Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3](=[C:7](SC)[C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=1)[C:4]([NH2:6])=[O:5])#[N:2].Cl.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][NH2:27])=[CH:22][CH:21]=1.[OH-].[Na+]>>[NH2:2][C:1]1[N:26]([C:23]2[CH:24]=[CH:25][C:20]([O:19][CH3:18])=[CH:21][CH:22]=2)[N:27]=[C:7]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[C:3]=1[C:4]([NH2:6])=[O:5]
Reactant: COc1ccc(NN)cc1
Reactant: CSC(=C(C#N)C(N)=O)c1ccc(C)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: COc1ccc(-n2nc(-c3ccc(C)cc3)c(C(N)=O)c2N)cc1
Yield: 31.3 %

Procedure:
The title compound was prepared from 2-cyano-3-methylthio-3-(4-tolyl) acrylamide (232 mg, 1.0 mmol), 4-methoxyphenylhydrazine hydrochloride (192 mg, 1.1 mmol) and sodium hydroxide (44 mg, 1.1 mmol) following the procedure used for the compound of Example 12. The crude product was purified by chromatography (SiO2, 75% ethyl acetate in hexane) and recrystallisation from ethyl acetate-hexane to give the title compound as white crystals (101 mg) m.p. 174-175°. δH (d6DMSO) 7.49-7.43 (4H, m), 7.28 (2H, d, J 7.8 Hz), 7.07 (2H, d, J 8.9 Hz), 6.32 (2H, br s), 3.81 (3H, s) and 2.29 (3H, s), one set of amino protons not observed. MS (ES+) 323 (MH+, 100%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:26])[CH:4]([C:9]1[CH:10]=[C:11]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)[CH:12]=[C:13]([OH:15])[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7].[F:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1>>[CH3:1][O:2][C:3](=[O:26])[CH:4]([C:9]1[CH:10]=[C:11]([C:16]2[CH:17]=[CH:18][C:19]([C:22]([F:23])([F:25])[F:24])=[CH:20][CH:21]=2)[CH:12]=[C:13]([O:15][C:31]2[CH:32]=[CH:33][C:28]([F:27])=[CH:29][CH:30]=2)[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7]
Reactant: COC(=O)C(CC(C)C)c1cc(O)cc(-c2ccc(C(F)(F)F)cc2)c1
Reactant: OB(O)c1ccc(F)cc1
Product: COC(=O)C(CC(C)C)c1cc(Oc2ccc(F)cc2)cc(-c2ccc(C(F)(F)F)cc2)c1
Yield: 43 %

Procedure:
The title compound was prepared in 43% yield from 2-(5-hydroxy-4′-trifluoromethyl-biphenyl-3-yl)-4-methyl-pentanoic acid methyl ester (prepared in Example 15, step (f)) and 4-fluorobenzeneboronic acid under the conditions described in Example 15, step (g).
Reaction SMILES: [NH2:1][N:2]1[N:11]=[C:10]([Cl:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:13].[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22](O)=[O:23])=[CH:17][CH:16]=1>>[Cl:12][C:10]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](=[O:13])[N:2]([NH:1][C:22](=[O:23])[CH2:21][C:18]2[CH:19]=[CH:20][C:15]([Cl:14])=[CH:16][CH:17]=2)[N:11]=1
Reactant: Nn1nc(Cl)c2ccccc2c1=O
Reactant: O=C(O)Cc1ccc(Cl)cc1
Product: O=C(Cc1ccc(Cl)cc1)Nn1nc(Cl)c2ccccc2c1=O

Procedure:
The product from Example 19A and 2-(4-chlorophenyl)acetic acid were processed using a method similar to that described in Example 17C to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.70 (s, 2H) 7.23-7.56 (m, 4H) 7.97-8.17 (m, 3H) 8.36 (d, J=7.63 Hz, 1H) 11.77 (s, 1H); MS (ESI) m/z 349 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:8]=[C:7]([CH3:9])[CH:6]=[C:5]([CH3:10])[C:3]=1[NH2:4].[F:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][C:19](Cl)=[O:20])=[CH:14][CH:13]=1>C(#N)C>[Br:1][C:2]1[CH:8]=[C:7]([CH3:9])[CH:6]=[C:5]([CH3:10])[C:3]=1[NH:4][C:19](=[O:20])[CH2:18][C:15]1[CH:16]=[CH:17][C:12]([F:11])=[CH:13][CH:14]=1
Reactant: Cc1cc(C)c(N)c(Br)c1
Reactant: O=C(Cl)Cc1ccc(F)cc1
Solvent: CC#N
Product: Cc1cc(C)c(NC(=O)Cc2ccc(F)cc2)c(Br)c1
Temperature: 150 °C
Yield: 66 %

Procedure:
2-Bromo-4,6-dimethyl-aniline (600 mg) and (4-fluoro-phenyl)-acetyl chloride (543 mg) were dissolved in acetonitrile (6 mL) and heated to 150° C. for 10 minutes in a sealed microwave process vial. The reaction was cooled to 0° C., the product filtered off and washed with cold acetonitrile (50 mL) affording 665 mg (66% yield) of the title compound as a white solid. LC-MS (m/z) 337 (MH+); tR=2.93, (UV, ELSD) 90%, 98%. 1H NMR (500 MHz, DMSO-d6): 2.05 (s, 6H), 2.25 (s, 3H), 3.63 (s, 2H), 7.05 (b, 1H), 7.15 (dt, 2H), 7.32 (b, 1H), 7.40 (dt, 2H), 9.67 (s, 1H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[CH:14]([OH:25])[CH2:15][O:16][CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:34]2[CH:39]=[CH:38][C:37]([C:40]3([C:43]([NH:45][S:46]([CH3:49])(=[O:48])=[O:47])=[O:44])[CH2:42][CH2:41]3)=[CH:36][CH:35]=2)O1>>[OH:25][CH:14]([C:9]1[C:10]([CH3:13])=[N:11][O:12][C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([C:34]2[CH:35]=[CH:36][C:37]([C:40]3([C:43]([NH:45][S:46]([CH3:49])(=[O:48])=[O:47])=[O:44])[CH2:42][CH2:41]3)=[CH:38][CH:39]=2)=[CH:3][CH:4]=1)[CH2:15][O:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: CC1(C)OB(c2ccc(C3(C(=O)NS(C)(=O)=O)CC3)cc2)OC1(C)C
Reactant: Cc1noc(-c2ccc(Br)cc2)c1C(O)COCCc1ccccc1
Product: Cc1noc(-c2ccc(-c3ccc(C4(C(=O)NS(C)(=O)=O)CC4)cc3)cc2)c1C(O)COCCc1ccccc1

Procedure:
Prepared according to the procedure described in Example 2, using 1-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-2-phenethyloxy-ethanol and N-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarbonyl}-methanesulfonamide.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][CH:7]=[C:8]2[C:13]([OH:15])=[O:14].[CH3:16]O>OS(O)(=O)=O>[CH3:16][O:14][C:13]([C:8]1[C:9]2[C:4](=[C:3]([O:2][CH3:1])[CH:12]=[CH:11][CH:10]=2)[CH2:5][CH2:6][CH:7]=1)=[O:15]
Reactant: COc1cccc2c1CCC=C2C(=O)O
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)C1=CCCc2c(OC)cccc21
Yield: 94 %

Procedure:
5-Methoxy-3,4-dihydronaphthalene-1-carboxylic acid (100 g, 490 mmol) was dissolved in 800 mL of methanol and 20 mL of 96% H2SO4, and heated at reflux for 18 hours. The reaction was then cooled and evaporated under reduced pressure to a volume of 100 mL, and quenched on ice. The aqueous mixture was extracted with diethyl ether (3×100 mL), and the organic phase was washed with water, 5% aqueous NaHCO3, brine, and then dried (MgSO4) and evaporated to yield 101 g (94%) of the title compound as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 2.36 (m, 2H), 2.78 (t, 3H), 3.83 (s, 6H), 6.82 (d, 1H), 7.14 (t, 1H), 7.19 (t, 1H), 7.40 (t, 1H).
Reaction SMILES: C(OC[O:10][CH2:11][C@@H:12]([CH3:27])[CH2:13][CH2:14][CH2:15][C:16]([CH3:26])([CH3:25])[O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])C1C=CC=CC=1.[H][H]>C(OCC)(=O)C.[Pd]>[Si:18]([O:17][C:16]([CH3:25])([CH3:26])[CH2:15][CH2:14][CH2:13][C@H:12]([CH3:27])[CH2:11][OH:10])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]
Reactant: C[C@@H](CCCC(C)(C)O[Si](C)(C)C(C)(C)C)COCOCc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: C[C@H](CO)CCCC(C)(C)O[Si](C)(C)C(C)(C)C
Yield: 78 %

Procedure:
2nd procedure. To a solution of compound 3 (0.5 g, 1.27 mmol) in ethyl acetate (25 mL) was added Pd/C (10%, 380 mg) at room temperature. The reaction mixture was hydrogenated for 3 h under the hydrogen pressure of 10 Pa. Then, the mixture was filtered and the solvent was evaporated under reduced pressure. The oily residue was applied on a silica Sep-Pak cartridge (5 g) and washed with hexane/AcOEt (9:1) producing an oily alcohol 4 (272 mg, 78%).
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:36]=[CH:35][C:8]([CH2:9][CH:10]([C:21]([NH:23][CH:24]([C:32](O)=[O:33])[CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:22])[NH:11][C:12](=[O:20])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:7][C:6]=1[Cl:37])[CH:2]=[CH2:3].Cl.[CH3:39][O:40][C:41](=[O:44])[CH2:42][NH2:43].C(N(CC)CC)C.C1CCC(N=C=NC2CCCCC2)CC1>O1CCCC1.C(Cl)(Cl)Cl>[CH3:39][O:40][C:41](=[O:44])[CH2:42][NH:43][C:32](=[O:33])[CH:24]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[NH:23][C:21](=[O:22])[CH:10]([CH2:9][C:8]1[CH:35]=[CH:36][C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[C:6]([Cl:37])[CH:7]=1)[NH:11][C:12](=[O:20])[CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: COC(=O)CN
Reactant: C=CCOc1ccc(CC(NC(=O)Cc2ccccc2)C(=O)NC(Cc2ccccc2)C(=O)O)cc1Cl
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Product: C=CCOc1ccc(CC(NC(=O)Cc2ccccc2)C(=O)NC(Cc2ccccc2)C(=O)NCC(=O)OC)cc1Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4-Allyloxy-3-chloro-phenylacetyl-(DL)-phenylalanyl-(DL)-phenylalanine (1.20 g) was dissolved in dry tetrahydrofuran (10 ml). To the solution was added glycine methyl ester hydrochloride (0.25 g) in dry chloroform (10 ml) containing dry triethylamine (0.28 ml). DCC (0.41 g) was added and the reaction mixture was stirred overnight at room temperature. DCU was then filtered off.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]([OH:16])=O)=[CH:9][CH:8]=1)=[O:6].[N:17]1(C(N)=O)[CH2:21]CC[CH2:18]1>>[CH3:18][N:17]([CH3:21])[C:14](=[O:16])[CH2:13][C:10]1[CH:11]=[CH:12][C:7]([C:5](=[O:6])[CH2:4][CH2:3][CH2:2][Cl:1])=[CH:8][CH:9]=1
Reactant: NC(=O)N1CCCC1
Reactant: O=C(O)Cc1ccc(C(=O)CCCCl)cc1
Product: CN(C)C(=O)Cc1ccc(C(=O)CCCCl)cc1

Procedure:
[4-(4-Chloro-butyryl)-phenyl]-acetic acid, pyrroldineamide;
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:3][CH:2]=1.Br[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])=[CH:17][CH:16]=1>C(#N)C>[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:8][CH2:9][N:10]([CH2:14][C:15]3[CH:16]=[CH:17][C:18]([CH2:21][CH2:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])=[CH:19][CH:20]=3)[CH2:11][CH2:12]2)=[CH:3][CH:2]=1
Reactant: COC(=O)CCCc1ccc(CBr)cc1
Reactant: c1cc(N2CCNCC2)ccn1
Solvent: CC#N
Product: COC(=O)CCCc1ccc(CN2CCN(c3ccncc3)CC2)cc1
Temperature: 30 °C

Procedure:
1-(4-Pyridyl)piperazine (1.63 g) was dissolved in warm acetonitrile (25 ml), the solution cooled to 30° C. and with stirring, a solution of methyl 4-(4-bromomethylphenyl)butyrate in acetonitrile (5 ml) added. After 30 minutes the resulting precipitate was removed by filtration and the filtrate concentrated in vacuo to give a yellow oil. Purification by flash chromatography on silica, eluting with 0 to 4% v/v methanol/dichloromethane gave a solid. Trituration with ether and removal of the insoluble solid gave a clear solution. Concentration of this solution gave the title compound, 0.90 g, as a white fluffy solid: m.p. 126°-127° C.; NMR (d6DMSO) δ8.14 (2H, d), 7.24 (2H, d), 7.14 (2H, d), 6.77 (2H, d), 3.59 (3H, s), 3.48 (2H, s), 3.30 (4H, t), 2.59 (2H, t), 2.47 (4H, t), 2.32 (2H, t), 1.63 (2H, m); m/e 354 (M+H)+ ; calculated for C21H27N3O2.0.25H2O: C, 70.4; H, 7.7; N, 11.7. found: C, 70.6; H, 7.6; N, 11.7%.
Reaction SMILES: [CH3:1][O:2][C:3]([N:5]1[C@@H:13]2[C@@H:8]([C@@:9]([OH:23])([C:14]#[C:15][C:16]3[CH:17]=[C:18]([CH3:22])[CH:19]=[CH:20][CH:21]=3)[CH2:10][CH2:11][CH2:12]2)[CH2:7][CH2:6]1)=[O:4].[C:24](O)(=[O:29])[CH2:25][CH2:26][CH2:27][CH3:28]>>[CH3:1][O:2][C:3]([N:5]1[C@H:13]2[C@H:8]([C@:9]([O:23][C:24](=[O:29])[CH2:25][CH2:26][CH2:27][CH3:28])([C:14]#[C:15][C:16]3[CH:17]=[C:18]([CH3:22])[CH:19]=[CH:20][CH:21]=3)[CH2:10][CH2:11][CH2:12]2)[CH2:7][CH2:6]1)=[O:4]
Reactant: CCCCC(=O)O
Reactant: COC(=O)N1CC[C@H]2[C@@H]1CCC[C@]2(O)C#Cc1cccc(C)c1
Product: CCCCC(=O)O[C@@]1(C#Cc2cccc(C)c2)CCC[C@@H]2[C@H]1CCN2C(=O)OC

Procedure:
Synthesis in analogy to the General Method 1 starting from (3aS,4R,7aS)-4-hydroxy-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester and pentanoic acid to yield (3aR,4S,7aR)-4-pentanoyloxy-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester. MS [M+Na]=420; RT=8.337 min; LC-MS Method III
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C@@H:4]([O:15][CH2:16][CH3:17])[CH2:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([OH:13])=[CH:8][C:7]=1[CH3:14].Cl[CH2:20][C:21]1[N:22]=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([CH:33]([CH3:35])[CH3:34])=[CH:29][CH:28]=2)[O:24][C:25]=1[CH3:26].C(C1C=CC(C=O)=CC=1)(C)C.O=P(Cl)(Cl)Cl.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+]>>[CH3:1][O:2][C:3](=[O:18])[C@@H:4]([O:15][CH2:16][CH3:17])[CH2:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([O:13][CH2:20][C:21]2[N:22]=[C:23]([C:27]3[CH:28]=[CH:29][C:30]([CH:33]([CH3:35])[CH3:34])=[CH:31][CH:32]=3)[O:24][C:25]=2[CH3:26])=[CH:8][C:7]=1[CH3:14]
Reactant: Cc1oc(-c2ccc(C(C)C)cc2)nc1CCl
Reactant: CCO[C@@H](Cc1c(C)cc(O)cc1C)C(=O)OC
Agent: CC(C)c1ccc(C=O)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O=P(Cl)(Cl)Cl
Product: CCO[C@@H](Cc1c(C)cc(OCc2nc(-c3ccc(C(C)C)cc3)oc2C)cc1C)C(=O)OC

Procedure:
In analogy to the procedure described in example 1 f], (2S)-2-ethoxy-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionic acid methyl ester (example 29 e]) was reacted with 4-chloromethyl-2-(4-isopropyl-phenyl)-5-methyl-oxazole (prepared from 4-isopropyl-benzaldehyde and diacetyl monoxyme followed by treatment with POCl3 in analogy to the procedures described in examples 5 a] and 2 b]) in the presence of cesium carbonate and potassium iodide to yield (S)-2-ethoxy-3-{4-[2-(4-isopropyl-phenyl)-5-methyl-oxazol-4-ylmethoxy]-2,6-dimethyl-phenyl}-propionic acid methyl ester as colorless liquid.
Reaction SMILES: [CH2:1]([CH:9]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14](B(O)O)[CH:15]=2)[O:10]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].Cl[C:22]1[N:27]=[CH:26][C:25]([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])=[CH:24][N:23]=1.C1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[CH2:28]([C:25]1[CH:24]=[N:23][C:22]([C:14]2[CH:15]=[C:16]3[C:11](=[CH:12][CH:13]=2)[O:10][CH:9]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH2:17]3)=[N:27][CH:26]=1)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37]
Reactant: CCCCCCCCCCc1cnc(Cl)nc1
Reactant: CCCCCCCCC1Cc2cc(B(O)O)ccc2O1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: O
Product: CCCCCCCCCCc1cnc(-c2ccc3c(c2)CC(CCCCCCCC)O3)nc1
Yield: 23.9 %

Procedure:
Under nitrogen atmosphere, 0.30 g (1.09 mM) of 2-octylcoumaran-5-boronic acid, 0.26 g (1.02 mM) of 2-chloro-5-decylpyrimidine and 1.5 ml of benzene were placed in a 20 ml-round-bottomed flask. Under stirring, 0.06 g of tetrakis(triphenylphosphine) palladium (0) and 1.5 ml of a 2M-sodium carbonate aqueous solution were added to the mixture, followed by refluxing for 5.5 hours. After the reaction, the reaction mixture was poured into water and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried with mirabilite and concentrated under reduced pressure to obtain a residue. The residue was purified by silica gel column chromatography and recrystallized from a mixture solvent of toluene and methanol to obtain 0.11 g of 5-(5-decylpyrimidine-2-yl)-2-octylcoumaran (Ex. Comp. No-I-17) (Yield: 22.5%). The product showed the following phase transition temperatures (°C.). ##STR96##
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])[CH3:2].[OH:8][C:9]([C:20]1[CH:36]=[C:35]2[N:23]([CH2:24][C:25]3[C:26]2=[N:27][C:28]2[C:33]([CH:34]=3)=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22](=[O:37])[C:21]=1[CH2:38][OH:39])([CH2:18][CH3:19])[CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].C(N(CC)CC)C>ClCCl>[C:1]([O:39][CH2:38][C:21]1[C:22](=[O:37])[N:23]2[C:35](=[CH:36][C:20]=1[C:9]([OH:8])([CH2:18][CH3:19])[CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:26]1=[N:27][C:28]3[C:33]([CH:34]=[C:25]1[CH2:24]2)=[CH:32][CH:31]=[CH:30][CH:29]=3)(=[O:3])[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: CCC(O)(CC(=O)OC(C)(C)C)c1cc2n(c(=O)c1CO)Cc1cc3ccccc3nc1-2
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCC(O)(CC(=O)OC(C)(C)C)c1cc2n(c(=O)c1COC(C)=O)Cc1cc3ccccc3nc1-2
Yield: 69.1 %

Procedure:
Acetic anhydride (70 μl, 0.7 mmol) is added dropwise to a solution of tert-butyl 3-hydroxy-3-[8-(hydroxymethyl)-9-oxo-9,11-dihydroindolizino[1,2-b]quinolin-7-yl]pentanoate (200 mg, 0.46 mmol) and triethylamine (140 μl, 1 mmol) in dichloromethane (5 ml) and the resultant mixture is agitated at ambient temperature for 21 hours. The volatile components are evaporated off and the residue is purified by chromatography on a silica gel column (1-2% MeOH/CH2Cl2), which produces 152 mg of sought compound in the form of a yellow solid, m.p. 195-196° C.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH:7]1[C:11](=[O:12])[CH:10]=[CH:9][CH2:8]1.[CH:13]1[C:14](/[CH:29]=[N:30]/[OH:31])=[CH:15][CH:16]=[N+:17]([CH2:19][N+:20]2[CH:25]=[CH:24][C:23](/[CH:26]=[N:27]/[OH:28])=[CH:22][CH:21]=2)[CH:18]=1.[Br-:32].[Br-].[C:34]1([CH3:44])[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:35]=1>N1C=CC=CC=1>[C:34]1([CH3:44])[CH:39]=[CH:38][C:37]([S:40]([O:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]2[C:11](=[O:12])[CH2:10][CH2:9][CH:8]=2)(=[O:42])=[O:41])=[CH:36][CH:35]=1.[CH:15]1[C:14](/[CH:29]=[N:30]/[OH:31])=[CH:13][CH:18]=[N+:17]([CH2:19][N+:20]2[CH:21]=[CH:22][C:23](/[CH:26]=[N:27]/[OH:28])=[CH:24][CH:25]=2)[CH:16]=1.[Br-:32].[Br-:32]
Reactant: O=C1C=CCC1CCCCCO
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: O/N=C/c1cc[n+](C[n+]2ccc(/C=N/O)cc2)cc1
Agent: [Br-]
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OCCCCCC2=CCCC2=O)cc1

Procedure:
Treatment of 2-(hydroxypentyl)-2-cyclopentenone methoxime (Example 25) with p-toluenesulfonyl chloride in pyridine in the manner described in Example 18 gives a colorless oil. IR (film) 1600, 1190, 1180, 1050, 885 cm-1.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][NH:8][C:9]([C:11]1[CH:20]=[C:14]2[CH2:15][NH:16][CH2:17][CH2:18][CH2:19][N:13]2[N:12]=1)=[O:10].[CH3:21][O:22][C:23]1[CH:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][CH:24]=1.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.CN1CCOCC1>C(Cl)Cl>[CH3:21][O:22][C:23]1[CH:31]=[CH:30][C:26]([C:27]([N:16]2[CH2:17][CH2:18][CH2:19][N:13]3[N:12]=[C:11]([C:9]([NH:8][O:7][CH:2]4[CH2:3][CH2:4][CH2:5][CH2:6][O:1]4)=[O:10])[CH:20]=[C:14]3[CH2:15]2)=[O:28])=[CH:25][CH:24]=1
Reactant: O=C(NOC1CCCCO1)c1cc2n(n1)CCCNC2
Reactant: COc1ccc(C(=O)O)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: COc1ccc(C(=O)N2CCCn3nc(C(=O)NOC4CCCCO4)cc3C2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture of N-(tetrahydro-2H-pyran-2-yloxy)-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2-carboxamide (0.0283 g, 0.101 mmol) and 4-methoxybenzoic acid (0.016 g, 0.105 mmol) in methylene chloride (1 mL) was added N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.0434 g, 0.114 mmol) and N-methylmorpholine (0.0333 mL, 0.303 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with methylene chloride (2 mL) and washed with aqueous NaHCO3 (2 mL). The aqueous layer was extracted with additional methylene chloride (3 mL) and the combined organic layers concentrated to afford Intermediate 30 as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([O:18][CH3:19])=[CH:5][C:6]2[O:10][N:9]=[C:8]([CH:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)[C:7]=2[CH:17]=1.[CH3:20][C:21]1[NH:22][C:23]2[C:28]([C:29]=1CCCS(C1C=CC=CC=1)(=O)=O)=[CH:27][CH:26]=[CH:25][CH:24]=2.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+]>O>[CH3:1][O:2][C:3]1[C:4]([O:18][CH3:19])=[CH:5][C:6]2[O:10][N:9]=[C:8]([CH:11]3[CH2:12][CH2:13][N:14]([C:29]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[NH:22][C:21]=4[CH3:20])[CH2:15][CH2:16]3)[C:7]=2[CH:17]=1
Reactant: COc1cc2onc(C3CCNCC3)c2cc1OC
Reactant: Cc1[nH]c2ccccc2c1CCCS(=O)(=O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc2onc(C3CCN(c4c(C)[nH]c5ccccc45)CC3)c2cc1OC
Temperature: 25 °C
Yield: 26.8 %

Procedure:
A stirred mixture of 5.0 g of 5,6-dimethoxy-3-(4-piperidyl)-1,2-benzisoxazole, 6.78 g of 2-methyl-3-(phenylsulfonylpropyl)indole, 120 ml of dimethylformamide and 15.0 g of anhydrous potassium carbonate was heated to 90° for 6 hrs and overnight at ambient temperature. The mixture was poured into water (300 ml) and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and the solvent was removed in vacuo to yield a solid. The solid was purified by passing it through a silica gel column (20:1) and eluting it with dichloromethane-methanol (1%). Recrystallization two times from ethanol-water yielded 2.0 g (24%) of product, mp 176°-178°.
Reaction SMILES: O=[C:2]([C:24]1[CH:28]=[CH:27][S:26][CH:25]=1)[CH2:3][NH:4][C:5]([C:7]1[S:8][C:9]2[C:15]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:14][CH:13]=[C:12]([O:22][CH3:23])[C:10]=2[N:11]=1)=O.FC(F)(F)C([O-])=O.[NH4+:36]>O>[CH3:23][O:22][C:12]1[C:10]2[N:11]=[C:7]([C:5]3[NH:4][CH:3]=[C:2]([C:24]4[CH:28]=[CH:27][S:26][CH:25]=4)[N:36]=3)[S:8][C:9]=2[C:15]([N:16]2[CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)=[CH:14][CH:13]=1
Reactant: [NH4+]
Reactant: COc1ccc(N2CCOCC2)c2sc(C(=O)NCC(=O)c3ccsc3)nc12
Agent: O=C([O-])C(F)(F)F
Solvent: O
Product: COc1ccc(N2CCOCC2)c2sc(-c3nc(-c4ccsc4)c[nH]3)nc12
Temperature: 25 °C
Yield: 62.9 %

Procedure:
A mixture of 0.10 g 4-methoxy-7-morpholin-4-yl-benzothiazole-2-carboxylic acid (2-oxo-2-thiophen-3-yl-ethyl)-amide and 0.32 g ammonium triflouroacetate was melted at 170° C. for 50 minutes and, after cooling to room temperature, suspended in water. Extraction with dichloromethane and chromatography on silicagel with ethylacetate/hexane 1:1 gave 0.06 g (59%) 4-methoxy-7-morpholin-4-yl-2-(4-thiophen-3-yl-1H-imidazol-2-yl)-benzothiazole as yellow solid; MS (ISP): m/e=399 (M+H+).
Reaction SMILES: C(OC(=O)[NH:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][N:17]1[CH2:21][CH:20]([OH:22])[CH2:19][CH:18]1[CH:23]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[O:24][CH:25]([C:34]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=1)[C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)C1C=CC=CC=1>C(OCC)(=O)C>[NH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][N:17]1[CH:18]([CH:23]([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[O:24][CH:25]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)[CH2:19][CH:20]([OH:22])[CH2:21]1
Reactant: COc1ccc(C(OC(c2ccccc2)C2CC(O)CN2CCCCCCNC(=O)OCc2ccccc2)c2ccc(OC)cc2)cc1
Solvent: CCOC(C)=O
Product: COc1ccc(C(OC(c2ccccc2)C2CC(O)CN2CCCCCCN)c2ccc(OC)cc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 92.5 %

Procedure:
Compound 30 (6.52 g, 10 mmol) was dissolved in ethyl acetate (100 mL) and purged with argon. To the solution was added 10% palladium on carbon (2 g). The flask was purged with hydrogen 2 times and stirred further at room temperature under hydrogen atmosphere for overnight. The disappearance of the starting material was confirmed by the TLC. The reaction mixture was filtered through a pad of Celite and washed with ethyl acetate. The combined organic layer was concentrated under reduced pressure to afford compound 31 (4.8 g, 93%) as white solid. This was used as such for the next step.
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4](=O)[CH2:5][CH2:6][CH2:7][C:8]([OH:10])=[O:9].[C:12]([O:18][CH2:19][CH3:20])(=[O:17])[CH2:13][C:14]([CH3:16])=O.C(O[Na])(C)=O.Cl>O>[CH2:19]([O:18][C:12]([C:13]1[C:4]([CH2:5][CH2:6][CH2:7][C:8]([OH:10])=[O:9])=[CH:3][NH:2][C:14]=1[CH3:16])=[O:17])[CH3:20]
Reactant: NCC(=O)CCCC(=O)O
Reactant: CCOC(=O)CC(C)=O
Agent: CC(=O)O[Na]
Agent: Cl
Solvent: O
Product: CCOC(=O)c1c(CCCC(=O)O)c[nH]c1C
Temperature: 25 °C
Yield: 70.6 %

Procedure:
6-amino-5-oxohexanoic acid hydrochloride (9.73 g, 49.8 mmol) was dissolved in H2O (35 mL), and ethyl acetoacetate (5.51 g, 42.34 mmol) and AcONa (20.3 g, 14.95 mmol) were added to the above-mentioned solution. The reaction solution was refluxed for 1 h, cooled to room temperature and 0.5N HCl was added until a pH of about 5 was reached. The combined organic layers were anidrified on Na2SO4, filtered and concentrated to give 7.15 g (yield: 60%) of the title compound as brown solid.