Methanol → HCID 67377441, compound

HRID 1667289Notes

Reaction equation

HRID 1667289 reaction equation
[Cl:1][C:2]1[CH:13]=[CH:12][C:5]([O:6][CH2:7]/[C:8](=[N:10]/[OH:11])/[NH2:9])=[CH:4][CH:3]=1.[O:14]=[C:15]1[C:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:19][CH2:18][CH2:17][N:16]1[CH2:33][C:34](O)=O.Cl.C(N=C=NCCCN(C)C)C.CO>ClCCCl.C(Cl)Cl>[Cl:1][C:2]1[CH:13]=[CH:12][C:5]([O:6][CH2:7][C:8]2[N:9]=[C:34]([CH2:33][N:16]3[CH2:17][CH2:18][CH2:19][C:20]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[C:15]3=[O:14])[O:11][N:10]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 958065979295-18-4HCID 673592802-(2-Oxo-3,3-diphenylpiperidin-1-yl)acetic acid

Product 1

HCID 67377441HCID 67377441, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of the product of Example 263A (148 mg, 0.738 mmol), the product of Example 68E (228 mg, 0.738 mmol), and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (283 mg, 1.48 mmol) in 1,2-dichloroethane (4 mL) was stirred at ambient temperature for 3 hours, then heated to reflux for 24 hours. The cooled reaction mixture was diluted with CH2Cl2 (100 mL) and washed with 1 N aqueous HCl (2×30 mL) and saturated aqueous NaHCO3 solution and brine, dried with Na2SO4, filtered, and concentrated in vacuo. The crude product was chromatographed on silica gel (Analogix® Intelliflash™ 280; SF15-24 g column; 40% ethyl acetate/hexanes) to give a viscous oil which was left standing overnight. Methanol (1 mL) was then added causing a solid to form which was collected by vacuum filtration, washed with hexanes, and air-dried to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.40-7.33 (m, 2H), 7.31-7.07 (m, 12H), 5.32 (s, 2H), 4.87 (s, 2H), 3.58 (t, J=6.3, 2H), 2.62-2.54 (m, 2H), 1.78-1.67 (m, 2H); MS (ESI+) m/z 474 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 24 hours
  3. customThe cooled reaction mixture
  4. washwashed with 1 N aqueous HCl (2×30 mL) and saturated aqueous NaHCO3 solution and brine
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was chromatographed on silica gel (Analogix® Intelliflash™ 280; SF15-24 g column; 40% ethyl acetate/hexanes)
  9. customto give a viscous oil which
  10. waitwas left
  11. customto form which
  12. filtrationwas collected by vacuum filtration
  13. washwashed with hexanes
  14. customair-dried

Sources & evidence

ORD record
ord-b235682465994bc1b6580e55ff4d67e5
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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