Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH2:2][C:3]([C@H:5]([C@@H:7]([C@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])=[O:4].O.S(=O)(=O)(O)O>CC(C)=O>[OH:1][CH2:2][C:3]([C@@H:5]([C@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])=[O:4].[CH3:2][C:3]([CH3:5])=[O:4].[CH3:2][C:3]([CH3:5])=[O:4]
Reactant: O=C(CO)[C@@H](O)[C@H](O)[C@@H](O)CO
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(C)=O
Product: O=C(CO)[C@H](O)[C@@H](O)[C@H](O)CO
Yield: 172.5 %

Procedure:
An amount of 100 g of L-sorbose, 1400 ml of hydrous acetone containing water in amounts of 1500 ppm, and 30 ml of concentrated sulfuric acid were placed in a 3 l-capacity flask. The mixture was reacted at 30° C. under stirring and under a reduced pressure for 1.5 hours in the same manner as in Example 1 except that the same hydrous acetone as above was used as an additive acetone, to provide 94.6 g (65.5% yield) of diacetone sorbose.
Reaction SMILES: [F:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[C:7](I)[C:3]=1[C:4]([OH:6])=[O:5].[N:13]1[NH:14][N:15]=[CH:16][CH:17]=1>>[F:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[C:7]([N:14]2[N:15]=[CH:16][CH:17]=[N:13]2)[C:3]=1[C:4]([OH:6])=[O:5]
Reactant: c1cn[nH]n1
Reactant: Cc1ccc(I)c(C(=O)O)c1F
Product: Cc1ccc(-n2nccn2)c(C(=O)O)c1F

Procedure:
The title compound was synthesized following the same general protocol as described in Example A11 using 2-fluoro-6-iodo-3-methylbenzoic acid and 2H-1,2,3-triazole. ESI-MS (m/z): 222 [M+1]+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[CH2:12](Br)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>>[CH2:12]([O:8][C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: BrCc1ccccc1
Reactant: Nc1ccc(O)cc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: Nc1ccc(OCc2ccccc2)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 96 h
Yield: 64 %

Procedure:
A solution containing 4-amino-3-nitro phenol (1.09 g, 7.07 mmole), benzylbromide (1.28 g, 7.5 mmole and cesium carbonate (2.43 g, 7.5 mmole) were stirred for 4 days at room temperature. After the reaction was complete, the reaction mixture was poured into ice water (500 ml), stirred 1 hour, and the resultant solid was filtered and dried under vacuum to provide the title compound (1.1 g, 64%).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].Cl[C:10](OCC)=[O:11]>>[O:8]1[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[NH:1][C:10]1=[O:11]
Reactant: CCOC(=O)Cl
Reactant: Nc1ccccc1O
Product: O=c1[nH]c2ccccc2o1

Procedure:
According to the reaction scheme, o-aminophenol is reacted with ethyl chloroformate, the resulting 3H-benzoxazol-2-one obtained is nitrated with nitric acid, the nitro group of the resulting compound of formula (IX) is reduced with hydrogen in the presence of a hydrogenation catalyst, such as palladium-on-charcoal, the 6-amino-3H-benzoxazol-2-one thus obtained is reacted with 2-methylthioimidazoline, preferably in the form of an acid addition salt such as the hydroiodide, and the resulting compound of formula (XII) is acidified to give 2-(4-amino-3-hydroxyphenylimino)-imidazolidine, which is reacted with formic acid in the presence of acetic anhydride, or with methylsulphonyl chloride, or with a compound NaNCO or R'NCO (wherein R' represents an alkyl radical having from 1 to 4 carbon atoms) to obtain an imidazolidine derivative of general formula (IB).
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1N.N([O-])=O.[Na+].[N:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>Cl.O>[N:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[S:10][C:2]1[NH:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:1]=1
Reactant: Nc1ccccc1Sc1nc2ccccc2[nH]1
Reactant: c1ccncc1
Agent: Cl
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: c1ccc(-c2ccccc2Sc2nc3ccccc3[nH]2)nc1

Procedure:
2-(1H-Benzimidazol-2-yl thio)benzenamine (8.5 g) in dilute hydrochloric acid (680 ml) was cooled (0° to -5°) with stirring and sodium nitrite (2.68 g) in water (85 ml) was added dropwise, keeping the temperature below 0°. The resulting diazonium salt solution was stirred at 0° for 0.5 hours, then added portionwise to pyridine (800 ml) with stirring at 80° for 1 hour. The pyridine was distilled off, and replaced with 880 ammonia which was in turn distilled off. The residue was treated with water and extracted into dichloromethane, washed, dried, evaporated under reduced pressure and purified by flash column chromatography using dichloromethane:ethyl acetate, 9:2 as eluant to give 3.07 g of the sub-title product.
Reaction SMILES: Br[C:2]1[C:3]2[CH:4]3[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18][CH:5]3[N:6](C(OC(C)(C)C)=O)[C:7]=2[CH:8]=[CH:9][CH:10]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[S:38]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39]1.N#N>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[S:38]1[CH:42]=[CH:41][C:40]([C:2]2[C:3]3[C@@H:4]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18][C@@H:5]4[NH:6][C:7]=3[CH:8]=[CH:9][CH:10]=2)=[CH:39]1
Reactant: CC(C)(C)OC(=O)N1CCC2c3c(Br)cccc3N(C(=O)OC(C)(C)C)C2CC1
Reactant: OB(O)c1ccsc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: N#N
Agent: O=P([O-])([O-])[O-]
Solvent: CN(C)C=O
Product: c1cc2c(c(-c3ccsc3)c1)[C@@H]1CCNCC[C@@H]1N2
Temperature: 80 °C
Yield: 60.5 %

Procedure:
A 30-mL shaker vial was charged with di(tert-butyl) 10-bromo-1,2,4,5,5a,10b-hexahydroazepino[4,5-b]indole-3,6-dicarboxylate (0.10 g, 0.214 mmol), potassium phosphate (0.068 g, 0.32 mmol), 3-thiopheneboronic acid (0.82 g, 0.642 mmol), and DMF (2 mL). The vial was purged with N2, and tetrakis(triphenylphosphine)palladium (0.025 g, 0.02 mmol) was added and the mixture was agitated at 250 RPM with heating at 80° C. overnight. The mixture was filtered through Celite, washing with MeOH (3-5 mL), and sulfonic acid resin (DOWEX®50W-X2, washed and dried, 4.8 meq/g dry weight) was added (1 g). The vial was then purged with N2, capped and agitated at 250 RPM with heating at 65° C. for 72 h. The mixture was filtered through a scintered funnel and the resin was washed 1:1 methylene chloride/methanol and then consecutively washed with MeOH and THF to ensure that all excess reagent was removed from the resin (the methanol and THF washes are alternated to swell and then shrink the resin to help expel reagents from inside the resin). The resin was then washed with 4M ammonium hydroxide in methanol (4×2 ml) and THF (2×2 ml) into an accurately weight round-bottomed flask. The filtrate was concentrated to give 0.035 g (60%) of a brown oil: MS (EI) m/z 271 (MH+); HPLC rt=2.78 min (100%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:28])[C:15]([C:25](=O)[CH3:26])=[CH:16][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=2[CH3:24])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:29]1([CH:35]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH2:36][CH2:37][O:38][C:39](=[O:44])/[CH:40]=[C:41](\[NH2:43])/[CH3:42])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CC(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]([C:15]2[CH:16]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=3[CH3:24])[C:40]([C:39]([O:38][CH2:37][CH2:36][CH:35]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[O:44])=[C:41]([CH3:42])[NH:43][C:25]=2[CH3:26])=[O:28])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(=O)C(=Cc1ccc(C)cc1C)C(=O)N1CCN(C(=O)OC(C)(C)C)CC1
Reactant: C/C(N)=C/C(=O)OCCC(c1ccccc1)c1ccccc1
Solvent: CC(C)O
Product: CC1=C(C(=O)OCCC(c2ccccc2)c2ccccc2)C(c2ccc(C)cc2C)C(C(=O)N2CCN(C(=O)OC(C)(C)C)CC2)=C(C)N1

Procedure:
648 mg (1.67 mmol) of 4-[2-acetyl-3-(2,4-dimethylphenyl)-2-propenoyl]-1-piperazinecarboxylic acid t-butyl ester and 493 mg (1.67 mmol) of 3-aminocrotonate (3,3-diphenylpropyl) ester were heated and stirred in 5 ml of 2-propanol at 80° C. for two nights. After evaporating 2-propanol under reduced pressure, the residue was purified by the silica gel chromatography (hexane/ethyl acetate=5/1 to 1/9) to obtain the title compound.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:33]=[CH:32][C:15]([O:16][C:17]2[C:22]([C:23]3[CH2:28][CH2:27][N:26]([C:29](=[O:31])[CH3:30])[CH2:25][CH:24]=3)=[CH:21][CH:20]=[CH:19][N:18]=2)=[CH:14][CH:13]=1)=[O:11].C(O)(=O)C>[Pd].O1CCCC1>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([OH:11])[C:12]1[CH:13]=[CH:14][C:15]([O:16][C:17]2[C:22]([CH:23]3[CH2:28][CH2:27][N:26]([C:29](=[O:31])[CH3:30])[CH2:25][CH2:24]3)=[CH:21][CH:20]=[CH:19][N:18]=2)=[CH:32][CH:33]=1
Reactant: CC(=O)N1CC=C(c2cccnc2Oc2ccc(C(=O)c3nc4ccccc4[nH]3)cc2)CC1
Agent: [Pd]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CC(=O)N1CCC(c2cccnc2Oc2ccc(C(O)c3nc4ccccc4[nH]3)cc2)CC1
Reaction time: 16 h

Procedure:
1-(4-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone (0.42 g, 0.96 mmol), acetic acid, glacial (0.11 mL, 1.92 mmol) and palladium on carbon, 10% (0.20 g, 0.19 mmol) were suspended in tetrahydrofuran (10 mL) in a pressure reactor. The mixture was hydrogenated at 50 psi for 16 h. The catalyst was filtered off and washed with THF. To the solution was added palladium on carbon, 10% (0.204 g, 0.192 mmol) and acetic acid, glacial (0.111 mL, 1.916 mmol) and the mixture was hydrogenated at 50 psi for another 24 h. The mixture was filtered through celite and washed with THF. The solvent was removed under reduced pressure and the residue was partitioned between DCM and saturated NaHCO3. The organic layer was dried and concentrated to give 1-(4-(2-(4-((1H-benzo[d]imidazol-2-yl)(hydroxy)methyl)phenoxy)pyridin-3-yl)piperidin-1-yl)ethanone as off-white solid.
Reaction SMILES: CO[C:3]([C:5]1[N:6]=[C:7]([C:24]#[N:25])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:9]=2)=[O:4].[CH3:26][O:27][C:28](=[O:34])[C:29]([CH3:33])([CH3:32])[CH2:30][NH2:31]>CCO>[CH3:26][O:27][C:28](=[O:34])[C:29]([CH3:33])([CH3:32])[CH2:30][NH:31][C:3]([C:5]1[N:6]=[C:7]([C:24]#[N:25])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:9]=2)=[O:4]
Reactant: COC(=O)c1nc(C#N)c2cc(CCc3ccccc3)ccc2c1O
Reactant: COC(=O)C(C)(C)CN
Solvent: CCO
Product: COC(=O)C(C)(C)CNC(=O)c1nc(C#N)c2cc(CCc3ccccc3)ccc2c1O
Temperature: 150 °C
Yield: 85 %

Procedure:
A mixture of 1-cyano-4-hydroxy-7-phenethyl-isoquinoline-3-carboxylic acid methyl ester (50 mg, 0.15 mmol) and 3-amino-2,2-dimethyl-propionic acid methyl ester (99 mg, 0.75 mmol) in EtOH (2 mL) was heated at 150° C. in a microwave reactor for 3 h. The solvent was evaporated, and the residue was purified by column chromatography (0-25% EtOAc/hexanes) to give 55 mg of the title compound. 1H NMR (CDCl3, 200 MHz): δ=14.0 (s, 1H), 8.20-8.40 (m, 2H), 7.98 (d, 1H, J=0.8
Reaction SMILES: [N:1]1[NH:2][N:3]=[C:4]([CH2:6][O:7][C:8]2[CH:9]=[CH:10][C:11]([N:14]3[CH:18]=[N:17][N:16]=[N:15]3)=[N:12][CH:13]=2)[CH:5]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:38][O:39][C:40]([C@H:42]1[CH2:47][C@@H:46](O)[CH2:45][CH2:44][N:43]1[C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])=[O:41]>C1COCC1>[N:14]1([C:11]2[N:12]=[CH:13][C:8]([O:7][CH2:6][C:4]3[CH:5]=[N:1][N:2]([CH:46]4[CH2:45][CH2:44][N:43]([C:49]([O:51][C:52]([CH3:53])([CH3:54])[CH3:55])=[O:50])[CH:42]([C:40]([O:39][CH3:38])=[O:41])[CH2:47]4)[N:3]=3)=[CH:9][CH:10]=2)[CH:18]=[N:17][N:16]=[N:15]1
Reactant: COC(=O)[C@H]1C[C@@H](O)CCN1C(=O)OC(C)(C)C
Reactant: c1cc(-n2cnnn2)ncc1OCc1cn[nH]n1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)C1CC(n2ncc(COc3ccc(-n4cnnn4)nc3)n2)CCN1C(=O)OC(C)(C)C
Temperature: 25 °C

Procedure:
To a solution of 5-((2H-1,2,3-triazol-4-yl)methoxy)-2-(1H-tetrazol-1-yl)pyridine (600 mg, 2.45 mmol), triphenylphosphine (1.5 eq.), and (2R,4S)—N-Boc-4-hydroxypiperidine-2-carboxylic acid methyl ester (1.5 eq.) dissolved in THF (20 mL) at 0° C. was added a solution of di-tertbutylazodicarboxylatc (1.5eq.) in THF (5 mL) drop wise. The reaction was allowed to warm to room temperature overnight and the solvents removed in vacuo The crude material was purified by flash column chromatography on silica gel to afford the desired product. 1H NMR (CDCl3): δ 9.44 (1H, s), 8.27 (1H, d), 8.03 (1H, d), 7.71 (1H, s), 7.58 (1H, dd), 5.27 (2H, s), 4.99-5.19 (1H, m), 4.57 (1H, m), 4.11-4.31 (1H, m), 3.79 (3H, s), 3.04-3.24 (1H, m), 2.75 (1H, m), 2.18-2.32 (2H, m), 2.05 (1H, m), 1.50 (9H, s). ES+-MS found: 486.1.
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)[C:8]([NH:10][C:11]2[S:12][CH:13]=[CH:14][N:15]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:36](Br)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C1COCC1>[CH:1]1([CH2:6][CH:7]([C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH2:25][CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)(=[O:24])=[O:23])=[CH:18][CH:17]=2)[C:8]([NH:10][C:11]2[S:12][CH:13]=[CH:14][N:15]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: BrCc1ccccc1
Reactant: CS(=O)(=O)c1ccc(C(CC2CCCC2)C(=O)Nc2nccs2)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: O=C(Nc1nccs1)C(CC1CCCC1)c1ccc(S(=O)(=O)CCc2ccccc2)cc1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
The title C compound, 3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-N-thiazol-2-yl-propionamide (0.58 mmol, 220 mg) is dissolved in 15 mL of THF and cooled to −78° C. LHMDS (1.2 mmol, 1.2 mL of 1.0 M solution) is added and the mixture is stirred to 1 h at −78° C. Benzyl bromide (0.6 mmol, 103 mg) is added and the mixture stirred at −78° C. for 2 h further. The reaction mixture is quenched with aqueous saturated ammonium chloride, the solvent is evaporated and the residue is partitioned between EtOAc and brine. The organic solution is dried and evaporated to an oil. Chromatography on silica (eluent: 35% EtOAc in hexanes) affords 3-cyclopentyl-2-[4-(2-phenyl-ethanesulfonyl)-phenyl]-N-thiazol-2-yl-propionamide: 1H NMR δ 11.8 (s, 1H), 7.86 (d, J=8, 2H), 7.55 (m, 3H), 7.05-7.32 (m, 6H) 3.8 (t, J=7.5, 1H), 3.33 (m, 2H), 3.05 (m, 2H), 2.29 (m, 1H), 1.0-1.9 (m, 8H); e/z (ES) 469 (M+1, 100%).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:12]=1[CH2:13]O)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1CCN2C(=NCCC2)CC1.C1C=CC(P([N:45]=[N+:46]=[N-:47])(C2C=CC=CC=2)=O)=CC=1>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:12]=1[CH2:13][N:45]=[N+:46]=[N-:47])[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: CC(NC(=O)OC(C)(C)C)c1ccc(Cl)cc1CO
Solvent: Cc1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Product: CC(NC(=O)OC(C)(C)C)c1ccc(Cl)cc1CN=[N+]=[N-]
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a stirred solution of 2-(1-tert-butyloxycarbonylaminoethyl)-5-chlorobenzyl alcohol from the previous step (0.272 g, 0.96 mmol) in toluene (20.0 mL) at ambient temperature under nitrogen atmosphere was added DBU (0.15 mL g, 1.0 mmol) and DPPA (0.25 mL, 1.14 mmol). The mixture was stirred at ambient temperature for 18 h. The reaction was partitioned between EtOAc and water. The EtOAc layer was separated, dried over anhydrous Na2SO4, and filtered. The filtrate solvent was removed under reduced pressure and the residue purified by flash silica gel chromatography using dichloromethane as an eluent. 2-(1-(tert-butyloxycarbonylamino)ethyl)-5-chloro-benzylazide was obtained as a yellow oil after concentration of desired fractions in vacuo (0.28 g; HPLC RT 3.71 min, method A).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH:17]([C:18]3[N:19]([CH3:27])[C:20]4[CH:25]=[CH:24][N:23]=[CH:22][C:21]=4[N:26]=3)[C:16](=O)[C:15]3[C:14]([C:29]([O:31]CC)=O)=[CH:13][CH:12]=[CH:11][C:10]=3[NH:9]2)=[CH:4][CH:3]=1.O.[NH2:35][NH2:36]>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[NH:9][C:10]3[C:15]4[C:16](=[N:35][NH:36][C:29](=[O:31])[C:14]=4[CH:13]=[CH:12][CH:11]=3)[CH:17]2[C:18]2[N:19]([CH3:27])[C:20]3[CH:25]=[CH:24][N:23]=[CH:22][C:21]=3[N:26]=2)=[CH:6][CH:7]=1
Reactant: NN
Reactant: CCOC(=O)c1cccc2c1C(=O)C(c1nc3cnccc3n1C)C(c1ccc(F)cc1)N2
Solvent: CO
Solvent: O
Product: Cn1c(C2c3n[nH]c(=O)c4cccc(c34)NC2c2ccc(F)cc2)nc2cnccc21
Temperature: 25 °C
Reaction time: 4 h
Yield: 5 %

Procedure:
The mixture of ethyl 2-(4-fluorophenyl)-3-(1-methyl-1H-imidazo[4,5-c]pyridin-2-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (150 mg, 0.34 mmol) and hydrazine monohydrate (2 mL) in methanol (5 mL) was stirred at room temperature for 4 h. Then methanol was evaporated under reduced pressure and the residue was extracted with ethyl acetate (20 mL×4). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated to give crude product, which was purified by chromatography (silica gel, DCM/MeOH=25:1 to 1:1) to give the title compound (6.7 mg, yield 5%). LC-MS (ESI) m/z: 413 (M+1)+. 1H-NMR (400 MHz, CD3OD) δ (ppm): 3.58 (s, 3H), 4.93-4.95 (d, J=11.6 Hz, 1H), 5.04-5.07 (d, J=11.6 Hz, 1H), 6.85-6.90 (t, J=8.8 Hz, 2H), 7.12-7.14 (d, J=8.0 Hz, 1H), 7.38-7.44 (m, 3H), 7.49-7.57 (m, 2H), 8.19-8.21 (d, J=5.6 Hz, 1H), 8.72 (s, 1H).
Reaction SMILES: COC[O:4][C:5]1[CH:6]=[C:7]([C:12]2[O:16][N:15]=[C:14]([CH3:17])[N:13]=2)[CH:8]=[CH:9][C:10]=1[CH3:11].Cl>O1CCCC1.CC(O)C.O1CCOCC1>[CH3:11][C:10]1[CH:9]=[CH:8][C:7]([C:12]2[O:16][N:15]=[C:14]([CH3:17])[N:13]=2)=[CH:6][C:5]=1[OH:4]
Reactant: COCOc1cc(-c2nc(C)no2)ccc1C
Agent: Cl
Solvent: C1CCOC1
Solvent: CC(C)O
Solvent: C1COCCO1
Product: Cc1noc(-c2ccc(C)c(O)c2)n1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of 5-(3-methyloxymethoxy-4-methyl-phenyl)-3-methyl-[1,2,4]oxadiazole (1.23 g, 5.25 mmol) (from Example 51 supra) in tetrahydrofuran/2-propanol (1:1, 30 mL) was added 13.1 mL of 4M HCl in dioxane (Aldrich). The reaction mixture was stirred at room temperature for 18 hours. The solution was concentrated. The residue was diluted with ethyl acetate, washed with water and brine, dried (magnesium sulfate) and concentrated. The residue was recrystallized from ethyl acetate/hexanes and dried to give 2-methyl-5-(3-methyl-[1,2,4]oxadiazol-5-yl)-phenol. (Yield 0.88 g, 88%).
Reaction SMILES: [CH:1]([C:4]([O:12][Si:13]([CH3:16])([CH3:15])[CH3:14])([CH2:8][CH2:9][CH2:10][CH3:11])[CH2:5][C:6]#[CH:7])=[C:2]=[CH2:3].CC(C)C(BC(C(C)C)C)C.C([N+]([O-])(CC)CC)C.[I:36]I>O1CCCC1.C(COC)OC>[I:36]/[CH:3]=[CH:2]/[CH2:1][C:4]([CH:5]=[C:6]=[CH2:7])([O:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: II
Reactant: C#CCC(C=C=C)(CCCC)O[Si](C)(C)C
Agent: CC(C)C(C)BC(C)C(C)C
Agent: CC[N+]([O-])(CC)CC
Solvent: COCCOC
Solvent: C1CCOC1
Product: C=C=CC(C/C=C/I)(CCCC)O[Si](C)(C)C
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To a stirred solution of 2.36 g. (10 mmol.) of 4-propadienyl-4-trimethylsilyloxy-1-octyne in 5 ml. of glyme is added to a solution of 11 mmol. of bis-(3-methyl-2-butyl)borane in 15 ml. of glyme at 0° C. The mixture is stirred at 25° C. for 90 minutes, cooled to 0° C., and treated portionwise with 3.0 g. of triethylamine oxide. The stirred mixture is maintained at 25°-30° C. for 45 minutes, diluted with 20 ml. of tetrahydrofuran and poured into 100 ml. of ice-cold 15% sodium hydroxide solution, followed immediately with a solution of 8.0 g. of iodine in 20 ml. of tetrahydrofuran. The mixture is stirred at ambient temperature for 30 minutes and then extracted with ether. The extract is washed successively with water, sodium thiosulfate solution and brine; dried over magnesium sulfate; and filtered. The residue obtained after solvent evaporation is subjected to chromatography on silica gel with heptane solvent to afford the title compound as a liquid.
Reaction SMILES: [CH:1]1([C:4]([NH:6][C:7]([NH2:9])=[S:8])=[O:5])[CH2:3][CH2:2]1.Br[CH2:11][C:12]([C:14]1[CH:23]=[CH:22][C:21]2[NH:20][C:19](=[O:24])[C:18]3[NH:25][CH:26]=[CH:27][C:17]=3[C:16]=2[CH:15]=1)=O.[CH2:28]([C:30]([O-:32])=[O:31])[CH3:29]>C(O)C>[CH:1]1([C:4]([NH:6][C:7]2[S:8][CH:11]=[C:12]([C:14]3[CH:23]=[CH:22][C:21]4[NH:20][C:19](=[O:24])[C:18]5[NH:25][CH:26]=[CH:27][C:17]=5[C:16]=4[CH:15]=3)[N:9]=2)=[O:5])[CH2:3][CH2:2]1.[CH2:28]([C:30]([O-:32])=[O:31])[CH3:29]
Reactant: O=C(CBr)c1ccc2[nH]c(=O)c3[nH]ccc3c2c1
Reactant: NC(=S)NC(=O)C1CC1
Agent: CCC(=O)[O-]
Solvent: CCO
Product: O=C(Nc1nc(-c2ccc3[nH]c(=O)c4[nH]ccc4c3c2)cs1)C1CC1
Temperature: 90 °C
Reaction time: 6 h
Yield: 27.9 %

Procedure:
57 mg (1.2 mmol) of cyclopropanecarbonyl-thiourea is added to a suspension of 124 mg (0.33 mmol) of 8-(2-bromo-acetyl)-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate in 3.5 mL of ethanol. The mixture is stirred at 90° C. for 6 hours then the mixture is cooled to room temperature. The solvent is evaporated, then the product is purified by preparative LCMS. After drying, 39 mg (28%) of 8-[2-(cyclopropanecarbonyl-amino)-thiazol-4-yl]-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate is obtained in the form of a beige solid.
Reaction SMILES: Cl.[NH2:2][C@@H:3]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([I:15])=[CH:11][CH:10]=1)[C:4]([O:6][CH3:7])=[O:5].[C:16]([O-])(=[O:18])[CH3:17].[Na+].C(OC(=O)C)(=O)C>Cl>[C:16]([NH:2][C@@H:3]([CH2:8][C:9]1[CH:10]=[CH:11][C:12]([I:15])=[CH:13][CH:14]=1)[C:4]([O:6][CH3:7])=[O:5])(=[O:18])[CH3:17]
Reactant: CC(=O)[O-]
Reactant: COC(=O)[C@@H](N)Cc1ccc(I)cc1
Agent: Cl
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Product: COC(=O)[C@H](Cc1ccc(I)cc1)NC(C)=O
Temperature: 0 °C
Yield: 56 %

Procedure:
To a solution of 93 (2.25 g, 6.80 mmol) in 10% HCl (10 mL) at 0° C. was added 4M sodium acetate (115 mL) and the resulting reaction was allowed to stir whilst equilibrating to 0° C. Acetic anhydride (50 mL) was added and the reaction allowed to proceed with vigorous stirring. After 1 h the product was collected by vacuum filtration, dissolved in ethyl acetate (30 mL) and washed with 2M sodium bicarbonate (2×30 mL). The organic layer was dried and evaporated to yield the title compound (1.31 g, 3.79 mmol, 56%) as a white solid. Mp 118-120° C. [α]D27 +93.8 (c. 0.1, CHCl3). 1H NMR (CDCl3, 300 MHz): δ 7.61 (d, J=8.4 Hz, 2H, ArH2′ and ArH6′); 6.84 (d, J=8.1 Hz, 2H, ArH3′ and ArH5′); 5.92 (d, J=7.2 Hz, 1H, NH); 4.87 (m, 1H, H2); 3.73 (s, 3H, OCH3); 3.11 (dd, J=6.0, 13.8, Hz, 1H, H3a); 3.03 (dd, J=5.4, 13.8 Hz, 1H, H3b); 1.99 (s, 3H, NCOCH3). Mass Spectrum (CI, +ve) m/z 348 (100%) [MH+]. HRMS calcd for C12H15NO3I 348.0097, found 348.0104.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].C[O:8][C:9](=O)[C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][C:17]=2[F:26])=[N:12][C:11]=1[CH3:27].Cl>O1CCCC1.[Cl-].[Na+].O>[F:26][C:17]1[CH:18]=[C:19]([C:22]([F:25])([F:24])[F:23])[CH:20]=[CH:21][C:16]=1[C:13]1[N:12]=[C:11]([CH3:27])[C:10]([CH2:9][OH:8])=[CH:15][CH:14]=1
Reactant: COC(=O)c1ccc(-c2ccc(C(F)(F)F)cc2F)nc1C
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: C1CCOC1
Product: Cc1nc(-c2ccc(C(F)(F)F)cc2F)ccc1CO
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
2.60 mg (68.44 mmol) lithium aluminium hydride were given to 110 ml tetrahydrofuran (THF) and stirred at room temperature (r. t.) for 20 min. A solution of 11.20 g (34.22 mmol) 6-(2-Fluoro-4-trifluoromethyl-phenyl)-2-methyl-nicotinic acid methyl ester in 110 ml THF was added drop by drop at 0° C. within 15 min., and the mixture stirred for 2 h at 0° C. 140 ml brine were added slowly at 0° C. and stirred continued for 1 h. The mixture was adjusted to pH=5 by slowly addition of conc. HCl. A formed salt precipitate was isolated by filtration and washed with THF. The combined THF-solutions were evaporated, the residue extracted twice with ethyl acetate, the organic phase dried (sodium sulphate) and evaporated. The obtained material (9.69 g, 99%) used without further purification.