Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[C:6]([CH3:13])([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[O:5][C:4](=[O:14])[CH:3]=1.[CH:15](=O)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[F:23][C:24]1[CH:32]=[C:31]2[C:27]([C:28]([CH2:33][CH2:34][NH:35][C:36](=[O:38])[CH3:37])=[CH:29][NH:30]2)=[CH:26][CH:25]=1>>[F:23][C:24]1[CH:32]=[C:31]2[C:27]([C:28]([CH2:33][CH2:34][NH:35][C:36](=[O:38])[CH3:37])=[C:29]([CH:15]([C:3]3[C:4](=[O:14])[O:5][C:6]([CH3:13])([C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)[C:2]=3[OH:1])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[NH:30]2)=[CH:26][CH:25]=1
Reactant: O=Cc1ccccc1
Reactant: CC(=O)NCCc1c[nH]c2cc(F)ccc12
Reactant: CC1(c2ccccc2)OC(=O)C=C1O
Product: CC(=O)NCCc1c(C(C2=C(O)C(C)(c3ccccc3)OC2=O)c2ccccc2)[nH]c2cc(F)ccc12

Procedure:
Using general procedure C, 4-hydroxy-5-methyl-5-phenyl-5H-furan-2-one (Example A2) was reacted with benzaldehyde and N-[2-(6-fluoro-1H-indol-3-yl)-ethyl]-acetamide (Example 18.1.) to give the title compound as pale brown solid. MS: 499.5 ([M+H]+).
Reaction SMILES: C(OC([N:6]1[CH2:15][CH2:14][C:13]2[C:12]3[N:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:17]=[CH:18][C:11]=3[S:10][C:9]=2[CH2:8][CH2:7]1)=O)C.[OH-].[K+]>CCO.O>[C:19]1([N:16]2[C:12]3[C:13]4[CH2:14][CH2:15][NH:6][CH2:7][CH2:8][C:9]=4[S:10][C:11]=3[CH:18]=[CH:17]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: CCOC(=O)N1CCc2sc3ccn(-c4ccccc4)c3c2CC1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: c1ccc(-n2ccc3sc4c(c32)CCNCC4)cc1
Temperature: 100 °C

Procedure:
To a stirred solution of the product from step (a) (0.066 g, 0.19 mmol) in EtOH (2 ml) was added 40% aqueous KOH (2 ml). The reaction mixture was heated to 100° C. until LCMS that the reaction was complete (usually 16-32 hours). The reaction mixture was cooled to RT, diluted with water (30 ml), and extracted with DCM (3×). The combined DCM extracts were dried (MgSO4), filtered, and solvent evaporated in vacuo to give the crude product. Purification by preparative HPLC gave the title compound as a tan solid. 1HNMR (CD3)2CO™ 7.52-7.50 (m, 2H), 7.44-7.41 (m, 3H), 6.97 (d, J=3 Hz, 1H), 6.42 (d, J=3 Hz, 1H), 2.92-2.89 (m, 4H), 2.74-2.71 (m, 2H), 2.52-2.49 (m, 2H), 2.06-2.04 (m, 1H); MS: ESI (positive): 269 (M+H).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[C:5]([O:10][CH2:11][C@H:12]3[CH2:16][CH2:15][CH2:14][N:13]3C(OC(C)(C)C)=O)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.CC(C)([O-])C.[K+].[C:30]1([S:36]([Cl:39])(=[O:38])=[O:37])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>C1COCC1>[ClH:39].[C:30]1([S:36]([N:1]2[C:9]3[C:4](=[C:5]([O:10][CH2:11][C@H:12]4[CH2:16][CH2:15][CH2:14][NH:13]4)[CH:6]=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)(=[O:38])=[O:37])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1COc1cccc2[nH]ccc12
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: Cl
Product: O=S(=O)(c1ccccc1)n1ccc2c(OC[C@H]3CCCN3)cccc21
Temperature: 25 °C
Reaction time: 0.05 h

Procedure:
A solution of t-butyl (2R)-2-[(1H-indol-4-yloxy)methyl]pyrrolidine-1-carboxylate (0.316 g, 1.0 mmol) in THF is treated with potassium t-butoxide (1.5 mL, 1.5 mmol, 1M in THF) at room temperature, stirred for 3 min, treated with benzenesulfonyl chloride (0.264 g, 1.5 mmol), stirred for 6 h under nitrogen at room temperature, quenched with IN aqueous HCl and water and diluted with EtOAc. The organic phase is separated, washed sequentially with water and brine, dried over MgSO4 and concentrated in vacuo. The resultant residue is treated with HCl (1.5 mL, 1N in Et2O), heated at reflux temperature for 3 h, cooled to room temperature and filtered. The filtercake is air-dried to afford the title compound as an off-white solid, 0.24 g, mp 204-206° C., identified by NMR and mass spectral analyses.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:9]=[C:8]([CH3:10])[NH:7][C:6](=[O:11])[C:5]=1[CH2:12][NH:13][C:14]([C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]([CH:25]([CH:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)[CH3:26])[C:17]=1[CH3:33])=[O:15].CN(C=O)C.C1COCC1.C(N(C(C)C)C(C)C)C.[C:53](Cl)(=[O:58])[O:54][CH:55]([CH3:57])[CH3:56].[Li+].[OH-]>>[CH3:2][O:3][C:4]1[CH:9]=[C:8]([CH3:10])[NH:7][C:6](=[O:11])[C:5]=1[CH2:12][NH:13][C:14]([C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]([CH:25]([CH:27]2[CH2:28][CH2:29][N:30]([C:53]([O:54][CH:55]([CH3:57])[CH3:56])=[O:58])[CH2:31][CH2:32]2)[CH3:26])[C:17]=1[CH3:33])=[O:15]
Reactant: CC(C)OC(=O)Cl
Reactant: COc1cc(C)[nH]c(=O)c1CNC(=O)c1c(C)n(C(C)C2CCNCC2)c2ccccc12
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(C)[nH]c(=O)c1CNC(=O)c1c(C)n(C(C)C2CCN(C(=O)OC(C)C)CC2)c2ccccc12
Temperature: 0 °C
Yield: 55.2 %

Procedure:
A 250 mL round bottom flask was charged with a magnetic stir bar, (R or S)—N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(piperidin-4-yl)ethyl)-1H-indole-3-carboxamide hydrochloride (0.467 g, 0.987 mmol) (Compound 326), DMF (2.468 ml, 0.987 mmol), THF (2.468 ml, 0.987 mmol), and N-ethyl-N-isopropylpropan-2-amine (0.638 g, 4.94 mmol). The reaction was cooled to 0° C. and isopropyl carbonochloridate (0.160 ml, 1.086 mmol) was added drop wise via syringe. The reaction was allowed to stir for 2 h to rt and was then treated with 5 N LiOH for 1H to remove any acylated pyridone. This material was extracted with ethyl acetate, washed with brine, dried with MgSO4 and filtered and conc. in vacuo. The resulting material was purified via silica gel chromatography (50 g) using ethyl acetate/MeOH (5:1) as eluent to afford pure title compound as a pale yellow solid (0.300 g, 0.545 mmol, 55.2% yield). LCMS 523 (M+1)+; 1H NMR (DMSO-d6, 400) MHz) δ 11.59 (br. s., 1H), 7.74 (d, J=7.8 Hz, 1H), 7.69 (t, J=4.9 Hz, 1H), 7.62 (d, J=7.8 Hz, 1H), 7.13-7.01 (m, 2H), 6.15 (s, 1H), 4.78-4.67 (m, 1H), 4.32 (d, J=4.9 Hz, 2H), 4.23-4.12 (m, 1H), 4.12-4.02 (m, 1H), 3.84 (s, 3H), 3.82-3.74 (m, 1H), 2.79-2.66 (m, 1H), 2.58 (s, 3H), 2.46-2.34 (m, 2H), 2.20 (s, 3H), 1.96-1.88 (m, 1H), 1.58-1.46 (m, 4H), 1.15 (d, J=6.0 Hz, 6H), 0.95-0.89 (m, 1H), 0.74-0.65 (m, 1H).
Reaction SMILES: [OH:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:15][CH:14]([CH2:16][O:17][C:18]3[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][CH:19]=3)[CH2:13][C:12]2=[O:28])=[CH:7][CH:6]=1.[CH3:29][S:30](Cl)(=[O:32])=[O:31].C(N(CC)CC)C>C(Cl)Cl>[CH3:29][S:30]([O:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:15][CH:14]([CH2:16][O:17][C:18]3[CH:19]=[CH:20][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:26][CH:27]=3)[CH2:13][C:12]2=[O:28])=[CH:7][CH:6]=1)(=[O:32])=[O:31]
Reactant: COC(=O)c1ccc(OCC2CC(=O)N(c3ccc(OCCO)cc3)C2)cc1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc(OCC2CC(=O)N(c3ccc(OCCOS(C)(=O)=O)cc3)C2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Methyl 4-[1-[4-(2-hydroxyethoxy)phenyl]-2-pyrrolidon-4-yl]methoxybenzoate (3.00 g) is dissolved in methylene chloride (30 ml) and the mixture is cooled with ice. Thereto are added methanesulfonyl chloride (0.90 ml) and triethylamine (2.16 ml) severally and the mixture is stirred at room temperature for 16 hours. The reaction mixture is concentrated under reduced pressure and ethyl acetate (60 ml) is added to the residue. The mixture is washed with water three times, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is subjected to silica gel column chromatography and eluted with chloroform to give the desired product (3.39 g) as powder.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]2C3[CH2:7][CH2:8][CH2:9][N:10]([C:14]([NH2:16])=[O:15])[C:11]=3[CH2:12][CH2:13][C:4]=2[CH:3]=1.ClC1C=CC=C(C(OO)=[O:27])C=1.[C:30](=[O:33])([O-])O.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[C:30](=[O:33])[CH2:7][CH2:8][CH2:9][N:10]([C:14]([NH2:16])=[O:15])[C:11](=[O:27])[CH2:12][CH2:13][C:4]=2[CH:3]=1
Reactant: O=C([O-])O
Reactant: NC(=O)N1CCCC2=C1CCc1cc(Cl)ccc12
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Solvent: ClCCl
Product: NC(=O)N1CCCC(=O)c2ccc(Cl)cc2CCC1=O
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
9.20 g (0.035 mol) of 8-chloro-2,3,5,6-tetrahydrobenzo[f]quinoline-4(1H)-carboxamide are suspended in 100 ml of methylene chloride and 14.1 g (0.071 mol) of m-chloroperbenzoic acid (85 percent) in 150 ml of methylene chloride are added dropwise thereto at 10-15°. After stirring at room temperature for 1.5 hours, the mixture is poured into saturated sodium hydrogen carbonate solution, extracted with methylene chloride, dried with magnesium sulfate and the solvent is distilled in a vacuum. The solid obtained is washed with hot ethyl acetate. Recrystallization from dioxane/ether yields 11-chloro-2,3,5,6,7,8-hexahydro-3,8-dioxo-4-benzazecine -4(1H)-carboxamide as white crystals with melting point 182-184°.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[CH3:5][CH:6]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([NH:15][C:16](=[O:18])[CH3:17])[CH:12]=2)[CH2:7]1>C(O)(C(F)(F)F)=O>[CH3:5][CH:6]1[CH2:14][C:13]2[C:8](=[CH:9][C:10]([N+:1]([O-:4])=[O:2])=[C:11]([NH:15][C:16](=[O:18])[CH3:17])[CH:12]=2)[CH2:7]1
Reactant: CC(=O)Nc1ccc2c(c1)CC(C)C2
Reactant: O=[N+]([O-])O
Solvent: O=C(O)C(F)(F)F
Product: CC(=O)Nc1cc2c(cc1[N+](=O)[O-])CC(C)C2
Temperature: 20 °C
Reaction time: 2 h
Yield: 96.3 %

Procedure:
A solution of nitric acid (70%, 3.2 mL, 50.3 mmol) in TFA (5 mL) was added dropwise to a stirred solution of acetamide 91 (3.93 g, 16.8 mmol) in TFA (40 mL) and the solution stirred at 20° C. for 2 h. The solution was poured into ice/water (400 mL) and stirred for 30 min. The precipitate was filtered, washed with water (3×30 mL), and dried. The solid was purified by chromatography, eluting with 10% EtOAc/pet. ether, to give nitroacetamide 92 (3.79 g, 96%) as a red solid: mp (EtOAc/pet. ether) 99-100° C.; 1H NMR δ 10.41 (br s, 1H, NH), 8.50 (s, 1H, H-7), 8.00 (s, 1H, H-4), 3.03-3.13 (m, 2H, CH2), 2.51-2.67 (m, 3H, H-2, CH2), 2.29 (s, 3H, COCH3), 1.14 (d, J=6.4 Hz, 3H, CH3); 13C NMR δ 169.0, 153.9, 139.4, 135.3, 133.7, 121.1, 117.7, 41.6, 40.2, 34.7, 25.6, 20.4. Anal. calcd for C12H14N2O3: C, 61.5; H, 6.0; N, 12.0. Found: C, 61.6; H, 6.2; N, 11.5%.
Reaction SMILES: Cl.[CH3:2][O:3][CH:4]1[CH2:7][NH:6][CH2:5]1.[C:8](#[N:11])[CH2:9]O.CCN(CC)CC>>[CH3:2][O:3][CH:4]1[CH2:7][N:6]([CH2:9][C:8]#[N:11])[CH2:5]1
Reactant: COC1CNC1
Reactant: N#CCO
Agent: Cl
Solvent: CCN(CC)CC
Product: COC1CN(CC#N)C1
Temperature: 50 °C
Yield: 57.2 %

Procedure:
A solution of 3-methoxyazetidine hydrochloride (275) (MacKenzie et al., PCT Int Appl. WO 9605193, 1996) (3.0 g, 24.4 mmol), aqueous glycolonitrile (55%, 3.4 mL, 34.3 mmol) and Et3N (5.2 mL, 37.3 mmol) was stirred at 20° C. for 3 h, then heated at 50° C. for 1 h. The solution was cooled and partitioned between water (50 mL) and Et2O (50 mL). The organic fraction was washed with water (2×50 mL) and brine (50 mL), dried and the solvent evaporated to give nitrile 276 (1.76 g, 57%) as a colourless oil: 1H NMR δ 4.06 (p, J=5.7 Hz, 1H, CHO), 3.61-3.66 (m, 2H, CH2N), 3.49 (s, 2H, CH2CN), 3.28 (s, 3H, OCH3), 3.22-3.27 (m, 2H, CH2N); MS (APCI) m/z 127 (MH+, 100%).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[CH:11]=[C:12]([CH2:16][C:17]([N:19]([CH3:21])[CH3:20])=[O:18])[CH:13]=[CH:14][CH:15]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C([OH:24])C.C(O)(=O)C.[Br-].[Br-].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>CC(O)(C)C.[Zn].O>[CH3:21][N:19]([CH3:20])[C:17](=[O:18])[CH2:16][C:12]1[CH:13]=[CH:14][CH:15]=[C:10]([C:5]2[CH:6]=[CH:7][CH:8]=[C:9]3[C:4]=2[CH2:3][C:2](=[O:24])[NH:1]3)[CH:11]=1
Reactant: CN(C)C(=O)Cc1cccc(-c2cccc3[nH]ccc23)c1
Reactant: CCO
Agent: [Br-]
Agent: [Zn]
Agent: c1cc[nH+]cc1
Solvent: O
Solvent: CC(C)(C)O
Solvent: CC(=O)O
Product: CN(C)C(=O)Cc1cccc(-c2cccc3c2CC(=O)N3)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To the suspension of 2-[3-(1H-indol-4-yl)-phenyl]-N,N-dimethyl-acetamide (1.6 g, 5 mmol) in t-BuOH:ethanol:acetic acid (332 mL:20 mL:24 mL) was added pyridinium tribromide (5 g, 15 mmol) portionwise. The mixture was stirred at room temperature for 3 hours, and then to the mixture was added acetic acid (22 mL). Water (0.7 mL) and zinc dust (5 g) were added to the reaction mixture portionwise. After stirring for one hour, any unreacted zinc was filtered off and most of the solvent was removed under reduced pressure. The residue was diluted with ethyl acetate, washed with 0.5 N HCl (2×), 10% Na2CO3 (2×), brine (2×), water, dried over Na2SO4, concentrated and triturated with ether to give N,N-dimethyl-2-[3-(2-oxo-2,3-dihydro-1H-indol-4-yl)-phenyl]-acetamide. MS m/z 293 [M−1].
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]3OC(=O)[S:13][N:12]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[S:17]([C:27]#[N:28])([C:20]1[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=1)(=[O:19])=[O:18].CCCCC>ClC1C=CC=CC=1Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:11]3[N:28]=[C:27]([S:17]([C:20]4[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=4)(=[O:19])=[O:18])[S:13][N:12]=3)[CH2:10][CH2:9]2)=[CH:6][CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)C#N)cc1
Reactant: O=c1oc(C2(c3ccc(Cl)cc3)CC2)ns1
Solvent: CCCCC
Solvent: Clc1ccccc1Cl
Product: Cc1ccc(S(=O)(=O)c2nc(C3(c4ccc(Cl)cc4)CC3)ns2)cc1
Yield: 83.5 %

Procedure:
5.00 g (19.71 mmol) of 5-[1-(4-chlorophenyl)cyclopropyl]-1,3,4-oxathiazol-2-one and 3.75 g (20.69 mmol) of tosyl cyanide are stirred in 14 ml of 1,2-dichlorobenzene at 160° C. for 1 h. Subsequently, the reaction mixture is cooled, 10 ml of pentane are added and the precipitate is filtered off and dried under vacuum. 6.43 g of product are obtained (86.7% purity, 72.3% yield; log P (pH2.3)=4.97).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:9][CH2:10][N:11]([CH2:14][CH2:15][CH2:16][CH2:17][N:18]3C(=O)C4=CC=CC=C4C3=O)[CH2:12][CH:13]=2)=[CH:4][CH:3]=1.O.NN>CO>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][CH2:17][NH2:18])[CH2:10][CH:9]=2)=[CH:6][CH:7]=1
Reactant: Cc1ccc(C2=CCN(CCCCN3C(=O)c4ccccc4C3=O)CC2)cc1
Agent: NN
Solvent: O
Solvent: CO
Product: Cc1ccc(C2=CCN(CCCCN)CC2)cc1
Yield: 150.1 %

Procedure:
A solution of N-[4-{4-{4-methylphenyl)-1,2,3,6-tetrahydropyridin-1-yl}butyl]phthalimide (0.98 g), hydrazine hydrate [0.17 g) in methanol (10 ml) was stirred under reflux for 4 hours. After evaporation of the solvent, the crude residue was mixed with chloroform and 1N sodium hydroxide. The chloroform layer was separated, dried over magnesium sulfate and evaporated to give an oil of 4-[4-(4-methylphenyl)-1,2,3,6-tetrahydropyridin-1-yl]butylamine (0.96 g).
Reaction SMILES: Cl.[OH:2][CH:3]1[O:11][C@H:10]([CH2:12][OH:13])[C@@H:8]([OH:9])[C@H:6]([OH:7])[C@H:4]1N.C[O-].[Na+].C(N(C(C)C)CC)(C)C>CS(C)=O>[O:2]=[CH:3][CH2:4][C@H:6]([C@@H:8]([C@@H:10]([CH2:12][OH:13])[OH:11])[OH:9])[OH:7]
Reactant: N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Product: O=CC[C@@H](O)[C@H](O)[C@H](O)CO
Temperature: 25 °C
Reaction time: 2 h

Procedure:
D-Glucosamine hydrochloride (13 mg, 0.06 mmol) was added to a solution containing sodium methoxide (3.24 mg, 0.06 mmol) in 3 mL DMSO. The reaction mixture was stirred at room temperature for 2 hrs, and purpurin-18-N-3′-(isothiocyanate)propylimide (19 mg, 0.028 mmol) and 50 μL diisopropylethylamine were added. The resulting solution was stirred under argon atmosphere for 20 hrs. After removing solvent and base by vacuum, the crude obtained was washed with both CH2Cl2 and, water and subsequently crystallized from MeOH. The desired 2-deoxyglucose conjugate (5) was obtained (8 mg). The filtrate was further concentrated and purified by silica gel plate chromatography (10% MeOH in CH2Cl2) to yield 4 mg of product. Thus, the total yield for 5 was 50% (12 mg). UV-vis in DMSO λmax: 366 nm (ε: 5.3×105), 419 (1.4×104), 550 (2.4×104), 648 (8.0×103) and 705 (5.2×104). Mass calcd for C44H53N7O9S: 878.3523 (M+Na)+; found by HRMS; 878.3542 (M+Na)+. 1H NMR (DMSO-d-6, δ ppm): 9.27, 9.16 and 8.85 (each s, 1H, for 10, 5 and 20-H), 8.01 (dd, 1H), 7.80 (br, 1H), 6.55 (br, 1H), 6.33 (d, 1H), 6.12 (d, 1H), 5.24-4.21 (9H), 3.80-3.40 (13H), 2.90 (s, 3H), 2.60 (m, 1H), 2.50-2.30 (m, 2H), 2.08 (m, 2H), 1.8 (m, 1H), 1.72 (d, 3H), 1.41 (t, 3H), −0.61 and −0.67 (each s, 1H, 2×NH).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:22])([F:21])[F:20])[CH2:9][C:10](O)=[O:11])=[CH:4][CH:3]=1.Cl.[CH3:24][NH:25][O:26][CH3:27]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:20])([F:21])[F:22])[CH2:9][C:10]([N:25]([O:26][CH3:27])[CH3:24])=[O:11])=[CH:6][CH:7]=1
Reactant: CNOC
Reactant: O=C(O)CC(c1ccc(Br)cc1)c1ccccc1C(F)(F)F
Agent: Cl
Product: CON(C)C(=O)CC(c1ccc(Br)cc1)c1ccccc1C(F)(F)F

Procedure:
In analogy to example 74, step 4, from 3-(4-bromo-phenyl)-3-(2-trifluoromethyl-phenyl)-propionic acid and N,O-dimethylhydroxylamine hydrochloride was prepared the title compound as a brown viscous oil, MS (ESI+): m/z=416.2 ([M+H]+, 1Br).
Reaction SMILES: [NH2:1][C:2]1[NH:3][C:4](=O)[C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:9]=[CH:8][C:6]=2[N:7]=1.C(N(CC)C(C)C)(C)C.[NH:29]1[CH:33]=[N:32][CH:31]=[N:30]1.P(Cl)(Cl)(Cl)=O>C(#N)C>[NH2:1][C:2]1[N:3]=[C:4]([C:33]2[N:32]=[CH:31][NH:30][N:29]=2)[C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:9]=[CH:8][C:6]=2[N:7]=1
Reactant: Nc1nc2ccc(-c3ccc(F)cc3)nc2c(=O)[nH]1
Reactant: c1nc[nH]n1
Solvent: CCN(C(C)C)C(C)C
Solvent: O=P(Cl)(Cl)Cl
Solvent: CC#N
Product: Nc1nc(-c2nc[nH]n2)c2nc(-c3ccc(F)cc3)ccc2n1
Temperature: 25 °C
Reaction time: 20 h
Yield: 103.5 %

Procedure:
To a stirred suspension of 2-amino-6-(4-fluorophenyl)-3H-pyrido[3,2-d]pyrimidin-4-one (2.56 g, 10 mmole) and N,N-diisopropylethylamine (3.5 mL, 20 mmol) in acetonitrile (75 mL) was added a suspension of 1,2,4-triazole (1.38 g, 20 mmol) and phosphorus oxychloride (1.8 mL, 20 mmol) in dry acetonitrile (75 mL), portion-wise. The reaction mixture was stirred at ambient temperature for 20 hours. Then to it was added N,N-diisopropylethylamine (3.5 mL, 20 mmol), followed by a suspension of 1,2,4-triazole (1.38 g, 20 mmol) and phosphorus oxychloride (1.8 mL, 20 mmol) in dry acetonitrile (50 mL). The reaction mixture was stirred for 3 days until all the starting material was consumed. The solid was collected by vacuum filtration, washed with small amounts of acetonitrile, dichloromethane and diethyl ether, and then dried under high vacuum for one day to afford 3.18 g of the title compound as a light yellow solid. which was characterized by its mass spectrum as follows: MS (m/z): 308.1 ([M+H]+, 100).
Reaction SMILES: O[CH2:2][C:3]1[N:7]([C:8]2[CH:9]=[C:10]([C:14]3[CH2:20][C:19](=[O:21])[NH:18][C:17]4[CH:22]=[C:23]([C:31]([F:34])([F:33])[F:32])[C:24]([N:26]([CH:28]([CH3:30])[CH3:29])[CH3:27])=[CH:25][C:16]=4[N:15]=3)[CH:11]=[CH:12][CH:13]=2)[N:6]=[N:5][CH:4]=1.S(Cl)(Cl)=O.[Cl-].[CH:40]1([NH2:43])[CH2:42][CH2:41]1>ClCCl.CN(C=O)C>[CH:40]1([NH:43][CH2:2][C:3]2[N:7]([C:8]3[CH:9]=[C:10]([C:14]4[CH2:20][C:19](=[O:21])[NH:18][C:17]5[CH:22]=[C:23]([C:31]([F:34])([F:33])[F:32])[C:24]([N:26]([CH:28]([CH3:29])[CH3:30])[CH3:27])=[CH:25][C:16]=5[N:15]=4)[CH:11]=[CH:12][CH:13]=3)[N:6]=[N:5][CH:4]=2)[CH2:42][CH2:41]1
Reactant: CC(C)N(C)c1cc2c(cc1C(F)(F)F)NC(=O)CC(c1cccc(-n3nncc3CO)c1)=N2
Reactant: NC1CC1
Agent: [Cl-]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: O=S(Cl)Cl
Product: CC(C)N(C)c1cc2c(cc1C(F)(F)F)NC(=O)CC(c1cccc(-n3nncc3CNC3CC3)c1)=N2

Procedure:
The title compound was prepared from 4-[3-(5-hydroxymethyl-[1,2,3]triazol-1-yl)-phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-1,3-dihydro-benzo[b][1,4]diazepin-2-one (Example 119) (236 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (70 mg, 27%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([NH2:17])[CH:15]=3)[N:10](COCCOC)[N:9]=2)=[CH:4][CH:3]=1.[C:24](Cl)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.O>N1C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([NH:17][C:24](=[O:31])[C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH:15]=3)[NH:10][N:9]=2)=[CH:6][CH:7]=1
Reactant: COCCOCn1nc(-c2ccc(F)cc2)c2cc(N)ccc21
Reactant: O=C(Cl)c1ccccc1
Solvent: c1ccncc1
Solvent: O
Product: O=C(Nc1ccc2[nH]nc(-c3ccc(F)cc3)c2c1)c1ccccc1
Temperature: 80 °C
Yield: 18.9 %

Procedure:
To a solution of 1-{[3-(4-fluorophenyl)-5-amino(1H-indazoly)]methoxy}-2-methoxyethane (100 mg, 0.32 mmol) in pyridine (3 mL) was added benzoyl chloride (45 μL, 0.38 mmol). The solution was stirred for 12 hours when water (80 mL) was added and the solid filtered. The solid was then taken up in methanol (3 mL) and 6N HCl (3 mL) and heated to 80° C. for 3 hours. Water (80 mL) was then added and the solid filtered and dried to give the title compound (20 mg, 19% yield). 1H NMR (DMSO-d6) δ 13.3 (br s, 1H), 10.37 (s, 1H), 8.57 (s, 1H), 8.0–7.9 (m, 5H), 7.78 (d, 1H), 7.6–7.5 (m, 4H), 7.40 (t, 2H); ES-MS (m/z) 332 [M+1]+.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]([OH:9])=O.Cl.CN(C)CCCN=C=NCC.N1(O)C2C=CC=CC=2N=N1.[F:32][C:33]1[CH:34]=[N:35][CH:36]=[CH:37][C:38]=1[C:39]1[C:40]([C:47]2[CH:48]=[N:49][CH:50]=[CH:51][CH:52]=2)=[N:41][C:42]([NH2:46])=[C:43]([NH2:45])[CH:44]=1>CN(C=O)C>[NH2:46][C:42]1[N:41]=[C:40]([C:47]2[CH:48]=[N:49][CH:50]=[CH:51][CH:52]=2)[C:39]([C:38]2[CH:37]=[CH:36][N:35]=[CH:34][C:33]=2[F:32])=[CH:44][C:43]=1[NH:45][C:7]([C:2]1[CH:3]=[N:4][CH:5]=[CH:6][N:1]=1)=[O:9]
Reactant: Nc1cc(-c2ccncc2F)c(-c2cccnc2)nc1N
Reactant: O=C(O)c1cnccn1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: Nc1nc(-c2cccnc2)c(-c2ccncc2F)cc1NC(=O)c1cnccn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 41.3 %

Procedure:
A solution of pyrazine-2-carboxylic acid (0.114 g, 0.924 mmol), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (0.178 g, 0.924 mmol) and 1H-1,2,3-benzotriazol-1-ol (0.096 g, 0.712 mmol) in DMF (6 mL) was heated at 40° C. for 15 minutes. Finally, 3″-fluoro-3,2′:3′,4″-terpyridine-5′,6′-diamine (Intermediate 1, 0.1 g, 0.356 mmol) in DMF (1 mL) was added and the mixture was stirred at room temperature overnight. The crude mixture was extracted between ethyl acetate and water. The organic layer was washed with 4% sodium bicarbonate aqueous solution and water, dried (MgSO4) and evaporated. The residue was purified by silica gel flash chromatography (90:10 dichloromethane/methanol) to give the title compound (0.057 g, 41% of yield).