Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH:2]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1[NH:13][C:14](=[O:29])[CH2:15][NH:16][CH2:17][C:18]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:22][CH2:21][CH2:20][CH2:19]1)[CH3:3].C(N(CC)CC)C.[C:37](Cl)(=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C(OCC)(=O)C>[CH3:3][CH:2]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:11])[CH3:12])[C:5]=1[NH:13][C:14](=[O:29])[CH2:15][N:16]([CH2:17][C:18]1([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:22][CH2:21][CH2:20][CH2:19]1)[C:37](=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH3:1]
Reactant: O=C(Cl)c1ccccc1
Reactant: CC(C)c1cccc(C(C)C)c1NC(=O)CNCC1(c2ccccc2)CCCC1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CC(C)c1cccc(C(C)C)c1NC(=O)CN(CC1(c2ccccc2)CCCC1)C(=O)c1ccccc1
Reaction time: 96 h

Procedure:
To a solution of 0.48 g of the product of Example 6 and excess triethylamine in ethyl acetate at room temperature was added 0.16 mL benzoyl chloride all at once. The reaction mixture was allowed to sit 4 days at room temperature. The solution was then diluted with ethyl acetate and washed with dilute HCl, NaHCO3, and NaCl solutions, dried over MgSO4, filtered, and concentrated to an oil which was crystallized from diethyl ether. The white solid was collected by filtration. 0.48 g (61%). NMR (CDCl3) δ 1.12 (12H, d), δ 1.6-2.15 (8H, m), δ 2.99 (2H, m), δ 3.27 (2H, bs), δ 3.80 (2H, bs), δ 6.20 (1H, bs) δ 7.04-7.42 (13H, m). IR (KBr) 3269, 2963, 2869, 1696, 1600, 1520, 1461, 1254, 1222, 703 cm-1.
Reaction SMILES: [C:1]([C:4]1[CH:17]=[CH:16][C:7]([CH2:8][CH:9]2[S:13][C:12](=[O:14])[NH:11][C:10]2=[O:15])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH:18](=O)[C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1>C(O)C.O>[CH3:26][O:25][C:22]1[CH:23]=[CH:24][C:19](/[CH:18]=[CH:2]/[C:1]([C:4]2[CH:17]=[CH:16][C:7]([CH2:8][CH:9]3[S:13][C:12](=[O:14])[NH:11][C:10]3=[O:15])=[CH:6][CH:5]=2)=[O:3])=[CH:20][CH:21]=1
Reactant: COc1ccc(C=O)cc1
Reactant: CC(=O)c1ccc(CC2SC(=O)NC2=O)cc1
Solvent: O
Solvent: CCO
Product: COc1ccc(/C=C/C(=O)c2ccc(CC3SC(=O)NC3=O)cc2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Hydrogen chloride was bubbled into an ice-cooled solution of 5-(4-acetylbenzyl)thiazolidine-2,4-dione (1.0 g, 4.0 mmol) and p-anisaldehyde (0.55 g, 4.0 mol) in ethanol (15 ml) for 1 hour. The solution was stirred overnight at room temperature, then diluted with water and the yellow precipitate of present title product collected and dried (1.37 g, 93%); m.p. 177°-180° C.
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[F:1][C:2]1[CH:11]=[C:10]([F:12])[C:9]([N+:13]([O-:15])=[O:14])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]
Reactant: O=[N+]([O-])[O-]
Reactant: COC(=O)c1ccc(F)cc1F
Agent: O=S(=O)(O)O
Agent: [K+]
Product: COC(=O)c1cc([N+](=O)[O-])c(F)cc1F
Temperature: 12.5 °C
Reaction time: 1 h
Yield: 63.4 %

Procedure:
To a solution of methyl 2,4-difluorobenzoate (50.0 g, 290.48 mmol, 1.00 equiv) in sulfuric acid (150 ml) was added a solution of potassium nitrate (35.23 g, 348.81 mmol) in sulfuric acid (30 ml) dropwise in an ice-water bath with stirring for 1 h at 0-25° C. The reaction was then quenched by the addition of ice-water. The solids were collected by filtration to afford methyl 2,4-difluoro-5-nitrobenzoate as a white solid (40.0 g, 63%).
Reaction SMILES: [CH3:1][C:2]([CH3:28])([CH3:27])[CH2:3][N:4]([CH3:26])[C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH:11][C:12]2[CH:13]=[C:14]([CH:19]=[CH:20][C:21]=2[CH3:22])[C:15]([NH:17][CH3:18])=[O:16])[C:6]=1[N+:23]([O-])=O.[H][H]>[Pd]>[NH2:23][C:6]1[C:7]([NH:11][C:12]2[CH:13]=[C:14]([CH:19]=[CH:20][C:21]=2[CH3:22])[C:15]([NH:17][CH3:18])=[O:16])=[N:8][CH:9]=[N:10][C:5]=1[N:4]([CH2:3][C:2]([CH3:28])([CH3:27])[CH3:1])[CH3:26]
Reactant: CNC(=O)c1ccc(C)c(Nc2ncnc(N(C)CC(C)(C)C)c2[N+](=O)[O-])c1
Reactant: [H][H]
Agent: [Pd]
Product: CNC(=O)c1ccc(C)c(Nc2ncnc(N(C)CC(C)(C)C)c2N)c1
Yield: 84.2 %

Procedure:
3-{6-[(2,2-Dimethyl-propyl)-methyl-amino]-5-nitro-pyrimidin-4-ylamino}-4,N-dimethyl-benzamide (0.31 g, 0.8 mmol)) was hydrogenated under 40 psi of hydrogen pressure in the presence of 10% Pd/C for 4 hours in Parr instrument. The catalyst was filtered off through celite and the filtrate was concentrated to afford the product (0.24 g, yield 84%). MS (m/z): 357 (M+H).
Reaction SMILES: [C:1]([C:5]1[C:6]([NH2:14])=[N:7][N:8]2[CH:13]=[CH:12][CH:11]=[N:10][C:9]=12)([CH3:4])([CH3:3])[CH3:2].[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23](O)=[O:24])=[CH:18][CH:17]=1>>[C:1]([C:5]1[C:6]([NH:14][C:23](=[O:24])[CH2:22][C:19]2[CH:20]=[CH:21][C:16]([Cl:15])=[CH:17][CH:18]=2)=[N:7][N:8]2[CH:13]=[CH:12][CH:11]=[N:10][C:9]=12)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1c(N)nn2cccnc12
Reactant: O=C(O)Cc1ccc(Cl)cc1
Product: CC(C)(C)c1c(NC(=O)Cc2ccc(Cl)cc2)nn2cccnc12

Procedure:
The product from Example 105B and 4-chlorophenylacetic acid were processed using the method analogous to that described in Example 137 to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.39 (s, 9H), 3.64 (s, 2H), 7.00 (dd, J=7.1, 4.0 Hz, 1H), 7.37-7.41 (m, 4H), 8.48 (dd, J=4.0, 1.6 Hz, 1H), 8.92 (dd, J=7.1, 1.6 Hz, 1H), 9.98 (s, 1H); MS (DCI) m/z 343 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:24])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[N:22][CH:21]=[CH:20][N:19]=3)[CH:14]=[C:15]([OH:16])[C:7]1=2)[CH3:2].[C:25]([O:29][C:30](=[O:36])[NH:31][CH2:32][CH2:33][CH2:34]Br)([CH3:28])([CH3:27])[CH3:26].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:24])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[N:22][CH:21]=[CH:20][N:19]=3)[CH:14]=[C:15]([O:16][CH2:34][CH2:33][CH2:32][NH:31][C:30]([O:29][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:36])[C:7]1=2)[CH3:2]
Reactant: CC(C)(C)OC(=O)NCCCBr
Reactant: CCOC(=O)CC1OB(O)c2cc(Oc3cnccn3)cc(O)c21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)CC1OB(O)c2cc(Oc3cnccn3)cc(OCCCNC(=O)OC(C)(C)C)c21
Yield: 59.6 %

Procedure:
A solution of [1,4-dihydroxy-6-(pyrazin-2-yloxy)-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester (100 mg, 0.303 mmol) in DMF (10 mL) was treated with (3-bromo-propyl)-carbamic acid tert-butyl ester (100 mg, 0.454 mmol) and potassium carbonate (209 mg, 1.52 mmol) at 50° C. for 5 h. The reaction was concentrated to dryness. The residue was diluted with MeOH/H2O and the mixture was adjusted pH to 3. The solution was purified by preparative HPLC to afford the title compound as a white solid (88 mg, 60%). MS calcd for (C23H30BN3O8+H)+: 488.2. MS found: (M+H)+=488.2.
Reaction SMILES: ClC1C=CSC=1C[C@H]([NH:11][S:12]([C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1)(=[O:14])=[O:13])CC.CC(C)([O-])C.[K+].[F:28][C:29]1[C:34]([N+:35]([O-:37])=[O:36])=[C:33](F)[CH:32]=[CH:31][N:30]=1>O1CCCC1>[F:28][C:29]1[C:34]([N+:35]([O-:37])=[O:36])=[C:33]([NH:11][S:12]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)(=[O:13])=[O:14])[CH:32]=[CH:31][N:30]=1
Reactant: O=[N+]([O-])c1c(F)ccnc1F
Reactant: CC[C@H](Cc1sccc1Cl)NS(=O)(=O)c1ccc(C)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)Nc2ccnc(F)c2[N+](=O)[O-])cc1
Temperature: 4 °C
Reaction time: 0.25 h
Yield: 129.3 %

Procedure:
A first solution containing 43.55 g (0.127 mol) of (R)-N-[1-[(3-chlorothien-2-yl)methyl]propyl]-4-methylbenzenesulfonamide in 71 ml of tetrahydrofuran (THF) is prepared and cooled to 4° C. 138 ml (0.138 mol) of a 1.0 M solution of potassium tert-butoxide in tetrahydrofuran is added dropwise to the first solution. The resulting mixture is stirred for 15 minutes at 20° C. 23.7 g (0.149 mol) of 2,4-difluoro-3-nitropyridine in 10 ml of tetrahydrofuran is then added and the mixture heated at 65° C. for 1 hour. The mixture is cooled to room temperature and partitioned between 150 ml of water and 300 ml of ethyl acetate. The layers are separated. The organic layer is washed twice with 150 ml of water, once with 100 ml of brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is slurried with 100 ml of methanol, then with 150 ml of heptane and then with 60 ml of methanol. The residue is vacuum dried at room temperature with a nitrogen bleed to afford (R)-N-[1-[3-chlorothien-2-yl)methyl]propyl]-N-(2-fluoro-3-nitropyrid-4-yl)-4-methylbenzenesulfonamide (51.1 g, 83.4% yield. 97.6 A% (HPLC)) as a white solid. MS (ion spray)(relative intensity) 484/486 (75), 312 (100).
Reaction SMILES: [F:1][C:2]([F:31])([F:30])[CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][O:22]CC1C=CC=CC=1>[Pd].C(O)(=O)C.C(O)C>[F:1][C:2]([F:30])([F:31])[CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][OH:22]
Reactant: FC(F)(F)COCCOCCOCCOCCOCCOCCOCc1ccccc1
Agent: [Pd]
Solvent: CCO
Solvent: CC(=O)O
Product: OCCOCCOCCOCCOCCOCCOCC(F)(F)F
Yield: 85.8 %

Procedure:
A stirred solution of the product of step (c) (16 g) and 10% palladium on carbon (1 g) in acetic acid:ethanol (1:1, 150 mL) was placed under an atmosphere of hydrogen at 20° C. for 24 hours. The reaction mixture was filtered through a pad of celite and the solvent was removed in vacuo to give the title compound (11 g). Mass spectrum m/z 382 [MNH4+]
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[C:12](=[O:14])[CH3:13].[Cl:15]N1C(=O)CCC1=O>C(O)(=O)C>[Cl:15][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([OH:1])=[C:3]([C:12](=[O:14])[CH3:13])[CH:4]=1
Reactant: CC(=O)c1ccc2ccccc2c1O
Reactant: O=C1CCC(=O)N1Cl
Solvent: CC(=O)O
Product: CC(=O)c1cc(Cl)c2ccccc2c1O
Temperature: 100 °C
Yield: 67.3 %

Procedure:
To a stirred solution of 1-(1-hydroxy-2-naphthyl)ethanone (5.00 g, 26.8 mmol, from Aldrich) in acetic acid (100 mL) was added N-chlorosuccinimide (3.94 g, 29.5 mmol) and the resulting mixture heated at 100° C. for 18 hours. After allowing to be cooled to ambient temperature, the reaction mixture was concentrated in vacuo and then diluted with ethyl acetate. The precipitated solid was collected by filtration to afford the desired product (3.98 g, 67%). LCMS calculated for C12H10ClO2 (M+H)+: m/z=221.0; Found: 221.1.
Reaction SMILES: CC1C=CC(S(O)(=O)=O)=CC=1.O.[NH2:13][C:14]1[C:15]([Cl:29])=[N:16][C:17]([Cl:28])=[CH:18][C:19]=1[NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24].[CH3:30][C@H:31]1[CH2:36][CH2:35][C@H:34]([C:37](=O)[CH3:38])[CH2:33][CH2:32]1>C1(C)C=CC=CC=1>[Cl:29][C:15]1[C:14]([N:13]=[C:37]([C@H:34]2[CH2:35][CH2:36][C@H:31]([CH3:30])[CH2:32][CH2:33]2)[CH3:38])=[C:19]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:24])([CH3:25])[CH3:26])[CH:18]=[C:17]([Cl:28])[N:16]=1
Reactant: CC(C)(C)OC(=O)Nc1cc(Cl)nc(Cl)c1N
Reactant: CC(=O)[C@H]1CC[C@H](C)CC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CC(=Nc1c(NC(=O)OC(C)(C)C)cc(Cl)nc1Cl)[C@H]1CC[C@H](C)CC1

Procedure:
p-TsOH.H2O (3.4 g, 0.018 mol) was added to a mixture of tert-butyl (3-amino-2,6-dichloropyridin-4-yl)carbamate (85 g, 0.306 mol) and 1-(trans-4-methylcyclohexyl)ethanone (64 g, 0.46 mol) in toluene (1.3 L). The mixture was heated to reflux with a Dean-Stark trap for 14 h. TLC (petroleum/ethyl acetate=5:1) showed about ⅔ of tert-butyl (3-amino-2,6-dichloropyridin-4-yl)carbamate was consumed. The solvent was removed under reduced pressure. The residue was purified by column chromatography (petroleum ether) to give crude tert-butyl (2,6-dichloro-3-((1-(trans-4-methylcyclohexyl)ethylidene)amino)pyridin-4-yl)carbamate.
Reaction SMILES: C([O:5][C:6](=[O:23])[CH2:7][N:8]([C:14](=[O:22])[CH:15]([CH3:21])[CH2:16][S:17][C:18](=[O:20])[CH3:19])[CH:9]1[CH2:13][CH2:12][CH2:11][CH2:10]1)(C)(C)C.C[Si](Cl)(C)C.[I-].[Na+].C(#N)C>O>[C:18]([S:17][CH2:16][CH:15]([CH3:21])[C:14]([N:8]([CH:9]1[CH2:10][CH2:11][CH2:12][CH2:13]1)[CH2:7][C:6]([OH:23])=[O:5])=[O:22])(=[O:20])[CH3:19]
Reactant: CC(=O)SCC(C)C(=O)N(CC(=O)OC(C)(C)C)C1CCCC1
Agent: C[Si](C)(C)Cl
Agent: [I-]
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: CC(=O)SCC(C)C(=O)N(CC(=O)O)C1CCCC1
Reaction time: 0.5 h
Yield: 90.8 %

Procedure:
N-(3-Acetylthio-2-methylpropanoyl)-N-cyclopentylglycine t-butyl ester (80.1 g, 0.23 mol), trimethylsilyl chloride (37.9 g, 0.35 mol), and sodium iodide (52.5 g, 0.35 mol) were added to acetonitrile (300 ml), and the reaction mixture was stirred at 45° C.-50° C. for 30 minutes. Water (50 ml) was then added and the mixture was concentrated. The residue was dissolved in saturated aqueous sodium bicarbonate (400 ml) and was washed with ethyl acetate (3×400 ml). The aqueous portion was separated, acidified (conc. hydrochloric acid), and extracted with ethyl acetate. The organic extracts were combined, dried over Na2SO4 and MgSO4, filtered and concentrated yielding the crude desired product as a brown oil (60 g, 90%). When this material was eluted through a high pressure liquid chromatography column with ethyl acetate/hexane/acetic acid (60:40:2) a slightly yellow oil was obtained. This compound was characterized as its DCHA salt which was prepared by adjusting to pH 9 an acetonitrile solution of the compound with DCHA. The salt was obtained as a white crystalline solid, m.p, 172°-174° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][NH2:6].C(=O)([O-])O.[Na+].Cl[C:16]([O:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:17]>O.C(Cl)Cl>[C:19]1([O:18][C:16](=[O:17])[NH:6][CH2:5][C:4]2[CH:7]=[CH:8][CH:9]=[C:2]([OH:1])[CH:3]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: NCc1cccc(O)c1
Reactant: O=C(Cl)Oc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: O=C(NCc1cccc(O)c1)Oc1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3-Hydroxybenzylamine (200 mg, 1.62 mmol) and Sodium hydrogen carbonate (273 mg, 3.25 mmol) suspended in water/DCM (4 ml, 1:1) is treated with phenyl chloroformate (0.204 ml, 1.62 mmol). After stirring at RT overnight, the reaction mixture is diluted with more DCM/water and the organic phase is separated. The organic portion is concentrated in vacuo to afford the titled compound. (MH+ 244)
Reaction SMILES: Cl/[CH:2]=[CH:3]\[C:4]#[C:5][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[CH3:13][Si:14]([C:17]#[CH:18])([CH3:16])[CH3:15].C(N)CC>CCOCC.[Cu](I)I>[Si:6]([C:5]#[C:4]/[CH:3]=[CH:2]\[C:18]#[C:17][Si:14]([CH3:16])([CH3:15])[CH3:13])([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]
Reactant: C#C[Si](C)(C)C
Reactant: CC(C)(C)[Si](C)(C)C#C/C=C\Cl
Agent: I[Cu]I
Solvent: CCOCC
Solvent: CCCN
Product: CC(C)(C)[Si](C)(C)C#C/C=C\C#C[Si](C)(C)C
Temperature: 23 °C
Reaction time: 0.17 h
Yield: 90.7 %

Procedure:
Tetrakistriphenylphosphine (4.75 g, 4.10 mmol, 0.48 equiv) was added to a solution of (Z)-1-chloro-4-(tert-butyldimethylsilyl)-1-buten-3-yne (17.2 g, 85.7 mmol, 1 equiv) in ether (160 mL) at -78° C. The resulting suspension was deoxygenated by alternately evacuating the reaction vessel and flushing with argon (5×), then was warmed to 23° C. In another flask, copper iodide (2.45 g, 12.8 mmol, 0.15 equiv) was added to a solution of trimethylsilylacetylene (17.0 mL, 120 mmol, 1.40 equiv) and n-propyl amine (27.5 mL, 334 mmol, 3.90 equiv) in ether (100 mL) at -78° C. The solution was deoxygenated (as above, 5×), then was stirred in an ice bath for 10 min causing the light green solution to turn reddish brown. The reddish brown solution was cooled to -78° C. and the palladium-containing suspension prepared above was added over 5 min via a wide-bore cannula. The mixture was deoxygenated (as above, 5×), then was stirred in an ice bath for 3 h and at 23° C. for 1 h. The reaction mixture was partitioned between saturated aqueous ammonium chloride solution (200 mL) and hexanes (300 mL). The aqueous layer was separated and extracted further with hexanes (2×300 mL). The combined organic layers were dried over sodium sulfate and were concentrated. The residue was filtered, then was purified by distillation under reduced pressure (bp 70°-80° C., 0.5 mmHg) to provide (Z)-1-(tert-butyl-dimethylsilyl)-6-trimethylsilyl-3-hexen-1,5-diyne as a light brown oil (20.4 g, 90%).
Reaction SMILES: C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:8]2[CH:12]=[C:11]([C:13]3[CH:14]=[CH:15][C:16]4[N:17]([CH:19]=[C:20]([C:22]([NH:24][C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)=[O:23])[N:21]=4)[CH:18]=3)[N:10]=[CH:9]2)C=CC=CC=1.[Cl:43]CCl>Cl.CO>[ClH:43].[NH:8]1[CH:12]=[C:11]([C:13]2[CH:14]=[CH:15][C:16]3[N:17]([CH:19]=[C:20]([C:22]([NH:24][C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)=[O:23])[N:21]=3)[CH:18]=2)[N:10]=[CH:9]1
Reactant: O=C(Nc1ccccc1)c1cn2cc(-c3cn(C(c4ccccc4)(c4ccccc4)c4ccccc4)cn3)ccc2n1
Reactant: ClCCl
Agent: Cl
Solvent: CO
Product: O=C(Nc1ccccc1)c1cn2cc(-c3c[nH]cn3)ccc2n1
Temperature: 70 °C
Reaction time: 60 h

Procedure:
A suspension of 270 mg of 6-(1-triphenylmethyl-1H-imidazol-4-yl)-N-phenyl-imidazo[1,2-a]pyridine-2-carboxamide in 4 mL of 2N hydrochloric acid is heated for 30 minutes at 70° C. and then diluted with 2 mL of methanol, heated for 45 minutes at reflux, diluted again by addition of 2 mL of dichloromethane and heated for a further 2 hours at reflux. The reaction mixture is stirred for 60 hours at room temperature. The precipitate is filtered off by suction, washed with methanol, water and then pentane and dried under reduced pressure to give 96 mg of 6-(1H-imidazol-4-yl)-N-phenylimidazo[1,2-a]pyridine-2-carboxamide hydrochloride (1:1) in the form of a white solid.
Reaction SMILES: [Si:1]([O:8][C@@H:9]([C@H:11]1[C:19](=[O:20])[N:18]2[C@@H:12]1[CH2:13][C:14](=O)[CH2:15][CH:16]=[C:17]2[C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=1)=[O:22])[CH3:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.F[C:45](F)(F)[S:46](OS(C(F)(F)F)(=O)=O)(=O)=O>C(#N)C>[Si:1]([O:8][C@@H:9]([C@H:11]1[C:19](=[O:20])[N:18]2[C@@H:12]1[CH2:13][C:14]([S:46][CH3:45])=[CH:15][CH:16]=[C:17]2[C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=1)=[O:22])[CH3:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=CCC(=O)C[C@H]12
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: CSC1=CC=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)[C@H]([C@@H](C)O[Si](C)(C)C(C)(C)C)[C@H]2C1
Temperature: -40 °C
Reaction time: 0.08 h
Yield: 48.7 %

Procedure:
To a solution of 4-nitrobenzyl (7R,8S)-8-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-5,9-dioxo-1-azabicyclo[5.2.0]non-2-ene-2-carboxylate (1.5 g, 3.07 mmol) in acetonitrile (15 ml) was added at 0° C. N,N-diisopropylethylamine (1.1 ml, 6.45 mmol). The reaction mixture was cooled at -40° C. and trifluoromethanesulfonic anhydride (0.57 ml; 3.38 mmol) was added. After 5 minutes, further N,N-diisopropylethylamine (1.1 ml, 6.45 mmol) was added to the reaction mixture. Methylmercaptan was then bubbled through the solution at -40° C. during a few seconds. The mixture was allowed to warm to ambient temperature over 1.5 hours. The solvent was evaporated and the residue purified by chromatography on silica gel eluting with ethyl acetate/dichloromethane 3:97 to give 4-nitrobenzyl (7R,8S)-8-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]5-methylthio-9-oxo-1-azabicyclo[5.2.0]non-2,4-diene-2-carboxylate (776 mg, 47%).
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O)=[O:2].Br[C:13]1[CH:14]=[N:15][CH:16]=[N:17][CH:18]=1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(#N)C>[N:15]1[CH:14]=[C:13]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[CH:1]=[O:2])[CH:18]=[N:17][CH:16]=1
Reactant: O=Cc1ccccc1B(O)O
Reactant: Brc1cncnc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: O=Cc1ccccc1-c1cncnc1
Temperature: 150 °C
Yield: 59.7 %

Procedure:
A microwave vial (20 ml) was charged with 2-formylphenylboronic acid (290 mg, 2.0 mmol), 5-bromo-pyrimidine (316 mg, 2.0 mmol) and 8 ml of acetonitrile. To this mixture was added 4 ml of aqueous sodium carbonate (1M), followed by 100 mg of dichlorobis-(triphenylphosphine)-palladium(II). The reaction vessel was sealed and heated at 150° C. for 5 minutes with microwave irradiation. After cooling, the reaction mixture was extracted with ethylacetate. The organic layer was evaporated to provide a crude material, which was purified by ISCO to give 220 mg of 2-pyrimidin-5-yl-benzaldehyde.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][NH:4][C:3]2[CH:7]=[N:8][CH:9]=[CH:10][C:2]1=2.[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1.C(N(CC)CC)C.Cl>ClCCl>[CH3:11][O:12][C:13]1[CH:14]=[CH:15][C:16]([S:19]([N:4]2[CH2:5][CH2:6][O:1][C:2]3[CH:10]=[CH:9][N:8]=[CH:7][C:3]2=3)(=[O:21])=[O:20])=[CH:17][CH:18]=1
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Reactant: c1cc2c(cn1)NCCO2
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(S(=O)(=O)N2CCOc3ccncc32)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 84 %

Procedure:
In a 25 ml flask, 3,4-dihydro-2H-pyrido[4,3-b][1,4]oxazine (370 mg, 2.72 mmol) and 4-methoxy-benzenesulfonyl chloride (618 mg, 2.99 mmol) were dissolved in dichloromethane (10 ml). Triethylamine (0.45 ml, 3.23 mmol) was added thereto and then stirred at room temperature for 2 hours. After neutralizing with 1N hydrochloric acid solution, the mixture was extracted with dichloromethane, and the combined organic layer was dried over anhydrous sodium sulfate (Na2SO4), filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica eluting with a solvent of dichloromethane. The fractions containing the product were collected and evaporated to obtain pale-green solid (700 mg, 84.1%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][C:13]#[N:14])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C1C(=O)N([Br:22])C(=O)C1.O>CN(C=O)C>[Br:22][C:6]1[CH:7]=[C:8]([O:9][CH3:10])[C:3]([O:2][CH3:1])=[CH:4][C:5]=1[CH2:11][CH2:12][C:13]#[N:14]
Reactant: COc1ccc(CCC#N)cc1OC
Reactant: O=C1CCC(=O)N1Br
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc(Br)c(CCC#N)cc1OC
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A solution of 1 g (5.3 mmoles) of 3-(3,4-dimethoxyphenyl)propanenitrile in 42 mL of DMF is cooled to 0° C. To the resulting solution there is added, little by little, 0.93 g of NBS (5.2 mmoles, 1 eq.). After stirring for 30 minutes at 0° C., the reaction mixture is brought back to ambient temperature and stirred for two hours. It is then hydrolysed using 170 mL of water and extracted twice with 130 mL of ethyl acetate. The organic phases are collected and then washed, first with saturated aqueous Na2S2O5 solution and then with water. After evaporating off the solvent under reduced pressure, 1.29 g of a colourless oil which crystallises into a white solid are obtained.