Ethyl Acetate → HCID 178508474, compound

HRID 2373917Notes

Reaction equation

HRID 2373917 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@@H:25]3[CH2:28][C@H:27]([O:29][CH2:30][C:31](OC(C)(C)C)=[O:32])[CH2:26]3)=[N:9][C:10]=2[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:12]=2)[CH:5]=[CH:6][N:7]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].CCOC(C)=O>C1COCC1>[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@@H:25]3[CH2:26][C@H:27]([O:29][CH2:30][CH2:31][OH:32])[CH2:28]3)=[N:9][C:10]=2[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:12]=2)[CH:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 21226445Aluminium lithium hydrideHCID 178451374HCID 178451374, compound

Product 1

HCID 178508474HCID 178508474, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

cis-tert-Butyl ({3-[8-amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}oxy)acetate (0.4 mmol, 200 mg) was dissolved in THF (2 mL) and charged with LiAlH4 (4 mmol, 4 mL, 1 M in THF) at −78° C., and stirred under rt for 1 h before the reaction mixture was heated to 50° C. for 16 h. Mixture was charged with EtOAc and allowed to stir at rt for 10 min, followed by an addition of Na2SO4.10H2O. The reaction mixture was passed through a pad of Celite and concentrated under reduced pressure. The crude oil was purified by silica gel column chromatography (Jones Flashmaster, 20 g/70 mL cartridge, eluting with 1-3% MeOH in DCM), yielding the title compound as a colorless oil; NMR 1H NMR (400 MHz, CD3OD) δ 7.47(td, 2H), 7.43-7.42 (m, 1H), 7.39-7.36 (m, 2H), 7.33-7.29 (m, 1H), 7.25 (t, J=2.0 Hz, 1H), 7.19 (td, J=1.2 Hz, 8 Hz, 1H), 7.13 (dd, J=2.4 Hz, 8.0 Hz, 1H), 6.98 (d, J=4.8 Hz, 1H), 5.17 (s, 2H), 4.16 (p, J=7.2 Hz, 1H), 3.66-3.65 (m, 2H), 3.51 (t, J=2.4 Hz, 2H), 3.50-3.43 (m, 1H), 2.88-2.81 (m, 2H), 2.46-2.38 (m, 2H). MS (ES+): m/z 431 (100) [MH+].

Workup

  1. temperaturewas heated to 50° C. for 16 h
  2. stirringto stir at rt for 10 min
  3. concentrationconcentrated under reduced pressure
  4. customThe crude oil was purified by silica gel column chromatography (Jones Flashmaster, 20 g/70 mL cartridge, eluting with 1-3% MeOH in DCM)

Sources & evidence

ORD record
ord-50eb135013d74a5cabfe4f6a7e7e3be9
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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