1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 178424689, compound

HRID 1488115Notes

Reaction equation

HRID 1488115 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([CH2:18][OH:19])[NH:5][C:6]=1[C:7]1[C:8]([CH3:17])=[CH:9][C:10]([CH3:16])=[C:11]([CH:15]=1)[C:12]([OH:14])=O.Cl.[F:21][C:22]1([C:26]2[CH:33]=[CH:32][C:29]([C:30]#[N:31])=[CH:28][CH:27]=2)[CH2:25][NH:24][CH2:23]1.CCN=C=NCCCN(C)C.Cl>CN(C)C=O.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[N:3]=[C:4]([CH2:18][OH:19])[NH:5][C:6]=1[C:7]1[C:8]([CH3:17])=[CH:9][C:10]([CH3:16])=[C:11]([CH:15]=1)[C:12]([N:24]1[CH2:23][C:22]([C:26]2[CH:27]=[CH:28][C:29]([C:30]#[N:31])=[CH:32][CH:33]=2)([F:21])[CH2:25]1)=[O:14]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 900213344-(3-Fluoroazetidin-3-yl)benzonitrile hydrochloride2×HCID 178424690HCID 178424690, compound2×

Product 1

HCID 178424689HCID 178424689, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

Into a 50-mL round-bottom flask, was placed a solution of 5-(4-chloro-2-(hydroxymethyl)-1H-imidazol-5-yl)-2,4-dimethylbenzoic acid (compound 230.6, 180 mg, 0.64 mmol) in N,N-dimethylformamide (15 mL). 4-(3-fluoroazetidin-3-yl)benzonitrile hydrochloride (compound 43.4, 165 mg, 0.78 mmol), EDC.HCl (245 mg, 1.28 mmol) and 4-dimethylaminopyridine (310 mg, 2.54 mmol) were added to the reaction. The reaction mixture was stirred overnight at 25° C. The reaction was then quenched with 5 mL of water. The reaction mixture was extracted with 3×10 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 5×10 mL of brine. The resulting mixture was concentrated under reduced pressure. The crude product (200 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001 (SHIMADZU)): Column, SunFire Prep C18 OBD Column, 5 μm, 19*150 mm; mobile phase, WATER WITH 0.05% TFA and ACN (26.0% ACN up to 39.0% in 10 min, up to 100.0% in 2 min, down to 26.0% in 1 min); Detector, Waters 2489, 254 and 220 nm. This resulted in 84 mg (30%) of the title compound as a white solid. m/z (ES+) 439 (M+H)+.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. customThe reaction was then quenched with 5 mL of water
  3. extractionThe reaction mixture was extracted with 3×10 mL of ethyl acetate
  4. washThe resulting mixture was washed with 5×10 mL of brine
  5. concentrationThe resulting mixture was concentrated under reduced pressure
  6. customThe crude product (200 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001 (SHIMADZU))
  7. waitmobile phase, WATER WITH 0.05% TFA and ACN (26.0% ACN up to 39.0% in 10 min
  8. waitup to 100.0% in 2 min
  9. waitdown to 26.0% in 1 min)

Sources & evidence

ORD record
ord-ebcaec7ce5214fc88902a78077310325
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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