m-Chloroperbenzoic acid → HCID 90417124, compound

HRID 710006Notes

Reaction equation

HRID 710006 reaction equation
[CH3:1][O:2][C:3]1[C:8]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]4[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=4)[CH:17]=3)=[C:11]([CH3:28])[N:10]=2)=[CH:7][N:6]=[C:5](SC)[N:4]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.Cl.[NH2:43][CH:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1>C(Cl)Cl>[CH3:1][O:2][C:3]1[C:8]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]4[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=4)[CH:17]=3)=[C:11]([CH3:28])[N:10]=2)=[CH:7][N:6]=[C:5]([NH:43][CH:44]2[CH2:49][CH2:48][O:47][CH2:46][CH2:45]2)[N:4]=1

Participants

5

Reactant 3

HCID 70297m-Chloroperbenzoic acidHCID 441186934-Aminotetrahydropyran hydrochloride3×HCID 90418683HCID 90418683, compound

Product 1

HCID 90417124HCID 90417124, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of Example C2 (0.200 g, 0.476 mmol) in DCM (5 mL) was treated with mCPBA (0.141 g, 0.571 mmol), stirred at RT for 3 h, treated with 4-aminotetrahydropyran hydrochloride (0.524 g, 3.81 mmol) and TEA (0.530 mL, 3.81 mmol) and stirred at RT overnight. Additional 4-aminotetrahydropyran hydrochloride (0.524 g, 3.81 mmol) and TEA (0.530 mL, 3.81 mmol) were added and the mixture stirred at RT for an additional 24 h. The mixture was concentrated to dryness, transferred to a sealed vessel with DMF (10 mL), treated with additional 4-aminotetrahydropyran hydrochloride (0.524 g, 3.81 mmol) and TEA (0.530 mL, 3.81 mmol) and heated at 60° C. overnight. The mixture was cooled to RT, the solids removed via filtration and washed with DCM. The filtrate was treated with satd. NaHCO3, extracted with DCM (3×) and the combined organics were washed with 5% LiCl (3×), then brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford 4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrimidin-2-amine (125 mg, 56%). MS (ESI) m/z: 474.2 (M+H+).

Workup

  1. stirringstirred at RT overnight
  2. stirringthe mixture stirred at RT for an additional 24 h
  3. concentrationThe mixture was concentrated to dryness
  4. customtransferred to a sealed vessel with DMF (10 mL)
  5. temperatureheated at 60° C. overnight
  6. temperatureThe mixture was cooled to RT
  7. customthe solids removed via filtration
  8. washwashed with DCM
  9. additionThe filtrate was treated with satd
  10. extractionNaHCO3, extracted with DCM (3×)
  11. washthe combined organics were washed with 5% LiCl (3×)
  12. dry with materialbrine, dried over Na2SO4
  13. concentrationconcentrated to dryness
  14. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-5e31e4fe07d74894828e1567186b8a58
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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