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

HRID 1884049Notes

Reaction equation

HRID 1884049 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

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 887MethanolSolventHCID 14798Sodium HydroxideSolvent

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 1 N 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 1 N-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, gluCH2), 2.31 (t, J=7 Hz, 2H, gluCH2), 4.27-4.38 (m, 1H, gluCH), 4.50 (d, J=6 Hz, 2H, C9—CH 2), 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, gluNH), 9.67 (s, 1H, Ar), 11.14 (br s, 1H, N2H), 12.32 (br s, 2H, CO2H's). Anal. Calculated for C25H23N5O6H2O: 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-b3ec091e6bd44783880cd4f3b6a9883b
Source dataset
uspto-grants-2004_07
Patent number
US06762188B1

Reaction notes

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