Acetone → 2-[5-(3-Bromo-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-ol

HRID 410542Notes

Reaction equation

HRID 410542 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[Br:13][C:14]1[CH:15]=[C:16]([NH:25][C:26]2[N:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][N:27]=2)[CH:17]=[C:18]([C:20]2[S:24][CH:23]=[N:22][CH:21]=2)[CH:19]=1.[CH3:36][C:37]([CH3:39])=[O:38]>C1COCC1>[Br:13][C:14]1[CH:19]=[C:18]([C:20]2[S:24][C:23]([C:37]([OH:38])([CH3:39])[CH3:36])=[N:22][CH:21]=2)[CH:17]=[C:16]([NH:25][C:26]2[N:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[CH:28][N:27]=2)[CH:15]=1

Participants

6

Reactant 4

HCID 180AcetoneHCID 7912DiisopropylamineHCID 58456408N-[3-bromo-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amineHCID 178418339Butyllithium

Product 1

HCID 672565992-[5-(3-Bromo-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-olYield 61.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of diisopropylamine (0.220 mL, 1.545 mmol) in 4 mL THF was cooled to 0° C., then n-BuLi (2.5 M in hexanes, 0.598 mL, 1.495 mmol) was added dropwise. The mixture was stirred at this temperature for 15 minutes, then cooled to −78° C. Intermediate 11 (200 mg, 0.498 mmol) was then added dropwise as a solution in 1.0 mL THF, and the mixture stirred for 30 minutes. Acetone (0.110 mL, 1.495 mmol) was then added, and the mixture was stirred at −78° C. for 30 minutes, then allowed to warm to room temperature. The reaction was quenched by the addition of ˜1 mL brine, then the mixture was diluted with ethyl acetate (100 mL) and washed with brine (100 mL). The organic extracts were dried (sodium sulfate) filtered, and concentrated in vacuo. Purification by chromatography on silica gel (80:20 to 40:60, hexanes:ethyl acetate) provided 141 mg (0.307 mmol, 61.6%) of 2-[5-(3-bromo-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-ol as an off-white solid.

Workup

  1. stirringthe mixture stirred for 30 minutes
  2. stirringthe mixture was stirred at −78° C. for 30 minutes
  3. temperatureto warm to room temperature
  4. customThe reaction was quenched by the addition of ˜1 mL brine
  5. additionthe mixture was diluted with ethyl acetate (100 mL)
  6. washwashed with brine (100 mL)
  7. dry with materialThe organic extracts were dried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by chromatography on silica gel (80:20 to 40:60, hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-2fb2618c5acd4086829c90990a1148f4
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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