Sodium hydride → 4-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-1,4-dihydropyrido[2,3-b]pyrazin-3(2H)-one

HRID 420688Notes

Reaction equation

HRID 420688 reaction equation
[H-].[Na+].[CH3:3][C:4]([Si:7]([CH3:37])([CH3:36])[O:8][CH2:9][C@@H:10]([NH:20][C:21]1[C:26]([NH:27][CH2:28][C:29](OCC)=[O:30])=[CH:25][CH:24]=[C:23]([O:34][CH3:35])[N:22]=1)[CH2:11][O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([CH3:6])[CH3:5]>C1COCC1>[CH3:3][C:4]([Si:7]([CH3:36])([CH3:37])[O:8][CH2:9][C@@H:10]([N:20]1[C:29](=[O:30])[CH2:28][NH:27][C:26]2[CH:25]=[CH:24][C:23]([O:34][CH3:35])=[N:22][C:21]1=2)[CH2:11][O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([CH3:6])[CH3:5]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 58001773ethyl N-[2-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)amino]-6-(methyloxy)-3-pyridinyl]glycinate

Product 1

HCID 666584654-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-1,4-dihydropyrido[2,3-b]pyrazin-3(2H)-oneYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of NaH (50.5 g, 57-63% dispersion in mineral oil, 1.26 mol) in THF (8.5 L) was added ethyl N-[2-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)amino]-6-(methyloxy)-3-pyridinyl]glycinate (577.8 g, 1.147 mol) at −5° C. When the addition was complete the mixture was warmed to room temperature and stirred for 30 min. The reaction was quenched by the addition of saturated aqueous NH4Cl (610 ml) and the mixture was stirred for 10 min. Na2SO4 (1 kg) was added and the mixture was stirred for 10 min before being filtered through celite. The filter cake was washed with EtOAc (5 L). The filtrate was evaporated and the dark purple oil was purification by column chromatography and mixtures of heptane and EtOAc as eluent to give 477 g (91%) of 4-((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)-6-(methyloxy)-1,4-dihydropyrido[2,3-b]pyrazin-3(2H)-one as a viscous purple oil.

Workup

  1. additionWhen the addition
  2. customThe reaction was quenched by the addition of saturated aqueous NH4Cl (610 ml)
  3. stirringthe mixture was stirred for 10 min
  4. additionNa2SO4 (1 kg) was added
  5. stirringthe mixture was stirred for 10 min
  6. filtrationbefore being filtered through celite
  7. washThe filter cake was washed with EtOAc (5 L)
  8. customThe filtrate was evaporated
  9. custompurification by column chromatography and mixtures of heptane and EtOAc as eluent

Sources & evidence

ORD record
ord-9e9b5ec36c7e4d20b10485ce69075b7f
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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