Hydrochloric Acid → HCID 178427569, compound

HRID 743146Notes

Reaction equation

HRID 743146 reaction equation
[N:1]1([C:13]([O:15]C(C)(C)C)=O)[CH2:12][CH2:11][CH2:10][C@H:2]1[C:3]([NH:5][CH2:6][C:7]([NH2:9])=[O:8])=[O:4].Cl.C(OCC)C.Cl.C[O-].[Na+].C1C=CC2N(O)N=NC=2C=1.[NH:40]([C:70]([O:72][CH2:73][CH:74]1[C:86]2[C:81](=[CH:82][CH:83]=[CH:84][CH:85]=2)[C:80]2[C:75]1=[CH:76][CH:77]=[CH:78][CH:79]=2)=[O:71])[C@H:41](C(O)=O)[CH2:42][CH2:43][CH2:44][NH:45][C:46](=[NH:66])[NH:47][S:48]([C:51]1[C:64]([CH3:65])=[C:62]([CH3:63])[C:61]2[O:60][C:57]([CH3:59])([CH3:58])[CH2:56][CH2:55][C:54]=2[C:52]=1[CH3:53])(=[O:50])=[O:49].CCN=C=NCCCN(C)C.CN1CCOCC1>CN(C=O)C.C1COCC1.C(OCC)C>[NH:40]([C:70]([O:72][CH2:73][CH:74]1[C:86]2[C:81](=[CH:82][CH:83]=[CH:84][CH:85]=2)[C:80]2[C:75]1=[CH:76][CH:77]=[CH:78][CH:79]=2)=[O:71])[C@H:41]([C:13]([N:1]1[CH2:12][CH2:11][CH2:10][C@H:2]1[C:3]([NH:5][CH2:6][C:7]([NH2:9])=[O:8])=[O:4])=[O:15])[CH2:42][CH2:43][CH2:44][NH:45][C:46](=[NH:66])[NH:47][S:48]([C:51]1[C:64]([CH3:65])=[C:62]([CH3:63])[C:61]2[O:60][C:57]([CH3:58])([CH3:59])[CH2:56][CH2:55][C:54]=2[C:52]=1[CH3:53])(=[O:50])=[O:49]

Participants

12

Reactant 8

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 7256544Boc-Pro-Gly-NH2HCID 10942334Sodium MethoxideHCID 10953452Ether hydrochlorideHCID 178427573HCID 178427573, compound

Product 1

HCID 178427569HCID 178427569, compoundYield 93.5%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

(See SEQUENCE ID NO: 10) 540 mg (2.0 mmol) of Boc-Pro-Gly-NH2 are dissolved in 5 ml abs. THF and mixed while stirring with 3 ml HCl/diethyl ether (abs. diethyl ether is for this saturated with hydrogen chloride at 0° C.). After 0.5 hours the solvent is removed under vacuum and co-evaporated three times with 5 ml toluene on each occasion. 110 mg (2.0 mmol) NaOMe are added to 5 ml abs. THF and after 5 min 5 ml DMF, 300 mg (2.0 mmol) HOBT and 1.32 g Fmoc-Arg(Pmc)-OH. Cooling to -10° C. takes place, 600 mg (3 mmol) EDCI are added and a pH of 7.0 is set with 0.33 ml NMM. After 15 hours of stirring the solvent is removed under vacuum, the resulting syrup absorbed in 150 ml ethyl acetate and the organic phase washed three times with 10 ml 0.5 N HCl, 10% NaHCO3 solution and H2O respectively. The organic phase is dried with MgSO4, the solvent distilled off under vacuum and the product precipitated from hexane. 1.52 g (93%) of thin-layer chromatographically identical Fmoc-Arg(Pmc)-Pro-Gly-NH2 are obtained as a colourless powder.

Workup

  1. dissolutionare dissolved in 5 ml abs
  2. customat 0° C.
  3. customAfter 0.5 hours the solvent is removed under vacuum
  4. additionare added
  5. customis removed under vacuum
  6. customthe resulting syrup absorbed in 150 ml ethyl acetate
  7. washthe organic phase washed three times with 10 ml 0.5 N HCl, 10% NaHCO3 solution and H2O respectively
  8. dry with materialThe organic phase is dried with MgSO4
  9. distillationthe solvent distilled off under vacuum
  10. customthe product precipitated from hexane

Sources & evidence

ORD record
ord-5413d16f89ec4ca6bf43e7328d0cc330
Source dataset
uspto-grants-1996_09
Patent number
US05556836

Reaction notes

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