Sodium Hydroxide → 3-{4-[2-(11-Ethyl-6,11-dihydro-5-methyl-6-oxo-5h-dipyrido[3,2-b:2',3'-e][1,4]diazepin-8-yl)ethoxy]-3-methylphenyl}-5-isoxazolecarboxylic acid

HRID 393274Notes

Reaction equation

HRID 393274 reaction equation
[CH2:1]([N:3]1[C:9]2[N:10]=[CH:11][C:12]([CH2:14][CH2:15][O:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]4[CH:27]=[C:26]([C:28]([O:30]CC)=[O:29])[O:25][N:24]=4)=[CH:19][C:18]=3[CH3:33])=[CH:13][C:8]=2[C:7](=[O:34])[N:6]([CH3:35])[C:5]2[CH:36]=[CH:37][CH:38]=[N:39][C:4]1=2)[CH3:2].[OH-].[Na+]>C1COCC1.CO>[CH2:1]([N:3]1[C:9]2[N:10]=[CH:11][C:12]([CH2:14][CH2:15][O:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]4[CH:27]=[C:26]([C:28]([OH:30])=[O:29])[O:25][N:24]=4)=[CH:19][C:18]=3[CH3:33])=[CH:13][C:8]=2[C:7](=[O:34])[N:6]([CH3:35])[C:5]2[CH:36]=[CH:37][CH:38]=[N:39][C:4]1=2)[CH3:2]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 22648860Ethyl 3-{4-[2-(11-ethyl-6,11-dihydro-5-methyl-6-oxo-5h-dipyrido[3,2-b:2',3'-e][1,4]diazepin-8-yl)ethoxy]-3-methylphenyl}-5-isoxazolecarboxylate

Product 1

HCID 30123423-{4-[2-(11-Ethyl-6,11-dihydro-5-methyl-6-oxo-5h-dipyrido[3,2-b:2',3'-e][1,4]diazepin-8-yl)ethoxy]-3-methylphenyl}-5-isoxazolecarboxylic acidYield 89%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl 3-{4-[2-(11-ethyl-6,11-dihydro-5-methyl-6-oxo-5H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-8-yl)ethoxy]-3-methylphenyl}-5-isoxazolecarboxylate (50.0 mg, 0.090 mmol) and aqueous 1 N NaOH solution (0.90 mL, 0.90 mmol) in THF (2 mL) and MeOH (0.5 mL) was stirred at 25° C. for 1 h. The reaction mixture was concentrated under reduced pressure, acidified with aqueous 4 N HCl solution and extracted with EtOAc (1×) and CH2Cl2 (1×). The combined organic layers were washed with water and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The resulting solid was triturated with EtOAc/Hexane to give the title compound (40 mg, 85% yield) as a pale yellow solid. A 1 N NaOH solution (78 μL, 0.078 mmol) was added to a solution of the title compound (39.0 mg, 0.078 mmol) in THF (3 mL). After 45 min, the mixture was concentrated. The residue was dissolved in water and MeCN then the solution was frozen and lyophilized to give the corresponding sodium salt of the title compound 1041 (40.5 mg, 100% yield) as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. extractionextracted with EtOAc (1×) and CH2Cl2 (1×)
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting solid was triturated with EtOAc/Hexane

Sources & evidence

ORD record
ord-a5ce6730c41040ce911daf723d3541c8
Source dataset
uspto-grants-2004_10
Patent number
US06806265B2

Reaction notes

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