Water → (2-bromo-7-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-ylcarbamoyl)-5H-pyrrolo[3,2-b]pyrazin-5-yl)methyl pivalate

HRID 246604Notes

Reaction equation

HRID 246604 reaction equation
[Br:1][C:2]1[N:7]=[C:6]2[C:8]([C:11]([NH:13][C:14]([CH3:25])([CH3:24])[CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])=[O:12])=[CH:9][NH:10][C:5]2=[N:4][CH:3]=1.[C:26]([O:32][CH2:33]Cl)(=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[C:26]([O:32][CH2:33][N:10]1[C:5]2[C:6](=[N:7][C:2]([Br:1])=[CH:3][N:4]=2)[C:8]([C:11](=[O:12])[NH:13][C:14]([CH3:25])([CH3:24])[CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:18])[CH3:19])=[CH:9]1)(=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 87885Chloromethyl pivalateHCID 866779982-Bromo-N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

Product 1

HCID 86677999(2-bromo-7-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-ylcarbamoyl)-5H-pyrrolo[3,2-b]pyrazin-5-yl)methyl pivalateYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of 2-bromo-N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide in DMF (5 mL) was added chloromethyl pivalate (288 mg, 1.92 mmol) followed by K2CO3 (353 mg, 2.56 mmol). The mixture was stirred at room temperature for 16 hours, then poured into water and extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine and dried over Na2SO4. After filtration and concentration, the residue was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (5:1, v/v) to give (2-bromo-7-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-ylcarbamoyl)-5H-pyrrolo[3,2-b]pyrazin-5-yl)methyl pivalate (305 mg, 44% over two steps) as a yellow solid. MS: (M+H)+=541; 1H NMR (300 MHz, CDCl3): δ 8.41 (s, 1H), 8.33 (s, 1H), 7.84 (s, 1H), 6.20 (s, 2H), 3.71 (s, 2H), 1.49 (s, 6H), 1.15 (s, 9H), 0.90 (s, 9H), 0.09 (s, 6H).

Workup

  1. extractionextracted with EtOAc (3×10 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationAfter filtration and concentration
  5. customthe residue was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (5:1

Sources & evidence

ORD record
ord-3acf7c29cab64309a767ee8cc9646bd1
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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