Dimethylformamide → 2-bromo-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246351Notes

Reaction equation

HRID 246351 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.CN(C(ON1N=[N:37][C:32]2[CH:33]=CC=N[C:31]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C=O)C.CC(N)C>O>[Br:1][C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:37][CH:32]([CH3:33])[CH3:31])=[O:13])=[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

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6363IsopropylamineHCID 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 585222792-bromo-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 94%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

2-Bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1.12 g, 3.01 mmol) and HATU (1.37 g, 3.61 mmol) were combined with DMF (5.2 mL) then propan-2-amine (711 mg, 1.03 mL, 12.0 mmol) was added via syringe. The reaction mixture was stirred at 25° C. After 14 h, water (50 mL) was added and the mixture extracted with EtOAc (4×50 mL). The combined organics were washed with water (30 mL), saturated sodium chloride solution (3×20 mL) and dried with MgSO4. Solvents were evaporated and the residue purified by chromatography (silica, 0 to 30% EtOAc in hexanes over 15 min) to yield 2-bromo-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (1.17 g, 2.83 mmol, 94%) as a white solid. MS (M+Na)+=435; 1H NMR (CDCl3) δ: 8.41 (s, 1H), 8.35 (s, 1H), 7.72 (d, J=4.9 Hz, 1H), 5.65 (s, 2H), 4.19-4.45 (m, 1H), 3.41-3.69 (m, 2H), 1.34 (d, J=6.8 Hz, 6H), 0.82-0.97 (m, 2H), −0.13-0.09 (m, 9H).

Workup

  1. extractionthe mixture extracted with EtOAc (4×50 mL)
  2. washThe combined organics were washed with water (30 mL), saturated sodium chloride solution (3×20 mL)
  3. dry with materialdried with MgSO4
  4. customSolvents were evaporated
  5. customthe residue purified by chromatography (silica, 0 to 30% EtOAc in hexanes over 15 min)

Sources & evidence

ORD record
ord-2900e02b2a304c13bd5105db2bacd313
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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