2,4-Difluoroaniline → 2-(2-((2,4-difluorophenyl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1055845노트

반응식

HRID 1055845 반응식
[H-].[Na+].[F:3][C:4]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:5]=1[NH2:6].Cl[C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[C:16]([C:23]3[NH:31][C:30]4[CH2:29][CH2:28][NH:27][C:26](=[O:32])[C:25]=4[CH:24]=3)[CH:17]=[CH:18][CH:19]=2)[N:14]=1>CN(C=O)C>[F:3][C:4]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:5]=1[NH:6][C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[C:16]([C:23]3[NH:31][C:30]4[CH2:29][CH2:28][NH:27][C:26](=[O:32])[C:25]=4[CH:24]=3)[CH:17]=[CH:18][CH:19]=2)[N:14]=1

참가 물질

5

반응물 3

HCID 97092,4-DifluoroanilineHCID 24758Sodium hydrideHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

생성물 1

HCID 897835532-(2-((2,4-difluorophenyl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one수율 21.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
70 °C

실험 절차

To NaH (60 wt % in mineral oil; 0.071 g, 1.763 mmol) in 1 mL DMF was added 2,4-difluoroaniline (0.178 ml, 1.763 mmol). After 10 min, 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 0.075 g, 0.252 mmol) was added as a solid and the reaction became dark red. The reaction was heated at 70° C. for 4 h, and then cooled to RT and partitioned between saturated aq. NH4Cl and EtOAc. The organic layer was separated and sequentially washed with saturated aq. NH4Cl and saturated aq. NaCl, and the organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography using 0-50% 90/10 DCM/MeOH in DCM. The product-containing fractions were concentrated to afford 2-(2-((2,4-difluorophenyl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.021 g, 0.054 mmol, 21% yield) as a brown solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.96 (1H, br. s), 9.27 (1H, s), 8.13 (1H, d, J=9.0 Hz), 7.83-8.00 (2H, m), 7.59 (1H, dt, J=7.6, 0.9 Hz), 7.46 (1H, ddd, J=11.2, 8.8, 2.9 Hz), 7.28 (1H, t, J=7.6 Hz), 7.17-7.24 (1H, m), 7.14 (1H, d, J=9.0 Hz), 6.89-6.96 (2H, m), 3.35-3.41 (2H, m), 2.57 (2H, t, J=6.9 Hz). m/z (ESI, +ve) 391.2 (M+H)+.

후처리

  1. temperaturecooled to RT
  2. custompartitioned between saturated aq. NH4Cl and EtOAc
  3. customThe organic layer was separated
  4. washsequentially washed with saturated aq. NH4Cl and saturated aq. NaCl
  5. dry with materialthe organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. additionThe material was treated with DCM
  9. custompurified by silica gel chromatography
  10. concentrationThe product-containing fractions were concentrated

출처 및 근거

ORD 기록
ord-35b363e6ca964ade8cbbd8d5399ee65e
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394297B2

반응 노트

불러오는 중…