Diethyl N-(4-aminobenzoyl)-L-glutamate → diethyl N-(4-(((3-amino-8-bromo-1,2, 5,6-tetrahydro-1-oxobenzo [f]quinazolin-9-yl) sulfonyl)amino)benzoyl)-L-glutamate

HRID 1377067

Reaction equation

HRID 1377067 reaction equation
[NH2:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:8]3[CH:13]=[C:14]([S:18](Cl)(=[O:20])=[O:19])[C:15]([Br:17])=[CH:16][C:7]=3[CH2:6][CH2:5][C:4]=2[N:3]=1.[CH2:22]([O:24][C:25](=[O:44])[C@H:26]([CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])[NH:27][C:28](=[O:36])[C:29]1[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=1)[CH3:23]>C(Cl)Cl>[NH2:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:8]3[CH:13]=[C:14]([S:18]([NH:35][C:32]4[CH:31]=[CH:30][C:29]([C:28]([NH:27][C@H:26]([C:25]([O:24][CH2:22][CH3:23])=[O:44])[CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[O:36])=[CH:34][CH:33]=4)(=[O:20])=[O:19])[C:15]([Br:17])=[CH:16][C:7]=3[CH2:6][CH2:5][C:4]=2[N:3]=1

Participants

4

Reactant 2

HCID 73002Diethyl N-(4-aminobenzoyl)-L-glutamateHCID 1361209353-Amino-8-bromo-5,6-dihydrobenzo[f]quinazolin-1(2h)-one-9-sulfonylchloride

Product 1

HCID 136041246diethyl N-(4-(((3-amino-8-bromo-1,2, 5,6-tetrahydro-1-oxobenzo [f]quinazolin-9-yl) sulfonyl)amino)benzoyl)-L-glutamateYield 26.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-Amino-8-bromo-5,6-dihydrobenzo[f]quinazolin-1(2H)-one-9-sulfonyl chloride (2.00 g, 4.50 mmole) and N-(4-aminobenzoyl)-L-glutamic acid diethyl ester (7.26 g,22.5 mmole) (Aldrich) were placed together in a test tube and melted at 175° C. The mixture was heated for 1 hour, 20 minutes, the cooled residue suspended in methylene chloride and filtered to remove undissolved solid. The filtrate was evaporated to dryness and the residue subjected to chromatography on a Waters Prep 500 instrument (silica column, elution with methanol/methylene chloride(1:24)). The combined fractions containing product were evaporated and the residue dried under high vacuum. The solid was suspended in boiling ethanol (900 ml), the suspension cooled to room temperature and filtered to give diethyl N-(4-(((3-amino-8-bromo-1,2, 5,6-tetrahydro-1-oxobenzo [f]quinazolin-9-yl) sulfonyl)amino)benzoyl) -L-glutamate (0.794 g, 26%). Mp>250° C. 1H NMR (DMSO-d6, 200 MHz) δ: 1.12 (t, J=7 Hz, 3H, ester-CH3), 1.14 (t, J=7 Hz, 3H, ester-CH3), 1.89-2.09 (m, 2H, glu-CH2), 2.37 (t, J=7 Hz, 2H, glu-CH2), 2.48-2.59 (m, 2H, Ar CH2), 2.77-2.85 (m, 2H, Ar CH2), 3.99 (q, J=7 Hz,2H,ester CH2), 4.05 (q, J=7 Hz, 2H, ester CH2), 4.29-4.40 (m, 1H, glu-CH), 6.84 (br s, 2H, NH2), 7.14 (d, J=9 Hz, 2H, Ar), 7.54 (s, 1H, Ar), 7.69 (d, J=9 Hz, 2H, Ar), 8.48 (d, J=8 Hz, 1H, NH), 9.37 (s, 1H, Ar), 10.87 (br s, 1H, NH), 11.04 (br s, 1H, NH). Anal. Calculated for C28H30BrN5O8S: 1/4 H2O C,49.38; H,4.51; Br,11.73; N, 10.20; S,4.71. Found: C,49.33; H,4.40; Br,11.79; N,10.20; S,4.74.

Workup

  1. temperatureThe mixture was heated for 1 hour, 20 minutes
  2. filtrationfiltered
  3. customto remove undissolved solid
  4. customThe filtrate was evaporated to dryness
  5. washthe residue subjected to chromatography on a Waters Prep 500 instrument (silica column, elution with methanol/methylene chloride(1:24))
  6. additionThe combined fractions containing product
  7. customwere evaporated
  8. customthe residue dried under high vacuum
  9. filtrationfiltered

Sources & evidence

ORD record
ord-e4d1660fc40540ef827749b12d239ada
Source dataset
uspto-grants-1997_09
Patent number
US05663337

Linked notes

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