Benzoic Acid → diethyl N-(4-((1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methoxy)benzoyl)-L-glutamate

HRID 1884045Notes

Reaction equation

HRID 1884045 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][O:18][C:19]4[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=4)[CH:15]=[CH:16][C:7]=3[CH:6]=[CH:5][C:4]=2[N:3]=1.Cl.[CH2:29]([O:31][C:32](=[O:42])[C@H:33]([CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])[NH2:34])[CH3:30].C(P(=O)(OCC)OCC)#N.C(N(CC)CC)C.C(O)(=O)C1C=CC=CC=1>CN(C=O)C.C(P(=O)(OCC)OCC)#N>[CH3:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:8]3[CH:13]=[C:14]([CH2:17][O:18][C:19]4[CH:27]=[CH:26][C:22]([C:23]([NH:34][C@H:33]([C:32]([O:31][CH2:29][CH3:30])=[O:42])[CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])=[O:24])=[CH:21][CH:20]=4)[CH:15]=[CH:16][C:7]=3[CH:6]=[CH:5][C:4]=2[N:3]=1

Participants

8

Reactant 5

HCID 243Benzoic AcidHCID 8471TriethylamineHCID 73960Glutamic acid diethyl ester hydrochlorideHCID 76257Diethyl cyanophosphonateHCID 1358381204-((1,2-Dihydro-3-methyl-1-oxobenz[f]quinazolin-9-yl)methoxy)benzoic acid

Product 1

HCID 136051872diethyl N-(4-((1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methoxy)benzoyl)-L-glutamateYield 64.7%

Reagents, catalysts & solvents 2

HCID 76257Diethyl cyanophosphonateCatalystHCID 6228DimethylformamideSolvent2×

Procedure

To a stirred suspension of 4-((1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methoxy)benzoic acid (0.19 g, 0.53 mmol) and L-glutamic acid diethyl ester hydrochloride (0.14 g, 0.58 mmol) (Aldrich) in DMF (3 ml) were added diethyl cyanophosphonate (0.09 ml, 0.6 mmol) (Aldrich) and triethylamine (0.15 ml, 1.1 mmol). Additional DMF (7 ml) was added but homogeneous solution was not obtained. The reaction mixture was stirred 45 minutes at room temperature and TLC analysis indicated remaining benzoic acid. Diethyl cyanophosphonate (2 drops) was added, the mixture stirred 45 minutes, and was then concentrated in vacuo. The residue was purified by chromatography on silica gel (50 g) eluting with ethanol:methylene chloride (1:9). The solid was filtered from a small volume of ethanol and dried under reduced pressure to give diethyl N-(4-((1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methoxy)benzoyl)-L-glutamate (0.187 g). 1H NMR (DMSO-d6, 300 MHz) δ: 1.16 (t, J=7 Hz, 3H, esterCH3), 1.18 (t, J=7 Hz, 3H, esterCH3), 1.90-2.18 (m, 2H, gluCH2), 2.43 (t, J=7 Hz, 2H, gluCH2), 2.44 (s, 3H, C3—CH3), 4.05 (q, J=7 Hz, 2H, esterCH2), 4.10 (q, J=6 Hz, 2H, esterCH2), 4.36-4.46 (m, 1H, gluCH), 5.43 (s, 2H, CH2O), 7.17 (d, J=9 Hz, 2H, Ar), 7.65 (d, J=9 Hz, 1H, Ar), 7.74 (dd, J=8, 2 Hz, 1H, Ar), 7.88 (d, J=9 Hz, 2H, Ar), 8.08 (d, J=8 Hz, 1H, Ar), 8.26 (d, J=9 Hz, 1H, Ar), 8.58 (d, J=7 Hz, 1H, gluNH), 9.94 (s, 1H, Ar), 12.59 (s, 1H, N2H). Anal. Calculated for C30H31N3O7.1/4H2O: C, 65.50; H, 5.77; N, 7.64. Found: C, 65.54; H, 5.77; N, 7.61.

Workup

  1. customhomogeneous solution was not obtained
  2. stirringthe mixture stirred 45 minutes
  3. concentrationwas then concentrated in vacuo
  4. customThe residue was purified by chromatography on silica gel (50 g)
  5. washeluting with ethanol:methylene chloride (1:9)
  6. filtrationThe solid was filtered from a small volume of ethanol
  7. customdried under reduced pressure

Sources & evidence

ORD record
ord-471ba71eea3a4ff695844e99d3f2c0fc
Source dataset
uspto-grants-2004_07
Patent number
US06762188B1

Reaction notes

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