1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 178437945, compound

HRID 541293Notes

Reaction equation

HRID 541293 reaction equation
[CH3:1][CH:2]1[CH2:7][CH:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][CH:9]=2)[CH2:5][CH2:4][NH:3]1.CCN=C=NCCCN(C)C.Cl.[CH:28]1([C:32]2[C:40]([C:41]3[NH:45][C:44]([CH2:46][CH3:47])=[N:43][N:42]=3)=[CH:39][C:35]([C:36](O)=[O:37])=[C:34]([CH3:48])[CH:33]=2)[CH2:31][CH2:30][CH2:29]1>CN(C)C=O.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[CH:28]1([C:32]2[C:40]([C:41]3[NH:45][C:44]([CH2:46][CH3:47])=[N:43][N:42]=3)=[CH:39][C:35]([C:36]([N:3]3[CH2:4][CH2:5][CH:6]([C:8]4[CH:9]=[CH:10][C:11]([C:12]#[N:13])=[CH:14][CH:15]=4)[CH2:7][CH:2]3[CH3:1])=[O:37])=[C:34]([CH3:48])[CH:33]=2)[CH2:29][CH2:30][CH2:31]1

Participants

7

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68288631HCID 68288631, compound2×HCID 178437946HCID 178437946, compound2×

Product 1

HCID 178437945HCID 178437945, compoundYield 1%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
25 °C

Procedure

To a round-bottom flask was added a solution of 4-(2-methylpiperidin-4-yl)benzonitrile (compound 176.3, 210 mg, 0.940 mmol, 1.00 equiv, 90%) in N,N-dimethylformamide (2 mL). EDC.HCl (404 mg, 2.11 mmol, 2.00 equiv), 4-dimethylaminopyridine (257 mg, 2.10 mmol, 2.00 equiv), and 4-cyclobutyl-5-(5-ethyl-4H-1,2,4-triazol-3-yl)-2-methylbenzoic acid (compound 176.4, 300 mg, 1.05 mmol, 1.00 equiv) were added to the reaction mixture. The resulting solution was stirred for 4 h at 25° C., then diluted with 50 mL of ethyl acetate. The resulting mixture was washed with 2×30 mL of NH4Cl (aq., sat.) and 2×30 mL of brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified using silica gel column chromatography with dichloromethane/methanol (20:1) as eluent. The crude product (˜20 mg) was further 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 (48% CH3CN up to 49% in 8 min, up to 100% in 3 min, down to 48% in 2 min); Detector, Waters 2489 254&220 nm. The fractions containing pure compound were combined and lyophilized to yield 3.8 mg (1%) of the title compound as a white solid. m/z (ES+) 468 (M+H)+.

Workup

  1. washThe resulting mixture was washed with 2×30 mL of NH4Cl (aq., sat.) and 2×30 mL of brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified
  5. customThe crude product (˜20 mg) was further purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  6. waitmobile phase, water with 0.05% TFA and CH3CN (48% CH3CN up to 49% in 8 min
  7. waitup to 100% in 3 min
  8. waitdown to 48% in 2 min)
  9. additionThe fractions containing pure compound

Sources & evidence

ORD record
ord-9963224cbce24affa528a8bad7d7ff15
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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