Dibutylamine → 2-Bromo-N,N-dibutyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxamide

HRID 528992Notes

Reaction equation

HRID 528992 reaction equation
[Br:1][C:2]1[N:3]([CH2:10][O:11][CH2:12][CH2:13][Si:14]([CH3:17])([CH3:16])[CH3:15])[CH:4]=[C:5]([C:7]([OH:9])=O)[N:6]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:42]([NH:46][CH2:47][CH2:48][CH2:49][CH3:50])[CH2:43][CH2:44][CH3:45].C(N(C(C)C)CC)(C)C>CN(C=O)C>[Br:1][C:2]1[N:3]([CH2:10][O:11][CH2:12][CH2:13][Si:14]([CH3:17])([CH3:16])[CH3:15])[CH:4]=[C:5]([C:7]([N:46]([CH2:47][CH2:48][CH2:49][CH3:50])[CH2:42][CH2:43][CH2:44][CH3:45])=[O:9])[N:6]=1

Participants

6

Reactant 4

HCID 8148DibutylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 709813012-Bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxylic acid

Product 1

HCID 710622212-Bromo-N,N-dibutyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxamideYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxylic acid (2.4 g, 7.47 mmol) in dry DMF (40 mL) was added HATU (4.26 g, 11.2 mmol), dibutylamine (1.15 g, 8.9 mmol) and diisopropyl ethylamine (2.84 g, 22.4 mmol) successively at 0° C. The reaction mixture was allowed to warm to room temperature over 30 minutes and stirring was continued for 16 h. The reaction mixture was concentrated in vacuo, diluted with EtOAc and washed with water. The organic layer was dried over Na2SO4 and concentrated in vacuo to give crude compound. The crude material was purified by flash chromatography (gradient from 20 to 30% EtOAc/hexanes) to provide the title compound (2.81 g, 87%). 1H NMR (CDCl3) δ 7.68 (s, 1H), 5.28 (s, 2H), 3.89 (t, J=8.0 Hz, 2H), 3.56 (t, J=8.0 Hz, 2H), 3.44 (t, J=8.0 Hz, 2H), 1.57-1.65 (m, 4H), 1.25-1.45 (m, 4H), 0.91-0.95 (m, 8H), 0.01 (s, 9H); MS(ESI+) m/z 434.2 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiondiluted with EtOAc
  3. washwashed with water
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customto give crude compound
  7. customThe crude material was purified by flash chromatography (gradient from 20 to 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e37eb19b446d40e9834d1a402269e4ac
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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