1,10-Phenanthroline → 1-(3-{[2-(4-amino-furazan-3-yl)-1-ethyl-1H-imidazo[4,5-c]pyridin-6-yl]oxy}phenyl)-4-(4-methyl-1-piperazinyl)-4-oxo-1-butanone

HRID 1986399Notes

Reaction equation

HRID 1986399 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]2[N:8]=[C:9]([C:13]3[C:14]([NH2:18])=[N:15][O:16][N:17]=3)[N:10]([CH2:11][CH3:12])[C:4]=2[CH:3]=1.NC1C=CC=CC=1.[OH:26][C:27]1[CH:28]=[C:29]([C:33](=[O:45])[CH2:34][CH2:35][C:36]([N:38]2[CH2:43][CH2:42][N:41]([CH3:44])[CH2:40][CH2:39]2)=[O:37])[CH:30]=[CH:31][CH:32]=1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.COCCOC.CO.[Cu]I.CS(C)=O>[NH2:18][C:14]1[C:13]([C:9]2[N:10]([CH2:11][CH3:12])[C:4]3[CH:3]=[C:2]([O:26][C:27]4[CH:28]=[C:29]([C:33](=[O:45])[CH2:34][CH2:35][C:36]([N:38]5[CH2:43][CH2:42][N:41]([CH3:44])[CH2:40][CH2:39]5)=[O:37])[CH:30]=[CH:31][CH:32]=4)[N:7]=[CH:6][C:5]=3[N:8]=2)=[N:17][O:16][N:15]=1

Participants

11

Reactant 5

HCID 13181,10-PhenanthrolineHCID 6115AnilineHCID 10796Cesium carbonateHCID 160998514-(6-Bromo-1-Ethyl-1h-Imidazo[4,5-C]pyridin-2-Yl)-1,2,5-Oxadiazol-3-AmineHCID 688734701-(3-Hydroxyphenyl)-4-(4-methyl-1-piperazinyl)-4-oxo-1-butanone

Product 1

HCID 577211811-(3-{[2-(4-amino-furazan-3-yl)-1-ethyl-1H-imidazo[4,5-c]pyridin-6-yl]oxy}phenyl)-4-(4-methyl-1-piperazinyl)-4-oxo-1-butanoneYield 5%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 1140TolueneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
170 °C

Procedure

Under argon, to a suspension of 4-(6-bromo-1-ethyl-1H-imidazo[4,5-c]pyridin-2-yl)-furazan-3-amine (prepared by the method of Example 8, Steps 3-7, substituting ethylamine for aniline in Step 3) (80 mg, 0.26 mmol) in toluene (4 mL) and DME (4 mL), was added the product of Step 2 (145 mg, 0.52 mmol), CuI (50 mg, 0.26 mmol), 1,10-phenanthroline (94 mg, 0.52 mmol), and Cs2CO3 (210 mg, 0.65 mmol). This mixture was then heated to 170° C. by microwave for 25 min. The reaction mixture was added DMSO (2.0 mL), diluted with EtOAC/MeOH, sonicated for 10 min, then filtered and concentrated. The residue was purified with reverse phase HPLC (10% MeCN/H2O→80% MeCN/H2O, containing 0.1% TFA), to afford the title compound as a pale yellow solid (7.3 mg, 5%). 1H NMR (400 MHz, MeOD) δ ppm 8.75 (s, 1H), 7.91 (d, 1H, 7.6 Hz), 7.73-7.75 (m, 1H), 7.59 (td, 1H, 8.0 Hz, 2.0 Hz), 7.45 (dt, 1H, 8 Hz, 0.8 Hz), 7.36 (s, 1H), 4.77 (q, 2H, 7.2 Hz), 3.40-3.58 (m, 8H), 2.86-3.14 (m, 4H), 2.98 (s, 3H), 1.50 (t, 3H, 7.2 Hz). MS (ES+) m/e 505 [M+H]+.

Workup

  1. customprepared by the method of Example 8, Steps 3-7
  2. customsonicated for 10 min
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified with reverse phase HPLC (10% MeCN/H2O→80% MeCN/H2O, containing 0.1% TFA)

Sources & evidence

ORD record
ord-e78040b79a88496ea7661aaa89367d82
Source dataset
uspto-grants-2009_06
Patent number
US07547779B2

Reaction notes

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