Hydrochloric Acid → (2S)-2-[5-[[(1,2-Dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl]amino]-1,3-dihydro-1-oxo-2H-isoindol-2-yl]pentanedioic acid

HRID 381587Notes

Reaction equation

HRID 381587 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]([CH2:35][CH2:36][C:37]([O:39]CC)=[O:38])[C:30]([O:32]CC)=[O:31])[CH2:22]5)[CH:15]=[CH:16][C:7]=3[CH:6]=[CH:5][C:4]=2[N:3]=1.Cl>[OH-].[Na+]>[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]([CH2:35][CH2:36][C:37]([OH:39])=[O:38])[C:30]([OH:32])=[O:31])[CH2:22]5)[CH:15]=[CH:16][C:7]=3[CH:6]=[CH:5][C:4]=2[N:3]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 135539140diethyl (S)-2-(5-(((1,2-dihydro-3-methyl-1-oxo-benzo-[f]quinazolin-9-yl)methyl)amino)-1-oxo-2-isoindolinyl)glutarate

Product 1

HCID 135403832(2S)-2-[5-[[(1,2-Dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl]amino]-1,3-dihydro-1-oxo-2H-isoindol-2-yl]pentanedioic acidYield 99%

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

A solution of diethyl(S)-2-(5-(((1,2-dihydro-3-methyl-1-oxo-benzo-[f]quinazolin-9-yl)methyl)amino)-1-oxo-2-isoindolinyl)glutarate (3.20 g, 5.75 mmol) in 0.2 N NaOH (140 ml) was stirred under nitrogen for 3 hours at room temperature. The solution was then slowly adjusted to pH 3 with 1 N HCl and the resulting suspension allowed to stir briefly. The white solid was filtered under nitrogen, washed with water, and dried under high vacuum to give (S)-2-(5-(((1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl)amino)-1-oxo-2-isoindolinyl)glutaric acid (2.85 g). 1H NMR (DMSO-d6/D2O, 300 MHz) δ: 1.86-2.34 (m, 4H, glu CH2CH2), 2.44 (s, 3H, CH3), 4.25 (very strongly coupled AB pair, 2H, glu NCH2Ar), 4.58 (s, 2H, C9—CH2), 4.67-4.75 (m, 1H, glu CH), 6.69-6.77 (m, 2H, Ar), 7.37 (d, J=8 Hz, 1H, Ar), 7.59 (d, J=9 Hz, 1H, Ar), 7.64 (dd, J=8,2 Hz, 1H, Ar), 8.01 (d, J=8 Hz, 1H, Ar), 8.22 (d, J=9 Hz, 1H, Ar), 9.85 (s, 1H, Ar). Anal. Calculated for C27H24N4O6.6H2O: C, 61.27; H, 5.18; N, 10.58. Found: C, 61.29; H, 5.18; N, 10.57.

Workup

  1. filtrationThe white solid was filtered under nitrogen
  2. washwashed with water
  3. customdried under high vacuum

Sources & evidence

ORD record
ord-1b1a233e82424e699abdd83799f49f11
Source dataset
uspto-grants-2001_10
Patent number
US06306865B1

Reaction notes

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