4-Methylmorpholine → HCID 68574976, compound

HRID 1470993Notes

Reaction equation

HRID 1470993 reaction equation
Cl.[NH:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[C:7]([NH2:9])=[O:8].[CH3:10][O:11][C:12]([NH:14][C@@H:15]([CH:19]([CH3:21])[CH3:20])[C:16](O)=[O:17])=[O:13].O.N1(O)C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1>ClCCl>[C:7]([C@@H:3]1[CH2:4][CH2:5][CH2:6][N:2]1[C:16](=[O:17])[C@@H:15]([NH:14][C:12](=[O:13])[O:11][CH3:10])[CH:19]([CH3:21])[CH3:20])(=[O:8])[NH2:9]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 12707183(S)-Pyrrolidine-2-carboxamide monohydrochloride

Product 1

HCID 68574976HCID 68574976, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the product of Example 116A (21.6 g, 144 mmol), the product of Example 116B (29.1 g, 166 mmol), 1H-benzo[d][1,2,3]triazol-1-ol hydrate (27.6 g, 180 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (34.6 g, 180 mmol) and 4-methylmorpholine (63.5 mL, 578 mmol) was dissolved in dichloromethane (960 mL) and stirred at room temperature for 18 hrs. The resultant solution was then concentrated to a residue, water was then added and the solution extracted with a 25% isopropanol in chloroform solution (2×2000 mL) the organic layer washed with brine then the organic extract dried over MgSO4, then concentrated to a yellow oil which was purified by column chromatography eluting with a gradient of 0-10% methanol in dichloromethane to provide 25 g (64%) of the title compound as a colorless solid. 1H NMR (400 MHz, DMSO-d6) δ 7.28 (m, 2H), 6.81 (s, 1H), 4.24 (dd, J=8.1, 4.4 Hz, 1H), 4.00 (t, J=8.4 Hz, 1H), 3.75 (m, 1H), 3.55 (m, 1H), 3.50 (s, 3H), 2.02 (m, 1H), 1.97 (m, 2H), 1.80 (m, 2H), 0.92 (d, J=6.7 Hz, 3H), 0.86 (d, J=8.6 Hz, 3H).

Workup

  1. concentrationThe resultant solution was then concentrated to a residue, water
  2. additionwas then added
  3. extractionthe solution extracted with a 25% isopropanol in chloroform solution (2×2000 mL) the organic layer
  4. washwashed with brine
  5. extractionthe organic extract
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated to a yellow oil which
  8. customwas purified by column chromatography
  9. washeluting with a gradient of 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-c2d7037a982c43658b0e04685de03346
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Reaction notes

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