Sodium hydride → HCID 54691510, compound

HRID 1244086Notes

Reaction equation

HRID 1244086 reaction equation
[H-].[Na+].C([N-]C(C)C)(C)C.[Li+].C([O:13][C:14]([C:16]1[C:20]([C:21]2[CH:26]=[C:25]([CH3:27])[CH:24]=[C:23]([CH3:28])[CH:22]=2)=[CH:19][S:18][C:17]=1[NH:29][C:30](=[O:34])[CH2:31][C:32]#[N:33])=O)C>C1COCC1>[CH3:27][C:25]1[CH:26]=[C:21]([C:20]2[C:16]3[C:14]([OH:13])=[C:31]([C:32]#[N:33])[C:30](=[O:34])[NH:29][C:17]=3[S:18][CH:19]=2)[CH:22]=[C:23]([CH3:28])[CH:24]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2724682Lithium diisopropylamide2×HCID 69607388HCID 69607388, compound

Product 1

HCID 54691510HCID 54691510, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of either NaH (60% suspension in mineral oil, pre washed with hexanes, 0.25 g, 6.2 mmol) held at room temperature or Lithium diisopropylamide (LDA, 2M solution in THF, 11.3 mmol, 5.6 mL) held at −78° C. in THF (30 mL) was added a solution of 2-(2-cyano-acetylamino)-4-(3,5-dimethyl-phenyl)-thiophene-3-carboxylic acid ethyl ester (0.968 g, 2.83 mmol) in THF (15 mL) dropwise via syringe over 10 minutes. The mixture was stirred at room temperature for 5 hours (or in the case of LDA, allowed to warm to room temperature over 16 hours), cooled to 0° C. and then quenched by dropwise addition of MeOH (5 mL) followed by 1N HCl to adjust the pH <3. The resultant slurry was filtered and the solid was washed with water (4×4 mL), ether (3×4 mL) and (Na2SO4), filtered and concentrated under reduced pressure to provide the target compound. The filtrate was concentrated and purified on a RP-HPLC system to provide additional compound. MS (ESI) m/e 295 (M−H)+; 1H NMR (300 MHz, MeOH-d4): δ ppm 12.53 (br s, 1H), 7.04 (s, 2H), 6.99 (s, 1H), 6.90 (s, 1H), 2.32 (s, 6H).

Workup

  1. customheld at room temperature
  2. temperaturecooled to 0° C.
  3. customquenched by dropwise addition of MeOH (5 mL)
  4. filtrationThe resultant slurry was filtered
  5. washthe solid was washed with water (4×4 mL), ether (3×4 mL) and (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto provide the target compound
  9. concentrationThe filtrate was concentrated
  10. custompurified on a RP-HPLC system
  11. customto provide additional compound

Sources & evidence

ORD record
ord-929911f541fe43f0adcf05d7c2864d15
Source dataset
uspto-grants-2006_10
Patent number
US07119205B2

Reaction notes

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