Hydrochloric Acid → HCID 58314014, compound

HRID 2036979Notes

Reaction equation

HRID 2036979 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-9f4d99c2f28e4546b23ea911539fc318
Source dataset
uspto-grants-2013_11
Patent number
US08575177B2

Reaction notes

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