Acryloyl chloride → HCID 86679609, 화합물

HRID 577664노트

반응식

HRID 577664 반응식
[NH2:1][C:2]1[CH:3]=[C:4]([CH:31]=[CH:32][CH:33]=1)[O:5][C:6]1[C:7]2[C:21]([F:22])=[CH:20][N:19]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:8]=2[N:9]=[C:10]([NH:12][C:13]2[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=2)[N:11]=1.[C:34](Cl)(=[O:37])[CH:35]=[CH2:36]>C(Cl)Cl>[F:22][C:21]1[C:7]2[C:6]([O:5][C:4]3[CH:3]=[C:2]([NH:1][C:34](=[O:37])[CH:35]=[CH2:36])[CH:33]=[CH:32][CH:31]=3)=[N:11][C:10]([NH:12][C:13]3[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=3)=[N:9][C:8]=2[N:19]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:28])([CH3:29])[CH3:30])[CH:20]=1

참가 물질

4

반응물 2

HCID 13140Acryloyl chloride3회HCID 86679610HCID 86679610, 화합물

생성물 1

HCID 86679609HCID 86679609, 화합물수율 55.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 4-(3-aminophenoxy)-5-fluoro-N-(1-methyl-1H-pyrazol-3-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (197 mg, 0.42 mmol) in DCM (20 mL) was added acryloyl chloride (34 μL, 0.42 mmol) and the reaction was stirred at rt for 45 min. Additional acryloyl chloride (34 μL, 0.42 mmol) was added and after another 2 hrs a final charge of acryloyl chloride (34 μL, 0.42 mmol) was added. After 30 min, the reaction was complete and was partitioned between DCM (30 mL) and saturated aqueous NaHCO3 (10 mL). The organic layer was separated, dried over Na2SO4 and evaporated to dryness. Purification via flash chromatography eluting with a gradient of 0%-80% EtOAc in heptane afforded the title compound (123 mg, 56 yield) as a solid. 1H NMR (400 MHz, methanol-d4) δ ppm 7.64 (s, 1H) 7.57 (d, J=8.81 Hz, 1H) 7.41 (t, J=8.18 Hz, 1H) 7.27 (d, J=1.76 Hz, 1H) 7.01 (dd, J=8.18, 2.14 Hz, 1H) 6.89 (d, J=2.27 Hz, 1H) 6.30-6.48 (m, 3H) 5.76 (dd, J=9.44, 2.14 Hz, 1H) 5.48 (s, 2H) 3.71 (s, 3H) 3.58 (t, J=8.06 Hz, 2H) 0.90 (t, J=8.06 Hz, 2H) −0.08 (s, 9H). m/z (APCI+) for C25H30FN7O3Si 524.2 (M+H)+.

후처리

  1. additionwas added
  2. waitAfter 30 min
  3. customwas partitioned between DCM (30 mL) and saturated aqueous NaHCO3 (10 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. customevaporated to dryness
  7. customPurification via flash chromatography
  8. washeluting with a gradient of 0%-80% EtOAc in heptane

출처 및 근거

ORD 기록
ord-0a7558a23e044422ba051605cca9b85a
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09040547B2

반응 노트

불러오는 중…