Hydrochloric Acid → HCID 58314014, compound

HRID 624760Notes

Reaction equation

HRID 624760 reaction equation
O(Cl)Cl.[P+5].[Br:5][C:6]1[N:7]=[C:8]([NH:15][CH:16]2[CH2:18][CH2:17]2)[C:9]2[N:10]([CH:12]=[CH:13][N:14]=2)[CH:11]=1.Cl.[OH-].[Na+].CN([CH:25]=[O:26])C>>[Br:5][C:6]1[N:7]=[C:8]([NH:15][CH:16]2[CH2:18][CH2:17]2)[C:9]2[N:10]([C:12]([CH:25]=[O:26])=[CH:13][N:14]=2)[CH:11]=1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 6228Dimethylformamide2×HCID 14798Sodium HydroxideHCID 58314000HCID 58314000, compoundHCID 178479711HCID 178479711, compound

Product 1

HCID 58314014HCID 58314014, compoundYield 49%

Conditions

Temperature
0 °C

Procedure

Phosphorus(V) oxychloride (3.9 mL, 42.68 mmol) was added dropwise to anhydrous DMF (16 mL) at 0° C. 6-bromo-N-cyclopropylimidazo[1,2-a]pyrazin-8-amine (900 mg, 3.56 mmol) was dissolved in anhydrous DMF (24 mL) and added over two minutes. The solution was place in an 85° C. oil bath for 5 h. The solution was cooled to 0° C. and conc. HCl (30 mL) was added. The mixture was basified to pH=10 w/3N NaOH (˜175 mL). The mixture was extracted with dichloromethane (3×250 mL), and the organics were washed with brine (500 mL). The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified via flash column chromatography (30% EtOAc/hexanes) to furnish 6-bromo-8-(cyclopropylamino)imidazo[1,2-a]pyrazine-3-carbaldehyde (490 mg, 49%). LCMS (ES): >95% pure, m/z 282 [M+1]+.

Workup

  1. additionadded over two minutes
  2. customin an 85° C.
  3. customfor 5 h
  4. extractionThe mixture was extracted with dichloromethane (3×250 mL)
  5. washthe organics were washed with brine (500 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified via flash column chromatography (30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-cd41ae5ed77d46f7a850a162be8592d7
Source dataset
uspto-grants-2016_04
Patent number
US09303033B2

Reaction notes

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