Sodium Hydroxide → N-[4-(diethoxymethyl)benzyl]-N-[(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)methyl]-1H-imidazole-2-carboxamide

HRID 68634Notes

Reaction equation

HRID 68634 reaction equation
[CH2:1]([O:3][CH:4]([O:27][CH2:28][CH3:29])[C:5]1[CH:10]=[CH:9][C:8]([CH2:11][NH:12][CH2:13][C:14]2[N:15]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:16]=[CH:17][N:18]=2)=[CH:7][CH:6]=1)[CH3:2].[NH:30]1[CH:34]=[CH:33][N:32]=[C:31]1[C:35](O)=[O:36].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[OH-].[Na+]>ClCCl>[CH2:1]([O:3][CH:4]([O:27][CH2:28][CH3:29])[C:5]1[CH:6]=[CH:7][C:8]([CH2:11][N:12]([CH2:13][C:14]2[N:15]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:16]=[CH:17][N:18]=2)[C:35]([C:31]2[NH:30][CH:34]=[CH:33][N:32]=2)=[O:36])=[CH:9][CH:10]=1)[CH3:2]

Participants

7

Reactant 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 5743211H-Imidazole-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 671649171-[4-(diethoxymethyl)phenyl]-N-[(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)methyl]methanamine

Product 1

HCID 67164206N-[4-(diethoxymethyl)benzyl]-N-[(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)methyl]-1H-imidazole-2-carboxamideYield 41.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the compound 16 (1.93 g), 1H-imidazole-2-carboxylic acid (773 mg) and diisopropylethylamine (2.97 g) in dichloromethane (15 mL), O-(7-azabenzotriazol-1-yl)N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (2.62 g) was added under ice cooling. The reaction mixture was stirred at room temperature for 4 hours. To the reaction mixture, an aqueous 1N sodium hydroxide solution (30 mL) was added. The aqueous layer was extracted twice with dichloromethane (50 mL). The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and then concentrated. The residue was purified by silica gel chromatography (ethyl acetate:methanol=1:0→10:1) to obtain the title compound (977 mg) having the following physical properties.

Workup

  1. extractionThe aqueous layer was extracted twice with dichloromethane (50 mL)
  2. washThe combined organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography (ethyl acetate:methanol=1:0→10:1)

Sources & evidence

ORD record
ord-d23f21d9a80a41688ce3947f9f4dbf3b
Source dataset
uspto-grants-2014_09
Patent number
US08822459B2

Reaction notes

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