Sodium Thiosulfate → HCID 56848810, compound

HRID 473199Notes

Reaction equation

HRID 473199 reaction equation
[F:1][C:2]([F:25])([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][N:19]=1)[C:3]1[N:12]=[C:11](SC)[C:10]2[C:5](=[CH:6][C:7]([C:15]([NH2:17])=[O:16])=[CH:8][CH:9]=2)[N:4]=1.ClC1C=CC=C(C(OO)=O)C=1.S([O-])([O-])(=O)=S.[Na+].[Na+].C(=O)(O)[O-].[Na+].[CH3:49][C:50]1[NH:54][N:53]=[C:52]([NH2:55])[CH:51]=1>C(Cl)Cl.C1COCC1>[F:1][C:2]([F:25])([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][N:19]=1)[C:3]1[N:12]=[C:11]([NH:55][C:52]2[CH:51]=[C:50]([CH3:49])[NH:54][N:53]=2)[C:10]2[C:5](=[CH:6][C:7]([C:15]([NH2:17])=[O:16])=[CH:8][CH:9]=2)[N:4]=1

Participants

8

Reactant 5

HCID 24477Sodium ThiosulfateHCID 70297m-Chloroperbenzoic acid2×HCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 516892Sodium BicarbonateHCID 66610165HCID 66610165, compound

Product 1

HCID 56848810HCID 56848810, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline-7-carboxamide (203 mg, 0.55 mmol) in DCM (5 mL) at 0° C. was added 3-chloroperbenzoic acid (70%, 205 mg, 0.84 mmol) and the mixture was stirred for 90 min. An additional amount of 3-chloroperbenzoic acid (70%, 68 mg, 0.28 mmol) was then added and the mixture was stirred for 15 min. The mixture was diluted with DCM and then aq sodium thiosulfate was added, followed by saturated aq sodium bicarbonate. The organic layer was separated, dried over sodium sulfate, and concentrated under reduced pressure. To the residue were added THF (5 mL) and 5-methyl-1H-pyrazol-3-amine (160 mg, 1.65 mmol) and the mixture was stirred at rt for 20 min and then concentrated under reduced pressure. The residue was purified by preparative HPLC (Varian diphenyl reverse phase column, eluted with gradient of solvent B=0.05% AcOH/ACN and solvent A=5% ACN/0.05% AcOH/H2O) to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazoline-7-carboxamide (21 mg, 10%). 1H NMR (300 MHz, DMSO-d6) δ ppm 2.19 (s, 3H) 6.04 (s, 1H) 7.69 (s, 1H) 7.97-8.10 (m, 3H) 8.26-8.42 (m, 2H) 8.67 (s, 1H) 8.76 (d, J=8.67 Hz, 1H) 10.85 (br s, 1H) 12.20 (br s, 1H); LC-MS (ESI) m/z 414 (M+H)+.

Workup

  1. stirringthe mixture was stirred for 15 min
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. stirringthe mixture was stirred at rt for 20 min
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative HPLC (Varian diphenyl 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-0850ab2074a94d90a079529b4e8cac69
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

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