Ethyl Acetate → 5-(4-(Benzofuran-6-yl)piperidine-1-carbonyl)-2-cyclobutyl-N,4-dimethylbenzamide

HRID 1487927Notes

Reaction equation

HRID 1487927 reaction equation
[O:1]1[C:5]2[CH:6]=[C:7]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)[CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1.[CH:16]1([C:20]2[C:28]([C:29](=[O:32])[NH:30][CH3:31])=[CH:27][C:23]([C:24](O)=[O:25])=[C:22]([CH3:33])[CH:21]=2)[CH2:19][CH2:18][CH2:17]1.CCN=C=NCCCN(C)C.Cl.CCOC(C)=O>CN(C)C1C=CN=CC=1.CN(C)C=O>[O:1]1[C:5]2[CH:6]=[C:7]([CH:10]3[CH2:15][CH2:14][N:13]([C:24]([C:23]4[C:22]([CH3:33])=[CH:21][C:20]([CH:16]5[CH2:19][CH2:18][CH2:17]5)=[C:28]([CH:27]=4)[C:29]([NH:30][CH3:31])=[O:32])=[O:25])[CH2:12][CH2:11]3)[CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 227291634-(Benzofuran-6-yl)piperidine2×HCID 900220514-Cyclobutyl-2-methyl-5-(methylcarbamoyl)benzoic acid2×

Product 1

HCID 900666845-(4-(Benzofuran-6-yl)piperidine-1-carbonyl)-2-cyclobutyl-N,4-dimethylbenzamideYield 20%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
15 °C

Procedure

Into a 25-mL round-bottom flask, was placed a solution of 4-(benzofuran-6-yl)piperidine (compound 63.6) (110 mg, 0.55 mmol), 4-cyclobutyl-2-methyl-5-(methylcarbamoyl)benzoic acid (compound 62.3, 135 mg, 0.55 mmol), EDC.HCl (210 mg, 1.10 mmol) and 4-dimethylaminopyridine (133.5 mg, 1.09 mmol) in N,N-dimethylformamide (3 mL). The resulting solution was stirred for 2 h at 15° C. then diluted EtOAc (60 mL). The resulting mixture was washed with aqueous saturated NH4Cl (2×20 mL) and brine (20 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product (110 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, water with 0.05% TFA and CH3CN (51.0% CH3CN up to 60.0% in 9 min, up to 100.0% in 5 min, down to 51.0% in 1 min); Detector, Waters 2489, 254 & 220 nm. The fractions containing pure compound were combined and lyophilized to yield the title compound as a white solid (46.0 mg, 20%). m/z (ES+) 431 (M+H)+.

Workup

  1. customInto a 25-mL round-bottom flask, was placed
  2. washThe resulting mixture was washed with aqueous saturated NH4Cl (2×20 mL) and brine (20 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product (110 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  7. waitmobile phase, water with 0.05% TFA and CH3CN (51.0% CH3CN up to 60.0% in 9 min
  8. waitup to 100.0% in 5 min
  9. waitdown to 51.0% in 1 min)
  10. additionThe fractions containing pure compound

Sources & evidence

ORD record
ord-ec743cd6d901458f85e10bb0a89458a3
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

Loading…