Piperidinocarbonitrile → HCID 90203749, compound

HRID 1480238Notes

Reaction equation

HRID 1480238 reaction equation
[NH2:1]/[C:2](=[N:27]\[OH:28])/[C:3]([NH:9][C:10]([C:12]1[CH:17]=[C:16]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])[C:15]([CH:24]2[CH2:26][CH2:25]2)=[CH:14][N:13]=1)=[O:11])([CH2:5][CH:6]1[CH2:8][CH2:7]1)[CH3:4].[N:29]1(C#N)CCCC[CH2:30]1>C(OCC)(=O)C>[NH2:29][C:30]1[O:28][N:27]=[C:2]([C:3]([NH:9][C:10]([C:12]2[CH:17]=[C:16]([O:18][CH2:19][C:20]([F:22])([F:23])[F:21])[C:15]([CH:24]3[CH2:25][CH2:26]3)=[CH:14][N:13]=2)=[O:11])([CH3:4])[CH2:5][CH:6]2[CH2:8][CH2:7]2)[N:1]=1

Participants

4

Reactant 2

HCID 73736PiperidinocarbonitrileHCID 90203779HCID 90203779, compound

Product 1

HCID 90203749HCID 90203749, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of N-[(2Z)-2-amino-1-(cyclopropylmethyl)-2-hydroxyimino-1-methyl-ethyl]-5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridine-2-carboxamide (example 165a, 30 mg, 74.9 μmol) in piperidine-1-carbonitrile (130 mg, 130 μl, 1.18 mmol) was heated at 130° C. in a sealed tube for 2 hours. The reaction mixture was cooled to room temperature and was diluted with ethyl acetate. The organic phase was washed with water. The organic phase was collected and the aqueous phase was back-extracted with ethyl acetate. Combined organic phases were dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient to yield the title compound (21 mg, 67%). MS (ESI, m/z): 426.6 (M+H+).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washThe organic phase was washed with water
  3. customThe organic phase was collected
  4. extractionthe aqueous phase was back-extracted with ethyl acetate
  5. dry with materialCombined organic phases were dried over sodium sulfate
  6. customevaporated down to dryness
  7. customThe crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient

Sources & evidence

ORD record
ord-1a21faf5753841f78dfcb7f28b246d6f
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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