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

HRID 2361407Notes

Reaction equation

HRID 2361407 reaction equation
[NH2:1][C:2]1[C:3]([CH3:26])=[C:4]([C:8]2[C:20]3[C:19]4[C:14](=[CH:15][C:16]([Br:21])=[CH:17][CH:18]=4)[NH:13][C:12]=3[C:11]([C:22]([NH2:24])=[O:23])=[N:10][C:9]=2[CH3:25])[CH:5]=[CH:6][CH:7]=1.[NH:27]1[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[C:30](=O)[O:29][C:28]1=O.[N+](O[La](O[N+]([O-])=O)O[N+]([O-])=O)([O-])=O.COC(OC)OC>O1CCCC1.C(OCC)(=O)C>[Br:21][C:16]1[CH:15]=[C:14]2[C:19]([C:20]3[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([N:1]5[C:30](=[O:29])[C:31]6[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=6)[N:27]=[CH:28]5)[C:3]=4[CH3:26])=[C:9]([CH3:25])[N:10]=[C:11]([C:22]([NH2:24])=[O:23])[C:12]=3[NH:13]2)=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 8359Isatoic AnhydrideHCID 9005Trimethyl orthoformateHCID 679952474-(3-amino-2-methylphenyl)-7-bromo-3-methyl-9H-pyrido[3,4-b]indole-1-carboxamideHCID 178526924HCID 178526924, compound

Product 1

HCID 679948107-bromo-3-methyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamideYield 182.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-(3-amino-2-methylphenyl)-7-bromo-3-methyl-9H-pyrido[3,4-b]indole-1-carboxamide (0.042 g, 0.103 mmol), 1H-benzo[d][1,3]oxazine-2,4-dione (0.042 g, 0.257 mmol), tris(nitrooxy)lanthanum, 6H2O (0.013 g, 0.031 mmol), and trimethoxymethane (0.337 mL, 3.08 mmol) in tetrahydrofuran (0.5 mL) in a sealed vial was heated at 90° C. for 12 h. The reaction mixture was then stirred overnight at room temperature. This reaction was repeated two additional times. The combined reaction mixtures were diluted with ethyl acetate, washed with water, washed with brine, and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by purification by flash silica gel chromatography using a mixture of ethyl acetate and hexane (20%-35%-50%-65%) afforded 7-bromo-3-methyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (0.101 g, 0.188 mmol, 59% yield) as a tan solid. LC/MS M+1=538.1 and 540.1.

Workup

  1. customThe combined reaction mixtures
  2. washwashed with water
  3. washwashed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationConcentration under reduced pressure
  6. customfollowed by purification by flash silica gel chromatography
  7. additiona mixture of ethyl acetate and hexane (20%-35%-50%-65%)

Sources & evidence

ORD record
ord-a2a8878534f14a869f274022c384550e
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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