Sodium hydride → HCID 68312845, compound

HRID 1530688Notes

Reaction equation

HRID 1530688 reaction equation
C(OC(N1CCC(C([O:20][C:21]2[CH:43]=[CH:42][C:24]3[C:25]4[N:29]([CH2:30][CH2:31][O:32][C:23]=3[CH:22]=2)[CH:28]=[C:27]([C:33]2[N:34]([CH:39]([CH3:41])[CH3:40])[N:35]=[C:36]([CH3:38])[N:37]=2)[N:26]=4)CC)CC1)=O)C1C=CC=CC=1.[H-].[Na+].[CH2:46]([O:48][C:49](=[O:63])[C:50](Br)([C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[C:51]([O:53][CH2:54][CH3:55])=[O:52])[CH3:47]>CN(C=O)C>[CH2:46]([O:48][C:49](=[O:63])[C:50]([O:20][C:21]1[CH:43]=[CH:42][C:24]2[C:25]3[N:29]([CH2:30][CH2:31][O:32][C:23]=2[CH:22]=1)[CH:28]=[C:27]([C:33]1[N:34]([CH:39]([CH3:41])[CH3:40])[N:35]=[C:36]([CH3:38])[N:37]=1)[N:26]=3)([C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[C:51]([O:53][CH2:54][CH3:55])=[O:52])[CH3:47]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 12491978HCID 12491978, compoundHCID 68312705HCID 68312705, compound

Product 1

HCID 68312845HCID 68312845, compoundYield 76.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-ol from Example 4 (300 mg, 0.922 mmol) in DMF (3 mL) was added sodium hydride (37 mg, 60% in oil, 0.925 mmol). The mixture was stirred at RT for 15 min, then a solution of 2-bromo-2-phenylmalonic acid diethyl ester (435 mg, 1.38 mmol) in DMF (0.5 mL) was added. The reaction mixture was stirred at RT for 30 min, and then at 90° C. for 2 h. The cooled reaction mixture was partitioned between water and EtOAc. The aqueous phase was extracted with EtOAc and the combined organic layers were washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-10% MeOH in DCM) affording the title compound as a colourless gum (0.3933 g, 76%). LCMS (Method J): RT 3.73 min [M+H]+ 560

Workup

  1. stirringThe reaction mixture was stirred at RT for 30 min
  2. waitat 90° C. for 2 h
  3. customThe cooled reaction mixture
  4. customwas partitioned between water and EtOAc
  5. extractionThe aqueous phase was extracted with EtOAc
  6. washthe combined organic layers were washed with water
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 2-10% MeOH in DCM)

Sources & evidence

ORD record
ord-780611dc580b4f1e8cdbec3befd9129e
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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