Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[C@@H:4]([NH:10][S:11]([C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=1)(=[O:13])=[O:12])[C@H:5]([OH:9])[CH:6]([CH3:8])[CH3:7].[O-]S(C(F)(F)F)(=O)=O.[C:30]1(C(C2C=CC=CC=2)=C[SH2+])C=CC=C[CH:31]=1.C(N(CC)CC)C>ClCCl.O>[CH3:1][O:2][C:3]([C@@H:4]1[C@@H:5]([CH:6]([CH3:8])[CH3:7])[O:9][CH2:31][CH2:30][N:10]1[S:11]([C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=1)(=[O:13])=[O:12])=[O:21]
Reactant: [SH2+]C=C(c1ccccc1)c1ccccc1
Reactant: COC(=O)[C@@H](NS(=O)(=O)c1ccc(C)cc1)[C@H](O)C(C)C
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: COC(=O)[C@@H]1[C@@H](C(C)C)OCCN1S(=O)(=O)c1ccc(C)cc1
Reaction time: 12 h

Procedure:
A mixture of (2S,3R)-3-hydroxy-4-methyl-2-(toluene-4-sulfonylamino)-pentanoic acid methyl ester (0.4 g, 1.27 mmol) and diphenylvinylsulfonium triflate (0.5 g, 1.4 mmol) in dichloromethane (10 mL) was added triethylamine dropwise at 0° C. After stirring for 12 hours, the mixture was diluted with water, and then extracted with ethyl acetate, then dried over sodium sulfate. After removal of solvent, the residue was purified by flash chromatopraphy (eluented with ethyl acetate/hexane=1:4) to afford the product as a white solid. MS: calc'd (MH+) 342, measured (MH+) 342.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH2:11]O)[CH:10]=1)[N:7]([CH:13]([CH3:15])[CH3:14])[N:6]=[CH:5]2.[CH3:16][O:17][C:18]([C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[NH:25][N:24]=[CH:23]2)=[O:19]>>[CH3:16][O:17][C:18]([C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[N:25]([CH2:11][C:9]1[CH:10]=[C:2]([Br:1])[CH:3]=[C:4]3[C:8]=1[N:7]([CH:13]([CH3:15])[CH3:14])[N:6]=[CH:5]3)[N:24]=[CH:23]2)=[O:19]
Reactant: COC(=O)c1ccc2[nH]ncc2c1
Reactant: CC(C)n1ncc2cc(Br)cc(CO)c21
Product: COC(=O)c1ccc2c(cnn2Cc2cc(Br)cc3cnn(C(C)C)c23)c1
Yield: 30 %

Procedure:
Compound 30 was prepared following general method 3A, using compound 22 as a starting material and 1H-indazole-5-carboxylic acid methyl ester as the heterocycle. Yield: 30%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][CH:18]4[CH2:23][CH2:22][CH2:21][CH2:20][C:19]4([CH3:27])[C:24]([O-:26])=[O:25])[C:14]([F:28])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.O.[Li+].[OH-]>CO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][CH:18]4[CH2:23][CH2:22][CH2:21][CH2:20][C:19]4([CH3:27])[C:24]([OH:26])=[O:25])[C:14]([F:28])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: CC1(C(=O)[O-])CCCCC1Nc1nc(-c2c[nH]c3ncc(Cl)cc23)ncc1F
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC1(C(=O)O)CCCCC1Nc1nc(-c2c[nH]c3ncc(Cl)cc23)ncc1F
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To a solution of (1R,3S)-methyl 3-((2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-1-methylcyclohexanecarboxylate, 52j, (0.035 g, 0.083 mmol) dissolved in MeOH (5 mL) and water (1 mL) was added LiOH (0.004 g, 0.168 mmol). The reaction was allowed to stir for 2 days at room temperature and then concentrated to dryness. The residue was washed with ethanol. The combined ethanol washings were concentrated in vacuo, yielding 30 mg of desired product as an off white solid.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:18]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=3)[C:3]=12.[F:30][C:31]([F:42])([F:41])[C:32]1[CH:33]=[C:34]([N:38]=[C:39]=[O:40])[CH:35]=[CH:36][CH:37]=1>C(Cl)Cl>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:18]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:39]([NH:38][C:34]4[CH:35]=[CH:36][CH:37]=[C:32]([C:31]([F:30])([F:41])[F:42])[CH:33]=4)=[O:40])=[CH:13][CH:12]=3)[C:3]=12
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](n2nc(-c3ccc(N)cc3)c3c(N)ncnc32)C1
Reactant: O=C=Nc1cccc(C(F)(F)F)c1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CC[C@@H](n2nc(-c3ccc(NC(=O)Nc4cccc(C(F)(F)F)c4)cc3)c3c(N)ncnc32)C1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
A solution of (R)-tert-butyl 3-(4-amino-3-(4-aminophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidine-1-carboxylate (0.100 g, 0.25 mmol) in CH2Cl2 (10 mL) was cooled in an ice-water bath. To this, 3-(trifluoromethyl)phenyl isocyanate (0.035 mL, 0.25 mmol) diluted in CH2Cl2 (5 mL) was added dropwise. The reaction was allowed to warm to room temperature and left stirring for 6 hours. The reaction proceeded until completion as judged by TLC and LC-MS, was concentrated in vacuo, resuspended in 50:50 H2O—CH3CN, and purified on a C18 column in CH3CN/H2O/0.1% TFA (1-100% gradient) to afford AD79. ESI-MS m/z [M+H]+ found 583.5, calculated 583.2.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][C:10]2[CH:34]=[CH:33][C:13]([C:14]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[N:18]([CH2:25][CH2:26][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:17]=3)=[O:15])=[CH:12][C:11]=2[O:35][CH2:36][CH2:37][CH2:38]Cl)=[CH:4][CH:3]=1.[CH3:40][O:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1[N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C)C=O.O>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][C:10]2[CH:34]=[CH:33][C:13]([C:14]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[N:18]([CH2:25][CH2:26][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:17]=3)=[O:15])=[CH:12][C:11]=2[O:35][CH2:36][CH2:37][CH2:38][N:51]2[CH2:50][CH2:49][N:48]([C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=3[O:41][CH3:40])[CH2:53][CH2:52]2)=[CH:4][CH:3]=1
Reactant: COc1ccccc1N1CCNCC1
Reactant: CCOC(=O)CCCn1cc(C(=O)c2ccc(OCc3ccc(C)cc3)c(OCCCCl)c2)c2ccccc21
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCCn1cc(C(=O)c2ccc(OCc3ccc(C)cc3)c(OCCCN3CCN(c4ccccc4OC)CC3)c2)c2ccccc21
Temperature: 60 °C
Reaction time: 8 h
Yield: 74.3 %

Procedure:
Ethyl 4-{3-[4-(4-methylphenylmethoxy)-3-(3-chloropropoxy)benzoyl]indol-1-yl}butanoate (2.59 g) obtained in Step 2 was dissolved in N,N-dimethylformamide (30 ml). 1-(2-Methoxyphenyl)piperazine (1.36 g), potassium carbonate (0.85 g), and potassium iodide (1.02 g) were added to the resultant solution and stirred overnight at 60° C. The reaction mixture was poured into water and extracted with ethyl acetate. The resultant extract was washed with brine and then dried. The solvent was distilled off. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:2), obtaining 2.47 g of ethyl 4-{3-{4-(4-methylphenylmethoxy)-3-{3-[4-(2-methoxyphenyl)piperazin-1-yl]propoxy}benzoyl}indol-1-yl}butanoate as a colorless oily substance.
Reaction SMILES: [O:1]=[C:2]1[CH2:6][S:5][C:4](=[S:7])[N:3]1[NH:8][C:9]1[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=1[C:11]([OH:13])=[O:12].[Cl:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:25]1[O:29][C:28]([CH:30]=O)=[CH:27][CH:26]=1.C(O)(=O)C.C(O)(=O)C.C(N)CN.S([O-])(O)=O.[Na+]>CO>[Cl:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:25]1[O:29][C:28]([CH:30]=[C:6]2[S:5][C:4](=[S:7])[N:3]([NH:8][C:9]3[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=3[C:11]([OH:13])=[O:12])[C:2]2=[O:1])=[CH:27][CH:26]=1
Reactant: O=Cc1ccc(-c2ccccc2Cl)o1
Reactant: O=C(O)c1ccccc1NN1C(=O)CSC1=S
Agent: O=S([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: NCCN
Solvent: CO
Product: O=C(O)c1ccccc1NN1C(=O)C(=Cc2ccc(-c3ccccc3Cl)o2)SC1=S
Temperature: 25 °C
Reaction time: 17 h
Yield: 90.8 %

Procedure:
A mixture of 2-(4-oxo-2-thioxo-thiazolidin-3-ylamino)-benzoic acid (0.090 g, 0.34 mmol), 5-(2-chloro-phenyl)-furan-2-carbaldehyde (0.074 g, 0.36 mmol) (purchased from Aldrich Chemical Co.) and ethylenediamine diacetate (0.065 g, 0.036 mmol) in methanol (8 mL) was stirred at room temperature for 17 h. The reaction mixture was poured into stirred 0.6 N aq sodium hydrogensulfite (50 mL). The mixture was vigorously stirred for 15 min. The solid product was filtered off and washed on funnel successively with 0.6 N aq sodium hydrogensulfite (2 mL), water (2×2 mL), ether (2 mL) and hexanes (2 mL). The material was dried in a vacuum oven at 65° C. for 19 h to afford 2-{5-[1-[5-(2-Chloro-phenyl)-furan-2-yl]-methylidene]-4-oxo-2-thioxo-thiazolidin-3-ylamino}-benzoic acid (141 mg, 92%) as a solid. 1H NMR (400 MHz, DMSO-d6): δ 6.55 (1H, d, J=8.0 Hz), 6.87 (1H, t, J=7.6 Hz), 7.32 (1H, t, J=7.6 Hz), 7.44-7.51 (3H, m), 7.62 (1H, d, J=8.0 Hz), 7.66 (1H, d, J=8.4 Hz), 7.80 (1H, s), 7.91 (1H, d, J=8.0 Hz), 7.97 (1H, d, J=8.0 Hz). LC/MS: APCI 457.2, HPLC 97.9%
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[CH3:7][O:8][C:9]([C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][C:19]=1[O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:14]([OH:16])=O)=[O:10].[NH:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1.O>ClCCl.CN(C)C=O>[C:22]1([CH2:21][O:20][C:19]2[CH:18]=[CH:17][C:13]([C:14]([N:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)=[O:16])=[CH:12][C:11]=2[C:9]([O:8][CH3:7])=[O:10])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: COC(=O)c1cc(C(=O)O)ccc1OCc1ccccc1
Reactant: C1CCNC1
Agent: O=C(Cl)C(=O)Cl
Solvent: O
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COC(=O)c1cc(C(=O)N2CCCC2)ccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Oxalyl chloride (0.61 ml, 6.99 mmol) was added dropwise to a stirred solution of 3-[(methyloxy)carbonyl]-4-[(phenylmethyl)oxy]benzoic acid (may be prepared as described in Description 49; 400 mg, 1.40 mmol) in dichloromethane (10 ml) and dimethylformamide (3 drops) at room temperature. The mixture was stirred at room temperature for 1 h. The solvent was removed, and the residue was dissolved in dichloromethane (5 ml). This mixture was added to a solution of pyrrolidine (497 mg, 6.99 mmol) in dichloromethane (5 ml) and the mixture was stirred at room temperature for 2 h. Water (60 ml) was added, and the mixture was extracted with dichloromethane (3×60 ml). The organic phase was washed with saturated brine (50 ml), dried over sodium sulfate, and evaporated in vacuo to give the crude product. The crude product was loaded onto a silica gel column (200 g), and was eluted with dichloromethane/methanol=50:1 to yield the title compound as a colourless oil. 400 mg.
Reaction SMILES: [CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].[H-].[Na+].Cl[CH2:9][CH2:10][C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:12].O>CN(C=O)C>[CH3:1][S:2]([NH:5][CH2:9][CH2:10][C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:12])(=[O:4])=[O:3]
Reactant: O=C(CCCl)c1ccccc1
Reactant: CS(N)(=O)=O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CS(=O)(=O)NCCC(=O)c1ccccc1
Reaction time: 0.33 h
Yield: 21.1 %

Procedure:
Methane sulfonamide (0.476 g, 5.00 mmol) was dissolved in DMF (10 mL), and to the solution was added 60% sodium hydride (0.275 g, 5.00 mmol), and the mixture was stirred in a water bath for 20 minutes. To the reaction mixture was added 3-chloropropiophenone (843 mg, 5.00 mol). The mixture was stirred in a water bath for one hour, and further stirred at room temperature for 15 hours. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=20/1) to give 3-(methylsulfonylamino)propiophenone (240 mg, 21%).
Reaction SMILES: [N:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([C@@H:4]3[CH2:11][NH2:12])[CH2:2]1)[CH2:8]2.[NH:13]1[C:21]2[C:16](=[CH:17][C:18]([C:22](O)=[O:23])=[CH:19][CH:20]=2)[CH:15]=[CH:14]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>N1C=CC=CC=1>[N:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([C@@H:4]3[CH2:11][NH:12][C:22]([C:18]3[CH:17]=[C:16]4[C:21](=[CH:20][CH:19]=3)[NH:13][CH:14]=[CH:15]4)=[O:23])[CH2:2]1)[CH2:8]2
Reactant: O=C(O)c1ccc2[nH]ccc2c1
Reactant: NCC1C2CC3CC1CN(C3)C2
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: c1ccncc1
Product: O=C(NCC1C2CC3CC1CN(C3)C2)c1ccc2[nH]ccc2c1

Procedure:
The product of Example 2B was reacted with indole-5-carboxylic acid, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, 1-hydroxybenzotriazole and 4-di(methylamino)pyridine in pyridine as described in Example 3 to afford the title compound: 1H NMR (methanol-d4, 500 MHz) δ 1.91 (br s, 2 H), 1.94-2.01 (m, 3 H), 2.11-2.18 (m, 2 H), 2.24 (t, J=7.93 Hz, 1 H), 3.16-3.21 (m, 2 H), 3.59-3.65 (m, 4 H), 6.54 (dd, J=3.05, 0.92 Hz, 1 H), 7.22-7.28 (m, 1 H), 7.32 (d, J=3.05 Hz, 1 H), 7.41-7.44 (m, 1 H), 7.60 (dd, J=8.54, 1.83 Hz, 1 H), 7.63-7.70 (m, 1 H), 8.10 ppm (d, J=1.83 Hz, 1 H); MS (ESI) m/z 310 (M+H)+.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH:11]=O.[C:13]1([CH2:19][C:20]([OH:22])=[O:21])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(OC(=O)C)(=O)C.Cl>C(N(CC)CC)C>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH:11]=[C:19]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:20]([OH:22])=[O:21]
Reactant: O=Cc1ccc2ccccc2c1
Reactant: O=C(O)Cc1ccccc1
Agent: Cl
Solvent: CC(=O)OC(C)=O
Solvent: CCN(CC)CC
Product: O=C(O)C(=Cc1ccc2ccccc2c1)c1ccccc1
Yield: 89 %

Procedure:
A mixture of 2-naphthaldehyde (5 g, 32 mmole), phenylacetic acid (4.4 g, 32 mmole), triethylamine (5 mL) and acetic anhydride (10 mL) were refluxed for 5 hours. The solution was poured into 2N HCl (150 mL) and a precipitate formed immediately. This was recrystallized from 50% aqueous ethanol to yield 7.8 g (89% yield) of a white power.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[C:4]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[O:6][CH:5]=1.C([O-])=O.[NH4+]>>[Cl:1][C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[CH:4]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[O:6][CH2:5]1
Reactant: O=c1c(-c2ccccc2Cl)coc2ccccc12
Agent: O=C[O-]
Agent: [NH4+]
Product: O=C1c2ccccc2OCC1c1ccccc1Cl
Temperature: 25 °C
Yield: 13.7 %

Procedure:
Compound 41 was prepared following the general procedure described by Wähälä and Hase, Heterocycles 1989, 28, (1), 183-186, herein incorporated by reference. To a 10 mL round bottom flask was added 2′-chloroisoflavone (152 mg, 0.592 mmol) and ammonium formate (149 mg, 2.37 mmol). The flask was purged with N2, followed by addition of methanol (8 mL) and 10% Pd/C (151 mg). The reaction was allowed to stir at room temperature and monitored by reverse phase HPLC. Upon consumption of starting material, the reaction mixture was passed through a pad of silica gel using EtOAc as the eluent. The solvent was concentrated in vacuo to afford crude 41. Purified by flash column chromatography (SiO2, 10% EtOAc/Hex) to afford 41 (21 mg, 14%) as an off-white solid. Analytical data for isoflavanone 41: 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J=9.5 Hz, 1H), 7.53 (app t, J=9 Hz, 1H), 7.39-7.28 (m, 4H), 7.09-7.03 (m, 2H), 4.71-4.66 (m, 2H), 4.04-4.01 (app t, J=6.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 192.4, 161.8, 136.3, 133.2, 129.1, 128.9, 128.1, 128.0, 121.9, 121.3, 118.1, 71.7, 52.6; GCMS: Mass calculated for C15H11ClO2, [M]+, 259. Found 225. 4′-fluoroisoflavanone (46). Prepared according to the general procedure using 4′-fluoroisoflavone (77 mg, 0.319 mmol), ammonium formate (81 mg, 1.28 mmol), methanol (6.4 mL) and 10% Pd/C (81 mg). Purified by flash column chromatography (SiO2, 10% EtOAc/Hex) to afford 46 (18 mg, 23%) as an off-white solid. Analytical data for isoflavanone 46: 1H NMR (500 MHz, CDCl3) δ 7.97 (d, J=9.5 Hz, 1H), 7.53 (app t, J=9 Hz, 1H), 7.29-7.26 (m, 2H), 7.09-7.03 (m, 3H), 4.70-4.62 (m, 2H), 4.02-3.99 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 205.8, 192.2, 191.9, 161.8, 136.4, 130.9, 130.5, 128.0, 122.0, 121.1, 118.1, 116.2, 116.0, 71.6, 51.8; LCMS: Mass calculated for C15H11FO2, [M+H]+, 243. Found 243.
Reaction SMILES: Cl[CH:2]([O:6][C:7]([NH:9][CH2:10][C:11]1([CH2:17][C:18]([OH:20])=[O:19])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[O:8])[CH:3]([CH3:5])[CH3:4].N12CCCN=C1CCCCC2.[C:32]([OH:40])(=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[N:35][CH:34]=1>CC(C)=O>[C:32]([O:40][CH:2]([O:6][C:7]([NH:9][CH2:10][C:11]1([CH2:17][C:18]([OH:20])=[O:19])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[O:8])[CH:3]([CH3:5])[CH3:4])(=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[N:35][CH:34]=1
Reactant: O=C(O)c1cccnc1
Reactant: CC(C)C(Cl)OC(=O)NCC1(CC(=O)O)CCCCC1
Solvent: CC(C)=O
Solvent: C1CCC2=NCCCN2CC1
Product: CC(C)C(OC(=O)NCC1(CC(=O)O)CCCCC1)OC(=O)c1cccnc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 14.5 %

Procedure:
A mixture of (93) (268 mg, 0.88 mmol), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (158 μL, 1.01 mmol), and nicotinic acid (637 mg, 5.2 mmol) in acetone was stirred at room temperature for 48 h. After filtration, the filtrate was concentrated in vacuo and the resulting residue was purified by reverse phase preparative HPLC to afford 50 mg (14%) of the title compound. 1H NMR (CD3OD, 400 MHz): δ 1.07 (d, J=6.8 Hz, 3H), 1.09 (d, J=6.8 Hz, 3H), 1.32-1.58 (m, 10H), 2.19 (m, 1H), 2.26 (s, 2H), 3.23 (m, 2H), 6.78 (d, J=4.8 Hz, 1H), 7.58 (m, 1H), 8.39 (d, J=6.4 Hz, 1H), 8.76 (d, J=4.4 Hz, 1H), 9.10 (s, 1H). MS (ESI) m/z 393.42 (M+H+).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)=[CH:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][N:16]3C(C)(C)[NH:20][C:21](=[O:22])[CH:15]3[CH2:14]2)=[CH:4][CH:3]=1.Cl.C(=O)([O-])[O-].[K+].[K+]>>[OH2:22].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)=[CH:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][NH:16][CH:15]([C:21]([NH2:20])=[O:22])[CH2:14]2)=[CH:4][CH:3]=1
Reactant: CC1(C)NC(=O)C2CN(CCCC=C(c3ccc(F)cc3)c3ccc(F)cc3)CCN21
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Product: NC(=O)C1CN(CCCC=C(c2ccc(F)cc2)c2ccc(F)cc2)CCN1
Product: O
Reaction time: 2 h
Yield: 50 %

Procedure:
A mixture of 60 parts of 7-[5,5-bis(4-fluorophenyl)-4-pentenyl]hexahydro-3,3-dimethylimidazo[1,5-a]pyrazin-1(5H)-one and 850 parts of a hydrochloric acid solution 0.5N was stirred for 2 hours at reflux temperature. After cooling, the reaction mixture was treated with potassium carbonate. The product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 1,1'-oxybisethane. The product was filtered off and dried, yielding 29.5 parts (50%) of 4-[5,5-bis(4-fluorophenyl)-4-pentenyl]-2-piperazinecarboxamide monohydrate; mp. 51.3° C. (int. 25).
Reaction SMILES: [CH2:1](O)[CH:2]=[CH2:3].C(N(CC)CC)C.C(Cl)Cl.[CH3:15][C:16]1[CH:29]=[C:28]2[C:19]([S:20][C:21]3[CH:22]=[C:23]([C:31](Cl)=[O:32])[CH:24]=[CH:25][C:26]=3[C:27]2=[O:30])=[CH:18][CH:17]=1.[OH2:34]>>[CH3:15][C:16]1[CH:29]=[C:28]2[C:19]([S:20][C:21]3[CH:22]=[C:23]([C:31]([O:32][CH2:3][CH:2]=[CH2:1])=[O:34])[CH:24]=[CH:25][C:26]=3[C:27]2=[O:30])=[CH:18][CH:17]=1
Reactant: C=CCO
Reactant: O
Reactant: Cc1ccc2sc3cc(C(=O)Cl)ccc3c(=O)c2c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=CCOC(=O)c1ccc2c(=O)c3cc(C)ccc3sc2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 52.6 %

Procedure:
1.13 g (19.4 mmoles) of prop-2-en-1-ol and 2.06 g (20.4 mmoles) of triethyl amine are added to the CH2Cl2 solution containing 5.34 g (18.5 mmoles) of 7-methyl-9-oxo-thioxanthene-3-carbonyl chloride. After approximately 1 hour at room temperature under stirring, the mixture is poured in water, the organic phase is separated and washed again with water. The organic phase is then separated, dehydrated and dried after purification on a flash column (SiO2— eluent: CH2O2). 3.02 g (52.6%) of a yellow solid with the following spectral properties are obtained:
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[CH:4][N:3]=1.[CH:9]1([NH2:14])[CH2:13][CH2:12][CH2:11][CH2:10]1.CCN(C(C)C)C(C)C>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([NH:14][CH:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:5]=[CH:4][N:3]=1.[Cl:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:14][CH:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[N:7]=1.[CH:9]1([NH2:14])[CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: Clc1ccnc(Cl)n1
Agent: NC1CCCC1
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: Clc1ccnc(NC2CCCC2)n1
Product: Clc1nccc(NC2CCCC2)n1

Procedure:
(2-Chloro-pyrimidin-4yl)-cyclopentyl-amine and (4-chloro-pyrimidin-2yl)-cyclopentyl-amine were synthesized from 2,4 dichloropyrimidine (1.0 g, 6.7 mmol), cyclopentylamine (860 mg, 10.1 mmol) and DIEA (3.5 mL, 20.2 mmol) following procedure P, method P2, using THF as solvent. The crude products were purified by silica gel chromatography eluting with DCM/ethyl acetate (9:1) to afford 2-Chloro-pyrimidin-4-yl)-cyclopentyl-amine (598 mg). LCMS m/z: 199 (M+1)+, and (4-chloro-pyrimidin-2-yl)-cyclopentyl-amine (285 mg). LCMS m/z: 199 (M+1)+.
Reaction SMILES: Cl.[NH2:2][OH:3].N.OC1C=C[CH:9]=[C:10]2[C:15]=1[N:14]=[CH:13][CH:12]=[CH:11]2.C(C1(CC#N)[O:23][CH2:22][CH2:21][O:20]1)(C)C>CO>[OH:3][N:2]=[C:13]([NH2:14])[CH2:12][C:11]1([CH:10]([CH3:9])[CH3:15])[O:23][CH2:22][CH2:21][O:20]1
Reactant: NO
Reactant: CC(C)C1(CC#N)OCCO1
Reactant: Oc1cccc2cccnc12
Agent: Cl
Agent: N
Solvent: CO
Product: CC(C)C1(CC(N)=NO)OCCO1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 94 %

Procedure:
To a solution of hydroxylamine hydrochloride (6.3 g, 91.7 mmol) in methanol (2.5 mL), liquid ammonia (15.7 mL, 7N in methanol) was added and the suspension stirred for 30 minutes at room temperature. A catalytic amount of 8-hydroxiquinoline was added to the mixture, followed by 2-(2-isopropyl-1,3-dioxolan-2-yl)acetonitrile (3.38 g, 22 mmol) as a solution in methanol (2.5 mL). The mixture was stirred at 70° C. overnight. After cooling to room temperature, the suspension was filtered off and washed with dichloromethane. The solution was concentrated under reduced pressure, and reconcentrated three times from toluene to afford N′-hydroxy-2-(2-isopropyl-1,3-dioxolan-2-yl)acetimidamide (3.9 g, 94%) as a yellow solid, which was used directly in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 5.01 (bs, 2H), 4.05-3.94 (m, 4H), 2.44 (s, 2H), 2.03-1.94 (m, 1H), 0.95 (d, 6H); LC-MS (ESI) m/z 189 (M+H)+.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH2:12])[CH:6]=[C:5]2[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:19][O:20][C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[CH:23]=O.[CH3:29][O:30][C:31]1[CH:38]=[CH:37][CH:36]=[CH:35][C:32]=1[CH2:33][NH2:34]>>[CH3:19][O:20][C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[CH2:23][NH:12][C:7]1[CH:6]=[C:5]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([NH:34][CH2:33][C:32]3[CH:35]=[CH:36][CH:37]=[CH:38][C:31]=3[O:30][CH3:29])[CH:3]=2)[N:8]=1
Reactant: Nc1cc(-c2ccccc2)c2cc(Cl)ccc2n1
Reactant: COc1ccccc1C=O
Reactant: COc1ccccc1CN
Product: COc1ccccc1CNc1ccc2nc(NCc3ccccc3OC)cc(-c3ccccc3)c2c1

Procedure:
The title compound, MS: m/e=476.3 (M+H+), was prepared in accordance with the general method of example 13 from 6-chloro-4-phenyl-quinolin-2-ylamine (CAS 51478-40), 2-methoxybenzaldehyde and 2-methoxybenzylamine.