Sodium borohydride → 3-(8-Chloro-1-iodoimidazo[1,5-a]pyrazin-3-yl)cyclobutanol

HRID 1028813Notes

Reaction equation

HRID 1028813 reaction equation
[Cl:1][C:2]1[C:3]2[N:4]([C:8]([CH:12]3[CH2:15][C:14](=[O:16])[CH2:13]3)=[N:9][C:10]=2[I:11])[CH:5]=[CH:6][N:7]=1.[BH4-].[Na+]>CO.C(Cl)Cl>[Cl:1][C:2]1[C:3]2[N:4]([C:8]([CH:12]3[CH2:13][CH:14]([OH:16])[CH2:15]3)=[N:9][C:10]=2[I:11])[CH:5]=[CH:6][N:7]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 16743592HCID 16743592, compound

Product 1

HCID 576809873-(8-Chloro-1-iodoimidazo[1,5-a]pyrazin-3-yl)cyclobutanol

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

3-(8-Chloro-1-iodo-imidazo[1,5-a]pyrazin-3-yl)-cyclobutanone (5.0 g, 14 mmol) was dissolved in a 1:1 mixture of methanol (35.0 mL) and CH2Cl2 (35.0 mL). To the solution mixture sodium tetrahydroborate (560 mg, 14.0 mmol) was added slowly, gas evolution was observed. After 4.5 h at rt under nitrogen, the reaction was concentrated in vacuo. The crude mix was dissolved in EtOAc and washed with water. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified using HPFC Jones 50 gram silica gel column eluting with 50% EtOAc: Hex to 100% EtOAc, to yield the title compound as a light yellow solid; MS (ES+): m/z 349.81 (100) [MH+], 351.50 (30) [MH+++]; HPLC: tR=2.49 min (OpenLynx, polar—5 min); 1H NMR (CDCl3, 400 MHz) δ 2.41-2.54 (m, 2H) 2.78-3.05 (m, 1H) 3.12-3.32 (m, 1H) 4.08-4.75 (m, 1H) 5.30 (s, 1H) 7.31 (d, J=5.05 Hz, 1H) 7.57 (d, J=4.80 Hz, 1H)

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. additionThe crude mix
  3. dissolutionwas dissolved in EtOAc
  4. washwashed with water
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified
  9. washeluting with 50% EtOAc

Sources & evidence

ORD record
ord-9ba6273fe4324ce7a0683385375e762f
Source dataset
uspto-grants-2014_05
Patent number
US08735405B2

Reaction notes

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