Tert-Butylamine → 2-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246289

Reaction equation

HRID 246289 reaction equation
[Br:1][C:2]1[N:3]=[C:4]2[C:10]([C:11]([OH:13])=O)=[CH:9][N:8]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:5]2=[N:6][CH:7]=1.[C:22]([NH2:26])([CH3:25])([CH3:24])[CH3:23].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:22]([NH:26][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([Br:1])[N:3]=2)[N:8]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[CH:9]=1)=[O:13])([CH3:25])([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 6385Tert-ButylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 584385252-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 100 ml round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1.00 g, 2.69 mmol) was dissolved in DMF (6 ml). tert-Butylamine (1.7 ml, 16.2 mmol) was added followed by HATU (1.12 g, 2.95 mmol). The yellow suspension was stirred at room temperature for 72 h then quenched with water and extracted with a mixture of diethyl ether and EtOAc. The organic layers were washed twice with water and once with brine then combined, dried over sodium sulfate, filtered and concentrated. The residue was triturated with petroleum ether to afford 989 mg (86%) of 2-bromo-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as an off-white powder. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.40 (s, 1H), 8.31 (s, 1H), 7.86 (s, 1H), 5.65 (s, 2H), 3.46-3.58 (m, 2H), 1.54 (s, 9H), 0.84-0.98 (m, 2H), −0.04 (s, 9H).

Workup

  1. customthen quenched with water
  2. extractionextracted with a mixture of diethyl ether and EtOAc
  3. washThe organic layers were washed twice with water and once with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was triturated with petroleum ether

Sources & evidence

ORD record
ord-ce4a741d740c415c80583333c34d1205
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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