Sodium Thiosulfate → HCID 178517773, compound

HRID 473217Notes

Reaction equation

HRID 473217 reaction equation
[CH:1]1([C:4]2[CH:5]=[CH:6][CH:7]=[C:8]3[C:13]=2[N:12]=[C:11]([C:14]([F:23])([F:22])[C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=2)[N:10]=[C:9]3SC)[CH2:3][CH2:2]1.ClC1C=CC=C(C(OO)=[O:34])C=1.S([O-])([O-])(=O)=S.[Na+].[Na+].C(=O)(O)[O-].[Na+].CC1NN=C(N)C=1>C(Cl)Cl.C1COCC1>[CH:1]1([C:4]2[CH:5]=[CH:6][CH:7]=[C:8]3[C:13]=2[N:12]=[C:11]([C:14]([F:23])([F:22])[C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=2)[N:10]=[C:9]3[OH:34])[CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 24477Sodium ThiosulfateHCID 70297m-Chloroperbenzoic acidHCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 516892Sodium BicarbonateHCID 666098168-Cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline

Product 1

HCID 178517773HCID 178517773, compoundYield 88.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To 8-cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline (150 mg, 0.41 mmol) in DCM (5 mL) cooled to 0° C. was added 3-chloroperbenzoic acid (70%, 42 mg, 0.17 mmol) and the mixture stirred for 15 min. The mixture was diluted with DCM and then a sodium thiosulfate solution, followed by a saturated sodium bicarbonate solution was added. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. To the obtained residue was added THF (4 mL) and 5-methyl-1H-pyrazol-3-amine (185 mg, 1.9 mmol) and the mixture stirred at rt for 30 min. The crude mixture was concentrated under reduced pressure and then purified by preparative HPLC (Varian C-18 reverse phase column, eluted with gradient of solvent B=0.05% formic acid/ACN and solvent A=5% ACN/0.05% formic acid/H2O) to afford 8-cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazolin-4-ol (50 mg, 37%). LC-MS (ESI) m/z 332 (M+H)+.

Workup

  1. additionwas added
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. stirringthe mixture stirred at rt for 30 min
  5. concentrationThe crude mixture was concentrated under reduced pressure
  6. custompurified by preparative HPLC (Varian C-18 reverse phase column
  7. washeluted with gradient of solvent B=0.05% formic acid/ACN and solvent A=5% ACN/0.05% formic acid/H2O)

Sources & evidence

ORD record
ord-fa015538d36644f8be85daecfb033d30
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

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