Diisopropylethylamine → 4-(1-(5-Formyl-2,4-dimethylbenzoyl)azetidin-3-yl)benzonitrile

HRID 1488001Notes

Reaction equation

HRID 1488001 reaction equation
[CH:1]([C:3]1[C:4]([CH3:13])=[CH:5][C:6]([CH3:12])=[C:7]([CH:11]=1)[C:8]([OH:10])=O)=[O:2].Cl.[NH:15]1[CH2:18][CH:17]([C:19]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=2)[CH2:16]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CCOC(C)=O>[CH:1]([C:3]1[C:4]([CH3:13])=[CH:5][C:6]([CH3:12])=[C:7]([CH:11]=1)[C:8]([N:15]1[CH2:18][CH:17]([C:19]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=2)[CH2:16]1)=[O:10])=[O:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 552549914-(Azetidin-3-yl)benzonitrile hydrochloride2×HCID 717431195-Formyl-2,4-dimethylbenzoic acid2×

Product 1

HCID 900213214-(1-(5-Formyl-2,4-dimethylbenzoyl)azetidin-3-yl)benzonitrileYield 54%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Into a 50-mL round-bottom flask, was placed a solution of 5-formyl-2,4-dimethylbenzoic acid (compound 151.3, 500 mg, 2.81 mmol) in DCM (10 mL) 4-(azetidin-3-yl)benzonitrile hydrochloride (compound 5.2, 545 mg, 2.80 mmol), DIEA (1.4 mL, 8.41 mmol) and HBTU (1.60 g, 4.22 mmol) were added. The reaction mixture was stirred for 3 h at room temperature. The reaction mixture was diluted with 150 mL of EtOAc, then washed with 2×50 mL of NH4Cl (sat.) and 1×50 mL of brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1/1) as eluent to furnish 480 mg (54%) of the title compound as a white solid.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. washwashed with 2×50 mL of NH4Cl (sat.) and 1×50 mL of brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1/1) as eluent

Sources & evidence

ORD record
ord-c710442cd95a4ebaae6cf9865cff7cd7
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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