Hydrochloric Acid → HCID 136070264, compound

HRID 369804Notes

Reaction equation

HRID 369804 reaction equation
[CH3:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:8]3[CH:13]=[C:14]([CH2:17][NH:18][C:19]4[CH:20]=[C:21]5[C:25](=[CH:26][CH:27]=4)[C:24](=[O:28])[N:23]([C@@H:29]([CH2:46][CH2:47][C:48]([O:50]CC)=[O:49])[C:30]([NH:32][C@H:33]([C:41]([O:43]CC)=[O:42])[CH2:34][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[O:31])[CH2:22]5)[CH:15]=[CH:16][C:7]=3[CH:6]=[CH:5][C:4]=2[N:3]=1.[OH-].[Na+].Cl>CCO>[C:48]([CH2:47][CH2:46][C@H:29]([N:23]1[CH2:22][C:21]2[C:25](=[CH:26][CH:27]=[C:19]([NH:18][CH2:17][C:14]3[CH:15]=[CH:16][C:7]4[CH:6]=[CH:5][C:4]5[N:3]=[C:2]([CH3:1])[NH:11][C:10](=[O:12])[C:9]=5[C:8]=4[CH:13]=3)[CH:20]=2)[C:24]1=[O:28])[C:30]([NH:32][C@H:33]([C:41]([OH:43])=[O:42])[CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)=[O:31])([OH:50])=[O:49]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 136136462HCID 136136462, compound

Product 1

HCID 136070264HCID 136070264, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a 100 mL 3-necked flask equipped with a magnetic stirrer and a nitrogen inlet were added 0.90 g of ethyl N-((S)-2-(5-(((1,2-dihydro-3-methyl-1-oxobenzo(f)quinazolin-9-yl)methyl)amino)-1-oxo-2-isoindolinyl)-4-(ethoxycarbonyl)butanoyl)-L-phenylalaninate, 3 mL of EtOH and 10 mL of 0.2N aqueous NaOH. The solution was stirred at RT under nitrogen for 2 h and was acidified to pH 3.0 by addition of 1N HCl. A white precipitate resulted which was separated by centrifugation. Analysis of this material by analytical HPLC (C18, 70:30:0.10 H2O:MeCN:TFA) indicated a major component at K'=1.93 (90%) and a minor component at k'=2.41. The crude product was purified by semi-preparative reverse phase HPLC (C18, 75:25:0.1 H2O:MeCN:TFA). Fractions containing pure product (k'=1.93 by analytical HPLC using above conditions) were combined and concentrated in vacuo to dryness. The residue was dissolved in 15 mL of 0.1N aqueous NaOH and the solution was adjusted to pH 3.0 by addition of 1N HCl. The resulting precipitate was collected by centrifugation, washed with four cycles of aqueous suspension-centrifugation-decantation, and lyophilized to afford 0.035 g (40%) of N-((S)-4-carboxy-2-(5-(((1,2-dihydro-3-methyl-1-oxobenzo(f)quinazolin-9-yl)methyl)amino)-1-oxo-2-isoindolinyl)butanoyl)-L-phenylalanine as a white powder, m.p. 180° C.

Workup

  1. customTo a 100 mL 3-necked flask equipped with a magnetic stirrer and a nitrogen inlet
  2. customA white precipitate resulted which
  3. customwas separated by centrifugation
  4. customThe crude product was purified by semi-preparative reverse phase HPLC (C18, 75:25:0.1 H2O:MeCN:TFA)
  5. additionFractions containing pure product (k'=1.93 by analytical HPLC
  6. concentrationconcentrated in vacuo to dryness
  7. dissolutionThe residue was dissolved in 15 mL of 0.1N aqueous NaOH
  8. additionthe solution was adjusted to pH 3.0 by addition of 1N HCl
  9. customThe resulting precipitate was collected by centrifugation
  10. washwashed with four cycles of aqueous suspension-centrifugation-decantation

Sources & evidence

ORD record
ord-b2f774a2dd984fa58a29b5cc86e69ccc
Source dataset
uspto-grants-2000_10
Patent number
US06140100

Reaction notes

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