Diisopropylethylamine → HCID 58158599, compound

HRID 2095931Notes

Reaction equation

HRID 2095931 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH2:11][NH:10][C:9]2=[O:14])=[CH:4][CH:3]=1.[C:15](=O)(OC(Cl)(Cl)Cl)[O:16]C(Cl)(Cl)Cl.[NH2:27][C:28]1[CH:49]=[CH:48][C:31]([O:32][C:33]2[CH:34]=[CH:35][C:36]3[N:37]([CH:39]=[C:40]([NH:42][C:43]([CH:45]4[CH2:47][CH2:46]4)=[O:44])[N:41]=3)[CH:38]=2)=[C:30]([F:50])[CH:29]=1.C(N(CC)C(C)C)(C)C.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C.O1CCCC1>[CH:45]1([C:43]([NH:42][C:40]2[N:41]=[C:36]3[CH:35]=[CH:34][C:33]([O:32][C:31]4[CH:48]=[CH:49][C:28]([NH:27][C:15]([N:10]5[CH2:11][CH2:12][CH2:13][N:8]([C:5]6[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=6)[C:9]5=[O:14])=[O:16])=[CH:29][C:30]=4[F:50])=[CH:38][N:37]3[CH:39]=2)=[O:44])[CH2:47][CH2:46]1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 58158605N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamideHCID 66968969HCID 66968969, compound

Product 1

HCID 58158599HCID 58158599, compoundYield 49.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21939870Tetrahydrofuran ethyl acetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 1-(4-fluorophenyl)tetrahydropyrimidin-2(1H)-one (360 mg, 1.8 mmol) in tetrahydrofuran (5 mL) was added bis(trichloromethyl) carbonate (330 mg, 1.1 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 (300 mg, 0.92 mmol) in tetrahydrofuran (8 mL) and N,N-diisopropylethylamine (360 mg, 2.8 mmol) were added to the mixture, and the mixture was stirred at room temperature for 30 min. Ethyl acetate/tetrahydrofuran and saturated aqueous sodium hydrogen carbonate solution were added to the mixture, and the aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×3). 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=40/60→90/10) to give the title compound (250 mg, 49%) as a white solid.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. stirringthe mixture was stirred at room temperature for 30 min
  3. extractionthe aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×3)
  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=40/60→90/10)

Sources & evidence

ORD record
ord-b8aa40c37fca4a829c2ed58d247b0f92
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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