4-Methylmorpholine → DCCI HOBt

HRID 2419495Notes

Reaction equation

HRID 2419495 reaction equation
N(C(OC(C)(C)C)=O)[C@H](C(N[C@H](C(N[C@H](C(N1CCC[C@H]1C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(O)=O)CC1C=CC=CC=1)=O)CC(C)C)=O)[C@@H](C)OCC1C=CC=CC=1)=O)C(C)C)=O)CC(C)C)=O)=O)[C@@H](C)OCC1C=CC=CC=1)=O)CCC(=O)N)=O)COCC1C=CC=CC=1.[CH:100]1[CH:101]=[CH:102][C:103]2[N:108]([OH:109])[N:107]=[N:106][C:104]=2[CH:105]=1.[CH2:110]1[CH2:115][CH2:114][CH:113]([N:116]=[C:117]=[N:118][CH:119]2[CH2:124][CH2:123][CH2:122][CH2:121][CH2:120]2)[CH2:112][CH2:111]1.CN1CCOCC1.Cl.C1(O)C=CC=CC=1>CN(C=O)C>[CH2:122]1[CH2:121][CH2:120][CH:119]([N:118]=[C:117]=[N:116][CH:113]2[CH2:114][CH2:115][CH2:110][CH2:111][CH2:112]2)[CH2:124][CH2:123]1.[CH:100]1[CH:101]=[CH:102][C:103]2[N:108]([OH:109])[N:107]=[N:106][C:104]=2[CH:105]=1

Participants

7

Reactant 5

HCID 79724-Methylmorpholine2×HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 18767354HCID 18767354, compoundHCID 131711193HCID 131711193, compound

Product 1

HCID 21712060DCCI HOBt

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a cold solution of Boc-Ser(Bzl)-Gln-Thr(Bzl)-Pro-Leu-Val-Thr(Bzl)-Leu-Phe-OH (XVII) (0.296g, 0.215 mmol) in DMF (3.5 ml), HOBt (0.07g, 0.43 mmol) was added, followed by DCC (0.049g, 0.236 mmol). The mixture was stirred for 1 hour at 0° C while pH 7 was maintained by addition of NMM. A pre-cooled solution of the tridecapeptide amine was added and the pH adjusted to 7-8 with NMM. Stirring was continued for 2 hours at 0° C and for 3 days at room temperature. The mixture was evaporated to a small volume and treated with 4% aq. NaHCO3. The crude precipitate was filtered and washed with H2O to neutral. After drying it was triturated repeatedly with boiling MeOH to produce a white powder, 0.452g (74% based on the tridecapeptide amine). Amino acid analysis (6N HCl-phenol, 110° C, 24 hr), Lys3.8, Asp2.03, Thr1.64, Ser0.83, Glu2.12, Pro1.00, Gly1.08, Ala2.07, Val1.06, Ile2.00, Leu1.96, Tyr0.99, Phe1.00. For elemental analysis a sample was freeze-dried from DMSO; mp sintered 283°-290° dec. [α]D25 -23.8° (c 0.5, DMSO). Anal. Calcd for C192H255N29O42 (3641.384): C, 63.33; H, 7.06; N, 11.16. Found: C, 61.16; H, 7.07; N, 10.96.

Workup

  1. stirringStirring
  2. waitwas continued for 2 hours at 0° C and for 3 days at room temperature
  3. customThe mixture was evaporated to a small volume
  4. additiontreated with 4% aq. NaHCO3
  5. filtrationThe crude precipitate was filtered
  6. washwashed with H2O to neutral
  7. customAfter drying it
  8. customwas triturated repeatedly with boiling MeOH
  9. customto produce a white powder, 0.452g (74%
  10. dry with materialFor elemental analysis a sample was freeze-dried from DMSO

Sources & evidence

ORD record
ord-315688ee2f444d18aca54b6488a85094
Source dataset
uspto-grants-1978_08
Patent number
US04105652

Reaction notes

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