Triethylamine → HCID 58451257, compound

HRID 2366798Notes

Reaction equation

HRID 2366798 reaction equation
[C:1](=[O:12])(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl.[NH2:13][C:14]1[CH:15]=[C:16]([CH:33]=[CH:34][C:35]=1[F:36])[O:17][C:18]1[N:23]=[C:22]2[S:24][C:25]([NH:27][C:28]([CH:30]3[CH2:32][CH2:31]3)=[O:29])=[N:26][C:21]2=[CH:20][CH:19]=1.C(N(CC)CC)C.[F:44][C:45]([F:55])([F:54])[C:46]1[CH:47]=[C:48]([CH2:52][NH2:53])[CH:49]=[CH:50][CH:51]=1>O1CCCC1.C(OCC)(=O)C>[F:36][C:35]1[CH:34]=[CH:33][C:16]([O:17][C:18]2[N:23]=[C:22]3[S:24][C:25]([NH:27][C:28]([CH:30]4[CH2:32][CH2:31]4)=[O:29])=[N:26][C:21]3=[CH:20][CH:19]=2)=[CH:15][C:14]=1[NH:13][C:1](=[O:12])[NH:53][CH2:52][C:48]1[CH:49]=[CH:50][CH:51]=[C:46]([C:45]([F:44])([F:54])[F:55])[CH:47]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 759623-(Trifluoromethyl)benzylamineHCID 94429TriphosgeneHCID 86646022N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 58451257HCID 58451257, compoundYield 143.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of bis(trichloromethyl) carbonate (30 mg, 0.102 mmol) in tetrahydrofuran (2 mL) was added dropwise a suspension of N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (100 mg, 0.290 mmol) produced in Example 16(vi) and triethylamine (80 μL, 0.580 mmol) in tetrahydrofuran (2 mL) at 0° C., and the mixture was stirred at 0° C. for 30 min. 1-[3-(Trifluoromethyl)phenyl]methanamine (50 μL, 0.348 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 2.5 hr. The reaction mixture was diluted with ethyl acetate (20 mL), and washed successively with aqueous sodium hydrogen carbonate solution (15 mL) and saturated brine (5 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=50/50→70/30), and the obtained solution was concentrated under reduced pressure. The obtained residue was washed with ethyl acetate (3 mL) to give the title compound (80 mg, 50%) as a white solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 2.5 hr
  2. washwashed successively with aqueous sodium hydrogen carbonate solution (15 mL) and saturated brine (5 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=50/50→70/30)
  6. concentrationthe obtained solution was concentrated under reduced pressure
  7. washThe obtained residue was washed with ethyl acetate (3 mL)

Sources & evidence

ORD record
ord-a792ebfecd9c4dc2a75ef084c45d3cce
Source dataset
uspto-grants-2014_04
Patent number
US08697874B2

Reaction notes

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