Diisopropylethylamine → 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

HRID 246227

Reaction equation

HRID 246227 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.[CH3:22][O:23][CH2:24][C@@H:25]([NH2:27])[CH3:26].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>CC(=O)OCC.CN(C=O)C>[CH3:22][O:23][CH2:24][C@@H:25]([NH:27][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])[CH3:26]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 70215362-Propanamine, 1-methoxy-, (2S)-HCID 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 866779092-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2.0 g, 5.37 mmol), (S)-1-methoxypropan-2-amine (718 mg, 8.06 mmol), and HATU (4.09 g, 10.7 mmol) were added DMF (20 mL) and DIPEA (3.75 mL, 21.5 mmol) at room temperature under nitrogen atmosphere. The resulting solution was stirred for 15 h at room temperature at which time LCMS analysis and TLC (1:1, Hex:EA, Rf=0.4) system indicated the presence of the desired compound. The reaction was diluted with water (−100 mL), the organic compound was extracted with ethyl acetate (3×50 mL) and the combined extracts were washed with brine solution. After drying over MgSO4, the filtrate was concentrated to obtain the crude light brown solid (−4.1 g) which was purified by chromatography using an ISCO (120 g) column eluting with hexanes (1 min), 0-30% EA in hexanes (2 min), 30-60% EA in hexanes (15 min) to obtain 1.9 g (80%) of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide as a white solid.

Sources & evidence

ORD record
ord-61938d87328b430497c95ad2f3a1a8ee
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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