Acetic Acid → HCID 135541375, compound

HRID 601173Notes

Reaction equation

HRID 601173 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]2[NH:7][C:8]([CH2:13][C:14]([O:16]CC)=O)=[N:9][S:10](=[O:12])(=[O:11])[C:5]=2[CH:4]=1.[CH3:21][CH:22]([CH3:37])[CH2:23][CH2:24][N:25]1[C:30]2[N:31]=[CH:32][CH:33]=[CH:34][C:29]=2[C:28](=O)[O:27]C1=O.[H-].[Na+].C(O)(=O)C>C1COCC1>[OH:27][C:28]1[C:29]2[C:30](=[N:31][CH:32]=[CH:33][CH:34]=2)[N:25]([CH2:24][CH2:23][CH:22]([CH3:37])[CH3:21])[C:14](=[O:16])[C:13]=1[C:8]1[NH:7][C:6]2[CH:19]=[CH:20][C:3]([O:2][CH3:1])=[CH:4][C:5]=2[S:10](=[O:11])(=[O:12])[N:9]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 102361501-(3-Methylbutyl)-2H-pyrido[2,3-d][1,3]oxazine-2,4(1H)-dioneHCID 46941516Ethyl (7-methoxy-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)acetate

Product 1

HCID 135541375HCID 135541375, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of the product of Example 183B (0.5 g, 1.6 mmol) and the product of Example 12A (0.375 g, 1.6 mmol) in anhydrous THF (16 mL) under nitrogen at 0° C. was added sodium hydride (95%, 0.162 g, 6.4 mmol). The reaction was heated at reflux for 4 hours, cooled to 0° C., and treated dropwise with glacial acetic acid (3 mL). The resulting mixture was heated at reflux for 2 hours, cooled to 25°, and diluted with ice water (150 mL). The resulting precipitate was collected by filtration, washed with water and recrystallized from dioxane/water to give the title compound (566 mg, 80%). The sodium salt of the title compound was prepared according to the procedure of Example 1D. MS (ESI−) m/z 441 (M−H)−. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.96 (d, J=6.62 Hz, 6 H) 1.48 (m, 2 H) 1.64 (m, 1 H) 3.82 (s, 3 H) 4.29 (m, 2 H) 7.16 (m, 4 H) 8.36 (dd, J=7.54, 2.02 Hz, 1 H) 8.52 (dd, J=4.60, 2.02 Hz, 1 H) 15.86 (s, 1 H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 4 hours
  3. temperatureThe resulting mixture was heated
  4. temperatureat reflux for 2 hours
  5. temperaturecooled to 25°
  6. filtrationThe resulting precipitate was collected by filtration
  7. washwashed with water
  8. customrecrystallized from dioxane/water

Sources & evidence

ORD record
ord-7b8440fa2f4046ab8961cf9bc4f1aafa
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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