium carbonate were reacted in 100 ml of methyl ethyl ketone for 2 hours by heating under reflux. After completion of the reaction, insoubles were removed from the reaction mixture by filtration, and the filtrate was then concentrated. Next, the resultant concentrate was dissolved in 300 ml of chloroform, and this chloroform solution was further washed with water. Afterward, the washed organic layer was dried over anhydrous magnesium sulfate and then treated with under reduced pressure to distill off the solvent, thereby obtaining 24.6 g of 3-(3-nitrophenoxy)propyl bromide (Compound d) in an oily state. This was used for a subsequent reaction without purifying.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]1[O:12][C:13]([CH:16]=[O:17])=[CH:14][CH:15]=1.[BH4-].[Na+].[CH3:21]O.[C:23](=[O:26])([O-])[O-].[K+].[K+]>C(O)C.O>[CH3:1][O:2][C:3](=[O:18])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]1[O:12][C:13]([CH2:16][O:17][C:23](=[O:26])[CH3:21])=[CH:14][CH:15]=1
Reactant: COC(=O)CCCCCCCc1ccc(C=O)o1
Reactant: CO
Reactant: O=C([O-])[O-]
Agent: [BH4-]
Agent: [K+]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: COC(=O)CCCCCCCc1ccc(COC(C)=O)o1
Temperature: 10 °C
Reaction time: 1.5 h

Procedure:
8.22 g of 8-(5-formyl-2-furyl)-octanoic acid methyl ester were dissolved in 100 ml of absolute ethanol, whereupon the solution was cooled to 10° C. 5.0 g. of sodium borohydride (98%) in 100 ml of ethanol were added in one portion while stirring. After 1.5 hours, 10 ml of methanol were added and the solution poured into 150 ml of water. 50 g of potassium carbonate were then added, the temperature being kept below 18° C. The solution was then extracted several times with ether while adding further quantities of potassium carbonate. After drying, the ether was driven off. 10 ml of pyridine were then added to the product, after which the mixture was again dried. The residue was dissolved in 65 ml of pyridine, after which 65 ml of acetic anhydride were added. The mixture was allowed to stand overnight and was then distilled under vacuum. A product having a boiling point of 148°-149° C at 0.2 mm Hg was obtained.
Reaction SMILES: C(O)=O.[NH2:4][CH2:5][CH2:6][C:7]1[CH:27]=[CH:26][C:10]([NH:11][CH:12]2[CH2:17][CH2:16][N:15]([C:18]([NH:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[O:19])[CH2:14][CH2:13]2)=[CH:9][CH:8]=1.C([Si]([O:45][C:46]1[CH:51]=[CH:50][C:49]([O:52][CH2:53][CH:54]2[CH2:56][O:55]2)=[CH:48][CH:47]=1)(C1C=CC=CC=1)C1C=CC=CC=1)(C)(C)C>>[F:24][C:22]([F:25])([F:23])[CH2:21][NH:20][C:18]([N:15]1[CH2:16][CH2:17][CH:12]([NH:11][C:10]2[CH:9]=[CH:8][C:7]([CH2:6][CH2:5][NH:4][CH2:56][C@H:54]([OH:55])[CH2:53][O:52][C:49]3[CH:50]=[CH:51][C:46]([OH:45])=[CH:47][CH:48]=3)=[CH:27][CH:26]=2)[CH2:13][CH2:14]1)=[O:19]
Reactant: NCCc1ccc(NC2CCN(C(=O)NCC(F)(F)F)CC2)cc1
Reactant: CC(C)(C)[Si](Oc1ccc(OCC2CO2)cc1)(c1ccccc1)c1ccccc1
Solvent: O=CO
Product: O=C(NCC(F)(F)F)N1CCC(Nc2ccc(CCNC[C@H](O)COc3ccc(O)cc3)cc2)CC1
Yield: 18.1 %

Procedure:
4-[4-(2-Aminoethyl)anilino]-N-(2,2,2-trifluoroethyl)-1-piperidinecarboxamide formate (0.60 g, 1.53 mmol) was reacted with tert-butyl-(4-oxiranylmethoxy-phenoxy)-diphenyl-silane (0.550 g, 1.38 mmol) according to Procedure G to give the title compound (eluant: 20:1 chloroform-methanol) (0.188 g, 0.25 mmol).
Reaction SMILES: O.O.[C:3]([O-:6])(=[O:5])[CH3:4].[U+2](=O)=O.[C:10]([O-])(=[O:12])[CH3:11]>[Co]>[C:10]1(=[O:12])[O:6][C:3](=[O:5])[CH:4]=[CH:11]1.[CH3:10][CH2:11][CH2:3][CH3:4]
Reactant: CC(=O)[O-]
Agent: [Co]
Agent: O=[U+2]=O
Solvent: O
Product: CCCC
Product: O=C1C=CC(=O)O1

Procedure:
Fluid bed catalyst having the formula V1.0 P1.2 U0.2 Ox was prepared according to the procedure set forth in Examples 1-7 above, except that 935.5 g uranyl acetate dihydrate was substituted for the cobalt compound. Results of the fluid bed (80 cc) production of maleic anhydride from n-butane using the catalyst of Example 8 are listed in Table I.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([O:22][CH3:23])[CH2:13][CH2:12][C:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)([C:14]#N)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[OH-:24].[K+].C(O)C[OH:28]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([O:22][CH3:23])[CH2:13][CH2:12][C:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)([C:14]([OH:28])=[O:24])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1
Reactant: COC1(c2ccc(F)cc2)CCC(C#N)(c2ccccc2)CC1
Reactant: [OH-]
Reactant: OCCO
Agent: [K+]
Product: COC1(c2ccc(F)cc2)CCC(C(=O)O)(c2ccccc2)CC1
Temperature: 200 °C
Reaction time: 5 h

Procedure:
500 mg of 4-(4-fluorophenyl)-4-methoxy-1-phenylcyclohexanecarbonitrile were dissolved in 30 ml of ethylene glycol and 272 mg of potassium hydroxide were added. The reaction mixture was subsequently stirred for 5 h at 200° C. After cooling, the reaction mixture was poured onto an ice/water mixture and extracted three times with MTB. The aqueous phase was acidified to pH=1 with 2 N hydrochloric acid. The precipitated crude product was filtered off with suction and dissolved in a little hot toluene. The crystals deposited during cooling were filtered off with suction and dried. 450 mg of the title compound were obtained as a white solid.
Reaction SMILES: [CH3:1][C:2]1([C:7]2[O:11][C:10]([CH2:12][N:13]3[N:17]=[C:16]([NH2:18])[CH:15]=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[C:19]1([CH3:34])[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:25]1[O:29][C:28]([CH3:30])=[N:27][C:26]=1[C:31](O)=[O:32]>>[C:2]([C:7]1[O:11][C:10]([CH2:12][N:13]2[N:17]=[C:16]([NH:18][C:31]([C:26]3[N:27]=[C:28]([CH3:30])[O:29][C:25]=3[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[CH3:34])=[O:32])[CH:15]=[N:14]2)=[CH:9][CH:8]=1)(=[O:6])[CH3:1]
Reactant: Cc1nc(C(=O)O)c(-c2ccccc2C)o1
Reactant: CC1(c2ccc(Cn3ncc(N)n3)o2)OCCO1
Product: CC(=O)c1ccc(Cn2ncc(NC(=O)c3nc(C)oc3-c3ccccc3C)n2)o1

Procedure:
Following general procedure A followed by L, starting from 2-[5-(2-methyl-[1,3]dioxolan-2-yl)-furan-2-ylmethyl]-2H-[1,2,3]triazol-4-ylamine and 5-(o-tolyl)-2-methyl-oxazole-4-carboxylic acid.
Reaction SMILES: C[O:2][C:3]([C:5]1([CH:11]=[N:12][O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4].[OH-].[Na+].Cl>C1COCC1.CO.O>[CH2:14]([O:13][N:12]=[CH:11][C:5]1([C:3]([OH:4])=[O:2])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: COC(=O)C1(C=NOCc2ccccc2)CCCCC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)C1(C=NOCc2ccccc2)CCCCC1
Temperature: 25 °C
Reaction time: 40 h

Procedure:
A mixture of 1-(benzyloxyimino-methyl)-cyclohexanecarboxylic acid methyl ester (1.75 g, 6.36 mmol) and sodium hydroxide (0.76 g, 19.1 mmol) in THF (10 mL), methanol (10 mL) and water (5 mL) was stirred at room temperature for 40 h. The reaction mixture was acidified to pH 4 with 3N aqueous HCl and was extracted with EtOAc (50 mL×2). The combined organic layers were dried (MgSO4) and were evaporated in vacuo to yield the title compound as a yellow oil. (1.59 g, 96%). MH+262.
Reaction SMILES: [CH3:1][C:2](=[C:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)[CH3:3].CCN(C(C)C)C(C)C.[Br:19][C:20]1[C:21](Cl)=[C:22]([C:28](=[O:35])[C:29]([O:31][CH:32]([CH3:34])[CH3:33])=[O:30])[C:23]([CH3:27])=[N:24][C:25]=1[CH3:26]>CC#N.CCOCC>[Br:19][C:20]1[C:21]([N:7]2[CH2:8][CH2:9][C:4](=[C:2]([CH3:3])[CH3:1])[CH2:5][CH2:6]2)=[C:22]([C:28](=[O:35])[C:29]([O:31][CH:32]([CH3:33])[CH3:34])=[O:30])[C:23]([CH3:27])=[N:24][C:25]=1[CH3:26]
Reactant: Cc1nc(C)c(C(=O)C(=O)OC(C)C)c(Cl)c1Br
Reactant: CC(C)=C1CCNCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Solvent: CCOCC
Product: CC(C)=C1CCN(c2c(Br)c(C)nc(C)c2C(=O)C(=O)OC(C)C)CC1
Temperature: 80 °C
Reaction time: 24 h
Yield: 61.6 %

Procedure:
To a solution of 4-(propan-2-ylidene)piperidine (500 mg, 3.99 mmol) and DIEA (2.1 mL, 11.98 mmol) in anhydrous CH3CN (30 mL) was added isopropyl 2-(5-bromo-4-chloro-2,6-dimethylpyridin-3-yl)-2-oxoacetate (1.48 g, 3.99 mmol) at rt. The resulting mixture was placed in a pre-heated oil bath (80° C.) and stirred for 24 h; cooled, diluted with ether, washed with water, brine, and dried (MgSO4). The crude product was charged (DCM) to an 80 g ISCO silica gel cartridge and gradient eluted (0-35% EtOAc/hexanes) using an Isolera chromatography station gave isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-(propan-2-ylidene)piperidin-1-yl)pyridin-3-yl)-2-oxoacetate 1.04 g (61.8%). 1H NMR (500 MHz, DMSO-d6) δ 5.09-5.04 (m, 1H), 3.50-3.48 (br. s, 2H), 3.03 (br. s, 2H), 2.60 (s, 3H), 2.30 (s, 3H), 2.23 (br. s, 4), 1.64 (s, 6H), 1.25 (d, J=6.2 Hz, 6H). UPLC (M+H)=425.3.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]([CH2:20][C:21]([OH:23])=O)[S:10]([C:13]1[C:14]([CH3:19])=[CH:15][CH:16]=[CH:17][CH:18]=1)(=[O:12])=[O:11].[CH2:24]([NH:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]([CH3:36])[CH3:35])=[CH:30][CH:29]=1)[CH3:25]>>[CH3:36][N:34]([CH3:35])[C:31]1[CH:32]=[CH:33][C:28]([CH2:27][N:26]([CH2:24][CH3:25])[C:21](=[O:23])[CH2:20][N:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[S:10]([C:13]2[C:14]([CH3:19])=[CH:15][CH:16]=[CH:17][CH:18]=2)(=[O:11])=[O:12])=[CH:29][CH:30]=1
Reactant: COc1ccccc1N(CC(=O)O)S(=O)(=O)c1ccccc1C
Reactant: CCNCc1ccc(N(C)C)cc1
Product: CCN(Cc1ccc(N(C)C)cc1)C(=O)CN(c1ccccc1OC)S(=O)(=O)c1ccccc1C

Procedure:
prepared by reaction of [(2-methoxy-phenyl)-(toluene-2-sulfonyl)-amino]-acetic acid with (4-ethylaminomethyl-phenyl)-dimethyl-amine
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[C:7]([C:9]([C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)([CH3:11])[CH3:10])[CH:6]=[CH:5][C:3]=1[OH:4].C(=O)([O-])[O-].[K+].[K+].F[C:26]1[CH:40]=[CH:39][C:29]([C:30]([C:32]2[CH:37]=[CH:36][C:35](F)=[CH:34][CH:33]=2)=[O:31])=[CH:28][CH:27]=1.C1(C)C=CC=CC=1>CN(C)C(=O)C>[CH3:1][C:2]1[CH:8]=[C:7]([C:9]([C:12]2[CH:13]=[CH:14][C:15]([OH:18])=[CH:16][CH:17]=2)([CH3:11])[CH3:10])[CH:6]=[CH:5][C:3]=1[OH:4].[C:30]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)(=[O:31])[C:29]1[CH:39]=[CH:40][CH:26]=[CH:27][CH:28]=1
Reactant: O=C(c1ccc(F)cc1)c1ccc(F)cc1
Agent: Cc1cc(C(C)(C)c2ccc(O)cc2)ccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CC(=O)N(C)C
Product: O=C(c1ccccc1)c1ccccc1

Procedure:
Polymerization was carried out similar to the P(BPZ-BNZPH) polymerization, except methylbisphenol-A (10.0000 g, 39.00 mmol), potassium carbonate (10.782 g, 78.00 mmol), 4,4′-difluorobenzophenone (8.5102 g, 39.00 mmol), toluene (50 g) and N,N-dimethylacetamide (85 g) were used. The yield was about 15.34 g. The number average molecular weight of the polymer was about 8.2 K.
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[H][H].Cl[CH2:14][CH2:15][CH2:16][C:17]#[CH:18]>CS(C)=O.O>[F:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:18][CH2:17][CH2:16][C:15]#[CH:14])=[CH:6][CH:5]=1
Reactant: [H][H]
Reactant: Oc1ccc(F)cc1
Reactant: C#CCCCCl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: C#CCCCOc1ccc(F)cc1
Temperature: 65 °C
Yield: 99.6 %

Procedure:
To a suspension of 960 mg (40 mmol) of sodium hydride in 50 mL of dimethyl sulfoxide is added 4.48 g (40 mmol) of 4-fluorophenol. The mixture is stirred until hydrogen evolution has ceased and then 4.10 g (40 mmol, 4.24 mL) of 5-chloro-1-pentyne is added. The mixture is heated to 65° C. for 1 hour, is diluted with water and is extracted with hexane. The hexane extract is washed with 2.5M aqueous sodium hydroxide and saturated brine and is dried over magnesium sulfate. The dried solution is filtered and rotoevaporated to give 7.1 g (99%) of title compound. IR: (film) 3310, 1508 cm-1 ; 1H NMR (CDCl3): δ1.97 (1H, t, J=3 Hz), 1.99 (2H, p, J=6 Hz), 2.40 (2H, dt, J=3, 7 Hz), 4.03 (2H, t, J=6 Hz), 6.84 (2H, m) and 6.96 (2H, t, J=8 Hz).
Reaction SMILES: [C:1](=[S:3])=[S:2].[Br:4][C:5]1[CH:11]=[CH:10][C:8]([NH2:9])=[CH:7][CH:6]=1.[CH2:12](N(CC)CC)C.IC>C(OCC)C>[Br:4][C:5]1[CH:11]=[CH:10][C:8]([NH:9][C:1]([S:3][CH3:12])=[S:2])=[CH:7][CH:6]=1
Reactant: CCN(CC)CC
Reactant: Nc1ccc(Br)cc1
Reactant: S=C=S
Solvent: CI
Solvent: CCOCC
Product: CSC(=S)Nc1ccc(Br)cc1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 89.2 %

Procedure:
To a stirred solution of carbon disulfide (6 mL, 100 mmol) at 0 ° C. under a nitrogen atmosphere was added a mixture of p-bromoaniline (1.72 g, 10 mmol) and triethylamine (1.4 mL, 10 mmol) dropwise via an addition funnel. The reaction mixture was stirred at 0 ° C. for 1.5 h, and then allowed to warm to room temperature overnight. To the reaction mixture was added iodomethane (0.62 mL, 10 mmol). The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with diethyl ether (40 mL), and the resulting precipitate was filtered off. The filtrate was concentrated under reduced pressure and trituration of the residue with hexane afforded the title compound of Step E (2.34 g) as a solid melting at 111-112 ° C. 300 MHz 1H NMR (CDCl3): δ 8.67 (s,1H), 7.53 (d,2H), 7.38 (d,2H), 2.67 (s,3H).