Water → 2,2,2-Trifluoro-N-{6-[3-(4-methoxy-3-methyl-benzoyl)-4-oxo-4H-quinolin-1-ylmethyl]-pyridin-2-yl}-acetamide

HRID 227007Notes

Reaction equation

HRID 227007 reaction equation
C[Si](C)(C)N[Si](C)(C)C.[K].[CH3:11][O:12][C:13]1[CH:31]=[CH:30][C:16]([C:17]([C:19]2[C:28](=[O:29])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[NH:21][CH:20]=2)=[O:18])=[CH:15][C:14]=1[CH3:32].Br[CH2:34][C:35]1[N:40]=[C:39]([NH:41][C:42](=[O:47])[C:43]([F:46])([F:45])[F:44])[CH:38]=[CH:37][CH:36]=1.O>O1CCCC1.C(OCC)(=O)C>[F:46][C:43]([F:44])([F:45])[C:42]([NH:41][C:39]1[CH:38]=[CH:37][CH:36]=[C:35]([CH2:34][N:21]2[C:22]3[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:28](=[O:29])[C:19]([C:17](=[O:18])[C:16]3[CH:30]=[CH:31][C:13]([O:12][CH3:11])=[C:14]([CH3:32])[CH:15]=3)=[CH:20]2)[N:40]=1)=[O:47]

Participants

7

Reactant 4

HCID 962WaterHCID 45051783Silanamine, 1,1,1-trimethyl-N-(trimethylsilyl)-, potassium saltHCID 57754672N-(6-bromomethyl-pyridin-2-yl)-2,2,2-trifluoro-acetamideHCID 577547583-(4-Methoxy-3-methyl-benzoyl)-1H-quinolin-4-one

Product 1

HCID 577547792,2,2-Trifluoro-N-{6-[3-(4-methoxy-3-methyl-benzoyl)-4-oxo-4H-quinolin-1-ylmethyl]-pyridin-2-yl}-acetamideYield 173.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Potassium hexamethyldisilazane (2.44 mL, 1.22 mmol, 0.5 M in THF) was added to a solution of 3-(4-Methoxy-3-methyl-benzoyl)-1H-quinolin-4-one (0.30 g, 1.02) in 10 mL of tetrahydrofuran. After the reaction was stirred at rt for 20 minutes, N-(6-Bromomethyl-pyridin-2-yl)-2,2,2-trifluoro-acetamide (0.35 g, 0.246 mmol) was added and stirred overnight at room temperature. Water and ethyl acetate were added and the two phases were separated. The aqueous phase was extracted with ethyl acetate (3×20 mL). The combined organic layers were dried with magnesium sulfate, filtered and concentrated in vacuo. The crude brown solid was purified by reverse phase HPLC with a C18 column, gradient of 20-70% acetonitrile—0.1% TFA to yield 212 mg of 2,2,2-Trifluoro-N-{6-[3-(4-methoxy-3-methyl-benzoyl)-4-oxo-4H-quinolin-1-ylmethyl]-pyridin-2-yl}-acetamide

Workup

  1. stirringstirred overnight at room temperature
  2. customthe two phases were separated
  3. extractionThe aqueous phase was extracted with ethyl acetate (3×20 mL)
  4. dry with materialThe combined organic layers were dried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude brown solid was purified by reverse phase HPLC with a C18 column, gradient of 20-70% acetonitrile—0.1% TFA

Sources & evidence

ORD record
ord-5f6f8193a68d4a29bb42c0a7c9495ae6
Source dataset
uspto-grants-2009_07
Patent number
US07557213B2

Reaction notes

Loading…