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Hydrochloric Acid → (S)-2-{4-[(3-Amino-1-oxo-1,2-dihydro-benzo[f]quinazolin-9-ylmethyl)-amino]-benzoylamino}-pentanedioic acid

HRID 2258704
Notes
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Reaction equation

HRID 2258704 reaction equation
[O:1]=[C:2]1[C:11]2[C:10]3[CH:12]=[C:13]([CH2:16][NH:17][C:18]4[CH:39]=[CH:38][C:21]([C:22]([NH:24][C@H:25]([C:33]([O:35]CC)=[O:34])[CH2:26][CH2:27][C:28]([O:30]CC)=[O:29])=[O:23])=[CH:20][CH:19]=4)[CH:14]=[CH:15][C:9]=3[CH:8]=[CH:7][C:6]=2[N:5]=[C:4]([NH:40]C(=O)C(C)(C)C)[NH:3]1.Cl>CO.[OH-].[Na+]>[NH2:40][C:4]1[NH:3][C:2](=[O:1])[C:11]2[C:10]3[CH:12]=[C:13]([CH2:16][NH:17][C:18]4[CH:19]=[CH:20][C:21]([C:22]([NH:24][C@H:25]([C:33]([OH:35])=[O:34])[CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[O:23])=[CH:38][CH:39]=4)[CH:14]=[CH:15][C:9]=3[CH:8]=[CH:7][C:6]=2[N:5]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 135448916Diethyl n-(4-(((1,2-dihydro-1-oxo-3-pivalamido-benzo[f]quinazolin-9-yl)methyl)amino)benzoyl)-l-glutamate

Product 1

HCID 135405044(S)-2-{4-[(3-Amino-1-oxo-1,2-dihydro-benzo[f]quinazolin-9-ylmethyl)-amino]-benzoylamino}-pentanedioic acidYield 91.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent
HCID 14798
Sodium Hydroxide
Solvent

Procedure

A solution of diethyl N-(4-(((1,2-dihydro-1-oxo-3-pivalamidobenzo[f]quinazolin-9-yl)methyl)amino)benzoyl)-L-glutamate (0.31 g, 0.49 mmol) in methanol (15 ml) and 1N NaOH (5 ml) was stirred under nitrogen at reflux for 1.5 hours and then allowed to cool. The solution was adjusted to pH 3 with 1N-HCl under nitrogen and the resulting precipitate was filtered under nitrogen, washed with water, and dried under high vacuum to give N-(4-(((3-amino-1,2-dihydro-1-oxobenzo[f]- quinazolin-9-yl)methyl)amino)benzoyl)-L-glutamic acid (0.22 g) as a white solid. 1H NMR (DMSO-d6, 300 MHz δ: 1.82-2.12 (m, 2H, glu CH2), 2.31 (t, J=7 Hz, 2H, glu CH2), 4.27-4.38 (m, 1H, glu CH), 4.50 (d, J=6 Hz, 2H, C9 -CH2), 6.55 (br s, 2H, NH2), 6.62 (d, J=9 Hz, 2H, Ar), 6.96 (t, J=6 Hz, 1H, ArNH), 7.26 (d, J=9 Hz, 1H, Ar), 7.44 (dd, J=8,2 Hz, 1H, Ar), 7.63 (d, J=9 Hz, 2H, Ar), 7.84 (d, J=8 Hz, 1H, Ar), 7.99 (d, J=9 Hz, 1H, Ar), 8.09 (d, J=8 Hz, 1H, glu NH), 9.67 (s, 1H, Ar), 11.14 (br s, 1H, N2H), 12.32 (br s, 2H, CO2H's). Anal. Calculated for C25H23N5O6.H2O: C, 59.17; H, 4.97; N, 13.80. Found: C, 59.31; H, 4.90; N, 13.72.

Workup

  1. temperatureat reflux for 1.5 hours
  2. temperatureto cool
  3. filtrationthe resulting precipitate was filtered under nitrogen
  4. washwashed with water
  5. customdried under high vacuum

Sources & evidence

ORD record
ord-6bcf62f7ccf64b51a80095997db6a7d5
Source dataset
uspto-grants-1997_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05661155

Reaction notes

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