Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([C:22]2[CH:27]=[CH:26][C:25]([N+:28]([O-])=O)=[CH:24][CH:23]=2)[C:8]([NH:10][C:11]2[S:12][C:13]3[C:18]([N:19]=2)=[CH:17][CH:16]=[C:15]([O:20][CH3:21])[N:14]=3)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1>C(O)C.C(O)(=O)C.[Fe]>[NH2:28][C:25]1[CH:26]=[CH:27][C:22]([CH:7]([CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)[C:8]([NH:10][C:11]2[S:12][C:13]3[C:18]([N:19]=2)=[CH:17][CH:16]=[C:15]([O:20][CH3:21])[N:14]=3)=[O:9])=[CH:23][CH:24]=1
Reactant: COc1ccc2nc(NC(=O)C(CC3CCCC3)c3ccc([N+](=O)[O-])cc3)sc2n1
Agent: [Fe]
Solvent: CC(=O)O
Solvent: CCO
Product: COc1ccc2nc(NC(=O)C(CC3CCCC3)c3ccc(N)cc3)sc2n1

Procedure:
The title C compound, 3-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-2-(4-nitro-phenyl)-propionamide (12 g, 28.2 mmol) is diluted with 160 mL of ethanol and 150 mL acetic acid. 8 g of iron powder (325 mesh, 0.14 mol) is added and the mixture heated to reflux. Once reflux begins the mixture is stirred vigorously and then heating is discontinued and the mixture is allowed to cool slowly. The solvents are removed and the residue is treated with 250 mL of water. Saturated sodium bicarbonate is added carefully to bring the mixture to a pH of 8-9. The mixture is extracted with ethyl acetate, washed with brine, dried and evaporated to give an orange solid which is triturated from hexane. The resulted solid is collected by filtration to afford 2-(4-amino-phenyl)-3-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-propionamide: 1H NMR (400 MHz, CDCl3) δ 1.0-1.1 (m, 2H), 1.4-1.8 (m, 5H), 1.8-1.9 (m, 2H), 2.1-2.25 (m, 2H), 3.6 (t, 1H, J=7.8), 3.98 (s, 3H), 6.7 (d, 1H, J=8.8), 6.8 (d, 2H, J=8.6), 7.2 (d, 2H, J=8.6), 7.8 (d, 1H, J=8.8).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[ClH:14].C=O.O.[C:18](O)(=O)C.C([BH3-])#N.[Na+].[Cl-].[NH4+]>CO>[ClH:14].[Br:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:13][CH2:12][N:11]([CH3:18])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(=O)O
Reactant: Brc1cccc(C2CCNCC2)c1
Agent: C=O
Agent: Cl
Agent: [BH3-]C#N
Solvent: O
Solvent: CO
Product: CN1CCC(c2cccc(Br)c2)CC1
Temperature: 10 °C

Procedure:
A mixture of 4-(3-bromo-phenyl)-piperidine; hydrochloride (1.0 g, 3.6 mmol), 37% formaldehyde in water (3.7 mL, 120 mmol), Acetic acid (0.25 mL, 4.4 mmol) and methanol (20 mL) was stirred for 15 minutes at room temperature. The mixture was cooled to 10° C. in an ice/water bath. Sodium cyanoborohydride (3.0 g, 48 mmol) was added portionwise. A mild exotherm was noted. The mixture was stirred and warmed to room temperature over 18 hours. The mixture was poured into saturated aqueous ammonium chloride (200 mL) and stirred for 1 hour at room temperature. The mixture was extracted with dichloromethane (3×75 ml). The combined organic layers were dried over magnesium sulfate, filtered and evaporated to an oil. The residue was triturated in ether (200 mL) and filtered. The filtrate was evaporated to an oil (0.585 g). The oil was dissolved in ether and stirred. Hydrogen chloride (2.0M in ether, 2.0 mL) was added dropwise and stirred for 30 minutes. The precipitate was filtered and rinsed with ether. 4-(3-Bromo-phenyl)-1-methyl-piperidine hydrochloride was isolated as a crude white solid (0.432 g, 41%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 10.52 (s, 1H), 7.47-7.41 (m, 2H), 7.37-7.21 (m, 2H), 3.52-3.41 (m, 2H), 3.10-2.95 (m, 2H), 2.85-2.78 (m, 1H), 2.75 (s, 3H), 2.15-2.78 (m, 4H). MS=254, 256 (MH)+. 129b) N-Methyl-N-(3-{2-[3-(1-methyl-piperidin-4-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-8-yl}-phenyl)-methanesulfonamide was prepared from N-[3-(2-amino-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-phenyl]-N-methyl-methanesulfonamide (75.0 mg, 0.236 mmol) and 4-(3-bromo-phenyl)-1-methyl-piperidine; hydrochloride (76.0 mg, 0.262 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (25.0 mg, 0.0457 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a pale yellow foam (0.093 g, 80%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.46 (d, J=6.6 Hz, 1H), 8.10-8.07 (m, 1H), 7.98 (d, J=7.8 Hz, 1H), 7.61 (d, J=7.2 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 7.49 (d, J=8.0 Hz, 1H), 7.46-7.40 (m, 2H), 7.27 (t, J=7.9 Hz, 1H), 6.98 (t, J=7.1 Hz, 1H), 6.88 (d, J=7.7 Hz, 1H), 6.83 (s, 1H), 3.42 (s, 3H), 3.03-2.96 (m, 2H), 2.90 (s, 3H), 2.55-2.45 (m, 1H), 2.34 (s, 3H), 2.12-2.00 (m, 2H), 1.90-1.80 (m, 4H). MS=491 (MH)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[NH:11][C:12]1[N:23]=[CH:22][CH:21]=[CH:20][C:13]=1[C:14]([NH:16][CH2:17][C:18]#[CH:19])=[O:15].[N:24]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=1)=[N+:25]=[N-:26].O.O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>S([O-])([O-])(=O)=O.[Cu+2].C(O)(C)(C)C>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[NH:11][C:12]1[N:23]=[CH:22][CH:21]=[CH:20][C:13]=1[C:14]([NH:16][CH2:17][C:18]1[N:26]=[N:25][N:24]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[CH:19]=1)=[O:15]
Reactant: C#CCNC(=O)c1cccnc1Nc1ccc(OC)cc1OC
Reactant: [N-]=[N+]=NCc1ccc(F)cc1
Agent: [Cu+2]
Agent: O=C1O[C@H]([C@@H](O)CO)C([O-])=C1O
Agent: O=S(=O)([O-])[O-]
Solvent: O
Solvent: CC(C)(C)O
Product: COc1ccc(Nc2ncccc2C(=O)NCc2cn(Cc3ccc(F)cc3)nn2)c(OC)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 75.2 %

Procedure:
Compound 8 (194 mg, 1 mmol) and 2,4-dimethoxyaniline (9 g, 153 mg, 1 mmol) were taken in ethylene glycol and heated at 140° C. for 6 h. Then the reaction mixture was cooled and extracted with ethyl acetate from the aqueous layer and concentrated in vacuum. The compound was further purified by column chromatography using 60-120 silica gel to obtain 2-(2,4-dimethoxyphenylamino)-N-(prop-2-ynyl)nicotinamide 10g as pure product. To a solution of 2-(2,4-dimethoxyphenylamino)-N-(prop-2-ynyl)nicotinamide (10 g, 150 mg, 0.48 mmol) and 1-(azidomethyl)-4-fluorobenzene (12b, 79 mg, 0.53 mmol) in 2:1 mixture of water and tert-butyl alcohol, sodium ascorbate (0.06 mmol) and copper (II) sulphate (0.005 mmol) were added sequentially. The reaction was stirred at room temperature for 12 h, TLC analysis indicated completion of reaction. The reaction mixture was concentrated under vacuum and extracted with EtOAc to give crude product. The crude was purified by column chromatography to afford pure product 2g (167 mg, 70%); mp: 146-148° C.; 1H NMR (300 MHz, CDCl3) δ 10.33 (s, 1H), 8.25 (dd, J=7.5, 1.5 Hz, 1H), 7.72 (dd, J=7.5, 1.5 Hz, 1H), 7.53 (s, 1H), 7.28-7.23 (m, 3H), 7.18-7.13 (m, 1H), 7.03 (t, J=8.3 Hz, 2H), 6.58-6.54 (m, 1H), 6.46 (s, 2H), 5.45 (s, 2H), 4.64 (d, J=5.2 Hz, 2H), 3.90 (s, 3H), 3.79 (s, 3H); MS (ESI m/z): 463 [M+H]+. Yield: 70%
Reaction SMILES: [C:1]1([C@H:7]([N:9]2[CH2:16][C:15](=[N:17]O)[C:11]3([CH2:14][CH2:13][CH2:12]3)[C:10]2=[O:19])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>CO.[Ni]>[NH2:17][CH:15]1[C:11]2([CH2:14][CH2:13][CH2:12]2)[C:10](=[O:19])[N:9]([C@@H:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH3:8])[CH2:16]1
Reactant: C[C@H](c1ccccc1)N1CC(=NO)C2(CCC2)C1=O
Agent: [Ni]
Solvent: CO
Product: C[C@H](c1ccccc1)N1CC(N)C2(CCC2)C1=O
Reaction time: 14.5 h

Procedure:
To a solution of 8.75 g of 6-[1-(R)-phenylethyl]-8-hydroxyimino-5-oxo-6-azaspiro[3.4]octane in 300 ml of methanol there was added 26 ml of Raney nickel, and reduction was carried out under a hydrogen atmosphere at room temperature for 14.5 hr. The catalyst was removed by filtration and the solvent was removed under reduced pressure. By the same procedure, 1.65 g of 6-[1-(R)-phenylethyl]-8-hydroxyimino-5-oxo-6-azaspiro-[3.4]octane was reduced using 5 ml of Raney nickel. The crude products were combined and purified by column chromatography using a column containing 380 g of silica gel. From a fraction of an eluant of 1% (v/v) methanolic chloroform, 3.2 g of the less polar isomer of the titled compound was obtained and 1.8 g of the more polar isomer thereof along with 4.4 g of a mixture of the two isomers. 1H-NMR(CDCl3) δ ppm;1.48(3H, d, J=7.2 Hz), 1.70-2.40(6H, m), 2.50(1H, dd, J=7.2, 12.6 Hz), 3.20-3.52(2H, m), 5.50(1H, q, J=7.2 Hz), 7.32(5H, s).
Reaction SMILES: [C:1]([C:8]1[CH:20]=[C:19]2[C:11]([C:12]3[CH:13]=[CH:14][C:15]([C:21](=[O:27])[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[CH:16][C:17]=3[CH2:18]2)=[CH:10][CH:9]=1)(=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C(Cl)Cl.[C:31](#[N:34])[CH:32]=[CH2:33]>CO>[C:31]([CH2:32][CH2:33][C:18]1([CH2:33][CH2:32][C:31]#[N:34])[C:17]2[CH:16]=[C:15]([C:21](=[O:27])[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH:14]=[CH:13][C:12]=2[C:11]2[C:19]1=[CH:20][C:8]([C:1](=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])=[CH:9][CH:10]=2)#[N:34]
Reactant: CCCCCC(=O)c1ccc2c(c1)Cc1cc(C(=O)CCCCC)ccc1-2
Reactant: C=CC#N
Solvent: ClCCl
Solvent: CO
Product: CCCCCC(=O)c1ccc2c(c1)C(CCC#N)(CCC#N)c1cc(C(=O)CCCCC)ccc1-2
Temperature: 25 °C
Reaction time: 3 h
Yield: 67.2 %

Procedure:
A 3-neck 250-mL round bottom flask was equipped with a condenser, a nitrogen inlet, an addition funnel, and a magnetic stir bar. The flask was then charged with 14.50 g of 1-(7-hexanoyl-9H-fluoren-2-yl)-hexan-1-one and 80 mL of methylene chloride. TRITON B (0.80 g, 40% methanol solution) was then added, followed by the drop wise addition of acrylonitrile (4.67 g) at a rate that kept the reaction temperature below 35° C. The reaction was then stirred at ambient temperature for three hours. The solvent was then removed under reduced pressure and the resulting solid was crystallized from ethanol to give 12.60 g of the title compound. 1H NMR (CDCl3, 300 MHz) δ 8.11-8.03 (m, 4H), 7.89 (m, 2H), 3.04 (m, 4H), 2.55 (m, 4H), 1.81 (m, 4H), 1.56 (m, 4H), 1.44-1.38 (m, 8H), 0.94 (m, 6H).
Reaction SMILES: C([O:3][P:4]([CH2:9][NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([S:23]([C:26]3[CH:30]=[C:29]([C:31]([NH:33]C(OC(C)(C)C)=O)=[NH:32])[S:28][C:27]=3[S:41][CH3:42])(=[O:25])=[O:24])[CH:18]=2)=[C:13]([CH3:43])[CH:12]=1)(=[O:8])[O:5]CC)C.I[Si](C)(C)C.Cl.C(O)(C(F)(F)F)=O.C(Cl)Cl>C(Cl)Cl.CO.O>[C:31]([C:29]1[S:28][C:27]([S:41][CH3:42])=[C:26]([S:23]([C:19]2[CH:18]=[C:17]([C:14]3[CH:15]=[CH:16][C:11]([NH:10][CH2:9][P:4](=[O:3])([OH:8])[OH:5])=[CH:12][C:13]=3[CH3:43])[CH:22]=[CH:21][CH:20]=2)(=[O:25])=[O:24])[CH:30]=1)(=[NH:32])[NH2:33]
Reactant: CCOP(=O)(CNc1ccc(-c2cccc(S(=O)(=O)c3cc(C(=N)NC(=O)OC(C)(C)C)sc3SC)c2)c(C)c1)OCC
Agent: C[Si](C)(C)I
Agent: Cl
Solvent: CO
Solvent: ClCCl
Solvent: O
Product: CSc1sc(C(=N)N)cc1S(=O)(=O)c1cccc(-c2ccc(NCP(=O)(O)O)cc2C)c1
Reaction time: 1 h
Yield: 37.7 %

Procedure:
To a solution of ({3′-[5-(tert-butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3-sulfonyl]-2-methyl-biphenyl-4-yl amino}-methyl) phosphonic acid diethyl ester (38 mg, 0.057 mmol) in DCM (1.2 mL) at 0° C. was added iodotrimethylsilane (25 μL) over 3 minutes period. After 1 h at 0° C., H2O was added. The mixture was stirred for 30 minutes, and then concentrated to give a brown solid. The solid was dissolved in MeOH (1.32 mL), 20% HCl was added, and stirred at ambient temperature for 3 h. The mixture was concentrated to give a brown solid. To this solid was added TFA/DCM (1:1, 3 mL) and stirred at ambient temperature for 40 minutes. The reaction mixture was then concentrated and purified by HPLC (C18 column, 10–70% CH3CN over 30 minutes) to give the title compound (11 mg, 38% yield) as a white solid.
Reaction SMILES: Br[C:2]1[C:7](=[O:8])[N:6]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:17]([C:22]#[N:23])=[CH:18][CH:19]=[CH:20][CH:21]=3)=[C:12]([F:24])[CH:11]=2)[C:5]([CH2:25][CH2:26][CH3:27])=[N:4][C:3]=1[CH3:28].[CH:29]([O:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1)([CH3:31])[CH3:30].C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[F:24][C:12]1[CH:11]=[C:10]([CH2:9][N:6]2[C:7](=[O:8])[C:2]([C:36]3[CH:37]=[CH:38][C:33]([O:32][CH:29]([CH3:31])[CH3:30])=[CH:34][CH:35]=3)=[C:3]([CH3:28])[N:4]=[C:5]2[CH2:25][CH2:26][CH3:27])[CH:15]=[CH:14][C:13]=1[C:16]1[C:17]([C:22]#[N:23])=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: CC(C)Oc1ccc(B(O)O)cc1
Reactant: CCCc1nc(C)c(Br)c(=O)n1Cc1ccc(-c2ccccc2C#N)c(F)c1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CCCc1nc(C)c(-c2ccc(OC(C)C)cc2)c(=O)n1Cc1ccc(-c2ccccc2C#N)c(F)c1
Temperature: 100 °C
Reaction time: 12 h
Yield: 98.7 %

Procedure:
A mixture of 4′-[(5-bromo-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl]-2′-fluorobiphenyl-2-carbonitrile (0.54 g), (4-isopropoxyphenyl)boronic acid (0.33 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.05 g), 2 M aqueous cesium carbonate solution (5 mL) and 1,4-dioxane (5 mL) was stirred at 100° C. for 12 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a colorless amorphous solid (0.6 g, 99%).
Reaction SMILES: [NH3:1].[CH2:2]([C:4]1[N:13]=[C:12]([CH2:14][CH3:15])[CH:11]=[C:10]2[C:5]=1[CH:6]=[C:7]([C:54]([O:56]CC)=O)[C:8](=[O:53])[N:9]2[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:29]2[N:30]=[N:31][N:32]([C:34]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[N:33]=2)=[CH:19][CH:18]=1)[CH3:3]>CO.ClCCl>[CH2:2]([C:4]1[N:13]=[C:12]([CH2:14][CH3:15])[CH:11]=[C:10]2[C:5]=1[CH:6]=[C:7]([C:54]([NH2:1])=[O:56])[C:8](=[O:53])[N:9]2[CH2:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:29]2[N:30]=[N:31][N:32]([C:34]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:47]3[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=3)[N:33]=2)=[CH:21][CH:22]=1)[CH3:3]
Reactant: N
Reactant: CCOC(=O)c1cc2c(CC)nc(CC)cc2n(Cc2ccc(-c3ccccc3-c3nnn(C(c4ccccc4)(c4ccccc4)c4ccccc4)n3)cc2)c1=O
Solvent: CO
Solvent: ClCCl
Product: CCc1cc2c(cc(C(N)=O)c(=O)n2Cc2ccc(-c3ccccc3-c3nnn(C(c4ccccc4)(c4ccccc4)c4ccccc4)n3)cc2)c(CC)n1
Reaction time: 72 h

Procedure:
Concentrated aqueous ammonia solution (d 0.88) was added dropwise to a solution of ethyl 5,7-diethyl-2-oxo-1-[(2'-(2-triphenylmethyl-2H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1,2-dihydro-1,6-naphthyridine-3-carboxylate (600 mg) in a mixture of methanol (7 ml) and dichloromethane (1.5 ml) until the solution became cloudy. Dichloromethane (2 ml) was added to give a clear solution and the mixture was stirred for 3 days. Volatile material was then removed by evaporation to give 5,7-diethyl-2-oxo-1-[(2'-(2-triphenylmethyl-2H-tetrazol-5-yl)-biphenyl-4-yl)methyl]-1,2-dihydro-1,6-naphthyridine-3-carboxamide as a solid (500 mg), which was used without further purification or characterisation.
Reaction SMILES: [CH:1]1[C:6]2=[C:7]3[C:15](=[CH:16][CH:17]=[C:5]2[CH:4]=[CH:3][CH:2]=1)[NH:14][C:13]1[C:8]3=[CH:9][CH:10]=[C:11]2[CH:21]=[CH:20][CH:19]=[CH:18][C:12]2=1.[Br:22]Br.O>ClCCl>[Br:22][C:10]1[CH:9]=[C:8]2[C:13]([NH:14][C:15]3[C:7]2=[C:6]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]2=[CH:17][CH:16]=3)=[C:12]2[CH:18]=[CH:19][CH:20]=[CH:21][C:11]=12
Reactant: c1ccc2c(c1)ccc1c2[nH]c2ccc3ccccc3c21
Reactant: BrBr
Solvent: ClCCl
Solvent: O
Product: Brc1cc2c([nH]c3ccc4ccccc4c32)c2ccccc12
Yield: 160.8 %

Procedure:
10.3 g of 7H-dibenzo[a,g]carbazole was dissolved in dichloromethane (150 mL) at 0° C. with stirring. To this was dropped a dichloromethane solution of bromine (3.1 g in dichloromethane). After being stirred at room temperature for 2 h, the solution was poured into 200 mL of water, filtered, and washed with 500 mL water. The white residue was recrystallized in ethanol and yielded 12-bromo-7H-dibenzo[a,g]carbazole as colorless crystals (10.8 g).
Reaction SMILES: [N:1]1([NH:7][C:8]([NH:10][C:11]2[C:16]3[C:17](=[O:34])[C:18]4[C:19](=[N:20][NH:21][C:22]=4[C:23]4[CH:33]=[CH:32][C:26]([O:27][CH2:28][C:29]([OH:31])=O)=[CH:25][CH:24]=4)[C:15]=3[CH:14]=[CH:13][CH:12]=2)=[O:9])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[NH2:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][O:47][CH2:48][CH2:49][O:50][CH2:51][CH2:52][NH:53][C:54]([CH2:56][CH2:57][C@H:58]([NH:66][C:67]([C:69]1[CH:74]=[CH:73][C:72]([NH:75][CH3:76])=[CH:71][CH:70]=1)=[O:68])[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[O:55].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH3:76][NH:75][C:72]1[CH:73]=[CH:74][C:69]([C:67]([NH:66][C@@H:58]([CH2:57][CH2:56][C:54](=[O:55])[NH:53][CH2:52][CH2:51][O:50][CH2:49][CH2:48][O:47][CH2:46][CH2:45][O:44][CH2:43][CH2:42][O:41][CH2:40][CH2:39][O:38][CH2:37][CH2:36][NH:35][C:29](=[O:31])[CH2:28][O:27][C:26]2[CH:32]=[CH:33][C:23]([C:22]3[NH:21][N:20]=[C:19]4[C:15]5[CH:14]=[CH:13][CH:12]=[C:11]([NH:10][C:8](=[O:9])[NH:7][N:1]6[CH2:6][CH2:5][O:4][CH2:3][CH2:2]6)[C:16]=5[C:17](=[O:34])[C:18]=34)=[CH:24][CH:25]=2)[C:59]([O:61][C:62]([CH3:65])([CH3:63])[CH3:64])=[O:60])=[O:68])=[CH:70][CH:71]=1
Reactant: O=C(O)COc1ccc(-c2[nH]nc3c2C(=O)c2c(NC(=O)NN4CCOCC4)cccc2-3)cc1
Reactant: CNc1ccc(C(=O)N[C@@H](CCC(=O)NCCOCCOCCOCCOCCOCCN)C(=O)OC(C)(C)C)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CNc1ccc(C(=O)N[C@@H](CCC(=O)NCCOCCOCCOCCOCCOCCNC(=O)COc2ccc(-c3[nH]nc4c3C(=O)c3c(NC(=O)NN5CCOCC5)cccc3-4)cc2)C(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Compound 25 (0.60 g, 1 mmol) and compound 26 (0.46 g, 1 mmol) were dissolved in 10 ml DMF and HBTU (0.7 g, 1.8 mmol) was added as a solid followed by DIEA (1.0 ml, 5.7 mmol). The reaction mixture was stirred at room temperature overnight, diluted with EtOAc and the organic phase washed with 0.5N NaOH, brine, dried over MgSO4, filtered and concentrated to an oil. This oil was purified by flash silica chromatography (10 to 20% MeOH/EtOAc) to give a yellow foam (0.65 g, 0.62 mmol, 62%, compound 28).
Reaction SMILES: [O:1]=[C:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:12][CH2:13][C:14](OCC)=[O:15])[CH:8]=2)[NH:3]1.[Cl-].[Ca+2].[Cl-].[BH4-].[Na+]>C(O)C.CCOC(C)=O>[OH:15][CH2:14][CH2:13][O:12][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[NH:3][C:2](=[O:1])[CH2:11][CH2:10]2
Reactant: CCOC(=O)COc1ccc2c(c1)CCC(=O)N2
Agent: [BH4-]
Agent: [Ca+2]
Agent: [Cl-]
Solvent: CCO
Solvent: CCOC(C)=O
Product: O=C1CCc2cc(OCCO)ccc2N1
Temperature: -10 °C
Reaction time: 5 h
Yield: 72.1 %

Procedure:
To a solution of ethyl 2-((2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)oxy)acetate (1.5 g, 6.02 mmol) in ethanol (25 mL), was added calcium chloride (0.334 g, 3.01 mmol). The resulting mixture was cooled to −10° C. and NaBH4 (0.455 g, 12.04 mmol) was added, then stirred at 23° C. for 5 h. The reaction mixture was diluted with EtOAc (50 ml), extracted with sat NaHCO3 solution and brine, dried over anhydrous sodium sulfate, and concentrated to afford a white solid. The crude material was purified by silica gel flash chromatography (12 g, 40-100% ethyl acetate in hexanes) to afford 6-(2-hydroxyethoxy)-3,4-dihydroquinolin-2(1H)-one (0.9 g, 64%) as a white solid. LCMS: RT 0.90 min. LCMS (ES-API), m/z 208.0 (M+H).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][CH3:9])[C:3]=1[C:10]#[C:11][C:12]1[CH:13]=[CH:14][C:15]([NH2:18])=[N:16][CH:17]=1.[CH2:19]([C:21]1[CH:26]=[C:25](B(O)O)[CH:24]=[CH:23][N:22]=1)[CH3:20].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:8]([C:4]1[C:3]([C:10]#[C:11][C:12]2[CH:13]=[CH:14][C:15]([NH2:18])=[N:16][CH:17]=2)=[C:2]([C:25]2[CH:24]=[CH:23][N:22]=[C:21]([CH2:19][CH3:20])[CH:26]=2)[CH:7]=[CH:6][N:5]=1)[CH3:9]
Reactant: CCc1nccc(Cl)c1C#Cc1ccc(N)nc1
Reactant: CCc1cc(B(O)O)ccn1
Agent: [Pd]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: COCCOC
Product: CCc1cc(-c2ccnc(CC)c2C#Cc2ccc(N)nc2)ccn1
Temperature: 190 °C
Reaction time: 5 h

Procedure:
The title compound is synthesized according to general procedure GP3 starting from 100 mg (0.39 mmol) 5-(4-Chloro-2-ethyl-pyridin-3-ylethynyl)-pyridin-2-ylamine (A-30) using 146 mg (˜60% purity, 0.58 mmoL) 2-ethyl-pyrid-4-yl boronic acid, 18 mg (0.02 mmol) Pd2(dba)3, 28 mg (0.06 mmol) XPhos and 107 mg (0.47 mmol) K3PO4 in a mixture of 6.0 mL DME. The reaction mixture is stirred twice under microwave irradiation at 190° C. for 300 min. The reaction mixture is concentrated in vaccuo and the crude product is purified by chromatography on silica gel using a DCM/MeOH-gradient. Yield: 9 mg (7%).
Reaction SMILES: C(N1CCN(C2SC(C(O)=O)=C(C)N=2)C1=O)C1C=CC=CC=1.[CH3:23][C:24]1[N:25]=[C:26]([N:32]2[CH2:36][CH2:35][N:34]([CH2:37][CH2:38][CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[C:33]2=[O:46])[S:27][C:28]=1[C:29]([OH:31])=O.[NH2:47][CH2:48][C:49]1[CH:50]=[N:51][CH:52]=[CH:53][CH:54]=1>>[CH3:23][C:24]1[N:25]=[C:26]([N:32]2[CH2:36][CH2:35][N:34]([CH2:37][CH2:38][CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[C:33]2=[O:46])[S:27][C:28]=1[C:29]([NH:47][CH2:48][C:49]1[CH:50]=[N:51][CH:52]=[CH:53][CH:54]=1)=[O:31]
Reactant: NCc1cccnc1
Reactant: Cc1nc(N2CCN(CCCc3ccccc3)C2=O)sc1C(=O)O
Agent: Cc1nc(N2CCN(Cc3ccccc3)C2=O)sc1C(=O)O
Product: Cc1nc(N2CCN(CCCc3ccccc3)C2=O)sc1C(=O)NCc1cccnc1
Yield: 62 %

Procedure:
Following the procedure as describe in Example 9, making variations as required to replace 2-(3-benzyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid with 4-methyl-2-(2-oxo-3-(3-phenylpropyl)imidazolidin-1-yl)thiazole-5-carboxylic acid to react with 3-(aminomethyl)pyridine, the title compound was obtained as a white powder in 62% yield: mp 127-128° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, CDCl3) 8.57 (s, 1H), 8.45 (d, J=4.2 Hz, 1H), 7.66 (d, J=7.5 Hz, 1H), 7.22-7.07 (m, 6H), 6.51 (t, J=5.7 Hz, 1H), 4.54 (d, J=5.7 Hz, 2H), 3.98-3.92 (m, 2H), 3.49-3.43 (m, 2H), 3.31 (t, J=6.9 Hz, 2H), 2.61-2.50 (m, 5H), 1.91-1.82 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 162.7, 157.4, 155.3, 153.6, 149.0, 148.6, 141.0, 135.8, 134.2, 128.4, 128.2, 126.1, 123.6, 116.7, 43.6, 42.1, 41.9, 41.3, 33.0, 28.7, 17.3; MS (ES+) m/z 436.3 (M+1).