Hydrochloric Acid → (R)-3-[1-(4,6-Dimethyl-1,2-benzisothiazol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-butyric acid

HRID 388470Notes

Reaction equation

HRID 388470 reaction equation
C[O:2][C:3](=[O:31])[CH2:4][C@H:5]([N:7]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]([CH2:18][C:19]2[C:23]3[C:24]([CH3:29])=[CH:25][C:26]([CH3:28])=[CH:27][C:22]=3[S:21][N:20]=2)[C:8]1=[O:30])[CH3:6].[Li+].[OH-].Cl>C1COCC1.O>[CH3:29][C:24]1[C:23]2[C:19]([CH2:18][N:9]3[C:10]4[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=4)[C:16](=[O:17])[N:7]([C@H:5]([CH3:6])[CH2:4][C:3]([OH:31])=[O:2])[C:8]3=[O:30])=[N:20][S:21][C:22]=2[CH:27]=[C:26]([CH3:28])[CH:25]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 68751053(R)-3-[1-(4,6-dimethyl-1,2-benzisothiazol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-butyric acid methyl ester

Product 1

HCID 68728800(R)-3-[1-(4,6-Dimethyl-1,2-benzisothiazol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-butyric acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-3-[1-(4,6-dimethyl-1,2-benzisothiazol-3-ylmethyl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-butyric acid methyl ester (60 mg, 0.14 mmol) in THF (1 mL) is added a solution of LiOH (8.5 mg, 0.20 mmol) in water (0.5 mL) and the resulting mixture is agitated at ambient temperature for 24 hours, heated at 50° C. for 6 hours, then agitated an additional 48 hours at ambient temperature. The reaction mixture is neutralized with 1N HCl (0.2 mL) then extracted with ethyl acetate (2×10 mL). The combined extracts are washed with water (1×10 mL) and brine (1×10 mL), dried with sodium sulfate and concentrated to provide the title compound. LCMS (ESMS): m/z 410 (M+H+).

Workup

  1. temperatureheated at 50° C. for 6 hours
  2. stirringagitated an additional 48 hours at ambient temperature
  3. extractionthen extracted with ethyl acetate (2×10 mL)
  4. washThe combined extracts are washed with water (1×10 mL) and brine (1×10 mL)
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-89f373c73fd747388310c6394560c397
Source dataset
uspto-grants-2013_02
Patent number
US08377949B2

Reaction notes

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