Isatoic Anhydride → 4-(2-Methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361297

반응식

HRID 2361297 반응식
[NH2:1][C:2]1[C:3]([CH3:30])=[C:4]([C:8]2[C:20]3[C:19]4[C:14](=[CH:15][C:16]([N:21]5[CH2:26][CH2:25][O:24][CH2:23][CH2:22]5)=[CH:17][CH:18]=4)[NH:13][C:12]=3[C:11]([C:27]([NH2:29])=[O:28])=[N:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[NH:31]1[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=2[C:34](=O)[O:33][C:32]1=O.COC(OC)OC.O.O.O.O.O.O.[N+]([O-])([O-])=O.[La+3].[N+]([O-])([O-])=O.[N+]([O-])([O-])=O>C1COCC1>[CH3:30][C:3]1[C:2]([N:1]2[C:34](=[O:33])[C:35]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[N:31]=[CH:32]2)=[CH:7][CH:6]=[CH:5][C:4]=1[C:8]1[C:20]2[C:19]3[C:14](=[CH:15][C:16]([N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)=[CH:17][CH:18]=3)[NH:13][C:12]=2[C:11]([C:27]([NH2:29])=[O:28])=[N:10][CH:9]=1

참가 물질

6

반응물 4

HCID 8359Isatoic AnhydrideHCID 9005Trimethyl orthoformateHCID 16211478Lanthanum nitrate hexahydrateHCID 679949134-(3-Amino-2-methylphenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxamide

생성물 1

HCID 679951304-(2-Methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxamide수율 17.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A burgundy solution of 4-(3-amino-2-methylphenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxamide (0.0612 g, 0.140 mmol), 1H-benzo[d][1,3]oxazine-2,4-dione (0.057 g, 0.351 mmol), trimethoxymethane (0.154 ml, 1.402 mmol) and lanthanum nitrate hexahydrate (0.018 g, 0.042 mmol) in THF (0.334 mL) in a sealed vial was stirred overnight at 95° C. The reaction was cooled to room temperature and concentrated in vacuo. The residue was dissolved in DMSO (0.2 mL) and MeOH (1.6 mL), and subjected to autoprep reverse phase HPLC. The appropriate fractions were collected, basified with NaHCO3 (solid), and concentrated in vacuo. The residue was extracted with CH2Cl2 (3×). The combine extract was dried over Na2SO4 and concentrated in vacuo to give the desired product (0.0135 g, 0.024 mmol, 17.1% yield) as a tan solid. LC/MS (M+H)=531.29; 1H NMR (500 MHz, DMSO-d6) (recognizable peaks for major atropoisomer) δ ppm 11.48 (1 H, s), 8.42 (1 H, s), 8.21-8.28 (2 H, m), 8.15 (1 H, s), 7.88-7.94 (1 H, m), 7.76-7.81 (1 H, m), 7.69-7.74 (1 H, m), 7.53-7.69 (4 H, m), 7.27 (1 H, d, J=2.22 Hz), 6.79-6.86 (1 H, m), 3.74-3.81 (4 H, m), 3.16-3.23 (4 H, m), 1.81 (3 H, s).

후처리

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in DMSO (0.2 mL)
  3. customThe appropriate fractions were collected
  4. concentrationconcentrated in vacuo
  5. extractionThe residue was extracted with CH2Cl2 (3×)
  6. extractionThe combine extract
  7. dry with materialwas dried over Na2SO4
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-7b5e59426e064ea3893cf449763c31cf
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08685969B2

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