Ethyl Acetate → HCID 11418161, compound

HRID 2373910Notes

Reaction equation

HRID 2373910 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]3[N:19]=[C:20]([CH:28]4[CH2:31][CH2:30][CH2:29]4)[N:21]4[CH:26]=[CH:25][N:24]=[C:23]([NH2:27])[C:22]=34)[CH:13]=2)[CH:5]=1.C(OCC)(=O)C>C1COCC1>[NH2:27][C:23]1[C:22]2[N:21]([C:20]([CH:28]3[CH2:31][CH2:30][CH2:29]3)=[N:19][C:18]=2[C:14]2[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=2)[O:11][CH2:10][C:6]2[CH:5]=[C:4]([CH2:3][OH:2])[CH:9]=[CH:8][CH:7]=2)[CH:26]=[CH:25][N:24]=1

Participants

4

Reactant 2

HCID 8857Ethyl AcetateHCID 11774683HCID 11774683, compound

Product 1

HCID 11418161HCID 11418161, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-[3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenoxymethyl]-benzoic acid methyl ester (600 mg, 1.40 mmol) in THF was cooled to −78° C. in an acetone/dry ice bath for 5.0 min. The reaction was purged with nitrogen and charged dropwise with 1M lithium aluminum hydride (LAH) (1.40 mL). After all the LAH was added, the solution was removed from the bath and allowed to warm to room temperature (rt). As the solution warmed, a white solid formed on the sides of the flask. The reaction mixture was then charged with ethyl acetate, Na2SO4.10H2O and silica. This solution was then concentrated in vacuo to a solid, and was chromatographed on silica gel [Jones Flashmaster, 50 g cartridge, eluting with 2% NH3 in MeOH:CH2Cl2] to yield the title compound as a white solid; 1H NMR (CDCl3, 400 MHz) δ 1.99-2.07 (m, 1H), 2.11-2.22 (m, 1H), 2.44-2.52 (m, 2H), 2.58-2.68 (m, 2H), 3.76-3.84 (m, 1H), 4.69 (s, 2H), 5.16 (s, 2H), 6.98 (d, J=13.2 Hz, 1H), 7.02-7.05 (m, 1H), 7.08 (d, J=4.8 Hz, 1H), 7.16-7.17 (m, 1H), 7.25-7.28 (m, 1H), 7.35-7.43 (m, 5H); MS (ES+): m/z 401.19 (100) [MH+].

Workup

  1. customThe reaction was purged with nitrogen
  2. additioncharged dropwise with 1M lithium aluminum hydride (LAH) (1.40 mL)
  3. additionAfter all the LAH was added
  4. customthe solution was removed from the bath
  5. temperatureAs the solution warmed
  6. customa white solid formed on the sides of the flask
  7. concentrationThis solution was then concentrated in vacuo to a solid
  8. customwas chromatographed on silica gel [Jones Flashmaster, 50 g cartridge, eluting with 2% NH3 in MeOH:CH2Cl2]

Sources & evidence

ORD record
ord-4e3764a8cc964988b1c6deffdb7efa93
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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