Tert-Butylamine → N-(tert-butyl)-4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-2-amine

HRID 710008Notes

Reaction equation

HRID 710008 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.[C:42]([NH2:46])([CH3:45])([CH3:44])[CH3:43]>C(Cl)Cl>[C:42]([NH:46][C:5]1[N:4]=[C:3]([O:2][CH3:1])[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]=1)([CH3:45])([CH3:44])[CH3:43]

Participants

5

Reactant 3

HCID 6385Tert-Butylamine3×HCID 70297m-Chloroperbenzoic acidHCID 90418683HCID 90418683, compound

Product 1

HCID 90418082N-(tert-butyl)-4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-2-amineYield 65.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of Example C2 (0.100 g, 0.238 mmol) in DCM (5 mL) was treated with mCPBA (0.059 g, 0.238 mmol), stirred at RT for 2 h, treated with t-butylamine (0.4 mL, 3.81 mmol) and stirred at RT overnight. Additional t-butylamine (0.4 mL, 3.81 mmol) was 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 (5 mL), treated with additional t-butylamine (0.4 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 N-(tert-butyl)-4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-2-amine (69 mg, 65%). MS (ESI) m/z: 446.3 (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 (5 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-40a62ead8e7148b9a8c4ec15c661f039
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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