Acetyl chloride → 1-[5-(2,4-Diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-phenyl]-ethanone

HRID 925159Notes

Reaction equation

HRID 925159 reaction equation
[CH:1]([C:4]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:5]=1[O:6][C:7]1[C:8]([NH2:14])=[N:9][C:10]([NH2:13])=[N:11][CH:12]=1)([CH3:3])[CH3:2].F[C:22](F)(F)[C:23](O)=[O:24].C(Cl)(=O)C.[Cl-].[Cl-].[Cl-].[Al+3]>ClC(Cl)C.O>[NH2:13][C:10]1[N:9]=[C:8]([NH2:14])[C:7]([O:6][C:5]2[C:4]([CH:1]([CH3:3])[CH3:2])=[CH:18][C:17]([O:19][CH3:20])=[C:16]([C:23](=[O:24])[CH3:22])[CH:15]=2)=[CH:12][N:11]=1

Participants

7

Reactant 4

HCID 6367Acetyl chlorideHCID 6422Trifluoroacetic acidHCID 6451240Aluminum(III) ChlorideHCID 161178165-(4-Methoxy-2-(propan-2-yl)phenoxy)pyrimidine-2,4-diamine

Product 1

HCID 573300761-[5-(2,4-Diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-phenyl]-ethanoneYield 31%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent

Procedure

5-(2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine in anhydrous dichloroethane (20 mL) was added to trifluoroacetic acid (0.06 mL, 0.77 mmol), acetyl chloride (0.31 mL, 4.37 mmol), and aluminum trichloride (583 mg, 4.37 mmol). After stirring for 22 hours at room temperature, water (1.2 mL) was added to the reaction at 0° C. The mixture was dried using anhydrous sodium sulfate and concentrated in vacuo. Aqueous sodium hydroxide (0.2 M, 10 mL) was added to the residue and the mixture was heated at 100° C. for 1 hour. After cooling, the reaction was extracted with dichloromethane. The dichloromethane layer was dried using anhydrous magnesium sulfate, concentrated, and purified with silica gel column chromatography eluting with 96/4/0.1 dichloromethane/methanol/ammonium hydroxide to yield 1-[5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-phenyl]-ethanone (72 mg, 31%) as off-white solid, MS (M+H)=317. Also recovered was 1-[5-(2,4-diamino-pyrimidin-5-yloxy)-2-hydroxy-4-isopropyl-phenyl]-ethanone (43 mg, 20%) as pale yellow solid, MS (M+H)=303.

Workup

  1. customThe mixture was dried
  2. concentrationconcentrated in vacuo
  3. additionAqueous sodium hydroxide (0.2 M, 10 mL) was added to the residue
  4. temperaturethe mixture was heated at 100° C. for 1 hour
  5. temperatureAfter cooling
  6. extractionthe reaction was extracted with dichloromethane
  7. dry with materialThe dichloromethane layer was dried
  8. concentrationconcentrated
  9. custompurified with silica gel column chromatography
  10. washeluting with 96/4/0.1 dichloromethane/methanol/ammonium hydroxide

Sources & evidence

ORD record
ord-14e5e50f926949cfaf95e92eaa1c4ace
Source dataset
uspto-grants-2016_03
Patent number
US09284279B2

Reaction notes

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