Ammonium thiocyanate → N-((5-(4-(4-Cyanophenyl)piperidine-1-carbonyl)-2-methylphenyl)carbamothioyl)isobutyramide

HRID 541413Notes

Reaction equation

HRID 541413 reaction equation
[NH4+].[N:2]#[C:3][S-:4].[CH3:5][CH:6]([CH3:10])[C:7](Cl)=[O:8].[NH2:11][C:12]1[CH:13]=[C:14]([CH:31]=[CH:32][C:33]=1[CH3:34])[C:15]([N:17]1[CH2:22][CH2:21][CH:20]([C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=2)[CH2:19][CH2:18]1)=[O:16]>CC(C)=O>[C:27]([C:26]1[CH:25]=[CH:24][C:23]([CH:20]2[CH2:19][CH2:18][N:17]([C:15]([C:14]3[CH:31]=[CH:32][C:33]([CH3:34])=[C:12]([NH:11][C:3]([NH:2][C:7](=[O:8])[CH:6]([CH3:10])[CH3:5])=[S:4])[CH:13]=3)=[O:16])[CH2:22][CH2:21]2)=[CH:30][CH:29]=1)#[N:28]

Participants

5

Reactant 3

HCID 15666Ammonium thiocyanateHCID 62325Isobutyryl chlorideHCID 576669154-(1-(3-Amino-4-methylbenzoyl)piperidin-4-yl)benzonitrile2×

Product 1

HCID 88923546N-((5-(4-(4-Cyanophenyl)piperidine-1-carbonyl)-2-methylphenyl)carbamothioyl)isobutyramideYield 79.6%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Conditions

Temperature
40 °C

Procedure

Into around-bottom flask, was placed a solution of NH4SCN (72 mg, 0.95 mmol, 2.00 equiv) in acetone (10 mL). A solution of 2-methylpropanoyl chloride (50 mg, 0.47 mmol, 1.00 equiv) in acetone was added (5 mL) dropwise at 25° C. and the reaction was stirred overnight at 40° C. in an oil bath. To this was added 4-(1-(3-amino-4-methylbenzoyl)piperidin-4-yl)benzonitrile (compound 121.1, 150 mg, 0.42 mmol, 1.00 equiv) at 25° C. The resulting solution was stiffed for 2 h at 25° C., then concentrated under reduced pressure. The residue was diluted with 100 mL of ethyl acetate. The organic layer was washed with 2×30 mL of brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified using silica gel column chromatography with dichloromethane/methanol (20:1) as eluent to furnish 150 mg (64%) of the title compound as a brown oil.

Workup

  1. customInto around-bottom flask, was placed
  2. waitThe resulting solution was stiffed for 2 h at 25° C.
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was diluted with 100 mL of ethyl acetate
  5. washThe organic layer was washed with 2×30 mL of brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified

Sources & evidence

ORD record
ord-4d2573f5724e4094a0bf5d2b338be423
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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