4-Methylmorpholine → HCID 86621120, compound

HRID 601718Notes

Reaction equation

HRID 601718 reaction equation
C(N1[C@H:12]([CH3:13])[C@H:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)OC1=O)(=O)CCCCC.Cl.[CH2:22]([O:24][C:25](=[O:36])[C@H:26]([CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[NH2:27])[CH3:23].CN(C([O:44]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CN(C=O)C>[CH2:11]([C@H:14]([CH2:15][CH2:16][CH2:17][CH3:18])[C:19]([NH:27][C@@H:26]([CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:25]([O:24][CH2:22][CH3:23])=[O:36])=[O:44])[CH:12]=[CH2:13]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 2734606Ethyl (2S)-2-amino-4-phenylbutanoate--hydrogen chloride (1/1)HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10858719HCID 10858719, compound

Product 1

HCID 86621120HCID 86621120, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the compound of step G (3) (421 mg, 2.69 mmol) and homophenylalanine ethyl ester hydrochloride (789 mg, 3.24 mmol) in DMF (30.1 mL) was added HATU (1.54 g, 3.24 mmol) and N-Methyl morpholine (1.24 mL, 9.42 mmol). The reaction was stirred at rt until LC showed conversion to product (<30 min). DMF was removed in vacuo, the residue suspended in water, and the product extracted 3 times to ethyl acetate. The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was suspended in a minimal amount of methylene chloride and filtered through glass wool. The solution was loaded onto a silica gel column, and pure product was obtained following elution with a ethyl acetate/hexane gradient (836 mg, 90%). 1H NMR (500 MHz, CDCl3) δ ppm 0.88 (t, J=7.02 Hz, 3H) 1.19-1.38 (m, 7H) 1.40-1.50 (m, 1H) 1.57-1.69 (m, 1H) 1.92-2.06 (m, 1H) 2.08-2.26 (m, 3H) 2.28-2.41 (m, 1H) 2.52-2.75 (m, 2H) 4.18 (q, J=7.32 Hz, 2H) 4.61-4.74 (m, 1H) 4.95-5.11 (m, 2H) 5.69-5.84 (m, 1H) 5.96 (d, J=7.63 Hz, 1H) 7.10-7.34 (m, 5H). HPLC retention time: 1.76 min (method A). MS (ESI) (M+H)+ 346.

Workup

  1. customto product (<30 min)
  2. customDMF was removed in vacuo
  3. extractionthe product extracted 3 times to ethyl acetate
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. filtrationfiltered through glass wool
  8. custompure product was obtained
  9. washelution with a ethyl acetate/hexane gradient (836 mg, 90%)

Sources & evidence

ORD record
ord-380d73af2f3a431c9f55b02f3cdc5c64
Source dataset
uspto-grants-2011_03
Patent number
US07902218B2

Reaction notes

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