4-Methylmorpholine → 4-(Cbz-valinyl-amino)-2-(N-((N-((3-pyridinyl)methyl)amino)-carbonyl)-valinyl-amino)-1,5-diphenyl-3-hydroxypentane

HRID 1078138Notes

Reaction equation

HRID 1078138 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][CH:8]=1.[C:9]([NH:19][C@H:20]([C:24]([NH:26][CH:27]([CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[CH:28]([OH:45])[CH:29]([NH:37][C:38](=[O:44])[C@H:39]([CH:41]([CH3:43])[CH3:42])[NH2:40])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:25])[CH:21]([CH3:23])[CH3:22])([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10].CN1CC[O:57][CH2:56]C1>[N+](C)([O-])=O.CN(C)C=O>[C:9]([NH:19][C@H:20]([C:24]([NH:26][CH:27]([CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[CH:28]([OH:45])[CH:29]([NH:37][C:38](=[O:44])[C@H:39]([CH:41]([CH3:43])[CH3:42])[NH:40][C:56]([NH:1][CH2:2][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][CH:8]=1)=[O:57])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:25])[CH:21]([CH3:23])[CH3:22])([O:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:10]

Participants

6

Reactant 3

HCID 79724-MethylmorpholineHCID 310183-PyridinemethanamineHCID 228456514-(Cbz-valinyl-amino)-2-(valinyl-amino)-1,5-diphenyl-3-hydroxypentane

Product 1

HCID 228644644-(Cbz-valinyl-amino)-2-(N-((N-((3-pyridinyl)methyl)amino)-carbonyl)-valinyl-amino)-1,5-diphenyl-3-hydroxypentaneYield 67.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6375NitromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 3-(aminomethyl)pyridine (12 μl, 0.11 mmol) in 0.5 ml of nitromethane was cooled to -20° C. and treated with 0.23 ml (0.12 mmol) of a 0.5M solution of carbonyl bis (N-methyl) imidazole triflate (Rappoport, et. al., J. Am. Chem. Soc. 1989, 111, 6856) in nitromethane. After 30 min, the solution was treated with a solution of 50 mg (0.08 mmol) of the resultant compound of Example 240 in 1.0 ml of dimethylformamide and 26 μL. (0.24 mmol) of 4-methylmorpholine. The resulting solution was stirred at 0° C. for 1 h, concentrated in vacuo, partitioned between chloroform and aqueous NaHCO3, dried over Na2SO4, and concentrated. The residue was purified by silica gel chromatography using 3% methanol in chloroform to provide 40 mg (65%) of the desired compound (Rf 0.4, 10% methanol in chloroform) as a white solid, m.p. 205°-206° C. Mass spectrum: (M+H)+ =737.

Workup

  1. concentrationconcentrated in vacuo
  2. custompartitioned between chloroform and aqueous NaHCO3
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-bbbec0d7479b43dbab23e9ca4cd941f4
Source dataset
uspto-grants-1996_08
Patent number
US05545750

Reaction notes

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