Cesium carbonate → N4-(2-(benzyloxy)-5-nitrophenyl)-5-fluoro-N2-(4-(2-methoxyethoxy)phenyl)pyrimidine-2,4-diamine

HRID 1482689노트

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HRID 1482689 반응식
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1[NH:18][C:19]1[C:24]([F:25])=[CH:23][N:22]=[C:21](Cl)[N:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:27][O:28][CH2:29][CH2:30][O:31][C:32]1[CH:38]=[CH:37][C:35]([NH2:36])=[CH:34][CH:33]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1[NH:18][C:19]1[C:24]([F:25])=[CH:23][N:22]=[C:21]([NH:36][C:35]2[CH:34]=[CH:33][C:32]([O:31][CH2:30][CH2:29][O:28][CH3:27])=[CH:38][CH:37]=2)[N:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 38798854-(2-Methoxyethoxy)anilineHCID 86724343N-(2-(benzyloxy)-5-nitrophenyl)-2-chloro-5-fluoropyrimidin-4-amine

생성물 1

HCID 86724344N4-(2-(benzyloxy)-5-nitrophenyl)-5-fluoro-N2-(4-(2-methoxyethoxy)phenyl)pyrimidine-2,4-diamine수율 36.2%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

반응 조건

온도
80 °C

실험 절차

In a 100 mL 3-neck RBF, N-(2-(benzyloxy)-5-nitrophenyl)-2-chloro-5-fluoropyrimidin-4-amine (0.205 g), 4-(2-methoxyethoxy)aniline (0.137 g), Cs2CO3 (0.266 g) and Xantphos (0.032 g) were taken in degassed 1,4-dioxane (8.0 mL) and reaction mixture was degassed under argon for 30 minutes. Palladium acetate (0.013 g) was added to reaction mixture and again it was degassed for 30 minutes. The reaction mixture was heated to 80° C. and stirred for 3.5 h. The reaction was monitored on TLC using hexane:ethyl acetate: (5:5) as mobile phase. After completion, the reaction mixture was allowed to cool at room temperature. The reaction mixture was poured into water and product was extracted with ethyl acetate (3×25 mL). The ethyl acetate layer washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure. Crude material was purified by triturating with diethyl ether to give 0.1 g of N4-(2-(benzyloxy)-5-nitrophenyl)-5-fluoro-N2-(4-(2-methoxyethoxy)phenyl)pyrimidine-2,4-diamine. 1H NMR: CDCl3 (400 MHz): 3.47 (d, 3H, J=11.6), 3.77 (dd, 2H, J=4.8, 8.8), 4.15 (t, 2H, J=4.8), 5.28 (s, 2H), 6.96 (d, 1H, J=8.8), 7.03 (d, 1H, J=8.8), 7.08 (d, 1H, J=9.2), 7.45 (m, 7H), 7.83 (s, 1H), 7.9 (d, 2H, J=2.8), 8.02 (dd, 1H, J=2.1, 6.8), 9.18 (s, 1H).

후처리

  1. customreaction mixture
  2. customwas degassed under argon for 30 minutes
  3. additionPalladium acetate (0.013 g) was added to reaction mixture and again it
  4. customwas degassed for 30 minutes
  5. temperatureto cool at room temperature
  6. additionThe reaction mixture was poured into water and product
  7. extractionwas extracted with ethyl acetate (3×25 mL)
  8. washThe ethyl acetate layer washed with brine solution
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customCrude material was purified
  12. customby triturating with diethyl ether

출처 및 근거

ORD 기록
ord-fb13ae1372ce44088a624e71bac03a87
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09415049B2

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