Hydrochloric Acid → 8-Butyl-2-(2-methoxyphenyl)-5,6,7,8-tetrahydro-imidazo[1,2-a]pyrazine

HRID 6767Notes

Reaction equation

HRID 6767 reaction equation
[CH2:1]([C:5]1[C:6]2[N:7]([CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[O:21][CH3:22])[N:14]=2)[CH2:8][C:9](=O)[N:10]=1)[CH2:2][CH2:3][CH3:4].Cl.C([O-])([O-])=O.[K+].[K+]>C1COCC1>[CH2:1]([CH:5]1[NH:10][CH2:9][CH2:8][N:7]2[CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[O:21][CH3:22])[N:14]=[C:6]12)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 220168358-Butyl-6-oxo-2-(2-methoxyphenyl)-imidazo[1,2-a]pyrazine

Product 1

HCID 220168108-Butyl-2-(2-methoxyphenyl)-5,6,7,8-tetrahydro-imidazo[1,2-a]pyrazineYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The product from Step 1.e. (6.13 g, 20.5 mmol) (compound vi where R3 is n-butyl, R4 is 2-methoxyphenyl, and R5 and R6 are H) was dissolved in THF (100 ml) and treated with 1M BH3H/TF (82.0 ml, 82.0 mmol) at room temperature for about 2 hours and then refluxed for about 3 hours. The mixture was cooled to room temperature and 4N HCl (50 ml) was added dropwise. The mixture was stirred at room temperature for about 2 hours then made basic by careful portionwise addition of solid K2CO3. Product was extracted with EtOAc (3×50 ml). The EtOAc layers were combined, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was dissolved in MeOH (about 50 ml), concentrated HCl (1.75 ml) was added and the solution was again concentrated under reduced pressure. The product was crystallized from MeOH/Et2O to yield 6.76 g (92%) of the desired product. Mass spec. 286.3 MH+, NMR (300 MHz DMSO-d6, 30° C.) 10.0–11.5 (2H, s broad), 8.05–8.15 (1H, d,d), 8.0–8.1 (1H, s), 7.35–7.5 (1H, t), 7.15–7.3 (1H, d), 7.0–7.15 (1H, t), 4.8–4.95 (1H, m), 4.4–4.65 (2H, m), 3.9–4.0 (3H, s), 3.65–3.8 (1H, m), 3.5–3.65 (1H, m), 2.45–2.65 (1H, m), 2.1–2.35 (1H, m), 1.5–1.7 (2H, m), 1.25–1.5 (2H, m), 0.85–1.0 (3H, t).

Workup

  1. additiontreated with 1M BH3H/TF (82.0 ml, 82.0 mmol) at room temperature for about 2 hours
  2. temperaturerefluxed for about 3 hours
  3. extractionProduct was extracted with EtOAc (3×50 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in MeOH (about 50 ml)
  8. additionconcentrated HCl (1.75 ml) was added
  9. concentrationthe solution was again concentrated under reduced pressure
  10. customThe product was crystallized from MeOH/Et2O

Sources & evidence

ORD record
ord-385bbc0308b1431c9eb6627be4f10839
Source dataset
uspto-grants-2006_08
Patent number
US07084135B1

Reaction notes

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