Diisopropylethylamine → HCID 131736677, compound

HRID 1482156Notes

Reaction equation

HRID 1482156 reaction equation
CCN(C(C)C)C(C)C.[NH2:10][C@H:11]([C:22]([N:24]1[CH2:31][CH2:30][CH2:29][C@H:25]1[C:26]([OH:28])=[O:27])=[O:23])[CH2:12][C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[NH:15][CH:14]=1.[NH:32]([C:54]([O:56][CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)=[O:55])[C@H:33]([C:44](ON1C(=O)CCC1=O)=[O:45])[CH2:34][C:35]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[NH:37][CH:36]=1.CC(S[As](C)C)([C@@H](N)C(O)=O)C.OS([O-])(=O)=O.[K+]>C(OCC)(=O)C.CC(N(C)C)=O>[NH:32]([C:54]([O:56][CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)=[O:55])[C@H:33]([C:44]([NH:10][C@H:11]([C:22]([N:24]1[CH2:31][CH2:30][CH2:29][C@H:25]1[C:26]([OH:28])=[O:27])=[O:23])[CH2:12][C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[NH:15][CH:14]=1)=[O:45])[CH2:34][C:35]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[NH:37][CH:36]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 1350803-[(Dimethylarsanyl)sulfanyl]valineHCID 516920Potassium bisulfateHCID 9839333L-Tryptophyl-L-prolineHCID 11048356Z-Trp-OSu

Product 1

HCID 131736677HCID 131736677, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolvent2×HCID 31374DimethylacetamideSolvent

Conditions

Temperature
5 °C

Procedure

DMA, 1.05 equivalents of DIPEA (Mw=129.2) and 1.05 equivalents of H-Trp-Pro-OH (Mw=301.3; purity=91.0%) were mixed at room temperature for at least 30 min until a solution had formed. The reaction mixture was then diluted with ethyl acetate and cooled to 5±5° C. Once this temperature was reached, 1.00 equivalent of Z-Trp-OSu (Mw=435.45; purity=98.0%) was added and stirring continued for at least 30 min before the solution was left to warm up to room temperature again. After the completion of the reaction was confirmed by HPLC, 0.2 eq of, DMAPA (N,N′-Dimethylaminopropylamine, Mw=102.2 g/mol) were added. The reaction mixture was diluted with ethyl acetate and washed with a 5% (weight) aqueous NaCl solution containing 2 equivalents of KHSO4. The organic phase was further washed first with a 5% (weight) aqueous NaCl solution and finally with water. The organic phase was partially concentrated in vacuo and the residue was suspended in ethyl acetate and further concentrated in order to eliminate the remaining water. The concentrated peptide solution was added in small portions to a cold (0±5° C.) mixture of MTBE/petroleum ether (45-55) (1/1) and the precipitate was kept at 0±5° C. for at least 30 min before filtration. After filtration, it was then washed with petroleum ether (45-55) and dried in vacuo at 45° C. A white solid was finally obtained.

Workup

  1. customhad formed
  2. waitcontinued for at least 30 min before the solution
  3. waitwas left
  4. temperatureto warm up to room temperature again
  5. additionwere added
  6. washwashed with a 5% (weight) aqueous NaCl solution
  7. washThe organic phase was further washed first with a 5% (weight) aqueous NaCl solution and finally with water
  8. concentrationThe organic phase was partially concentrated in vacuo
  9. concentrationfurther concentrated in order
  10. additionThe concentrated peptide solution was added in small portions to a cold (0±5° C.) mixture of MTBE/petroleum ether (45-55) (1/1)
  11. filtrationthe precipitate was kept at 0±5° C. for at least 30 min before filtration
  12. filtrationAfter filtration, it
  13. washwas then washed with petroleum ether (45-55)
  14. customdried in vacuo at 45° C
  15. customA white solid was finally obtained

Sources & evidence

ORD record
ord-dc8f33c877dd4d47af4f3ba3c3e4de1e
Source dataset
uspto-grants-2016_08
Patent number
US09409946B2

Reaction notes

Loading…