Diisopropylethylamine → 2-(4-Fluorophenyl)-N-methyl-5-(3-(2-phenylpyrrolidine-1-carbonyl)phenyl)benzofuran-3-carboxamide

HRID 1025127Notes

Reaction equation

HRID 1025127 reaction equation
[C:1]1([CH:7]2[CH2:11][CH2:10][CH2:9][NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[O:20][C:21]3[CH:31]=[CH:30][C:29]([C:32]4[CH:33]=[C:34]([CH:38]=[CH:39][CH:40]=4)[C:35](O)=[O:36])=[CH:28][C:22]=3[C:23]=2[C:24](=[O:27])[NH:25][CH3:26])=[CH:15][CH:14]=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>CN(C=O)C.CO>[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[O:20][C:21]3[CH:31]=[CH:30][C:29]([C:32]4[CH:40]=[CH:39][CH:38]=[C:34]([C:35]([N:8]5[CH2:9][CH2:10][CH2:11][CH:7]5[C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)=[O:36])[CH:33]=4)=[CH:28][C:22]=3[C:23]=2[C:24]([NH:25][CH3:26])=[O:27])=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2618922-PhenylpyrrolidineHCID 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 acid

Product 1

HCID 592752662-(4-Fluorophenyl)-N-methyl-5-(3-(2-phenylpyrrolidine-1-carbonyl)phenyl)benzofuran-3-carboxamideYield 79.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

2-Phenylpyrrolidine (20 mg, 0.14 mmol) was added to a stirred suspension of 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoic acid (20 mg, 0.051 mmol), HATU (25 mg, 0.066 mmol), and DIPEA (50 μL, 0.29 mmol) in DMF (0.5 mL). The reaction was stirred at r.t. overnight. The reaction was then diluted with MeOH, filtered, and purified by prep HPLC. Concentration afforded the title compound (21 mg, 78% yield) as a light pink solid. 1H NMR (˜3:2 ratio of amide rotamers, 500 MHz, DMSO-d6) δ ppm 8.44-8.56 (m, 1 H) 7.96-8.07 (m, 2 H) 7.74-7.89 (m, 3 H) 7.56-7.67 (m, 2 H) 7.30-7.45 (m, 5.4; H) 7.16-7.29 (m, 2.6; H) 7.09 (d, J=7.02 Hz, 1H) 5.19 (t, J=6.71 Hz, 0.6; H) 4.98 (d, J=6.41 Hz, 0.4; H) 3.75-3.92 (m, 1.4; H) 3.53-3.64 (m, 0.6; H) 2.87 (m, 3 H) 2.40 (dd, J=12.36, 6.56 Hz, 0.6; H) 2.30-2.38 (m, 0.4; H) 1.73-1.92 (m, 3 H). LC/MS was performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters Micromass. LC/MS method: solvent A=10% CH3CN/90% H2O/0.1% TFA, solvent B=90% CH3CN/10% H2O/0.1% TFA, start % B=0, final % B=100, gradient time=3 min, stop time=4 min, flow rate=4 ml/min, column: Sunfire C18 5 μm 4.6×50 mm; HPLC Rt=1.86 min, (ES+) m/z (MH+)=519. Analytical 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, 3.5 μm 4.6×150 mm, Rt=14.38 min, purity=99%; column: Waters Xbridge Phenyl column 3.5 μm 4.6×150 mm, Rt=13.01 min, purity=99%.

Workup

  1. filtrationfiltered
  2. custompurified by prep HPLC
  3. concentrationConcentration

Sources & evidence

ORD record
ord-43decf85ca3947cc82b4b6e5d6df5bb5
Source dataset
uspto-grants-2014_05
Patent number
US08722688B2

Reaction notes

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