Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][NH:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH3:13])[CH:5]=1.CNCC1C=CC2C(=CC=CC=2)C=1CCC.Cl.[O:31]=[C:32]1[NH:45][C:35]2=[N:36][CH:37]=[C:38](/[CH:40]=[CH:41]/[C:42](O)=[O:43])[CH:39]=[C:34]2[O:33]1.Cl.CN1CC2C=C(/C=C/C(O)=O)C=NC=2NC(=O)C1>>[CH3:1][N:2]([CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH3:13])[CH:5]=1)[C:42](=[O:43])/[CH:41]=[CH:40]/[C:38]1[CH:39]=[C:34]2[O:33][C:32](=[O:31])[NH:45][C:35]2=[N:36][CH:37]=1
Reactant: O=C(O)/C=C/c1cnc2[nH]c(=O)oc2c1
Reactant: CNCc1cn(C)c2ccccc12
Agent: CCCc1c(CNC)ccc2ccccc12
Agent: CN1CC(=O)Nc2ncc(/C=C/C(=O)O)cc2C1
Agent: Cl
Product: CN(Cc1cn(C)c2ccccc12)C(=O)/C=C/c1cnc2[nH]c(=O)oc2c1
Yield: 23 %

Procedure:
According to the procedure of Example 1 (a), except substituting methyl-(1-methyl-1H-indol-3-ylmethyl)amine for the methyl-(1-propyl-naphthalen-2-ylmethyl)amine, and substituting (E)-3-(2-oxo-2,3-dihydro-oxazolo[4,5-b]pyridine-6-yl)acrylic acid hydrochloride for the (E)-3-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid hydrochloride, the title compound (0.075 g, 23%) was prepared as a light brown solid: 1H NMR (300 MHz, CDCl3) δ 8.28-8.24 (m, 1H), 7.82 (d, J=15.4 Hz, 1H), 7.71-7.49 (m, 2H), 7.37-6.87 (m, 5H), 4.88-4.86 (m, 2H), 3.78 (s, 3H), 3.16-3.12 (m, 3H); MS (ESI) m/e 363 (M+H)+.
Reaction SMILES: [CH3:1][NH:2][C@@H:3]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C@H:6]([C:13]2[CH:14]=[CH:15][C:16]([Cl:20])=[C:17]([Cl:19])[CH:18]=2)[CH2:5][CH2:4]1.[C:21]([OH:26])(=[O:25])[C@H:22]([CH3:24])[OH:23]>C(OCC)(=O)C>[CH3:1][NH:2][C@@H:3]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C@H:6]([C:13]2[CH:14]=[CH:15][C:16]([Cl:20])=[C:17]([Cl:19])[CH:18]=2)[CH2:5][CH2:4]1.[C:21]([O-:26])(=[O:25])[C@H:22]([CH3:24])[OH:23]
Reactant: C[C@H](O)C(=O)O
Agent: CN[C@H]1CC[C@@H](c2ccc(Cl)c(Cl)c2)c2ccccc21
Solvent: CCOC(C)=O
Product: C[C@H](O)C(=O)[O-]
Temperature: 40 °C

Procedure:
Sertraline base (the compound of Preparation AA, 1.0 g) was dissolved in ethyl acetate (20 mL) in a 50 mL round bottom flask and the solution was heated to 40° C. L-Lactic acid (342.5 mg) was separately dissolved in ethyl acetate (5 mL). The L-latic acid solution was added in small portions to the solution in the round bottom flask which was constantly stirred with a magnetic stirred. The reaction mixture was stirred at 40° C. for 2 hours after the addition of the L-lactic acid solution was complete. The reaction mixture was then allowed to cool to room temperature and the solids were filtered. The solids were washed with 5 mL of ethyl acetate and then dried under vacuum at 40° C. for 24 hours. The dried solid was identified as the L-lactate salt of sertraline. The yield was calculated to be 86%. mp 153° C.
Reaction SMILES: [CH2:1]1[CH2:10][O:9][C:8]2[CH:7]=[CH:6][C:5]([NH:11][C:12]3[C:17]([F:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]4[CH:25]=[CH:24][CH:23]=[C:22](O)[CH:21]=4)[N:13]=3)=[CH:4][C:3]=2[O:2]1.ClC1N=C(NC2C=CC3OCCOC=3C=2)C(F)=CN=1.[CH2:46]([N:53]1[CH2:58][CH2:57][N:56](C2C=CC(N)=CC=2)[CH2:55][CH2:54]1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>>[CH2:46]([N:53]1[CH2:58][CH2:57][N:56]([C:23]2[CH:22]=[CH:21][C:20]([NH:19][C:14]3[N:13]=[C:12]([NH:11][C:5]4[CH:6]=[CH:7][C:8]5[O:9][CH2:10][CH2:1][O:2][C:3]=5[CH:4]=4)[C:17]([F:18])=[CH:16][N:15]=3)=[CH:25][CH:24]=2)[CH2:55][CH2:54]1)[C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1
Reactant: Oc1cccc(Nc2ncc(F)c(Nc3ccc4c(c3)OCCO4)n2)c1
Reactant: Nc1ccc(N2CCN(Cc3ccccc3)CC2)cc1
Agent: Fc1cnc(Cl)nc1Nc1ccc2c(c1)OCCO2
Product: Fc1cnc(Nc2ccc(N3CCN(Cc4ccccc4)CC3)cc2)nc1Nc1ccc2c(c1)OCCO2
Yield: 33 %

Procedure:
In a manner analogous to the preparation of N4-(3,4-ethylenedioxyphenyl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine, the reaction of 2-chloro-N4-(3,4-ethylendioxyphenyl)-5-fluoro-4-pyrimidineamine (50 mg, 0.18 mmol) and 4-(4-benzylpiperazino)aniline (142 mg, 0.53 mmol) resulted N2-[4-(N-benzylpiperazino)phenyl]-N4-(3,4-ethylenedioxyphenyl)-5-fluoro-2,4-pyrimidinediamine (30 mg, 33%). 1H NMR (CDCl3): δ 2.63 (t, J=4.8 Hz, 4H), 3.16 (t, J=4.8 Hz, 4H), 3.58 (s, 2H), 4.27 (m, 4H), 6.56 (d, 1H, NH), 6.70 (br, 1H, NH), 6.82 (d, J=8.7 Hz, 1H), 6.89 (d, J=9.0 Hz, 2H), 6.96 (dd, J=2.7 and 8.7 Hz, 1H), 7.28 (d, J=2.7 Hz, 1H), 7.30-7.36 (m, 5H), 7.39 (d, J=8.7 Hz, 2H), 7.88 (d, J=3.3 Hz, 1H); 19F NMR (282 MHz, CDCl3): 6-168.94; LCMS: ret. time: 18.12 min.; purity: 98.42%; MS (m/e): 512.95 (MH+).
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.[CH2:12]([O:14][C:15](OCC)(OCC)[CH2:16][CH3:17])[CH3:13]>>[C:2]1([N:1]=[C:15]([O:14][CH2:12][CH3:13])[CH2:16][CH3:17])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1
Reactant: Nc1cccc2ccccc12
Reactant: CCOC(CC)(OCC)OCC
Product: CCOC(CC)=Nc1cccc2ccccc12

Procedure:
The title compound was prepared from 1-aminonaphthalene and triethylorthopropionate according to the following procedure: DeWolfe, R. H. J. Org. Chem. 1962, 27, 490-493.
Reaction SMILES: C(OC([N:8]1[CH2:13][C:12]([C:14]2[CH:19]=[C:18]([CH:20]3[CH2:25][CH2:24][N:23]([C:26](=[O:28])[CH3:27])[CH2:22][CH2:21]3)[CH:17]=[CH:16][C:15]=2[NH:29][C:30]([C:32]2[N:33](COCC[Si](C)(C)C)[CH:34]=[C:35]([C:37]#[N:38])[N:36]=2)=[O:31])=[CH:11][CH2:10][CH2:9]1)=O)(C)(C)C.CCO.[C:50]([OH:56])([C:52]([F:55])([F:54])[F:53])=[O:51]>C(Cl)Cl>[C:50]([OH:56])([C:52]([F:55])([F:54])[F:53])=[O:51].[F:53][C:52]([F:55])([F:54])[C:50]([OH:56])=[O:51].[C:26]([N:23]1[CH2:22][CH2:21][CH:20]([C:18]2[CH:17]=[CH:16][C:15]([NH:29][C:30]([C:32]3[NH:33][CH:34]=[C:35]([C:37]#[N:38])[N:36]=3)=[O:31])=[C:14]([C:12]3[CH2:13][NH:8][CH2:9][CH2:10][CH:11]=3)[CH:19]=2)[CH2:25][CH2:24]1)(=[O:28])[CH3:27]
Reactant: CC(=O)N1CCC(c2ccc(NC(=O)c3nc(C#N)cn3COCC[Si](C)(C)C)c(C3=CCCN(C(=O)OC(C)(C)C)C3)c2)CC1
Solvent: CCO
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(=O)N1CCC(c2ccc(NC(=O)c3nc(C#N)c[nH]3)c(C3=CCCNC3)c2)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 22 %

Procedure:
A solution of 5-(5-(1-acetyl-piperidin-4-yl)-2-{[4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (as prepared in the previous step, 0.40 g, 0.61 mmol) in CH2Cl2 (20 mL) and EtOH (0.4 mL) was treated with TFA (3 mL). The solution was stirred at room temperature for 0.5 h. The solvents were evaporated in vacuo, and the residue was immediately taken up in EtOH (25 mL) and stored at 5° C. for 11 h. The solution was concentrated in vacuo, and the residue was taken up in CH2Cl2 (20 mL) and EtOH (0.4 mL) then treated with TFA (6 mL). The reaction was stirred at room temperature for 2 h, and the solvents were evaporated in vacuo. Reverse phase HPLC (C-18 column) (10 to 80% acetonitrile in water with 0.1% TFA over 30 min) afforded the title compound (56.9 mg, 22%) as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 8.06 (s, 1H), 7.81 (d, 1H, J=8.4 Hz), 7.32 (d, 1H, J=8.4 Hz), 7.22 (s, 1H), 6.10-6.03 (m, 1H), 4.74-4.64 (m, 2H), 4.11-4.02 (m, 1H), 3.95 (s, 2H), 3.50-3.37 (m, 2H), 3.29-3.20 (m, 1H), 2.93-2.82 (m, 1H), 2.80-2.69 (m, 1H), 2.62-2.53 (m, 2H), 2.16 (s, 3H), 1.98-1.84 (m, 2H), 1.78-1.54 (m, 2H). LC-MS (ESI, m/z): Calcd. for C23H26N6O2 419.2 (M+H). found 419.2.
Reaction SMILES: [CH:1]1([C:4]2[CH:5]=[C:6]([CH:20]=[CH:21][CH:22]=2)[CH2:7][CH:8]2[C:15]3[CH:14]=[C:13]([C:16]([O:18]C)=[O:17])[NH:12][C:11]=3[CH2:10][CH2:9]2)[CH2:3][CH2:2]1.[OH-].[Li+].CO>C1COCC1>[CH:1]1([C:4]2[CH:5]=[C:6]([CH:20]=[CH:21][CH:22]=2)[CH2:7][CH:8]2[C:15]3[CH:14]=[C:13]([C:16]([OH:18])=[O:17])[NH:12][C:11]=3[CH2:10][CH2:9]2)[CH2:3][CH2:2]1
Reactant: COC(=O)c1cc2c([nH]1)CCC2Cc1cccc(C2CC2)c1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)c1cc2c([nH]1)CCC2Cc1cccc(C2CC2)c1

Procedure:
The title compound was synthesized from methyl 4-(3-cyclopropylbenzyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (0.020 g, 0.068 mmol) and lithium hydroxide (0.030 g, 0.71 mmol in 1 mL water), according to General Procedure 7. A 1:1 mixture of methanol (MeOH) and THF (2 mL) was used. The resulting product was purified by reverse phase HPLC, eluting with a gradient of 40-100% MeOH: water (with 0.1% formic acid) to afford the title compound: 2.2 mg, 12% yield. 1H NMR (400 MHz, METHANOL-d4) δ ppm 0.61-0.66 (m, 2H), 0.92 (s, 2H), 1.86 (s, 1H), 2.06 (s, 1H), 2.49 (s, 1H), 2.59 (s, 2H), 2.72 (d, J=7.03 Hz, 2H), 3.23 (s, 1H), 6.30 (s, 1H), 6.84 (s, 1H), 6.96 (s, 1H), 7.12 (s, 1H); LCMS-MS (ESI−) 280.1 (M−H); HPLC (UV=100%), (ELSD=100%).
Reaction SMILES: O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.P(=O)(O)(O)O.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH2:28][CH2:29][C:30]([NH2:32])=[O:31])[CH:25]=[CH:26][CH:27]=1.[CH:33](=O)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>O.C(O)(=O)C>[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]2[CH:33]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[NH:32][C:30](=[O:31])[CH2:29][CH2:28][C:24]=2[CH:23]=1
Reactant: O=Cc1ccccc1
Reactant: COc1cccc(CCC(N)=O)c1
Agent: O=P(O)(O)O
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Solvent: O
Solvent: CC(=O)O
Product: COc1ccc2c(c1)CCC(=O)NC2c1ccccc1
Temperature: 170 °C
Yield: 11 %

Procedure:
To a mixture of 73 g. of phosphorus pentoxide and 43.5 ml. of 85% phosphoric acid, rendered homogeneous by heating at 170° C., is added at room temperature a solution of 9.0 g. (0.05 moles) of 3-(3-methoxyphenyl)-propionamide and 5.9 g. (0.055 moles) of benzaldehyde in 104 ml. of glacial acetic acid. Stirring under an atmosphere of nitrogen is maintained for 3 days and then the reaction mixture is poured into 1 liter water; a precipitate appears, which is filtered off, washed neutral with water and dried. After separation by chromatography and recrystallization from ethanol, 1.5 g. (11% of theory) of pure 7-methoxy-1-phenyl-1,2,4,5-tetrahydro-3H-2-benzazepin-3-one is obtained. M.P. 185-186° C.
Reaction SMILES: [CH2:1]([C:3]1[C:8](=[O:9])[NH:7][C:6]([CH3:10])=[C:5]([C:11]2[CH:12]=[N:13][CH:14]=[C:15]([C:17]([OH:19])=O)[CH:16]=2)[CH:4]=1)[CH3:2].[CH3:20][C:21]1[N:26]=[CH:25][C:24]([CH:27]([NH2:30])[CH2:28][CH3:29])=[CH:23][CH:22]=1>>[CH3:20][C:21]1[N:26]=[CH:25][C:24]([CH:27]([NH:30][C:17]([C:15]2[CH:16]=[C:11]([C:5]3[CH:4]=[C:3]([CH2:1][CH3:2])[C:8](=[O:9])[NH:7][C:6]=3[CH3:10])[CH:12]=[N:13][CH:14]=2)=[O:19])[CH2:28][CH3:29])=[CH:23][CH:22]=1
Reactant: CCC(N)c1ccc(C)nc1
Reactant: CCc1cc(-c2cncc(C(=O)O)c2)c(C)[nH]c1=O
Product: CCc1cc(-c2cncc(C(=O)NC(CC)c3ccc(C)nc3)c2)c(C)[nH]c1=O

Procedure:
Method 1, Example 205 is substantially repeated except for utilizing 5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid and 1-(6-methyl-pyridin-3-yl)-propyl amine to afford the title compound. MS: m/e=391 (M+H).
Reaction SMILES: Br[CH2:2][C@@H:3]([NH:5][C:6]1[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][C:7]=1[C:8]([NH:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=1)=[O:9])[CH3:4].[C-:28]#[N:29].[Na+]>CS(C)=O.C(OCC)(=O)C>[C:26]([C:23]1[CH:24]=[CH:25][C:6]([NH:5][C@@H:3]([CH3:4])[CH2:2][C:28]#[N:29])=[C:7]([CH:22]=1)[C:8]([NH:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=1)=[O:9])#[N:27]
Reactant: [C-]#N
Reactant: COc1ccc(CNC(=O)c2cc(C#N)ccc2N[C@@H](C)CBr)cc1OC
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: COc1ccc(CNC(=O)c2cc(C#N)ccc2N[C@@H](C)CC#N)cc1OC
Temperature: 90 °C
Yield: 71.3 %

Procedure:
To a solution of (S)-2-(2-bromo-1-methylethylamino)-5-cyano-N-(3,4-dimethoxybenzyl)benzamide (117 mg) in dimethylsulfoxide (2 mL) was added sodium cyanide (26.5 mg), and the mixture was stirred for an hour at 90° C. The resulting mixture was diluted with ethyl acetate and washed successively with water and brine. The organic layer was dried over sodium sulfate and evaporated in vacuo. The residue was subjected to a silica gel column chromatography eluting with a mixture of chloroform and ethyl acetate (9:1) to give (S)-5-cyano-2-(2-cyano-1-methylethylamino)-N-(3,4-dimethoxybenzyl)benzamide (73 mg) as a solid substance.
Reaction SMILES: C([N:8]1[C:12]([C:13]([OH:15])=[O:14])=[CH:11][C:10]([C:16]([F:19])([F:18])[F:17])=[N:9]1)C1C=CC=CC=1.[Na]>N>[F:19][C:16]([F:17])([F:18])[C:10]1[CH:11]=[C:12]([C:13]([OH:15])=[O:14])[NH:8][N:9]=1
Reactant: O=C(O)c1cc(C(F)(F)F)nn1Cc1ccccc1
Agent: N
Agent: [Na]
Product: O=C(O)c1cc(C(F)(F)F)n[nH]1
Yield: 84.1 %

Procedure:
About 50 ml ammonia were condensed into a three-neck-flask in an ethanol-dry ice bath and 100 mg (3.70 mmol) 2-benzyl-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid were added. To the solution sodium was added in small portions until the blue color stayed for more then 5 minutes (about 260 mg, 11.3 mmol). The ammonia was evaporated overnight. Water was added and acidified with 2N HCl solution. The aqueous phase was extracted twice with ethyl acetate, the combined organic phases were dried over Na2SO4, the solvent was evaporated in vacuo to give 560 mg (3.11 mmol, 84%) 5-trifluoromethyl-2H-pyrazole-3-carboxylic acid as a yellow solid that was used without further purification. MS: M=179.0 (API−)
Reaction SMILES: [CH:1]1([NH:6][C:7]([NH:9][C:10]([C:29]2[CH:34]=[CH:33][C:32]([N:35]=C(C3C=CC=CC=3)C3C=CC=CC=3)=[CH:31][N:30]=2)([C:18]2[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([F:28])[CH:19]=2)[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.C1COCC1.CCOC(C)=O>Cl>[NH2:35][C:32]1[CH:33]=[CH:34][C:29]([C:10]([NH:9][C:7]([NH:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:8])([C:18]2[CH:23]=[C:22]([C:24]([F:26])([F:27])[F:25])[CH:21]=[C:20]([F:28])[CH:19]=2)[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:30][CH:31]=1
Reactant: O=C(NC1CCCC1)NC(Cc1ccccc1)(c1cc(F)cc(C(F)(F)F)c1)c1ccc(N=C(c2ccccc2)c2ccccc2)cn1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Nc1ccc(C(Cc2ccccc2)(NC(=O)NC2CCCC2)c2cc(F)cc(C(F)(F)F)c2)nc1
Yield: 90.3 %

Procedure:
1-Cyclopentyl-3-(1-(5-(diphenylmethyleneamino)pyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)urea (77 mg, 0. 12 mmol) was stirred in 2N HCl (1.5 mL) and THF (6 mL) at room temperature for 30 min. LC-MS showed completion of the reaction. EtOAc was added and the solution was washed with saturated NaHCO3, H2O, brine, dried (Na2SO4), filtered, and concentrated to dryness. The residue was purified by flash chromatography (silica gel, hexanes/EtOAc, came out 45-50% EtOAc in hexanes) to give 1-(1-(5-aminopyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-cyclopentylurea as colorless film (52 mg, yield: 90.3%). LC-MS ESI 487.32 (M+H) (10-90% MeOH in H2O with 0.1% TFA in a 4-min run, retention time=3.29 min). 1H NMR (400 MHz, CDCl3) δ ppm 1.23-1.32 (m, 1 H), 1.39-1.50 (m, 1 H), 1.58-1.69 (m, 4 H), 1.86 (dt, J=12.47, 6.24 Hz, 1 H), 1.99-2.08 (m, 1 H), 3.54 (d, J=12.47 Hz, 1 H), 3.74 (s, br, 1 H), 3.89-4.00 (m, 1 H), 4.33 (d, J=7.09 Hz, 1 H), 4.44 (d, J=12.47 Hz, 1H), 6.65-6.72 (m, 2 H), 6.88-6.93 (m, 1 H), 6.97-7.02 (m, 1 H), 7.07-7.19 (m, 4 H), 7.22-7.31 (m, 1 H), 7.39 (d, J=10.03 Hz, 1 H), 7.55 (s, 1 H), 7.75 (d, J=2.69 Hz, 1H).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].I[CH2:14][CH3:15].Cl>C1COCC1.O>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[CH2:14][CH3:15])=[CH:4][CH:3]=1
Reactant: CCI
Reactant: Brc1ccc2cc[nH]c2c1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCn1ccc2ccc(Br)cc21
Temperature: 25 °C
Reaction time: 0.58 h
Yield: 70.4 %

Procedure:
A solution of 6-bromoindole (1.01 g, 5.15 mmol) in THF (10 mL) was cooled in an ice bath. Sodium hydride (0.459 g of 60% dispersion in oil, 11.5 mmol) was added. After stirring for 35 minutes at room temperature under nitrogen, the reaction mixture was again cooled in an ice bath, and iodoethane (0.90 mL, 11 mmol) was added. The mixture was stirred for 2 hours at room temperature, poured into excess water, acidified with 2N hydrochloric acid and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was purified by flash chromatography using hexane as an eluant to yield 6-bromo-1-ethyl-1H-indole (0.812 g, 71%) as a yellow oil. 1HNMR (300 MHz, DMSO-d6): δ7.75 (s, 1H), 7.5 (d, 1H, J=7.8 Hz), 7.45 (d, 1H, J=3.9 Hz), 7.15 (dd, 1H, J=7.8 Hz and 1.6 Hz), 6.45 (s, 1H), 4.2 (q, 2H, J=7.1 Hz), and 1.35 ppm (t, 3H, J=7.0 Hz).
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][O:11][C:12]1[CH:19]=[C:18]([O:20][CH3:21])[C:17]([C:22]2[S:23][CH:24]=[CH:25][CH:26]=2)=[CH:16][C:13]=1[CH:14]=O.[C:27]([C:30]1[CH:35]=[CH:34][C:33]([S:36]([NH2:39])(=[O:38])=[O:37])=[CH:32][CH:31]=1)(=[O:29])[CH3:28]>>[NH:3]1[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:1]=[C:2]1[CH2:10][O:11][C:12]1[CH:19]=[C:18]([O:20][CH3:21])[C:17]([C:22]2[S:23][CH:24]=[CH:25][CH:26]=2)=[CH:16][C:13]=1/[CH:14]=[CH:28]/[C:27]([C:30]1[CH:31]=[CH:32][C:33]([S:36]([NH2:39])(=[O:38])=[O:37])=[CH:34][CH:35]=1)=[O:29]
Reactant: CC(=O)c1ccc(S(N)(=O)=O)cc1
Reactant: COc1cc(OCc2nc3ccccc3[nH]2)c(C=O)cc1-c1cccs1
Product: COc1cc(OCc2nc3ccccc3[nH]2)c(/C=C/C(=O)c2ccc(S(N)(=O)=O)cc2)cc1-c1cccs1
Yield: 56 %

Procedure:
The title compound was prepared by condensing 2-(1H-benzoimidazol-2-ylmethoxy)-4-methoxy-5-thiophen-2-yl-benzaldehyde (Ex-113A) and 4-acetyl-benzenesulfonamide (Ex-26A) in a similar manner as described in Ex-22. Light orange solid, 56% yield, mp 235–237° C. (dec). 1H-NMR (300 MHz, DMSO-d6) δ 8.27 (s, 1H), 8.19 (d, 2H, J=8.4 Hz), 8.11 (d, 1H, J=15.4 Hz), 7.98 (d, 1H, J=15.4 Hz), 7.89 (d, 2H, J=8.4 Hz), 7.66–7.70 (m, 3H), 7.53–7.55 (m, 3H), 7.22–7.27 (m, 2H), 7.12–7.15 (m, 2H), 5.59 (s, 2H), 4.01 (s, 3H). MS (ESI) m/z=546 ([M+H]+, 100%). Anal. Calcd. for C28H23N3O5S2: C, 61.64; H, 4.25; N, 7.70; S, 11.75. Found: C, 61.49; H, 4.47; N, 7.74; S, 11.58.
Reaction SMILES: [CH3:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])=[CH:9][CH:8]=2)[C:5]([C:22]2[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=2)=[CH:4][CH:3]=1.O[C@@H:30]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:31]([O:33][CH2:34][CH3:35])=[O:32].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1(C)C=CC=CC=1.O>[CH3:1][C:2]1[N:6]([C:7]2[CH:8]=[CH:9][C:10]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])=[CH:11][CH:12]=2)[C:5]([C:22]2[CH:23]=[CH:24][C:25]([O:28][C@H:30]([CH2:36][C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:26][CH:27]=2)=[CH:4][CH:3]=1
Reactant: CCCCCCCCOc1ccc(-n2c(C)ccc2-c2ccc(O)cc2)cc1
Reactant: CCOC(=O)[C@@H](O)Cc1ccccc1
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CCCCCCCCOc1ccc(-n2c(C)ccc2-c2ccc(O[C@H](Cc3ccccc3)C(=O)OCC)cc2)cc1
Temperature: 80 °C
Reaction time: 12 h
Yield: 39.6 %

Procedure:
To a solution of 4-[5-methyl-1-(4-octyloxyphenyl)-1H-pyrrol-2-yl]phenol (740 mg, 1.96 mmol), ethyl (S)-2-hydroxy-3-phenylpropanoate (570 mg, 2.94 mmol) and triphenylphosphine (770 mg, 2.94 mmol) in toluene (2 ml) was added 1,1′-(azodicarbonyl)dipiperidine (741 mg, 2.94 mmol) and the mixture was stirred at 80° C. for 12 hours. The reaction solution was poured into water and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate anhydride and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=30:1) to give the object compound as an oily substance. 420 mg (yield: 39.6%)
Reaction SMILES: [CH2:1]([C:8]1[C:9]([NH:22][C:23](=[O:31])[CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[N:10][CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20]C)=[CH:16][CH:15]=2)[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl>[CH2:1]([C:8]1[C:9]([NH:22][C:23](=[O:31])[CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[N:10][CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=2)[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1ccc(-c2cnc(NC(=O)Cc3ccccc3)c(Cc3ccccc3)n2)cc1
Agent: BrB(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=C(Cc1ccccc1)Nc1ncc(-c2ccc(O)cc2)nc1Cc1ccccc1
Temperature: 25 °C
Yield: 44.1 %

Procedure:
Under an argon atmosphere, 3-benzyl-5-(4-methoxyphenyl)-2-(phenylacetylamino)pyrazine (c-16) (250 mg, 611 was dissolved in anhydrous dichloromethane (15 mL) and to this was added 1.0 M solution of boron tribromide in dichloromethane (2.15 mL, 2.15 mmol) while stirring at room temperature, and heated to reflux for 15 h. After refluxing, it was cooled to room temperature, and to this was added saturated aqueous solution of sodium bicarbonate to stop the reaction, and concentrated under reduced pressure using a rotary evaporator to remove dichloromethane. The suspension was filtered and the residue was dried to give 270 mg of the crude product as a pale yellow solid. Recrystallization from methanol gave 3-benzyl-5-(4-hydroxyphenyl)-2-(phenylacetylamino)pyrazine (h-coelenteramide) (c-13) as a colorless solid (107 mg, 44.1%). Rf=0.20 (dichloromethane/ethyl acetate=4/1). Mp. 259-261° C. UV (MeOH) λmax (log ε) 332 (4.38), 294.5 (4.38), 276 (4.35). UV (pH 7.4 PB, 1% DMSO) λmax (log ε) 345.5 (3.52), 303 (3.57). 1H NMR (400 MHz, DMSO-d6) δ 3.67 (s, 2H), 4.01 (s, 2H), 6.84-6.89 (AA′BB′, 2H), 7.02 (d, J=6.9 Hz, 2H), 7.11-7.23 (m, 4H), 7.23-7.30 (m, 1H), 7.32-7.37 (m, 4H), 7.90-7.95 (AA′BB′, 2H), 8.82 (s, 1H), 9.87 (s, 1H), 10.48 (s, 1H). 13C NMR (75.5 MHz, DMSO-d6) δ 39.7, 42.4, 115.8 (2C), 126.2, 126.4, 126.7, 128.1 (2C), 128.3 (2C), 128.4 (2C), 128.9 (2C), 129.3 (2C), 135.6, 136.9, 138.3, 143.3, 148.6, 150.5, 159.1, 169.9. IR (KBr, cm−1) 662, 702, 712, 727, 843, 1157, 1173, 1231, 1281, 1321, 1355, 1368, 1452, 1495, 1523, 1541, 1584, 1595, 1611, 1668, 3063, 3169, 3264. HRMS (FAB+) m/z 396.1706 (M+H, C25H22N3O2 requires 396.1712).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[N:6][CH:5]=[CH:4][N:3]=1.CC(C)([O-])C.[K+].[Cl:14][C:15]1[C:20]([N+:21]([O-:23])=[O:22])=[C:19](Cl)[CH:18]=[C:17]([CH3:25])[N:16]=1.[NH4+].[Cl-]>CS(C)=O>[Cl:14][C:15]1[C:20]([N+:21]([O-:23])=[O:22])=[C:19]([NH:1][C:2]2[CH:7]=[N:6][CH:5]=[CH:4][N:3]=2)[CH:18]=[C:17]([CH3:25])[N:16]=1
Reactant: Cc1cc(Cl)c([N+](=O)[O-])c(Cl)n1
Reactant: Nc1cnccn1
Agent: CC(C)(C)[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: CS(C)=O
Product: Cc1cc(Nc2cnccn2)c([N+](=O)[O-])c(Cl)n1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 22.5 %

Procedure:
To a solution of 2-aminopyrazine (0.900 g, 9.47 mmol) in DMSO (40 mL) was added potassium tert-butoxide (2.13 g, 18.9 mmol) followed by 2,4-dichloro-6-methyl-3-nitropyridine (2.00 g, 9.47 mmol). After stirring for 30 min at rt, sat. NH4Cl solution was added. The organic layer was separated and the water layer was extracted with CH2Cl2 three times. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. Chromatography on silica gel (0-70% ethyl acetatehexanes) provided the desired product (567 mg, 23%). MS (ESI) mass calcd. C10H8ClN5O2, 265.04. m/z found, 266.0 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 8.69-8.62 (br s, 1H), 8.38-8.34 (m, 2H), 8.34-8.29 (m, 2H), 2.59-2.56 (m, 3H).