2-Bromoethanol → HCID 44545940, compound

HRID 1958662Notes

Reaction equation

HRID 1958662 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]2[NH:11][C:12]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[N:26]=3)=[C:13]([C:15]3[CH:16]=[C:17]4[C:22](=[CH:23][CH:24]=3)[N:21]=[CH:20][CH:19]=[CH:18]4)[N:14]=2)=[CH:5][C:3]=1[NH2:4].Br[CH2:33][CH2:34][OH:35].C(N(CC)C(C)C)(C)C>C1(C)C=CC=CC=1.CN(C=O)C.O>[F:1][C:2]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]2[NH:11][C:12]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[N:26]=3)=[C:13]([C:15]3[CH:16]=[C:17]4[C:22](=[CH:23][CH:24]=3)[N:21]=[CH:20][CH:19]=[CH:18]4)[N:14]=2)=[CH:5][C:3]=1[NH:4][CH2:33][CH2:34][OH:35]

Participants

7

Reactant 3

HCID 108982-Bromoethanol2×HCID 81531DiisopropylethylamineHCID 44546067HCID 44546067, compound

Product 1

HCID 44545940HCID 44545940, compoundYield 34.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a suspension of 2-fluoro-5-((5-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-imidazol-2-yl)methyl)aniline (Example 73) (100 mg, 0.244 mmol) in toluene (450 uL) and DMF (0.2 mL) were added 2-bromoethanol (21 uL, 0.293 mmol), N,N-diisopropylethylamine (300 uL, 1.72 mmol) and the mixture was stirred at 70° C. After 5 hours, additional 2-bromoethanol (5 uL) was added, and stirred at 100° C. for overnight. The reaction mixture was cooled to room temperature, diluted with H2O (4 mL), and extracted with CH2Cl2 (2 mL, 3 times). The organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by MPLC on NH silica gel (MeOH:CH2Cl2=1:50 (v/v)) to afford the title compound (38 mg, 34%). 1H NMR (300 MHz, CDCl3) δ 2.49 (3H, s), 3.31 (2H, bs), 3.83 (2H, t), 4.10 (2H, s), 6.56-6.60 (1H, m), 6.76 (1H, d), 6.87-6.96 (2H, m), 7.22 (1H, d), 7.34-7.42 (2H, m), 7.93 (1H, d), 8.09 (1H, d), 8.15 (2H, bs), 8.90 (1H, dd), 10.45 (1H, bs). MS (ESI) m/z 454 (MH+).

Workup

  1. stirringstirred at 100° C. for overnight
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted with CH2Cl2 (2 mL, 3 times)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe residue was purified by MPLC on NH silica gel (MeOH:CH2Cl2=1:50 (v/v))

Sources & evidence

ORD record
ord-d5895b82bc0449a998c9fd95ed41aa66
Source dataset
uspto-grants-2013_04
Patent number
US08410146B2

Reaction notes

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