HCID 11379871, compound → HCID 86758458, compound

HRID 2304365Notes

Reaction equation

HRID 2304365 reaction equation
[C:1]([S:9][C@@H:10]([CH2:14][CH2:15][CH2:16][N:17]1[C:25](=[O:26])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]1=[O:27])[C:11](O)=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28][C:29]([CH3:45])([CH3:44])[C@H:30]([NH:35][C:36](=[O:43])[C@@H:37]([NH2:42])[CH2:38][CH:39]([CH3:41])[CH3:40])[C:31](=[O:34])[NH:32][CH3:33]>C(OCC)(=O)C.O>[CH3:45][C:29]([CH3:28])([CH3:44])[C@H:30]([NH:35][C:36](=[O:43])[C@@H:37]([NH:42][CH2:11][C@@H:10]([S:9][C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:14][CH2:15][CH2:16][N:17]1[C:25](=[O:26])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]1=[O:27])[CH2:38][CH:39]([CH3:41])[CH3:40])[C:31](=[O:34])[NH:32][CH3:33]

Participants

5

Reactant 2

HCID 11379871HCID 11379871, compoundHCID 15972983HCID 15972983, compound

Product 1

HCID 86758458HCID 86758458, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-2-Benzoylsulfanyl-5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)pentanoic acid (62.6 g, 0.163 mol) and (S)-2-amino-4-methylpentanoic acid (2,2-dimethyl-1-(S)-methylcarbamoylpropyl)amide (40 g, 0.155 mol) were dissolved in a biphasic mixture of ethyl acetate (480 mL) and water (240 mL) at 45° C. and stirred to equilibrate for 10 min. An HPLC reference sample was removed for t=0. The PeptiCLEC-TR enzyme (40 mL) is added to the reaction and the reaction is stirred at 45° C. Samples are removed at regular intervals for HPLC analysis which shows that the reaction is complete in 2 hours. Filtration of tile enzyme followed by acidic then basic aqueous washes gives a solution of (S)-2-[(S)-2-benzoylsulfanyl-5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)pentanylamino]-4-methylpentanoic acid (2,2-dimethyl-1(S)-methylcarbamoylpropyl)amide which is then evaporated to dryness to give the product as a glass foam 80 g, 83%.

Workup

  1. customAn HPLC reference sample was removed for t=0
  2. additionThe PeptiCLEC-TR enzyme (40 mL) is added to the reaction
  3. stirringthe reaction is stirred at 45° C
  4. customSamples are removed at regular intervals for HPLC analysis which
  5. waitis complete in 2 hours
  6. filtrationFiltration of tile enzyme

Sources & evidence

ORD record
ord-fec03a3ad02842a1bf7ac0207e77e2c9
Source dataset
uspto-grants-2002_08
Patent number
US06436697B1

Reaction notes

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