Sodium hydride → HCID 68312811, compound

HRID 1530709Notes

Reaction equation

HRID 1530709 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:61])[C:50](Br)([CH2:56][CH:57]([CH3:59])[CH3:58])[C:51]([O:53][CH2:54][CH3:55])=[O:52])[CH3:47]>CN(C=O)C>[CH2:46]([O:48][C:49](=[O:61])[C:50]([CH2:56][CH:57]([CH3:59])[CH3:58])([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:51]([O:53][CH2:54][CH3:55])=[O:52])[CH3:47]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 68312705HCID 68312705, compoundHCID 86671481HCID 86671481, compound

Product 1

HCID 68312811HCID 68312811, compoundYield 51%

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 (465 mg, 1.429 mmol) in DMF (8 mL) was added sodium hydride (57.2 mg, 60% in oil, 1.429 mmol). The mixture was stirred at RT for 15 min, then a solution of 2-bromo-2-isobutylmalonic acid diethyl ester (633 mg, 2.14 mmol) in DMF (1 mL) was added. The reaction mixture was stirred at 70° C. for 4 h. The cooled reaction mixture was partitioned between water and EtOAc. The aqueous phase was extracted with EtOAc. The combined organic phases 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 (0.39 g, 51%). LCMS (Method B): RT 3.96 min [M+H]+ 540.

Workup

  1. stirringThe reaction mixture was stirred at 70° C. for 4 h
  2. customThe cooled reaction mixture
  3. customwas partitioned between water and EtOAc
  4. extractionThe aqueous phase was extracted with EtOAc
  5. washThe combined organic phases were washed with water
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 2-10% MeOH in DCM)

Sources & evidence

ORD record
ord-fa8fd87d0dd94bbfbc6f98c54271e1d8
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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