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

HRID 245869Notes

Reaction equation

HRID 245869 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.Cl.[CH3:23][O:24][CH2:25][C@@H:26]([NH2:28])[CH3:27].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O.CN(C=O)C>[CH3:23][O:24][CH2:25][C@@H:26]([NH:28][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])[CH3:27]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 54596079(S)-1-methoxypropan-2-amine hydrochlorideHCID 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)-amideYield 90.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

In a round-bottomed flask were combined 2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (120 mg, 0.32 mmol) and (S)-1-methoxypropan-2-amine hydrochloride (61 mg, 0.49 mmol). DMF (1.5 mL) was added followed by N,N-diisopropylethylamine (0.15 mL, 0.86 mmol) and HATU (135 mg, 0.36 mmol). The yellow reaction mixture was stirred at room temperature overnight then water was added. The resulting suspension was filtered and the filter cake was washed with water and petroleum ether then dried under high vacuum to provide 129 mg (90%) of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide as an off-white powder.

Workup

  1. customIn a round-bottomed flask were combined
  2. filtrationThe resulting suspension was filtered
  3. washthe filter cake was washed with water and petroleum ether
  4. customthen dried under high vacuum

Sources & evidence

ORD record
ord-03920af917dd49acad8e1aae70f45c75
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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