Diisopropylethylamine → HCID 58158644, compound

HRID 2095953Notes

Reaction equation

HRID 2095953 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]([CH3:14])[CH2:12][CH2:11][NH:10][C:9]2=[O:15])=[CH:4][CH:3]=1.[C:16](=O)(OC(Cl)(Cl)Cl)[O:17]C(Cl)(Cl)Cl.[NH2:28][C:29]1[CH:50]=[CH:49][C:32]([O:33][C:34]2[CH:35]=[CH:36][C:37]3[N:38]([CH:40]=[C:41]([NH:43][C:44]([CH:46]4[CH2:48][CH2:47]4)=[O:45])[N:42]=3)[CH:39]=2)=[C:31]([F:51])[CH:30]=1.C(N(CC)C(C)C)(C)C.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C.O1CCCC1>[CH:46]1([C:44]([NH:43][C:41]2[N:42]=[C:37]3[CH:36]=[CH:35][C:34]([O:33][C:32]4[CH:49]=[CH:50][C:29]([NH:28][C:16]([N:10]5[CH2:11][CH2:12][CH:13]([CH3:14])[N:8]([C:5]6[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=6)[C:9]5=[O:15])=[O:17])=[CH:30][C:31]=4[F:51])=[CH:39][N:38]3[CH:40]=2)=[O:45])[CH2:48][CH2:47]1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 58158560HCID 58158560, compoundHCID 58158605N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 58158644HCID 58158644, compoundYield 9.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21939870Tetrahydrofuran ethyl acetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 1-(4-fluorophenyl)-6-methyltetrahydropyrimidin-2(1H)-one (240 mg, 1.1 mmol) in tetrahydrofuran (5 mL) was added bis(trichloromethyl) carbonate (170 mg, 0.57 mmol), and the mixture was stirred at 70° C. for 3.5 hr. The mixture was cooled to room temperature, a solution of N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (250 mg, 0.76 mmol) in tetrahydrofuran (8 mL) and N,N-diisopropylethylamine (300 mg, 2.3 mmol) were added to the mixture, and the mixture was stirred at room temperature for 1 hr. Ethyl acetate/tetrahydrofuran and saturated aqueous sodium hydrogen carbonate solution 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 filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=50/50→100/0) to give the title compound (29 mg, 7%) as a white solid.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. stirringthe mixture was stirred at room temperature for 1 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. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=50/50→100/0)

Sources & evidence

ORD record
ord-57d05293b0e44880977547021f577af8
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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