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

HRID 1055847ノート

反応式

HRID 1055847 の反応式
[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

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 1230512,4-DifluorophenolHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-76615ffb98b94cbcbaa8241f9183e3b9
出典データセット
uspto-grants-2016_07
特許番号
US09394297B2

反応ノート

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