Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1COCC1.[CH3:6][C:7]1[C:12]([C:13](OC)=[O:14])=[CH:11][C:10]([Cl:17])=[CH:9][N:8]=1.[H-].[Li+].[B+3].[H-].[H-].[H-]>O>[Cl:17][C:10]1[CH:11]=[C:12]([CH2:13][OH:14])[C:7]([CH3:6])=[N:8][CH:9]=1
Reactant: COC(=O)c1cc(Cl)cnc1C
Agent: [B+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1ncc(Cl)cc1CO
Temperature: 25 °C
Reaction time: 2 h
Yield: 30.6 %

Procedure:
To a THF (30 mL) solution of 5-chrolo-2-methyl nicotinic acid methyl ester (CAS# 350597-49-8) (1.0 g), boron lithium hydride (0.153 g) was added at 0° C. The reaction solution was agitated at room temperature for 2 hours. The reaction solution was added to iced water and the reaction solution was extracted with ethyl acetate. The obtained organic layer was washed with a saturated salt solution, and it concentrated under reduced pressure after dried over anhydrous magnesium sulfate. 0.26 g of the title compound was obtained by the residue was purified by silica gel chromatography (elution solvent: heptane-ethyl acetate system).
Reaction SMILES: [CH3:1][Si](C=[N+]=[N-])(C)C.[CH:8]1([NH:11][C:12]2[C:20]([N+:21]([O-:23])=[O:22])=[CH:19][CH:18]=[C:17]([F:24])[C:13]=2[C:14]([OH:16])=[O:15])[CH2:10][CH2:9]1>CO.C(Cl)Cl>[CH3:1][O:15][C:14](=[O:16])[C:13]1[C:17]([F:24])=[CH:18][CH:19]=[C:20]([N+:21]([O-:23])=[O:22])[C:12]=1[NH:11][CH:8]1[CH2:9][CH2:10]1
Reactant: O=C(O)c1c(F)ccc([N+](=O)[O-])c1NC1CC1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: ClCCl
Solvent: CO
Product: COC(=O)c1c(F)ccc([N+](=O)[O-])c1NC1CC1
Reaction time: 0.25 h
Yield: 98 %

Procedure:
Trimethylsilyldiazomethane (2M in hexane, 2.6 mL, 5.21 mmol) was added dropwise to a solution of 2-cyclopropylamino-6-fluoro-3-nitrobenzoic acid (836 mg, 3.48 mmol) in MeOH (4 mL) and DCM (16 mL) at 0° C. The solution was stirred for 15 min then the volatiles were removed under reduced pressure to afford the title compound (867 mg, 98%). LCMS (Method C): RT 3.50 min [M+H]+ 255.10
Reaction SMILES: [Mg].[CH2:2]1[O:14][C:5]([C:7]2[CH:12]=[CH:11][C:10](Br)=[CH:9][CH:8]=2)([CH3:6])[O:4][CH2:3]1.C1OC(C2C=CC=CC=2)(CBr)OC1.[C:28](Cl)(=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30]>O1CCCC1>[CH3:6][C:5]1([C:7]2[CH:12]=[CH:11][C:10]([C:28](=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:9][CH:8]=2)[O:14][CH2:2][CH2:3][O:4]1
Reactant: CC1(c2ccc(Br)cc2)OCCO1
Reactant: CC(C)(C)C(=O)Cl
Agent: BrCC1(c2ccccc2)OCCO1
Agent: [Mg]
Solvent: C1CCOC1
Product: CC(C)(C)C(=O)c1ccc(C2(C)OCCO2)cc1
Temperature: -60 °C
Reaction time: 1 h

Procedure:
To a suspension of 12.4 g (0.51 g-atoms) magnesium turnings in 190 ml tetrahydrofuran under a nitrogen atmosphere there is added 10 ml. of a solution of 103 g (0.424 mole) of 4'-bromoacetophenone ethylene ketal in 130 ml dry tetrahydrofuran. The reaction is started and the remainder of the bromoacetophenone ethylene ketal solution is added dropwise at a rate that maintains a moderate reflux. After the addition is complete, the mixture is refluxed for one hour. The resulting Grignard solution is added dropwise to a cold solution of 51.1 g (0.424 mole) pivaloyl chloride in 120 ml of dry tetrahydrofuran at a rate that maintains the temperature at 0° C. After addition the resulting solution is stirred for 1 hour at -60° C and then 1 additional hour at -10° C. The mixture is then poured onto ice and extracted with ether, the ether is washed with 2N sodium hydroxide and salt water, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The resulting residue is triturated with petroleum ether to give 4'-(2-methyl-2-dioxolanyl)pivalophenone, m.p. 75°-82° C.
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[CH:17]=[CH:16][NH:15][C:12]3=[N:13][CH:14]=2)O1.Cl[C:20]1[N:25]=[C:24]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[CH:23]=[N:22][CH:21]=1.C([O-])([O-])=O.[Cs+].[Cs+].CO.C(Cl)(Cl)Cl>CN(C=O)C.C(Cl)(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:15]1[C:12]2=[N:13][CH:14]=[C:9]([C:20]3[N:25]=[C:24]([N:26]4[CH2:27][CH2:28][O:29][CH2:30][CH2:31]4)[CH:23]=[N:22][CH:21]=3)[CH:10]=[C:11]2[CH:17]=[CH:16]1
Reactant: CC1(C)OB(c2cnc3[nH]ccc3c2)OC1(C)C
Reactant: Clc1cncc(N2CCOCC2)n1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CO
Solvent: ClC(Cl)Cl
Solvent: CN(C)C=O
Product: c1cc2cc(-c3cncc(N4CCOCC4)n3)cnc2[nH]1
Temperature: 100 °C
Yield: 22.2 %

Procedure:
A stirred solution of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (147) (100 mg, 0.4 mmol) and 4-(6-chloropyrazin-2-yl)morpholine (103) (80 mg, 0.4 mmol) in DMF (5 mL) was degassed and purged with nitrogen for 10 min. To this reaction mixture was added Cs2CO3 (333 mg, 1.0 mmol, 2.5 eq) and the reaction mixture was purged again for another 10 min followed by the addition of Pd(PPh3)4 (0.018 mg, 0.016 mmol, 0.04 eq). The resulting reaction mixture was heated to 100° C., overnight under sealed tube condition. After completion of the reaction the mass was diluted with chloroform and filtered through Celite and the solvents were removed to obtain the crude product. The crude was passed through neutral alumina eluting with 2-3% MeOH/CHCl3 provided a white coloured solid 25 mg of 4-(6-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazin-2-yl)morpholine 148. 1H NMR (400 MHz, CDCl3) δ: 8.96 (s, 1H), 8.95 (s, 1H), 8.84 (s, 1H), 8.54 (d, J=1.95, 1H), 8.43 (s, 1H), 8.07 (s, H), 7.36 (m, 1H), 3.71 (t, 4H), 3.69 (bt, 4H); MS m/z 281.90 (M+H)+.
Reaction SMILES: [C:1](=[O:4])([O-])[O-:2].[K+].[K+].[CH3:7][O:8][C:9]1[CH:10]=[C:11]([C:19](=C)[C:20](O)=O)[CH:12]=[C:13]([O:17][CH3:18])[C:14]=1[O:15][CH3:16].C>[Pd].O>[CH3:18][O:17][C:13]1[CH:12]=[C:11]([CH2:19][CH2:20][C:1]([OH:2])=[O:4])[CH:10]=[C:9]([O:8][CH3:7])[C:14]=1[O:15][CH3:16]
Reactant: O=C([O-])[O-]
Reactant: C=C(C(=O)O)c1cc(OC)c(OC)c(OC)c1
Agent: [Pd]
Agent: [K+]
Solvent: O
Product: COc1cc(CCC(=O)O)cc(OC)c1OC
Reaction time: 1 h
Yield: 167.5 %

Procedure:
6.8 g of potassium carbonate is added to a solution of 21.44 g of 3,4,5-trimethoxyphenylpropenoic acid and 45 ml of water then the medium is hydrogenated for one hour under a pressure of 1200-1300 mbars in the presence of 1.8 g activated charcoal with 10% palladium, in this way 2.1 l of hydrogen is absorbed. The reaction medium is filtered, followed by washing with water and acidifying with 50 ml of hydrochloric acid (2N). After separation, the residue is washed with water and dried under reduced pressure at ambient temperature. In this way 19.8 g of the expected product is obtained (M.P.=102-103° C.)
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([N+:9]([O-])=O)[CH:3]=1.C(O)(C)C.C([O-])=O.[K+].C(OCCC)(=O)C>O.[Pd]>[NH2:9][C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[CH:6][C:5]=1[OH:8]
Reactant: O=[N+]([O-])c1cc(F)ccc1O
Agent: [Pd]
Agent: O=C[O-]
Agent: [K+]
Solvent: CC(C)O
Solvent: CCCOC(C)=O
Solvent: O
Product: Nc1cc(F)ccc1O
Yield: 91.2 %

Procedure:
In a 500-ml flask, place 39.3 g (0.25 m) of 4-fluoro-2-nitrophenol (2a) and 120 ml of isopropyl alcohol and warm to 40° C. Add 1.5 g of 5% Pd/C wet with 1.5 ml of water and stir the mixture vigorously. Add a solution of 84.1 g (1.0 m) of potassium formate in 85 ml of water in drop wise over an hour keeping the temperature at 45°-53° C. Stir the mixture at 50° C. for 2.5 hrs. Add 150 ml of propyl acetate and 100 ml of water and stir for a few min. Filter off catalyst and wash with 100 ml of propyl acetate and 100 ml of water. Separate propyl acetate solution, and wash with 150 ml water and 150 ml of brine containing 1-2 g sodium hydrosulfite. Dry propyl acetate solution over magnesium sulfate and concentrate to approximately 75 ml. Add 300 ml of heptane slowly with gentle stirring. Concentrate under a reduced pressure till most of propyl acetate evaporated. Add 150 ml of heptane to resulting mush and cool in an ice bath for about an hour. Collect solid, wash with heptane, and dry in a vacuum oven to give 29.0 g (91%) of 2-amino-4-fluorophenol (3a; X=F) as gray solids.
Reaction SMILES: [NH2:1][S:2]([CH2:5][C:6]1[CH:15]=[CH:14][CH:13]=[CH:12][C:7]=1[C:8](OC)=[O:9])(=[O:4])=[O:3].O.[NH2:17][NH2:18]>C(O)C>[NH2:1][S:2]([CH2:5][C:6]1[CH:15]=[CH:14][CH:13]=[CH:12][C:7]=1[C:8]([NH:17][NH2:18])=[O:9])(=[O:4])=[O:3]
Reactant: NN
Reactant: COC(=O)c1ccccc1CS(N)(=O)=O
Solvent: O
Solvent: CCO
Product: NNC(=O)c1ccccc1CS(N)(=O)=O
Temperature: 20 °C
Yield: 58.3 %

Procedure:
To a suspension of 84 g of methyl 2-[(aminosulfonyl)methyl]benzoate in 300 ml of absolute ethanol was added dropwise 22 g of hydrazine monohydrate. The thick suspension was heated at reflux for about 16 hours to yield a solution, then a thick suspension, at reflux temperature. The suspension was cooled to 20° C., filtered, and the residue was washed 1×100 ml of water and suction dried about three hours to provide 49 g of the subject compound; m.p. 221°-222° C.
Reaction SMILES: ClC1C=CC=CC=1.[C:8]([N:10]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[CH2:14][CH2:13][C:12]2[CH:21]=[CH:22][CH:23]=[CH:24][C:11]1=2)#[N:9].[OH2:25]>>[C:8]([N:10]1[C:11]2[CH:24]=[CH:23][CH:22]=[CH:21][C:12]=2[CH:13]([OH:25])[CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]1=2)#[N:9]
Reactant: N#CN1c2ccccc2CCc2ccccc21
Reactant: O
Solvent: Clc1ccccc1
Product: N#CN1c2ccccc2CC(O)c2ccccc21
Temperature: 87.5 °C

Procedure:
190 ml of chlorobenzene, 25 g of (I) and 17 g of N,N-dibromohydantoin are loaded into a 500 ml pyrex round-bottom flask, under nitrogen, and irradiated from the outside with a 300 watt halogen lamp, keeping temperature between 70 and 75° C. for 3 hours. 150 ml of water and 5 g of PEG 6000 are added, heating to 85-90° C for 2 hours. After decanting at 60° C., water is removed and the organic phase is washed with further water (2×100 ml). Chlorobenzene is evaporated off under vacuum at 5 mm/Hg and the residue is taken up with 50 ml of ethyl acetate. The mixture is cooled to 0° C., filtered and dried at 60° C. for 4 hours, to obtain 16 g of (VI), m.p. 110-111° C., with good purity.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[N:20][NH:21][CH:22]=3)=[CH:14][N:13]=2)[CH2:11][CH2:10][CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O.[ClH:31].O1CCOCC1>C(Cl)Cl>[ClH:31].[ClH:31].[NH:20]1[CH:19]=[C:18]([C:15]2[CH:16]=[CH:17][C:12]([C:8]3([NH2:7])[CH2:11][CH2:10][CH2:9]3)=[N:13][CH:14]=2)[CH:22]=[N:21]1
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-c3cn[nH]c3)cn2)CCC1
Agent: Cl
Solvent: C1COCCO1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: NC1(c2ccc(-c3cn[nH]c3)cn2)CCC1
Reaction time: 15 h

Procedure:
To a solution of {1-[5-(1H-pyrazol-4-yl)-pyridin-2-yl]-cyclobutyl}-carbamic acid tert-butyl ester (300 mg, 0.96 mmol) in CH2Cl2 (5 mL) was added TFA (0.37 mL, 4.8 mmol). After 15 h, 4M HCl in dioxane (1.2 mL, 4.8 mmol) was added. After 1 h, the reaction was concentrated in-vacuo to yield 303 mg of the title compound, m/z 215.4 [M+H]+.
Reaction SMILES: [NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([C:10]([O:12][CH3:13])=[O:11])[C:4]=2[CH:3]=[CH:2]1.[Cl:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=1)[CH:18]=O.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[Cl:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=1)[CH2:18][C:3]1[C:4]2[C:5]([C:10]([O:12][CH3:13])=[O:11])=[CH:6][CH:7]=[CH:8][C:9]=2[NH:1][CH:2]=1
Reactant: COC(=O)c1cccc2[nH]ccc12
Reactant: O=Cc1cccc(Cl)c1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC(=O)c1cccc2[nH]cc(Cc3cccc(Cl)c3)c12
Temperature: 25 °C
Yield: 70.2 %

Procedure:
To a solution of commercially available methyl 1H-indole-4-carboxylate (5 g, 28.5 mmol) in 100 mL dichloromethane, at 0° C., was added 3-chlorobenzaldehyde (5 mL, 43.8 mmol), triethylsilane (15 mL, 93.9 mmol) and trifluoroacetic acid (5 mL, 64.9 mmol), and the resulting solution was stirred for ON as it warmed to rt. The reaction was then quenched with saturated aqueous sodium bicarbonate and the solution was extracted with dichloromethane. The organic phases were then combined, washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The resultant solid was washed with cold 10:1 hexanes:dichloromethane to yield 6 g of the title compound as a white solid. 1H NMR (500 MHz, d6-acetone): δ 8.5 (s, 1H), 8.0 (m, 2H), 7.4-7.1 (m, 5H), 5.7 (s, 2H), 4.0 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:35])[CH:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=3)[N:11]([C:20](Cl)=[O:21])[C:10]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][C:24]=3[O:31][CH:32]([CH3:34])[CH3:33])=[N:9]2)=[CH:4][CH:3]=1.Cl.Cl.[N:38]1([CH2:44][C:45]([NH2:47])=[O:46])[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]2([CH3:35])[C@@H:12]([C:13]3[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=3)[N:11]([C:20]([N:41]3[CH2:42][CH2:43][N:38]([CH2:44][C:45]([NH2:47])=[O:46])[CH2:39][CH2:40]3)=[O:21])[C:10]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][C:24]=3[O:31][CH:32]([CH3:33])[CH3:34])=[N:9]2)=[CH:6][CH:7]=1
Reactant: NC(=O)CN1CCNCC1
Reactant: COc1ccc(C2=NC(C)(c3ccc(Cl)cc3)C(c3ccc(Cl)cc3)N2C(=O)Cl)c(OC(C)C)c1
Agent: Cl
Product: COc1ccc(C2=N[C@@](C)(c3ccc(Cl)cc3)[C@@H](c3ccc(Cl)cc3)N2C(=O)N2CCN(CC(N)=O)CC2)c(OC(C)C)c1

Procedure:
In a manner analogous to the method described in example 5, rac-(4S*,5R*)-4,5-bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4-methyl-4,5-dihydro-imidazole-1-carbonyl chloride was reacted with 2-piperazin-1-yl-acetamide dihydrochloride (Matrix Scientific) to give the title compound. LC-MS: 638.2 [(M+H)+]
Reaction SMILES: [Cl:1][C:2]1[CH:36]=[CH:35][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:17][CH2:18][CH2:19][O:20]C4CCCCO4)[C:12](=[O:27])[N:11]([CH3:28])[C:10]=3[N:9]=[C:8]2[CH2:29][CH2:30][CH2:31][O:32]CC)=[CH:4][CH:3]=1.C(Cl)(=O)C>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:17][CH2:18][CH2:19][OH:20])[C:12](=[O:27])[N:11]([CH3:28])[C:10]=3[N:9]=[C:8]2[CH2:29][CH2:30][CH2:31][OH:32])=[CH:35][CH:36]=1
Reactant: CCOCCCc1nc2c(c(=O)n(CCCOC3CCCCO3)c(=O)n2C)n1Cc1ccc(Cl)cc1
Solvent: CC(=O)Cl
Solvent: CCO
Product: Cn1c(=O)n(CCCO)c(=O)c2c1nc(CCCO)n2Cc1ccc(Cl)cc1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 60.4 %

Procedure:
To a solution of 7-(4-chlorobenzyl)-8-(3-hydroxypropyl)-3-methyl-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-purine-2,6(3H,7H)-dione (30 mg, 0.061 mmol, example 48, step 3) in ethyl alcohol (20 mL) was added acetyl chloride (0.2 mL, 2.80 mmol). The reaction was stirred at 0° C. for 10 min. The mixture was concentrated to give a crude product, which was purified by preparative HPLC to give 7-(4-chlorobenzyl)-1,8-bis(3-hydroxypropyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (15 mg, 60.6% yield) as a white solid. 1H-NMR (CD3OD) δ 7.37-7.35(d, 2H), 7.21-7.22(d, 2H), 5.62(s, 2H), 4.11-4.08(t, 2H), 3.62-3.59(t, 4H), 3.56(s, 3H), 2.87-2.83(t, 2H), 1.95-1.83(m, 4H). LCMS retention time 1.801 min; LCMS MH+ 407.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]3[CH:15]=[N:16][C:17]([CH2:20][NH:21][CH:22]=O)=[CH:18][CH:19]=3)=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][C:3]=1[CH3:24].O=P(Cl)(Cl)Cl>C1C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]3[CH:19]=[CH:18][C:17]4[N:16]([CH:22]=[N:21][CH:20]=4)[CH:15]=3)=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][C:3]=1[CH3:24]
Reactant: Cc1cc(-c2ncccc2-c2ccc(CNC=O)nc2)ccc1F
Solvent: c1ccccc1
Solvent: O=P(Cl)(Cl)Cl
Product: Cc1cc(-c2ncccc2-c2ccc3cncn3c2)ccc1F
Temperature: 25 °C
Yield: 53.8 %

Procedure:
6-(2-(4-Fluoro-3-methylphenyl)pyridin-3-yl)imidazo[1,5-a]pyridine (Compound 269) can be prepared via the reactions shown in the first two steps of Scheme 20: (2′-(4-Fluoro-3-methylphenyl)-[3,3′-bipyridin]-6-yl)methanamine (2.18 g) and formic acid (15 mL) were stirred and heated under nitrogen atmosphere at 100° C. After 72 h, the reaction mixture was concentrated and partitioned between CH2Cl2/aq. NaHCO3. Usual work-up and purification by flash column chromatography (Combiflash® companion System® with RediSep® silica gel column 40 g and 50-100% EtOAC/hexanes as elutant) provided 630 mg of N-((2′-(4-fluoro-3-methylphenyl)-[3,3′-bipyridin]-6-yl)methyl)formamide as an off white solid. N-((2′-(4-fluoro-3-methylphenyl)-[3,3′-bipyridin]-6-yl)methyl)formamide (630 mg) and POCl3 (3 mL) were stirred and heated in benzene (20 mL) overnight at 75° C. The reaction mixture was cooled to room temperature and concentrated. Subsequently, ice/water solution was added to the crude residue followed by CH2Cl2 and aq. NaHCO3. Upon allowing the solution warm to room temperature, organic layer was separated, stirred over Na2SO4, filtered and concentrated. Purification of the crude residue by flash column chromatography (Combiflash® companion System® with RediSep® silica gel column 40 g and 2-8% MeOH/CH2Cl2 as an eluting solvent) provided 320 mg of 6-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)imidazo[1,5-a]pyridine as an off-white solid.
Reaction SMILES: [NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[Br:12]Br.Br>C(Cl)(Cl)Cl>[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:8]([Br:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]
Reactant: Nc1c(Cl)cccc1C(=O)O
Reactant: BrBr
Agent: Br
Solvent: ClC(Cl)Cl
Product: Nc1c(Cl)cc(Br)cc1C(=O)O
Temperature: 25 °C
Reaction time: 16 h
Yield: 87 %

Procedure:
To a suspension of 2-amino-3-chlorobenzoic acid (2 g, 11.6 mmol) in chloroform (120 mL) was added dropwise bromine (1.1 equiv.) in chloroform (12 mL) solution. The mixture was stirred at room temperature for 16 hrs. The resulting white solid was collected by filtration and washed thoroughly with methylene chloride until the filtrate was colorless. The solid was air-dried to give 3.35 g of white powder as HBr salt of 2-amino-5-bromo-3-chlorobenzoic acid (87% yield). ES/MS m/z 250/252 (MH+).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][CH2:11][CH2:12][C:13]([OH:15])=O)([O-])=O.ClC1C=CC(NCCC(O)=O)=C([N+]([O-])=O)C=1.ClC1C([N+]([O-])=O)=C(NCCC(O)=O)C=CC=1.C(O)(=O)C=C.[N+](C1C=CC=C2C=1NCCC2=O)([O-])=O.ClC1C([N+]([O-])=O)=C2C(C(=O)CCN2)=CC=1.FC1C=C2C(=C([N+]([O-])=O)C=1)NCCC2=O.CC1C([N+]([O-])=O)=C2C(C(=O)CCN2)=CC=1.[Sn](Cl)(Cl)(Cl)Cl.Cl.Cl.[Sn]>Cl.[Fe].C(O)(=O)C.[Fe]>[NH2:1][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:5]=1[NH:10][CH2:11][CH2:12][C:13]2=[O:15]
Reactant: O=C(O)CCNc1ccccc1[N+](=O)[O-]
Agent: [Fe]
Agent: C=CC(=O)O
Agent: Cc1ccc2c(c1[N+](=O)[O-])NCCC2=O
Solvent: CC(=O)O
Product: Nc1cccc2c1NCCC2=O

Procedure:
By Friedel-Crafts reaction, known compounds 3-(2nitrophenylamino)propionic acid, 3-(4-chloro-2-nitrophenylamino)propionic acid, 3-(3-chloro-2-nitrophenylamino)propionic acid [Ann. Chim. (Rome), volume 55, page 182 (1965)] or substituted N-(2-carboxyethyl)-2-nitroanilin compounds, which can generally be prepared by reacting known substituted 2-nitroaniline with acrylic acid, are converted into novel 2,3-dihydro-8-nitro-4(1H)-quinolinone compounds such as 7-chloro-2,3-dihydro-8-nitro-4(1H)-quinolinone, 6-fluoro-2,3-dihydro-8-nitro-4(1H)-quinolinone and 2,3-dihydro-7-methyl-8-nitro-4(1H)-quinolinone. The 2,3-dihydro-8-nitro-4(1H)-quinolinone compounds are reduced by tin chloride - hydrochloric acid, tin - hydrochloric acid, iron - hydrochloric acid, iron - acetic acid or by catalytic hydrogenation to give 8-amino-2,3-dihydro-4(1H)-quinolinone compounds represented by the formula (IV): ##STR4## wherein R2, R3 and R4 have the same significances as defined above.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-])=O>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[NH2:9]
Reactant: COc1cc(N2CCOCC2)ccc1[N+](=O)[O-]
Solvent: CO
Product: COc1cc(N2CCOCC2)ccc1N
Yield: 97 %

Procedure:
A 1 L round bottom flask charged with 4-(3-methoxy-4-nitrophenyl)morpholine (15.7 g, 66 mmol) in 300 mL MeOH, was evacuated and then backfilled with argon. This sequence was repeated two additional times. The reaction vessel was kept under a stream of argon and Pd(C) (10%, 1.57 g) was added. After the addition of Pd (C) was complete the reaction vessel was evacuated and backfilled with hydrogen gas. This evacuation/backfill sequence was repeated twice. After 18 h the hydrogen gas was evacuated by introducing argon into the round bottom flask. The reaction mixture was filtered through a pad of Celite. The Celite was washed with 200 mL EtOAc. The volatiles were evaporated to yield 13.4 g of 2-methoxy-4-morpholinoaniline (64 mmol, 97%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]([NH2:18])=[S:17])[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1.Br[CH:20]1[CH2:25][CH2:24][CH2:23][CH:22]([C:26]2[O:30][N:29]=[C:28]([CH3:31])[N:27]=2)[C:21]1=O>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]2[S:17][C:20]3[CH2:25][CH2:24][CH2:23][CH:22]([C:26]4[O:30][N:29]=[C:28]([CH3:31])[N:27]=4)[C:21]=3[N:18]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1
Reactant: Cc1noc(C2CCCC(Br)C2=O)n1
Reactant: COc1cc(NC(N)=S)ccc1-n1cnc(C)c1
Product: COc1cc(Nc2nc3c(s2)CCCC3c2nc(C)no2)ccc1-n1cnc(C)c1

Procedure:
The title compound was prepared from [3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-thiourea (70 mg, 0.27 mmol) and crude 2-bromo-6-(3-methyl-[1,2,4]oxadiazol-5-yl)-cyclohexanone (173 mg, ca. 0.5 mmol) using in analogous manner the procedure described in example 1b). Obtained as a light-brown foam (25 mg, 22%). MS ISP (m/e): 423.1 (100) [(M+H)+].
Reaction SMILES: Cl[CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([C:14]([O:16][CH3:17])=[O:15])[C:7]([C:10]([O:12][CH3:13])=[O:11])=[N:8][CH:9]=1.[N+](=C1CCCCCCCCCC1C1CCCCCCCCCC1)=[N-]>C1(C)C=CC=CC=1>[CH:3]([C:4]1[CH:5]=[C:6]([C:14]([O:16][CH3:17])=[O:15])[C:7]([C:10]([O:12][CH3:13])=[O:11])=[N:8][CH:9]=1)=[CH2:2]
Reactant: COC(=O)c1cc(CCCl)cnc1C(=O)OC
Agent: [N-]=[N+]=C1CCCCCCCCCC1C1CCCCCCCCCC1
Solvent: Cc1ccccc1
Product: C=Cc1cnc(C(=O)OC)c(C(=O)OC)c1

Procedure:
A solution of 2 g of 5-(2-chloroethyl)-pyridine-2,3-dicarboxylic acid, dimethyl ester and 0.13 mL diazobicycloundecane (DBU) in 40 mL of toluene is heated at reflux for 11/2 hours, cooled, and filtered. The filtrate is concentrated in vacuo, and the residue is chromatographed on silica gel using hexane-ethyl acetate mixtures to afford the desired product as a colorless oil.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([Br:8])[C:5]([OH:9])=[CH:4][C:3]=1[OH:10].C(N(CC)CC)C.[C:18](Cl)(=[O:20])[CH3:19]>ClCCl>[C:18]([O:9][C:5]1[CH:4]=[C:3]([OH:10])[C:2]([Br:1])=[CH:7][C:6]=1[Br:8])(=[O:20])[CH3:19]
Reactant: Oc1cc(O)c(Br)cc1Br
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)Oc1cc(O)c(Br)cc1Br
Temperature: 0 °C
Reaction time: 8 h
Yield: 54.9 %

Procedure:
Under nitrogen, 4,6-dibromo-1,3-benzenediol (10.58 gram, 39.5 millimoles, 1.0 equivalent) and triethylamine (11.0 milliliter, 7.99 grams, 79.0 millimoles, 2.0 equivalents) dissolved in dichloromethane (80 milliliters) were cooled to 0° C. Acetyl chloride (3.09 milliliters, 43.4 millimoles, 1.1 equivalents) were added over the course of 17 minutes. The reaction was allowed to warm to room temperature and was stirred overnight. The reaction was worked up by removal of the volatiles by rotary evaporation. The solid residue was taken up in 100 milliliters ethyl acetate. The mixture was allowed to stir for 5 minutes, and the precipitate was removed by filtration. The product was purified by gradient flash column chromatography (ethyl acetate in hexane, 0 to 40%). The product was obtained in the form of a colorless solid (6.73 grams, 21.7 millimoles, 55%). m.p.: 121.3° C.; 1H-NMR (400 MHz, CDCl3) δ 7.69 (s, 1H), 6.85 (s, 1H), 5.59 (s, 1H), 2.34 (s, 3H); 13C NMR (101 MHz, THF) δ 168.12, 155.60, 149.52, 136.49, 112.77, 108.40, 106.30, 20.59; FTIR 570, 647, 690, 707, 768, 842, 872, 920, 1025, 1060, 1168, 1206, 1240, 1367, 1394, 1489, 1580, 1599, 1718, 2936, 2993, 3082, 3296 cm−1; UV/Vis: 221, 229 (overlapping), 292 nm; ESI/MS/MS of m/z=309: 309 [M79Br/81Br-H]−, 267 [M79Br/81Br—(CH2C═O, H)]−, 81 [81Br]−, 79 [79Br]−; HRMS (ESI−): calc. for C8H5Br2O3− [M-H]− 306.8605, found 306.8622.