Dimethylamine → 5-(3-(1-(Dimethylamino)-2-methyl-1-oxopropan-2-ylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 1877591Notes

Reaction equation

HRID 1877591 reaction equation
[CH3:1][NH:2][CH3:3].C1COCC1.[F:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[O:17][C:18]3[CH:28]=[CH:27][C:26]([C:29]4[CH:30]=[C:31]([CH:41]=[CH:42][CH:43]=4)[C:32]([NH:34][C:35]([CH3:40])([CH3:39])[C:36](O)=[O:37])=[O:33])=[CH:25][C:19]=3[C:20]=2[C:21](=[O:24])[NH:22][CH3:23])=[CH:12][CH:11]=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>[CH3:1][N:2]([CH3:3])[C:36](=[O:37])[C:35]([NH:34][C:32]([C:31]1[CH:30]=[C:29]([C:26]2[CH:27]=[CH:28][C:18]3[O:17][C:16]([C:13]4[CH:12]=[CH:11][C:10]([F:9])=[CH:15][CH:14]=4)=[C:20]([C:21]([NH:22][CH3:23])=[O:24])[C:19]=3[CH:25]=2)[CH:43]=[CH:42][CH:41]=1)=[O:33])([CH3:39])[CH3:40]

Participants

7

Reactant 5

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592755572-(3-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzamido)-2-methylpropanoic acid

Product 1

HCID 592754265-(3-(1-(Dimethylamino)-2-methyl-1-oxopropan-2-ylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamideYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of dimethylamine in THF (2 molar, 0.10 mL, 0.20 mmol) was added to 2-(3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzamido)-2-methylpropanoic acid (17 mg, 0.036 mmol) and HATU (15 mg, 0.039 mmol) in a 1 dram vial. DMF (0.3 mL) was added, the vial was capped, and the homogeneous solution was stirred at r.t. for 1 h, at which point DIPEA (50 μL, 0.29 mmol) was added. Stirring was continued for 3 h, at which point the reaction was filtered and purified directly by prep HPLC. Concentration of the collected fractions afforded the title compound as a white solid (13 mg, 71% yield). 1H NMR (500 MHz, CD3OD) δ ppm 8.09-8.17 (m, 1H) 7.90-7.98 (m, 3H) 7.86 (d, J=7.94 Hz, 1H) 7.79-7.84 (m, 1H) 7.63-7.72 (m, 2H) 7.57 (t, J=7.63 Hz, 1H) 7.20-7.32 (m, 2H) 3.14 (br. s., 3H) 2.98 (s, 6H) 1.61 (s, 6H). LC/MS was performed on a Shimadzu-VP instrument with UV detection at 220 nm and Waters Micromass. LC/MS method: solvent A=5% CH3CN/95% H2O/10 mM NH4OAc, solvent B=95% CH3CN/5% H2O/10 mM NH4OAc, start % B=0, final % B=100, gradient time=2 min, stop time=3 min, flow rate=5 ml/min, column: XBridge C18 5 μm 4.6×50 mm; HPLC Rt=1.29 min, (ES+) m/z (MH+)=502. 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=14.80 min, purity=100%; column: Waters Xbridge Phenyl 3.5 μm 4.6×150 mm, Rt=10.37 min, purity=100%.

Workup

  1. customthe vial was capped
  2. additionwas added
  3. filtrationwas filtered
  4. custompurified directly by prep HPLC

Sources & evidence

ORD record
ord-8ed2f646ee94443ab86d39139be2e7d0
Source dataset
uspto-grants-2012_11
Patent number
US08309558B2

Reaction notes

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