4-Methylmorpholine → HCID 20622837, compound

HRID 2121253Notes

Reaction equation

HRID 2121253 reaction equation
[CH2:1]([N:8]([CH2:15][C:16]1[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[C:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH3:31])[CH:17]=1)[C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:33][O:34][C:35](=[O:42])[C@H:36]([CH2:38][CH2:39][S:40][CH3:41])[NH2:37].C1C=C2C(N(O)N=NC2=CC=1)=O.CCN=C=NCCCN(C)C.CN1CCOCC1>CN(C=O)C.O>[CH3:33][O:34][C:35](=[O:42])[C@H:36]([CH2:38][CH2:39][S:40][CH3:41])[NH:37][C:20](=[O:21])[C:19]1[CH:23]=[CH:24][C:16]([CH2:15][N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)=[CH:17][C:18]=1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH3:31]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 730263-hydroxy-1,2,3-benzotriazin-4(3H)-oneHCID 11435579L-Methionine, methyl ester, hydrochlorideHCID 11795733HCID 11795733, compound

Product 1

HCID 20622837HCID 20622837, compoundYield 96.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of product of Example 407B (12.34 g, 29 mmol) in DMF (80 mL) was added successively methionine methyl ester hydrochloride (7.53 g, 37.7 mmol, 1.3 eq), HOOBt (5.21 g, 31.9 mmol, 1.1 eq), EDCI (6.11 g, 31.9 mmol, 1.1 eq) and 4-methylmorpholine (5.1 mL, 46.4 mmol, 1.6 eq). The mixture was stirred overnight, then poured into water and extracted with ethyl acetate. The organic solution was washed successively with water, sodium carbonate and sodium chloride, dried (Na2SO4), concentrated in vacuo, and the residue purified by flash chromatography on silica gel eluting with 70% ethyl acetate—hexanes changing to 100% ethyl acetate to yield the title compound (15.51 g, 96%).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic solution was washed successively with water, sodium carbonate and sodium chloride
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customthe residue purified by flash chromatography on silica gel eluting with 70% ethyl acetate—hexanes changing to 100% ethyl acetate

Sources & evidence

ORD record
ord-8d9fb0dec63944e38497c0aab758f074
Source dataset
uspto-grants-2004_02
Patent number
US06693123B2

Reaction notes

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