4-Methylmorpholine → HCID 131718973, compound

HRID 1654589Notes

Reaction equation

HRID 1654589 reaction equation
[NH:1]([C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[C@H:2]([C:15]([OH:17])=O)[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[NH:28]1[CH2:67][CH2:66][CH2:65][C@H:29]1[C:30]([NH:32][C@H:33]([C:44]([NH:46][C@H:47]([C:52]([NH:54][C@H:55]([C:60]([O:62][CH2:63][CH3:64])=[O:61])[CH2:56][CH:57]([CH3:59])[CH3:58])=[O:53])[C:48]([CH3:51])([CH3:50])[CH3:49])=[O:45])[CH2:34][C:35]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[NH:37][CH:36]=1)=[O:31].CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[NH3:1].[NH:1]([C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[C@H:2]([C:15]([N:28]1[CH2:67][CH2:66][CH2:65][C@H:29]1[C:30]([NH:32][C@H:33]([C:44]([NH:46][C@H:47]([C:52]([NH:54][C@H:55]([C:60]([O:62][CH2:63][CH3:64])=[O:61])[CH2:56][CH:57]([CH3:59])[CH3:58])=[O:53])[C:48]([CH3:51])([CH3:50])[CH3:49])=[O:45])[CH2:34][C:35]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[NH:37][CH:36]=1)=[O:31])=[O:17])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 98765IN2-(benzyloxycarbonyl)-N6-(tert-butoxycarbonyl)-L-lysineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 131718974HCID 131718974, compound

Product 2

HCID 222AmmoniaYield 0.1%HCID 131718973HCID 131718973, compoundYield 147.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Z-Lys(BOC) (0.75 g, 1.98 mmol), Pro-Trp-Tle-Leu-OEt (Seq ID No: 7), (1.0 g, 1.8 mmol) (prepared by catalytic hydrogenation of Z-Pro-Tle-Leu-OEt (Seq ID No: 7) over palladium on charcoal), and NMM (0.36 mL) is dissolved in 15 mL DMF, cooled to 0° C., and treated with TBTU (0.635 g, 1.98 mmol). The reaction is stirred at 0° C. for 1 hour then removed from the ice bath and stirred at room temperature for 3 hours. The mixture is poured into 150 mL of a saturated solution of sodium carbonate which is then extracted with two 150 mL portions of ethyl acetate. The combined organic extracts are washed with 150 mL of 1 M KHSO4, water and brine, and then dried over sodium sulfate. The solvents are removed under reduced pressure and the residue is chromatographed on silica gel. (2% MeOH in chloroform with 0.1% NH3) to give Z-Lys(BOC)-Pro-Trp-Tle-Leu-OEt (Seq ID No: 9) (1.34 g). FABMS M+1 818 (M-tBu)

Workup

  1. customthen removed from the ice bath
  2. stirringstirred at room temperature for 3 hours
  3. additionThe mixture is poured into 150 mL of a saturated solution of sodium carbonate which
  4. extractionis then extracted with two 150 mL portions of ethyl acetate
  5. washThe combined organic extracts are washed with 150 mL of 1 M KHSO4, water and brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvents are removed under reduced pressure
  8. customthe residue is chromatographed on silica gel

Sources & evidence

ORD record
ord-31e431dbd3da41cf966cb018a0e61d58
Source dataset
uspto-grants-1995_04
Patent number
US05407916

Reaction notes

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