Trichloroacetyl chloride → N-(4,5-dimethylisoxazol-3-yl)-4-(tetrahydro-2H-pyran-4-carbonyl)-1,4-diazepane-1-carboxamide

HRID 1920722Notes

Reaction equation

HRID 1920722 reaction equation
[CH3:1][C:2]1[C:3]([NH2:8])=[N:4][O:5][C:6]=1[CH3:7].C(N(CC)C(C)C)(C)C.ClC(Cl)(Cl)[C:20](Cl)=[O:21].C([O-])(O)=O.[Na+].[N:30]1([C:37]([CH:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)=[O:38])[CH2:36][CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[CH3:1][C:2]1[C:3]([NH:8][C:20]([N:33]2[CH2:34][CH2:35][CH2:36][N:30]([C:37]([CH:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[O:38])[CH2:31][CH2:32]2)=[O:21])=[N:4][O:5][C:6]=1[CH3:7]

Participants

8

Reactant 6

HCID 6420Trichloroacetyl chlorideHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 841484,5-Dimethylisoxazol-3-amineHCID 516892Sodium BicarbonateHCID 28776660(1,4-Diazepan-1-yl)(tetrahydro-2H-pyran-4-yl)methanone

Product 1

HCID 54583456N-(4,5-dimethylisoxazol-3-yl)-4-(tetrahydro-2H-pyran-4-carbonyl)-1,4-diazepane-1-carboxamideYield 4.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 90 mg (0.8 mmol) of 4,5-dimethyl-isoxazol-3-ylamine in DCM (2 mL) was added N,N-diisopropylethylamine (278 μL, 1.6 mmol), followed by 89 μL (0.8 mmol) of trichloroacetylchloride. The reaction mixture was shaken on an orbital shaker for 18 h. Saturated aqueous NaHCO3 solution (3 mL) was added to the reaction mixture. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was dissolved in DMF (3 mL) and added to 487 mg (0.88 mmol) of [1,4]diazepan-1-yl-(tetrahydro-pyran-4-yl)-methanone (triple trifluoroacetic acid salt). To this solution 339 mg (3.2 mmol) of Na2CO3 were added and the mixture was heated in a sealed tube at 100° C. for 18 h. The reaction was cooled to room temperature, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by mass-triggered preparative LC-MS to afford 12 mg of 4-(tetrahydro-pyran-4-carbonyl)-[1,4]diazepane-1-carboxylic acid (4,5-dimethyl-isoxazol-3-yl)-amide.

Workup

  1. dry with materialThe organic layer was dried over Na2SO4
  2. filtrationfiltered
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in DMF (3 mL)
  5. temperatureThe reaction was cooled to room temperature
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by mass-triggered preparative LC-MS

Sources & evidence

ORD record
ord-0ad3a3ecde494f789b69a8e19ba90bc6
Source dataset
uspto-grants-2012_05
Patent number
US08173638B2

Reaction notes

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