Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1C2C(COC(=O)[NH:17][C:18]3[CH:23]=[CH:22][C:21]([S:24][C:25]4[CH:30]=[CH:29][C:28]([C:31](=[O:39])[NH:32][C:33]5[S:37][N:36]=[C:35]([CH3:38])[CH:34]=5)=[CH:27][C:26]=4[NH:40][C:41]4[C:42]5[CH:50]=[CH:49][C:48]([CH:51]([CH3:53])[CH3:52])=[N:47][C:43]=5[N:44]=[CH:45][N:46]=4)=[CH:20][CH:19]=3)C3C(=CC=CC=3)C=2C=CC=1.O.[OH-].[Li+].Cl>O1CCOCC1.O.C(OCC)(=O)C>[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([S:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]([NH:32][C:33]3[S:37][N:36]=[C:35]([CH3:38])[CH:34]=3)=[O:39])=[CH:27][C:26]=2[NH:40][C:41]2[C:42]3[CH:50]=[CH:49][C:48]([CH:51]([CH3:53])[CH3:52])=[N:47][C:43]=3[N:44]=[CH:45][N:46]=2)=[CH:20][CH:19]=1
Reactant: Cc1cc(NC(=O)c2ccc(Sc3ccc(NC(=O)OCC4c5ccccc5-c5ccccc54)cc3)c(Nc3ncnc4nc(C(C)C)ccc34)c2)sn1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Solvent: CCOC(C)=O
Product: Cc1cc(NC(=O)c2ccc(Sc3ccc(N)cc3)c(Nc3ncnc4nc(C(C)C)ccc34)c2)sn1
Temperature: 70 °C
Yield: 71.1 %

Procedure:
A solution of the product of Example 167C (117 mg, 0.156 mmol) in 1,4-dioxane (4 mL) was treated with a solution of lithium hydroxide monohydrate (13.1 mg, 0.312 mmol) in water (2 mL) at ambient temperature, then heated at 70° C. for 1 hour. The reaction was cooled to room temperature, diluted with ethyl acetate (50 mL) and water (25 mL), adjusted the aqueous pH to 5 with 1N aqueous hydrochloric acid, and separated the layers. The organic phase was washed with water (2×25 mL) and brine (25 mL), dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation in vacuo. Purification of the residue by silica gel chromatography eluting with 5% methanol/methylene chloride afforded the title compound as a light yellow solid (58.5 mg, 71%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 1.34 (d, J=6.99 Hz, 6 H) 2.33 (s, 3 H) 3.14-3.30 (m, 1 H) 5.63 (s, 2 H) 6.65 (d, J=8.46 Hz, 2 H) 6.87 (s, 1 H) 6.91 (d, J=8.82 Hz, 1 H) 7.15 (d, J=8.46 Hz, 2 H) 7.65 (d, J=8.09 Hz, 1 H) 7.86 (d, J=7.72 Hz, 1 H) 8.03 (s, 1 H) 8.59 (s, 1 H) 8.89 (d, J=8.09 Hz, 1 H) 10.19 (s, 1 H) 12.17 (s, 1 H); MS (ESI+) m/z 528 (M+H)+, (ESI−) m/z 526 (M−H)−.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[Cl:12])[C:5](=[N:7][OH:8])[NH2:6].[Br:13][C:14]1[CH:18]=[CH:17][O:16][C:15]=1[C:19](Cl)=O>N1C=CC=CC=1>[NH2:1][C:2]1[CH:3]=[C:4]([C:5]2[N:6]=[C:19]([C:15]3[O:16][CH:17]=[CH:18][C:14]=3[Br:13])[O:8][N:7]=2)[CH:9]=[CH:10][C:11]=1[Cl:12]
Reactant: NC(=NO)c1ccc(Cl)c(N)c1
Reactant: O=C(Cl)c1occc1Br
Solvent: c1ccncc1
Product: Nc1cc(-c2noc(-c3occc3Br)n2)ccc1Cl

Procedure:
The title compound was prepared from 3-amino-4-chloro-benzamidoxime (293 mg, 1.58 mmol) and 3-bromofuran-2-carbonyl chloride (329 mg, 1.57 mmol) in pyridine (2.8 mL) under reflux similar to Example 1b, yielded 289 mg (54%) as a white solid. 1H NMR (CDCl3): 7.66 (d, J=1.64 Hz, 1H), 7.59 (d, J=1.92 Hz, 1H), 7.50 (dd, J1=8.38 Hz, J2=2.07 Hz, 1H), 7.37 (d, J=8.24 Hz, 1H), 6.75 (d, J=1.93 Hz, 1H), 4.22 (s, 2H).
Reaction SMILES: C1(O[C:8](=[O:21])[NH:9][C:10]2[C:11]([O:19][CH3:20])=[N:12][C:13]([CH3:18])=[C:14]([CH2:16][CH3:17])[CH:15]=2)C=CC=CC=1.[CH2:22]([C:26]1[CH:31]=[CH:30][C:29]([N:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)=[CH:28][CH:27]=1)[CH2:23][CH2:24][CH3:25]>>[CH2:16]([C:14]1[CH:15]=[C:10]([NH:9][C:8]([N:35]2[CH2:36][CH2:37][N:32]([C:29]3[CH:30]=[CH:31][C:26]([CH2:22][CH2:23][CH2:24][CH3:25])=[CH:27][CH:28]=3)[CH2:33][CH2:34]2)=[O:21])[C:11]([O:19][CH3:20])=[N:12][C:13]=1[CH3:18])[CH3:17]
Reactant: CCCCc1ccc(N2CCNCC2)cc1
Reactant: CCc1cc(NC(=O)Oc2ccccc2)c(OC)nc1C
Product: CCCCc1ccc(N2CCN(C(=O)Nc3cc(CC)c(C)nc3OC)CC2)cc1
Yield: 57 %

Procedure:
Phenyl-N-(5-ethyl-2-methoxy-6-methylpyridin-3-yl)carbamate and 1-(4-normalbutylphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound.
Reaction SMILES: [CH2:1]([N:3]1[C:7]2=[N:8][CH:9]=[C:10]([C:13](=O)[C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[C:11]([OH:12])=[C:6]2[CH:5]=[N:4]1)[CH3:2].Cl.[NH2:23]O>N1C=CC=CC=1>[CH2:1]([N:3]1[C:7]2=[N:8][CH:9]=[C:10]3[C:13]([C:14]4[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=4)=[N:23][O:12][C:11]3=[C:6]2[CH:5]=[N:4]1)[CH3:2]
Reactant: CCn1ncc2c(O)c(C(=O)c3ccc(F)cc3)cnc21
Reactant: NO
Agent: Cl
Solvent: c1ccncc1
Product: CCn1ncc2c3onc(-c4ccc(F)cc4)c3cnc21

Procedure:
1-Ethyl-5-(4-fluorobenzoyl)-4-hydroxy-1H-pyrazolo[3,4-b]pyridine (3.35 g) was refluxed overnight in 75 ml of pyridine containing 4.0 g of hydroxylamine hydrochloride. The solvent was then evaporated and the residue triturated with 5% hydrochloric acid The product thus obtained was washed with methanol and then chromatographed over silica gel (5% methanol/dichloromethane) to remove a trace of fluorescent impurity. After recrystallization from ethyl acetate/hexane, 2.83 g of product was obtained, mp 175°-176° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:14]=[N:15][N:16]3[CH:21]=[CH:20][C:19]([N:22]4[C@@H:26]([C:27]5[CH:32]=[CH:31][C:30]([F:33])=[CH:29][N:28]=5)[CH2:25][O:24][C:23]4=[O:34])=[N:18][C:17]=23)[CH:5]=[CH:6][C:7]=1[C:8]1[N:12]=[CH:11][NH:10][N:9]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[P:41]([O:53][CH2:54]Cl)([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42]>CN(C=O)C.CCOC(C)=O>[P:41]([O:53][CH2:54][N:10]1[CH:11]=[N:12][C:8]([C:7]2[CH:6]=[CH:5][C:4]([C:13]3[CH:14]=[N:15][N:16]4[CH:21]=[CH:20][C:19]([N:22]5[C@@H:26]([C:27]6[CH:32]=[CH:31][C:30]([F:33])=[CH:29][N:28]=6)[CH2:25][O:24][C:23]5=[O:34])=[N:18][C:17]=34)=[CH:3][C:2]=2[F:1])=[N:9]1)([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])([O:48][C:49]([CH3:50])([CH3:51])[CH3:52])=[O:42]
Reactant: CC(C)(C)OP(=O)(OCCl)OC(C)(C)C
Reactant: O=C1OC[C@H](c2ccc(F)cn2)N1c1ccn2ncc(-c3ccc(-c4nc[nH]n4)c(F)c3)c2n1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)(C)OP(=O)(OCn1cnc(-c2ccc(-c3cnn4ccc(N5C(=O)OC[C@@H]5c5ccc(F)cn5)nc34)cc2F)n1)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 28.6 %

Procedure:
To a solution of (S)-3-(3-(3-fluoro-4-(1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(5-fluoropyridin-2-yl)oxazolidin-2-one (0.66 g, 1.4 mmol) in DMF (10 mL) was added cesium carbonate (0.47 g, 1.4 mmol) followed by di-tert-butyl chloromethyl phosphate (1.1 g, 4.3 mmol) and the reaction mixture was stirred overnight at ambient temperature, then diluted with EtOAc (100 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The crude material was chromatographed twice on silica gel using EtOAc as eluent to yield (S)-di-tert-butyl (3-(2-fluoro-4-(5-(4-(5-fluoropyridin-2-yl)-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)phenyl)-1H-1,2,4-triazol-1-yl)methyl phosphate (0.27 g, 0.40 mmol, 28% yield).
Reaction SMILES: [CH:1]1(N=C=NC2CCCCC2)[CH2:6]CCC[CH2:2]1.[Cl:16][C:17]1[CH:25]=[CH:24][C:23]([NH:26][C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[S:28])=[CH:22][C:18]=1[C:19]([OH:21])=[O:20].C(O)(C)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Cl:16][C:17]1[CH:25]=[CH:24][C:23]([NH:26][C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[S:28])=[CH:22][C:18]=1[C:19]([O:21][CH:1]([CH3:6])[CH3:2])=[O:20]
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: CC(C)OC(=S)Nc1ccc(Cl)c(C(=O)O)c1
Agent: CN(C)c1ccncc1
Solvent: CC(C)O
Solvent: ClCCl
Product: CC(C)OC(=O)c1cc(NC(=S)OC(C)C)ccc1Cl

Procedure:
This is the preparation of compound 32 using 1,3-dicyclohexylcarbodiimide. A mixture of 2-chloro-5-[[(1-methylethoxy)thioxomethyl]amino]benzoic acid (2 g, 0.007 mol), isopropyl alcohol (1.3 g, 0.02 mol), 4-dimethylaminopyridine (0.85 g, 0.007 mol) in 25 ml methylene chloride was stirred in an ice bath and 1,3-dicyclohexylcarbodiimide (1.7 g 0.008 mol) added. The mixture was allowed to come to ambient temperature and stirred overnight. The precipitated solid was filtered off and the filtrate washed with dilute hydrochloric acid and aqueous 5% sodium bicarbonate. After drying over magnesium sulfate, filtering and removing the methylene chloride, the product was crystallized from toluene/petroleum ether. Yield 1.2 g m.p. 89° C. A mixed m.p. with authentic compound 32 also gave m.p. 89°-90° C. The N.M.R. spectrum was identical with that of authentic compound 32.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:6]=[C:7]([C:11]([O:13][CH:14]([CH3:16])[CH3:15])=[O:12])[S:8][C:9]=1[CH3:10])=O.[NH2:17][C:18]([NH2:20])=[S:19]>>[NH2:20][C:18]1[S:19][CH:2]=[C:3]([C:5]2[CH:6]=[C:7]([C:11]([O:13][CH:14]([CH3:16])[CH3:15])=[O:12])[S:8][C:9]=2[CH3:10])[N:17]=1
Reactant: Cc1sc(C(=O)OC(C)C)cc1C(=O)CBr
Reactant: NC(N)=S
Product: Cc1sc(C(=O)OC(C)C)cc1-c1csc(N)n1
Yield: 107.1 %

Procedure:
A solution of 260 mg (0.85 mmol) of isopropyl 4-(2-bromoacetyl)-5-methylthiophene-2-carboxylate was reacted with 65 mg (0.85 mmol) of thiourea in a manner similar to Example 8, step (a) to give isopropyl 4-(2-amino(1,3-thiazol-4-yl))-5-methylthiophene-2-carboxylate (257 mg, quantitive yield) as a white solid. 1H-NMR (DMSO-d6; 300 MHz) δ7.90 (s, 1H), 6.93 (s, 1H), 5.09 (septet, 1H, J=6.2 Hz), 2.61 (s, 3H), 1.29 (d, 6H, J=6.2 Hz). Mass spectrum (ESI, m/z): Calcd. for C12H14N2O2S2 283.1 (M+H), found 283.1
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[NH:9][NH2:10].[C:11]([O:16][CH2:17][CH3:18])(=[O:15])[C:12]([CH3:14])=O.C(O)(=O)C>C(O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[NH:9][N:10]=[C:12]([CH3:14])[C:11]([O:16][CH2:17][CH3:18])=[O:15]
Reactant: CCOC(=O)C(C)=O
Reactant: NNc1ccc(Cl)cc1Cl
Solvent: CC(=O)O
Solvent: CCO
Product: CCOC(=O)C(C)=NNc1ccc(Cl)cc1Cl
Temperature: 25 °C
Yield: 82.4 %

Procedure:
A mixture of 2,4-dichlorophenylhydrazine (16.00 g, 0.075 mol), ethyl pyruvate (14.47 g, 10.3 mL, 0.12 mol), glacial acetic acid (0.9 mL), absolute ethanol (105 mL) was refluxed for 2 hours. After cooling at room temperature, the solid which formed was filtered and recrystallized from ethanol to give 17.0 g (83%) of the title compound, mp 118-120° C. (from ethanol).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:31])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][CH2:14][C:15]2[CH:20]=[C:19]([O:21][Si](C(C)(C)C)(C)C)[CH:18]=[C:17]([Br:29])[CH:16]=2)=[CH:9][C:8]=1[CH3:30])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(=O)([O-])[O-].[Na+].[Na+].O>C1COCC1.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:31])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][CH2:14][C:15]2[CH:20]=[C:19]([OH:21])[CH:18]=[C:17]([Br:29])[CH:16]=2)=[CH:9][C:8]=1[CH3:30])[CH3:2]
Reactant: CCOC(=O)COc1ccc(SCc2cc(Br)cc(O[Si](C)(C)C(C)(C)C)c2)cc1C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: CCOC(=O)COc1ccc(SCc2cc(O)cc(Br)c2)cc1C
Temperature: 60 °C
Reaction time: 2 h

Procedure:
{4-[3-Bromo-5-(tert-butyl-dimethyl-silanyloxy)-benzylsulfanyl]-2-methylphenoxy}-acetic acid ethyl ester 7 g, 13.3 mmol) was dissolved in THF under an atmosphere of nitrogen. Tetrabutylammonium fluoride 1 N in THF (15 mL) was added, and the reaction mixture was stirred at 60° C. for 2 h. Saturated sodium carbonate and water were added together with ethyl acetate, and the organic phase was separated. The organic phase was washed with water, dried, and evaporated to dryness. Yield: 3.2 g. HPLC-MS: m/z: 435.4 (M+Na); Rt: 2.22 min.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:4][N:3]=1.C([Sn](CCCC)(CCCC)/[CH:28]=[CH:29]/[C:30]([O:32][CH2:33][CH3:34])=[O:31])CCC.[F-].[K+]>CN(C)C=O.O>[O:16]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[CH2:9][O:8][C:5]1[CH:6]=[CH:7][C:2](/[CH:28]=[CH:29]/[C:30]([O:32][CH2:33][CH3:34])=[O:31])=[N:3][CH:4]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: Brc1ccc(OCc2ccccc2Oc2ccccc2)cn1
Reactant: CCCC[Sn](/C=C/C(=O)OCC)(CCCC)CCCC
Agent: [F-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)/C=C/c1ccc(OCc2ccccc2Oc2ccccc2)cn1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
To a solution of 2-bromo-5-((2-phenoxybenzyl)oxy)pyridine (1.0 g) in dimethylformamide (7 ml), 1.26 g of ethyl (2E)-3-(tributylstannyl)acrylate and 350 mg of tetrakis triphenylphosphine palladium were added, and the reaction solution was stirred overnight at 100° C. under nitrogen atmosphere. The reaction solution was cooled, then 15 ml of a saturated aqueous potassium fluoride solution was added, and the reaction solution was stirred for 1 hour, followed by removing insoluble matters by filtration through Celite and the filtrate was concentrated under reduced pressure. The residue obtained was diluted with water, extracted with diethyl ether, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue obtained was purified by silica gel column chromatography (eluent: ethyl acetate/hexane (0:100-25:75-30:70)) to afford the title compound as a yellow solid.
Reaction SMILES: [CH2:1]([CH:8]1[CH2:13][CH2:12][CH2:11][N:10]([CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([NH:22]C(OC(C)(C)C)=O)=[CH:18][CH:17]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BrH:30]>>[BrH:30].[CH2:1]([CH:8]1[CH2:13][CH2:12][CH2:11][N:10]([CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)Nc1ccc(CCN2CCCC(Cc3ccccc3)C2)cc1
Agent: Br
Product: Nc1ccc(CCN2CCCC(Cc3ccccc3)C2)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 55 %

Procedure:
3-benzyl-1-[2-(4-tert-butoxycarbonylaminophenyl)ethyl]piperidine (0.67 g, 1.69 mmol) was dissolved in HBr (saturated solution in methanol, 10 mL) and the resulting solution stirred at 25° C. for 20 h. Then, after concentration in vacuum, the resultant mixture was treated with NaHCO3 (water saturated solution, 50 mL) and extracted twice with EtOAc (2×50 mL). The collected organic phase was washed with brine (50 mL), dried and concentrated in vacuum. The crude compound was purified by filtration on silica gel using CH2C2/MeOH as eluant to afford the free amine as a pale yellow oil (0.272 g, 55%). 1H NMR (CDCl3): 0.85-1.05 (m, 1H), 1.5-1.9 (m, 4H), 1.9-2.1 (m, 2H), 2.4-2.6 (m, 4H), 2.65-2.8 (m, 2H), 2.85-3.05 (m, 2H), 3.53 (bs, 2H), 6.61 (d, J=8.1 Hz, 2H), 6.97 (d, J=8.1 Hz, 2H), 7.145 (d, J=7.8 Hz, 2H), 7.18 (d, J=7.2, 1H), 7.275 (t, J=7.2 Hz, 2H).
Reaction SMILES: [C:1]([N:6]([CH2:9][CH2:10][CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)[CH2:7][CH3:8])([O:3][CH2:4][CH3:5])=[O:2].C(O[CH:21]1[C:34]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[O:28][C:27]2[C:22]1=[CH:23][CH:24]=[CH:25][CH:26]=2)(=O)C>C1C=CC=CC=1>[CH:23]1[C:22]2[CH:21]([N:14]3[CH2:13][CH2:12][CH:11]([CH2:10][CH2:9][N:6]([C:1]([O:3][CH2:4][CH3:5])=[O:2])[CH2:7][CH3:8])[CH2:16][CH2:15]3)[C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[O:28][C:27]=2[CH:26]=[CH:25][CH:24]=1
Reactant: CC(=O)OC1c2ccccc2Oc2ccccc21
Reactant: CCOC(=O)N(CC)CCC1CCNCC1
Solvent: c1ccccc1
Product: CCOC(=O)N(CC)CCC1CCN(C2c3ccccc3Oc3ccccc32)CC1

Procedure:
Reaction of the above prepared 4-[2-(N-carboethoxy-N-ethylamino)ethyl]piperidine with 9-acetoxyxanthene in benzene by the procedure of Example 3 gives 1-(9-xanthenyl)-4-[2-(N-carboethoxy-N-ethylamino)ethyl]piperidine.
Reaction SMILES: [CH3:1][C:2]1[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:3]=1[C:4]([C:6]1[N:10]([CH3:11])[C:9]([CH:12]([C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][C:20]=2F)C(OCC=C)=O)=[CH:8][CH:7]=1)=[O:5].N1CCOCC1>C1COCC1.[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>[CH3:1][C:2]1[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:3]=1[C:4]([C:6]1[N:10]([CH3:11])[C:9]([CH2:12][C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=2)=[CH:8][CH:7]=1)=[O:5]
Reactant: C=CCOC(=O)C(c1ccc([N+](=O)[O-])cc1F)c1ccc(C(=O)c2ccc(C)cc2C)n1C
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCN1
Solvent: C1CCOC1
Product: Cc1ccc(C(=O)c2ccc(Cc3ccc([N+](=O)[O-])cc3)n2C)c(C)c1
Reaction time: 1.5 h
Yield: 98.1 %

Procedure:
To a solution of allyl 2-[5-(2,4-dimethylbenzoyl)-1-methylpyrrol-2-yl)-2-(2-fluoro-4-nitrophenyl)acetate (3.6 g, 7.99 mmol) [prepared as described in Example 6, Step (d)] in anhydrous THF (40 ml) was added morpholine (6.99 ml, 79.90 mmol) and tetrakis(triphenylphosphine) palladium (9 mg, 0.008 mmol)). After 1.5 h, the solvent was evaporated and the residue was partitioned between ether and 1N NaHSO4. The organic layer was separated, dried over magnesium sulfate, and concentrated to dryness. Purification by column chromatography (ethyl acetate/hexane) gave 4-[5-(2,4-dimethylbenzoyl)-1-methyl-pyrrol-2-yl-methyl)nitrobenzene (2.73 g, 93%) as a pale yellow oil. ##STR37##
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[C:12]([NH:20][NH2:21])(=O)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(O)C>[C:13]1([C:12]2[N:3]3[CH:4]=[CH:5][C:6]4[C:11]([C:2]3=[N:21][N:20]=2)=[CH:10][CH:9]=[CH:8][CH:7]=4)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: NNC(=O)c1ccccc1
Reactant: Clc1nccc2ccccc12
Solvent: CCO
Product: c1ccc(-c2nnc3c4ccccc4ccn23)cc1

Procedure:
To a solution of 1-chloro-isoquinoline (4 g, 24.45 mmol) in ethanol (50 ml) was added benzoic acid hydrazide (4 g, 29.34 mmol) and the mixture was stirred at reflux temperature for 16 hrs. The reaction mixture was cooled and the precipitate was filtered off and recrystallised from ethanol (50 ml) affording 1.9 g of impure (NMR) title compound. The filtrate was purified by silicagel chromatography using a mixture of ethyl acetate/heptane (1:2) as eluent. Pure fractions were collected and the solvent evaporated in vacuo affording 0.2 g (3%) of the title compound as a solid.
Reaction SMILES: N#N.[N+:3]([C:6]1[CH:7]=[N:8][N:9]([CH2:11][C:12]2[O:16][C:15]([CH:17]([OH:19])[CH3:18])=[CH:14][CH:13]=2)[CH:10]=1)([O-:5])=[O:4]>C(C#N)(C)=O.O=[Mn]=O>[N+:3]([C:6]1[CH:7]=[N:8][N:9]([CH2:11][C:12]2[O:16][C:15]([C:17](=[O:19])[CH3:18])=[CH:14][CH:13]=2)[CH:10]=1)([O-:5])=[O:4]
Reactant: CC(O)c1ccc(Cn2cc([N+](=O)[O-])cn2)o1
Agent: O=[Mn]=O
Agent: CC(=O)C#N
Agent: N#N
Product: CC(=O)c1ccc(Cn2cc([N+](=O)[O-])cn2)o1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 1-[5-(4-nitro-pyrazol-1-ylmethyl)-furan-2-yl]-ethanol (4.94 g, 20.82 mmol) in AcCN (200.0 mL) was treated at rt with MnO2 (12.07 g, 124.90 mmol) and the reaction mixture was stirred at rt overnight before being filtered through Celite. The solvent was removed under reduced pressure. Purification of the residue by FC (50:00 hept-EA) gave the title compound as a yellow solid. TLC: rf (50:50 hept-EA)=0.26. LC-MS-conditions 02: tR=0.83 min. 1H NMR (400 MHz, CDCl3) δ 2.47 (s, 3H), 5.41 (s, 2H), 6.60 (d, J=3.3 Hz, 1H), 7.17 (d, J=3.3 Hz, 1H), 8.10 (s, 1H), 8.25 (s, 1H).
Reaction SMILES: [CH:1](=O)[CH2:2][CH2:3][CH3:4].[CH2:6]([NH2:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>C1(C)C=CC=CC=1>[CH:1](=[N:13][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCC=O
Reactant: NCc1ccccc1
Solvent: Cc1ccccc1
Product: CCCC=NCc1ccccc1

Procedure:
This material is a known compound prepared in the standard fashion. To about 100 mL of toluene was added 28 mL of butyraldehyde, 34 mL of benzylamine, and several grams of 3A molecular sieves. The mixture became warm and turbid after standing for a few minutes. After standing for several hours the mixture was colorless and transparent. The imine product was isolated by distillation under vacuum and characterized by NMR spectroscopy.
Reaction SMILES: [O:1]=[C:2]1[NH:6][C:5](=[O:7])[C:4](=[CH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH:16]=3)=[CH:11][CH:10]=2)[S:3]1.[H][H]>O1CCOCC1.[Pd]>[O:1]=[C:2]1[NH:6][C:5](=[O:7])[CH:4]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:26])([CH3:28])[CH3:27])[CH:16]=3)=[CH:13][CH:14]=2)[S:3]1
Reactant: [H][H]
Reactant: CN(Cc1cccc(-c2ccc(C=C3SC(=O)NC3=O)cc2)c1)C(=O)OC(C)(C)C
Agent: [Pd]
Solvent: C1COCCO1
Product: CN(Cc1cccc(-c2ccc(CC3SC(=O)NC3=O)cc2)c1)C(=O)OC(C)(C)C
Temperature: 50 °C

Procedure:
30 g (71 mmol) of tert-butyl [4′-(2,4-dioxothiazolidin-5-ylidenemethyl)biphenyl-3-ylmethyl]methylcarbamate in 500 ml of dioxane are placed in a reactor. The reaction medium is degassed, followed by addition of g (1 equivalent by mass) of 10% palladium-on-charcoal. The system is placed under 3 bar of hydrogen and heated at 50° C. for seven hours. The reaction medium is filtered through Celite and evaporated, and the residue obtained is purified by chromatography on a column of silica with an fluent mixture of dichloromethane and methanol (98/2). After evaporation of the solvents, 18 g (60%) of the expected product are collected.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([CH3:16])=[O:15])=[CH:10][C:9]=1[Br:17].Cl>CCOCC>[Br:17][C:9]1[CH:10]=[C:11]([CH:14]([OH:15])[CH3:16])[CH:12]=[CH:13][C:8]=1[CH3:7]
Reactant: CC(=O)c1ccc(C)c(Br)c1
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: CCOCC
Product: Cc1ccc(C(C)O)cc1Br
Yield: 81 %

Procedure:
Lithium aluminum hydride (6.45 g, 170 mmol) was added to a 250 mL round-bottom flask equipped with a magnetic stirrer bar and a septum. The flask was dried under vacuum and then filled with nitrogen. Anhydrous ether (50 mL) was first injected into the flask. Subsequently, a solution of 3-bromo-4-methylacetophenone (38 g, 180 mmol) in anhydrous ether (50 mL) was injected into the flask dropwise. The reaction mixture was stirred until no more gas was generated. The mixture was poured into a dilute HCl aqueous solution (240 mL), extracted with ethyl acetate (4×30 mL), washed over a saturated NH4Cl aqueous solution (50 mL), dried over anhydrous magnesium sulfate, and concentrated under vacuum to give a crude product. The crude product was further purified by distillation under reduced pressure (130° C., 4 mm Hg) to give 31.35 g (81% yield) of the desired product. 1H NMR (300 MHz, CDCl3) δ 1.47 (3H, t, J=6.4 Hz), 1.76 (1H, s), 2.38 (3H, s), 4.84 (1H, q, J=6.4 Hz), 7.20 (2H, s), 7.55 (1H, s); 3C NMR (75 MHz, CDCl3) δ 22.54, 25.16, 69.33, 124.30, 124.93, 129.34, 130.82, 136.88, 145.27; IR (neat) 3024 (s), 2997 (s), 2927 (m), 1605 (w), 1562 (w), 1494 (m), 1452 (m), 1381 (m), 1331 (w), 1255 (m), 1091 (m), 1038 (m), 1009 (m), 908 (m), 822 (m), 733 (s) cm−1; MS m/z 214 (M+), 199, 197, 171, 169, 119, 91; HRMS calcd for C9H11OBr 213.9993, found 213.9995.
Reaction SMILES: C1(S(CC2C(C(OCC)=O)=C(O)C([C:23]3[CH:27]=[CH:26][O:25][CH:24]=3)=CC=2)(=O)=O)C=CC=CC=1.Br[C:29]1[C:30]([O:50][CH3:51])=[C:31]([C:36]([CH2:39][S:40]([C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([OH:49])[CH:44]=2)(=[O:42])=[O:41])=[CH:37][CH:38]=1)[C:32]([O:34][CH3:35])=[O:33]>>[O:25]1[CH:26]=[CH:27][C:23]([C:29]2[C:30]([O:50][CH3:51])=[C:31]([C:36]([CH2:39][S:40]([C:43]3[CH:48]=[CH:47][CH:46]=[C:45]([OH:49])[CH:44]=3)(=[O:42])=[O:41])=[CH:37][CH:38]=2)[C:32]([O:34][CH3:35])=[O:33])=[CH:24]1
Reactant: CCOC(=O)c1c(CS(=O)(=O)c2ccccc2)ccc(-c2ccoc2)c1O
Reactant: COC(=O)c1c(CS(=O)(=O)c2cccc(O)c2)ccc(Br)c1OC
Product: COC(=O)c1c(CS(=O)(=O)c2cccc(O)c2)ccc(-c2ccoc2)c1OC

Procedure:
Prepared by proceeding in a similar manner to Intermediate 36, starting from methyl 3-bromo-6-(3-hydroxybenzenesulphonylmethyl)-2-methoxybenzoate (Intermediate 141)