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

反応式

HRID 1377067 の反応式
[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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e4d1660fc40540ef827749b12d239ada
出典データセット
uspto-grants-1997_09
特許番号
US05663337

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