Ethyl Acetate → HCID 178455937, compound

HRID 268504Notes

Reaction equation

HRID 268504 reaction equation
[NH:1]1[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([NH:9][C@H:10]([C:21]([N:23]1[CH2:30][CH2:29][CH2:28][C@H:24]1[C:25](O)=[O:26])=[O:22])[CH2:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)=[O:8].C(OC(Cl)=O)C(C)C.[NH2:39][C@H:40]([C:48]([N:50]1[CH2:88][CH2:87][CH2:86][C@H:51]1[C:52]([NH:54][C@H:55]([C:61]([NH:63][C@H:64]([C:69]([N:71]1[CH2:85][CH2:84][CH2:83][C@H:72]1[C:73]([N:75]1[CH2:82][CH2:81][CH2:80][C@H:76]1[C:77]([OH:79])=[O:78])=[O:74])=[O:70])[C@H:65]([CH2:67][CH3:68])[CH3:66])=[O:62])[CH2:56][CH2:57][C:58](=[O:60])[NH2:59])=[O:53])=[O:49])[CH2:41][CH2:42][CH2:43][NH:44][C:45](=[NH:47])[NH2:46].CCOC(C)=O>CN(C=O)C.CC(O)=O>[NH:1]1[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([NH:9][C@H:10]([C:21]([N:23]1[CH2:30][CH2:29][CH2:28][C@H:24]1[C:25]([NH:39][C@H:40]([C:48]([N:50]1[CH2:88][CH2:87][CH2:86][C@H:51]1[C:52]([NH:54][C@H:55]([C:61]([NH:63][C@H:64]([C:69]([N:71]1[CH2:85][CH2:84][CH2:83][C@H:72]1[C:73]([N:75]1[CH2:82][CH2:81][CH2:80][C@H:76]1[C:77]([OH:79])=[O:78])=[O:74])=[O:70])[C@H:65]([CH2:67][CH3:68])[CH3:66])=[O:62])[CH2:56][CH2:57][C:58](=[O:60])[NH2:59])=[O:53])=[O:49])[CH2:41][CH2:42][CH2:43][NH:44][C:45](=[NH:46])[NH2:47])=[O:26])=[O:22])[CH2:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)=[O:8]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 62365Isobutyl chloroformateHCID 227887495-Oxo-L-prolyl-L-tryptophyl-L-prolineHCID 178455939HCID 178455939, compound

Product 1

HCID 178455937HCID 178455937, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent2×

Procedure

The tripeptide, from part C, Pyr-Trp-Pro (23.3 mmoles) is dissolved in DMF (85 ml) and 3.27 ml (23.3 mmoles) TEA, the solution cooled to -20° (inside the flask, or -35° to -40° in the cooling bath) and kept at this temperature for 15-20 minutes. To this cold solution 3.19 ml of isobutyloxycarbonyl chloride is added and then a time of 30 minutes is allowed for the mixed anhydride to be formed at the same temperature. A solution of Arg-Pro-Gln-Ile-Pro-Pro (16.5 g) in DMF (100 ml) is precooled to about 0° and then added into the solution of the mixed anhydride. At this moment, the pH value is adjusted to 8 with TEA (8.5 ml) while the temperature of 0° is maintained. After 20 to 24 hours at room temperature, the volume of the solvents is reduced to 1/3-1/4 and poured into 20-25 volumes of EtOAc containing 3 % of AcOH. The precipitate is washed thoroughly with EtOAc and then dried in vacuo over KOH overnight to yield the title compound. This material is dissolved in water, sterilized by filtration, and the sterile aqueous solution freeze-dried to a free flowing powder. The powder is reconstituted for injection with water for injection or saline.

Workup

  1. customa time of 30 minutes
  2. customto be formed at the same temperature
  3. customis precooled to about 0°
  4. temperatureis maintained
  5. waitAfter 20 to 24 hours at room temperature
  6. washThe precipitate is washed thoroughly with EtOAc
  7. dry with materialdried in vacuo over KOH overnight

Sources & evidence

ORD record
ord-e02a60ef8f7446beb49fa3bb0f63bda8
Source dataset
uspto-grants-1976_03
Patent number
US03947575

Reaction notes

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