Hydrochloric Acid → HCID 131716233, compound

HRID 329550Notes

Reaction equation

HRID 329550 reaction equation
C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[NH:18]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@H:19]([C:21]([OH:23])=O)[CH3:20].CCN(C(C)C)C(C)C.Cl.[NH2:41][C@H:42]([C:48]([NH:50][C@H:51]([C:61]([NH:63][CH2:64][C:65]([NH:67][C@H:68]([C:73]([NH:75][CH2:76][C:77]([O:79][CH3:80])=[O:78])=[O:74])[CH2:69][CH:70]([CH3:72])[CH3:71])=[O:66])=[O:62])[CH2:52][O:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)=[O:49])[CH2:43][CH2:44][C:45](=[O:47])[NH2:46]>>[NH:18]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@H:19]([C:21]([NH:41][C@H:42]([C:48]([NH:50][C@H:51]([C:61]([NH:63][CH2:64][C:65]([NH:67][C@H:68]([C:73]([NH:75][CH2:76][C:77]([O:79][CH3:80])=[O:78])=[O:74])[CH2:69][CH:70]([CH3:71])[CH3:72])=[O:66])=[O:62])[CH2:52][O:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)=[O:49])[CH2:43][CH2:44][C:45](=[O:47])[NH2:46])=[O:23])[CH3:20]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 85082Tert-butoxycarbonylalanineHCID 199401P,P-Diphenylphosphinic azideHCID 15779956HCID 15779956, compound

Product 1

HCID 131716233HCID 131716233, compoundYield 99.1%

Conditions

Temperature
0 °C

Procedure

The title compound of this example: DPPA (12.38 g, 45 mmol) was added to a cooled solution (0° C.) of Boc-Ala-OH (3.2 g, 45 mmol) and DIEA (7.8 mL, 45 mmol). The mixture was stirred at 0° C. for 15 min. The pentapeptide from paragraph (d), HCl.H-Gln-Ser(Bzl)-Gly-Leu-Gly-OCH3 (9.0 g, 15 mmol), was added to the mixture. The mixture was stirred for 18 h while the temperature of the mixture gradually came to room temperature. The mixture was concentrated to dryness. The resultant solid was triturated with EtOAc, collected on a filter, and washed with Et2O and then with hexane. The collected solid was suspended in Et2O and the suspension stirred vigorously for 1 h. The solid was collected on a filter and dried to give Boc-Ala-Gln-Ser(Bzl)-Gly-Leu-Gly-OCH3 (10.94 g). The latter compound (6.0 g, 8.15 mmol) was suspended in dioxane (150 mL) and H2 0 (200 mL). The suspension was stirred and cooled to 0° C. A solution of NaOH (425 mg, 10.6 mmol) was added dropwise to the cooled suspension. The mixture was stirred at room temperature until it became clear (2 h). The mixture was rendered acidic (pH=4) by the addition of acetic acid and then concentrated under reduced pressure (after addition of isopropanol to prevent foaming). The residue was dissolved in the minimum amount of butanol/H2O/acetic acid (4:5:1). The solution was passed through a column of Sephadex (tradename for a brand of cross linked chains of organic compounds derived from dextran). The pure fractions were combined to give the desired hexapeptide i.e. the title compound of this example, as the HCl addition salt (4.90 g).

Workup

  1. stirringThe mixture was stirred for 18 h while the temperature of the mixture
  2. customgradually came to room temperature
  3. concentrationThe mixture was concentrated to dryness
  4. customThe resultant solid was triturated with EtOAc
  5. customcollected on a filter
  6. washwashed with Et2O
  7. stirringthe suspension stirred vigorously for 1 h
  8. customThe solid was collected on
  9. filtrationa filter
  10. customdried

Sources & evidence

ORD record
ord-5784fa20cb744a4fb31b01632261e907
Source dataset
uspto-grants-1990_01
Patent number
US04891358

Reaction notes

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