Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O=[C:2]([CH3:28])[C@H:3]([NH:8][C:9]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]([O:6][CH3:7])=[O:5].C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:40][C@@H:41]([CH2:46][C:47]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[NH:49][CH:48]=1)[C:42]([O:44][CH3:45])=[O:43].C([BH3-])#N.[Na+]>CO.C(Cl)(Cl)Cl>[CH3:45][O:44][C:42]([C@@H:41]([NH:40][C@H:2]([CH3:28])[C@H:3]([NH:8][C:9]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]([O:6][CH3:7])=[O:5])[CH2:46][C:47]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[NH:49][CH:48]=1)=[O:43]
Reactant: COC(=O)[C@@H](NC(c1ccccc1)(c1ccccc1)c1ccccc1)C(C)=O
Reactant: COC(=O)[C@@H](N)Cc1c[nH]c2ccccc12
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: ClC(Cl)Cl
Product: COC(=O)[C@H](Cc1c[nH]c2ccccc12)N[C@H](C)[C@H](NC(c1ccccc1)(c1ccccc1)c1ccccc1)C(=O)OC
Temperature: 25 °C
Reaction time: 24 h
Yield: 20.3 %

Procedure:
To a mixture of methyl (2S)-3-oxo-2-tritylaminobutyrate (2.00 g) and methyl (2S)-2-amino-3-(3-indolyl)propionate mono-p-toluenesulfonate (3.13 g) in methanol (30 ml) was added sodium cyanoborohydride (360 mg) and the mixture was stirred for 1 day at room temperature. The mixture was diluted with chloroform and washed successively with water and brine. The organic phase was separated and dried over magnesium sulfate, and the solvent was evaporated in vacuo. The residue was chromatographed on a silica gel (50 g) column and the elution was carried out with a mixture of n-hexane and ethyl acetate (4:1). The object fractions were collected and evaporated in vacuo to give methyl (2S,3R)-3-[[(1S)-1-methoxycarbonyl-2-(3-indolyl)ethyl]amino]-2-tritylaminobutyrate (625 mg) as a pale yellow oil.
Reaction SMILES: [CH3:1][N:2]([CH3:20])[C:3]([C:5]1[O:6][C:7]2[C:13]([N:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)=[CH:12][CH:11]=[CH:10][C:8]=2[CH:9]=1)=[O:4].[CH:21]([C:23]1[N:28]=[CH:27][C:26]([NH:29][C:30](=[O:32])[CH3:31])=[CH:25][CH:24]=1)=[CH2:22]>>[C:30]([NH:29][C:26]1[CH:25]=[CH:24][C:23]([CH2:21][CH2:22][N:17]2[CH2:18][CH2:19][N:14]([C:13]3[C:7]4[O:6][C:5]([C:3]([N:2]([CH3:20])[CH3:1])=[O:4])=[CH:9][C:8]=4[CH:10]=[CH:11][CH:12]=3)[CH2:15][CH2:16]2)=[N:28][CH:27]=1)(=[O:32])[CH3:31]
Reactant: CN(C)C(=O)c1cc2cccc(N3CCNCC3)c2o1
Reactant: C=Cc1ccc(NC(C)=O)cn1
Product: CC(=O)Nc1ccc(CCN2CCN(c3cccc4cc(C(=O)N(C)C)oc34)CC2)nc1

Procedure:
The compound was prepared according to the procedure disclosed in Example 43 starting from N,N-dimethyl-7-(piperazin-1-yl)benzofuran-2-carboxamide (0.075 g, 0.27 mmol) (Example 39d) and N-(6-vinylpyridin-3-yl)acetamide (0.16 g, 0.96 mmol). The product was purified by preparative HPLC to give the title compound. Yield: 0.055 g (46%).
Reaction SMILES: N(C(OC(C)C)=O)=NC(OC(C)C)=O.[OH:15][CH2:16][CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1.[Br:29][C:30]1[CH:35]=[CH:34][C:33](O)=[CH:32][CH:31]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1.CCOCC>[Br:29][C:30]1[CH:35]=[CH:34][C:33]([O:15][CH2:16][CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)=[CH:32][CH:31]=1
Reactant: CC(C)OC(=O)N1CCC(CO)CC1
Reactant: Oc1ccc(Br)cc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC(C)OC(=O)N1CCC(COc2ccc(Br)cc2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 54.6 %

Procedure:
Diisopropyl azodicarboxylate (9.1 mL, 46.27 mmol) in THF (15 mL) was added dropwise to a solution of 1-methylethyl 4-(hydroxymethyl)-1-piperidinecarboxylate (7.76 g, 38.56 mmol), 4-bromophenol (6.67 g, 38.56 mmol) and Ph3P (13.15 g, 50.12 mmol) in THF (85 mL) at −20° C. The reaction mixture was allowed to warm to ambient temperature and stirred at ambient temperature overnight. The mixture was concentrated, and the residue was purified by chromatography on a silica gel column using 0 to 25% EtOAc/hexane to give the crude product. The crude product was taken up in Et2O (250 mL) and washed with 1N NaOH (aq). The organic extracts were dried over MgSO4, filtered, and the filtrate was concentrated to give 7.5 g (55%) of 1-methylethyl 4-{[(4-bromophenyl)oxy]methyl}-1-piperidinecarboxylate as a white solid. 1H NMR (400 MHz, CDCl3): δ7.35 (d, 2H, J=8.9 Hz), 6.75 (d, 2H, J=8.9 Hz), 4.96-4.83 (m, 1H), 4.24-4.14 (m, 2H), 3.75 (d, 2H, J=6.4 Hz), 2.81-2.71 (m, 2H), 2.02-1.87 (m, 1H), 1.85-1.75 (m, 2H), 1.33-1.13 (m, 8H); LRMS (ESI), m/z 356/358 (M+H).
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[C:5]([O:9]C)[N:4]=[C:3]1[CH:11]([CH3:13])[CH3:12].Cl>CC(C)=O.CCOCC>[CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[C:5]([OH:9])[N:4]=[C:3]1[CH:11]([CH3:13])[CH3:12]
Reactant: COc1cc(=O)n(C)c(C(C)C)n1
Agent: Cl
Solvent: CC(C)=O
Solvent: CCOCC
Product: CC(C)c1nc(O)cc(=O)n1C
Yield: 7 %

Procedure:
6 g (0.33 mol) of 1-methyl-2-isopropyl-4-methoxy-6-oxo-1,6-dihydro-pyrimidine (for preparation, see line 15 this page) were dissolved in 30 ml of acetone and converted to the hydrochloride by adding a solution of hydrochloric acid in ether. The salt was filtered off and after drying was warmed for 20 minutes to 150°-155° C. After the elimination of methyl chloride had ceased, the material was cooled, triturated with ether and filtered off. 3.9 g (92% of theory) of 1-methyl-2-isopropyl-4-hydroxy-6-oxo-1,6-dihydro-pyrimidine were thus obtained in the form of a colourless powder of melting point 159° C.
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[OH:13])[O:9][C:8]([C:14]([OH:16])=[O:15])=[C:7]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1)[C:6]2=O)[CH3:2].O.[NH2:27][NH2:28]>C(O)C>[CH2:1]([C:3]1[C:12]([OH:13])=[CH:11][C:10]([OH:9])=[C:5]([C:6]2[C:7]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)=[C:8]([C:14]([OH:16])=[O:15])[NH:27][N:28]=2)[CH:4]=1)[CH3:2]
Reactant: NN
Reactant: CCc1cc2c(=O)c(-c3ccc(OC)cc3)c(C(=O)O)oc2cc1O
Solvent: O
Solvent: CCO
Product: CCc1cc(-c2n[nH]c(C(=O)O)c2-c2ccc(OC)cc2)c(O)cc1O
Temperature: 70 °C
Reaction time: 4 h

Procedure:
6-Ethyl-7-hydroxy-3-(4-methoxyphenyl)-4-oxo-chromene-2-carboxylic acid (13.6 g, 41.73 mmol) and hydrazine monohydrate (6.1 ml, 125.19 mmol) were suspended in ethanol (200 ml) at room temperature. The mixture was then heated slowly to 70° C. and stirred at this temperature for 4 hours. The mixture was cooled to room temperature and all volatile components were removed in vacuum. The residue was partitioned between water (11) and Ethyl acetate (1.41). Then the aqueous phase was separated. The organic phase yielded some product. The remainder of the product was extracted from the aqueous phase with Ethyl acetate (4×500 ml). The combined organic extracts were dried over Magnesium sulfate and evaporated to dryness under vacuum resulting in a further quantity of the desired product. The combined isolated product portions yielded 6.99 g (51%) of a light brown solid. 1H NMR Spectrum: δH (400 MHz, DMSO-6d) 0.84 (3H t, J=7.5 Hz), 2.23 (2H q, J=7.5 Hz), 3.38 (1H s, br), 3.74 (3H, s), 6.36 (1H, s), 6.56 (1H, s), 6.85 (2H d, J=8.7 Hz), 7.13 (2H d, J=8.7 Hz), 9.3 (1H s, br), 9.4 (1H s, br), 12.8 (1H s, br); Mass Spectrum: (M+H+) 355.04, (M+H−) 353.09.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[NH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([C:16]#[N:17])=[CH:8]1.O1CCCC1>O1CCOCC1>[NH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([CH2:16][NH2:17])=[CH:8]1
Reactant: N#Cc1c[nH]c2ccccc12
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1COCCO1
Solvent: C1CCOC1
Product: NCc1c[nH]c2ccccc12
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 54.5 %

Procedure:
Lithium aluminum hydride (100 mg) was added to a solution of 1H-indole-3-carbonitrile (100 mg) in 15 mL of 2:1 dioxane:tetrahydrofuran. The mixture was refluxed for 0.5 h, then cooled to 0 C and quenched by the sequential addition of 0.1 mL water, 0.1 mL 3 N sodium hydroxide, and 0.3 mL more water. After the mixture was stirred for 15 min at rt, the aluminum salts were removed by filtration and the solvent was evaporated to give 56 mg of C-(1H-indol-3-yl)methylamine.
Reaction SMILES: [CH2:1]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1Br)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].[Mg].CN(C)[CH:20]=[O:21].[Cl-].[NH4+]>O1CCCC1.C(Cl)(Cl)(Cl)Cl>[CH2:1]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH:20]=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CN(C)C=O
Reactant: CCCCCCCCCc1ccccc1Br
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: ClC(Cl)(Cl)Cl
Product: CCCCCCCCCc1ccccc1C=O
Reaction time: 1 h

Procedure:
A third of a solution of 22 g of 2-nonylbromobenzene in 35 ml of tetrahydrofuran is added to a mixture, stirred under an argon atmosphere, of 3.4 g of magnesium turnings, 25 ml of tetrahydrofuran and 3 drops of carbon tetrachloride and the whole is heated at the boil under reflux for 30 minutes. The remainder of the 2-nonylbromobenzene solution is then added dropwise over a period of one hour and the reaction mixture is maintained under reflux for 2 hours. After dilution with 40 ml of tetrahydrofuran the whole is cooled in an ice bath to approximately 5° and a solution of 11.6 ml of dimethylformamide in 20 ml of tetrahydrofuran is added dropwise over a period of 15 minutes. After stirrin9 for one hour at room temperature, 250 ml of saturated ammonium chloride solution are added to the reaction mixture, the organic layer is separated off and the aqueous layer is extracted three times with ether. The residue that remains after the combined ethereal extracts have been dried and concentrated by evaporation is purified by chromatography on silica gel with mixtures of petroleum ether with an increasing amount of methylene chloride, yielding the desired 2-nonylbenzaldehyde in the form of a pale yellow liquid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[C:4]1[C:9]([Cl:10])=[CH:8][CH:7]=[C:6]([CH:11]=O)[C:5]=1[F:13].[NH2:15][OH:16]>C(O)C>[CH3:1][O:2][C:3](=[O:14])[C:4]1[C:9]([Cl:10])=[CH:8][CH:7]=[C:6]([CH:11]=[N:15][OH:16])[C:5]=1[F:13]
Reactant: COC(=O)c1c(Cl)ccc(C=O)c1F
Reactant: NO
Solvent: CCO
Product: COC(=O)c1c(Cl)ccc(C=NO)c1F
Reaction time: 16 h

Procedure:
To a solution of methyl-6-chloro-2-fluoro-3-formylbenzoate (930 mg, 4294 μmol) in ethanol (14.5 ml) at RT was added hydroxylamine (50 wt. % aqueous solution) (1316 μl, 21469 μmol) and the solution was stirred for 16 hrs. The volatiles were removed under reduced pressure, and the residue was diluted with water, which caused a solid to precipitate. The solid was collected by filtration and washed with water and dried in vacuo to give an off-white solid.
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[C:6]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[N:7][O:8][C:9]=1[C:10]([O:12]C)=[O:11])=[O:4].[Li+].[OH-]>CO.O>[CH3:1][NH:2][C:3]([C:5]1[C:6]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[N:7][O:8][C:9]=1[C:10]([OH:12])=[O:11])=[O:4]
Reactant: CNC(=O)c1c(-c2ccccc2)noc1C(=O)OC
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CNC(=O)c1c(-c2ccccc2)noc1C(=O)O
Temperature: 25 °C
Reaction time: 1 h
Yield: 100 %

Procedure:
To a suspension of methyl 4-(methylcarbamoyl)-3-phenylisoxazole-5-carboxylate (35 mg, 0.134 mmol) in MeOH (0.8 mL) and water (0.2 mL) was added LiOH, Hydrate (6.77 mg, 0.161 mmol) and the mixture was allowed to stir at rt for 1 hr. during which time the reaction became homogeneous. The volatiles were removed in vacuo and the residue was partitioned between DCM (20 mL) and saturated potassium bisulfate solution (10 mL). The aqueous layer was extracted with DCM (10 mL) and the combined organic layers were dried (MgSO4) and concentrated to afford 4-(methylcarbamoyl)-3-phenylisoxazole-5-carboxylic acid (33 mg, 0.134 mmol, 100% yield) as a slightly off-white foam. HPLC retention time=0.88 minutes (YMC Combi 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1 TFA a 2 minute gradient. MS: (M+H)=247.13.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][C:10]2[CH:15]=[CH:14][N:13]=[CH:12][N:11]=2)=[CH:4][CH:3]=1.[I-].[NH2:18][N+:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>O.C(O)(C)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:10]3[CH:15]=[CH:14][N:13]=[CH:12][N:11]=3)=[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][N:19]3[N:18]=2)=[CH:4][CH:3]=1
Reactant: N[n+]1ccccc1
Reactant: O=C(Cc1ccncn1)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CC(C)O
Product: Fc1ccc(-c2nn3ccccc3c2-c2ccncn2)cc1
Temperature: 100 °C
Reaction time: 16 h

Procedure:
A solution of 1-(4-fluorophenyl)-2-(4-pyrimidinyl)-ethanone (21.6 g, 0.1 mol), 1-aminopyridinium iodide (22.2 g, 0.1 mol) and potassium carbonate (41.4 g, 0.3 mol) in a mixture of water (300 mL) and isopropanol (300 mL) was heated and stirred at 100° C. for 16 hours. The isopropanol was removed under vacuum and the resulting aqueous phase extracted with dichloromethane (5×200 mL). The dichloromethane extracts were combined and the solvent evaporated under reduced pressure to leave a red solid which was purified by silica gel chromatography eluting with a hexane/ethyl acetate to give the title compound as a yellow solid, 9.16 g (32%). 1H NMR (DMSO-d6): δ 7.07 (d, J=5.4 Hz, 1H), 7.14 (t, J=6.8 Hz, 1H), 7.32 (t, J=8.7 Hz, 2H), 7.35 (t, J=7.8 Hz, 1H), 7.60 (dd, J=5.7, 8.7 Hz, 2H), 8.40 (d, J=8.9 Hz, 1H), 8.54 (d, J=5.3 Hz, 1H), 8.83 (d, J=7.1 Hz, 1H), 9.16 (s, 1H), APESI+MS m/z 291 (M+1).
Reaction SMILES: [C:1]([OH:22])(=[O:21])[CH2:2][CH2:3][CH2:4]/[CH:5]=[CH:6]\[CH2:7]/[CH:8]=[CH:9]\[CH2:10]/[CH:11]=[CH:12]\[CH2:13]/[CH:14]=[CH:15]\[CH2:16]/[CH:17]=[CH:18]\[CH2:19][CH3:20].C([O-])([O-])=O.[K+].[K+].Cl[CH2:30][CH2:31][CH2:32][N:33]1[CH2:38][C@H:37]([OH:39])[C@@H:36]([OH:40])[C@H:35]([OH:41])[C@H:34]1[CH2:42][OH:43]>CN(C=O)C>[C:1]([O:22][CH2:30][CH2:31][CH2:32][N:33]1[CH2:38][CH:37]([OH:39])[CH:36]([OH:40])[C@H:35]([OH:41])[CH:34]1[CH2:42][OH:43])(=[O:21])[CH2:2][CH2:3][CH2:4]/[CH:5]=[CH:6]\[CH2:7]/[CH:8]=[CH:9]\[CH2:10]/[CH:11]=[CH:12]\[CH2:13]/[CH:14]=[CH:15]\[CH2:16]/[CH:17]=[CH:18]\[CH2:19][CH3:20]
Reactant: CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)O
Reactant: OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)CN1CCCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)OCCCN1CC(O)C(O)[C@H](O)C1CO
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
To a stirred solution of (5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoic acid 6 (6.94 g, 22.95 mmol) in DMF (25 mL) was added K2CO3 (12.69 g, 91.78 mmol) at room temperature and the mixture was stirred for 30 min. Then a solution of hydrochloride salt of (2R,3R,4R,5S)-1-(3-chloropropyl)-2-(hydroxymethyl)piperidine-3,4,5-triol 5 (5.5 g, 22.95 mmol) in DMF (25 mL) was added to the reaction mixture and the mixture was heated at 60° C. for 36 h. The reaction mixture was then filtered through a celite pad, washed with DCM (100 mL). The filtrate was concentrate under reduced pressure to get crude which was purified by column chromatography using 100-200 mesh silica gel and eluting with 6% methanol in DCM to afford 3-[(3R)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]propyl (5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoate, compound 7 (4.5 g, 39%) as brown oil.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:24])[C@H:15]([CH2:20][CH2:21][S:22][CH3:23])[NH:16][C:17](=[O:19])[CH3:18])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[C:17]([NH:16][C@H:15]([C:14]([N:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1)=[O:24])[CH2:20][CH2:21][S:22][CH3:23])(=[O:19])[CH3:18]
Reactant: CSCC[C@H](NC(C)=O)C(=O)N1CCN(C(=O)OC(C)(C)C)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CSCC[C@H](NC(C)=O)C(=O)N1CCNCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 33.7 %

Procedure:
To a solution of 8.6 g (0.024 mol) of 1-(t-butoxycarbonyl) -4-(N-acetyl-L-methionyl)piperazine in 60 ml of dichloromethane was added 10 ml of trifluoroacetic acid and the mixture was stirred at room temperature overnight. The solution was extracted with water and the resulting aqueous solution was made basic with sodium hydroxide. The product was extracted with dichloromethane, dried over sodium sulfate, and filtered. Evaporation of the solvent gave 2.1 g of 1-(N-acetyl-L-methionyl)piperazine, as an oil: IR (film) 3304, 3051, 2917, 2861, 1645, 1546, 1448, 1377 cm−1; NMR (CDCl3) δ 1.95 (m, 2 H), 2.02 (s, 3 H), 2.10 (s, 3 H), 2.54 (m, 2 H), 2.98 (m, 4 H), 3.74 (m, 4 H), 5.10 (m, 1 H), 6.40 (b, 0.5 H), 6.48 (b, 0.5 H).
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:19][CH2:20][CH3:21])(=[O:18])[CH2:14][CH2:15][CH:16]=[CH2:17].[C:22]([Si:26]([O:29][CH2:30][CH2:31][O:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39]I)=[CH:35][CH:34]=1)([CH3:28])[CH3:27])([CH3:25])([CH3:24])[CH3:23]>C1COCC1>[Si:26]([O:29][CH2:30][CH2:31][O:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][CH:14]([CH2:15][CH:16]=[CH2:17])[C:13]([O:19][CH2:20][CH3:21])=[O:18])=[CH:35][CH:34]=1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:28])[CH3:27]
Reactant: CC(C)(C)[Si](C)(C)OCCOc1ccc(CI)cc1
Reactant: C=CCCC(=O)OCC
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: C=CCC(Cc1ccc(OCCO[Si](C)(C)C(C)(C)C)cc1)C(=O)OCC
Temperature: -78 °C
Reaction time: 0.25 h

Procedure:
To a solution of diisopropylamine (1.1 eq.) in THF (0.12 M) was added, at −78° C., n-butyllithium (1.6 M hexane solution, 1.1 eq.) over a period of 5 min. The resulting mixture was stirred at −78° C. for 15 min and then warmed at RT for 10 min. With the reaction mixture re-cooled to −78° C., ethyl pent-4-enoate (1.1 eq.) was added dropwise as a 1.6 M THF solution. The resulting solution was stirred for 30 min at −78° C. Finally, tert-butyl{2-[4-(iodomethyl)phenoxy]ethoxy}dimethylsilane (1 eq.) was added dropwise as a 1.5 M THF solution. The reaction mixture was allowed to warm slowly to RT over 12 h. After the reaction was carefully quenched with the addition of a sat. aq. NH4Cl solution, the reaction mixture was extracted with ether. The combined organic extracts were washed with brine, dried over MgSO4, filtered and the filtrate concentrated in vacuo. Purification of the crude product thus obtained by way of column chromatography (SiO2, 10:1 (v/v) Hex:ether) afforded the title compound as a colorless oil.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[N:18]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[Cl:25])[N:17]=[C:16]([C:26]([OH:29])([CH3:28])[CH3:27])[CH:15]=3)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:37](Cl)(=[O:39])[CH3:38]>C(#N)C>[Cl:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[N:18]1[C:14]([C:11]2[CH:12]=[CH:13][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:37](=[O:39])[CH3:38])[CH:3]=3)=[CH:9][CH:10]=2)=[CH:15][C:16]([C:26]([OH:29])([CH3:27])[CH3:28])=[N:17]1
Reactant: CC(C)(O)c1cc(-c2ccc(-c3cccc(N)c3)cc2)n(-c2ccccc2Cl)n1
Reactant: CC(=O)Cl
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CC(=O)Nc1cccc(-c2ccc(-c3cc(C(C)(C)O)nn3-c3ccccc3Cl)cc2)c1
Temperature: 75 °C
Reaction time: 8 h
Yield: 48.4 %

Procedure:
To a solution of 2-(5-(3′-aminobiphenyl-4-yl)-1-(2-chlorophenyl)-1H-pyrazol-3-yl)propan-2-ol (370 mg, 037 mmol) in acetonitrile (1.6 mL) was added triethylamine (0.12 mL, 0.86 mmol) followed by acetyl chloride (27 μL, 380 μmol). The reaction vial was then shaken at 75° C. overnight. After cooling the reaction solution was concentrated under reduced pressure and the crude product was purified by flash column chromatography eluting with a gradient from 0% to 100% EtOAc/hexane to afford N-(4′-(1-(2-chlorophenyl)-3-(2-hydroxypropan-2-yl)-1H-pyrazol-5-yl)biphenyl-3-yl)acetamide (82 mg, 49% yield) as an oil. 1H NMR (400 MHz CDCl3): δ 7.79 (1H, s), 7.49-7.42 (4H, m), 7.41-732 (4H, m), 7.31-7.21 (3H, m), 6.54 (1H, s), 2.68 (1H, s), 2.19 (3H, s), 1.69 (6H, s). MS(ES): 445[M+H]+. The following compounds are prepared essentially according to the previous examples:
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[CH2:7][CH2:6][N:5]2[CH:8]=[N:9][CH:10]=[C:4]2[C:3]1=[O:11].[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([Mg]Br)=[CH:17][CH:16]=1.Cl>O1CCCC1>[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:3]2([OH:11])[C:2]([CH3:12])([CH3:1])[CH2:7][CH2:6][N:5]3[CH:8]=[N:9][CH:10]=[C:4]23)=[CH:17][CH:16]=1
Reactant: COc1ccc([Mg]Br)cc1
Reactant: CC1(C)CCn2cncc2C1=O
Agent: Cl
Solvent: C1CCOC1
Product: COc1ccc(C2(O)c3cncn3CCC2(C)C)cc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of 7.90 mmol of 7,7-dimethyl-6,7-dihydro-5H-imidazo[1,5-a]pyridin-8-one in 50 ml of tetrahydrofuran is admixed at 0-5° C. with 15.8 mmol of 4-methoxyphenylmagnesium bromide (0.5M solution in tetrahydrofuran). The reaction solution is subsequently stirred at 0° C. for 1 hour and then at room temperature for 16 hours. The reaction solution is hydrolysed with 0.5N HCl and extracted with tert-butyl methyl ether. The aqueous phase is rendered basic with saturated aqueous sodium hydrogen carbonate solution and the precipitated solid is isolated by filtration and dried. The title compound is obtained as a grey solid and used without further purification for the next stage. Rt=5.42 (Gradient I).
Reaction SMILES: [I:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][O:7][CH:8]([C:17]2[N:21]([CH3:22])[CH:20]=[N:19][CH:18]=2)[C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=2)=[C:4]([N+:25]([O-])=O)[CH:3]=1.O.O.Cl[Sn]Cl.Cl>CO>[NH2:25][C:4]1[CH:3]=[C:2]([I:1])[CH:24]=[CH:23][C:5]=1[CH2:6][O:7][CH:8]([C:17]1[N:21]([CH3:22])[CH:20]=[N:19][CH:18]=1)[C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=1
Reactant: Cn1cncc1C(OCc1ccc(I)cc1[N+](=O)[O-])c1ccc(C#N)cc1
Agent: Cl
Agent: Cl[Sn]Cl
Solvent: CO
Solvent: O
Product: Cn1cncc1C(OCc1ccc(I)cc1N)c1ccc(C#N)cc1
Reaction time: 12 h

Procedure:
A solution of Example 46B (0.8 g, 2.1 mmol) in methanol (50 mL) at room temperature was treated with SnCl2.2H2O (1.41 g, 6.3 mmol) and concentrated HCl (20 mL), stirred for 12 hours, and concentrated. The concentrate was treated with aqueous NaOH and extracted with ethyl acetate. The combined extracts were washed with brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with CH2Cl2:CH3OH:NH4OH (100:3:3, v/v) to provide the desired product. MS (DCI/NH3) m/z 445 (M+H)+.
Reaction SMILES: C(OCCO)C.Br[C:8]1[N:13]([C:14]2C=CC(C)=C[CH:15]=2)[C:12](=[O:21])[CH:11]=[C:10]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:9]=1.C(N)C[NH2:30]>>[O:21]=[C:12]1[N:13]2[CH2:14][CH2:15][NH:30][C:8]2=[CH:9][C:10]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:11]1
Reactant: NCCN
Reactant: Cc1ccc(-n2c(Br)cc(-c3ccccc3)cc2=O)cc1
Solvent: CCOCCO
Product: O=c1cc(-c2ccccc2)cc2n1CCN2

Procedure:
In 3 ml. of 2-ethoxyethanol were refluxed 1.05 g. of 6-bromo-1-(4-methylphenyl)-4-phenyl-2-pyridone and 0.4 g. of ethylenediamine for 5 hours. Then, by treating the reaction mixture as in Example 5, 0.35 g. of 5-oxo-7-phenyl-1,2,3,5-tetrahydroimidazo[1,2-a]pyridine was obtained.