Oxolane--water (1/1) → 3-(8-Chloro-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl)cyclobutanone

HRID 422705Notes

Reaction equation

HRID 422705 reaction equation
[Cl:1][C:2]1[C:3]2[N:4]([C:8]([CH:27]3[CH2:30][C:29](CO)([OH:31])[CH2:28]3)=[N:9][C:10]=2[C:11]2[CH:20]=[C:19]3[C:14]([CH:15]=[CH:16][C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1.C1COCC1.O>CCOC(C)=O>[Cl:1][C:2]1[C:3]2[N:4]([C:8]([CH:27]3[CH2:28][C:29](=[O:31])[CH2:30]3)=[N:9][C:10]=2[C:11]2[CH:20]=[C:19]3[C:14]([CH:15]=[CH:16][C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1

Participants

4

Reactant 2

HCID 21881883Oxolane--water (1/1)HCID 536290393-[8-Chloro-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-(hydroxymethyl)cyclobutanol

Product 1

HCID 469372693-(8-Chloro-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl)cyclobutanone

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-[8-chloro-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-(hydroxymethyl)cyclobutanol (7.6 mmol) in a THF-water mixture (200 mL, 3:1) was added NaIO4 (1.95 g, 9.2 mmol) at 0° C. The reaction mixture was slowly warmed to rt and stirred for 4 h. The reaction mixture was diluted with EtOAc (200 mL) and washed with brine (2×75 mL). The organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (Jones Flashmaster, 70 g/150 mL cartridge), eluting with 1:9 EtOAc/Hex→1:1 EtOAc/Hex to afford the desired product as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 3.70-3.62 (m, 2H), 3.94-3.85 (m, 3H), 7.56-7.45 (m, 4H), 7.64 (d, J=5.2, 1H), 7.94-7.89 (m, 3H), 8.20-8.18 (m, 2H), 8.28 (dd, J=0.4 Hz, 8.4 Hz, 1H), 8.52 (t, J=0.8 Hz, 1H). MS (ES+): m/z 425/427 (3/1) [MH+]. HPLC: tR=3.7 min (Mass Directed purification system polar 5 min method).

Workup

  1. washwashed with brine (2×75 mL)
  2. dry with materialThe organic phase was dried over anhydrous Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by silica gel chromatography (Jones Flashmaster, 70 g/150 mL cartridge)
  5. washeluting with 1:9 EtOAc/Hex→1

Sources & evidence

ORD record
ord-56a8846f5abb41ffb2570222a0a14887
Source dataset
uspto-grants-2012_01
Patent number
US08101613B2

Reaction notes

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