1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 18511987, compound

HRID 1370893Notes

Reaction equation

HRID 1370893 reaction equation
[CH2:1]([N:8]([CH2:21][C:22]1[CH:39]=[CH:38][C:25]([O:26][C:27]2[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][C:35](O)=[O:36])=[CH:29][CH:28]=2)=[CH:24][CH:23]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][S:16]([CH3:19])(=[O:18])=[O:17])[C:10]=1[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C[O:42][C:43](=[O:46])[CH2:44][NH2:45].C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.C(OCC)C>[CH2:1]([N:8]([CH2:21][C:22]1[CH:23]=[CH:24][C:25]([O:26][C:27]2[CH:28]=[CH:29][C:30]([CH2:33][CH2:34][C:35]([NH:45][CH2:44][C:43]([OH:46])=[O:42])=[O:36])=[CH:31][CH:32]=2)=[CH:38][CH:39]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][S:16]([CH3:19])(=[O:17])=[O:18])[C:10]=1[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 122755Glycine methyl ester hydrochlorideHCID 18511931HCID 18511931, compound

Product 1

HCID 18511987HCID 18511987, compoundYield 87.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of the product from Example 104A (0.065 g, 0.119 mmoles), glycine methyl ester hydrochloride (0.0300 g, 0.24 mmoles), and diisopropylethylamine (0.042 mL, 0.24 mmoles) in DMF (0.3 mL) was treated with EDAC (0.032 g, 0.167 mmoles) and HOBT (0.0225 g, 0.167 mmoles). The resulting mixture was shaken for 12 h. The crude products were diluted with diethyl ether, extracted with sat. NH4Cl, extracted with H2O (2×), rinsed with brine, dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel. The product was dissolved in EtOH (0.5 mL) and THF (0.5 mL) and treated with 2N NaOH (1.0 mL) for 4 h. The resulting mixture was poured into 3N HCl and extracted with ethyl acetate (2×). The combined organics were rinsed with brine, dried (Na2SO4), and concentrated under reduced pressure. Purification by preparative HPLC (CH3CN:0.1% trifluoroacetic acid in H2O) on a YMC ODS Guardpak column yielded the title compound (0.0625 g, 87%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ8.97 (s, 1 H), 8.18 (t, 1 H), 7.23 (m, 9 H), 7.00 (m, 3 H), 6.86 (m, 4 H), 4.05 (s, 2 H), 4.01 (s, 2 H), 3.73 (d, 2 H), 2.91 (s, 3 H), 2.79 (t, 2 H), 2.40 (m, 3 H), 2.39 (s, 3 H); MS (APCI) m/z 602 (M+H+).

Workup

  1. extractionextracted with sat. NH4Cl
  2. extractionextracted with H2O (2×)
  3. washrinsed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography on silica gel
  7. dissolutionThe product was dissolved in EtOH (0.5 mL)
  8. additionTHF (0.5 mL) and treated with 2N NaOH (1.0 mL) for 4 h
  9. additionThe resulting mixture was poured into 3N HCl
  10. extractionextracted with ethyl acetate (2×)
  11. washThe combined organics were rinsed with brine
  12. dry with materialdried (Na2SO4)
  13. concentrationconcentrated under reduced pressure
  14. customPurification by preparative HPLC (CH3CN:0.1% trifluoroacetic acid in H2O) on a YMC ODS Guardpak column

Sources & evidence

ORD record
ord-14024a49360e436f80ebb0f883173e13
Source dataset
uspto-grants-2003_06
Patent number
US06583180B2

Reaction notes

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