Acetic Acid → HCID 86740705, compound

HRID 1380084Notes

Reaction equation

HRID 1380084 reaction equation
[CH:1](=[C:8]1[C:12]2=[N:13][C:14]3[CH:15]=[C:16]([NH:22][C:23]([C:25]4[CH:26]=[C:27]([CH:32]=[CH:33][CH:34]=4)[C:28]([O:30][CH3:31])=[O:29])=[O:24])[CH:17]=[CH:18][C:19]=3[C:20](=[O:21])[N:11]2[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].CI.[C:39](O)(=O)C>CN(C)C=O>[CH3:39][N:22]([C:16]1[CH:17]=[CH:18][C:19]2[C:20](=[O:21])[N:11]3[CH2:10][CH2:9][C:8](=[CH:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[C:12]3=[N:13][C:14]=2[CH:15]=1)[C:23]([C:25]1[CH:26]=[C:27]([CH:32]=[CH:33][CH:34]=1)[C:28]([O:30][CH3:31])=[O:29])=[O:24]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86740706HCID 86740706, compound

Product 1

HCID 86740705HCID 86740705, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3-[N-(3-benzylidene-9-oxo-1,2,3,9-tetrahydro-pyrrolo[2,1-b]quinazolin-6-yl)-aminocarbonyl]-benzoic acid, methyl ester (0.85 g) dissolved in dimethylformamide (40 ml) was added to a suspension of 50% NaH (0.18 g) in dimethylformamide (5 ml) and the mixture was stirred at room temperature for 1 hour and then reacted with methyl iodide (0.54 g) at room temperature for 17 hours. The reaction mixture was diluted with ice water and then acidified with acetic acid: the precipitate was filtered and purified over a flash column using chloroform-ethyl acetate 3:1 as eluant. A further purification from isopropyl ether gave 3-[N-methyl-N-(3-benzylidene-9-oxo-1,2,3,9-tetrahydro-pyrrolo[2,1-b]quinazolin-6-yl)-aminocarbonyl]-benzoic acid, methyl ester, m.p. 200°-202° C. (0.42 g), which was dissolved in dimethylformamide (20 ml) and treated with 5% aqueous NaOH (3.6 ml) at room temperature for 2 hours. The precipitate, 3-[N-methyl-N-(3-benzylidene-9-oxo-1,2,3,9-tetrahydro-pyrrolo[2,1-b]quinazolin-6-yl)-aminocarbonyl]-benzoic acid, sodium salt, m.p. >300° C., was filtered and then dissolved in formic acid: the solution was diluted with water to give a precipitate which was filtered and washed with water until neutral. Crystallization from dichloromethane-methanol gave 0.2 g of 3-[N-methyl-N-(3-benzylidene-9-oxo-1,2,3,9-tetrahydro-pyrrolo[2,1-b]quinazolin-6-yl)-aminocarbonyl]-benzoic acid, m.p. 302°-304° C., NMR (CDCl3) δ ppm.: 3.38 (m) (2H, C- 2 protons), 3.61 (s) (3H, CH3), 4.32 (t) (2H, C-1 protons), 7.14 (dd) (1H, C-7 proton), 7.32 (t) (1H, C-5 benzoyl proton), 7.35-7.85 (m) (7H, C-4 and C-6 benzoyl protons and phenyl protons), 7.88 (bs) (1H, --CH=), 8.00 (bd) (1H, C-5 proton), 8.13 (d) (1H, C-8 proton), 8.15 (bs) (1H, C-2 benzoyl proton).

Workup

  1. filtrationthe precipitate was filtered
  2. custompurified over a flash column
  3. customA further purification from isopropyl ether

Sources & evidence

ORD record
ord-b67591e07227485fab2566d9a13e04fe
Source dataset
uspto-grants-1986_04
Patent number
US04579847

Reaction notes

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