Diisopropylethylamine → 4-methyl-N-(1-phenylcyclopropyl)-3-(pyridazin-4-yl)benzamide

HRID 2188976Notes

Reaction equation

HRID 2188976 reaction equation
Cl.[C:2]1([CH:8]2[CH2:10][CH:9]2N)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([N:15](C(C)C)CC)(C)C.[CH3:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][C:23]=1[C:31]1[CH:36]=[CH:35][N:34]=[N:33][CH:32]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([NH:15][C:8]2([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:10][CH2:9]2)=[O:27])=[CH:24][C:23]=1[C:31]1[CH:36]=[CH:35][N:34]=[N:33][CH:32]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 119576732-Phenylcyclopropanamine hydrochlorideHCID 667640094-Methyl-3-(pyridazin-4-yl)benzoic acid

Product 1

HCID 667636614-methyl-N-(1-phenylcyclopropyl)-3-(pyridazin-4-yl)benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 2-phenylcyclopropanamine hydrochloride (0.13 g, 0.76 mmol), diisopropylethylamine (0.88 mL, 5.0 mmol), 4-methyl-3-(pyridazin-4-yl)benzoic acid (0.14 g, 0.63 mmol) and DMF (4.2 mL) was added HATU (0.48 g, 1.3 mmol) in one portion. The solution was maintained at room temperature for 40 min. and concentrated to a residue. The residue thus obtained was purified on silica gel (0-8% methanol/dichloromethane, 45 min gradient) to afford 4-methyl-N-(1-phenylcyclopropyl)-3-(pyridazin-4-yl)benzamide. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 9.22-9.28 (m, 1 H), 9.18 (d, J=1.22 Hz, 1 H), 7.75-7.85 (m, 1 H), 7.70 (d, J=1.83 Hz, 1 H), 7.51 (dd, J=5.19, 2.44 Hz, 1 H), 7.37-7.42 (m, 1 H), 7.23-7.33 (m, 5 H), 7.15-7.21 (m, 2 H), 3.70 (dt, J=13.12, 6.56 Hz, 3 H), 3.17 (q, J=7.32 Hz, 3 H), 2.30-2.40 (m, 3 H). LCMS retention time: 1.655 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Sunfire C18, 5 micron, C18, 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% CH3CN/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3CN/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 330 (MH+).

Workup

  1. concentrationconcentrated to a residue
  2. customThe residue thus obtained
  3. customwas purified on silica gel (0-8% methanol/dichloromethane, 45 min gradient)

Sources & evidence

ORD record
ord-4e443faab60e44c9a569f2ac11396ebf
Source dataset
uspto-grants-2012_12
Patent number
US08324212B2

Reaction notes

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