Hydrochloric Acid → 1-(Tetrahydro-pyran-4-carbonyl)-piperidine-3-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide

HRID 336181Notes

Reaction equation

HRID 336181 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=O)[CH2:3][CH2:2]1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:33]([C:37]1[O:41][N:40]=[C:39]([NH:42][C:43]([CH:45]2[CH2:50][CH2:49][CH2:48][NH:47][CH2:46]2)=[O:44])[CH:38]=1)([CH3:36])([CH3:35])[CH3:34].Cl.C(N(CC)CC)C>CN(C=O)C.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[C:33]([C:37]1[O:41][N:40]=[C:39]([NH:42][C:43]([CH:45]2[CH2:50][CH2:49][CH2:48][N:47]([C:7]([CH:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)=[O:9])[CH2:46]2)=[O:44])[CH:38]=1)([CH3:36])([CH3:34])[CH3:35]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 219302Oxane-4-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 58563805Piperidine-3-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide

Product 1

HCID 585639321-(Tetrahydro-pyran-4-carbonyl)-piperidine-3-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tetrahydro-pyran-4-carboxylic acid (54.66 mg; 0.42 mmol) and 1-hydroxybenzotriazole hydrate (56.76 mg; 0.42 mmol) in anhydrous DMF (1.5 mL) is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (80.52 mg; 0.42 mmol) and the reaction mixture is stirred at room temperature for 15 minutes. After this time, piperidine-3-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide; hydrochloride (90 mg; 0.313 mmol), triethylamine (0.044 mL; 0.313 mmol) and 4-dimethylaminopyridine (4.1 mg; 0.034 mmol) are added. The reaction mixture is stirred at room temperature for 18 hours. The mixture is diluted with ethyl acetate and then washed with water, saturated NaHCO3 aqueous solution then brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography on silica using methanol/methylene chloride then recrystallization from hot ethyl acetate provides the title compound, m/z 364 [M+H+].

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 18 hours
  2. washwashed with water, saturated NaHCO3 aqueous solution
  3. dry with materialbrine, dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography on silica
  7. customrecrystallization from hot ethyl acetate

Sources & evidence

ORD record
ord-bc9bb14d04e54c0884144f62b9ea7976
Source dataset
uspto-grants-2014_11
Patent number
US08889670B2

Reaction notes

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