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

HRID 1482717노트

반응식

HRID 1482717 반응식
[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

참가 물질

4

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6422Trifluoroacetic acid용매

반응 조건

온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-bdad9d3bc9bb41c59ca0d108487c4380
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09415049B2

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