Sodium hydride → 2-[benzothiazol-2(3H)-ylidene]-2-[5-(4-methylpiperazine-1-carbonyl)-4-trifluoromethylpyrimidin-2-yl]acetamide hydrochloride

HRID 1091666Notes

Reaction equation

HRID 1091666 reaction equation
[H-].[Na+].[S:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[C:4]1[CH2:12][C:13]([NH2:15])=[O:14].[Cl:16][C:17]1[N:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[C:20]([C:27]([N:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)=[O:28])=[CH:19][N:18]=1>C1COCC1>[ClH:16].[S:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[NH:5][C:4]1=[C:12]([C:17]1[N:22]=[C:21]([C:23]([F:24])([F:26])[F:25])[C:20]([C:27]([N:29]2[CH2:30][CH2:31][N:32]([CH3:35])[CH2:33][CH2:34]2)=[O:28])=[CH:19][N:18]=1)[C:13]([NH2:15])=[O:14]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 220161072-(1,3-Benzothiazol-2-yl)acetamideHCID 86640516(2-Chloro-4-trifluoromethylpyrimidin-5-yl)(4-methylpiperazin-1-yl)methanone

Product 1

HCID 665934462-[benzothiazol-2(3H)-ylidene]-2-[5-(4-methylpiperazine-1-carbonyl)-4-trifluoromethylpyrimidin-2-yl]acetamide hydrochlorideYield 33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride 99% (50.8 mg, 2.1 mmol) was added to a suspension of 2-(benzothiazol-2-yl)acetamide (103 mg, 0.53 mmol) in THF (2 mL), and the resulting yellow suspension was stirred at room temperature for 15 min. The mixture was cooled to 0° C. and (2-chloro-4-trifluoromethyl-pyrimidin-5-yl)(4-methylpiperazin-1-yl)methanone (0.18 g, 0.53 mmol) was added. The mixture was stirred at room temperature overnight and the solvent was then removed under reduced pressure. The residue was suspended in water and the pH adjusted to 7 with 1N hydrochloric acid. The solid was collected by filtration and partitioned between EA and water. The EA phase was separated, washed with brine, dried over magnesium sulfate, and concentrated under vacuum. The resulting material was purified by reverse phase preparative HPLC to give 2-[benzothiazol-2(3H)-ylidene]-2-[5-(4-methylpiperazine-1-carbonyl)-4-trifluoromethylpyrimidin-2-yl]acetamide hydrochloride (87 mg, 33% yield) as a yellow solid.

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. stirringThe mixture was stirred at room temperature overnight
  3. customthe solvent was then removed under reduced pressure
  4. filtrationThe solid was collected by filtration
  5. custompartitioned between EA and water
  6. customThe EA phase was separated
  7. washwashed with brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under vacuum
  10. customThe resulting material was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-7084c0c89fbd4a35a963bd540ba77bc0
Source dataset
uspto-grants-2012_03
Patent number
US08129396B2

Reaction notes

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