L-Malic Acid → 2-((s)-2-((r)-3-Methyl-1-((s)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butyl)-5-oxo-1,3,2-dioxaborolan-4-yl)acetic acid

HRID 707678Notes

Reaction equation

HRID 707678 reaction equation
O1B([C@@H](NC(=O)[C@@H](NC(C2C=NC=CN=2)=O)CC2C=CC=CC=2)CC(C)C)[O:5][B:4]([C@@H:32]([NH:37][C:38](=[O:56])[C@@H:39]([NH:47][C:48]([C:50]2[CH:55]=[N:54][CH:53]=[CH:52][N:51]=2)=[O:49])[CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:33][CH:34]([CH3:36])[CH3:35])[O:3]B1[C@@H](NC(=O)[C@@H](NC(C1C=NC=CN=1)=O)CC1C=CC=CC=1)CC(C)C.[C:82](O)(=[O:89])[C@H:83]([CH2:85][C:86]([OH:88])=[O:87])O>C1COCC1>[CH3:35][CH:34]([CH3:36])[CH2:33][C@@H:32]([B:4]1[O:5][C@@H:83]([CH2:85][C:86]([OH:88])=[O:87])[C:82](=[O:89])[O:3]1)[NH:37][C:38](=[O:56])[C@@H:39]([NH:47][C:48]([C:50]1[CH:55]=[N:54][CH:53]=[CH:52][N:51]=1)=[O:49])[CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

4

Reactant 2

HCID 222656L-Malic AcidHCID 60071654Bortezomib boronic anhydride

Product 1

HCID 690382542-((s)-2-((r)-3-Methyl-1-((s)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butyl)-5-oxo-1,3,2-dioxaborolan-4-yl)acetic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of N,N′,N″-(boroxin-2,4,6-triyltris{[(1R)-3-methylbutane-1,1-diyl]imino[(2S)-1-oxo-3-phenylpropane-1,2-diyl]})tripyrazine-2-carboxamide (0.500 g, 0.455 mmol) and L-malic acid (213.6 mg, 0.55 mmol) were mixed in THF (5 mL). The mixture was heated to form a solution. The solution was cooled uncontrolled until the internal temperature was about 25° C. White solid precipitated out and the resultant slurry was agitated at ambient temperature for 1 h. The slurry was filtered to collect solid 2-((S)-2-((R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butyl)-5-oxo-1,3,2-dioxaborolan-4-yl)acetic acid (0.625 g, 95%). MS (m/z) in CH3CN: [M+H] calculated for C23H28BN4O7, 483.2051. found, 483.2.

Workup

  1. temperatureThe mixture was heated
  2. customto form a solution
  3. temperatureThe solution was cooled uncontrolled until the internal temperature
  4. customwas about 25° C
  5. customWhite solid precipitated out
  6. filtrationThe slurry was filtered
  7. customto collect solid 2-((S)-2-((R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butyl)-5-oxo-1,3,2-dioxaborolan-4-yl)acetic acid (0.625 g, 95%)

Sources & evidence

ORD record
ord-195f893fa6e74507a369853ea1c33977
Source dataset
uspto-grants-2015_11
Patent number
US09175018B2

Reaction notes

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