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

HRID 381602

반응식

HRID 381602 반응식
[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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 76257Diethyl cyanophosphonate촉매HCID 6228Dimethylformamide용매2회

실험 절차

To a stirred suspension of 4-((1,2-dihydro-3-methyl-1-oxobenz[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, ester CH3), 1.18 (t, J=7 Hz, 3H, ester CH3), 1.90-2.18 (m, 2H, glu CH2), 2.43 (t, J=7 Hz, 2H, glu CH2), 2.44 (s, 3H, C3—CH3), 4.05 (q, J=7 Hz, 2H; ester CH2), 4.10 (q, J=6 Hz, 2H, ester CH2), 4.36-4.46 (m, 1H, glu CH), 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, glu NH), 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.

후처리

  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

출처 및 근거

ORD 기록
ord-2755872769be413ea95580b4e9040cb8
출처 데이터셋
uspto-grants-2001_10
특허 번호
US06306865B1

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