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

HRID 2274299ノート

反応式

HRID 2274299 の反応式
[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

参加物

4

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6422Trifluoroacetic acid溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-42d4a599b65242c6b0a75c73b3403ee3
出典データセット
uspto-grants-2015_09
特許番号
US09126950B2

反応ノート

読み込み中…