Diisopropylethylamine → 2-(4-Fluorophenyl)-N-methyl-5-(3-(2-(pyridin-4-yl)propan-2-ylcarbamoyl)phenyl)benzofuran-3-carboxamide

HRID 1671909Notes

Reaction equation

HRID 1671909 reaction equation
Cl.Cl.[N:3]1[CH:8]=[CH:7][C:6]([C:9]([NH2:12])([CH3:11])[CH3:10])=[CH:5][CH:4]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[F:46][C:47]1[CH:52]=[CH:51][C:50]([C:53]2[O:54][C:55]3[CH:65]=[CH:64][C:63]([C:66]4[CH:67]=[C:68]([CH:72]=[CH:73][CH:74]=4)[C:69](O)=[O:70])=[CH:62][C:56]=3[C:57]=2[C:58](=[O:61])[NH:59][CH3:60])=[CH:49][CH:48]=1>CN(C=O)C>[F:46][C:47]1[CH:52]=[CH:51][C:50]([C:53]2[O:54][C:55]3[CH:65]=[CH:64][C:63]([C:66]4[CH:74]=[CH:73][CH:72]=[C:68]([C:69](=[O:70])[NH:12][C:9]([C:6]5[CH:7]=[CH:8][N:3]=[CH:4][CH:5]=5)([CH3:11])[CH3:10])[CH:67]=4)=[CH:62][C:56]=3[C:57]=2[C:58]([NH:59][CH3:60])=[O:61])=[CH:49][CH:48]=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 592754243-[2-(4-Fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-5-yl]benzoic acidHCID 672114862-(Pyridin-4-yl)propan-2-amine dihydrochloride

Product 1

HCID 592752082-(4-Fluorophenyl)-N-methyl-5-(3-(2-(pyridin-4-yl)propan-2-ylcarbamoyl)phenyl)benzofuran-3-carboxamideYield 28.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(pyridin-4-yl)propan-2-amine dihydrochloride (26 mg, 0.123 mmol) was added to a stirring solution of HATU (59 mg, 0.154 mmol), DIEA (54 μL, 0.308 mmol), and 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoic acid (40 mg, 0.103 mmol) in DMF (1 mL) at rt. It was allowed to stir for 1 hour. The reaction was purified by preparative reverse phase HPLC on a C18 column using a suitably buffered H2O/CH3CN gradient, and concentrated to give the titled compound (15 mg, 27%). 1H NMR (500 MHz, DMSO-d6) d ppm 8.73 (1H, s), 8.50-8.55 (1H, m), 8.48 (2H, dd, J=4.58, 1.53 Hz), 8.16 (1H, s), 7.97-8.04 (2H, m), 7.91-7.94 (1H, m), 7.88 (1H, d, J=7.63 Hz), 7.85 (1H, d, J=7.93 Hz), 7.75-7.82 (2H, m), 7.58 (1H, t, J=7.63 Hz), 7.36-7.43 (4H, m), 2.86 (3H, d, J=4.58 Hz), 1.68 (6H, s). LC-MS retention time: 1.59 min; m/z (MH+): 508. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters XBridge 5u 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 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode. Additional HPLC method: Solvent A=5% CH3CN/95% H2O/0.1% TFA, Solvent B=95% CH3CN/5% H2O/0.1% TFA, Start % B=10, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min. Column: Waters Sunfire C-18, 4.6×150 mm, 3.5 mm, Rt=8.60 min, purity=95%; Column: Waters Xbridge Phenyl column 4.6×150 mm, 3.5 mm, Rt=9.26 min, purity=96%.

Workup

  1. customThe reaction was purified by preparative reverse phase HPLC on a C18 column
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-3d399281d5084ac4872b431e1d7f7bb4
Source dataset
uspto-grants-2011_08
Patent number
US07994171B2

Reaction notes

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