Dicyclohexylcarbodiimide → HCID 131727877, compound

HRID 1442635Notes

Reaction equation

HRID 1442635 reaction equation
C([NH:18][C@H:19]([C:24]([S:26][NH:27][C@H:28]([CH2:36][OH:37])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:25])[C@H:20]([CH2:22][CH3:23])[CH3:21])(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O.[CH:38]1[C:50]2[CH:49]([CH2:51][O:52][C:53]([NH:55][C@@H:56]([C:61]([OH:63])=O)[CH2:57][CH:58]([CH3:60])[CH3:59])=[O:54])[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[C:42]=2[CH:41]=[CH:40][CH:39]=1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1>N1CCCCC1.CN(C=O)C>[C:53]([NH:55][C@@H:56]([C:61]([NH:18][C@H:19]([C:24]([S:26][NH:27][C@H:28]([CH2:36][OH:37])[CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:25])[C@H:20]([CH2:22][CH3:23])[CH3:21])=[O:63])[CH2:57][CH:58]([CH3:59])[CH3:60])([O:52][CH2:51][CH:49]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:42]2[C:50]1=[CH:38][CH:39]=[CH:40][CH:41]=2)=[O:54]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 1549477Fmoc-D-leucineHCID 131727878HCID 131727878, compound

Product 1

HCID 131727877HCID 131727877, compoundYield 17.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8082PiperidineSolvent

Conditions

Temperature
25 °C

Procedure

Dipeptide Fmoc-NH-L-Ile-S-Phe-CH2OH (1b) (2.0 g, 4.11 mmol) was taken in 20% piperidine in DMF (20 mL) and stirred for 15 minutes at 25° C., TLC examination showed complete removal of the Fmoc protecting group (NH2-L-Ile-S-Phe-CH2OH), further confirmed by LC/MS examination, which showed M+−1 (263.3) peak. The reaction mixture was concentrated in vacuo, excess of the piperidine was removed by co-evaporating with toluene (2×20 mL), the free amino dipeptide was further dried over high vacumn for 30 minutes, and then redissolved in dry DMF (5 mL) and added to the mixture of N-(9-fluorenylmethoxycarbonyl)-D-leucine (1.59 g, 4.52 mmol), DCC (931 mg, 4.52 mmol) and HOBt (610.0 mg, 4.52 mmol) in dry DMF (150 mL) at 25° C. The stirring was further continued for 14 h at 25° C. After 14 h white colored crystals precipitated out (DCU), which was filtered. The filterate was checked on TLC (5% MeOH: CH2Cl2) which showed formation of a new compound at higher Rf (0.5), LC/MS also showed molecular ion peak corresponding to the tripeptide 2b with other impurities peaks. The crude product was chromatographed on silica gel (Silica gel 60, 63-200μ) column and eluted with 4% MeOH: CH2Cl2 to give 450 mg of the tripeptide Fmoc-NH-D-Leu-L-Ile-S-Phe-CH2OH (2b) as a white solid. Checked on LC/MS which showed M++1 (600.3) and M++Na (622.3).

Workup

  1. customremoval of the Fmoc protecting group (NH2-L-Ile-S-Phe-CH2OH)
  2. concentrationThe reaction mixture was concentrated in vacuo, excess of the piperidine
  3. customwas removed by co-evaporating with toluene (2×20 mL)
  4. dry with materialthe free amino dipeptide was further dried over high vacumn for 30 minutes
  5. dissolutionredissolved in dry DMF (5 mL)
  6. waitThe stirring was further continued for 14 h at 25° C
  7. customAfter 14 h white colored crystals precipitated out (DCU), which
  8. filtrationwas filtered
  9. customThe crude product was chromatographed on silica gel (Silica gel 60, 63-200μ) column
  10. washeluted with 4% MeOH

Sources & evidence

ORD record
ord-29746daa39d042048dae7a07838cc7be
Source dataset
uspto-grants-2010_02
Patent number
US07659244B2

Reaction notes

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