1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 67377356, compound

HRID 1667287Notes

Reaction equation

HRID 1667287 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9]/[C:10](=[N:13]/[H])/[NH:11][OH:12].[O:15]=[C:16]1[C:21]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:20][CH2:19][CH2:18][N:17]1[CH2:34][C:35](O)=O.Cl.C(N=C=NCCCN(C)C)C>ClCCCl.C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][C:10]1[N:13]=[C:35]([CH2:34][N:17]2[CH2:18][CH2:19][CH2:20][C:21]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:16]2=[O:15])[O:12][N:11]=1

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 673592802-(2-Oxo-3,3-diphenylpiperidin-1-yl)acetic acidHCID 178506469HCID 178506469, compound

Product 1

HCID 67377356HCID 67377356, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of the product of Example 262A (180 mg, 0.91 mmol), the product of Example 68E (280 mg, 0.901 mmol), and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (347 mg, 1.81 mmol) in 1,2-dichloroethane (4 mL) was stirred at ambient temperature for 3.5 hours and then heated to reflux for 16 hours. The cooled reaction mixture was diluted with CH2Cl2, washed with 1 N aqueous HCl and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was chromatographed on silica gel twice using ethyl acetate/hexanes as eluant, then finally purified by preparative HPLC on a Phenomenex® Luna® C8(2) 5 um 100 Å AXIA column (30 mm×75 mm). A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/minute (0-0.5 minutes 10% A, 0.5-7.0 minutes linear gradient 10-95% A, 7.0-10.0 minutes 95% A, 10.0-12.0 minutes linear gradient 95-10% A). Samples were injected in 1.5 mL dimethyl sulfoxide:methanol (1:1). The dried down fractions were taken up in CH2Cl2 and combined and concentrated in vacuo. Hexane was added to the residue, which caused the product to solidify. The resulting material was collected by vacuum filtration and dried in the vacuum oven at 50° C. for 4 hours to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.46-7.41 (m, 1H), 7.35-7.16 (m, 13H), 4.83 (s, 2H), 3.56 (t, J=6.3, 2H), 3.20-3.10 (m, 2H), 3.09-3.00 (m, 2H), 2.62-2.55 (m, 2H), 1.79-1.67 (m, 2H); MS (ESI+) m/z 472 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 16 hours
  3. customThe cooled reaction mixture
  4. washwashed with 1 N aqueous HCl and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was chromatographed on silica gel twice using ethyl acetate/hexanes as eluant
  9. customfinally purified by preparative HPLC on a Phenomenex® Luna® C8(2) 5 um 100 Å AXIA column (30 mm×75 mm)
  10. customwas used, at a flow rate of 50 mL/minute (0-0.5 minutes 10% A, 0.5-7.0 minutes linear gradient 10-95% A, 7.0-10.0 minutes 95% A, 10.0-12.0 minutes linear gradient 95-10% A)
  11. customThe dried down fractions
  12. concentrationcombined and concentrated in vacuo
  13. additionHexane was added to the residue, which
  14. filtrationThe resulting material was collected by vacuum filtration
  15. customdried in the vacuum oven at 50° C. for 4 hours

Sources & evidence

ORD record
ord-a662d03c8cdc437db8f1175e9db273ac
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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