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

반응식

HRID 1377067 반응식
[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

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-e4d1660fc40540ef827749b12d239ada
출처 데이터셋
uspto-grants-1997_09
특허 번호
US05663337

연결된 노트

불러오는 중…