Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([CH3:13])([CH3:12])[NH2:11])=[CH:4][CH:3]=1.FC(F)(F)[C:16]1[CH:17]=[C:18]([C:22]([CH:24]=O)=[O:23])[CH:19]=[CH:20][CH:21]=1.C1(C(C=O)=O)C=CC=CC=1>>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([NH:11][CH2:24][CH:22]([OH:23])[C:18]2[CH:19]=[CH:20][CH:21]=[CH:16][CH:17]=2)([CH3:13])[CH3:12])=[CH:4][CH:3]=1
Reactant: O=CC(=O)c1cccc(C(F)(F)F)c1
Reactant: Cc1ccc(CCC(C)(C)N)cc1
Agent: O=CC(=O)c1ccccc1
Product: Cc1ccc(CCC(C)(C)NCC(O)c2ccccc2)cc1

Procedure:
The title compound was prepared in the manner described in Example 9, replacing 2-(4-methylphenyl)-1,1-dimethylethanamine by 3-(4-methylphenyl)-1,1-dimethylpropanamine and 3-trifluoromethylphenyl glyoxal by phenylglyoxal. The chromatographed material was recrystallised from hexane to give the title compound m.p. 107-110. τ (CDCl3) 8.95 (6H, s), 8.2-8.7 (2H, m), 7.8 (3H, s), 7.3-7.7 (4H, m), 5.7-6.5 (2H, m), 5.5 (1H, t, J=6 Hz), 2.9 (4H, s), 2.7 (4H, m).
Reaction SMILES: [N:1]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]([OH:12])=O)=[N+:2]=[N-:3].C1N=CN(C(N2C=NC=C2)=O)C=1.N#N.[CH2:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C1COCC1>[N:1]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]([NH:34][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:12])=[N+:2]=[N-:3]
Reactant: NCc1ccccc1
Reactant: [N-]=[N+]=NCCCCCCC(=O)O
Agent: N#N
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: [N-]=[N+]=NCCCCCCC(=O)NCc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
7-azido-N-(phenylmethyl)heptanamide (65) was synthesized from 7-zidoheptanoic acid (64) as shown above. To 120 mg crude 7-azidoheptanoic acid (64) (0.7 mmol, 1.0 eq) was added 1 mL anhydrous THF. To the stirring solution was added 120 mg CDI (0.74 mmol, 1.06 eq) at room temperature. N2 was rapidly evolved from the yellowish slurry. The resulting transparent solution stirred at room temperature for 0.5 h. To the solution was then added 82.5 mg benzylamine (0.77 mmol, 1.1 eq). The solution was stirred 2 h at room temperature followed by solvent removal in vacuo and silica gel chromatography (2:2:1; petroleum ether:Et2O:EtOAc) to render 65 in as a waxy solid (108 mg, 60%). Lyophilization from 50% aqueous CH3CN afforded a fluffy white powder. m.p. slightly above ambient temperature.
Reaction SMILES: [F:1][C:2]([F:28])([F:27])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([N:9]2[CH2:14][C@@H:13]3[CH2:15][C@H:10]2[CH2:11][N:12]3[C:16]([C@@:18]23[CH2:25][CH2:24][CH2:23][C@@H:22]2[CH2:21][C:20](=O)[CH2:19]3)=[O:17])[CH:4]=1.[NH:29]1[CH2:34][CH2:33][CH:32]([C:35]2[CH:36]=[C:37]([CH:43]=[CH:44][CH:45]=2)[C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:31][CH2:30]1.[BH4-].[Na+].C(=O)(O)[O-].[Na+].C(OC(C)C)(=O)C1C=CC=CC=1>ClC(Cl)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].CO>[F:28][C:2]([F:27])([F:1])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([N:9]2[CH2:14][C@@H:13]3[CH2:15][C@H:10]2[CH2:11][N:12]3[C:16]([C@@:18]23[CH2:25][CH2:24][CH2:23][C@@H:22]2[CH2:21][C@H:20]([N:29]2[CH2:34][CH2:33][CH:32]([C:35]4[CH:36]=[C:37]([CH:43]=[CH:44][CH:45]=4)[C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:31][CH2:30]2)[CH2:19]3)=[O:17])[CH:4]=1
Reactant: CCOC(=O)c1cccc(C2CCNCC2)c1
Reactant: O=C1C[C@H]2CCC[C@@]2(C(=O)N2C[C@@H]3C[C@H]2CN3c2cc(C(F)(F)F)ccn2)C1
Agent: [Ti+4]
Agent: CC(C)OC(=O)c1ccccc1
Agent: CC(C)[O-]
Solvent: CO
Solvent: CC(Cl)Cl
Product: CCOC(=O)c1cccc(C2CCN([C@H]3C[C@H]4CCC[C@@]4(C(=O)N4C[C@@H]5C[C@H]4CN5c4cc(C(F)(F)F)ccn4)C3)CC2)c1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A mixture of Example 9E (200 mg, 0.5 mmol), ethyl 3-(piperidin-4-yl)benzoate (125 mg, 0.56 mmol) in dichloroethane (20 mL) was added titanium(IV) isopropoxide (0.6 ml, 2.03 mmol) at room temperature. The mixture was stirred at room temperature for 12 hours. Sodium borohydride (96.7 mg, 2.54 mmol) and methanol (1 mL) were added to the reaction mixture and stirred for another 2 hours. LC-MS indicated that the reaction was complete. Aqueous Sodium bicarbonate (20 mL) was added to the reaction mixture. The reaction mixture was extracted with dichloromethane (3×30 mL). The organic fractions were dried with sodium sulfate, filtered, and concentrated. The residue was purified by chromatography (eluent: 20 to 80% ethylacetate in petroleum ether) on silica to give a mixture of the title compound and isopropyl benzoate.
Reaction SMILES: [CH3:1][CH:2]([C:8](OCC)=O)[C:3]([O:5]CC)=[O:4].[CH:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][C:14]=1[C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1CBr>O.[Na]>[CH:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][C:14]=1[C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1[CH2:8][CH:2]([CH3:1])[C:3]([OH:5])=[O:4]
Reactant: BrCc1ccccc1-c1ccc2ccccc2c1
Reactant: CCOC(=O)C(C)C(=O)OCC
Agent: [Na]
Solvent: O
Product: CC(Cc1ccccc1-c1ccc2ccccc2c1)C(=O)O
Temperature: 130 °C
Yield: 83774.2 %

Procedure:
70 g (0.37 mmol) of diethyl methylmalonate dissolved in 50 cm3 of H2O-free EtOH were added dropwise at room temperature to 8.5 g (0.37 mmol) of sodium in 100 cm3 of H2O-free EtOH. 110 g (0.37 mmol) of 26 in 200 cm3 of H2O-free EtOH were subsequently added dropwise, and the mixture was refluxed for 3 hours. 62 g (1.1 mol) of KOB dissolved in 100 cm3 of H2O were added at room temperature, and the mixture was refluxed for a further 4 hours. The solvent was removed in vacuo, H2O was added to the residue until the latter had dissolved completely, and the mixture was acidified to pH 1 by means of concentrated aqueous HCl. The precipitate which had formed was filtered off with suction, dried and heated at 130° C. for 1 hour, giving 90 g (84%) of 27 as a viscous oil.
Reaction SMILES: [NH2:1][CH2:2][CH:3]([OH:14])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]([F:13])[CH:7]=1.Cl[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17].C(N(CC)C(C)C)(C)C.CN(C=O)C>C1COCC1.CN(C)C1C=CN=CC=1>[F:13][C:8]1[CH:7]=[C:6]([CH:11]=[CH:10][C:9]=1[F:12])[O:5][CH2:4][CH:3]([OH:14])[CH2:2][NH:1][C:16](=[O:17])[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: NCC(O)COc1ccc(F)c(F)c1
Agent: CN(C)c1ccncc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: O=C(NCC(O)COc1ccc(F)c(F)c1)OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
1 of rac-1-amino-3-(3,4-difluorophenoxy)propan-2-ol (4.9 mmol, 1 equivalent) was dissolved in 16 ml of THF, and 0.76 ml of benzyl chloroformate (0.9 g, 5.4 mmol, 1.1 equivalents) and then 2.6 ml of N,N-diisopropylethylamine (1.9 g, 14.8 mmol, 3 equivalents) and 0.12 g of 4-dimethylaminopyridine were added. The mixture was stirred at RT for 30 min. 2 ml of DMF were then added, and the mixture was stirred at RT overnight. The mixture was concentrated and the residue was then taken up in ethyl acetate. The organic phase was washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered and concentrated. This gave 2.2 g (96% of theory, purity 73%) as a crude product which was reacted without further purification.
Reaction SMILES: [Br:1][C:2]1[C:7]([OH:8])=[C:6]([O:9][CH3:10])[C:5]([O:11][CH:12]([F:14])[F:13])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:22][C:23]1([CH2:27][O:28][CH3:29])[CH2:26][O:25][CH2:24]1>C(#N)C>[Br:1][C:2]1[C:7]([O:8][CH2:22][C:23]2([CH2:27][O:28][CH3:29])[CH2:26][O:25][CH2:24]2)=[C:6]([O:9][CH3:10])[C:5]([O:11][CH:12]([F:13])[F:14])=[CH:4][CH:3]=1
Reactant: COCC1(CBr)COC1
Reactant: COc1c(OC(F)F)ccc(Br)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COCC1(COc2c(Br)ccc(OC(F)F)c2OC)COC1
Temperature: 80 °C
Yield: 70.5 %

Procedure:
To a stirring solution of 6-bromo-3-(difluoromethoxy)-2-methoxyphenol (0.3 g, 1.11 mmol) in acetonitrile (10 mL) was added potassium carbonate (0.46 g, 3.34 mmol) and followed by 3-(bromomethyl)-3-(methoxymethyl)oxetane (0.43 g, 2.22 mmol) and the resultant reaction mixture was heated to 80° C. for 16 h. The reaction mixture was cooled to RT, filtered through celite and the filtrate was concentrated under reduced pressure to afford 3-((6-bromo-3-(difluoromethoxy)-2-methoxyphenoxy)methyl)-3-(methoxymethyl)oxetane as a solid (0.3 g, 70%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH3:17])[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1)=[CH:7]2.[S:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[S:23](Cl)(=[O:25])=[O:24]>>[CH3:17][C:4]1[CH:5]=[C:6]2[C:10](=[C:2]([NH:1][S:23]([C:19]3[S:18][CH:22]=[CH:21][CH:20]=3)(=[O:25])=[O:24])[CH:3]=1)[NH:9][C:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1)=[CH:7]2
Reactant: O=S(=O)(Cl)c1cccs1
Reactant: Cc1cc(N)c2[nH]c(-c3ccccn3)cc2c1
Product: Cc1cc(NS(=O)(=O)c2cccs2)c2[nH]c(-c3ccccn3)cc2c1

Procedure:
7-Amino-5-methyl-2-(pyridin-2-yl)-1H-indole prepared in Step A of Example 1 and 2-thiophenesulfonylchloride were reacted according to the same procedure as Example 22 to give the title compound.
Reaction SMILES: FC(F)(F)C(O)=O.C([O:12][C:13]([CH2:15][C@@H:16]([C:30]([NH:32][C:33]1[CH:38]=[CH:37][C:36]([CH:39]([C:71]2[CH:76]=[CH:75][C:74]([NH:77][C:78](=[O:101])[C@H:79]([CH2:93][C:94]([O:96]C(C)(C)C)=[O:95])[NH:80][C:81](=[O:92])[CH2:82][C:83]3[C:91]4[C:86](=[CH:87][CH:88]=[CH:89][CH:90]=4)[NH:85][CH:84]=3)=[CH:73][CH:72]=2)[C:40]2[CH:45]=[CH:44][C:43]([NH:46][C:47](=[O:70])[C@H:48]([CH2:62][C:63]([O:65]C(C)(C)C)=[O:64])[NH:49][C:50](=[O:61])[CH2:51][C:52]3[C:60]4[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=4)[NH:54][CH:53]=3)=[CH:42][CH:41]=2)=[CH:35][CH:34]=1)=[O:31])[NH:17][C:18](=[O:29])[CH2:19][C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[NH:22][CH:21]=1)=[O:14])(C)(C)C>CO>[NH:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:20]([CH2:19][C:18]([NH:17][C@H:16]([C:30]([NH:32][C:33]2[CH:34]=[CH:35][C:36]([CH:39]([C:71]3[CH:72]=[CH:73][C:74]([NH:77][C:78](=[O:101])[C@H:79]([CH2:93][C:94](=[O:95])[OH:96])[NH:80][C:81](=[O:92])[CH2:82][C:83]4[C:91]5[C:86](=[CH:87][CH:88]=[CH:89][CH:90]=5)[NH:85][CH:84]=4)=[CH:75][CH:76]=3)[C:40]3[CH:45]=[CH:44][C:43]([NH:46][C:47](=[O:70])[C@H:48]([CH2:62][C:63](=[O:64])[OH:65])[NH:49][C:50](=[O:61])[CH2:51][C:52]4[C:60]5[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=5)[NH:54][CH:53]=4)=[CH:42][CH:41]=3)=[CH:37][CH:38]=2)=[O:31])[CH2:15][C:13](=[O:12])[OH:14])=[O:29])=[CH:21]1
Reactant: CC(C)(C)OC(=O)C[C@H](NC(=O)Cc1c[nH]c2ccccc12)C(=O)Nc1ccc(C(c2ccc(NC(=O)[C@H](CC(=O)OC(C)(C)C)NC(=O)Cc3c[nH]c4ccccc34)cc2)c2ccc(NC(=O)[C@H](CC(=O)OC(C)(C)C)NC(=O)Cc3c[nH]c4ccccc34)cc2)cc1
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Product: O=C(O)C[C@H](NC(=O)Cc1c[nH]c2ccccc12)C(=O)Nc1ccc(C(c2ccc(NC(=O)[C@H](CC(=O)O)NC(=O)Cc3c[nH]c4ccccc34)cc2)c2ccc(NC(=O)[C@H](CC(=O)O)NC(=O)Cc3c[nH]c4ccccc34)cc2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 3 %

Procedure:
A methanol solution containing trifluoroacetic acid (40%, 6 ml) was added to the tris[4-[β-t-butoxycarbonyl-N-[2-(1H-indol-3-yl)acetyl]-L-alanyl]aminophenyl]methane (50 mg) at room temperature, and the mixture was stirred at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure, and a portion of the residue was purified by preparative high performance liquid chromatography using methanol/trifluoroacetic acid (100/0.1) and water/trifluoroacetic acid (100/0.1) as a mixed eluent, to obtain 1.3 mg of the title compound.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.[CH2:11]=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C1(C(N)C2CCCCC2)CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1([B-](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.O1CCCC1>[C:8]([C:5]1[CH:6]=[CH:7][C:2](/[CH:11]=[CH:12]/[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:3][CH:4]=1)(=[O:10])[CH3:9]
Reactant: C=Cc1ccccc1
Reactant: CC(=O)c1ccc(Cl)cc1
Agent: [Pd]
Agent: CC(C)(C)[PH+](C(C)(C)C)C(C)(C)C
Agent: NC(C1CCCCC1)C1CCCCC1
Solvent: C1CCOC1
Product: CC(=O)c1ccc(/C=C/c2ccccc2)cc1
Yield: 75 %

Procedure:
A 30-mil four-necked flask was equipped with a stirrer, a thermometer and a reflux condenser. 0.773 g (5 mmol) of 4′-chloroacetophenone, 1.042 g (10 mmol) of styrene, 0.034 g (0.038 mmol) of tris(dibenzylideneacetone)dipalladium (0), 1.074 g (5.5 mmol) of dicyclohexylmethylamine and 5 ml of tetrahydrofuran were weighed in the flask, followed by stirring. Further, 0.078 g (0.15 mmol) of tri-tert-butylphosphonium tetraphenylborate obtained in Example A-1 was weighed in air and added into the flask. The flask was purged with argon, followed by stirring at 30° C. for 37 hours. After the completion of the reaction, 5 ml of toluene and 10 ml of saturated sodium chloride solution were added, followed by separation. The organic phase was purified by column chromatography to afford 0.834 g of (trans)-4-acetylstilbene (yield: 75 mol % based on 4′-chloroacetophenone). The identification of the product was made by mass spectroscopy, 1H-NMR and 13C-NMR.
Reaction SMILES: [F:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][C:11]([S:14]([O-])(=[O:16])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[Na+].P(Cl)(Cl)(Cl)(Cl)[Cl:22]>C(Cl)Cl>[F:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][C:11]([S:14]([Cl:22])(=[O:16])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: O=S(=O)([O-])c1ccc(OCc2ccc(F)cc2)cc1
Agent: [Na+]
Solvent: ClCCl
Product: O=S(=O)(Cl)c1ccc(OCc2ccc(F)cc2)cc1

Procedure:
To a slurry of sodium 4(4-fluorobenzyloxy)benzenesulfonate (0.5 grams, 1.64 mmole), in methylene chloride (5 mL) was added phosphorus pentachloride (275 mg, 1.31 mmole). The resulting mixture was heated at reflux for 7 hours. After cooling in an ice bath and quenching with water (15 mL), the mixture was extracted with ethyl acetate. The organic phase was washed brine, dried over sodium sulfate, and concentrated to afford 4-(4-fluorobenzyloxy)benzenesulfonyl chloride a white solid (130 mg, 26%).
Reaction SMILES: [CH3:1][CH:2]([CH3:16])[CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:13][CH2:14][CH3:15])=[C:10]([SH:12])[CH:11]=1.[OH-].[K+].[K+].[C:20]([C:25]([O-:27])=[O:26])#[C:21][C:22]([OH:24])=[O:23]>O>[CH3:1][CH:2]([CH3:16])[CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:13][CH2:14][CH3:15])=[C:10]([S:12]/[C:21](=[CH:20]\[C:25]([OH:27])=[O:26])/[C:22]([OH:24])=[O:23])[CH:11]=1
Reactant: CCCc1ccc(OCCC(C)C)cc1S
Reactant: O=C([O-])C#CC(=O)O
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: CCCc1ccc(OCCC(C)C)cc1S/C(=C\C(=O)O)C(=O)O

Procedure:
A solution of 95.7 parts of 5-(3-methylbutoxy)-2-propylthiophenol, 54 parts of potassium hydroxide and 73 parts of acetylene dicarboxylic acid mono potassium salt in 350 parts of water was refluxed for 40 minutes and cooled. The mixture was filtered through Whatman 54 filter paper to remove an oil residue and the filtrate was acidified to pH 1 with concentrated hydrochloric acid. The resulting yellow precipitate was collected, washed with water and dried in vacuo to give 67.8 parts of the desired product as a yellow powder, mp 121° - 129°C Crystallization from 15% ethanol-water afforded pure [5-(3-methylbutoxy)-2-propylphenylthio] fumaric acid, m.p. 131° - 133°C.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:11]2[S:12][C:13]([CH2:16]Cl)=[CH:14][CH:15]=2)[CH2:10][CH:9]=[CH:8][CH2:7]1)=[O:5])[CH3:2].[CH2:18]([O:20][C:21]([C:23]1[NH:24][C:25]([CH2:30][CH2:31][CH3:32])=[N:26][C:27]=1[CH2:28][CH3:29])=[O:22])[CH3:19]>>[CH2:18]([O:20][C:21]([C:23]1[N:24]([CH2:16][C:13]2[S:12][C:11]([C:6]3([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:10][CH:9]=[CH:8][CH2:7]3)=[CH:15][CH:14]=2)[C:25]([CH2:30][CH2:31][CH3:32])=[N:26][C:27]=1[CH2:28][CH3:29])=[O:22])[CH3:19]
Reactant: CCCc1nc(CC)c(C(=O)OCC)[nH]1
Reactant: CCOC(=O)C1(c2ccc(CCl)s2)CC=CC1
Product: CCCc1nc(CC)c(C(=O)OCC)n1Cc1ccc(C2(C(=O)OCC)CC=CC2)s1

Procedure:
Alkylation was carried out on 1-(5-chloromethylthiophen-2-yl)cyclopent-3-ene carboxylic acid ethyl ester (5) as described in Example 1, Step 5, using 5-ethyl-2-propyl-3H-imidazole-4-carboxylic acid ethyl ester (74) to obtain the title compound (73).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([O:9][C:10]1[CH:11]=[C:12]([C:19]2[S:20][CH:21]=[C:22]([C:24]3[CH:29]=[CH:28][C:27]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])=[C:26]([C:38](OC)=[O:39])[CH:25]=3)[N:23]=2)[CH:13]=[CH:14][C:15]=1[O:16][CH2:17][CH3:18])[CH3:8].O.S([O-])([O-])(=O)=O.[Na+].[Na+]>O1CCCC1>[CH2:7]([O:9][C:10]1[CH:11]=[C:12]([C:19]2[S:20][CH:21]=[C:22]([C:24]3[CH:29]=[CH:28][C:27]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])=[C:26]([CH2:38][OH:39])[CH:25]=3)[N:23]=2)[CH:13]=[CH:14][C:15]=1[O:16][CH2:17][CH3:18])[CH3:8]
Reactant: CCOc1ccc(-c2nc(-c3ccc(O[Si](C)(C)C(C)(C)C)c(C(=O)OC)c3)cs2)cc1OCC
Agent: O=S(=O)([O-])[O-]
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Solvent: O
Product: CCOc1ccc(-c2nc(-c3ccc(O[Si](C)(C)C(C)(C)C)c(CO)c3)cs2)cc1OCC
Reaction time: 7 h
Yield: 24 %

Procedure:
548 mg of lithium aluminum hydride was added to a solution of 5.43 g of 2-(3,4-diethoxyphenyl)-4-(3-methoxycarbonyl-4-tert-butyldimethylsilyloxyphenyl)-thiazole in 100 ml of tetrahydrofuran, with ice-cooling. The mixture was stirred at the same temperature for 7 hours. To the reaction mixture were added 1.1 ml of water and 3 g of sodium sulfate. The resulting mixture was filtered through Celite. The filtrate was subjected to distillation to remove the solvent. To the residue were added 200 ml of ethyl acetate and 50 ml of water. The mixture was neutralized with 5N hydrochloric acid. The insoluble was removed by filtration. The filtrate was subjected to phas separation. The organic layer was washed with 50 ml of water, dried over anhydrous magnesium sulfate and subjected to distillation to remove the solvent. The residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=10/1 by v/v) and recrystallized from ethyl acetate-n-hexane to obtain 1.23 g of 2-(3,4-diethoxyphenyl)-4-(3-hydroxymethyl-4-tert-butyldimethylsilyloxyphenyl)thiazole.
Reaction SMILES: [CH2:1]([N:3]([CH:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH:26][C:27]([C:29]4[S:30][CH:31]=[CH:32][CH:33]=4)=[NH:28])[CH:24]=3)[NH:19][CH:18]=2)[CH2:12]1)C(=O)OC(C)(C)C)[CH3:2].C(O)(C(F)(F)F)=O.[NH4+].[OH-]>ClCCl>[CH2:1]([NH:3][CH:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([NH:26][C:27]([C:29]4[S:30][CH:31]=[CH:32][CH:33]=4)=[NH:28])[CH:24]=3)[NH:19][CH:18]=2)[CH2:12]1)[CH3:2]
Reactant: CCN(C(=O)OC(C)(C)C)C1CCCC(c2c[nH]c3ccc(NC(=N)c4cccs4)cc23)C1
Agent: [NH4+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCNC1CCCC(c2c[nH]c3ccc(NC(=N)c4cccs4)cc23)C1
Temperature: 0 °C
Reaction time: 2 h
Yield: 378.9 %

Procedure:
tert-Butyl ethyl(3-(5-(thiophene-2-carboximidamido)-1H-indol-3-yl)cyclohexyl)carbamate (0.17 g, 0.36 mmol) was treated with 20% TFA solution (20 mL) in dichloromethane at 0° C. and the mixture left to stir for 2 hours at 0° C. The solution then was neutralized with 10% NH4OH solution, the organic layer separated and evaporated. The crude was purified by column chromatography (20% 2N NH3 in MeOH: 80% CH2Cl2) to give the final product as a yellow solid (0.50 g, 85%). 1H-NMR (DMSO-d6) δ 1.11 (t, 3H, J=6.9 Hz), 1.21-1.53 (m, 4H), 1.81-2.11 (m, 3H), 2.27-2.37 (m, 1H), 2.82-2.88 (m, 3H), 2.99-3.07 (m, 1H), 6.22 (s, 2H, NH), 6.64 (d, 1H, J=8.4 Hz), 7.01-7.03 (m, 2H), 7.10 (dd, 1H, J=3.6, 5.1 Hz), 7.28 (d, 1H, J=8.7 Hz), 7.59 (d, 1H, J=5.1 Hz), 7.71 (d, 1H, J=3.0 Hz), 10.62 (s, 1H, NH); ESI-MS (m/z, %) 367 (MH+, 50), 322 (100), ESI-HRMS calc. for C21H27N4S (MH+) 367.1950 found 367.1968.
Reaction SMILES: [O:1]1[CH:3]([CH2:4][O:5][C:6]2[S:7][C:8]([C:11]([NH:13][CH2:14][CH2:15][C:16]#[C:17][CH:18]([CH3:20])[CH3:19])=[O:12])=[CH:9][N:10]=2)[CH2:2]1.[CH:21]([NH2:24])([CH3:23])[CH3:22]>C(O)C>[CH:21]([NH:24][CH2:2][CH:3]([OH:1])[CH2:4][O:5][C:6]1[S:7][C:8]([C:11]([NH:13][CH2:14][CH2:15][C:16]#[C:17][CH:18]([CH3:20])[CH3:19])=[O:12])=[CH:9][N:10]=1)([CH3:23])[CH3:22]
Reactant: CC(C)C#CCCNC(=O)c1cnc(OCC2CO2)s1
Reactant: CC(C)N
Solvent: CCO
Product: CC(C)C#CCCNC(=O)c1cnc(OCC(O)CNC(C)C)s1
Temperature: -20 °C
Reaction time: 12 h

Procedure:
This example illustrates methods for preparing the compounds of the present invention. In this example a mixture containing 12 g. (0.0314 mole) of 1,2-epoxy-3-[5-(5-methylhex-3-ynylaminocarbonyl)thiazol-2-yloxy]propane, 12 g. (0.203 mole) of isopropylamine and 20 ml. of ethanol is allowed to stand at room temperature for 12 hours. The mixture is then evaporated under vacuum to remove the solvent and the resulting residue dissolved in 50 ml. of ethyl acetate and cooled to -20° C, and maintained at this temperature for 2 hours. The mixture is then filtered and the resulting filter cake washed with cold (about 0° C) ethyl ether and then recrystallized from ethyl acetate affording 1-isopropylamino-3-[5-(5-methylhex-3-ynylaminocarbonyl)thiazol-2-yloxy]-propan-2-ol.
Reaction SMILES: [CH3:1][N:2]([CH2:7][C:8]1[S:12][C:11]2[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=2[C:9]=1[CH3:17])[C:3](=[O:6])[CH:4]=[CH2:5].[CH2:18]([O:20][C:21]([C:23]1[C:24](=[O:34])[NH:25][C:26]2[C:31]([CH:32]=1)=[CH:30][C:29](Br)=[CH:28][N:27]=2)=[O:22])[CH3:19].CCN(C(C)C)C(C)C>C(C#N)C.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:18]([O:20][C:21]([C:23]1[C:24](=[O:34])[NH:25][C:26]2[C:31]([CH:32]=1)=[CH:30][C:29](/[CH:5]=[CH:4]/[C:3](=[O:6])[N:2]([CH3:1])[CH2:7][C:8]1[S:12][C:11]3[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=3[C:9]=1[CH3:17])=[CH:28][N:27]=2)=[O:22])[CH3:19]
Reactant: C=CC(=O)N(C)Cc1sc2ccccc2c1C
Reactant: CCOC(=O)c1cc2cc(Br)cnc2[nH]c1=O
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: CCC#N
Product: CCOC(=O)c1cc2cc(/C=C/C(=O)N(C)Cc3sc4ccccc4c3C)cnc2[nH]c1=O
Temperature: 25 °C
Yield: 56.3 %

Procedure:
A suspension of N-methyl-N-(3-methyl-benzo[b]thiophen-2-ylmethyl)acrylamide (500 mg, 2.04 mmol), 6-bromo-2-oxo-1,2-dihydro-[1,8]naphthyridine-3-carboxylic acid ethyl ester (665 mg, 2.24 mmol), (o-tol)3P (135 mg, 0.44 mmol) and DIEA (0.4 mL, 2.45 mmol) in EtCN (10 mL) and DMF (10 mL) was deoxygenated with argon for 30 min. Pd(OAc)2 (50 mg, 0.22 mmol) was added, the mixture was deoxygenated with argon for 20 min and then heated to reflux overnight. The mixture was cooled to room temperature and concentrated. The residue was partitioned between CH2Cl2 and H2O. The organic layer was washed with satd NaCl, dried (Na2SO4) and concentrated. Purification by column chromatography (silica gel, 89:10:1 CH2Cl2/MeOH/conc NH4OH) gave the title compound (530 mg, 56%) as a yellow solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 12.63 (s, 1H), 8.98 (d, J=2.1 Hz, 1H), 8.67 (s, 1H), 8.44-8.42 (m, 1H), 7.88 (d, J=7.6 Hz, 1H), 7.75-7.52 (m, 2H), 7.43-7.31 (m, 3H), 5.14-4.91 (m, 2H), 4.32-4.25 (m, 2H), 3.18-2.96 (m, 3H), 2.43 (s, 3H), 1.33-1.27 (m, 3H); MS (ESI) m/e 462 (M+H)+.
Reaction SMILES: [C:1]([OH:6])(=[O:5])[C:2]([CH3:4])=[CH2:3].[CH:7]([O:9][CH2:10][CH:11]([CH3:13])[CH3:12])=[CH2:8].FF>C(=O)([O-])O.[Na+]>[C:1]([O:6][CH:7]([O:9][CH2:10][CH:11]([CH3:13])[CH3:12])[CH3:8])(=[O:5])[C:2]([CH3:4])=[CH2:3]
Reactant: C=COCC(C)C
Reactant: C=C(C)C(=O)O
Agent: FF
Agent: O=C([O-])O
Agent: [Na+]
Product: C=C(C)C(=O)OC(C)OCC(C)C
Yield: 66.1 %

Procedure:
Into a 50-mL eggplant-shaped flask, 8.61 g (100 mmol) of methacrylic acid and 20.0 g (200 mmol) of isobutyl vinyl ether were placed. A fluorine resin-coated stirring piece was dropped into the flask. The mixed solution inside the flask was heated for 6 hours by immersing the flask in an oil bath whose temperature was controlled to 60° C. while stirring the mixed solution by the stirring piece with the use of a magnetic stirrer. After the heating, the whole of the mixed solution was mixed with 20 ml of aqueous sodium hydrogencarbonate solution (concentration: 5 wt %). The resulting mixed solution was left still and separated into an organic phase and an aqueous phase. The organic phase was extracted, dried with sodium sulfate to remove therefrom moisture content, and then, filtrated. The thus-obtained filtrate was concentrated under the conditions of a temperature of 40° C. and a pressure of 30 hPa by a rotary evaporator. By this, 12.32 g of 1-(2-methylpropoxy)ethyl methacrylate of the following formula was obtained in the form of a pale yellow liquid as a protected carboxyl-containing monomer for providing a repeating unit B2 in a polymer.