Triethylamine → HCID 46219902, compound

HRID 2366801Notes

Reaction equation

HRID 2366801 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:54])([F:53])[C:46]1[N:51]=[CH:50][C:49]([NH2:52])=[CH:48][CH:47]=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:52][C:49]1[CH:50]=[N:51][C:46]([C:45]([F:54])([F:44])[F:53])=[CH:47][CH:48]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 27377445-Amino-2-(trifluoromethyl)pyridineHCID 86646022N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 46219902HCID 46219902, compoundYield 73.6%

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. 6-(Trifluoromethyl)pyridin-3-amine (56 mg, 0.348 mmol) was added to the reaction mixture, and the mixture was stirred at 50° C. for 2 hr and at room temperature for 4 days. The reaction mixture was diluted with ethyl acetate (20 mL) and washed with aqueous sodium hydrogen carbonate solution (15 mL), and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the obtained residue was washed with acetone (3 mL) to give the title compound (40 mg, 26%) as a white solid.

Workup

  1. stirringthe mixture was stirred at 50° C. for 2 hr and at room temperature for 4 days
  2. washwashed with aqueous sodium hydrogen carbonate solution (15 mL)
  3. filtrationthe insoluble material was filtered off
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. washthe obtained residue was washed with acetone (3 mL)

Sources & evidence

ORD record
ord-18e5266ae9874615bd149c9805c86321
Source dataset
uspto-grants-2014_04
Patent number
US08697874B2

Reaction notes

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