N-(1-(1-((2-Chloro-6-methylpyridin-4-yl)methyl)-1H-imidazol-2-yl)-2-(7-methyl-1H-indazol-5-yl)ethyl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide → N-[2-(7-methyl-1H-indazol-5-yl)-1-[1-[(2-methyl-4-pyridinyl)methyl]imidazol-2-yl]ethyl]-4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxamide

HRID 2099828Notes

Reaction equation

HRID 2099828 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[CH:13]=[CH:12][N:11]=[C:10]2[CH:14]([NH:26][C:27]([N:29]2[CH2:34][CH2:33][CH:32]([N:35]3[CH2:44][C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[NH:37][C:36]3=[O:45])[CH2:31][CH2:30]2)=[O:28])[CH2:15][C:16]2[CH:17]=[C:18]3[C:22](=[C:23]([CH3:25])[CH:24]=2)[NH:21][N:20]=[CH:19]3)[CH:5]=[C:4]([CH3:46])[N:3]=1>CO.[Pd]>[CH3:25][C:23]1[CH:24]=[C:16]([CH2:15][CH:14]([NH:26][C:27]([N:29]2[CH2:30][CH2:31][CH:32]([N:35]3[CH2:44][C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[NH:37][C:36]3=[O:45])[CH2:33][CH2:34]2)=[O:28])[C:10]2[N:9]([CH2:8][C:6]3[CH:7]=[CH:2][N:3]=[C:4]([CH3:46])[CH:5]=3)[CH:13]=[CH:12][N:11]=2)[CH:17]=[C:18]2[C:22]=1[NH:21][N:20]=[CH:19]2

Participants

4

Reactant 1

HCID 11422298N-(1-(1-((2-Chloro-6-methylpyridin-4-yl)methyl)-1H-imidazol-2-yl)-2-(7-methyl-1H-indazol-5-yl)ethyl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide

Product 1

HCID 11478962N-[2-(7-methyl-1H-indazol-5-yl)-1-[1-[(2-methyl-4-pyridinyl)methyl]imidazol-2-yl]ethyl]-4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxamide

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

N-(1-(1-((2-Chloro-6-methylpyridin-4-yl)methyl)-1H-imidazol-2-yl)-2-(7-methyl-1H-indazol-5-yl)ethyl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide (15.0 mg, 0.024 mmol) in methanol (1.0 mL) was flushed with nitrogen, and treated with palladium (10% on charcoal, 1.5 mg). The flask was flushed with hydrogen and allowed to stir under an atmosphere of hydrogen overnight. After 24 h, the reaction was charged with additional palladium (10% on charcoal, 1.5 mg). The flask was flushed with hydrogen and allowed to stir under an atmosphere of hydrogen overnight. The reaction was flushed with nitrogen, filtered through celite, and concentrated in vacuo. Column chromatography gave 2.4 mg (17%). 1H-NMR (CD3OD, 500 MHz) δ 1.49-1.63 (m, 4H), 2.32 (s, 3H), 2.43 (s, 3H), 2.69-2.78 (m, 2H), 3.98-4.12 (m, 2H), 5.11-5.24 (m, 3H), 5.39 (d, J=17.1, 1H), 6.55 (d, J=0.9, 1H), 6.72 (s, 1H), 6.80 (d, J=7.9, 1H), 6.85 (s, 1H), 6.97 (dd, J=7.6, 7.3, 1H), 7.06 (s, 1H), 7.10-7.76 (m, 6H), 8.03 (d, J=5.2, 1H). Mass spec.: 604.96 (MH)+.

Workup

  1. customThe flask was flushed with hydrogen
  2. waitAfter 24 h
  3. additionthe reaction was charged with additional palladium (10% on charcoal, 1.5 mg)
  4. customThe flask was flushed with hydrogen
  5. stirringto stir under an atmosphere of hydrogen overnight
  6. customThe reaction was flushed with nitrogen
  7. filtrationfiltered through celite
  8. concentrationconcentrated in vacuo
  9. customColumn chromatography gave 2.4 mg (17%)

Sources & evidence

ORD record
ord-1980e7ebc94d42ebae551b2def1c64c9
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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