epsilon-tert-Butyloxycarbonyl-lysine → HCID 87554045, compound

HRID 2369800Notes

Reaction equation

HRID 2369800 reaction equation
[C:1]([O:5][C:6](=[O:24])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([OH:23])=O)([CH3:4])([CH3:3])[CH3:2].[B-](F)(F)(F)F.CN(C(ON1C(=O)CCC1=O)=[N+](C)C)C.[NH:45]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[C@H:46]([C:52]([OH:54])=[O:53])[CH2:47][CH2:48][CH2:49][CH2:50][NH2:51]>CN(C=O)C>[C:1]([O:5][C:6](=[O:24])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21](=[O:23])[NH:51][CH2:50][CH2:49][CH2:48][CH2:47][C@H:46]([NH:45][C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[C:52]([OH:54])=[O:53])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 2733284epsilon-tert-Butyloxycarbonyl-lysineHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 5781772316-(Tert-butoxy)-16-oxohexadecanoic acid

Product 1

HCID 87554045HCID 87554045, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Hexadecanedioic acid mono-tert-butyl ester can be activated with TSTU in similar fashion to the method described in Example 1, Step 6. The product can be reacted with Boc-Lys-OH in DMF at RT for 16 h. After concentrating under vacuum, AcOEt can be added the residue and the mixture can be washed with 0.2 N HCl. The organic phase is then dried over MgSO4 and concentrated under vacuum to yield the crude product, 15-((S)-5-tert-Butoxycarbonylamino-5-carboxypentylcarbamoyl)pentadecanoic acid tert-butyl ester. This can either be used without further purification or purified by flash chromatography. This compound can be activated with TSTU in similar fashion to the method described in Example 1, Step 6 to yield 15-[(S)-5-tert-butoxycarbonylamino-5-(2,5-dioxopyrrolidin-1-yloxycarbonyl) pentylcarbamoyl]pentadecanoic acid tert-butyl ester, and this compound can be coupled to insulin and deprotected to yield the title compound as described in Example 1, Step 7 using prepatative HPLC to isolate the product.

Workup

  1. concentrationAfter concentrating under vacuum, AcOEt
  2. additioncan be added the residue
  3. washthe mixture can be washed with 0.2 N HCl
  4. dry with materialThe organic phase is then dried over MgSO4
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-561880c8f4c34575ada51a40348d4d41
Source dataset
uspto-grants-2014_04
Patent number
US08710000B2

Reaction notes

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