Diethyl Malonate → HCID 67113019, compound

HRID 1177482Notes

Reaction equation

HRID 1177482 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][CH:16]([CH2:43]Br)[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[S:25][C:26]3[C:31]([N:32]=2)=[CH:30][CH:29]=[C:28]([C:33]2([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[CH2:35][CH2:34]2)[N:27]=3)=[C:20]([F:42])[CH:19]=1>CN(C=O)C>[F:42][C:20]1[CH:19]=[C:18]([CH2:17][CH:16]2[CH2:43][C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])([C:3]([O:11][CH2:12][CH3:13])=[O:10])[CH2:15]2)[CH:23]=[CH:22][C:21]=1[C:24]1[S:25][C:26]2[C:31]([N:32]=1)=[CH:30][CH:29]=[C:28]([C:33]1([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH2:34][CH2:35]1)[N:27]=2

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 67111732HCID 67111732, compound

Product 1

HCID 67113019HCID 67113019, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a slurry of sodium hydride (0.206 g, 5.14 mmol) in 7 mL DMF was added diethyl malonate (0.690 mL, 4.57 mmol) dropwise via syringe (bubbling). After 3 min, the reaction mixture was clear, and solid 2-(4-(3-bromo-2-(bromomethyl)propyl)-2-fluorophenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine (0.640 g, 1.14 mmol) was added, the reaction mixture was sealed, and heated to 100° C. After 1 h, the reaction mixture was partitioned between sat'd aq. NH4Cl and EtOAc. The org layer was washed with water, brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The resulting material was purified by silica gel chromatography, EA/hexanes gradient, to give diethyl 3-((3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)cyclobutane-1,1-dicarboxylate as a white solid. MS (ESI) m/z: calculated: 558.2; Observed: 559.1 (M++1).

Workup

  1. custom(bubbling)
  2. customthe reaction mixture was sealed
  3. waitAfter 1 h
  4. customthe reaction mixture was partitioned between sat'd aq. NH4Cl and EtOAc
  5. washThe org layer was washed with water, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting material was purified by silica gel chromatography, EA/hexanes gradient

Sources & evidence

ORD record
ord-dc29c273bcb846c7b7e0f46a2ea1a6a2
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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