m-Chloroperbenzoic acid → HCID 56848627, compound

HRID 473145Notes

Reaction equation

HRID 473145 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](SC)=[N:7][C:8]([C:12]([F:21])([F:20])[C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=3)=[N:9]2)=[CH:4][CH:3]=1.ClC1C=C(C=CC=1)C(OO)=O.[CH3:35][C:36]1[NH:40][N:39]=[C:38]([NH2:41])[CH:37]=1>C(Cl)Cl.C1COCC1>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:41][C:38]3[CH:37]=[C:36]([CH3:35])[NH:40][N:39]=3)=[N:7][C:8]([C:12]([F:21])([F:20])[C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=3)=[N:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 70297m-Chloroperbenzoic acid2×HCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 66609624HCID 66609624, compound

Product 1

HCID 56848627HCID 56848627, compoundYield 3.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To 7-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline (100 mg, 0.25 mmol) in DCM (3 mL) at 0° C. was added 70% meta-chloroperoxybenzoic acid (74 mg, 0.30 mmol) and the mixture was stirred at 0° C. for 80 min. Then additional 70% meta-chloroperoxybenzoic acid (70%, 15 mg, 0.086 mmol) was added and the mixture was stirred at 0° C. for 10 min. The mixture was diluted with DCM (10 mL), washed with saturated aq NaHCO3 (20 mL) and saturated aq sodium thiosulfate (20 mL), dried over Na2SO4 and concentrated under reduced pressure. To the residue (133 mg) at rt was added 5-methyl-1H-pyrazol-3-amine (92 mg, 0.96 mmol) in THF (3 mL). The mixture was stirred for 40 min and then concentrated under reduced pressure. The residue was purified by preparative HPLC (Phenomenex C-18 reverse phase column, eluted with gradient of solvent B=0.05% AcOH/ACN and solvent A=5% ACN/0.05% AcOH/H2O) to afford 7-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine (4.42 mg, 3.1%). 1H NMR (300 MHz, DMSO-d6) δ 12.09-12.33 (m, 1H), 10.73-10.99 (m, 1H), 8.66 (s, 2H), 8.00 (d, J=5.5 Hz, 3H), 7.74-7.87 (m, 1H), 5.95 (br s, 1H), 2.16 (s, 3H); LC-MS (ESI) m/z 449/451 (M+H)+.

Workup

  1. stirringthe mixture was stirred at 0° C. for 10 min
  2. washwashed with saturated aq NaHCO3 (20 mL) and saturated aq sodium thiosulfate (20 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. stirringThe mixture was stirred for 40 min
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative HPLC (Phenomenex C-18 reverse phase column
  8. washeluted with gradient of solvent B=0.05% AcOH/ACN and solvent A=5% ACN/0.05% AcOH/H2O)

Sources & evidence

ORD record
ord-eaa765e51e364d88a2df3f89bc6033ed
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

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