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 2271791Notes

Reaction equation

HRID 2271791 reaction equation
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]

Participants

4

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-74d32fa1e0614a13b9c4ef999e6ee605
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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