Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.Br[CH2:11][CH2:12][CH:13]1[O:18][CH2:17][CH2:16]C[O:14]1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.C(#N)C>[O:18]1[CH2:17][CH2:16][O:14][CH:13]1[CH2:12][CH2:11][O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1
Reactant: BrCCC1OCCCO1
Reactant: O=Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: O=Cc1ccc(OCCC2OCCO2)cc1
Yield: 104.5 %

Procedure:
In a 500 ml flask, 120 ml of acetonitrile, 13.8 g of 4-hydroxybenzaldehyde, 19.9 g of 2-(2-bromoethyl)-1,3-dioxane, 1.8 g of potassium iodide, and 35.8 g of potassium carbonate were placed and then, reacted at 80° C. for 5 hr. Thereafter, to the reaction mixture was added 200 ml of ethyl acetate and washed once with a saturated aqueous potassium carbonate solution, distilled water and saturated saline. The washed organic phase was dried over anhydrous magnesium sulfate and the solvent was removed, to give 23.7 g of 4-(2-[1,3]-dioxolan-2-yl-ethoxy)benzaldehyde.
Reaction SMILES: [CH2:1]([N:3]([C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[CH2:4][CH2:5][CH2:6]OS(C1C=CC(C)=CC=1)(=O)=O)[CH3:2].[I-:28].[Na+].C(OCC)(=O)C.O>CC(C)=O>[CH2:1]([N:3]([C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[CH2:4][CH2:5][CH2:6][I:28])[CH3:2]
Reactant: [I-]
Reactant: CCN(CCCOS(=O)(=O)c1ccc(C)cc1)C(=O)OCc1ccccc1
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CC(C)=O
Product: CCN(CCCI)C(=O)OCc1ccccc1
Yield: 76.3 %

Procedure:
N-Ethyl 3-benzyloxycarbonylamino-1-tosyloxypropane (1.02 g) was dissolved in acetone (20 ml), and to the resulting solution was added sodium iodide (0.80 g). The resultant mixture was stirred at 45° C. for 2 hours. Ethyl acetate and water were added to the reaction solution obtained, and the organic layer so separated was washed with water and then dried over magnesiumsulfate. The solvent was evaporated off from the solution, and the residue was purified by a silica gel chromatography, thus to afford the titled compound (0.69 g; 76%).
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[N:4][N:5]([CH3:11])[C:6]=1[O:7][CH:8]([F:10])[F:9].[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([CH2:33]Cl)=[C:24]([CH:32]=1)[O:25][CH:26]([CH3:31])[C:27]([O:29][CH3:30])=[O:28].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O.CCCCCCC>[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([CH2:33][O:18][C:15]2[CH:16]=[CH:17][C:12]([C:3]3[C:2]([Cl:1])=[C:6]([O:7][CH:8]([F:9])[F:10])[N:5]([CH3:11])[N:4]=3)=[CH:13][CH:14]=2)=[C:24]([CH:32]=1)[O:25][CH:26]([CH3:31])[C:27]([O:29][CH3:30])=[O:28]
Reactant: Cn1nc(-c2ccc(O)cc2)c(Cl)c1OC(F)F
Reactant: COC(=O)C(C)Oc1cc(Cl)ccc1CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Product: COC(=O)C(C)Oc1cc(Cl)ccc1COc1ccc(-c2nn(C)c(OC(F)F)c2Cl)cc1
Yield: 45.2 %

Procedure:
This compound was prepared in a manner analogous to that of Step I of Example 1, using 0.82 gram (0.0030 mole) of 4-(4-chloro-5-difluoromethoxy-1-methylpyrazol-3-yl)phenol, 0.95 gram (0.0036 mole) of methyl 2-(5-chloro-2-chloromethylphenoxy)propanoate (prepared in Steps A through D of this Example), and 0.62 gram (0.0045 mole) of potassium carbonate in N,N-dimethylformamide. The crude reaction product was subjected to column chromatography on silica gel, using 1:4 ethyl acetate and heptane as the eluant. The product-containing fractions were combined and concentrated under reduced pressure to an oil. The oil was triturated with heptane, yielding 0.68 gram of title compound, mp 61-64° C. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][N:3]=1.[NH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1>>[N:10]1([C:2]2[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][N:3]=2)[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1
Reactant: C1COCCN1
Reactant: N#Cc1ccnc(Cl)c1
Product: N#Cc1ccnc(N2CCOCC2)c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 52.9 %

Procedure:
A mixture of 2-chloro-4-cyanopyridine (2.5 g, 18 mmol) and morpholine (6.29 g, 72 mmol) was heated at 110°-120° C. for 4 hours. The reaction mixture was cooled, poured into ice-water (15 ml) and stirred for 30 minutes. A yellow solid was obtained, which was collected by filtration, washed with water and dried in vacuo at 70° C. in the presence of P2O5 to afford 1.8 g (53%) of 2-(4-morpholinyl)-4-cyanopyridine, m.p. 135°-136.5° C.
Reaction SMILES: [NH2:1][C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(O)(=O)CC.C(=O)CCC>CO>[NH2:1][CH:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: N[C@@H](Cc1ccccc1)C(=O)O
Solvent: CCC(=O)O
Solvent: CCCC=O
Solvent: CO
Product: NC(Cc1ccccc1)C(=O)O
Temperature: 100 °C
Reaction time: 3 h
Yield: 90 %

Procedure:
3 g of L-phenylalanine, 90 ml of 80% propionic acid and 0.3 ml (0.2 mole per mole of L-phenylalanine) of n-butyraldehyde were admixed. The mixture was stirred at 100° C. for 3 hours. After the reaction, the mixture was condensed to dryness, and 10 ml of methanol were added to the residue. The methanolic mixture was ice-cooled, and the crystalline precipitates were collected by filtration. 2.70 g of DL-phenylalanine were thereby obtained.
Reaction SMILES: C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[N:11]1([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:16][CH2:15][CH:14]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[CH2:13][CH2:12]1.Br[CH2:35][CH2:36][CH:37]=[CH2:38].O>O1CCCC1>[CH2:38]([C:14]1([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[CH2:13][CH2:12][N:11]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:16][CH2:15]1)[CH2:37][CH:36]=[CH2:35]
Reactant: C=CCCBr
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)OCc2ccccc2)CC1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: C=CCCC1(C(=O)OCc2ccccc2)CCN(C(=O)OC(C)(C)C)CC1
Temperature: -78 °C
Reaction time: 2 h
Yield: 36.6 %

Procedure:
Lithium hexamethyldisilazide (1M in tetrahydrofuran, 15.7 mL, 15.7 mmol) was added dropwise to a stirred, cooled (−78° C.) solution of 1-(1,1-dimethylethyl) 4-phenylmethyl 1,4-piperidinedicarboxylate (2.50 g, 7.83 mmol) in tetrahydrofuran (50 mL) and the mixture was stirred at −78° C. for 2 hours. 4-Bromo-1-butene (1.99 mL, 19.6 mmol) was added dropwise and the mixture was stirred at −78° C. for 1 hour, then at room temperature for 2 hours. Water (100 mL) was added and the mixture was extracted with ethyl acetate (2×100 mL). The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane/EtOAc (90:10) to give the title compound (1.07 g, 37%). 1H NMR (400 MHz CDCl3) δ 7.4–7.3 (5H, m), 5.75–5.6 (1H, m), 5.15 (2H, s), 4.93 (1H, br d, J 7 Hz), 4.90 (1H, br s), 3.95–3.75 (2H, m), 2.93–2.78 (2H, m), 2.13 (2H, br d, J 10 Hz), 1.95–1.85 (2H, m), 1.65–1.55 (2H, m), 1.44 (9H, s), and 1.43–1.30 (2H, m).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11].[C:13](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O>C(#N)C>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([O:1][CH3:13])=[C:3]([N+:10]([O-:12])=[O:11])[CH:4]=1)#[N:7]
Reactant: O=C([O-])[O-]
Reactant: N#Cc1ccc(O)c([N+](=O)[O-])c1
Agent: [K+]
Solvent: COS(=O)(=O)OC
Solvent: CC#N
Product: COc1ccc(C#N)cc1[N+](=O)[O-]
Yield: 96.9 %

Procedure:
A suspension of 8.37 g of 4-hydroxy-3-nitrobenzonitrile, 27.64 g of anhydrous potassium carbonate and 6 mL of dimethyl sulphate in 60 mL of acetonitrile was stirred at reflux for 2 hours. The solvent was removed by evaporation in vacuo. The residue was taken up in 100 mL of water and extracted with 3×80 mL of chloroform. The combined organic layers were dried over sodium sulphate and the solvent was evaporated off to afford 8.8 g (98.8%) of Compound 18A as an ivory solid.
Reaction SMILES: [O:1]=[S:2]1(=[O:30])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][N:5]([C:13]2[CH:22]=[C:21]([NH:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27])[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([CH3:29])[CH:19]=3)[N:14]=2)[CH2:4][CH2:3]1.S(Cl)(Cl)=O.[CH3:35]O>>[O:30]=[S:2]1(=[O:1])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][N:5]([C:13]2[CH:22]=[C:21]([NH:23][CH2:24][CH2:25][C:26]([O:28][CH3:35])=[O:27])[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([CH3:29])[CH:19]=3)[N:14]=2)[CH2:4][CH2:3]1
Reactant: CO
Reactant: Cc1ccc2nc(N3CCS(=O)(=O)c4ccccc4C3)cc(NCCC(=O)O)c2c1
Solvent: O=S(Cl)Cl
Product: COC(=O)CCNc1cc(N2CCS(=O)(=O)c3ccccc3C2)nc2ccc(C)cc12
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
To a solution of N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-beta-alanine (85 mg, 0.2 mmol, prepared in analogy to the one in Example 14-2) in methanol (10 mL) at 0° C. was added thionyl chloride (1.5 mL) carefully. The mixture was stirred at room temperature for 20 minutes, and then refluxed at 80° C. for 2 hours. After being cooled to room temperature, the mixture was concentrated in vacuo. The residue was dissolved in dichloromethane, washed with a saturated aqueous solution of sodium bicarbonate, water and brine, then dried over sodium sulfate, and concentrated in vacuo to afford the crude product which was directly used for the next step without further purification.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([N+:9]([O-:11])=[O:10])[C:3]=1[OH:12].CN([CH:16]=[O:17])C.[C:18]([O-])([O-])=O.[K+].[K+]>>[Cl:8][C:6]1[CH:5]=[C:4]([N+:9]([O-:11])=[O:10])[C:3]2[O:12][CH2:18][C:16](=[O:17])[NH:1][C:2]=2[CH:7]=1
Reactant: CN(C)C=O
Reactant: Nc1cc(Cl)cc([N+](=O)[O-])c1O
Reactant: O=C([O-])[O-]
Agent: [K+]
Product: O=C1COc2c(cc(Cl)cc2[N+](=O)[O-])N1
Temperature: 25 °C
Reaction time: 20 h
Yield: 18.7 %

Procedure:
To a solution of 2-amino-4-chloro-6-nitrophenol (5 g, 26.5 mmol) in DMF (20 ml) ethylbromoacetate (3 ml, 26.5 mmol) and K2CO3 (4 g, 29.15 mmol) were added and the reaction was stirred at room temperature for 20 hours. The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with NaOH 5%, water and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by crystallization from ether/AcOEt gave 1.13 g of a beige solid. Yield: 19%. 1HNMR (DMSO, 200 MHz) δ 4.79 (2H, s), 7.15 (1H, d, J=2.6 Hz), 7.66 (1H, d, J=2.8 Hz), 11.21 (1H, bs)
Reaction SMILES: [C:1]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)(=[S:3])[NH2:2].[Br:14][C:15]1[CH:24]=[CH:23][C:18]([C:19](=O)[CH2:20]Br)=[CH:17][CH:16]=1>>[Br:14][C:15]1[CH:24]=[CH:23][C:18]([C:19]2[N:2]=[C:1]([C:4]3[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=3)[S:3][CH:20]=2)=[CH:17][CH:16]=1
Reactant: COC(=O)c1ccc(C(N)=S)cc1
Reactant: O=C(CBr)c1ccc(Br)cc1
Product: COC(=O)c1ccc(-c2nc(-c3ccc(Br)cc3)cs2)cc1
Yield: 73 %

Procedure:
In the same manner as in Example 74, methyl 4-thiocarbamoylbenzoate was reacted with 4-bromophenacyl bromide to obtain methyl 4-[4-(4-bromophenyl)-2-thiazolyl]benzoate. The product was recrystallized from ethanol. Yield: 73%. Colorless prisms. Melting point: 206 to 207° C.
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]=[C:8]([NH:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[S:9][CH:10]=1)=[O:5])C.O1CCCC1.[OH-].[Na+]>CO>[N:14]1[CH:15]=[CH:16][CH:17]=[C:12]([NH:11][C:8]2[S:9][CH:10]=[C:6]([C:4]([OH:5])=[O:3])[N:7]=2)[CH:13]=1
Reactant: CCOC(=O)c1csc(Nc2cccnc2)n1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)c1csc(Nc2cccnc2)n1

Procedure:
2-(Pyridin-3-ylamino)-thiazole-4-carboxylic acid (165 mg) was prepared according to General Procedure C using 2-(pyridin-3-ylamino)-thiazole-4-carboxylic acid ethyl ester in methanol:tetrahydrofuran:2N NaOH (1:1:1, 1.5 mL). The solvents were evaporated and the compound was dried. The crude product was used without further purification.
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C([O-])([O-])=O.[K+].[K+].Br[CH2:21][CH2:22][O:23][CH3:24]>C(#N)C.O>[C:1]([N:8]1[CH2:9][CH2:10][N:11]([CH2:21][CH2:22][O:23][CH3:24])[CH2:12][CH2:13]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: COCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: COCCN1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 80 °C
Yield: 75.4 %

Procedure:
A solution of N-Boc-piperazine (1.00 g, 5.31 mmol) in acetonitrile (30 ml) was treated with K2CO3 (2.20 g, 15.9 mmol) and (2-bromoethyl)methyl ether (812 μl, 5.84 mmol) and heated to 80° C. for 18 h. The cooled mixture was diluted with water and extracted with DCM. The combined organcs were dried over MgSO4, filtered and evaporated and the residue purified by column chromatography on SiO2, eluting with 5% EtOH in DCM to afford 1-Boc-4-(2-methoxy-ethyl)-piperazine as a clear oil (978 mg, 76%). 1H NMR (400 MHz, DMSO-d6) δ 3.41 (t, J=5.8 Hz, 2H), 3.29-3.25 (m, 4H), 3.21 (s, 3H), 2.45 (t, J=5.8 Hz, 2H), 2.33 (t, J=5.0 Hz, 4H), 1.38 (s, 9H).
Reaction SMILES: CC[N:3](C1C=CC=CC=1)CC.[C:12]1([CH3:22])[CH:17]=[CH:16][C:15]([S:18](Cl)(=[O:20])=[O:19])=[CH:14][CH:13]=1>C1COCC1>[CH3:22][C:12]1[CH:17]=[CH:16][C:15]([S:18]([NH2:3])(=[O:20])=[O:19])=[CH:14][CH:13]=1
Reactant: CCN(CC)c1ccccc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: C1CCOC1
Product: Cc1ccc(S(N)(=O)=O)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 333.7 %

Procedure:
Diethylaniline (0.33 μL, 2.1 μmol, 1.1 equiv) was added in one portion to a stirred solution of the amine (1.0 mg, 1.9 μmol, 1 equiv) in THF (0.1 mL) at 0° C. under an argon atmosphere and the solution was stirred for 5 min. p-Toluenesulfonyl chloride (0.73 mg, 3.8 μmol, 2.0 equiv) was then added in one portion to the above solution at 0° C. The reaction mixture was stirred at 0° C. for 1 hr and then quenched with a 1:1 mixture of saturated aqueous sodium hydrogen carbonate solution and water (4 mL). The mixture was diluted with ethyl acetate (10 mL) and the layers were separated. The aqueous layer was extracted with ethyl acetate (10 mL) and the combined organic layer was dried over sodium sulfate. Concentration in vacuo left a yellow oil, which was purified by flash column chromatography (60% ethyl acetate-hexanes) to give the 4-methylphenyl sulfonamide derivative (1.2 mg, 93%) as a white solid.
Reaction SMILES: [C:1]([Cu])#[N:2].Br[C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[N:12]1[CH:16]=[CH:15][CH:14]=[N:13]1>CN(C=O)C>[F:11][C:8]1[CH:9]=[CH:10][C:5]([C:1]#[N:2])=[C:6]([N:12]2[CH:16]=[CH:15][CH:14]=[N:13]2)[CH:7]=1
Reactant: N#C[Cu]
Reactant: Fc1ccc(Br)c(-n2cccn2)c1
Solvent: CN(C)C=O
Product: N#Cc1ccc(F)cc1-n1cccn1
Temperature: 110 °C
Yield: 72.4 %

Procedure:
To a stirred suspension of CuCN (358 mg, 4.0 mmol, Aldrich) in DMF (2 mL, Sure Seal) was added a solution of 1-(2-Bromo-5-fluoro-phenyl)-1H-pyrazole (964 mg, 4.0 mmol) in DMF (2 mL) and the resulting clear solution was stirred in an oil bath heated at 110° C. under nitrogen for 1.5 h. After cooling, the mixture was concentrated in vacuo and the residue mixed with 14% aqueous NH4OH (10 mL) was stirred at room temperature for 0.5 h. To this was added EtOAc (15 mL) and the mixture stirred for additional 0.5 h. The EtOAc extract was washed with dil. NH4OH and then with brine, dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography (SiO2, 0–10% EtOAc/CH2Cl2) to obtain 542 mg of the title compound as a white crystalline solid: TLC Rf 0.42 (CH2Cl2); HPLC rt=1.94 min. LC/MS m/z 188 (M+H); 1H NMR (CDCl3, 500 MHz) δ ppm 6.55 (1H, dd, J=2.6, 1.7 Hz, 9-CH), 7.10–7.13 (1H, m, 5-CH), 7.59 (1H, dd, J=9.5, 2.5 Hz, 3-CH), 7.76 (1H, dd, J=8.7, 5.5 Hz, 6-CH), 7.80 (1H, d, J=1.2 Hz, 10-CH), 8.25 (1H, d, J=2.7 Hz, 8-CH); 13C NMR (CDCl3, 125.8 Hz) δ ppm 100.5 (d, J=3.8 Hz, 1-C), 109.1 (9-CH), 111.9 (d, J=27 Hz, 3-CH), 114.9 (d, J=23 Hz, 5-CH), 116.6 (7-CN), 129.5 (8-CH), 136.7 (d, J=10 Hz, 6-CH), 142.8 (10-CH), 144.2 (d, J=12 Hz, 2-C), 165.5 (d, J=258 Hz, 4-CF); HRMS (ESI) calcd for C10H7FN3 (M+H) 189.0576. found 189.0568 (δ −4.5 ppm); UV (MeOH) λ max 224 nm (ε 2.54×104), 261 nm (ε 1.20×104); Anal. calcd for C10H7FN3: C, 64.16; H, 3.24; N, 22.45. found C, 64.02; H, 3.16; N, 22.68.
Reaction SMILES: [CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][CH:3]=1.[NH:11]1[CH:15]=[CH:14][N:13]=[CH:12]1.BrBr>O1CCOCC1.Cl>[N:11]1([C:3]2[NH:4][C:5]3[C:10]([C:2]=2[CH3:1])=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:15]=[CH:14][N:13]=[CH:12]1
Reactant: Cc1c[nH]c2ccccc12
Reactant: c1c[nH]cn1
Agent: BrBr
Agent: Cl
Solvent: C1COCCO1
Product: Cc1c(-n2ccnc2)[nH]c2ccccc12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 3-methylindole (7.87 g) and imidazole (20.42 g) in dioxane (350 ml) stirring at 10° is added a solution of bromine (3.1 ml) in dioxane (125 ml) dropwise over a period of 25 hrs. Upon complete addition, the cooling bath is removed and the resulting yellow suspension is allowed to warm to room temperature while stirring overnight. The solid which had formed is removed by vacuum filtration. The filtrate is concentrated in vacuo to give an amber oil. This oil is suspended in 2 N HCl (100 ml) and washed with ether (3×100 ml). The acidic layer is made basic to pH 10 with 3 N NaOH and extracted with ether (6×100 ml). The ether extract is dried (MgSO4), filtered and concentrated in vacuo to give a partially crystalline residue. This residue is triturated with petroleum ether/ether and the solid which resulted is collected and recrystallized from acetonitrile (30 ml) to give 2-(1-imidazolyl)-3-methylindole, m.p. 156°-158°.
Reaction SMILES: [N:1]1[C:10]2[N:9]3[CH:11]=[CH:12][CH:13]=[C:8]3[CH2:7][NH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[F:21][C:22]1[CH:23]=[CH:24][C:25]([CH3:40])=[C:26]([CH:39]=1)[C:27]([NH:29][C:30]1[N:35]=[CH:34][C:33]([C:36](Cl)=[O:37])=[CH:32][CH:31]=1)=[O:28].O>ClCCl>[N:1]1[C:10]2[N:9]3[CH:11]=[CH:12][CH:13]=[C:8]3[CH2:7][N:6]([C:36]([C:33]3[CH:32]=[CH:31][C:30]([NH:29][C:27](=[O:28])[C:26]4[CH:39]=[C:22]([F:21])[CH:23]=[CH:24][C:25]=4[CH3:40])=[N:35][CH:34]=3)=[O:37])[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: c1cnc2c(c1)NCc1cccn1-2
Reactant: Cc1ccc(F)cc1C(=O)Nc1ccc(C(=O)Cl)cn1
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: Cc1ccc(F)cc1C(=O)Nc1ccc(C(=O)N2Cc3cccn3-c3ncccc32)cn1
Temperature: 25 °C
Reaction time: 16 h
Yield: 44.4 %

Procedure:
To a chilled (0° C.) solution of 0.343 g of 5,6-dihydropyrido[3,2-e]pyrrolo[1,2-a]pyrazine and 1.1 ml of triethylamine in 5 ml of dichloromethane is added 1.17 g of 6-(5-fluoro-2-methylbenzoyl)aminopyridine-3-carbonyl chloride. The mixture is stirred at room temperature for 16 hours. To the mixture is added 50 ml of dichloromethane and 20 ml of water. The organic layer is separated and washed with 20 ml each of 1M NaHCO3 and brine. The organic layer is dried (Na2SO4) and passed through a thin pad of hydrous magnesium silicate and the pad washed with dichloromethane. The filtrate is concentrated and the residue chromatographed on silica gel prep-plates with ethyl acetate-hexane (1:1) as eluent. The product is crystallized from ethyl acetate to give 0.38 g of white crystals, m.p. 226°-234° C.
Reaction SMILES: [C:1]([O-:4])(=[O:3])[CH3:2].[CH:5]12[CH2:11][CH:8]([CH:9]=[CH:10]1)[CH2:7][CH:6]2[C:12]([O:14]C(C)(C)C)=[O:13].C([C:21]12[CH2:27][CH:24]([CH:25]=[CH:26]1)[CH2:23][CH:22]2[C:28]([O:30]O)=[O:29])C.[CH:32]12[CH2:38][CH:35]([CH:36]=[CH:37]1)[CH2:34][CH:33]2[C:39]([OH:41])=[O:40].CC(N=NC(C#N)(C)C)(C#N)C>>[C:1]([O-:4])(=[O:3])[CH3:2].[CH:5]12[CH2:11][CH:8]([CH:9]=[CH:10]1)[CH2:7][CH:6]2[C:12]([O-:14])=[O:13].[CH:21]12[CH2:27][CH:24]([CH:25]=[CH:26]1)[CH2:23][CH:22]2[C:28]([O:30][CH2:33][CH2:39][OH:40])=[O:29].[CH:32]12[CH2:38][CH:35]([CH:36]=[CH:37]1)[CH2:34][CH:33]2[C:39]([OH:41])=[O:40]
Reactant: CC(C)(C)OC(=O)C1CC2C=CC1C2
Reactant: CCC12C=CC(CC1C(=O)OO)C2
Agent: CC(=O)[O-]
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: O=C(O)C1CC2C=CC1C2
Product: O=C(OCCO)C1CC2C=CC1C2
Product: O=C([O-])C1CC2C=CC1C2

Procedure:
3-Maleimidepropyl acetate (6) (0.5 to 1 mol), 0.01 to 1 mol of t-butyl-5-norbornene-2-carboxylate (19), 0.05 to 1 mol of 2-hydroxy ethyl 5-norbornene-2-carboxylate (21), and 0.01 to 0.3 mol of 5-norbornene-2-carboxylic acid (20) were dissolved in 240 to 290 g of THE solvent to which was added 0.5 to 20 g of AIBN as a polymerization initiator. The reaction mixture was allowed to react at 60° C. to 75° C. for 4 to 24 hours under an argon atmosphere. The resulting crude resin was precipitated with hexane and dried to obtain poly[3-maleimidepropyl acetate/5-norbornene-2- carboxylate/ 2-hydroxyethyl 5-norbornene-2-carboxylate/5-norbornene-2-carboxylic acid] copolymer resin.
Reaction SMILES: [NH:1]=[C:2]1[NH:6][C:5]([C:11]([F:14])([F:13])[F:12])([C:7]([F:10])([F:9])[F:8])[C:4](=[C:15]([F:20])[C:16]([F:19])([F:18])[F:17])[S:3]1.[CH3:21][O:22][C:23]1[CH:33]=[CH:32][CH:31]=[CH:30][C:24]=1[C:25]([N:27]=[C:28]=[O:29])=[O:26]>C1(C)C=CC=CC=1>[F:14][C:11]([F:12])([F:13])[C:5]1([C:7]([F:10])([F:9])[F:8])[C:4](=[C:15]([F:20])[C:16]([F:17])([F:18])[F:19])[S:3][C:2]([NH:1][C:28]([NH:27][C:25](=[O:26])[C:24]2[CH:30]=[CH:31][CH:32]=[CH:33][C:23]=2[O:22][CH3:21])=[O:29])=[N:6]1
Reactant: COc1ccccc1C(=O)N=C=O
Reactant: N=C1NC(C(F)(F)F)(C(F)(F)F)C(=C(F)C(F)(F)F)S1
Solvent: Cc1ccccc1
Product: COc1ccccc1C(=O)NC(=O)NC1=NC(C(F)(F)F)(C(F)(F)F)C(=C(F)C(F)(F)F)S1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
In toluene (10 ml) was dissolved 2-imino-4,4-bis(trifluoromethyl)-5-(tetrafluoroethylidene)-1,3-thiazolidine (1.0 g), and 2-methoxybenzoylisocyanate (0.4 g) which is a starting compound was added thereto and the mixture was stirred at room temperature for 3 hours.
Reaction SMILES: [ClH:1].[CH2:2]([C:5]1[N:6]=[C:7]([NH2:10])[NH:8][CH:9]=1)[C:3]#[CH:4].[N:11]([CH2:14][C:15]1[CH:19]=[CH:18][S:17][CH:16]=1)=[N+:12]=[N-:13]>>[ClH:1].[S:17]1[CH:18]=[CH:19][C:15]([CH2:14][N:11]2[CH:4]=[C:3]([CH2:2][C:5]3[N:6]=[C:7]([NH2:10])[NH:8][CH:9]=3)[N:13]=[N:12]2)=[CH:16]1
Reactant: C#CCc1c[nH]c(N)n1
Reactant: [N-]=[N+]=NCc1ccsc1
Agent: Cl
Product: Nc1nc(Cc2cn(Cc3ccsc3)nn2)c[nH]1
Yield: 44 %

Procedure:
4-Prop-2-ynyl-1H-imidazol-2-ylamine hydrochloride (0.096 (0.061 mmol) was reacted with 3-azidomethyl thiophene (0.102 g, 0.732 mmol) following the general procedure for click reactions outlined above to produce 4-(1-Thiophen-3-ylmethyl-1H-[1,2,3]triazol-4-ylmethyl)-1Himidazol-2-ylamine hydrochloride (0.079 g, 44%) of a pale yellow solid. 1H NMR (300 MHz, CD3OD) δ 8.18 (s, 1H), δ 7.44 (s, 1H), δ 7.30 (d, 1H), δ 6.98 (d, 1H), δ 6.53 (s, 1H), δ 5.57 (s, 2H), δ 3.95 (s, 2H) ppm; 13C (75 MHz, CD3OD) δ 145.7, 145.1, 143.7, 139.7, 129.8, 121.8, 111.5, 109.8, 109.2, 52.7, 21.5 ppm; HRMS (ESI) calcd for C11H12N6S (M+) 260.0919. found 260.0919.
Reaction SMILES: [C:1]([O-:9])(=[O:8])[C:2]1C=CC=C[CH:3]=1.[NH2+:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.O.[CH:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH3:3][CH:2]1[C:18]2[CH:19]=[CH:20][C:21]([N:10]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3)=[CH:22][C:17]=2[O:9][C:1]1=[O:8]
Reactant: C1CC[NH2+]CC1
Reactant: c1ccccc1
Reactant: O=C([O-])c1ccccc1
Solvent: O
Product: CC1C(=O)Oc2cc(N3CCCCC3)ccc21

Procedure:
A mixture of 9.1 g (0.05 mole) of 4-methyl-3-(3-oxobutyl)-maleic acid anhydride and 11 g (0.053 mole) of piperidinium benzoate in 200 ml of benzene is heated under reflux for 48 hours using a water separator. The benzene is removed in vacuo and the residue that remains is partitioned between methylene chloride and saturated sodium bicarbonate solution. The crude product remaining after drying and after removal of the methylene chloride is chromatographed over silica gel with petroleum ether/ether. Subsequent recrystallisation from ether/petroleum ether yields 3-methyl-6-(piperidin-1-yl)-benzofuran-2(3H)-one having a melting point of 78°-80° C.