Sodium Hydroxide → N-[4-(4-amino-2-butyl-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)butyl]-4-[[2-(dimethylamino)ethoxy](phenyl)methyl]benzamide

HRID 1265058Notes

Reaction equation

HRID 1265058 reaction equation
[CH2:1]([C:5]1[N:6]([CH2:23][CH2:24][CH2:25][CH2:26][NH:27][C:28](=[O:48])[C:29]2[CH:34]=[CH:33][C:32]([CH:35]([O:42][CH2:43][CH2:44][N:45]([CH3:47])[CH3:46])[C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[CH:31][CH:30]=2)[C:7]2[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]=[C:9](OC3C=CC=CC=3)[C:8]=2[N:22]=1)[CH2:2][CH2:3][CH3:4].C([O-])(=O)C.[NH4+:53].[OH-].[Na+]>O>[NH2:53][C:9]1[C:8]2[N:22]=[C:5]([CH2:1][CH2:2][CH2:3][CH3:4])[N:6]([CH2:23][CH2:24][CH2:25][CH2:26][NH:27][C:28](=[O:48])[C:29]3[CH:34]=[CH:33][C:32]([CH:35]([O:42][CH2:43][CH2:44][N:45]([CH3:46])[CH3:47])[C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[CH:31][CH:30]=3)[C:7]=2[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 517165Ammonium AcetateHCID 12109134HCID 12109134, compound

Product 1

HCID 10218514N-[4-(4-amino-2-butyl-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)butyl]-4-[[2-(dimethylamino)ethoxy](phenyl)methyl]benzamideYield 15.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

N-[4-(2-Butyl-6,7-dimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl)butyl]-4-[[2-(dimethylamino)ethoxy](phenyl)methyl]benzamide (101 mg, 0.16 mmol) and ammonium acetate (1.1 g) were placed into a pressure tube along with a stir bar. The tube was sealed and heated at 150° C. for 16 hours. The reaction was cooled to room temperature and diluted with water. The resulting cloudy aqueous mixture was made basic with 10% aqueous sodium hydroxide and extracted with chloroform (3×25 mL). The combined organic fractions were washed with water followed by brine, dried (Na2SO4), decanted and evaporated to provide a yellow oil. Purification by flash column chromatography (silica gel, 95:5 dichloromethane/methanol gradient to 9:1 dichloromethane/methanol and finally 94:5:1 dichloromethane/methanol/triethylamine) provided 14 mg of N-[4-(4-amino-2-butyl-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)butyl]-4-[[2-(dimethylamino)ethoxy](phenyl)methyl]benzamide as a yellow oil. 1H-NMR (500 MHz, DMSO-d6) δ8.41 (t, J=5.5 Hz, 1H), 7.76 (d, J=8.3 Hz, 2H); 7.43 (d, J=8.3, 2H), 7.37-7.31 (m, 4H), 7.26-7.22 (m, 1H), 5.84 (bs, 2H), 5.52 (s, 1H), 4.22 (t, J=7.7 Hz, 2H), 3.49 (t, J=5.8 Hz, 2H), 3.29 (dd, J=6.4, 12.4 Hz, 2H), 2.76 (t, J=7.7 Hz, 2H), 2.58 (t, J=5.7 Hz, 2H), 2.32 (s, 3H), 2.27 (s, 3H), 2.22 (s, 6H), 1.73-1.65 (m, 4H), 1.61-1.55 (m, 2H), 1.35 (sextet, J=7.4 Hz, 2H), 0.86 (t, J=7.4 Hz, 3H); 13C-NMR (125 MHz, DMSO-d6) δ165.9, 153.0, 148.1, 145.4, 142.0, 138.6, 133.5, 128.23, 127.4, 127.3, 127.1, 126.4, 126.1, 124.5, 103.0, 82.0, 66.3, 58.0, 45.2, 43.6, 38.4, 29.3, 28.8, 26.1, 26.0, 21.7, 21.0, 13.6, 12.2.

Workup

  1. customThe tube was sealed
  2. temperatureThe reaction was cooled to room temperature
  3. extractionextracted with chloroform (3×25 mL)
  4. washThe combined organic fractions were washed with water
  5. dry with materialdried (Na2SO4)
  6. customdecanted
  7. customevaporated
  8. customto provide a yellow oil
  9. customPurification by flash column chromatography (silica gel, 95:5 dichloromethane/methanol gradient to 9:1 dichloromethane/methanol and finally 94:5:1 dichloromethane/methanol/triethylamine)

Sources & evidence

ORD record
ord-bdddf3cfdbe14d3ab1d6f3dd8b5d4e99
Source dataset
uspto-grants-2003_04
Patent number
US06545017B1

Reaction notes

Loading…