m-Chloroperbenzoic acid → HCID 53629045, compound

HRID 422638Notes

Reaction equation

HRID 422638 reaction equation
[Cl:1][C:2]1[C:3]2[N:4]([C:8]([CH:27]3[CH2:30][CH2:29][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.C1C=C(Cl)C=C(C(OO)=[O:39])C=1>C(Cl)CCl>[Cl:1][C:2]1[C:3]2[N:4]([C:8]([CH:27]3[CH2:30][CH2:29][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[O-:39])=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1

Participants

4

Reactant 2

HCID 70297m-Chloroperbenzoic acid2×HCID 53629044HCID 53629044, compound

Product 1

HCID 53629045HCID 53629045, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a cooled (ice-H2O) solution of 7-(8-chloro-3-cyclobutylimidazo[1,5-a]pyrazin-1-yl)-2-phenylquinoline (197 mg, 0.48 mmol) in ClCH2CH2Cl (20 mL) was added mCPBA (97 mg, max 0.43 mmol, max. 77% Aldrich) in one portion. The solution was stirred at the temperature for 30 min and then allowed to warm to rt by removing the cooling bath and stirred at rt (2 h). The reaction mixture was again cooled (ice-H2O) and treated with another portion of mCPBA (107 mg, max 0.48 mmol), stirred for 30 min at the temperature and then overnight at rt (15 h). After that time the crude mixture was filtered through hydromatrix (25 mL) pretreated with 2 M aq NaOH (10 mL). The hydromatrix column was washed with DCM (˜100 mL) and the filtrate was concentrated under reduced pressure. The resultant yellow residue was purified by flash chromatography on silica gel (70 g cartridge, 0→0.75→4% MeOH in DCM) to yield 7-(8-chloro-3-cyclobutylimidazo[1,5-a]pyrazin-1-yl)-2-phenylquinoline 1-oxide as a yellow gum. A cooled (−10° C.) i-PrOH (15 mL) solution of 7-(8-chloro-3-cyclobutylimidazo[1,5-a]pyrazin-1-yl)-2-phenylquinoline 1-oxide (50 mg) in a Parr bomb was saturated with NH3(g) for 3 min. The vessel was sealed and heated at 100-110° C. (bath temperature) for 2 d. The reaction mixture was then cooled to rt, concentrated under reduced pressure and purified by flash chromatography on silica gel (0-4% MeOH+2%˜6 M NH3 in MeOH. A trituration with hexanes (3×) provided the title material as a bright yellow solid; 1H NMR (400 MHz, CDCl3) δ 9.12 (s, 1H), 8.16 (dd, J=8.2 Hz, 1.8 Hz, 1H), 8.04-7.96 (m, 3H), 7.79 (d, J=8.8 Hz, 1H), 7.57-7.43 (m, 4H), 7.16 (d, J=5.2 Hz, 1H), 7.13 (d, J=4.8 Hz, 1H), 5.30 (s, 2H), 3.85 (quintet, J=8.2 Hz, 1H), 2.69-2.60 (m, 2H), 2.55-2.50 (m, 2H), 2.30-2.15 (m, 1H), 2.15-2.00 (m, 1H); MS (ES+): m/z 408.13 (100) [MH+]; HPLC: tR=2.14 min (OpenLynx, polar—5 min).

Workup

  1. customby removing the cooling bath
  2. stirringstirred at rt (2 h)
  3. temperatureThe reaction mixture was again cooled (ice-H2O)
  4. stirringstirred for 30 min at the temperature
  5. customovernight
  6. customat rt
  7. custom(15 h)
  8. filtrationAfter that time the crude mixture was filtered through hydromatrix (25 mL)
  9. washThe hydromatrix column was washed with DCM (˜100 mL)
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe resultant yellow residue was purified by flash chromatography on silica gel (70 g cartridge, 0→0.75→4% MeOH in DCM)

Sources & evidence

ORD record
ord-216f780c7e744c3fb3be08bd909f8b81
Source dataset
uspto-grants-2012_01
Patent number
US08101613B2

Reaction notes

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