Triethylamine → HCID 58158495, compound

HRID 2095954Notes

Reaction equation

HRID 2095954 reaction equation
[C:1](=O)(OC(Cl)(Cl)Cl)[O:2]C(Cl)(Cl)Cl.[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:21](=[O:27])[NH:22][CH2:23][CH2:24][C:25]=2[CH3:26])=[CH:16][CH:15]=1.C(N(CC)CC)C.[NH2:35][C:36]1[CH:57]=[CH:56][C:39]([O:40][C:41]2[CH:42]=[CH:43][C:44]3[N:45]([CH:47]=[C:48]([NH:50][C:51]([CH:53]4[CH2:55][CH2:54]4)=[O:52])[N:49]=3)[CH:46]=2)=[C:38]([F:58])[CH:37]=1>O1CCCC1.[Cl-].[Na+].O.C(OCC)(=O)C.O1CCCC1>[CH:53]1([C:51]([NH:50][C:48]2[N:49]=[C:44]3[CH:43]=[CH:42][C:41]([O:40][C:39]4[CH:56]=[CH:57][C:36]([NH:35][C:1]([N:22]5[C:21](=[O:27])[C:20]([C:17]6[CH:18]=[CH:19][C:14]([F:13])=[CH:15][CH:16]=6)=[C:25]([CH3:26])[CH2:24][CH2:23]5)=[O:2])=[CH:37][C:38]=4[F:58])=[CH:46][N:45]3[CH:47]=2)=[O:52])[CH2:55][CH2:54]1

Participants

8

Reactant 4

HCID 8471Triethylamine2×HCID 94429TriphosgeneHCID 58158583HCID 58158583, compoundHCID 58158605N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 58158495HCID 58158495, compoundYield 70.9%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent3×HCID 21939870Tetrahydrofuran ethyl acetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of bis(trichloromethyl) carbonate (127 mg, 0.43 mmol) in tetrahydrofuran (4 mL) were slowly added a solution of 3-(4-fluorophenyl)-4-methyl-5,6-dihydropyridin-2(1H)-one (240 mg, 1.2 mmol) and triethylamine (240 mg, 2.3 mmol) in tetrahydrofuran (2 mL) under ice-cooling, and the mixture was stirred at 0° C. for 40 min and at room temperature for 15 min. A solution of N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (250 mg, 0.78 mmol) in tetrahydrofuran (4 mL) and triethylamine (79 mg, 0.78 mmol) were added to the mixture, and the mixture was stirred at room temperature for 2 hr. Ethyl acetate/tetrahydrofuran and saturated brine were added to the mixture, and the aqueous layer was extracted 3 times with ethyl acetate/tetrahydrofuran. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=40/60→90/10) to give the title compound (170 mg, 39%) as a white solid.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at room temperature for 2 hr
  3. extractionthe aqueous layer was extracted 3 times with ethyl acetate/tetrahydrofuran
  4. washThe combined organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=40/60→90/10)

Sources & evidence

ORD record
ord-00ad7d8d6fa54bc9a64ea904373209d9
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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