Hydrogen Peroxide → {3-[8-Amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol

HRID 2373882Notes

Reaction equation

HRID 2373882 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:16]=[C:17]([CH:25]3[CH2:28][CH:27]([CH2:29][OH:30])[CH2:26]3)[N:18]3[CH:23]=[CH:22][N:21]=[C:20](Cl)[C:19]=23)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC1C=C(C2[N:46]=C(C3CC(=C)C3)N3C=CN=C(Cl)C=23)C=CC=1)C1C=CC=CC=1.B1C2CCCC1CCC2.[OH-].[Na+].OO>C1COCC1>[NH2:46][C:20]1[C:19]2[N:18]([C:17]([CH:25]3[CH2:28][CH:27]([CH2:29][OH:30])[CH2:26]3)=[N:16][C:15]=2[C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:10]=2)[CH:23]=[CH:22][N:21]=1

Participants

7

Reactant 5

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 598527401-(3-Benzyloxyphenyl)-8-chloro-3-(3-methylenecyclobutyl)-imidazo[1,5-a]pyrazineHCID 59852798{3-[1-(3-Benzyloxyphenyl)-8-chloro-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol

Product 1

HCID 11406927{3-[8-Amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

{3-[1-(3-Benzyloxyphenyl)-8-chloro-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol: To a solution of 1-(3-benzyloxyphenyl)-8-chloro-3-(3-methylenecyclobutyl)-imidazo[1,5-a]pyrazine (345 mg, 0.86 mmol) in dry THF (5 mL) was added 9-BBN (2.6 mL, 1.3 mmol, 0.5 M in THF) dropwise at 0° C. under nitrogen atmosphere. The temperature was slowly warmed to rt overnight. Upon which time TLC showed the reaction was complete. The mixture was cooled to 0° C., and 2 mL 1N aq. NaOH and 0.4 mL 30% aq. H2O2 were added, the resulting mixture was stirred at 0° C. for 10 min, then rt for 30 min. The resulting white solid was filtered off, the filtrate was diluted with ethyl acetate (60 mL), washed with brine (3×20 mL), and dried over anhydrous sodium sulfate. The filtrate was concentrated under reduced pressure, and the crude material was purified by silica gel column chromatography (eluting with 100% ethyl acetate), yielding the title compound as a yellow viscous oil, a mixture of cis and trans isomers. MS (ES, Pos.): MS (ES, Pos.): m/z 420/422 (3/1) [MH+]. 1H NMR (CDCl3, 400 MHz) δ 2.32 (br s, 1H), 2.60-2.85 (m, 5H), 3.88-4.11 (m, 3H), 5.36 (s, 2H), 7.27 (m, 1H), 7.48-7.69 (m, 9H), 7.77 (d, J=5.0 Hz, 1H).

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. waitrt for 30 min
  3. filtrationThe resulting white solid was filtered off
  4. additionthe filtrate was diluted with ethyl acetate (60 mL)
  5. washwashed with brine (3×20 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe crude material was purified by silica gel column chromatography (eluting with 100% ethyl acetate)

Sources & evidence

ORD record
ord-92e7706d67b74227a9fc88fbb4f14e84
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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