Hydrochloric Acid → (1 aS,5aS)-2-(4-cyano-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid

HRID 1624025Notes

Reaction equation

HRID 1624025 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[C:15]3[C@H:14]4[CH2:16][C@H:13]4[CH2:12][C:11]=3[C:10]([C:17]([OH:19])=[O:18])=[N:9]2)[CH:3]=1.[H-].[Na+].O.Cl.C[C:25]([N:27](C)C)=O>[C-]#N.[Zn+2].[C-]#N>[C:25]([C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[C:15]3[C@H:14]4[CH2:16][C@H:13]4[CH2:12][C:11]=3[C:10]([C:17]([OH:19])=[O:18])=[N:9]2)[CH:3]=1)#[N:27]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 24758Sodium hydrideHCID 31374DimethylacetamideHCID 68182378(1 aS,5aS)-2-(4-Bromo-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid

Product 1

HCID 68182462(1 aS,5aS)-2-(4-cyano-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst

Conditions

Temperature
120 °C

Procedure

(1aS,5aS)-2-(4-Bromo-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (0.87 g, 2.72 mmol) was dissolved in DMA (10 mL). Sodium hydride (0.109 g, 2.72 mmol) was added, and nitrogen was bubbled through the mixture for 10 min. Zinc(II) cyanide (0.638 g, 5.44 mmol) and palladium tetrakistriphenylphosphine, (0.157 g, 0.136 mmol) were added. The reaction was stirred under microwave heating in a sealed tube at 120° C. for 2 h. Water (25 mL) and 6 M aqueous HCl (1 mL) were added. The mixture was extracted with 25% iPrOH/dichloromethane (3×25 mL) (The biphasic mixture was filtered after the first extraction to clear up an emulsion). The combined organic extracts were dried (MgSO4), filtered, then concentrated. The residue was purified by flash chromatography to give the title compound (0.68 g) as a tan solid. LCMS m/z=267.0 [M+H]+.

Workup

  1. customnitrogen was bubbled through the mixture for 10 min
  2. extractionThe mixture was extracted with 25% iPrOH/dichloromethane (3×25 mL) (The biphasic mixture
  3. filtrationwas filtered
  4. extractionafter the first extraction
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-5cd5ed6fd7e54041a2d64005eefbd96c
Source dataset
uspto-grants-2014_07
Patent number
US08778950B2

Reaction notes

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