Diethyl Malonate → HCID 67112866, compound

HRID 1177480Notes

Reaction equation

HRID 1177480 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Br[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[S:23][C:24]3[C:29]([N:30]=2)=[CH:28][CH:27]=[C:26]([C:31]2([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[CH2:33][CH2:32]2)[N:25]=3)=[C:18]([F:40])[CH:17]=1>COCCOC>[F:40][C:18]1[CH:17]=[C:16]([CH2:15][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10])[CH:21]=[CH:20][C:19]=1[C:22]1[S:23][C:24]2[C:29]([N:30]=1)=[CH:28][CH:27]=[C:26]([C:31]1([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH2:32][CH2:33]1)[N:25]=2

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 67111838HCID 67111838, compound

Product 1

HCID 67112866HCID 67112866, compound

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a slurry of NaH (0.55 g, 14 mmol) in 40 mL DME under nitrogen was added diethyl malonate (2.1 mL, 14 mmol) slowly dropwise. After addition of 1 mL, the reaction mixture was warm, so cooled to 0° C. and continued addition. To the resulting clear solution was added a slurry of 2-(4-(bromomethyl)-2-fluorophenyl)-5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine (3.00 g, 6.8 mmol) as a solid. After 1 h, the reaction mixture was quenched with sat'd aq. Ammonium chloride and DCM, and the aq. Layer was extracted with DCM, and the combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting oil was purified by silica gel chromatography, 40 g, 0-30% EA/hexanes. Product containing fractions were combined and concentrated and triturated with hexanes to give diethyl 2-((3-fluoro-4-(5-(1-phenyl-cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)malonate as an off-white solid. MS (ESI) m/z: calculated: 518.2; Observed: 519.1 (M++1).

Workup

  1. additionAfter addition of 1 mL
  2. temperaturethe reaction mixture was warm
  3. additionaddition
  4. customthe reaction mixture was quenched with sat'd aq. Ammonium chloride and DCM
  5. extractionthe aq. Layer was extracted with DCM
  6. dry with materialthe combined organics were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting oil was purified by silica gel chromatography, 40 g, 0-30% EA/hexanes
  10. additionProduct containing fractions
  11. concentrationconcentrated
  12. customtriturated with hexanes

Sources & evidence

ORD record
ord-d227c4e311864409a7b512c96c4489d7
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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