Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 4-(1-(2-Ethyl-5-formyl-4-methylbenzoyl)piperidin-4-yl)benzonitrile

HRID 541339Notes

Reaction equation

HRID 541339 reaction equation
[CH2:1]([C:3]1[CH:11]=[C:10]([CH3:12])[C:9]([CH:13]=[O:14])=[CH:8][C:4]=1[C:5]([OH:7])=O)[CH3:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH:40]1[CH2:45][CH2:44][CH:43]([C:46]2[CH:53]=[CH:52][C:49]([C:50]#[N:51])=[CH:48][CH:47]=2)[CH2:42][CH2:41]1>CN(C)C=O.CCN(C(C)C)C(C)C>[CH2:1]([C:3]1[CH:11]=[C:10]([CH3:12])[C:9]([CH:13]=[O:14])=[CH:8][C:4]=1[C:5]([N:40]1[CH2:45][CH2:44][CH:43]([C:46]2[CH:53]=[CH:52][C:49]([C:50]#[N:51])=[CH:48][CH:47]=2)[CH2:42][CH2:41]1)=[O:7])[CH3:2]

Participants

6

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)2×HCID 866725372-Ethyl-5-formyl-4-methylbenzoic acid2×

Product 1

HCID 866725384-(1-(2-Ethyl-5-formyl-4-methylbenzoyl)piperidin-4-yl)benzonitrileYield 85.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent2×

Conditions

Temperature
25 °C

Procedure

To a round-bottom flask was added a solution of 2-ethyl-5-formyl-4-methylbenzoic acid (compound 211.4, 450 mg, 2.34 mmol, 1.00 equiv) in N,N-dimethylformamide (5 mL). DIEA (907 mg, 7.02 mmol, 3.00 equiv) and HBTU (1.30 g, 3.43 mmol, 1.50 equiv) were added to the reaction mixture. The resulting solution was stirred for 30 min at 25° C. A solution of 4-(piperidin-4-yl)benzonitrile hydrochloride (compound 1.5, 624 mg, 2.80 mmol, 1.20 equiv) in DIEA (2 mL) was added dropwise. The resulting solution was stirred for 30 min at 25° C., then quenched with 20 mL of water. The aqueous phase was extracted with 3×30 mL of ethyl acetate. The combined organic layers were washed with 1×50 mL of brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (5:1) as eluent to furnish 720 mg (85%) of the title compound as a yellow solid.

Workup

  1. stirringThe resulting solution was stirred for 30 min at 25° C.
  2. customquenched with 20 mL of water
  3. extractionThe aqueous phase was extracted with 3×30 mL of ethyl acetate
  4. washThe combined organic layers were washed with 1×50 mL of brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified

Sources & evidence

ORD record
ord-daf62af2d4d94d60a35d4b873ae4b02b
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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