m-Chloroperbenzoic acid → (R)-2-(6-(8-Chloroisoquinolin-3-ylamino)-3-cyanopyrazin-2-yloxy)-N,N-dimethylpropan-1-amine oxide

HRID 40692Notes

Reaction equation

HRID 40692 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]=[N:9][C:8]([NH:12][C:13]1[N:14]=[C:15]([O:21][C@H:22]([CH3:27])[CH2:23][N:24]([CH3:26])[CH3:25])[C:16]([C:19]#[N:20])=[N:17][CH:18]=1)=[CH:7]2.ClC1C=C(C=CC=1)C(OO)=[O:33]>C(Cl)Cl.O>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]=[N:9][C:8]([NH:12][C:13]1[N:14]=[C:15]([O:21][C@H:22]([CH3:27])[CH2:23][N+:24]([O-:33])([CH3:26])[CH3:25])[C:16]([C:19]#[N:20])=[N:17][CH:18]=1)=[CH:7]2

Participants

5

Reactant 2

HCID 70297m-Chloroperbenzoic acidHCID 442039485-[(8-Chloro-3-isoquinolinyl)amino]-3-{[(2R)-1-(dimethylamino)-2-propanyl]oxy}-2-pyrazinecarbonitrile

Product 1

HCID 86649405(R)-2-(6-(8-Chloroisoquinolin-3-ylamino)-3-cyanopyrazin-2-yloxy)-N,N-dimethylpropan-1-amine oxideYield 73.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

(R)-5-(8-Chloroisoquinolin-3-ylamino)-3-(1-(dimethylamino)propan-2-yloxy)pyrazine-2-carbonitrile (30 mg, 0.078 mmol) was dissolved in DCM (1 mL) and cooled to −10° C. 3-Chloroperoxybenzoic acid (77% wt., 12 mg, 0.086 mmol) dissolved in DCM (1 mL) was added dropwise to the solution. The reaction mixture was stirred at −10° C. for 15 minutes, and was then warmed to room temperature. The reaction mixture was diluted with water, the layers partitioned and the aqueous phase extracted with DCM. The combined organic phases were washed with brine, dried (Na2SO4) and concentrated to dryness. The residue was dissolved in methanol and absorbed on to an SPE (TsOH) cartridge. The cartridge was washed with methanol and the compound eluted with 2 M and 7 M ammonia in methanol. Preparative HPLC afforded the title compound (23 mg, 0.057 mmol, 73%). 1H NMR (d6-DMSO, 400 MHz) δ 9.25 (s, 1H), 8.39 (s, 1H), 8.30 (s, 1H), 8.12 (s, 1H), 7.73-7.71 (m, 1H), 7.57-7.56 (m, 1H), 6.10-6.07 (m, 1H), 4.16-4.10 (m, 1H), 3.77 (br d, 1H, J=14 Hz), 3.43 (s, 3H), 3.28 (s, 3H), 1.44 (d, 3H, J=6.6 Hz). LC-MS (2) Rt=2.20 min; m/z (ESI+) 399 & 401 (M+H).

Workup

  1. additionwas added dropwise to the solution
  2. temperaturewas then warmed to room temperature
  3. customthe layers partitioned
  4. extractionthe aqueous phase extracted with DCM
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated to dryness
  8. dissolutionThe residue was dissolved in methanol
  9. customabsorbed on to an SPE (TsOH) cartridge
  10. washThe cartridge was washed with methanol
  11. washthe compound eluted with 2 M and 7 M ammonia in methanol

Sources & evidence

ORD record
ord-2061007ebe7149fcb41727662e0c372a
Source dataset
uspto-grants-2013_09
Patent number
US08530468B2

Reaction notes

Loading…