1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 178494678, compound

HRID 1487879Notes

Reaction equation

HRID 1487879 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([CH2:17][O:18][CH3:19])[NH:5][C:6]=1[C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=1[CH3:16])[C:10]([OH:12])=O.CCN=C=NCCCN(C)C.Cl.Cl.[NH:33]1[CH2:38][CH2:37][CH:36]([C:39]2[CH:46]=[CH:45][C:42]([C:43]#[N:44])=[CH:41][CH:40]=2)[CH2:35][CH2:34]1>CN(C)C=O.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[N:3]=[C:4]([CH2:17][O:18][CH3:19])[NH:5][C:6]=1[C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=1[CH3:16])[C:10]([N:33]1[CH2:38][CH2:37][CH:36]([C:39]2[CH:46]=[CH:45][C:42]([C:43]#[N:44])=[CH:41][CH:40]=2)[CH2:35][CH2:34]1)=[O:12]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)2×HCID 178494679HCID 178494679, compound2×

Product 1

HCID 178494678HCID 178494678, compoundYield 47.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

Into a 50-mL round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 3-(4-chloro-2-(methoxymethyl)-1H-imidazol-5-yl)-4-methylbenzoic acid (compound 27.5, 20 mg, 0.07 mmol) in N,N-dimethylformamide (3 mL). 4-Dimethylaminopyridine (17.4 mg, 0.14 mmol), EDC.HCl (27 mg, 0.14 mmol), 4-(piperidin-4-yl)benzonitrile hydrochloride (compound 1.2, 15.5 mg, 0.07 mmol, 1.00 equiv) were added and the resulting solution was stirred for 12 h at room temperature. The reaction was quenched with water (10 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine (10 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue 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 (35% CH3CN up to 50% in 7 min, up to 100% in 3 min, down to 35% in 1 min); Detector, Waters 2489, 254 & 220 nm. The fractions containing pure compound were combined and lyophilized to yield 15 mg (47%) of the title compound as a white solid. m/z (ES+) 449 (M+H)+.

Workup

  1. customInto a 50-mL round-bottom flask, which was purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customThe reaction was quenched with water (10 mL)
  4. extractionextracted with ethyl acetate (3×10 mL)
  5. washThe combined organic layers were washed with brine (10 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  10. waitmobile phase, water with 0.05% TFA and CH3CN (35% CH3CN up to 50% in 7 min
  11. waitup to 100% in 3 min
  12. waitdown to 35% in 1 min)
  13. additionThe fractions containing pure compound

Sources & evidence

ORD record
ord-3d0334a965fd4827b808c4fae7680cd6
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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