2-Amino-2-methyl-1-propanol → 2-Bromo-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 522945Notes

Reaction equation

HRID 522945 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.[NH2:22][C:23]([CH3:27])([CH3:26])[CH2:24][OH:25].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CCOC(C)=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.CN(C=O)C>[Br:1][C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:22][C:23]([CH3:27])([CH3:26])[CH2:24][OH:25])=[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

8

Reactant 4

HCID 118072-Amino-2-methyl-1-propanolHCID 81531DiisopropylethylamineHCID 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 715756472-Bromo-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 82%

Reagents, catalysts & solvents 3

HCID 311Citric AcidSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2 g, 5.37 mmol), 2-amino-2-methylpropan-1-ol (575 mg, 6.45 mmol) and HATU (2.25 g, 5.91 mmol) was added DIPEA (2.08 g, 2.81 mL, 16.1 mmol) and DMF (18 mL). The mixture was stirred at room temperature for 16 h then was diluted with EtOAc and 10% citric acid. The phases were separated and the organic phase was then washed successively with 10% citric acid, NaHCO3 and brine. The organic phase was dried (MgSO4), filtered and purified by chromatography (silica, 20-60% ethyl acetate in hexanes) to give 2-bromo-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (1.95 g, 4.4 mmol, 82%) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm: 8.47 (s, 1H), 8.34 (s, 1H), 8.13 (s, 1H), 5.69 (s, 2H), 3.78 (s, 2H), 3.57 (t, J=8.4 Hz, 3H), 1.52 (s, 60.96 (t, J=8.4 Hz, 3H), 0.00 (s, 9H).

Workup

  1. customThe phases were separated
  2. washthe organic phase was then washed successively with 10% citric acid, NaHCO3 and brine
  3. dry with materialThe organic phase was dried (MgSO4)
  4. filtrationfiltered
  5. custompurified by chromatography (silica, 20-60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-c192b3c40e1b46779e029704285b3abd
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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