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

HRID 381602

反応式

HRID 381602 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 76257Diethyl cyanophosphonate触媒HCID 6228Dimethylformamide溶媒2 回

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-2755872769be413ea95580b4e9040cb8
出典データセット
uspto-grants-2001_10
特許番号
US06306865B1

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