m-Chloroperbenzoic acid → HCID 56848631, compound

HRID 473148Notes

Reaction equation

HRID 473148 reaction equation
[CH:1]1([C:4]2[CH:13]=[C:12]3[C:7]([C:8](SC)=[N:9][C:10]([C:14]([F:23])([F:22])[C:15]4[CH:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=4)=[N:11]3)=[CH:6][CH:5]=2)[CH2:3][CH2:2]1.ClC1C=C(C=CC=1)C(OO)=O.[CH3:37][C:38]1[NH:42][N:41]=[C:40]([NH2:43])[CH:39]=1>C(Cl)Cl.C1COCC1>[CH:1]1([C:4]2[CH:13]=[C:12]3[C:7]([C:8]([NH:43][C:40]4[CH:39]=[C:38]([CH3:37])[NH:42][N:41]=4)=[N:9][C:10]([C:14]([F:23])([F:22])[C:15]4[CH:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=4)=[N:11]3)=[CH:6][CH:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 70297m-Chloroperbenzoic acidHCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 66609573HCID 66609573, compound

Product 1

HCID 56848631HCID 56848631, compoundYield 8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To 7-cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline from Step A (137 mg, 0.378 mmol) in DCM (5 mL) at 0° C. was added 70% meta-chloroperoxybenzoic acid (139 mg, 0.567 mmol). The mixture was stirred for at 0° C. for 20 min, then DCM (15 mL) was added and the mixture was washed with saturated aq NaHCO3 (20 mL) and saturated aq sodium thiosulfate (20 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. To the residue was added 5-methyl-1H-pyrazol-3-amine (0.107 g, 1.01 mmol) in THF (5 mL) and the mixture was stirred at room temperature for 40 min and then concentrated under reduced pressure. The residue was purified by reverse phase HPLC (Phenomenex C-18 reverse phase column, eluted with gradient of solvent B=0.05% AcOH/CH3CN and solvent A=0.05% aq AcOH) to afford 7-cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine (12 mg, 8%) 1H NMR (300 MHz, DMSO-d6) δ 12.07-12.19 (m, 1H), 10.51-10.63 (m, 1H), 8.66 (s, 1H), 8.54 (d, J=8.7 Hz, 1H), 7.94-8.04 (m, 2H), 7.51 (s, 1H), 7.36 (d, J=8.7 Hz, 1H), 5.97 (s, 1H), 2.10-2.21 (m, 4H), 1.09 (dd, J=2.3, 8.1 Hz, 2H), 0.87-0.94 (m, 2H); LC-MS (ESI) m/z 411 (M+H)+

Workup

  1. washthe mixture was washed with saturated aq NaHCO3 (20 mL) and saturated aq sodium thiosulfate (20 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. stirringthe mixture was stirred at room temperature for 40 min
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by reverse phase HPLC (Phenomenex C-18 reverse phase column
  7. washeluted with gradient of solvent B=0.05% AcOH/CH3CN and solvent A=0.05% aq AcOH)

Sources & evidence

ORD record
ord-93bb0ff9931f453da1a7071eb3d6c520
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

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