Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:39][C:40](=[O:49])[O:41][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[C:8]([C:12]([NH:14][C:15]3[CH:16]=[N:17][CH:18]=[CH:19][C:20]=3[N:21]3[CH2:26][C@H:25]([C:27]([F:30])([F:29])[F:28])[CH2:24][C@H:23]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:22]3)=[O:13])=[N:9]2)=[CH:4][CH:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1.[CH3:64][N:65]1[CH2:70][CH:69]=[C:68](B2OC(C)(C)C(C)(C)O2)[CH2:67][CH2:66]1>C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.NC1C=CC=CC=1C1C=CC=CC=1[Pd]Cl.O>[C:35]([O:34][C:32]([NH:31][C@H:23]1[CH2:24][C@@H:25]([C:27]([F:29])([F:28])[F:30])[CH2:26][N:21]([C:20]2[CH:19]=[CH:18][N:17]=[CH:16][C:15]=2[NH:14][C:12]([C:8]2[C:7]([NH:39][C:40](=[O:49])[O:41][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[CH:6][C:5]3[C:10](=[CH:11][C:2]([C:68]4[CH2:69][CH2:70][N:65]([CH3:64])[CH2:66][CH:67]=4)=[CH:3][CH:4]=3)[N:9]=2)=[O:13])[CH2:22]1)=[O:33])([CH3:38])([CH3:37])[CH3:36]
Reactant: CC(C)(C)OC(=O)N[C@H]1C[C@@H](C(F)(F)F)CN(c2ccncc2NC(=O)c2nc3cc(Br)ccc3cc2NC(=O)OCc2ccccc2)C1
Reactant: CN1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Agent: Nc1ccccc1-c1ccccc1[Pd]Cl
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: O=P([O-])([O-])[O-]
Solvent: C1COCCO1
Solvent: O
Product: CN1CC=C(c2ccc3cc(NC(=O)OCc4ccccc4)c(C(=O)Nc4cnccc4N4C[C@@H](NC(=O)OC(C)(C)C)C[C@@H](C(F)(F)F)C4)nc3c2)CC1
Temperature: 90 °C

Procedure:
A pressure vial was charged with benzyl {7-bromo-2-[({4-[(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-(trifluoromethyl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]quinolin-3-yl}carbamate (0.032 g, 0.043 mmol), K3PO4 (0.0181 g, 0.0852 mmol), 1,4-dioxane (0.55 mL), water (0.092 mL) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (0.014 g, 0.063 mmol). The mixture was purged with nitrogen for 10 min. Dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (0.0022 g, 0.0028 mmol) was added. The mixture was sealed with screw cap, then heated at 90° C. for 1.5 h. The mixture was quenched with water, then extracted with EtOAc. The combined organic layers were dried and concentrated under reduced pressure. The residue was purified by flash chromatography on 20 g silica gel, eluting with 0-30% MeOH in EtOAc, to yield the sub-title compound. LCMS calc. for C40H45F3N7O5 [M+H]+: m/z=760.3. found: 760.4.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([OH:16])[C:5]([C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][N:10]=2)=[N:6][C:7]=1[CH3:8].[CH2:17]([O:24][C:25]1[CH:34]=[C:33]2[C:28]([C:29](Cl)=[CH:30][CH:31]=[N:32]2)=[CH:27][C:26]=1[O:36][CH3:37])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C1C=CN=CC=1.CS(C)=O>[CH2:17]([O:24][C:25]1[CH:34]=[C:33]2[C:28]([C:29]([O:16][C:4]3[C:5]([C:9]4[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][N:10]=4)=[N:6][C:7]([CH3:8])=[C:2]([CH3:1])[CH:3]=3)=[CH:30][CH:31]=[N:32]2)=[CH:27][C:26]=1[O:36][CH3:37])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: Cc1ccc(-c2nc(C)c(C)cc2O)nc1
Reactant: COc1cc2c(Cl)ccnc2cc1OCc1ccccc1
Agent: CN(C)c1ccncc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CS(C)=O
Solvent: O
Product: COc1cc2c(Oc3cc(C)c(C)nc3-c3ccc(C)cn3)ccnc2cc1OCc1ccccc1
Temperature: 130 °C
Reaction time: 8 h
Yield: 75.4 %

Procedure:
5,6,5′-Trimethyl-[2,2′]bipyridin-3-ol (300 mg), 7-benzyloxy-4-chloro-6-methoxyquinoline (1.26 g), 4-dimethylaminopyridine (513 mg), and cesium carbonate (1.37 g) were suspended in dimethyl sulfoxide (6 ml), and the suspension was stirred at 130° C. overnight. The reaction solution was cooled to room temperature, water was then added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was then washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography using chloroform-methanol to give the title compound (504 mg, yield 75%).
Reaction SMILES: [CH3:1][C:2]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:12]=[CH:13][C:14]([N+:25]([O-])=O)=[C:15]([CH:17]=[C:18]3[NH:22][C:21](=[O:23])[NH:20][C:19]3=O)[CH:16]=2)OCC[O:3]1.CO.II>CN(C)C=O.[Pd].S([O-])([O-])(=O)=S.[Na+].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>[O:3]=[C:2]([CH3:1])[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]2[N:25]=[C:19]3[NH:20][C:21](=[O:23])[NH:22][C:18]3=[CH:17][C:15]=2[CH:16]=1
Reactant: CC1(CCCOc2ccc([N+](=O)[O-])c(C=C3NC(=O)NC3=O)c2)OCCO1
Agent: [Pd]
Agent: II
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Solvent: CO
Product: CC(=O)CCCOc1ccc2nc3[nH]c(=O)[nH]c3cc2c1
Reaction time: 18 h
Yield: 84.2 %

Procedure:
A solution of 5-[[5-[3-(2-methyl-1,3-dioxolan-2-yl)propoxy]-2-nitrophenyl]methylene]-2,4-imidazolidinedione (34.7 g, 92 mmol) in dimethylformamide (500 mL) was hydrogenated over 10% palladium on charcoal (3.5 g) at 200 p.s.i. in a low pressure hydrogenator. After 18 hours, the mixture was filtered through kieselguhr and concentrated in vacuo to afford a beige solid which was suspended in refluxing methanol (500 mL). Iodine (23.3 g, 92 mmol) was added portionwise and the mixture heated at reflux for a further 30 minutes before being cooled and diluted with 10% sodium thiosulfate solution (230 mL) and 10% sodium carbonate solution (75 mL). The mixture was concentrated to a volume of approximately 400 mL, the precipitate filtered off, washed with water and dried in vacuo of 70° C. to afford 1,3-dihydro-7-(4-oxopentoxy)-2H-imidazo[4,5-b]quinolin-2-one (22.1 g, 84%). An analytical sample was prepared by crystallizing a 10 g portion from aqueous dimethylformamide to give 7.8 g of pure material which had m.p. 294°-296° C. (dec.).
Reaction SMILES: [CH:1]([NH:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)C(C)C)C.[C:33](Cl)(=[O:37])/[CH:34]=[CH:35]/[CH3:36].CS(C)=O>C1C=CC=CC=1>[C:33]([N:14]([CH:1]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH2:15][CH2:16][CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])(=[O:37])/[CH:34]=[CH:35]/[CH3:36]
Reactant: C/C=C/C(=O)Cl
Reactant: CCOC(=O)CCCCNC(c1ccccc1)c1ccccc1
Solvent: c1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Product: C/C=C/C(=O)N(CCCCC(=O)OCC)C(c1ccccc1)c1ccccc1
Yield: 99.6 %

Procedure:
Analogously to Example 19, 7 g of ethyl 5-benzhydrylaminovalerate and 3.2 g of ethyldiisopropylamine are dissolved in 100 ml of benzene and reacted with 2.6 g of crotonyl chloride. As reaction product one obtains 8.5 g of ethyl N-crotonoyl-5-benzhydrylaminovalerate as a viscous non-distillable oil. The saponification of this ester yields 6 g (76%) of N-crotonoyl-5-benzhydrylaminovaleric acid (M.P. 88° to 89°).
Reaction SMILES: [C:1]([O:5][C:6](=[O:36])[NH:7][CH2:8][C:9]1[N:10]([CH2:32][CH:33]([CH3:35])[CH3:34])[C:11](=[O:31])[C:12]2[C:17]([C:18]=1[O:19][CH2:20][CH2:21][CH2:22][CH3:23])=[CH:16][C:15](/[CH:24]=[CH:25]/[C:26]1[N:27]=[CH:28][S:29][CH:30]=1)=[CH:14][CH:13]=2)([CH3:4])([CH3:3])[CH3:2]>O1CCCC1.[C].[Pd]>[C:1]([O:5][C:6](=[O:36])[NH:7][CH2:8][C:9]1[N:10]([CH2:32][CH:33]([CH3:35])[CH3:34])[C:11](=[O:31])[C:12]2[C:17]([C:18]=1[O:19][CH2:20][CH2:21][CH2:22][CH3:23])=[CH:16][C:15]([CH2:24][CH2:25][C:26]1[N:27]=[CH:28][S:29][CH:30]=1)=[CH:14][CH:13]=2)([CH3:4])([CH3:2])[CH3:3]
Reactant: CCCCOc1c(CNC(=O)OC(C)(C)C)n(CC(C)C)c(=O)c2ccc(/C=C/c3cscn3)cc12
Agent: [Pd]
Solvent: C1CCOC1
Product: CCCCOc1c(CNC(=O)OC(C)(C)C)n(CC(C)C)c(=O)c2ccc(CCc3cscn3)cc12
Temperature: 25 °C
Reaction time: 2 h
Yield: 97.3 %

Procedure:
A suspension of tert-butyl{4-butoxy-2-isobutyl-1-oxo-6-[(E)-2-(1,3-thiazol-4-yl)ethenyl]-1,2-dihydro-3-isoquinolinyl}methylcarbamate (0.21 g, 0.4 mmol) and 5% palladium carbon (0.2 g) in tetrahydrofuran (10 ml) was stirred under a hydrogen atmosphere at room temperature for 2 h. The catalyst was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give tert-butyl{4-butoxy-2-isobutyl-1-oxo-6-[2-(1,3-thiazol-4-yl)ethyl]-1,2-dihydro-3-isoquinolinyl}methylcarbamate (0.20 g, 95.2%) as crystals.
Reaction SMILES: [CH:1]1([N:7]2[C:11]3[CH:12]=[C:13]([O:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([O:24]C)=O)[CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH3:33][NH:34][CH3:35]>>[CH:1]1([N:7]2[C:11]3[CH:12]=[C:13]([O:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([N:34]([CH3:35])[CH3:33])=[O:24])[CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COC(=O)CCCCCOc1ccc2nc(-c3ccccc3)n(C3CCCCC3)c2c1
Reactant: CNC
Agent: Cl
Product: CN(C)C(=O)CCCCCOc1ccc2nc(-c3ccccc3)n(C3CCCCC3)c2c1

Procedure:
1-Cyclohexyl-6-[(5-(methoxycarbonyl)pentyl)oxy]-2-phenyl-benzimidazole is reacted according to general operating instructions 7 with dimethylamine hydrochloride. 1-Cyclo-hexyl-6-[(5-((N,N-dimethylamino)carbonyl)pentyl)oxy]-2-phenyl-benzimidazole is obtained as a solid.
Reaction SMILES: [CH:1]1([CH2:7][C:8]([OH:10])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].[CH2:13]([C@H:15]1[CH2:20][C@H:19]2[C@H:21]3[C@H:30]([CH2:31][CH2:32][C@:17]2([CH3:18])[C@H:16]1[O:34][C:35](=[O:38])[CH2:36]Br)[C@@H:29]1[C:24](=[CH:25][C:26](=[O:33])[CH2:27][CH2:28]1)[CH2:23][CH2:22]3)[CH3:14].CN(C=O)C>CC(C)=O.C(OCC)(=O)C.O>[CH2:13]([C@H:15]1[CH2:20][C@H:19]2[C@H:21]3[C@H:30]([CH2:31][CH2:32][C@:17]2([CH3:18])[C@H:16]1[O:34][C:35](=[O:38])[CH2:36][O:9][C:8](=[O:10])[CH2:7][CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[C@@H:29]1[C:24](=[CH:25][C:26](=[O:33])[CH2:27][CH2:28]1)[CH2:23][CH2:22]3)[CH3:14]
Reactant: CC[C@H]1C[C@H]2[C@@H]3CCC4=CC(=O)CC[C@@H]4[C@H]3CC[C@]2(C)[C@H]1OC(=O)CBr
Reactant: O=C(O)CC1CCCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CC(C)=O
Product: CC[C@H]1C[C@H]2[C@@H]3CCC4=CC(=O)CC[C@@H]4[C@H]3CC[C@]2(C)[C@H]1OC(=O)COC(=O)CC1CCCCC1
Yield: 96.1 %

Procedure:
In 20 ml of acetone is dissolved 0.65 g of cyclohexylacetic acid, and 2.5 ml of 2N-NaOH, 1.0 g of 16β-ethyl-17β-bromoacetoxy-4-estren-3-one and 20 ml of DMF are serially added to the above solution. The mixture is refluxed for 5 hours. After cooling, the reaction mixture is poured into a mixture of 100 ml of water and 150 ml of ethyl acetate. The ethyl acetate layer is separated and the aqueous layer is extracted with 100 ml of ethyl acetate. These organic layers are combined, washed with water and saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent is then distilled off under reduced pressure and the residue is subjected to silica gel column chromatography. Following passage of 200 ml of n-hexane-diisopropyl ether (6:4), elution is carried out with 600 ml of a 1:1 mixture of the same solvents. The eluate is evaporated under reduced pressure to remove the solvent, giving 1.1 g of the above-identified compound as a light-yellow viscous oil.
Reaction SMILES: [C:1]([C:3]1[C:8]2[N:9]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:18]C)[C:13]=3[CH2:20][CH3:21])[S:11][C:7]=2[CH:6]=[C:5]([O:22]C)[CH:4]=1)#[N:2].B(Br)(Br)Br>>[C:1]([C:3]1[C:8]2[N:9]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([OH:18])[C:13]=3[CH2:20][CH3:21])[S:11][C:7]=2[CH:6]=[C:5]([OH:22])[CH:4]=1)#[N:2]
Reactant: CCc1c(OC)cccc1-c1nc2c(C#N)cc(OC)cc2s1
Agent: BrB(Br)Br
Product: CCc1c(O)cccc1-c1nc2c(C#N)cc(O)cc2s1
Yield: 32.7 %

Procedure:
4-Cyano-6-methoxy-2-(2-ethyl-3-methoxy-phenyl)-benzothiazole (0.1 g, 0.31 mmol) was treated with boron tribromide under standard condition to give the title compound (30 mg, 33% yield) as a yellow solid. Mass spec:MH+=297.
Reaction SMILES: [CH2:1]([OH:5])[C@@H:2]([OH:4])[CH3:3].[Si:6](Cl)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].N1C=CN=C1.CN(C)C=O>C(OCC)(=O)C>[Si:6]([O:5][CH2:1][C@@H:2]([OH:4])[CH3:3])([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: C[C@H](O)CO
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: C[C@H](O)CO[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 12 h
Yield: 105.1 %

Procedure:
A solution of (S)-propane-1,2-diol (1.9 mL, 26 mmol), tert-butyldimethylsilyl chloride (4.87 g, 32 mmol), and imidazole (4.5 g, 66 mmol) in anhydrous dimethylformamide (6.6 mL, 26 mmol) was allowed to stir at ambient temperature for 12 hours. The reaction mixture was poured into ethyl acetate (50 mL) and washed sequentially with saturated aqueous sodium bicarbonate (30 mL) and water (30 mL). The organic extract was dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (5.2 g, 104%) which was used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][NH:20][CH2:19]4)[C:14]([F:24])=[CH:13][N:12]=3)=[CH:9][N:8]([S:25]([C:28]3[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=3)(=[O:27])=[O:26])[C:5]2=[N:6][CH:7]=1.[C:35]([O:39][C:40](=[O:43])CBr)([CH3:38])([CH3:37])[CH3:36].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.[Na+].[Cl-]>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][N:20]([C:40]([O:39][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:43])[CH2:19]4)[C:14]([F:24])=[CH:13][N:12]=3)=[CH:9][N:8]([S:25]([C:28]3[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=3)(=[O:27])=[O:26])[C:5]2=[N:6][CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3ncc(F)c(N[C@H]4CCCNC4)n3)c3cc(Cl)cnc32)cc1
Reactant: CC(C)(C)OC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1ccc(S(=O)(=O)n2cc(-c3ncc(F)c(N[C@H]4CCCN(C(=O)OC(C)(C)C)C4)n3)c3cc(Cl)cnc32)cc1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
To a solution of 2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[5,4-b]pyridin-3-yl]-5-fluoro-N-[(3S)-3-piperidyl]pyrimidin-4-amine, 1c, (0.25 g, 0.50 mmol) in DMF was added tert-butylbromoacetate (0.08 mL, 0.55 mmol) and Na2CO3 (0.11 g, 0.99 mmol). The reaction mixture was stirred at room temperature for 6 h. The resulting thick white precipitate was diluted with aqueous saturated NaCl solution and washed with water. The white solid was dissolved in CH2Cl2 and the solution was dried (MgSO4), filtered and concentrated in vacuo. The crude was purified via silica gel chromatography (0%-5% MeOH/CH2Cl2) to afford the desired product, 2a, as a white solid.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:32])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15]CC2C=CC=CC=2)=[CH:11][C:10]=1[CH2:23][NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])([CH3:7])[CH3:6])[CH3:2]>C1COCC1>[CH2:1]([O:3][C:4](=[O:32])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH2:23][NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])([CH3:7])[CH3:6])[CH3:2]
Reactant: CCOC(=O)C(C)(C)Oc1ccc(OCc2ccccc2)cc1CNC(=O)OC(C)(C)C
Solvent: C1CCOC1
Product: CCOC(=O)C(C)(C)Oc1ccc(O)cc1CNC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 18 h
Yield: 68.4 %

Procedure:
A solution of 2-[4-benzyloxy-2-(tert-butoxycarbonylamino-methyl)-phenoxy]-2-methyl-propionic acid ethyl ester (0.38 g, 0.86 mmol) in THF (15 mL) was treated with 5% Pd-on-carbon (47 mg) and shaken under a hydrogen atmosphere (60 psi) at ambient temperature for 18 h. The mixture was filtered through Celite and concentrated. The crude product was purified by radial chromatography (hexanes/EtOAc 2.5/1) to give the title compound (208 mg g, 69%).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].C(OC([N:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21]OS(C)(=O)=O)[CH2:15][CH2:14]1)=O)C.C(=O)([O-])O.[Na+]>C(OCC)(=O)C.CN(C)C=O>[N:1]1([CH2:21][CH2:20][CH2:19][N:16]2[CH2:17][CH2:18][NH:13][CH2:14][CH2:15]2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: CCOC(=O)N1CCN(CCCOS(C)(=O)=O)CC1
Reactant: c1c[nH]cn1
Agent: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: c1cn(CCCN2CCNCC2)cn1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 71.6 %

Procedure:
To a solution of imidazole 0.68 g and N,N-dimethylformamide 20 ml was added 60% sodium hydride 0.60 g under ice-cooling, followed by stirring at room temperature for 5 minutes. To the resultant mixture was added 1-ethoxycarbonyl-4-(3-mesyloxypropyl)piperazine 3.68 g and the mixture was stirred at room temperature overnight. To the reaction mixture were added saturated solution of sodium hydrogen carbonate 50 ml and ethyl acetate 200 ml and the organic layer was taken using a separating funnel, dried over anhydrous magnesium sulfate and the solvent distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (eluent: 10% methanol-ethyl acetate), and dissolved in ethanol 25 ml. To the solution was added 10% sodium hydroxide 25 ml and the mixture refluxed overnight. After cooling, ethyl acetate 100 ml was added to the solution, the organic layer was separated, and the aqueous layer extracted with ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 1.39 g of 1-[3-(1-imidazolyl)propyl]piperazine.
Reaction SMILES: Cl[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1.[OH:11][CH:12]1[CH2:16][CH2:15][O:14][CH2:13]1.[OH-].[K+].Cl>CS(C)=O>[O:14]1[CH2:15][CH2:16][CH:12]([O:11][C:2]2[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=2)[CH2:13]1
Reactant: O=C(O)c1ccc(Cl)nc1
Reactant: OC1CCOC1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Product: O=C(O)c1ccc(OC2CCOC2)nc1
Temperature: 25 °C

Procedure:
To 6-chloro-nicotinic acid (415 mg, 2.59 mmol), was added 3-hydroxytetrahydrofuran (468 mg, 5.16 mmol), potassium hydroxide (579 mg, 10.3 mmol) and DMSO (5 mL). The mixture was heated at 120 C for 24 h. Further potassium hydroxide (579 mg) and 3-hydroxytetrahydrofuran (468 mg) was added and the mixture heated at 120 C for 24 h. The reaction was allowed to cool to room temperature, acidified to pH=1-2 with a 2M aq. solution of HCl (13 mL) and extracted into EtOAc (3×5 mL). The combined extracts were washed with water (5×20 mL), saturated brine (2×20 mL) and dried over anhydrous sodium sulfate. Evaporation of the solvent afforded the title compound as an orange solid which was dried under high vacuum to remove traces of solvent (209 mg, 39%). Method B HPLC-MS: MH+ requires m/z=210. Found: m/z=210, Rt=1.32 min (100%).
Reaction SMILES: C[O:2][C:3](=O)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].O.[NH2:15][NH2:16]>C(O)C>[C:3]([NH:15][NH2:16])(=[O:2])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: NN
Reactant: CCCCCCCCCC(=O)OC
Solvent: O
Solvent: CCO
Product: CCCCCCCCCC(=O)NN
Temperature: 25 °C
Reaction time: 8 h
Yield: 94 %

Procedure:
17.5 g of decanoic acid methyl ester is dissolved in 1 l of absolute ethanol and mixed with 350 ml of hydrazine hydrate. It is refluxed for 3 hours and then stirred overnight at room temperature. The solution is concentrated by evaporation to about 300 ml and allowed to stand until the product is crystallized out. After it is filtered off and dried, 16.6 g (=94% of theory) of decanoic acid hydrazide is obtained.
Reaction SMILES: CO[C:3]([C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:14]=1[N:13]=[CH:12][N:11]=[C:10]2[NH:15][C@@H:16]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:17][N:18]=[N+:19]=[N-:20])=[O:4].[OH-].[NH4+:28]>C(O)(C)C.C1COCC1.O>[N:18]([CH2:17][C@@H:16]([NH:15][C:10]1[C:9]2[C:14](=[C:5]([C:3]([NH2:28])=[O:4])[CH:6]=[CH:7][CH:8]=2)[N:13]=[CH:12][N:11]=1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[N+:19]=[N-:20]
Reactant: COC(=O)c1cccc2c(N[C@H](CN=[N+]=[N-])c3ccccc3)ncnc12
Reactant: [NH4+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CC(C)O
Product: [N-]=[N+]=NC[C@@H](Nc1ncnc2c(C(N)=O)cccc12)c1ccccc1
Reaction time: 24 h

Procedure:
To a solution of 4-((S)-2-Azido-1-phenyl-ethylamino)-quinazoline-8-carboxylic acid methyl ester (0.5 g, 1.48 mmol) in isopropanol (0.5 mL) and THF (0.5 mL) was added ammonium hydroxide (28-30% solution, 7.5 mL). The reaction was stirred for 24 hours then diluted with water. Solid formed collected by filtration and dried under vacuum (0.28 g, 57%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.72-3.81 (m, 1 H) 3.91 (dd, J=12.57, 9.98 Hz, 1 H) 5.73-5.85 (m, 1 H) 7.25-7.32 (m, 1 H) 7.36 (t, J=7.47 Hz, 2 H) 7.52 (d, J=7.27 Hz, 2 H) 7.71 (t, J=7.86 Hz, 1 H) 7.77-7.88 (m, 1 H) 8.60 (dd, J=7.47, 1.32 Hz, 1 H) 8.58 (s, 1 H) 8.66 (dd, J=8.32, 1.39 Hz, 1 H) 8.95 (d, J=8.30 Hz, 1 H) 10.26 (br. s., 1 H).
Reaction SMILES: [Si]([O:8][CH:9]1[C:17]2[C:12](=[C:13]([C:18]3[S:19][C:20]([C:23]4[CH:24]=[CH:25][C:26]([O:31][CH:32]([CH3:34])[CH3:33])=[C:27]([CH:30]=4)[C:28]#[N:29])=[CH:21][N:22]=3)[CH:14]=[CH:15][CH:16]=2)[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.Cl>O1CCOCC1>[OH:8][CH:9]1[C:17]2[C:12](=[C:13]([C:18]3[S:19][C:20]([C:23]4[CH:24]=[CH:25][C:26]([O:31][CH:32]([CH3:34])[CH3:33])=[C:27]([CH:30]=4)[C:28]#[N:29])=[CH:21][N:22]=3)[CH:14]=[CH:15][CH:16]=2)[CH2:11][CH2:10]1
Reactant: CC(C)Oc1ccc(-c2cnc(-c3cccc4c3CCC4O[Si](C)(C)C(C)(C)C)s2)cc1C#N
Agent: Cl
Solvent: C1COCCO1
Product: CC(C)Oc1ccc(-c2cnc(-c3cccc4c3CCC4O)s2)cc1C#N
Temperature: 25 °C
Reaction time: 2 h
Yield: 55.9 %

Procedure:
Prepared using General Procedure 3. To crude 5-(2-(1-(tert-butyldimethylsilyloxy)-2,3-dihydro-1H-inden-4-yl)thiazol-5-yl)-2-isopropoxybenzonitrile (0.043 g, 0.095 mmol) was added 4N HCl in dioxane (1.0 mL). The reaction mixture was stirred at room temperature for 2 h. The solvent was concentrated under a stream of N2 and the mixture dissolved in MeOH (1.0 mL). The crude product was purified by preparative HPLC to yield 0.02 g (43%) of 5-(2-(1-hydroxy-2,3-dihydro-1H-inden-4-yl)thiazol-5-yl)-2-isopropoxybenzonitrile 222. LCMS-ESI (m/z): calcd for: C22H20N2O2S: 376.5; found 377.1 [M+H] +, tR=3.31 min.