Water → tert-butyl (1-{4-[2-(2-aminopyridin-3-yl)-5-{3-[4-(dimethylcarbamoyl)piperidin-1-yl]phenyl}-3H-imidazo[4,5-b]pyridin-3-yl]phenyl}cyclobutyl)carbamate

HRID 1852915Notes

Reaction equation

HRID 1852915 reaction equation
[CH3:1][N:2]([CH3:45])[C:3]([CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:12]=[C:13]([C:17]3[N:22]=[C:21]([NH:23][C:24]4[CH:29]=[CH:28][C:27]([C:30]5([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:33][CH2:32][CH2:31]5)=[CH:26][CH:25]=4)[C:20]([N+:42]([O-])=O)=[CH:19][CH:18]=3)[CH:14]=[CH:15][CH:16]=2)[CH2:7][CH2:6]1)=[O:4].[NH2:46][C:47]1[N:54]=[CH:53][CH:52]=[CH:51][C:48]=1[CH:49]=O.O.[OH-].[Na+]>C1COCC1.CO.C(OCC)C.[Pd]>[NH2:46][C:47]1[C:48]([C:49]2[N:23]([C:24]3[CH:29]=[CH:28][C:27]([C:30]4([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:33][CH2:32][CH2:31]4)=[CH:26][CH:25]=3)[C:21]3=[N:22][C:17]([C:13]4[CH:14]=[CH:15][CH:16]=[C:11]([N:8]5[CH2:9][CH2:10][CH:5]([C:3](=[O:4])[N:2]([CH3:45])[CH3:1])[CH2:6][CH2:7]5)[CH:12]=4)=[CH:18][CH:19]=[C:20]3[N:42]=2)=[CH:51][CH:52]=[CH:53][N:54]=1

Participants

8

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 7376333-Pyridinecarboxaldehyde, 2-amino-HCID 71142508Tert-butyl (1-{4-[(6-{3-[4-(dimethylcarbamoyl)piperidin-1-yl]phenyl}-3-nitropyridin-2-yl)amino]phenyl}cyclobutyl)carbamate

Product 1

HCID 71142509tert-butyl (1-{4-[2-(2-aminopyridin-3-yl)-5-{3-[4-(dimethylcarbamoyl)piperidin-1-yl]phenyl}-3H-imidazo[4,5-b]pyridin-3-yl]phenyl}cyclobutyl)carbamateYield 62%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 3283Diethyl EtherSolventHCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl (1-{4-[(6-{3-[4-(dimethylcarbamoyl)piperidin-1-yl]phenyl}-3-nitropyridin-2-yl)amino]phenyl}cyclobutyl)carbamate (5.4 g, 8.9 mmol) in THF/MeOH (150 mL, 1:1), was added Pd on carbone (5% wet, 1 g). The mixture was stirred under hydrogen gas (1 atm) for 2 h. The mixture was filtered through celite and evaporated. The residue was dissolved in acetic acid (30 mL) and 2-aminonicotinaldehyde (1.1 g, 9.3 mmol) was added then the mixture was stirred at rt for 1 h. The mixture was heated at 80° C. for 1 h and the mixture was poured into water and neutralized with sodium hydroxide (20 g). The solid was collected by filtration and purified with silica gel column chromatography (hexane/ethyl acetate/methanol, 10:0:0 to 0:10:1) to give a pale orange solid. The solid was slurried in diethyl ether (200 mL) and collected to give the titled compound as a pale yellow solid (3.4 g, 62%).

Workup

  1. filtrationThe mixture was filtered through celite
  2. customevaporated
  3. dissolutionThe residue was dissolved in acetic acid (30 mL)
  4. stirringthe mixture was stirred at rt for 1 h
  5. filtrationThe solid was collected by filtration
  6. custompurified with silica gel column chromatography (hexane/ethyl acetate/methanol, 10:0:0 to 0:10:1)
  7. customto give a pale orange solid
  8. customcollected

Sources & evidence

ORD record
ord-6f7226aff75a4071af7e2fa5ad500893
Source dataset
uspto-grants-2015_02
Patent number
US08962619B2

Reaction notes

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