Sodium hydride → 2-(2-(2,4-difluorophenoxy)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1055847노트

반응식

HRID 1055847 반응식
[H-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[OH:11].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:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[O:11][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 24758Sodium hydrideHCID 1230512,4-DifluorophenolHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

생성물 1

HCID 897834682-(2-(2,4-difluorophenoxy)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one수율 37%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
90 °C

실험 절차

To NaH (60 wt % in mineral oil; 0.071 g, 1.763 mmol) in 1 mL DMF was added 2,4-difluorophenol (0.229 g, 1.76 mmol). After 10 min, a clear/colorless solution resulted. 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 and the reaction became dark red. The reaction was sealed and heated to 90° C. for 4 h, then cooled to RT and stirred overnight. The reaction was cooled and partitioned between saturated aq. NH4Cl and EtOAc. The organic layer was washed with saturated aq. NaHCO3 (1×), water (1×), saturated aq. NaCl (1×), and the organics 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-difluorophenoxy)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.036 g, 0.092 mmol, 37% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 10.99 (1H, br. s), 8.52 (1H, d, J=9.0 Hz), 8.09 (1H, dd, J=7.6, 1.4 Hz), 7.79-7.85 (1H, m), 7.55-7.69 (2H, m), 7.51 (1H, t, J=7.7 Hz), 7.47 (1H, d, J=9.0 Hz), 7.30 (1H, dddd, J=9.2, 7.9, 3.1, 1.5 Hz), 6.91-6.94 (1H, m), 6.90 (1H, d, J=2.3 Hz), 3.34-3.40 (2H, m), 2.52-2.57 (2H, m). m/z (ESI, +ve) 392.1 (M+H)+.

후처리

  1. customa clear/colorless solution resulted
  2. customThe reaction was sealed
  3. temperaturecooled to RT
  4. temperatureThe reaction was cooled
  5. custompartitioned between saturated aq. NH4Cl and EtOAc
  6. washThe organic layer was washed with saturated aq. NaHCO3 (1×), water (1×), saturated aq. NaCl (1×)
  7. dry with materialthe organics were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. additionThe material was treated with DCM
  11. custompurified by silica gel chromatography
  12. concentrationThe product-containing fractions were concentrated

출처 및 근거

ORD 기록
ord-76615ffb98b94cbcbaa8241f9183e3b9
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394297B2

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