1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 178436214, compound

HRID 541334Notes

Reaction equation

HRID 541334 reaction equation
[CH2:1]([C:3]1[CH:11]=[C:10]([CH2:12][CH3:13])[C:9]([C:14]2[NH:18][C:17]([CH2:19][CH2:20][O:21][CH3:22])=[N:16][N:15]=2)=[CH:8][C:4]=1[C:5]([OH:7])=O)[CH3:2].Cl.[NH:24]1[CH2:29][CH2:28][CH:27]([C:30]2[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=2)[CH2:26][CH2:25]1.CCN=C=NCCCN(C)C.Cl>CN(C)C=O.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[CH2:1]([C:3]1[CH:11]=[C:10]([CH2:12][CH3:13])[C:9]([C:14]2[NH:18][C:17]([CH2:19][CH2:20][O:21][CH3:22])=[N:16][N:15]=2)=[CH:8][C:4]=1[C:5]([N:24]1[CH2:29][CH2:28][CH:27]([C:30]2[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=2)[CH2:26][CH2:25]1)=[O:7])[CH3:2]

Participants

7

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)2×HCID 178436215HCID 178436215, compound2×

Product 1

HCID 178436214HCID 178436214, compoundYield 42.4%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a round-bottom flask was added a solution of 2,4-diethyl-5-(5-(2-methoxyethyl)-4H-1,2,4-triazol-3-yl)benzoic acid (compound 209.1, 300 mg, 0.940 mmol, 1.00 equiv, 95%) in N,N-dimethylformamide (20 mL). 4-(Piperidin-4-yl)benzonitrile hydrochloride (compound 1.5, 243 mg, 1.09 mmol, 1.10 equiv), EDC.HCl (380 mg, 1.98 mmol, 2.00 equiv), and 4-dimethylaminopyridine (240 mg, 1.96 mmol, 2.09 equiv) were added to the reaction mixture. The resulting solution was stirred overnight at room temperature, then diluted with 100 mL of ethyl acetate. The organic layer was washed with 3×15 mL of brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified using silica gel column chromatography with ethyl acetate as eluent. The crude product (300 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001 (SHIMADZU)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (35% CH3CN up to 60% in 8 min, up to 100% in 1 min, down to 35% in 1 min); Detector, Waters 2489 254&220 nm. The fractions containing pure compound were combined and lyophilized to yield 188 mg (42%) of the title compound as a white solid. m/z (ES+) 472 (M+H)+.

Workup

  1. washThe organic layer was washed with 3×15 mL of brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified
  5. customThe crude product (300 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001 (SHIMADZU))
  6. waitmobile phase, water with 0.05% TFA and CH3CN (35% CH3CN up to 60% in 8 min
  7. waitup to 100% in 1 min
  8. waitdown to 35% in 1 min)
  9. additionThe fractions containing pure compound

Sources & evidence

ORD record
ord-8390e48a16bf45529e49cacbd459b0ee
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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