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2,6-Dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol → 1-(6-(3,5-Dichloro-4-hydroxyphenyl)-4-(4-((dimethylamino)methyl)phenylamino)quinolin-3-yl)ethanone

HRID 2271791
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HRID 2271791 반응식
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12](=[O:14])[CH3:13])=[C:5]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][N:23]([CH3:25])[CH3:24])=[CH:18][CH:17]=1.[Cl:26][C:27]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[C:29]([Cl:42])[C:28]=1[OH:43]>ClCCl.CO>[Cl:26][C:27]1[CH:32]=[C:31]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][C:6]([C:12](=[O:14])[CH3:13])=[C:5]3[NH:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][N:23]([CH3:24])[CH3:25])=[CH:18][CH:17]=2)[CH:30]=[C:29]([Cl:42])[C:28]=1[OH:43]
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참가 물질

4

반응물 2

HCID 667151272,6-Dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 667157981-(6-Bromo-4-(4-((dimethylamino)methyl)phenylamino)quinolin-3-yl)ethanone

생성물 1

HCID 682985471-(6-(3,5-Dichloro-4-hydroxyphenyl)-4-(4-((dimethylamino)methyl)phenylamino)quinolin-3-yl)ethanone수율 122.7%

시약·촉매·용매 1

HCID 21226129Dichloromethane methanol용매

실험 절차

Following general procedure F, 1-(6-bromo-4-(4-((dimethylamino)methyl)phenylamino)quinolin-3-yl)ethanone (2.0 g, 5.09 mmol) was reacted with 2,6-dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (2.2 g, 7.6 mmol) to obtain the free base. The purified product was suspended in dichloromethane/methanol (1:1, 40 mL) and HBr gas was bubbled through the suspension until a solution formed. The solution was concentrated to dryness and the resultant solid was triturated with diethyl ether. The mixture was filtered, washed with diethyl ether, and dried to obtain desired product (3.0 g, 94% over two steps) as a yellow solid: 1H NMR (300 MHz, DMSO) δ 11.93 (s, 1H), 10.59 (s, 1H), 9.81 (s, 1H), 9.24 (s, 1H), 8.37 (m, 2H), 8.11 (d, J=8.8 Hz, 1H), 7.66 (d, J=8.5 Hz, 2H), 7.56 (s, 2H), 7.51 (d, J=8.5 Hz, 2H), 4.39 (d, J=4.0 Hz, 2H), 2.74 (d, J=4.0 Hz, 6H), 2.54 (s, 3H). APCI MS m/z 480 [C26H23Cl2N3O2+H]+; HPLC>99% (AUC), tR=4.79 min.

후처리

  1. customto obtain the free base
  2. customHBr gas was bubbled through the suspension until a solution
  3. customformed
  4. concentrationThe solution was concentrated to dryness
  5. customthe resultant solid was triturated with diethyl ether
  6. filtrationThe mixture was filtered
  7. washwashed with diethyl ether
  8. customdried

출처 및 근거

ORD 기록
ord-74d32fa1e0614a13b9c4ef999e6ee605
출처 데이터셋
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09120749B2

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