Trifluoroacetic anhydride → US10112934, Example 6

HRID 538651Notes

Reaction equation

O[N:2]=[CH:3][C:4]([C:7]1[CH:11]=[C:10]([NH:12][C:13]([C@@H:15]2[CH2:19][CH2:18][CH2:17][N:16]2[CH:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)=[O:14])[O:9][N:8]=1)([CH3:6])[CH3:5].FC(F)(F)C(OC(=O)C(F)(F)F)=O>>[C:3]([C:4]([CH3:6])([CH3:5])[C:7]1[CH:11]=[C:10]([NH:12][C:13]([C@@H:15]2[CH2:19][CH2:18][CH2:17][N:16]2[CH:20]2[CH2:21][CH2:22][O:23][CH2:24][CH2:25]2)=[O:14])[O:9][N:8]=1)#[N:2]

Participants

Reactant 2

HCID 9845Trifluoroacetic anhydride

HCID 131731961(S)-1-(tetrahydro-pyran-4-yl)-pyrrolidine-2-carboxylic acid [3-(2-hydroxyimino-1,1-dimethyl-ethyl)-isoxazol-5-yl]-amide

Product 1

HCID 86297584US10112934, Example 6Yield 44%

Conditions

Temperature: 100 °C

Procedure

79.0 mg (0.23 mmol) of (S)-1-(tetrahydro-pyran-4-yl)-pyrrolidine-2-carboxylic acid [3-(2-hydroxyimino-1,1-dimethyl-ethyl)-isoxazol-5-yl]amide are added to 1.00 mL trifluoroacetic anhydride and stirred at 100° C. for 3 h. The solvent is removed under reduced pressure. The residue is purified by HPLC-MS to afford 32.6 mg of (S)-1-(tetrahydro-pyran-4-yl)-pyrrolidine-2-carboxylic acid[3-(cyano-dimethyl-methyl)-isoxazol-5-yl]amide. Yield: 44%; ESI-MS: 333 [M+H]+; HPLC (Rt): 0.66 min (method F); 1H-NMR (400 MHz, DMSO-d6): 1.31-1.53 (m, 2H), 1.57-1.65 (m, 1H), 1.69 (s, 6H), 1.69-1.81 (m, 4H), 2.01-2.14 (m, 1H), 2.50-2.66 (m, 2H), 3.08-3.14 (m, 1H), 3.20-3.32 (m, 2H), 3.47-3.52 (m, 1H), 3.77-3.88 (m, 2H), 6.46 (s, 1H), 9.70 (s, 1H) ppm.

Workup

customThe solvent is removed under reduced pressure
customThe residue is purified by HPLC-MS

Sources & evidence

ORD record: ord-e15f84a3baeb4de3b862a66ec76747ed
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08865744B1

Reaction notes

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