Hydrochloric Acid → HCID 135430807, compound

HRID 277703Notes

Reaction equation

HRID 277703 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:40]=[CH:39][C:22]([C:23]([NH:25][C@H:26]([C:34]([O:36]CC)=[O:35])[CH2:27][CH2:28][C:29]([O:31]CC)=[O:30])=[O:24])=[C:21]([F:41])[CH:20]=4)[CH:15]=[CH:16][C:7]=3[CH:6]=[CH:5][C:4]=2[N:3]=1.Cl>C(O)C.[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:40]=[CH:39][C:22]([C:23]([NH:25][C@H:26]([C:34]([OH:36])=[O:35])[CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[O:24])=[C:21]([F:41])[CH:20]=4)[CH:15]=[CH:16][C:7]=3[CH:6]=[CH:5][C:4]=2[N:3]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 135437974HCID 135437974, compound

Product 1

HCID 135430807HCID 135430807, compoundYield 101.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of diethyl N-(4-(((1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl)amino)-2-fluorobenzoyl)-L-glutamate (2.3 g, 4.1 mmol) in ethanol (25 ml) and 0.2 N NaOH (100 ml) was stirred under nitrogen at room temperature for 3 hours. The solution was adjusted to pH 7 with 1N HCl and reduced in volume under vacuum to remove the ethanol. The product was precipitated by acidifying the solution with 1N HCl to pH 3 with stirring under nitrogen. The suspension was stirred 15 minutes, filtered under nitrogen, washed with water, pressed with a sheet of latex to remove excess water, and dried under high vacuum to give N-(4-(((1,2-dihydro-3-methyl-1-oxobenzo[f]quina-zolin-9-yl)methyl)amino)-2-fluorobenzoyl)-L-glutamic acid as a white solid (2.1 g). 1H NMR (DMSO-d6, 300 MHz) d: 1.82-2.12 (m, 2H, glu CH2), 2.29 (t, J=7 Hz, 2H, glu CH2), 2.43 (s, 3H, C3-CH3), 4.32-4.42 (m, 1H, glu CH), 4.57 (d, J=6 Hz, 2H, C9-CH2), 6.39 (dd, J=15.2 Hz, 1H, Ar), 6.53 (dd, J=9.2 Hz, 1H, Ar), 7.30 (t, J=6 Hz, 1H, ArNH), 7.47 (dd, J=9.9 Hz, 1H, Ar), 7.59 (d, J=9 Hz, 1H, Ar), 7.61 (dd, J=8.2 Hz, 1H, Ar), 7.73 (t, J=7 Hz, 1H, glu NH), 8.01 (d, J=8 Hz, 1H, Ar), 8.22 (d, J=9 Hz, 1H, Ar), 9.85 (s, 1H, Ar), 12.42 (br s, 2H, CO2H's), 12.53 (s, 1H, N2H). Anal. Calculated for C26H23FN4O6.3/2 H2O.1/3 NaCl: C, 56.49: H, 4.74: N, 10.14; Cl, 2.12: Na, 1.37, Found: C, 56.48; H, 4.64; N, 10.20; Cl, 2.01; Na, 1.30.

Workup

  1. customto remove the ethanol
  2. customThe product was precipitated
  3. stirringThe suspension was stirred 15 minutes
  4. filtrationfiltered under nitrogen
  5. washwashed with water
  6. customto remove excess water
  7. customdried under high vacuum

Sources & evidence

ORD record
ord-c91524f4a8e64b3d9d31ab9d5bbd5099
Source dataset
uspto-grants-2002_03
Patent number
US06358952B1

Reaction notes

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