Dimethylformamide → US10570125, Example 1

HRID 538644Notes

Reaction equation

HRID 538644 reaction equation
[CH3:1][C:2]([S:7]([CH2:10][CH2:11][CH2:12][C:13]([F:16])([F:15])[F:14])(=[O:9])=[O:8])([CH3:6])[C:3]([OH:5])=O.S(Cl)(Cl)=O.CN(C=O)C.CCN(C(C)C)C(C)C.[NH2:35][C:36]1[O:40][N:39]=[C:38]([C:41]([CH3:45])([CH3:44])[C:42]#[N:43])[CH:37]=1>C1(C)C=CC=CC=1>[C:42]([C:41]([CH3:45])([CH3:44])[C:38]1[CH:37]=[C:36]([NH:35][C:3](=[O:5])[C:2]([CH3:1])([S:7]([CH2:10][CH2:11][CH2:12][C:13]([F:16])([F:15])[F:14])(=[O:9])=[O:8])[CH3:6])[O:40][N:39]=1)#[N:43]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 592531612-Methyl-2-(4,4,4-trifluorobutane-1-sulfonyl)-propionic acid2×HCID 668766082-(5-Aminoisoxazol-3-yl)-2-methylpropanenitrile2×

Product 1

HCID 86297381US10570125, Example 1Yield 52.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To 100 mg (0.38 mmol) of 2-methyl-2-(4,4,4-trifluoro-butane-1-sulfonyl)-propionic acid (intermediate 5) in toluene (4.07 mL) are added 55.3 μL (0.76 mmol) thionyl chloride and 3.10 μL (0.04 mmol) DMF. The solution is stirred at reflux for 1 h. In a second flask 78.7 μL (0.46 mmol) DIPEA are added to 63.4 mg (0.42 mmol) of 2-(5-amino-isoxazol-3-yl)-2-methyl-propionitrile (intermediate 7) in toluene (2.03 mL). The mixture is stirred at RT for 5 min, then added to the acid chloride and stirring is continued at RT for 16 h. The reaction mixture is purified by HPLC-MS to afford 78.7 mg of N-[3-(cyano-dimethyl-methyl)-isoxazol-5-yl]-2-methyl-2-(4,4,4-trifluoro-butane-1-sulfonyl)-propionamide. Yield: 52%; ESI-MS: 396 [M+H]+; HPLC (Rt): 1.14 min (method G); 1H-NMR (400 MHz, DMSO-d6): 1.68 (s, 6H), 1.70 (s, 6H), 1.86-1.91 (m, 2H), 2.47-2.52 (m, 2H), 3.34-3.40 (m, 2H), 6.57 (s, 1H), 11.64 (s, 1H) ppm.

Workup

  1. temperatureat reflux for 1 h
  2. stirringThe mixture is stirred at RT for 5 min
  3. stirringstirring
  4. customThe reaction mixture is purified by HPLC-MS

Sources & evidence

ORD record
ord-9a44e784f46346aabbdbc4c7feb4fe99
Source dataset
uspto-grants-2014_10
Patent number
US08865744B1

Reaction notes

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