1-Bromo-3-methylbutane → HCID 11858031, compound

HRID 1993358Notes

Reaction equation

HRID 1993358 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])N=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:27]=[CH:26][C:25]([NH:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:24][N:23]=2)=[CH:18][C:17]=1[F:35].[H-].[Na+].Br[CH2:39][CH2:40][CH:41]([CH3:43])[CH3:42].[CH2:44]1COCC1>>[CH3:14][O:13][C:12]1[CH:11]=[C:10]2[C:5](=[CH:4][C:3]=1[O:2][CH3:1])[C:6]([O:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]3[N:23]=[CH:24][C:25]([N:28]([CH2:39][CH2:40][CH:41]([CH3:43])[CH3:42])[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:26][N:27]=3)=[CH:18][C:17]=1[F:35])=[CH:7][CH:8]=[CH:44]2

Participants

5

Reactant 4

HCID 78911-Bromo-3-methylbutaneHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 11857505HCID 11857505, compound

Product 1

HCID 11858031HCID 11858031, compound

Conditions

Temperature
50 °C

Procedure

In a 10 mL dry flask with stirring bar was placed {2-[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-pyrimidin-5-yl}-phenyl-amine (Example 39, 0.030 g, 0.06 mmol) under N2. Anhydrous THF (1.5 mL) was added, followed by the addition of NaH (60% dispersion, 0.10 g, 2.5 mmol). The resulting yellow mixture was heated at 50° C. for 20 min, then cooled to RT. 1-Bromo-3-methylbutane (0.20 mL) was added, and the resulting yellow mixture was heated at 50° C. for 4.5 h. The reaction was quenched with NH4Cl (half sat.) and the slurry was filtered, then washed with H2O. The brown solid was dissolved in CH2Cl2 and was purified on silica (50%-100% EtOAc in hexanes) to afford the title compound as a yellow solid. MS (ESI pos. ion) m/z: 539. Calc'd for C32H31FN4O3: 538.24.

Workup

  1. customIn a 10 mL dry flask
  2. temperaturecooled to RT
  3. temperaturethe resulting yellow mixture was heated at 50° C. for 4.5 h
  4. customThe reaction was quenched with NH4Cl (half sat.)
  5. filtrationthe slurry was filtered
  6. washwashed with H2O
  7. dissolutionThe brown solid was dissolved in CH2Cl2
  8. customwas purified on silica (50%-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-8aee5e32ce7842ce86d0df0f923f4894
Source dataset
uspto-grants-2010_01
Patent number
US07652009B2

Reaction notes

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