Dichloromethane methanol → 2-(4-((5-Fluoro-4-((3-(methylamino)phenyl)amino)pyrimidin-2-yl)amino)phenoxy)ethanol

HRID 1482717Notes

Reaction equation

HRID 1482717 reaction equation
[F:1][C:2]1[C:3]([NH:25][C:26]2[CH:27]=[C:28]([N:32](C)[C:33](=O)OC(C)(C)C)[CH:29]=[CH:30][CH:31]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][O:18]COCCOC)=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C(Cl)Cl.CO>FC(F)(F)C(O)=O>[F:1][C:2]1[C:3]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([NH:32][CH3:33])[CH:27]=2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([O:15][CH2:16][CH2:17][OH:18])=[CH:13][CH:14]=2)=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 21226129Dichloromethane methanolHCID 86724364Tert-butyl (3-((5-fluoro-2-((4-(2-((2-methoxyethoxy)methoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)(methyl)carbamate

Product 1

HCID 867243662-(4-((5-Fluoro-4-((3-(methylamino)phenyl)amino)pyrimidin-2-yl)amino)phenoxy)ethanolYield 39.6%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

In a 25 mL, 3-neck RBF equipped with a calcium chloride guard tube, tert-butyl (3-((5-fluoro-2-((4-(2-((2-methoxyethoxy)methoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)(methyl)carbamate (0.4 g) in was charged in trifluoroacetic acid (6.0 mL) at 0° C. The reaction mixture was stirred at 0° C. for 8 hr. The reaction was monitored by TLC using DCM:methanol (9.6:0.4) as mobile phase. After completion of the reaction, the reaction mixture was quenched in water and neutralized with sodium bicarbonate. Product was extracted in DCM and the organic layer was washed with brine, dried over sodium sulfate and concentrated completely under reduce pressure at 40° C. Crude material was purified by using Combiflash chromatography. Product was eluted with 1.7% methanol in DCM and concentrated to give 0.105 g of 2-(4-((5-fluoro-4-((3-(methylamino)phenyl)amino)pyrimidin-2-yl)amino)phenoxy)ethanol. M+1=457.8. 1H NMR: DMSO-d6 (400 MHz): 2.65 (d, 3H, J=5.2), 3.69 (t, 2H, J=4.8), 3.92 (t, 2H, J=4.8), 4.85 (t, 1H, J=5.6), 5.54 (d, 1H, J=4.8), 6.29 (s, 1H), 6.79 (d, 2H, J=8.8), 6.86 (s, 1H), 7.03 (s, 2H), 7.55 (d, 2H, J=9.2), 8.02 (s, 1H), 8.93 (s, 1H), 9.04 (s, 1H).

Workup

  1. customIn a 25 mL, 3-neck RBF equipped with a calcium chloride guard tube
  2. customAfter completion of the reaction
  3. customthe reaction mixture was quenched in water and neutralized with sodium bicarbonate
  4. extractionProduct was extracted in DCM
  5. washthe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated completely
  8. customat 40° C
  9. customCrude material was purified
  10. washProduct was eluted with 1.7% methanol in DCM
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-bdad9d3bc9bb41c59ca0d108487c4380
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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