4-(2-Methoxyethoxy)aniline → Tert-butyl (3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)carbamate

HRID 1482722Notes

Reaction equation

HRID 1482722 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[C:11]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH:12]=[CH:13][CH:14]=2)[C:5]([F:23])=[CH:4][N:3]=1.[CH3:24][O:25][CH2:26][CH2:27][O:28][C:29]1[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][CH:30]=1>C(O)(CC)(C)C.C(O)(=O)C>[F:23][C:5]1[C:6]([NH:8][C:9]2[CH:10]=[C:11]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH:12]=[CH:13][CH:14]=2)=[N:7][C:2]([NH:33][C:32]2[CH:31]=[CH:30][C:29]([O:28][CH2:27][CH2:26][O:25][CH3:24])=[CH:35][CH:34]=2)=[N:3][CH:4]=1

Participants

5

Reactant 2

HCID 38798854-(2-Methoxyethoxy)anilineHCID 59174297Tert-butyl (3-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate

Product 1

HCID 59174353Tert-butyl (3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)carbamate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 64052-Methyl-2-butanolSolvent

Procedure

tert-Butyl (3-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate (800 mg, 2.37 mmoL) and 4-(2-methoxyethoxy)aniline (576 mg, 2.84 mmoL) were suspended in tert-amyl alcohol (14 mL) and acetic acid (5 drops). Heated to reflux for 4 h. After cooling, solvent was removed via rotary evaporation. The dark oil was partitioned between water/brine and THF (10 mL each), agitated, and separated layers and dried organic phase over sodium sulfate. The solvent was removed via rotary evaporation to afford a purple solid, 0.55 g. LC/MS (RT=2.997/(M+1)) 470.2. Additional 150 mg of product minus the (BOC) protecting group crystallized from the aqueous layer

Workup

  1. temperatureHeated
  2. temperatureto reflux for 4 h
  3. temperatureAfter cooling
  4. customsolvent was removed via rotary evaporation
  5. customThe dark oil was partitioned between water/brine and THF (10 mL each)
  6. customseparated layers and dried organic phase over sodium sulfate
  7. customThe solvent was removed via rotary evaporation
  8. customto afford a purple solid, 0.55 g
  9. customLC/MS (RT=2.997/(M+1)) 470.2
  10. customcrystallized from the aqueous layer

Sources & evidence

ORD record
ord-98549ce6a52a4c03b83a2dec0552b369
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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